Ramamurthi & Tandon's Manual of Neurosurgery (PDFDrive)

Ramamurthi & Tandon’s
MANUAL OF
NEUROSURGERY
Ramamurthi & Tandon’s
MANUAL OF
NEUROSURGERY
Prakash Narain Tandon

MBBS MS FRCS DSc (hc) FNA FNASc FASc FTWAS FAMS FRSM
Emeritus Professor, Department of Neurosurgery
All India Institute of Medical Sciences, New Delhi
President, National Brain Research Centre Society
Manesar, Gurgaon, Haryana, India
Ravi Ramamurthi
MS FRCS Ed (SN)
Head, Department of Neurosurgery
Dr Achanta Lakshmipathi Neurosurgical Centre
Postgraduate Institute of Neurological Surgery
Voluntary Health Services Hospital
Taramani, Chennai, Tamil Nadu, India
Pradeep Kumar Jain N

MBBS DNB (Neurosurgery)
Dr Achanta Lakshmipathi Neurosurgical Centre
Postgraduate Institute of Neurological Surgery
Voluntary Health Services Hospital
Taramani, Chennai, Tamil Nadu, India
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Ramamurthi & Tandon’s Manual of Neurosurgery
First Edition: 2014
ISBN: 978-93-5152-192-1
Printed at
PREFACE
In the era of rapid advances in knowledge, techniques and technologies, it is

difficult for a textbook to remain contemporary for any length of time. On the
other hand, timely updating requires herculean effort, especially as it entails
cooperation of a large number of contributors of a multi-authored book.
Keeping in view the above, we have attempted a new experiment of bringing
out this concise edition of the book in a totally new format, i.e. converting
the text in bulleted form, retaining the essential information but excluding
the supportive evidence provided in the detailed textbook. At the same time,
opportunity is taken to add recent advances. The publication of our Textbook
of Neurosurgery (Third Edition) and the Textbook of Operative Neurosurgery
(First Edition) has resulted in an abridged version of the voluminous material.
The book is divided into XVII sections covering all important areas of
neurosurgery, e.g. diagnostics, congenital malformations, head and spinal
injuries, infections, vascular malformations, central nervous system tumours,
etc. In addition, there are chapters on special neurosurgical techniques,
such as stereotactic and functional neurosurgery, surgery for epilepsy,
movement disorders, psychosurgery and pain. Each section has a number of
sub-sections, for example, the section on infections includes brain abscess,
subdural empyema, tuberculosis, fungal infections, cysticercosis, etc. Each
sub-section provides stand-alone comprehensive information on the subject.
This format of the text, as well as the multiple authorship of the book, has no
doubt resulted in some duplication of information. Nevertheless, enormous
amount of information has been restricted to a manageable number of pages.
We hope, the students and ever busy practicing neurosurgeons will find
this new format as an aide-memoir for ready reference. For greater details,
reference can be made from the full-text editions of our earlier textbook.
We take this opportunity to profusely thank all the authors, who
notwithstanding their extremely busy life provided their valuable, updated
contributions in the new format. Special thanks are due to Shri Jitendar P
Vij (Group Chairman), Mr Ankit Vij (Managing Director) and Tarun Duneja
(Director-Publishing) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New
Delhi, India, for their cooperation and the excellent quality of this publication.
Prakash Narain Tandon

Ravi Ramamurthi
Pradeep Kumar Jain N
CONTENTS
SECTION I: DIAGNOSTICS
1. Electrodiagnosis 1
Manjari Tripathi, Priya Gupta, Sarat Chandra P
2. Intracranial Pressure 13
Ravi Ramamurthi, Nigel Peter Symss
3. Neuro-ophthalmology 19
Tandon R, Saxena R, Phuljhele S
4. Neuro-otology 27
Sathiya Murali, Srividya, Mohan Kameswaran, Kiran Natarajan
5. Neuroendocrinology 38
Ravi Ramamurthi, Ravindranath Kapu
6. Intra-operative Monitoring 45
Babu KS, Rajasekar V
7. Conventional Radiology 53
Ravi Ramamurthi, Goutham Cugati
8. Basic Principles of CT Scan and MRI Scan 60

Veena Norhona
9. Radiology: Intracranial Tumours 70

Kesavdas
10. Radiology: Intracranial Infections 84

Bejoy Thomas
SECTION II: CONGENITAL

11. Embryology: Skull and Vertebral Column 95
Muthukumar N
12. Embryology: Brain and Spinal Cord 101

Muthukumar N
13. Congenital Malformations of Cerebrum 110

Venkatramana NK, Ravi Shankar S
14. Encephalocoeles 119

Ashok Kumar Mahapatra
15. Intracranial Arachnoid Cysts 127

Chidambaram Balasubramaniam, Vani Santosh
16. Craniofacial Deformities (Craniostenosis) 137

Uday Andar, Nitin Mokal
17. Spinal Dysraphic States 142

Venkatramana NK
18. Hydrocephalus 152

Venkatramana NK
viii
19. Endoscopic Management of Hydrocephalus 161

Aaron Mohanty
20. Normal Pressure Hydrocephalus 167

Sanjay Behari, Das NK, Vimal Kumar V
21. Bony Anomalies of the Craniovertebral Junction 178

Sanjay Behari, Rabi N Sahu, Vijendra Kumar Jain
22. Syringomyelia 182

Suresh Nair, Girish Menon, BRM Rao
SECTION III: HEAD INJURIES

23. Biomechanics of Head Injury 192
Deepak Agrawal, Ashok Kumar Mahapatra
24. Pathology 196

Sankar SK, Anita Mahadevan
25. Concussion Brain 215

Sandeep Vaishya, Khan Z
26. Cerebral Contusions 219

27. Diffuse Axonal Injury 224

Rajkumar, Vivek Kumar Vaid, Ashok Kumar Mahapatra
28. Fat Embolism 229

Krishna Reddy A
29. Paediatric Head Injuries 233

Chidambaram Balasubramaniam, Ramachandran B
30. Clinical Assessment of a Head Injured Patient 244

Rajkumar, Samir Kumar Kalra, Ashok Kumar Mahapatra
31. Fluid and Electrolyte Balance in Head Injury 250

Sharma RR
32. Scalp Injuries 263

Krishna Reddy A
33. Acute Subdural Haematomas 270

Sanjay Behari, Anuj Chaitley, Manish Singh Sharma, Ashok Kumar Mahapatra
34. Extradural Haematomas 274

Ashok Kumar Mahapatra, Vivek Kumar Vaid, Rajkumar
35. Traumatic Intracerebral Haematomas 278

36. Traumatic Brainstem Haemorrhage 285

Ashok Kumar Mahapatra, Deepak Agrawal
37. Complications and Sequelae of Head Injuries 288

Khosla VK, Gupta SK, Mukherjee KK, Chhabra R
38. Cranioplasty 297

Ramesh Kumar Sharma, Mathuriya SN
39. Maxillofacial Injuries 303

Arun Kumar Singh, DN Upadhyay
40. Traumatic Cerebrospinal Fluid Fistulae 309

Ravi Ramamurthi, Amit Kapoor
Contents
ix
41. Missile Injuries of the Brain 315

Harjinder S Bhatoe
42. Endocrine Abnormalities Following

Traumatic Brain Injuries 321
Deepak Kumar Gupta, Ashok Kumar Mahapatra
43. Optic Nerve Injury 325

Ashok Kumar Mahapatra, Deepak Kumar Gupta
SECTION IV: SPINAL INJURIES

44. Assessment and Emergency Management of
Acute Spinal Injuries 332
Anil Pande, Pradeep Kumar Jain N
45. Biomechanics of the Spine 349

Anil Pande, Goutham Cugati
46. Injuries of the Craniovertebral Junction and

Upper Cervical Spine 359
Sarat Chandra P, Vamsi Yerramani
47. Injuries of Subaxial Cervical Spine 371

Anil Pande, Ravindranath Kapu
48. Whiplash Injury 380

Harjinder S Bhatoe
49. Thoracic and Thoracolumbar Injuries 383

Ramakrishna Easwaran
50. Lumbar and Lumbosacral Injuries 393

51. Penetrating Injuries of the Spine 397

Harjinder S Bhatoe
SECTION V: PERIPHERAL NERVE

52. Anatomy and Physiology of the Peripheral Nerve 402
Sharma M, Gupta A, Mehta VS
53. General Principles of Management of

Peripheral Nerve Injuries 409
David A Omahen, Hazem Eltahawy, Abhit Guha
54. Surgical Anatomy and Management of

Brachial Plexus Injuries 416
Venkataswami R, Purushothaman V
55. Management of Injuries to Specific

Peripheral Nerve 422
Gupta A, Ahmad FU, Mehta VS
56. Entrapment Syndromes 425

Gupta A, Ahmad FU, Mehta VS
SECTION VI: INFECTIONS

57. Brain Abscess 437
Dharkar SR, Sardana VR, Purohit D
x
58. Scalp and Skull Infections 446

59. Subdural Empyema 450

Mathuriya SN, Pathak A, Khandelwal N
60. Spinal Epidural and Intramedullary Abscess 453

Ashish Suri, Shashwat Mishra, Ajay Garg
61. Tuberculosis of the Central Nervous System 459

PN Tandon, Anil Pande
62. Tuberculous Meningitis 466

PN Tandon, Anil Pande
63. Tuberculosis of the Spine 475

Sridhar K
64. Surgery for Leprosy 484

Sridhar K
65. Cysticercosis 489

BS Sharma, Sarat Chandra P
66. Hydatid Disease 499

Dharkar SR, Vikram M
67. Other Parasitic Infestations of the Brain 503

Sridhar K, Vikram M
68. Spinal Hydatidosis 505

Harjinder S Bhatoe
69. Fungal Infections 511

Anil Pande
70. Viral Infections 522

Ravi Ramamurthi, Ramamurthi B, Ravindranath Kapu
71. Acquired Immunodeficiency Syndrome and the

Neurosurgeon 529
Sarat Chandra P, Vivek Tandon
SECTION VII: VASCULAR DISORDERS

72. Subarachnoid Haemorrhage 538
Chandramouli BA, Arivazhagan A
73. General Principles of Management of

Intracranial Aneurysms 547
Tewari Manoj Kumar, Mathuriya SN, Khandelwal N
74. Vasospasm and its Management 559

Anil Pande, Ravi Ramamurthi
75. Cerebral Protection 573

Ravikant Palur, Ganesh K Murthy
76. Paraclinoid Aneurysms 586

Vijendra Kumar Jain, Sanjay Behari, Bernard Lyngdoh
77. Internal Carotid Bifurcation Aneurysms 591

Mathuriya SN, Tewari Manoj Kumar, Mukharjee KK, Paramjeet Singh
78 Anterior Communicating Artery Aneurysms 596

Mathuriya SN
79. Distal Anterior Cerebral Artery Aneurysm 606

Ravi Ramamurthi, Shivaram Bojja
Contents
xi
80. Middle Cerebral Artery Aneurysms 608

Mathuriya SN, Pathak A, Gupta Vivek, Grover VK
81. Posterior Circulation Aneurysms 613

Ashish Suri, Sachin A Borkar, Nalin K Mishra
82. Giant Aneurysms 621

Sanjay Behari, Rabi Narayan Sahu, Rupant K Das, Vijendra Kumar Jain
83. Incidental Intracranial Aneurysms 629

Suresh Nair, A Mathew, G Menon
84. Multiple Intracranial Aneurysms 634

Mahmoud Rashidi, Anthony Sin, Anil Nanda
85. Intracranial Aneurysms of Infective Origin 638

Sanjay Behari, Vivek Vaid, Awadhesh K Jaiswal, Vijendra Kumar Jain
86. Intracavernous Aneurysms 642

BS Sharma, VS Mehta
87. Contemporary Endovascular Treatment of

Intracranial Aneurysms 647
Uday Limaye, Anand S
88. Vascular Malformations of the Brain 652

89. Surgical Management of Cerebral AVMs 661

Ravi Ramamurthi, Ravindranath Kapu
90. Embolisation of Intracranial Vascular Malformation 667

Anil Karapurkar, Nishant Aditya
91. Stereotactic Radiosurgery for

Cerebral AVMs 672
Ganapathy K
92. Vein of Galen Malformations 677

Anil Nanda
93. Cavernomas of the Brain 682

CE Deopujari
94. Other Vascular Malformations of the Brain 688

Ravi Ramamurthi, Harinivas
95. Carotid Cavernous Fistula 693

96. Dural Arteriovenous Malformations 700

97. Embolisation of Spinal Vascular Malformations 705

Anil Karapurkar, Nishant Aditya
98. Spontaneous Intracerebral Haemorrhage 711

Ajaya Nand Jha, Vipul Gupta
99. Surgery for Stroke 718

Vincent Thamburaj A
SECTION VIII: TUMOURS OF THE

SPINE AND SPINAL CORD
100. Clinical Features and Diagnosis 735
Ravi Ramamurthi, Santhosh Mohan Rao K
xii
101. Vertebral Tumours 747

Deepu Banerji, Pallav Garg, Manoj Jain, Sanjay Behari
102. Spinal Schwannomas and Meningiomas 761

Trimurti D Nadkarni
103. Intramedullary Tumours 766

Bhawani S Sharma, Manish S Sharma
104. Congenital Tumours of the Spine 775

CE Deopujari, AB Kakani
105. Paediatric Spinal Tumours 782

Venkatramana NK
SECTION IX: DISC DISEASE AND

OTHER SPINAL PATHOLOGIES
106. Pathophysiology of Disc Degeneration 790
107. Cervical Disc Disease and Spondylosis:

Clinical Features and Diagnosis 797
CE Deopujari, Rajiv Kumar
108. Cervical Disc Disease and Spondylosis

Management 801
CE Deopujari, Rajiv Kumar, Rajan Shah
109. Cervical Ossification of Posterior

Longitudinal Ligament 807
Anil Pande, M Vikram, Ravi Ramamurthi
110. Thoracic Disc Prolapse 817

111. Lumbar Disc Disease 821

Manas Kumar Panigrahi, Rajesh Reddy S
112. Lumbar Canal Stenosis 831

Manas Kumar Panigrahi, Debabrat Biswal
113. Spondylolisthesis 839

114. Fluorosis 847

Raja Reddy D, Srikanth R Deme
115. Osteoporosis 855

Ramakrishna Easwaran, S Sundarrajan
SECTION X: PATHOLOGY OF
INTRACRANIAL TUMOURS
116. Classification of Tumours of the Nervous System 865
Vani Santhosh
117. Pathogenesis: Tumours of the Nervous System 872

Radhakrishnan VV
118. Germ Cell Tumours of the Central

Nervous System 880
Vani Santhosh
Contents
xiii
119. Embryonal Tumours of the

Central Nervous System 883
Chitra Sarkar, MC Sharma
120. Tumours of Meninges 892

Sundaram C, Shantveer G Uppin
121. Pituitary Tumours, Sellar and Suprasellar Lesions 904

Geeta Chacko
122. Lymphomas and Metastatic Tumours of

Nervous System 918
Sundaram C, T Roshni Paul
123. Cerebral Oedema in Relation to Neoplasias of

Nervous System 927
Shankar SK
124. Tumour Markers in Tumours of Nervous System 939

Chitra Sarkar, Vaishali Suri, MC Sharma
125. Tumours of Cranial and Peripheral Nerves 944

Sundaram C, Anita Mahadevan
126. Tumours of the Choroid Plexus 952

Yasha TC
127. Pineal Parenchymal Tumours 957

Vani Santhosh
128. Neuronal and Mixed Neuronal Glial Tumours 960

Sharma MC, Chitra Sarkar
SECTION XI: CRANIAL AND

INTRACRANIAL TUMOURS
129. Clinical Features of Intracranial Tumours 967
Ravi Ramamurthi, Santosh Mohan Rao K
130. Supratentorial Astrocytomas 990

131. Cerebellar Astrocytomas 1010

132. Brainstem Gliomas 1016

Sarat Chandra P, VS Mehta
133. Hypothalamic-Optic Nerve Gliomas 1024

134. Oligodendrogliomas 1032

135. Ependymomas 1037

Harjinder S Bhatoe
136. Medulloblastomas 1043

BS Sharma
137. Metastatic Brain Tumours 1049

Ravi Ramamurthi, Harinivas
138. Radiation Therapy for Malignant Brain Tumours 1057

Julka PK, Haresh KP, Rath GK
xiv
139. Adjuvant Therapies for Malignant Brain Tumours 1065

Raj Kumar R, Ashok Kumar Mahapatra
140. Colloid Cyst 1071

Nigel Peter Symss, Ravi Ramamurthi
141. Choroid Plexus Tumours 1076

Vasudevan MC
142. Pineal Region Tumours: Clinical Features and

Management 1080
143. Pituitary Tumours Overview 1088

Ravi Ramamurthi
144. Prolactinomas 1094

Ravi Ramamurthi, Prasad AN
145. Growth Hormone Secreting Adenomas 1098

146. Cushing’s Disease and Syndrome 1102

Deepu Banerji, Sanjay Behari
147. Other Secreting Adenomas of the Pituitary 1109

Deepu Banerji, Archana Juneja
148. Non-functioning Pituitary Adenomas 1113

Manas Kumar Panigrahi, Naveen Mehrotra, Amit Kumar T
149. Pituitary Apoplexy 1118

Ravi Ramamurthi, Vikram M, Goutham Cugati
150. Giant Invasive Pituitary Adenomas 1121

151. Perioperative Endocrine Management of

Pituitary Adenomas 1125
Murthy S
152. Empty Sella Syndrome 1134

Ravi Ramamurthi, Murali Mohan S
153. Diencephalic Syndrome 1140

Anil Pande, Murali Mohan S
154. Other Tumours of the Sellar Region 1145

Sanjay Behari, Anooj Chatley, Abrar Ahad Wani, Manoj Jain
155. Craniopharyngioma 1164

SN Bhagwathi, Suresh Sankhla
156. Dermoids and Epidermoids 1174

157. Teratomas 1182

158. Acoustic Schwannomas 1186

Ravi Ramamurthi, Murali Mohan S
159. Trigeminal Schwannomas 1205

BS Sharma, Ramdurg S, Sarat Chandra P
160. Jugular Foramen Lesions 1210

Siddhartha Ghosh
161. Other Intracranial Schwannomas 1219

Contents
xv
162. Phakomatoses 1225

163. Convexity Meningiomas 1231

Vasudevan MC
164. Parasagittal and Falx Meningiomas 1237

Vasudevan MC
165. Olfactory Groove Meningioma 1240

166. Sphenoidal Wing Meningiomas 1246

Trimurti D Nadkarni
167. Tentorial Meningiomas 1251

Vijendra Kumar Jain, Sanjay Behari, Pramod Giri
168. Posterior Fossa Meningiomas 1258

Amitabha Chanda, Abhijit Guha
169. Petroclival Meningiomas 1267

Trimurti D Nadkarni
170. Foramen Magnum Meningiomas 1271

Shrivastava RK, Chandranath Sen
171. Intraventricular Meningiomas 1277

Harjinder S Bhatoe, Prakash Singh, Vibha Dutta
172. Haemangioblastomas 1281

Ravi Ramamurthi
173. Primary Central Nervous System Lymphomas 1286

Sanjay Behari, Punita Lal, Samir Kalra, Manoj Jain
174. Intracranial Melanomas and Other Tumours 1294

Bhawani S Sharma, Sumit Sinha
175. Benign Intracranial Tension 1299

Nigel Peter Symss, Ravi Ramamurthi
176. Tumours of the Cranial Vault 1304

Narayanan R, Ravi Ramamurthi
SECTION XII: SKULL BASE SURGERY

177. Clival Chordomas 1322
Chandranath Sen
178. Transfacial Transmaxillary Approaches to

Anterior Skull Base 1326
Sojan Ipe, Bobby Jose
179. Approaches to the Lateral Skull Base 1333

Atul Goel, Muzumdar D
180. Transpharyngeal Approach to the

Craniovertebral Junction 1341
AH Menezes
181. Reconstruction of the Skull Convexity and Base 1346

Atul Goel, Muzumdar D
182. Orbital Tumours 1353

Aadil S Chagla
xvi
SECTION XIII: STEREOTAXY

183. Stereotaxy: General Principles 1363
Ravi Ramamurthi, Vikram M
184. Stereotaxy: Brain Tumours 1370

Murali Mohan S, Ravi Ramamurthi
185. Involuntary Movements: Anatomy and

Pathophysiology 1374
Srinivasan AV
186. Stereotaxy for Parkinson’s Disease 1379

Dilip Panicker, Paresh K Doshi
187. Surgery for Movement Disorders 1384

Paresh K Doshi, Animesh Upadhyay
188. Gamma Knife Radiosurgery 1391

Manish Singh Sharma, BS Sharma
189. Psychosurgery 1397

Ramamurthi B, V Balasubramaniam, Ravi Ramamurthi,
Santosh Mohan Rao K
190. Neural Transplantation and Stem Cell 1408

PN Tandon
SECTION XIV: PAIN

191. Pain: Anatomy and Physiology 1411
Ravi Ramamurthi, Santosh Mohan Rao K
192. Management of Pain 1425

Nigel Peter Symss
193. Trigeminal Neuralgia 1443

194. Glossopharyngeal and Other Cranial Neuralgia 1450

195. Microvascular Decompression 1456

Ravi Ramamurthi, Manish Singh
SECTION XV: EPILEPSY

196. Epilepsy: Overview 1462
Dinesh Nayak S, Radhakrishnan K
197. Epilepsy: Medical Management 1471

Ashalatha, Radhakrishnan K
198. Surgery for Epilepsy: General Principles 1475

Bhaskara Rao Malla, Jayanti Mani
199. Surgery for Temporal Epilepsy 1487

Bhaskara Rao Malla, Jayanti Mani
SECTION XVI: CEREBRAL PALSY

200. Stereotaxy for Cerebral Palsy 1495
Kanaka TS, Balasubramaniam V, Sampathkumar M
201. Surgery for Spasticity 1501

AK Purohit, Jagan Mohan Reddy K
Contents
xvii
SECTION XVII: MISCELLANEOUS

202. Anaesthesia for Neurosurgery 1512
Gupta D, Srivastava S
203. Positioning in Neurosurgery 1531

Indira Devi, Nitin Garg N, Shukla D
204. Operation Theatre for Neurosurgery 1534

Rahmathulla G, Ajaya Nand Jha
205. Basic Neurosurgical Instruments 1538

Sanjay Behari, Singh RK, Lyngdoh B, Jain S, Chhabra DK
206. Navigation in Brain and Spinal Surgery 1555

Ajaya Nand Jha, Rahmathulla G
207. Endoscopy in Brain Tumour Surgery 1566

Manas Kumar Panigrahi
208. Orthotics 1572

PK Sethi
209. Principles of Physiotherapy 1577

Sangeetha Ranganath
Index 1581
Section I: Diagnostics
1
CHAPTER
Electrodiagnosis
Manjari Tripathi  Priya Gupta  Sarat Chandra P
NERVE CONDUCTION STUDIES

•• Physiologically, the nerve transmits an electrical impulse across its axon
both antidromically and orthodromically.
•• Each stimulus has a proximal as well as distal transmission. This property is
used to assess compound muscle action potential (CMAP), sensory nerve
action potential (SNAP), F-response, H-reflex and SSR.
•• Each potential is described by its latency, amplitude, area and configuration.
•• To obtain the velocity, the nerve is stimulated at two different sites and
recording is done on the same muscle, and the difference in response
latency is multiplied by the distance between these two stimulation sites.
Definition of Related Terms

•• Latency: This is the time in milliseconds from the application of a stimulus
to the initial deflection from the baseline, either positive or negative, and is
the time required for the action potentials in the fastest conducting fibres
to activate the muscle fibres.
•• Conduction velocity: It is calculated by measuring the difference in
distance and latency between sites of stimulation in metres per second.
•• Amplitude: It is measured in height in millivolts from the baseline to the
peak of the negative phase (upward deflection). It is proportional to the
number of muscle fibres activated and gives an estimate of the amount of
functioning nerve and muscle.
•• F-response: It results from the backfiring of antidromically activated anterior
horn cells. It is especially helpful in assessment of motor conduction of the
proximal segment of a stimulated axon along with the entire length of the
peripheral axon.
•• H-reflex: It is an electrically elicited spinal monosynaptic reflex and
bypasses the muscle spindles. The group 1A sensory fibres and alpha
motor neurons form the respective afferent and efferent arcs of this reflex.
The H-reflex latency and amplitude are helpful in the diagnosis of mild-S1
radiculopathy.
Types of Neuropathy
The following are the types of neuropathy:
•• Demyelinating neuropathy
•• Axonal neuropathy
•• Mixed demyelinative/Axonal neuropathy.
Section I • Diagnostics
2
Important Points to Remember

• Do not trust electrophysiological studies (EPS) if they do not match your clinical
examination finding.
• The role of EPS is to corroborate clinical history and examination, and is not a
substitute for the latter.
• While interpreting nerve conduction study (NCS), normative data of the con-
cerned laboratory should be available before interpretation.
ELECTROMYOGRAPHY
•• The pattern of electrical activity in muscle [i.e. electromyography (EMG)],
both at rest and during activity, may be recorded from a needle electrode
inserted into the muscle.
•• The nature and pattern of abnormalities relate to disorders at different
levels of the motor unit.
•• Before planning to start EMG, the clinician should have relevant NCS and
clinical details of the patient.
Electromyography Findings
At rest
•• Insertion activity
•• Spontaneous activity.
At voluntary movements
•• Assessment of individually recruited motor unit action potential (MUAP)
•• Size
•• Shape
•• Stability
•• Assessment of activation pattern of MUAPs
•• Recruitment
•• Interference pattern (IP).
Insertional Activity
It lasts for a few hundred milliseconds, usually 300−500 ms. Appear as a cluster
of positive or negative repetitive high-frequency spikes.
Increased insertional activity indicates instability of the muscle mem-
brane indicating:
•• Denervation, usually an early finding 1−2 weeks after nerve injury
•• Myotonic disorders
•• Necrotising myopathies, such as inflammatory myopathies.
Decreased insertional activity suggests either fibrotic or severely
atrophied muscles or functionally unexcitable muscles (e.g. during attacks of
familial periodic paralysis).
Spontaneous Activity
Normal
•• Normally no spontaneous activity is seen except at the motor endplate
region.
•• Two types of normal endplate spontaneous activity are present.
•• Endplate noise: These are extracellularly recorded miniature endplate
potentials and non-propagating depolarisations. It is caused by spontaneous
Chapter 1 • Electrodiagnosis
3
release of acetylcholine quanta. These are negative potentials, irregular

in rhythm, with amplitude of 10−50 uV and duration of 1−2 milliseconds
(sounds like a “sea shell held to the ear”).
•• Endplate spikes: These are discharges of single muscle fibres generated
by activation of intramuscular nerve terminals irritated by the needle. They
may originate in the intrafusal muscle fibres. They are irregular having
an initial negative deflection, firing at 5−50 impulses per second, with
amplitude of 100−200 pV with duration of 3−4 milliseconds (sounds like
“clacking or buzzing”).
Abnormal
•• Fibrillation potentials
•• Fasciculation potentials
•• Complex repetitive discharges
•• Myotonic discharges
•• Myokemic discharges
•• Neuromyotonic discharges
•• Cramps.
Fibrillation potentials
•• These are spontaneous action potentials of denervated single muscle
fibres.
•• They result from the resting membrane potential of the denervated fibre
and usually appear 10−21 days after muscle denervation.
•• They are brief spikes (usually triphasic with initial positivity) or positive
waves (initial positivity with slow negativity, sawtooth appearance), fire
regularly at 1−30 Hz, with an amplitude of 20−200 pV; gradually decreasing
with time, with a duration of 1−5 milliseconds (sounds like “crisp and
clicking” and “tick-tock of a clock”).
Causes
•• Denervation, useful in localising lesions affecting motor neurons, spinal
roots, plexus or peripheral nerve.
•• May persist in paraspinous muscles for years after surgery.
•• Inflammatory myopathy.
Grading system is used (from 0 to 4) to semiquantitate fibrillation potentials
0 – no fibrillations
+1 – persistent single trains of potentials (> 2 seconds) in at least two
areas
+2 – moderate number of potentials in three or more areas
+3 – many potentials in all areas
+4 – abundant spontaneous potentials nearly filling the oscilloscope.
Fasciculation potentials
•• Fasciculation potentials are spontaneous discharges of a motor unit.
•• They originate from the motor axon anywhere along its length.
•• Their size and shape are like MUAPs, have an irregular rhythm and a lower
firing rate than voluntary MUAPs (sounds like “corn popping”).
Causes
•• Diseases of anterior horn cells (MND)
•• Radiculopathies
•• Entrapment neuropathies
•• Peripheral polyneuropathies
4
•• Cramp fasciculation syndrome

•• Others: tetany, thyrotoxicosis and overdose of anticholinesterase medication
•• They may also occur in healthy people.
Complex repetitive discharges
•• These result from the nearly synchronous firing of a group of muscle fibres.
•• One fibre in the complex serves as a pacemaker, driving one or several
other fibres so that the individual spikes in the complex fire in the same
order as the discharge recurs.
•• One of the late-activated fibres re-excites the principal pacemaker to repeat
the cycle. They are shaped containing 10 or more distinct spikes, regular in
rhythm, firing at 5−100 Hz, typically begin abruptly, with an amplitude of 50
pV−1 mV, with a duration of 50−1000 milliseconds (sounds like “machine
gun” on the loudspeaker).
•• Complex repetitive discharges are non-specific and seen in many chronic
disorders, including chronic neuropathies and myopathies.
•• They may also be found in the iliopsoas or cervical paraspinal muscles of
apparently healthy people, probably implying a clinically silent neuropathic
process.
Myotonic discharges
•• Abnormal insertional activity of recurring single-fibre potentials wax and
wane in the range of 10 LIV−1 mV, varying inversely with the firing rate of
20−150 Hz (accelerating or decelerating motorcycle or chainsaw).
•• Myotonic discharges may occur with or without clinical myotonia in the
myotonic dystrophies (types I and II) and other myopathies.
Myokymic discharges
•• These originate ectopically in motor nerve fibres and result from complex
bursts of grouped repetitive discharges in which motor units fire repetitively.
•• Usually with 2−10 spikes with a firing rate of 30−40 Hz, each burst recurs
at regular intervals of 1−5 seconds (sounds like “marching soldiers” on
the speaker).
Neuromyotonic discharges
•• Here, the muscle fibres fire repetitively at high frequency (150−250 Hz)
and produce a pinging sound on the speaker.
•• They continue during sleep and diminish in intensity with distal nerve blocks.
Cramp discharges
•• These include sustained involuntary muscle contraction during cramps.
•• The discharge consists of MUAPs, with a firing rate of 40−60 Hz, with
abrupt onset and cessation.
MOTOR UNIT ACTION POTENTIALS

•• The MUAP is the extracellular electrode recording of a small portion of a
motor unit.
•• They are triphasic in shape, measured as total peak-to-peak amplitude.
•• It normally varies from several hundred microvolts to a few millivolts.
•• Duration: It normally varies from 5−15 milliseconds. Long-duration MUAPs
with high amplitude are the best indicators of reinnervation. Short-duration
MUAPs with low amplitude are seen in disorders associated with loss of
muscle fibres, like myopathies.
5
•• Phase: This is the deviation of the signal from its beginning until its return
to the baseline. An MUAP having more than four phases is considered
polyphasic. Increased polyphasics is a nonspecific abnormality seen both
in myopathies and neuropathies.
•• Late component (satellite or linked potential): This is a time locked
waveform to the main MUAP, but separated from it by an isoelectric interval.
It implicates early reinnervation of muscle fibres by collateral sprouts from
adjacent motor units.
•• Complexity: The MUAP with greater than 4 phases or a satellite potential
is said to be complex.
•• Variability: These include changes in shape of the MUAP on consecutive
discharges. It indicates deficient neuromuscular transmission. They may
indicate NMJ disorder, MND, polyneuropathy or radiculopathy and early
stage of reinnervation.
Electrodiagnostic Findings in Nerve Injury

The electrodiagnostic findings (EDX) provide information about:
•• Site of the injury
•• Underlying pathophysiology
•• Rate of recovery.
Neuropraxia
•• No axonal degeneration, only conduction block: focal site of demyelination.
•• Aetiology: Compression or traction injury.
•• Large myelinated fibres are more susceptible to compression and ischae-
mia (motor).
Electrodiagnostic findings
•• Nerve conduction is normal distally, but altered across the injury site
(consider axonal loss if amplitude decreased proximally and distally).
•• Needle EMG shows decreased recruitment, but no abnormal spontaneous
potentials.
•• Normal conduction returns in days/weeks (due to remyelination of the
damaged segment).
Axonotmesis
•• Axonotmesis implies axon damage with preservation of the endoneurium,
perineurium and epineurium, and there will be Wallerian degeneration of
the axon.
•• Motor NCS lost day 4−7 (NMJ fragmentation).
•• Sensory NCS lost day 8−10.
•• Preservation of endoneurium allows for regeneration with reinnervation.
•• Recovery time dependent on distance for reinnervation.
Electrodiagnostic findings
•• Day 0−3: same as neuropraxia.
•• Day 4−7: decreased motor amplitude.
•• Day 8−10: decreased sensory amplitude.
•• Day 10−14: abnormal spontaneous potentials on EMG (PSW, Fibs).
•• Month 6−12: “nascent pot’s (S > M) and “jitter”.
•• Performing EDX too early may lead to misleading information (wait 2−4
weeks).
6
•• An early sign of axonotmesis is decreased CMAP amplitude (30−40% lower

than the contralateral side).
•• Repeat testing will be required in about 2−3 weeks.
Neurotmesis
•• Disruption of axon, endoneurium and connective tissue (perineurium and
epineurium).
•• Poor prognosis for reinnervation.
•• EDX finding are the same as above.
SENSORY EVOKED POTENTIALS

•• Recording of spinal or cerebral potentials elicited by stimulation of specific
afferent pathways helps in monitoring the functional integrity of these
pathways, although it does not indicate the pathologic basis of lesions
involving them.
Somatosensory-evoked Potentials
•• The somatosensory-evoked potentials (SEPs) are obtained by multiple
electrical stimulations of peripheral nerves.
•• The electrical signals generated are measured at the level of the peripheral
nerves (over the brachial plexus or popliteal fossa), spinal cord (lumbar as
well as high cervical), and cortex (scalp).
•• These recordings are made over the scalp and skin on the neck and the
back (over the spinous processes of the vertebrae) to monitor these signals
in the cortex and the spinal cord.
•• This method relies mostly on the stimulation of the large myelinated
somatosensory fibres, which transmit the impulses to the spinal cord by
the posterior column system.
•• Median nerve stimulation at the wrist or posterior tibial nerve stimulation at
the popliteal fossa or medial malleolus (ankle) is commonly used.
•• Electrode sites on the scalp are marked using the 10−20 international
system (Figs 1A and B). The recording sites preferred by the authors are
C3, C4, CZ, FPZ, FZ, A1 and A2.
•• The recommended stimulus is a monophasic pulse of 10−20 mA and 100
µs duration.
•• The stimulus is applied to the median nerve at the wrist or the posterior tibial
nerve at the ankle near the site where the nerve passes posterior to the
medial malleolus. Spinal cord intra-operative SEP monitoring often involves
the posterior tibial nerve; but, when surgery is above the eighth cervical
spinal cord level, then median nerve intraoperative SEP monitoring is used.
Role of Somatosensory-evoked Potential in
Neurosurgical Diseases
•• Disorders of the peripheral nerves
•• Plexus lesion
•• Radiculopathy
•• Thoracic outlet syndrome
•• Cervical myeloradiculopathy
•• Malingering
•• Intraoperative assessment of the functional integrity of neural pathways.
7
Figs 1A and B: (A) Actual representative areas of the brain in the 10–20
system. (B) Landmarks and measurements of the 10–20 system
Disorders Associated with Unrecordable

Intraoperative SEPs Include
•• The most frequent conditions leading to the problem of poor data acquisition
are neural tube defects and severe spastic quadriparesis with atrophy of
the lower extremities.
•• Sequelae of spinal cord trauma
•• Advanced spondylosis with myelopathy
•• Scoliosis with myelopathy
•• Peripheral neuropathy
•• Spinal cord tumour.
BRAINSTEM AUDITORY- EVOKED POTENTIALS

Brainstem auditory-evoked potentials (BAEPs) are elicited by monaural
stimulation with repetitive clicks and are recorded between the vertex of the
scalp and the mastoid process or earlobe (Fig. 2).
The presence, latency and interpeak latency of the first five positive
potentials recorded at the vertex are evaluated.
Brainstem Auditory-evoked Potential Wave Generators

Wave I : Distal acoustic nerve
Wave II : Proximal acoustic nerve/cochlear nucleus
Wave III : Superior olivary complex at the level of the lower pons
8
Fig. 2: Normal brainstem auditory-evoked potential wave
Wave IV : Lateral lemniscus

Wave V : Inferior colliculus or upper pons
•• The findings are helpful in screening for acoustic neuromas, detecting
brainstem pathology and evaluating comatose patients.
•• The BAEPs are normal in coma due to metabolic/toxic disorders or
bihemispheric disease, but abnormal in the presence of brainstem
pathology.
•• Intraoperative BAEP monitoring has been shown to be useful for
preservation of hearing and vestibular nerve function during the resection
of acoustic neuroma and other posterior fossa surgeries.
•• The types of surgeries in which BAEPs are also used include posterior
fossa and petroclival skull-base tumours, arteriovenous malformations,
aneurysms and decompressive procedures in patients with Chiari
malformation.
The BAEP changes seen during surgery can be divided into three types:
•• Type 1: Gradual and persistent prolongation of the waveforms of 1 ms or
more. Postoperative type 1 BAEP abnormalities are not accompanied by
clinically significant hearing deficits, but careful audiological testing may
reveal some minor hearing loss.
•• Type 2: When there is a sudden loss of wave I through wave V ipsilateral to
the side of the surgery without return to the baseline. Hearing impairment is
often observed postoperatively on the same side of the surgery when type
2 changes are seen during surgery.
•• Type 3: When the contralateral BAEP waveforms become abnormal during
posterior fossa surgery, the prognosis is poor. Type 3 changes are often
associated with other signs of brainstem dysfunction.
VISUAL EVOKED POTENTIALS

•• The visual evoked potential (VEP) is an evoked electrophysiological
potential that can be extracted using signal averaging from the
electroencephalographic activity recorded at the scalp.
•• The VEP can provide important diagnostic information regarding the
functional integrity of the visual system.
•• Elicited by monocular stimulation with a reversing checkerboard pattern,
they are recorded from the occipital region in the midline and on either
side of the scalp.
•• The VEP peak latency, amplitude and waveform are age-dependent.
9
Fig. 3: Normal pattern of reversal visual evoked potential
•• The VEP peak latency refers to the term implicit time used to describe the
time from the stimulus to the maximum deflection of electroretinograms. The
VEP peak latency may also be referred to as ‘time to peak’ or ‘peak time’.
•• The component of major clinical importance is the so-called P100 response,
a positive peak having a latency of approximately 100 ms. (Fig. 3).
•• The VEPs are most useful in detecting dysfunction of the visual pathways
anterior to the optic chiasm.
•• In patients with acute severe optic neuritis, the P100 is frequently lost or
grossly attenuated.
•• The VEP findings are, therefore, helpful in indicating previous or subclinical
optic neuritis.
•• They may also be abnormal with ocular abnormalities and with other causes
of optic nerve disease such as ischaemia or compression by a tumour.
•• Normal VEPs may be elicited by flash stimuli in patients with cortical blindness.
CARPAL TUNNEL SYNDROME

Aim of nerve conduction study (NCS) and EMG:
•• To demonstrate a distal lesion of the median nerve.
•• To exclude other peripheral conditions that can result in similar symptoms
like high median neuropathy, C6-C7 radiculopathy, lesions of the brachial
plexus or even polyneuropathy.
•• To assess severity of carpal tunnel syndrome (CTS) and for therapeutic
decisions.
•• Baseline to assess the outcome after intervention.
Electrodiagnostic Grading of Carpal Tunnel Syndrome
Grade 1: Very mild CTS—normal standard tests, abnormal comparative tests.
Grade 2: Mild CTS—abnormal sensory with a normal motor response.
Grade 3: Moderate CTS—abnormal median sensory and motor response.
Grade 4: Severe CTS—absence of sensory response, abnormal distal motor
latency.
Grade 5: Extreme CTS—absence of median motor and sensory responses.
Electrophysiological Findings
Sensory Latency
•• Most important, most sensitive and earliest indicator of CTS is prolonged
sensory latency.
•• May show diminished amplitude and is often absent.
•• Latencies of 1−2 ms are considered mild, whereas latencies of more than
6 ms are considered severe.
10
Distal Motor Latency

•• Prolonged, but is not as sensitive an indicator as sensory latency.
•• Motor latency abnormalities tend to occur later in the course of the disease.
•• Latencies of 1−2 ms are considered mild, whereas latencies of more than
6 ms are considered severe.
Postoperative Changes
•• There is an immediate increase in motor conduction velocity following
release of the carpal tunnel.
•• After one week, this value decreases to an intermediate value and then
gradually returns to normal in the next 8−12 weeks.
Criteria for the Electrodiagnostic Evaluation of

Unilateral Neurogenic Thoracic Outlet Syndrome
All three of the following criteria must be found in the affected limb:
•• Amplitude of median motor response is reduced.
•• Amplitude of ulnar sensory response is reduced.
•• EMG evidence of denervation in muscles innervated by the lower trunk of
the brachial plexus.
ACOUSTIC NEUROMA
•• The results of pre-operative brainstem auditory-evoked response (BAER)
studies were useful in predicting the outcome of hearing preservation
attempts.
•• Patients with intact BAER waveform morphology and normal or delayed
latencies had a higher probability of hearing preservation in comparison
to those with abnormal pre-operative BAER morphology.
•• A characteristic finding on ABR in a person with an acoustic neuroma would be
a wave I with nothing after it—no waves 3 or 5 (10−20% of cases). A wave I−III
interval delay is common, and a wave V delay occurs in 40−60% of cases.
ELECTROENCEPHALOGRAPHY
•• The electroencephalogram (EEG) was developed by the German
psychiatrist, Hans Berger, in 1929.
•• The EEG continues to play a central role in the diagnosis and management
of patients with seizure disorders.
•• The electroencephalograph records spontaneous electrical activity
generated in the cerebral cortex.
•• This activity reflects the electrical currents that flow in the extracellular
spaces of the brain, and these reflect the summated effects of innumerable
excitatory and inhibitory synaptic potentials upon cortical neurons.
•• This spontaneous activity of cortical neurons is influenced and synchronised
by subcortical structures, particularly the thalamus and upper brainstem
reticular formation.
•• Afferent impulses from these deep structures are probably responsible for
entraining cortical neurons to produce characteristic rhythmic brain wave
patterns such as alpha rhythm and sleep spindles.
•• The EEG provides confirmation of Hughlings Jackson’s concept of
epilepsy—that it represents a recurrent, sudden, excessive discharge of
cortical neurons; but like other ancillary tests, it must be used in conjunction
with clinical data.
11
Applications of EEG
Diagnosis of Epilepsy
•• Differential diagnosis of paroxysmal neurological events.
•• Distinction between a focal and generalised seizure disorder.
•• Identification of specific epilepsy syndromes.
•• Recognition of photosensitivity and reflex epilepsies.
Management of Epilepsy
•• Assessing risk of recurrence after an unprovoked seizure.
•• Selection of antiepileptic treatment.
•• Likelihood of seizure relapse if medication is withdrawn.
•• Identification of irritative zone in epilepsy surgery candidates.
•• Investigation of cognitive decline, especially when rapidly progressive.
•• Monitoring in the management of status epilepticus.
•• Detection of non-convulsive status.
Indications for Video-electroencephalography Monitoring
•• Identification of epileptic paroxysmal electrographic and/or behavioural
abnormalities.
•• Verification of the epileptic nature of the new “spells” in a patient with
previously documented and controlled seizures.
•• Classification of clinical seizure type(s) in a patient with documented but
poorly characterised epilepsy.
•• Characterisation (lateralisation, localisation, distribution) of EEG abnormali-
ties, both ictal and interictal, associated with seizure disorders.
•• Quantification of the number or frequency of seizures and/or interictal
discharges and their relationship to naturally occurring events or cycles.
Quantitative documentation of the EEG response (ictal and interictal) to a
therapeutic intervention or modification (e.g. drug alteration).
Partial Seizures
•• Partial seizures, in scalp EEGs, are metamorphic, i.e. they show two or
more distinct phases.
•• The most common patterns consist of a series of rhythmic waves, sequential
spikes/sharp waves, a mixture of spikes and rhythmic waves or regional
voltage attenuation.
•• Most often the initial frequency of temporal lobe seizures is in the alpha
or theta range with slower frequencies occurring in a lesser proportion.
•• Extratemporal seizures, however, often start in the beta frequencies rather
than slower frequencies.
•• Focal electrodecremental events are of excellent localising value, reflecting
intense neuronal depolarisation or high-frequency firing.
•• It is important to recognise that simple partial seizures, especially those
with sensory rather than motor symptoms, may not be associated with
discernable changes in routine scalp EEG in up to 80% of patients.
Generalised Seizures
•• Typical absence seizures are characterised by isomorphic and stereotyped
patterns that do not evolve as partial seizures. However, the spike-wave
discharges may change from 3.5 or 4 Hz at the onset to 2 or 3 Hz as the
seizure progresses. Also, the spike amplitude may decrease during the
later part of the seizure.
12
•• Atypical absence attacks frequently show gradual onset and offset with
spike-wave discharges occurring at frequencies less than 3 Hz.
•• Generalised tonic-clonic seizures may be preceded by diffuse polyspike-wave
complexes. Ictal recordings during the tonic phase typically show generalised
attenuation with or without high-frequency rhythmic waves that gradually
increase in voltage (“epileptic recruiting rhythm”) and evolve into polyspikes
•• Myoclonic seizures are associated with 10−15 Hz polyspikes with or without
slow waves, whereas tonic seizures show generalised paroxysmal fast
activity or diffuse voltage attenuation preceded or followed by sharp and
slow wave complexes.
•• Generalised atonic seizures may show 2−3 Hz spike-wave discharges or
may not be associated with any scalp EEG change.
ELECTROCORTICOGRAPHY
•• This is a technique of placing grids or strips directly on the brain for
recording EEG activity to localise the epileptogenic focus during surgery
for epilepsy.
•• Electrocorticography (ECoG) along with cortical stimulation mapping was
first described by Penfield in 1939.
•• The hypothesis for successful epilepsy surgery is based on the principle
that removal of both lesional as well as the surrounding epileptogenic area
is necessary for achieving seizure freedom. For greater precision, either
intraoperative or extraoperative, subdural ECoG is often used to guide
surgical resection of both the lesion and the epileptogenic zone.
•• The area of interictal spiking or the irritative zone is often wider than the
ictal onset zone (area where the seizure originates) which is considered
as a gold standard for localising the epileptogenic zone.
•• Intraoperative ECoG is widely utilised for electrical mapping of the
epileptogenic zone during epilepsy surgery. It is useful to delineate the
margins of the epileptogenic zone, guides the surgeon in achieving
resection and is also of value to evaluate the completeness of resection.
•• It has been found to be particularly useful in resective surgeries of
neocortical foci (especially developmental lesions like cortical dysplasias)
and for tailored resections in hippocampal sclerosis. The ECoG can be a
valuable tool during multiple subpial transections (MST).
The obvious advantages of intraoperative ECoG are:
•• They allow placement of recording and stimulation electrodes.
•• Recordings can be performed before and after each stage of resection to
assess the completeness of surgery.
•• It allows direct electrical stimulation of the brain so that the regions involved
in functions may be spared by the resection (e.g. eloquent cortex).
•• No risks associated with long-term placement, e.g. infection.
The major limitations of ECoG are:
•• The limited sampling time.
•• Spontaneous epileptiform activity consists exclusively of interictal spikes
and sharp waves, and seizures are rarely recorded. Thus, in most of
the cases, localisation of the ictal focus is based on a hypothesis that it
corresponds to the interictal activity, which is yet to be proven.
•• It is difficult to distinguish primary ED from secondarily propagated
discharges arising at a distant epileptogenic site.
•• Both the background activity and the ED may be altered by the anaesthetics,
narcotic analgesics and by the surgery itself.
2
CHAPTER
Intracranial Pressure
Ravi Ramamurthi  Nigel Peter Symss
HISTORY
•• Quincke, in 1891, first reported the measurement of intracranial pressure
through the lumbar route.
•• Later studies by Quickenstedt, Ayala and Ayer established the range of
normal ICP and demonstrated the effect of changes in body position and
respiration, especially the Valsalva manoeuvre.
•• Lundberg, in 1960, published his classic monograph on the continuous
recording of ICP using an indwelling intraventricular catheter in a large
series of 130 neurosurgical patients. He described three waveforms and
sought to correlate the clinical features with changes in the pressure wave
pattern.
•• However, it was not before the 1970s that ICP monitoring came to be
routinely used in clinical neurosurgery (Fig. 1).
ANATOMY AND PHYSIOLOGY

•• The cranium can be likened to a rigid sphere. The three main components
of this sphere are brain, blood and cerebrospinal fluid (CSF) occupying
1400 mL, 75 mL and 75 mL of space, respectively. The contents of the
intracranial space are bound by the dura and communicate with the spinal
canal through the foramen magnum.
•• Since the thick bones of the calvarium are essentially non-distensible,
the volume of the intracranial space is virtually constant regardless of
the pressure generated within it. Therefore, any change in the volume of
the brain causes a reciprocal change in the volume of other intracranial
components, i.e. either blood or CSF. This is the basis of the modified
Fig. 1: Diagrammatic representation of ICP monitoring. Figure showing

various methods of monitoring the ICP. (A) Intraventricular catheters.
(B) Intraparenchymal catheters. (C) Epidural catheters. (D) Subarachnoid bolt
14
Monro-Kellie doctrine introduced into neurosurgery by Cushing. However,

the Monro-Kellie doctrine does not hold true in infants because the skull
is not rigid.
•• The normal ICP is pulsatile due to the respiratory and cardiac cycle. The
cardiac pulsations are reflected in the ICP through pulsations of the choroid
plexus, and the cerebral and spinal arteries.
•• The variations in venous return and cardiac output with respiratory
excursions possibly account for changes in the ICP with the respiratory
cycle.
•• The normal CSF pressure measured through the lumbar route ranges from
50 to 200 mm of H2O in the lateral decubitus position. The amplitude of the
pressure wave can be as much as 5 cm of H2O due to the combined effect
of the cardiac and respiratory cycles.
•• As the ICP increases, the pulse pressure generally increases.
•• Lundberg described three pressure waves namely: A waves; B waves and
C waves (Fig. 2).
A Waves
•• A waves are pathological, there is a rapid rise in ICP up to 50−100 mmHg
followed by a variable period during which the ICP remains elevated
followed by a rapid fall to the baseline.
•• The A waves that persist for longer periods (usually 5−20 minutes) are
called plateau waves.
•• Smaller A waves termed “atypical” or “truncated” A waves, that often do
not exceed an elevation of 50 mmHg, are also clinically important early
indicators of neurological deterioration.
•• The A waves are accompanied by clinical features of raised ICP, e.g.
headache, vomiting, decerebrate posturing, pupillary changes, bradycardia
and hypertension, and respond to CSF drainage, hyperventilation and
osmotic diuretics.
B Waves
•• Occur at the rate of 0.2−2 per minute and are related to respiration.
•• B waves may be vasomotor in origin. Lundberg initially described them
in patients with intracranial hypertension, though they can also occur in
normal individuals.
•• B waves are said to be one of the best predictors of outcome after surgery
for normal pressure hydrocephalus.
Fig. 2: Lundberg’s CSF pressure waves

Chapter 2 • Intracranial Pressure
15
C Waves
•• These are of low amplitude with a frequency of 4−8 per minute. These
waves are thought to be related to Traube-Hering-Mayer waves.
•• These waves are of little clinical significance.
•• Increased ICP is indicated by a sustained elevation in pressure above
15 mmHg or when intermittent A or B waves are recorded.
VOLUME-PRESSURE RELATIONSHIP
•• The cranium being rigid and non-distensible, any increase in the volume
of a component would be accompanied by a reciprocal decrease in the
volume of the other two components. Once the volume buffering capacity
is exhausted, the ICP would begin to rise.
•• During gradual expansion of a mass lesion, the volume displaced may be
CSF, intravascular blood or brain tissue water. Of the three components,
CSF appears to be the main buffer and is the first to be displaced as
evidenced by compressed ventricles and obliterated subarachnoid spaces.
•• The rate of expansion of an intracranial mass is also important. A rapidly
growing intracranial mass lesion may outpace the compensatory shift
of CSF and then even the smallest increase in mass could produce a
life-threatening increase in ICP. Thus, a large haematoma could be
accommodated within a few hours without a dangerous rise in ICP.
•• Langfitt et al. studied the volume-pressure relationship in the rhesus
monkey (Fig. 3). The flat portion of the curve was termed the period of
spatial compensation, and the vertical portion was called the period of
spatial decompensation. The curve may shift to the left if the intracranial
mass expands very rapidly or if there is a pre-existing pathology in the
brain reducing the amount of displaceable volume. The classical pressure-
volume curve is exponential. In a semi-logarithmic co-ordinate system, the
curve would be linear.
•• Various mathematical models have been described to define the volume-
pressure relationship (Fig. 4).
•• Compliance is defined as change in volume per unit change in pressure
(dV/dP). It is a measure of the distensibility of the intracranial space. The
higher the compliance, the larger is the extra volume that the cranium can
accommodate without a precipitous rise in pressure.
Fig. 3: The lineal relationship between the volume and the pressure semi-
logarithmic co-ordinate systems
16
Fig. 4: Intracranial volume-pressure relationship. Note that the elastance at

point ‘a1’ is more than at point ‘a’
•• Elastance is inversely related to compliance (dP/dV). It is a measure of

the resistance offered to an expanding intracranial mass. The slope of the
volume-pressure curve is the elastance.
•• In the horizontal limb of the volume-pressure curve, compliance is high
and the elastance is low, while in the vertical limb, compliance is low and
the elastance is high.
PATHOLOGY OF INCREASED
INTRACRANIAL PRESSURE
•• Intracranial hypertension can lead to secondary changes by interfering
with the cerebral blood flow (CBF) and by producing brain herniation and
pressure on critical structures.
•• The average normal CBF is 50 mL/100 g/min. Ischaemic changes can
develop when the CBF drops to 20 mL/100 g/min.
•• The ICP influences the CBF through changes in the cerebral perfusion
pressure (CPP).
•• The CPP is defined as the difference between mean arterial pressure (MAP)
and ICP, i.e. CPP = MAP – ICP. A rise in ICP would lead to a fall in CPP
unless buffered by a rise in MAP.
•• ICP and CPP monitoring are important in the management of head injury
patients. However, there are other brain-related measures defined as
‘pressures’, such as cerebral intratissue pressure, critical closing pressure,
‘optimal’ CPP, non-invasive CPP (nCPP) and noninvasive ICP (nICP), and
interhemispherical pressure gradients, which currently draw more attention
in the management of head-injured patients.
•• Raised ICP can cause arterial hypertension (the Cushing response),
bradycardia and respiratory changes.
Intracranial Pressure Monitoring

•• ICP monitoring has extensively been used in patients with head injury.
It is most useful in neurologically stable (GCS 9 or more) patients with
a traumatic intracranial haematoma, in whom the decision to surgically
evacuate the haematoma is equivocal. A patient with persistently high ICP
or a progressively rising ICP not responding to decongestants would merit
surgical intervention.
Chapter 2 • Intracranial Pressure
17
•• The current Brain Trauma Foundation recommendation of ICP monitoring

in those patients presenting with a GCS score <8 with an abnormal CT
scan or a normal CT scan with age >40 years, systolic blood pressure <90
mmHg or exhibiting posturing should be followed.
•• Some neurosurgical centres monitor ICP in patients with aneurysmal
subarachnoid haemorrhage (SAH).
•• Continuous ICP monitoring in patients with suspected arrested
hydrocephalus and normal pressure hydrocephalus can help to choose
patients who may benefit from a CSF diversionary procedure.
•• Neurosurgical patients who are paralysed and are being electively ventilated
in the postoperative period should undergo ICP monitoring. Even in patients
who are not being artificially ventilated, postoperative ICP monitoring can
be beneficial if the haemostasis was difficult or the brain was not lax at
the end of surgery.
•• Contraindications to ICP monitoring include widespread scalp infection,
any intracranial infection, open compound injury and bleeding diathesis.
Monitoring Systems
Monitoring systems can be divided into:
Fluid coupled system: It involves a fluid-filled catheter or a hollow bolt placed
in the ventricle, subarachnoid space or the subdural space, connected to a
pressure transducer through a fluid-filled line. The transducer converts the
hydraulic pressure into an electrical signal which can be displayed digitally
or on an oscilloscope.
Non-fluid coupled systems: In this, the transducer is mounted on the moni-
toring device itself. The monitoring devices have variously been designed for
use in the ventricle, brain parenchyma, subdural and epidural space. This de-
sign has the advantage of being solid state and can be used in the ventricle,
parenchyma or in the subdural space.
The telemetric system consists of an implanted transducer which is
telemetered through the intact scalp. This system should particularly be useful
for long-term ambulatory monitoring.
1. Epidural monitoring: This is performed by placing the device in the epi-
dural space via a burr hole. These are simple to insert with a low infection
rate. It is relatively safe in conditions, like fulminant hepatic failure, where
haemostatic abnormalities may coexist and insertion of a parenchymal or
ventricular device could be dangerous.
2. Subarachnoid and subdural devices: The subarachnoid and subdural
devices are similar. The most commonly used devices for fluid coupled
subdural pressure monitoring are the hollow screw or bolt devices, the
“subdural cap catheter” and simple catheters placed in the subdural space.
Intracranial pressure can also be measured from a subarachnoid catheter.
The use of the Camino fibreoptic subdural device for the measurement
of ICP in patients has been found comparable with recordings from the
intraventricular fluid-filled catheter.
3. Parenchymal monitoring: This has become popular in some centres since
the availability of non-fluid-filled devices, like the fibreoptic system and the
piezoresistive microtransducers which can easily and safely be implanted
into the brain parenchyma.
18
Parenchymal monitoring has been useful in patients with small ventricles

or large shifts, in large craniectomies or open compound injuries with dural
loss where placement of an epidural or subdural device may be difficult.
4. Intraventricular monitoring: This remains one of the most popular
techniques and is probably the procedure of choice in patients with ven-
triculomegaly.
•• It is very accurate, and is the current gold standard against which other
methods are compared.
•• A variety of sets are available commercially, but basically they all consist of
a ventricular catheter which is fluid coupled to a strain gauge transducer.
•• The placement of the catheter is simple and the standard landmarks for
a ventricular tap are followed. It is usually placed in the frontal horn and
tunnelled from its site of exit from the skull to the point of exit from the
scalp. Placement of the catheter is verified by the drainage of fluid and an
adequate waveform on the monitor.
•• It offers the added advantage of therapeutic drainage of CSF to lower the
ICP, and can also be used to perform CSF dynamic studies.
•• The major disadvantage is that it may be difficult to insert in patients with
small ventricles or significant shifts. The risk of infection varies from 8% at
5 days to 40% at 12 days. Intracranial hemorrhage can occur. The failure
rate is considerably lower than with the subarachnoid bolt.
•• ICP monitoring from the operative cavity in the posterior fossa using a fluid-
filled catheter is safer and more accurate than supratentorial monitoring
after posterior fossa surgery. It also has the added advantage of allowing
drainage of CSF or collected blood whenever required.
3
CHAPTER
Neuro-ophthalmology
Tandon R  Saxena R  Phuljhele S
EFFECTS OF BRAIN TUMOURS ON

VISUAL PATHWAYS
Direct effects:
•• Direct compression.
Indirect effects: Papilloedema
•• Impact of tumour resection
•• Post-radiation neuropathy
•• Toxic effects due to chemotherapy
•• Metastatic lesions to retina or infiltration of optic nerve
•• Haematological effects like ischemia, venous engorgement.
THE NORMAL FIELD OF VISION

•• The visual field is a three-dimensional area which is visible through each
eye when fixating at a central target.
•• The field of vision is centred at a fixation point of each eye, as an asymmetric
oval shape extending maximally on the temporal side for about 90 degrees.
•• The superior and inferior fields have an extension of 40 and 60 degrees,
respectively. Nasally it is restricted by the nasal bridge and measures up
to 40 degrees.
•• There is binocular representation of the visual fields for 60 degrees to the
right and left of a common fixation point.
THE NORMAL VISUAL PATHWAY

•• The visual pathway begins with stimulation of photoreceptors of the retina
and processing in the ganglion cells. The axons of the ganglion cells
converge to form the optic nerve.
•• The nerve then travels through the optic canal and emerges in the
intracranial cavity at the sellar region. At this juncture, the nasal fibres of
the optic nerve cross to form the optic chiasm. The contralateral nasal fibres
and ipsilateral temporal fibres continue together as the optic tract, which
provides for one-half of the binocular visual field.
•• The optic tract is relayed in the ipsilateral lateral geniculate body (LGB)
where sorting of fibres occurs.
•• The third order neurons commence from the LGB and continue as the optic
radiation that terminates in the visual cortex (area 17) of the occipital lobe
(Fig. 1).
20
Fig. 1: Visual pathway
ASSESSMENT OF VISUAL FIELD

•• The process of estimating and mapping the field of vision is called perimetry.
The field of vision of a patient can be assessed by various methods;
the easiest and convenient for bed-side examination is confrontation
examination. This is a crude and subjective evaluation, wherein the
examiner compares the visual field of the patient to his own field of vision.
•• More sophisticated methods used routinely in clinical practice include
Goldmann perimetry and automated perimetry, which are objective and,
hence, more reliable methods. These techniques can precisely map and
record the peripheral (full extent) as well as central (central 30°) field of
vision, respectively.
INTERPRETATION OF VISUAL FIELD

Terminologies
Isopter: It is a line joining the retinal points of the same sensitivity.
Constriction: It implies that there is generalised decrease in sensitivity of
the retina and, on kinetic perimetry, it encloses a smaller area than normal.
Hemianopia: When one-half of the visual field is involved either in one or
both the eyes.
Homonymous: When the defects are present in the visual fields of both the
eyes and are on the same side of the vertical meridian.
Heteronymous: When the defects are present in the visual fields of both the
eyes but are on the opposite sides of the vertical meridian.
Scotoma: It is a localised area of decreased sensitivity. It may be absolute,
when the patient cannot see even the brightest possible stimulus or it may be
relative if some of the stimuli are seen. They can be classified either by their
location or by shape.
Congruency: The extent to which the homonymous field defect in one eye
resembles that in the other eye in terms of shape, size, depth and slope of
the margins.
Chapter 3 • Neuro-ophthalmology
21
Table 1: Visual field defects according to the location of the tumour

Location of tumours Structure involved Type of field defect
Orbit
• Optic nerve glioma • Optic nerve Total field loss (early lesions
may present with central or
• Optic nerve meningioma centrocecal field defect)
Sella
• Pituitary adenoma • Chiasma • Bitemporal field defect
• Craniopharyngioma • Chiasma • Bitemporal field defect
• Meningioma • Willebrand’s knee • Junctional scotoma
• Optic tract • Homonymous hemianopia
(macular splitting)
Mid brain
• Craniopharyngioma
• Meningioma
• Large pituitary adenoma
• Aneurysms
• Hamartomas • Lateral geniculate body • Sectoral defects
Parietal lobe
• Meningiomas • Superior part of optic • Inferior quadrantic field
• Gliomas radiation defect
• Metastasis • Homonymous hemianopia
• Vascular (macular splitting)
Temporal lobe
• Gliomas • Inferior part of optic • Superior quadrantic field
• Metastasis radiation defect (usually incongru-
• Vascular ous in nature)
Visual cortex
• Gliomas • Occipital lobe • Homonymous hemianopia
• Meningiomas sparing macula. (Complete
• Metastasis or partial depending upon
• Vascular the size of the tumour)
VISUAL FIELD DEFECTS

•• The arrangement of visual fibres in a particular region of the visual pathway
determines the characteristics and shape of visual field defects.
•• In general, lesions anterior to the optic chiasma produce monocular defects,
while lesions affecting the chiasma and beyond are always bilateral.
•• Heteronymous defects are seen in chiasmal lesions, while all lesions affecting
the visual pathway beyond the chiasma produce homonymous lesions.
•• The more posterior a lesion is in the visual pathway, the more congruent
field defect it will produce. For example, a lesion of the occipital lobe will
produce a more congruent field defect than that of the optic tract.
Retina
•• The visual field and the retina have an inverted and reversed relationship.
Thus, light rays from the temporal visual field stimulate the ganglion cells
of the nasal retina. The axons of these ganglion cells form the nerve fibre
layer and finally converge at the optic nerve head and exit as the optic nerve.
•• The innermost layer of the retina, retinal nerve fibre layer (RNFL) bundles
converge in a specific pattern to form the optic nerve head.
•• The macular fibres are centrally placed, while fibres from the upper part of
the retina lie superiorly and those from the lower retina are placed inferiorly
in the optic nerve.
22
•• The layer of the retina that is affected by the disease process determines
the pattern of field defect. Lesions in the outer retina have no particular
definite boundaries, so they can produce field defects of varying shapes and
sizes, while involvement of the RNFL produces a field defect corresponding
to the particular pattern of the nerve fibre bundle affected.
•• Papillomacular bundle involvement results in a central scotoma,
centrocecal scotoma or paracentral scotoma.
•• Arcuate nerve fibre bundle lesions may cause a variety of field defects
like—Bjerrum or arcuate scotoma, Seidel scotoma, Nasal step of Ronne,
depending on the site of the lesion. Arcuate field defect is seen in many
conditions, apart from anterior optic nerve lesions (see the following box):
 Glaucoma
 Chorioretinal lesions
 Juxtapapillary choroiditis
 Myopia with peripapillary atrophy
 Central retinal artery occlusion
 Branch retinal artery occlusion
 Ophthalmic artery or carotid artery occlusion
 Drusen
 Optic nerve pit
 Chronic papilloedema
 Anterior optic nerve lesions
 Involvement of the nasal fibre bundle leads to temporal wedge-shaped defects.
Optic Nerve
•• The optic nerve is formed by the axons of retinal ganglion cells that
converge to form the nerve fibre bundles. It is about 50 mm in length and
can be divided into four parts: optic nerve head (intraocular part 1 mm),
intraorbital (25 mm), intracanalicular (10 mm) and intracranial (15 mm).
•• The above described arrangement of the nerve fibres is maintained
throughout the optic nerve, such that even lesions involving the posterior
part of the optic nerve produce a pattern corresponding to the nerve fibre
bundle involved (Fig. 2).
•• In addition to the field defects described above, the involvement of axons
at the superior or inferior pole of the optic disc produce altitudinal defects.
The Chiasma
•• It is formed by the crossing of the nasal fibres of each optic nerve. It is
located over the diaphragm sella and is posteriorly related to the wall of
the third ventricle.
•• In 80% located directly over the sella
(central); in such cases, pituitary
lesions involve the chiasma first. In
about 10%, it is located more an-
teriorly over the tuberculum sellae
(prefixed); here pituitary lesions will
involve the optic tract first. In the
remaining 10% of cases, it is located
more posteriorly over the dorsum
sella, where pituitary lesions involve Fig. 2: Arrangement of nerve
the optic nerve first. fibres in optic nerve
23
•• Anteriorly, the chiasma is related to the anterior cerebral arteries and their
communicating branches. Posteriorly, it is related to the hypophyseal
stalk and the pituitary body. It is immediately inferior to the floor of the
third ventricle and lies above the hypophysis. Laterally, it is related to the
internal carotid artery and the cavernous sinus.
•• At the chiasma, the fibres representing the nasal visual field (temporal
fibres) are present in the lateral part. The inferonasal fibres (superior
temporal field) cross anteriorly in the chiasma and loop forward into the
contralateral optic nerve, forming von Willebrand’s knee and then continue
in the contralateral optic tract. The nasal macular fibres decussate most
posteriorly. The upper nasal fibres (inferior temporal field) cross in the
middle (Fig. 3). Thus, the right optic tract constitutes the right nasal field
(right temporal axons) and the left temporal field (left nasal decussated
fibres) representing the left half of the visual space.
•• A patient presents with varying signs and symptoms, depending upon the
type, size and site of the lesion. Pituitary adenoma presents with signs of
compression of the visual pathways, as well as other features of hormonal
disturbance. There may be unilateral or bilateral loss of vision, as a result
of concurrent compression of the optic nerve by the tumour. Relative
afferent pupillary defect may be present in unilateral lesions. Lesions of the
cavernous sinus and large pituitary adenomas compress the motor nerves
of the eye, leading to ocular motility disorders. See-saw nystagmus and
oscillopsia are features of tumour or trauma.
•• Field Defects:
–– Bitemporal hemianopia: Lesions that affect the body of the chiasma
produce bitemporal hemianopia. Lesions of the pituitary gland, i.e.
tumours, inflammation or haemorrhage are the common conditions.
Inferior bitemporal hemianopia is characteristic of craniopharyngioma.
Saccular aneurysms of vessels in the circle of Willis can also lead to
bitemporal hemianopia.
–– Junctional scotoma: It is produced when a lesion involves the junc-
tion of the optic nerve and chiasma, leading to an optic nerve defect
in the ipsilateral eye and superior temporal (involvement of von Wille-
brand’s knee) defect in the contralateral eye.
–– Binasal field defects: A large mass lesion compressing one side of
the optic chiasma, on further enlargement, causes a midline shift of
the chiasma with subsequent compression of the other side as well,
leading to a binasal field loss presentation. This pattern of field loss
Fig. 3: Decussation of optic nerve fibres at the chiasma

24
can also be seen with empty sella syndrome (ESSD), arachnoiditis and
after surgery for pituitary tumours.
–– Homonymous hemianopia: This type of field defect is commonly
seen in cases where the chiasma is prefixed. Thus, any lesion which
affects the chiasma can also affect the optic tract, leading to homony-
mous hemianopia. Large pituitary adenomas and craniopharyngiomas
are the most common causes.
–– Lesions that affect the posterior part of the chiasma cause central
bitemporal hemianopia.
Optic Tract and Lateral Geniculate Body

•• The optic tract runs superiorly and posteriorly from the optic chiasma and
curves around the brainstem to terminate in the LGB. The LGB is a part of
the thalamus and is situated along the lateral aspect of the midbrain. Each
geniculate body consists of six layers of neurons and second order fibres,
travelling through the optic tract, are relayed in different layers of the LGB.
It receives dual blood supply from the anterior and lateral choroidal arteries,
which nourish the fibres from the superior and the inferior homonymous
quadrants of the retina, respectively. The optic tracts lie between the tuber
cinereum and the anterior perforated substance.
•• Each optic tract is formed by the temporal fibres of the ipsilateral eye and
the nasal fibres from the contralateral eye.
•• The axons from the ipsilateral eye are relayed in nuclei layers 2, 3 and 5,
while the axons from the contralateral side relay in 1, 4 and 6 nuclei layer.
The fibres from the upper part of the retina occupy the medial half of the
anterior one-third of the LGB. The lower retinal fibres occupy the lateral half
of the anterior one-third of the LGB, while the macular fibres are relayed in
the posterior two-third of the LGB.
•• The most useful sign of localising a lesion between the optic tract and
LGB is involvement of the pupil. Optic tract lesions are associated with
various pupillary abnormalities including RAPD on the contralateral side,
Wernicke’s hemianopic pupil and Behr’s pupil, while in lesions of the LGB,
pupillary reactions are spared.
•• Lesions affecting the optic tracts are craniopharyngiomas, meningiomas,
and large pituitary adenomas, demyelinating diseases, vascular lesions,
such as aneurysms, arteriovenous malformations and hamartomas.
•• Lesions affecting the LGB include infarction, tumours, trauma and
inflammatory disorders.
•• Complete optic tract disruption on one side leads to complete macular
splitting homonymous hemianopia, while partial involvement will cause
an incongruous field defect. Similarly, a defect in one LGB will produce
complete homonymous hemianopia, while partial lesions of the LGB cause
a sectoral field defect.
Optic Radiations
•• The optic radiations are geniculocalcarine pathways that extend from the
LGB to the visual cortex. They cross the Wernicke’s area as optic peduncles
and travel in the retrolenticular part of the internal capsule.
•• The fibres, after exiting from the LGB, rotate by 90 degrees again to regain
their original arrangement. Thus, the superior fibres lie in the upper part
of the radiation, the inferior fibres in the lower part and the macular fibres
lie in the centre.
25
Fig. 4: Arrangement of optic radiations

•• Arrangement of fibres in the temporal lobe: The inferior fibres from
the corresponding superior visual fields of both eyes commence from the
anterolateral part of the LGB, sweep anteriorly and then laterally along
the temporal horn of the lateral ventricle to form Meyer’s loop, then extend
posteriorly to end in the area below the calcarine fissure of the occipital
cortex (Fig. 4). The clinical features of temporal lobe lesions are seizures,
paragnosia, involuntary movement of the mouth, and visual and auditory
hallucinations. Aphasia is characteristic of left temporal lobe lesions. The
most common temporal lobe lesions are tumours, which include glioma
and metastasis. Surgical resection of the tumour (when more than 8 cm),
itself may produce field defects. Anterior choroidal artery occlusion may
affect the optic radiation in the temporal lobe and LGB. Other lesions are
trauma, demyelination and abscess.
•• Arrangement of fibres in the parietal lobe: The superior fibres that carry
the inferior field travel directly through the lower portions of the parietal
cortex to the occipital lobe area above the calcarine fissure (Fig. 4).
Clinical Features of Parietal Lobe Involvement
•• The two most important localising signs of a parietal lobe lesion are loss
of normal optokinetic response and conjugate deviation of the eyes. The
involvement of the right parietal lobe leads to deficit of spatial orientation
of the left space, thus the patient may neglect the left half of the body.
Involvement of the left parietal lobe is associated with Gerstmann’s
syndrome (agraphia, acalculia and visual agnosia). The differential
diagnosis of lesions involving the parietal lobe, include infarction,
haemorrhage, AVM and tumours.
•• Lesions involving the optic radiations produce field defects which are
homonymous and more congruous. The involvement of the anterior temporal
lobe will produce contralateral homonymous superior quadrantanopia. In
more extensive lesions, the defect may extend inferiorly but the hemianopia
will be denser superiorly. The defects are wedge shaped defects of varying
sizes and are homonymous and incongruous.
•• Lesions involving the parietal lobe produce an inferior homonymous field
defect that is classically described as pie on the floor. These defects are
usually more extensive and more congruous than temporal lobe defects.
The homonymous hemianopia of the parietal lobe is always associated with
macular splitting.
Visual Cortex
•• The primary visual cortex (area 17) is located on the medial surface of
the occipital lobe near the calcarine fissure. Brodmann’s area 18 and
26
19 are associated visual areas which help in further processing of visual

information.
•• The right visual cortex receives impulses from the left temporal field and the
right nasal field. The orientation of fibres in the optic radiation is maintained
in the visual cortex. The central field is represented at the occipital tip and
is separated from the representation of peripheral fibres. The superior
fibres (representing inferior field) are relayed in the area superior to the
calcarine fissure while the inferior fibres (superior field) are projected to
the area inferior to the fissure.
•• Occlusion of the left posterior cerebral artery causes infarction of the left
calcarine cortex, along with the splenium of the corpus callosum, which
produces field defects in the right side and alexia without agraphia. Other
signs include headache, visual agnosia and dyschromatopsia, which are
mainly secondary to the infarction. Tumours lead to isolated visual field
defects and palinopsia. Tumours affecting the occipital lobe are gliomas,
meningiomas and metastasis. Bilateral occipital disease is usually due
to vascular lesions which include thromboembolism, haemorrhage,
hyperviscosity syndromes and vasculitis. This is also a feature following
bilateral tentorial herniation, which results in bilateral occipital infarct
resulting in blindness.
•• Field Defects:
–– Occipital lobe lesions produce field defects that are homonymous and
highly congruous.
–– Complete homonymous hemianopia sparing the macula: The
macular area is a watershed zone of anastomoses between the mid-
dle and the posterior cerebral arteries. Ischaemia of the occipital lobe
results in sparing of the central 3–5 degrees of the visual field due to
its dual blood supply.
–– Central homonymous hemianopia: A lesion affecting the tip of the
occipital lobe would produce a field defect in the macular area which is
homonymous. In such cases, at least 5 degrees of the central field is
spared in both eyes on the side of hemianopia.
–– Quadrantic field defects: Lesions of the area below the calcarine
fissure would give rise to a homonymous superior quadrantic defect.
Similarly, a lesion involving the area above the calcarine fissure would
lead to an inferior homonymous defect.
Involvement of the occipital lobe bilaterally may lead to bilateral
homonymous hemianopia with sparing of central tubular vision. This should
be differentiated from other causes of constricted visual field like malingering,
glaucoma and retinitis pigmentosa.
SPECIAL VISUAL FIELD DEFECTS

Baring of Blind Spot
•• When a small degree of field is mapped, the isopter may be constricted
and any scotoma outside the isopter may be continuous with the blind spot
causing baring of the blind spot.
Binasal Hemianopia
•• They are bilateral nasal defects usually caused by involvement of arcuate
fibres of both eyes. Rarely, caused by pressure upon the temporal aspect of
the optic nerve or anterior portion of the chiasma, as in cases of aneurysm,
pituitary tumour and vascular infarction.
4
CHAPTER
Neuro-otology
Sathiya Murali  Srividya  Mohan Kameswaran  Kiran Natarajan
QUANTITATIVE TESTS FOR VESTIBULAR

FUNCTION
Electronystagmography
•• Electronystagmography (ENG) remains the most useful laboratory test
in the evaluation of patients with complaints of dizziness or vestibular
disturbance.
•• ENG can provide diagnostic information when there is a suspicion of
unilateral or bilateral vestibular hypofunction.
Electro-oculography
•• Electro-oculography (EOG) is typically used to record eye movements
during ENG testing based on the corneo-retinal potential (electrical charge
potential between cornea and retina).
•• The eye acts as an electrical dipole along its long axis. Movement of this
dipole relative to the surface electrodes produces an electrical signal
corresponding to eye position. Horizontal eye movements can typically be
resolved to an accuracy of 0.5°. The sensitivity of EOG is less than that of
direct visual inspection (approximately 0.1°).
•• Visual inspection of small amplitude eye movements directly or with
Frenzel’s lenses or an ophthalmoscope is important for documentation of
low amplitude nystagmus.
Video-oculography/Videonystagmography
•• Video-oculography (VOG) is infrared (IR) imaging analysis which uses
the conventional black and white camera. The eyes are illuminated with
IR light. Eyes are not reactive to IR light, and hence can be viewed while
in total darkness, thus eye fixation is eliminated. The eye movements are
recorded by an IR video camera and converted into a digital format through
software that documents the eye movements.
•• Horizontal and vertical tracings of eye movements are recorded by the
camera tracking the pupil of the eye.
•• Advantages of VOG include accuracy of 0.1–0.5°, contact free recording of
eye movements and ease of handling. Rotatory eye movements in benign
paroxysmal positional vertigo (BPPV) can be detected only in VOG.
•• Static tests include spontaneous nystagmus and gaze nystagmus.
Spontaneous nystagmus is suitable for recording non-evoked eye
movements with eyes closed and with eyes open.
28
Gaze Nystagmus
•• Here, the eye movements are measured while the patient is fixating on
a target.
•• Nystagmus caused by CNS lesions can be differentiated from that caused
by peripheral vestibular lesions.
•• CNS nystagmus may be horizontal, vertical or rotatory.
•• If horizontal, CNS nystagmus usually beats to the right in rightward gaze
and to the left on leftward gaze, and is usually not suppressed by ocular
fixation. This is in contrast to nystagmus caused by a peripheral lesion. Here
it is horizontal, always beats in one direction (usually toward the normal
side and suppressed by ocular fixation).
•• Nystagmus is named after the direction of the fast component which is the
corrective movement of the eyes generated by the CNS. The vestibular
system generates the slow phase of nystagmus which is directed to the
opposite side (Table 1).
DYNAMIC TESTING
Saccade Testing
•• The patient is instructed to fixate a series of randomly displayed dots or
lights at eccentricities of 5–30° saccades.
•• Saccades typically begin with a latency of 180–200 milliseconds after
presentation of a target. Saccade velocity increases linearly with amplitude
up to about 20° but remains relatively constant for higher amplitudes. Healthy
subjects consistently undershoot the target for saccades more than 20°.
•• Asymmetries in saccade amplitude or peak velocities can provide localising
information.
Smooth Pursuit
•• The patient is asked to watch a target that moves horizontally in a sinusoidal
fashion at a low frequency with position amplitude of 20° in each direction.
•• Inspection of the waveform of the tracking eye movement is often of greater
diagnostic use than absolute measure of gain and phase.
•• “Catch up’’ saccades are typically made when pursuit responses are decreased.
•• Saccadic pursuit is characterised by the occurrence of these saccades in a
“stair-step’’ pattern. Such patterns are seen in cerebellar disease and also
may occur with decreases in pursuit gain that occur with ageing.
Table 1: Features differentiating central from peripheral causes of vertigo

Features Central Peripheral
Imbalance Severe, mostly constant Mild to moderate, mostly
episodic
Neurologic symptoms Frequent Rare
Nystagmus Changes direction in different Unidirectional in all gaze
gaze positions positions
No change with visual fixation Decreases with visual fixation
Hearing loss Rare Frequent
Nausea Variable, may be absent Severe
Recovery by central Slow Rapid
compensation
Chapter 4 • Neuro-otology
29
•• Saccadic substitution of smooth pursuit is seen in neurological lesions.

•• Disorganisation of pursuit eye movements with wandering slowed inaccurate
tracking is seen in brainstem lesions.
Optokinetic Testing
•• Testing is often performed with the subject surrounded by a visual scene
that moves completely in one direction at velocities of 30–60° per second.
•• The optokinetic tracing response is a nystagmus in the plane of motion of
the visual scene.
•• Asymmetries in OKAN have been reported in patients with unilateral
vestibular hypofunction induced by removal of an acoustic neuroma and
other CNS lesions. Responses are greater in amplitude and longer in
duration for stimulus and eye movement toward the side of the lesion.
Caloric Testing
•• Caloric testing remains the most useful laboratory test in determining the
responsiveness of a labyrinth.
•• It is one of the few tests that allow one labyrinth to be studied independently
of the other.
•• Caloric testing relies on stimulating or cooling the vestibular system by
alternately heating and cooling the external auditory canal with water or air.
•• The horizontal canal is affected most by such temperature effects, because
it is located closest to the external auditory canal and is oriented in the
plane of the temperature gradient that is produced in the temporal bone
from irrigation with water.
•• Calorics cause a response in two ways. The first is a convective component,
with the temperature gradient across the horizontal canal resulting in a
density difference within the endolymph of the canal. When the horizontal
canal is oriented in the plane of gravity, the more dense fluid falls to the
lower position in the canal, whereas the less dense fluid moves to the upper
portion in the canal. In the presence of gravity, there is a flow of endolymph
from the cooler (more dense) region to the warmer (less dense) region. This
movement of fluid within the canal deflects the cupula, thereby leading to
a change in discharge rate of vestibular nerve afferents. Endolymph flows
toward the ampulla for warm irrigation and away from the ampulla for cold
irrigation. This effect depends on head position.
•• Alternate binaural caloric testing as pioneered by Fitzgerald and Hallpike
is the most commonly used testing protocol. Cool water (30°C) and warm
water (44°C) are administered for 60–90 seconds to each ear in a set order
such as right warm, left warm, right cold and left cold. Such a stimulus
results in heating effect in the temporal bone that lasts for 10–20 minutes.
•• Cold caloric test has been utilized to evaluate brain stem function in
comatose patients and for diagnosis of brain death.
Rotatory Chair
•• Unlike caloric tests, rotational tests analyse the responses of both labyrinths
together.
•• Rotatory chair testing is useful in assessing vestibular function in patients
with suspected bilateral vestibular hypofunction, in patients receiving
vestibulotoxic medications and in children who may not tolerate caloric
testing.
30
•• Cerebellar abnormalities produce specific changes that can be evaluated

with rotatory chair testing.
Vestibular Evoked Myogenic Potentials

•• Vestibular evoked myogenic potentials (VEMP) is a sound-evoked muscle
reflex, or sonomotor response that can be recorded using evoked potential
techniques by acoustical stimulation of the saccule.
•• VEMP has become an important investigative modality in the evaluation
of patients with balance disorders.
•• The responses are abolished on the side of surgery after unilateral
vestibular neurectomy.
•• VEMP may be absent in basilar artery migraine, Ménière’s disease,
idiopathic bilateral vestibulopathy (IBV) and vestibular schwannoma.
•• VEMP may be increased in superior semicircular canal dehiscence
syndrome and perilymphatic fistula.
•• Asymmetrical amplitudes may be seen in Tullio’s phenomenon and
spasmodic torticollis. Delayed VEMP is seen in cases of technical error,
central lesions like brainstem stroke, multiple sclerosis, spinocerebellar
degeneration and migraine.
Computerised Dynamic Posturography

•• Computerised dynamic posturography (CDP) is a series of vestibulo-spinal
tests for quantitatively assessing balance function in different set-ups which
simulate conditions encountered in our day-to-day life.
•• CDP tests the two faculties of the balance system separately. The first
portion is tested by the sensory organisation test (SOT) and the second
portion by motor coordination test (MCT).
•• The functional integrity of the sensory system (i.e. the inputs to the balance
system, viz. the visual, proprioceptive and vestibular) is assessed by the
SOT. This test detects any defect in the subject’s ability to effectively use
the somatosensory/visual/vestibular inputs to maintain balance and the
ability of the CNS to select the appropriate input when contradictory and
conflicting information is sent through these three input systems.
•• The second part of the CDP test is the Motor Coordination Test or Motor
Control Test (MCT). It is useful in assessing the integrity of efferent motor
pathways in the control of balance.
Cranio-corpography
•• Cranio-corpography (CCG) basically consists of photographically recording
the patient’s head and body movements as he or she performs the
Unterberger’s stepping test and the Romberg’s test.
•• CCG is a very quick, non-invasive and very simple objective test of
vestibular and balance functions.
•• It is totally physiological, easily repeatable and provides a photographic
and quantifiable record, and can even be done in children and in patients
with perforated ear drums.
INVESTIGATIONS FOR THE AUDITORY SYSTEM

•• Puret one audiogram
•• Impedance audiometry.
31
•• Electrophysiological tests:
– Otoacoustic emissions (OAE)
– Electrocochleography (ECoG)
– Auditory brainstem response (ABR)
– Auditory steady state response (ASSR)
– Middle latency responses (MLR)
– Long latency response (LLR).
Pure Tone Audiogram

•• Pure tone audiogram is a subjective test, which is used to detect if there
is definite hearing loss, its type (sensorineural/conductive) and degree of
the hearing loss.
•• It helps in measurement of hearing threshold at various frequencies.
•• The disadvantages of the test are that it is purely subjective, cannot be
performed in a child, a patient who is not co-operative and in unconscious
patients.
Impedance Audiometry
•• Impedance audiometry has been one of the major advancements in the
field of otology and neuro-otology in recent times.
•• The uses of impedance can briefly be summarised as:
–– Objective differentiation between conductive and sensorineural hear-
ing loss.
–– Measurement of middle ear pressure (tympanometry) and evaluation
of Eustachian tube function.
–– Differential diagnosis of whether the lesion is cochlear or retrocochlear.
–– Identification of site of lesion in facial palsy and certain brainstem pa-
thologies (stapedial reflex test).
ELECTROPHYSIOLOGICAL TESTS
Otoacoustic Emissions
•• Otoacoustic emissions (OAE) are biological sounds from the normal
cochlea. This sound is generated in the outer hair cells of the cochlea.
•• This is another objective test for hearing screening in neonates and young
children which has now become popular.
Electrocochleography
•• Electrocochleography (ECoG) is a short latency evoked potential that
reflects the summed activity of a large number of peripheral auditory nerve
fibres as well as the response of generators located within the cochlea itself.
•• The ECoG consists of three distinct evoked potentials:
1. The cochlear microphonic (CM)
2. The summating potential (SP)
3. Compound action potential (AP)
•• The CM and the SP are both intracellular potentials.
•• The CM is a potential that mirrors the stimulus and it reflects the
instantaneous displacement of the basilar membrane.
•• The SP is characterised by a baseline shift in the CM and it is also thought
to originate from within the hair cells of the organ of Corti.
32
•• The AP is the third evoked potential of the ECoG complex. It is a recording

of the synchronous response of a large number of auditory nerve fibres to
the acoustic stimulation.
•• The ECoG is recorded either extratympanically or intratympanically. It is
rerecorded extratympanically via an active electrode placed within the
ear canal or on the drum itself and a reference electrode placed on the
contralateral mastoid process. Intratympanically, the ECoG is recorded
using a transtympanic needle electrode placed on the promontory of the
middle ear.
Clinical Applications
•• To assess hearing in the paediatric age group.
•• Tool to assess auditory status in patients suspected of having Ménière’s
disease.
•• As a part of retrocochlear assessment.
•• During otoneurologic surgery.
Auditory Brainstem Response

•• Auditory brainstem response (ABR) is a recording of the synchronised
response of a large number of neurons in the lower portions of the auditory
pathways was first described by Sohmer and Feinmesser in 1967. Origin
of various waves has been described in Table 2.
•• The ABR is recorded using differential amplification with the active electrode
positioned at the vertex or high forehead with reference electrodes
positioned at the mastoids or the ear lobes.
•• It requires brief acoustic stimulus with a relatively rapid onset. The most
common stimulus used to evoke the ABR is a 100-millisecond rectangular
pulse or click. A click is the ideal stimulus for eliciting the ABR as it results
in a large number of auditory nerve fibres firing at approximately the same
time.
•• It is a tool for estimating auditory sensitivity as well as for a range of
otoneurologic applications.
•• It is by far the most commonly used of the auditory evoked potentials, due
to the fact that it can be recorded by non-invasive techniques and is easy
to record, not strongly affected by attention, sleep state, sedation and
anaesthesia or age.
•• Historically, the recording of ABR has been to assist with detection of
lesions affecting the auditory pathways between the cochlea and the inferior
colliculus. Such lesions like vestibular schwannomas and pathology, caused
Table 2: Origin of various waves of auditory brainstem response

Wave Site of origin
I Cochlear nerve (distal end)
II Cochlear nerve (proximal end)
III Cochlear nucleus
IV Superior olivary complex
V Lateral lemniscus/inferior colliculus
VI and VII Neural generators, not definitely known
33
by factors such as multiple sclerosis, stroke or trauma.

•• It is used to monitor the status of the auditory nerve during skull base
surgery, because ABR is not strongly affected by anaesthesia. It provides
continuous feedback about the status of the auditory nerve during surgery.
Auditory Steady State Response

Auditory steady state response (ASSR) is a far-field auditory potential that is
evoked using continuous stimulation.
As a potential clinical tool, it has several advantages over the more
commonly used ABR. For example, with ASSR, it is easier to distinguish
between severe and profound hearing loss as opposed to ABR.
Vestibular Function Test in Unconscious Patients
Vestibulo-ocular reflex elicited by irrigating the external auditory canal with ice
cold water has proved to be a very reliable bedside investigation to evaluate
unconscious patients.
It not only provides objective indication of the depth of unconsciousness,
evidence of ocular nerve palsies, internuclear ophthalmoplegia but is also a
guide to prognosis.
COCHLEAR AND BRAINSTEM IMPLANTS

Mohan Kameswaran, Kiran Natarajan
•• Auditory neural prostheses, such as cochlear implants and brainstem

implants, have proved to be extremely useful innovations in neuro-
otology in the last decade. This has been made possible due to advances
in biomedical engineering and the development of materials that are
biocompatible.
•• Cochlear and auditory brainstem implants offer safe and effective hearing
habilitation and rehabilitation for profoundly deafened adults and children.
•• Auditory neural prosthetic intervention must be done as early as possible
due to the phenomenon of neural plasticity. Neural plasticity is the ability
of the central nervous system to be programmed to learn a new task. This
fades between 6 years and 8 years of age.
•• Electrophysiological tests and imaging modalities are now available to
accurately pinpoint the level of lesion in the auditory pathway. In 99% of
sensorineural hearing loss, including congenital hearing impairment, the
primary pathology is in the cochlea.
COCHLEAR IMPLANTS
•• A cochlear implant is a surgically implantable device that helps restore
hearing in patients with severe or profound hearing loss, unresponsive
to amplification by hearing aids. Cochlear implants are electronic devices
designed to detect mechanical sound energy and convert it into electrical
signals that can be delivered to the cochlear nerve, bypassing the damaged
hair cells of the cochlea. The implant helps convert sound into electrical
signals. These signals are then sent to an array of electrodes implanted
surgically in the cochlea. The implant system preserves the tonotopic map
of the cochlea.
34
Components
•• The implant has external components consisting of a microphone which
receives sound and transduces it into an electrical waveform, a speech
processor which divides the signals into components for each of the
electrodes and a transmitting coil which sends the signals across the scalp
to the internal components.
•• The internal components include a receiver-stimulator which receives the
signals from the transmitting coil and sends it to the electrode array which
is implanted in the scala tympani of the cochlea.
Selection Criteria
•• Bilateral profound cochlear hearing loss unresponsive to amplification by
the most powerful hearing aids is the indication for an implant.
•• All children below the age of 10 years who have congenital or acquired
profound hearing loss and who will not benefit from conventional hearing
aids and all adults who have lost hearing after acquisition of language are
candidates.
•• The only true pre-requisite is an intact auditory nerve.
•• The minimum age for implantation in children has come down and children
as young as 6 months of age have been implanted. As the cochlea is at
full size at birth, there is no anatomic difficulty with electrode insertion in
very young children.
Contraindications
•• Cochlear aplasia, absence of auditory nerves, retro-cochlear cause of
deafness, central deafness, presence of external or middle ear infections
and co-existent severe medical illness are contraindications.
Pre-operative Evaluation
•• Pre-operative evaluation includes a complete ear, nose and throat (ENT),
and head and neck examination, including assessment for additional
handicaps, haematological tests, TORCH serology, if required, and
skiagram of chest and ECG for assessing fitness for surgery.
•• Audiological and electrophysiological investigations include:
–– Pure tone and impedance audiometry otoacoustic emissions (OAE)
–– Brainstem evoked response audiometry (BERA)
–– Auditory steady state response (ASSR)
–– Aided audiometry
–– Hearing aid trial.
•• Magnetic resonance imaging is the gold standard for the assessment of
cochlear anatomy and the vestibulocochlear bundle. It reveals anomalies
like Mondini’s and Michel’s aplasia, labyrinthitis ossificans and absent
eighth nerve.
Surgery of Cochlear Implantation

•• The goal of cochlear implant surgery is to insert the entire electrode array
into the scala tympani with as little damage as possible to the structure of the
inner ear. Surgery is essentially the same for children and adults because
the anatomic structures are of adult configuration at birth. However, in very
young children, there is a slightly increased risk of facial palsy.
35
The steps of surgery are:

•• Incision: An extended post-auricular incision to expose the mastoid cortex.
The incision made more than 1 cm from the body of the implant.
•• Simple mastoidectomy: The mastoid is drilled out to expose the mastoid
antrum.
•• Posterior tympanotomy: The facial recess is opened and the promontory
and round window niche are exposed without exposing the facial nerve.
•• Well for receiver-stimulator: This is fashioned in the skull behind the
mastoid cavity using a template as a guide and a groove is made to connect
it to the mastoid cavity. Tie-down holes are made on either side of the well
for securing the implant.
•• Cochleostomy: The basal turn of the cochlea is opened anterior to the round
window to make the axis of introduction of the electrode array straighter.
•• Insertion of electrode array: The electrode array is inserted atraumatically
into the scala tympani using a claw. Once the electrodes are inserted,
diathermy should not be used.
– Fixation of the device and electrode array and wound closure is done.
Electrophysiologic Testing or Neural Response Telemetry

•• Neural response telemetry (NRT) is performed after implanting the electrode
array.
•• This assures the team that the device is functioning and that the patient is
receiving an auditory stimulus and responding appropriately.
Post-operative Care
•• The patient is called for review three weeks post-operatively for switch-on
of the device.
•• Frequent mapping sessions are required and prolonged and intensive
rehabilitation after implantation is essential. Rehabilitation aims at improving
receptive language skills and expressive skills.
Complications of Cochlear Implantation

•• Major complications include facial palsy, and implant exposure due to flap
loss and wound infection.
•• Other complications include facial nerve stimulation, device failure,
deterioration of hearing, tinnitus, temporary balance problems, numbness of
the scalp, loss of taste, electrode/device extrusion, CSF leak and meningitis.
AUDITORY BRAINSTEM IMPLANTATION

•• Auditory brainstem implant (ABI) is an effective means of hearing
rehabilitation in patients with neurofibromatosis type 2.
•• In such patients with damaged cochlear nerves on both sides, the brainstem
implant bypasses the cochlear nerves and directly stimulates the cochlear
nucleus. The cochlear nucleus has tonotopicity.
Indications for Auditory Brainstem Implant

•• Multichannel ABIs are indicated for patients with neurofibromatosis
type 2 (NF2) and schwannomas involving the internal auditory canal or
cerebellopontine angle.
36
•• ABI is being considered for non-tumour patients and even in children with
congenital hearing loss before the loss of neuronal plasticity.
•• In the near future, it may be used in bilateral temporal bone fractures and
demyelinating diseases affecting the eighth cranial nerves, but sparing at
least one cochlear nucleus.
•• Auditory brainstem implantation has also been used in cases of bilateral
totally ossified cochlear in which a cochlear implant cannot be used.
•• The current criteria for ABI include evidence of bilateral seventh and eighth
cranial nerve tumours involving the IAC or cerebellopontine angle, language
competency, age > 12 years or older, psychologic suitability, willingness to
comply with research follow-up protocol and realistic expectations.
•• A multi-disciplinary approach is essential involving neurotologists,
neurosurgeons, audiologists and anaesthetists.
•• Prior to planning the surgery, assessment of the tumour and the hearing
is vital.
•• Comprehensive audiological tests, including pure tone audiometry,
brainstem evoked response audiometry, otoacoustic emissions and
auditory steady state response (ASSR), are required.
•• Pre-operative MRI is very important because it may signal potential
problems leading to non-stimulation such as a large lateral recess or tumor
damage to the cochlear nucleus region and also helps to rule out other
intracranial and spinal tumours.
Auditory Brainstem Implant Surgery

•• For successful ABI surgery, a few important issues, such as patient
selection, choice of device, choice of approach, technique of tumor removal,
knowledge of micro-anatomical variations, intra-operative identification
of the cochlear nucleus and prevention of complications, have to be
considered.
•• Nerve monitoring is required and neuromuscular blocking agents should be
avoided during monitoring. EMG monitoring of V, VII and IX nerves is done.
•• There are several approaches described for tumour removal and placement
of ABI.
–– Trans-labyrinthine approach provides optimal access for both
removal of the tumour and placement of the electrode array. Disadvan-
tages with trans-labyrinthine approach are limited exposure of cranial
nerves and vessels in the posterior fossa.
–– The lateral suboccipital approach is preferred by most neurosur-
geons as it is fast, safe and offers very good exposure of the lateral
posterior fossa.
–– The middle cranial fossa approach is only possible with angled en-
doscopes; however, it is technically the most difficult and places the
facial nerve at greatest risk.
•• After craniectomy is performed, a seat for receiver-stimulator is created
in the area postero-superior to the craniectomy. Tie-down holes are then
placed on either side of the receiver-stimulator for securing the implant.
•• The cochlear nerve is followed medially as it enters the lateral recess of
the fourth ventricle.
37
•• The ABI is inserted in the lateral recess of the fourth ventricle, which is
adjacent to both cochlear nuclei.
•• Between the bulging of the cochlear nucleus and the ponto-bulbar body,
a small straight vein is a constant finding and an important landmark. The
typical straight vein at the cochlear nucleus heading to the entrance of the
foramen of Luschka is found in 76%.
•• The taenia of the choroid plexus at the entrance of the fourth ventricle is
dissected and the device is advanced into the lateral recess of the fourth
ventricle over the surface of the cochlear nuclei.
•• Activation of the device is done 3–6 weeks later.
•• Contraindications to ABI include previous stereotactic radiotherapy
which has the risk of radiation necrosis of the cochlear nucleus region and
anatomic distortion and fibrosis. ABI may not be possible in very large
tumours which cause distortion of the brainstem.
Auditory Midbrain Implants

•• The auditory midbrain implant (AMI) is a new hearing prosthesis designed
for stimulation of the auditory midbrain, particularly the inferior colliculus
central nucleus (ICC).
•• AMIs are placed in the ICC. They may prove to be a safe and potential al-
ternative for hearing restoration in neuro fibromatosis Type 2 (NF2) patients
and may help in enhancement in lip-reading capabilities and environmental
awareness and some improvement in speech perception performance.
5
CHAPTER
Neuroendocrinology
Ravi Ramamurthi  Ravindranath Kapu
INTRODUCTON
•• The anterior pituitary secretes the following hormones:
–– Prolactin (PRL)
–– Growth hormone (GH)
–– Adrenocorticotropic hormone (ACTH)
–– Thyroid-stimulating hormone (TSH)
–– Gonadotrophic hormones which are follicle stimulating hormone (FSH)
and luteinising hormone (LH).
•• The posterior pituitary secretes: Antidiuretic hormone (ADH or vasopressin)
and oxytocin.
•• Pituitary hormones are measured by radioimmunoassay (RIA),
immunoradiometric assay (IRMA) or enzyme-linked immunosorbent assay
(ELISA).
•• The reserve capacity of the pituitary gland, in its response to stress, must
be tested with provocative tests (dynamic testing).
•• Normal basal level listed in Table 1.
Table 1: Normal basal levels

Free Tri-iodothyronine (T3) 2.2–5.0 pg/mL
Free Thyroxine (T4) 0.7–2.2 ng/dL
Thyroid stimulating hormone ND–9 u IU/mL
17 OH Progesterone 50–180 ng/dL
Progesterone Post-ovulatory Above 5 ng/mL
Testosterone Male 360–990 ng/dL
Female 15–110 ng/dL
Prolactin Male ND–15 ng/mL
Female ND–20 ng/mL
Growth hormone Fasting adults ND–5 ng/mL
Fasting children ND–10 ng/mL
Cortisol Morning sample 5–25 µg/dL
Evening sample 2.5–12.5 µg/dL
17 Ketosteroids Male 9–24 mg/24 hours
Female 5–17 mg/24 hours
DHEA Male 80–560 µg/dL
Female 35–430 µg/dL
Chapter 5 • Neuroendocrinology
39
PROLACTIN
•• The basal level of PRL is 5–20 ng/mL. The average is 10 ng/mL in women
and is 20–25% lower in men and in post-menopausal women.
•• PRL levels vary through the day with a circadian rhythm and the highest
levels are noted during sleep. Stress induce variations in PRL levels.
•• Physical activity, general anaesthesia, surgery, myocardial infarction,
seizures, and nipple and chest wall stimulation may increase PRL levels.
During pregnancy and lactation, PRL levels increase to 200–300 ng/mL.
•• Prolactin is secreted by lactotrophic cells located in the lateral wings of
the anterior pituitary.
•• These cells constitute 20% of adult anterior pituitary cells and are
derived from acidophilic stem cells, which are also the precursor cells for
somatotrophs.
•• Physiological hypertrophy of lactotroph cells occur in states where there
is excess oestrogen as in the foetus and in women during the second and
third trimester of pregnancy.
•• Prolactin contains 198 amino acid residues which were identified in 1977.
•• Prolactin receptors are present in the ovaries, mammary glands, pituitary
gland, heart, thymus, lung, spleen, liver, pancreas, kidney, adrenal gland,
uterus, skeletal muscle and areas of the central nervous system.
•• PRL causes activation of Janus kinase 2, a tyrosine kinase that initiates
the JAK-STAT pathway and also activation of mitogen-activated protein
kinases and Src kinase.
•• Substances which inhibit the release of PRL: Dopamine, gamma-
aminobutyric acid (GABA), gonadotropin-releasing hormone
(GnRH)-associated peptide and somatostatin. There is also a negative
autoregulatory effect of PRL itself.
•• The predominant control of PRL is inhibitory, but three substances,
thyrotropin releasing hormone (TRH), vasoactive intestinal peptide (VIP)
and serotonin are PRL releasing substances.
•• Oestrogens increase the secretion of PRL and are responsible for the
increase in pituitary size and PRL production during pregnancy.
•• T3 and glucocorticoids inhibit PRL release. Epileptic seizures can also
increase the PRL levels.
•• The TRH stimulation test is the most effective. Baseline fasting TSH and
PRL levels are measured and 500 ng of TRH is given intravenously over
30 seconds. The serum levels are measured at 15-minute intervals up to
an hour. Any rise of over 100% is normal. Anything less is indicative of
inadequate lactotroph reserve.
•• The other substances that can be used for dynamic testing are
chlorpromazine and metoclopramide to increase PRL secretion and L-dopa
and nomifensine to reduce PRL secretion.
GROWTH HORMONE
•• This is a 191 amino acid polypeptide with a molecular weight of 22,124
Daltons.
•• It is secreted in a pulsatile fashion with surges of secretion occurring at 3–5
hour intervals and the serum levels vary with the time of day.
•• The normal serum level of growth hormone is up to 5 ng/mL. Young
adolescents secrete human growth hormone (HGH) at the rate of about
700 µg/day, while healthy adults secrete HGH at the rate of about 400 µg/day.
40
•• It is secreted by the somatotroph cells within the lateral wings of the anterior
pituitary gland. The most predictable levels of these GH peaks occur about
an hour after the onset of sleep.
•• Growth hormone secretion is controlled by two polypeptides which
are secreted by the hypothalamus and reach the pituitary through the
hypothalamo-hypophyseal portal circulation. Growth hormone-releasing
hormone (GHRH) stimulates the secretion of GH, while somatostatin (SRIF)
suppresses the release.
•• The hypothalamic control of these peptides is regulated by the brainstem
and the limbic system.
•• The effects produced by GH are due to stimulation of insulin-like growth
factor 1 (IGF-1), which is also known as somatomedin C.
•• Substances that stimulate GH secretion are encephalin, glucagons, alpha
melanocyte stimulating hormone, vasopressin, diazepam, oestrogens,
norepinephrine, L-Dopa, clonidine, apomorphine.
•• The substances that suppress GH secretion are SRIF from the
periventricular nucleus, hyperglycaemia, isoproterenol, glucocorticoids and
elevated levels of free fatty acid.
•• GH levels are measured in the serum in the basal state as well as after
provocative tests. The basal level is tested in a fasting patient at 8.00 am.
The blood may also be drawn at 12 noon, 4 pm and 8.00 pm. Normally, all
values must be below 2 ng/mL. The normal range is 0–5 ng/mL.
The dynamic tests used to determine GH reserve are:
•• Insulin-induced hypoglycaemia: It is contraindicated in patients with
ischaemic heart disease, cerebrovascular disease, seizures and adrenal
insufficiency.
•• The arginine test:
The dynamic tests that are used when there is acromegaly are:
•• Oral glucose tolerance test (OGTT): After overnight fasting, 75 grams of
glucose is given orally. Blood samples are taken at 30-minute intervals for
up to 2 hours. Failure of suppression indicates acromegaly.
•• TRH test: A more than two-fold increase above the basal levels is called
an “inappropriately high response” and is often associated with active
acromegaly.
•• Somatomedin C estimation is done by RIA. The normal fasting value is
0.67 µg/mL (range 0.31–1.4) and the mean in acromegalics is 6.8 µg/mL
(range 2.6–21.7). This assay is useful in the post-treatment follow-up of
acromegalics.
ADRENOCORTICOTROPIC
HORMONE AND CORTISOL
•• Cortisol is essential for the physiological and biochemical response to
stress, both endogenous and exogenous.
•• Cortisol is secreted from the zona fasciculata, the second layer of the
adrenal cortex.
•• Cortisol secretion is controlled by ACTH, which is secreted by the anterior
pituitary and is in turn controlled by corticotropin-releasing hormone (CRH)
from the paraventricular nucleus of the hypothalamus.
•• Corticotrophs in the anterior pituitary produce ACTH and these constitute
10–20% of the cells. They are concentrated in the central portion of the
41
gland, though some cells are also present in the lateral wings and in the
pars intermedia.
•• It is difficult to measure ACTH in the serum as its half-life is only 20 minutes.
•• Basal levels of plasma and urinary cortisol are measured. The mean plasma
cortisol level should be 5–25 µg/dL.
•• Dynamic tests are used to evaluate the status of the hypothalamic-pituitary-
adrenal (HPA) axis, in its response to stress and in hyper-functioning states.
Urinary-free Cortisol Excretion Rate

•• It is one of the best methods for quantifying hypercortisolism in which
unmetabolised cortisol is measured.
•• Urinary-free cortisol (UFC) is measured in a carefully collected 24-hour urine
sample. The normal range is between 30 nmol/day and 150 nmol/day. The
sensitivity of the UFC method for the diagnosis of Cushing’s syndrome is
between 95% and 100%.
The tests used for assessing normal function are:
•• Insulin-induced hypoglycaemia (Insulin tolerance tests, ITT): An
increase in cortisol level to more than 12 µg/mL is considered an adequate
response and demonstrates an intact hypothalamic-pituitary-adrenal axis.
•• ACTH stimulation test: Plasma cortisol should be more than 18 µg/mL
and the increment should be more than 7 µg/mL.
•• Metyrapone test:
The dynamic tests used in hypercortisolaemia are:
•• Low-dose dexamethasone test: The cortisol should normally be
suppressed to below 2/µg/mL. This response practically excludes Cushing’s
syndrome. This test is also useful in postoperative assessment.
•• High-dose dexamethasone test: This is used in the differential diagnosis
of Cushing’s syndrome and where the low-dose dexamethasone test is
abnormal.
•• CRH stimulation test: This is also a test for differential diagnosis of
Cushing’s syndrome. Patients with Cushing’s disease exhibit a normal or
exaggerated response, whereas there is no response with ectopic ACTH
syndrome or adrenal tumours.
•• Venous sampling for ACTH gradient: This is done when the results of
other tests are not definitive and computed tomography (CT) and magnetic
resonance imaging (MRI) images do not reveal a microadenoma. If an
ectopic source of ACTH cannot be excluded, then venous sampling is
done at various levels including the internal jugular vein, the right ventricle
and the inferior vena cava at the level of the diaphragm and the coeliac,
the renal and the femoral veins. Inferior petrosal vein sampling also helps
in locating the site of a pituitary microadenoma when there is a doubt.
Tests for Hypocortisolism

Morning Plasma Cortisol Level (Between 8 am and 9 am)
•• Cortisol levels more than 500 nmol/L at this time practically exclude adrenal
insufficiency, while a level less than 100 nmol/L is almost diagnostic of
adrenal insufficiency.
•• In a patient with such a low plasma cortisol, measurement of ACTH in the
same blood sample allows the distinction between primary (elevated ACTH)
and secondary (normal or low ACTH) adrenal insufficiency.
42
THYROID
•• Tetraiodothyroxine (T4) is the major hormone secreted by the thyroid gland,
but tri-iodothyronine (T3) is the metabolically active hormone.
•• Thyroid hormones control development, growth and metabolic rate.
•• Thyroid hormone secretion is controlled by TSH secreted by the anterior
pituitary.
•• It is a glycoprotein with two subunits, alpha and beta.
•• Thyrotropin releasing hormone tonically stimulates the release of TSH.
Thyrotropin releasing hormone is synthesized in the paraventricular nucleus
of the hypothalamus.
•• The hypothalamic-pituitary-thyroid axis is controlled primarily by the
circulating thyroid hormone in a negative feedback system.
•• Hypothyroidism and hyperthyroidism are diagnosed on the basis of
determination of T3 and T4. Free T4 is a good screening test of thyroid
function, because it takes into account both T3 uptake and total T4 in the
serum.
•• T3 and T4 are low, TSH stimulation will enable differentiation between
primary and secondary hypothyroidism. This differentiation is also possible
by the TRH stimulation test.
•• Mass spectrometry is a new advanced technique by which the hormones
can be quantitatively assessed in biological fluids.
•• Thyrotropin-releasing hormone stimulation test: The normal basal
values range from 0.3 IU/mL to 3.5 IU/mL. In a patient with low thyroid
hormones, impaired TSH response to TRH indicates deficient TSH at the
pituitary level. A delayed TSH response to TRH, i.e. when the TSH level is
higher at 60 minutes than at 30 minutes, is characteristic of hypothalamic
dysfunction.
•• Basal TSH level in the upper normal range, or slightly elevated in the
presence of raised T3 and T4, is called inappropriate secretion of TSH
and is characteristic of TSH secreting pituitary adenoma. The TSH alpha
subunit is measured by a specific RIA. This is elevated in TSH secreting
pituitary adenoma.
Newer Methods
Index Methods
These are free hormone estimate tests. These tests use either an immunoassay
for thyroxine-binding globulin (TBG) or a T4 or T3 “uptake” test called thyroid
hormone binding ratio (THBR).
Indexes Using a Thyroid Hormone
Binding Ratio or “Uptake” Test
“Classical” uptake test is a method in which a trace amount of radiolabelled
T3 or T4 is added to the specimen and it is allowed to distribute across the
thyroid hormone binding proteins like the endogenous hormone.
GONADOTROPINS
•• Luteinising hormone and FSH are the gonadotropins and they are
synthesised by gonadotrophs in the anterior pituitary.
•• They have a common alpha subunit with TSH and HCG. LH and FSH are
controlled by the hypothalamic-pituitary-gonadal axis.
43
•• LH and FSH release is controlled by GnRH, which is a decapeptide

synthesised in the hypothalamus. GnRH release is regulated by several
molecules including neurotransmitters, glial cell factors, sex steroids,
kisspeptin (Kp) and neuropeptide.
•• LH and FSH travel through the systemic circulation and in turn stimulate
the gonadal steroids testosterone, oestradiol and progesterone. They
also stimulate the peptides, inhibins and activins, as also gametogenesis.
A negative feedback is exerted on the pituitary and hypothalamus by the
gonadal hormones.
•• LH and FSH are secreted in a pulsatile fashion over 24 hours. The pattern
in men is fairly constant at 90–120 minutes whereas, in women, it changes
with changes in the menstrual cycle. This pulsatile secretion is due to the
pulsatile release of GnRH from the hypothalamic neurons.
•• Various other substances also regulate the hypothalamic-pituitary-gonadal
axis. Prolactin inhibits GnRH secretion and causes hypogonadism.
•• The Buserelin Stimulation Test: This is a highly specific and sensitive
GnRH agonist test. It is used for investigating males with delayed puberty.
ANTIDIURETIC HORMONE (VASOPRESSIN)

•• The prohormones, a neurophysin and a glycopeptide, which are
enzymatically converted into ADH are synthesised in the hypothalamus.
•• This occurs in the magnoc ellular neurons of the supraoptic and
paraventricular nuclei.
•• The prohormones are contained in neurosecretory granules and transported
to the posterior pituitary through the axons in the infundibulum.
•• The neurophysin and glycopeptide are secreted along with ADH and have
no known biological activity.
•• Antidiuretic hormone secretion is controlled by osmotic as well as
volume regulation. These receptors are located in the anterior part of the
hypothalamus.
•• ADH is released even if there is a 1% increase in the plasma osmolality.
The normal plasma osmolality is 285–295 mOsm/kg water. The osmotic
receptors respond mainly to extracellular sodium.
•• The volume regulation receptors are found in the aorta, carotid sinus and
left atrium. The impulses reach the brainstem through the glossopharyngeal
and vagus nerves and ascend through multisynaptic pathways to end in
the magnocellular neurons of the hypothalamus.
•• ADH is released only when there is a 10–15% reduction in blood pressure.
•• The substances that reduce the action of ADH are endogenous
prostaglandins, hypocalcaemia, hypokalaemia, lithium, demeclocycline,
water, ethanol, phenytoin and anticholinergic drugs.
•• The conditions and substances that stimulate the release of ADH or
enhance its action are hypothyroidism, hypoadrenocortisolism, nicotine,
chlorpropamide, cholinergic drugs, clofibrate, barbiturates, morphine,
carbamazepine and anesthetic agents.
•• The two syndromes that are produced by disorders of ADH secretion are
syndrome of inappropriate ADH secretion (SIADH) caused by excessive
ADH and diabetes insipidus (DI) caused by diminished secretion of ADH.
•• The water deprivation test is used in suspected DI.
•• In central DI, the urine osmolality does not rise and the urine output remains
high. The plasma osmolality becomes higher than 295 mOsm/kg. Urine
44
osmolality below 400 mOsm/kg is diagnostic of DI and if it is more than 700

mOsm/kg in any of the morning samples of urine, it rules out DI.
•• Administration of deamino-delta-d-arginine vasopressin (DDAVP) can also
help in differentiating central and nephrogenic DI.
•• In nephrogenic DI, there will be no changes in the urine output and serum
and urine osmolality on administration of DDAVP, whereas in central DI,
changes will occur.
6
CHAPTER Intra-operative
Monitoring
Babu KS  Rajasekar V
INTRODUCTION
•• Our body generates many electrical signals. Heart, skeletal muscles,
peripheral muscles and different segments of the central nervous system
generate these electrical signals, while the brain generates spontaneous
electrical activity, which is recorded as an electroencephalogram (EEG).
•• The central nervous system also produces an electrical response to specific
stimuli. The type of stimulus varies depending on the sensory modality
that is being stimulated. Flashes of light are used to evoke visual evoked
potentials (VEP), auditory clicks for auditory evoked potentials (AEP) and
electrical stimulation of the peripheral nerves to evoke sensory responses,
along their ascending pathway called somatosensory evoked potentials
(SEP). Motor evoked potentials (MEP) are evoked by transcranial electrical
or magnetic stimulation of the cortex. These are the most common types
of intra-operative monitoring (IOM) techniques used in the OT.
The Prime Objective of IOM is:
•• To identify new neurological dysfunction early and prevent it before it
becomes irreversible
•• To provide reassurance to the surgeon that no damage has occurred till that
point in surgery, so that more radical excision of masses can be performed.
CHOOSING AN INTRA-OPERATIVE
MONITORING MACHINE
•• The majority of models, which are currently available in the market for IOM
have facilities to do AEP, VEP, SEP, EEG and electromyography (EMG).
•• Some of them have specialised features for microelectrode recording during
pallidotomy and thalamotomy.
RECORDING ELECTRODES
•• Standard 8 mm EEG reusable gold disk electrodes are the most popular,
as they are non-corrosive and need less maintenance. These electrodes
need to be properly anchored to the patient, as most of these electrodes
will be out of reach during surgery.
•• For a corticogram, subdural strip electrodes are used. They are useful in
epilepsy surgery, cortical localisation of the central sulcus, recording “after
discharge” during cortical stimulation of eloquent areas, particularly, the
speech areas during awake craniotomy.
•• Similarly, depth electrodes are also commercially available; again they vary
in the number of electrode points and the inter-electrode distance. They
are usually made of platinum.
46
•• For spinal cord surgeries epidural electrodes are very useful for recording
over the scalp electrodes.
•• Subdermal needle electrodes are also very useful for recording EEG,
EP and compound muscle action potentials (CMAP). They are inserted
tangentially into the skin. Needles have inter-electrode impedances, which
are about five to ten times that of stickons and, because of this, they are
more liable to produce noise-contaminated records in electrically hostile
environments.
BIPOLAR AND MONOPOLAR ELECTRICAL

STIMULATION
•• Both bipolar and monopolar electrical stimulation are popular and they have
their advantages and disadvantages.
•• In bipolar stimulation, the spread of the stimulating current is limited
between the two electrodes, which are adjacent to each other, while, in
monopolar stimulation, one probe is placed on the neural structure that is
to be identified, while the second electrode is placed indifferently, which is
usually the exposed muscle at the operating site.
•• In contrast to monopolar stimulation, bipolar stimulation requires orientation
of the probe tips longitudinally along the nerve. Therefore, in cases in which
the course of the nerve is not known (i.e. nerve encased by tumour), a
monopolar stimulus design is useful.
•• Monopolar stimulation for facial nerve stimulation, brainstem mapping of
the motor nuclei, spinal nerves in tethered cord and cortical stimulation
under general anaesthesia are being used.
•• Bipolar stimulation in awake craniotomy cases for mapping of the eloquent
areas, so that the spread of the current is local and specific responses could
be obtained and determined.
VISUAL EVOKED POTENTIAL

•• Flashes of light-emitting diode (LED) fixed in goggles are the most common
type used for intra-operative stimulation of the eyes.
•• The patient’s eyes are kept closed with an adhesive and the light is flashed
on to the closed eyelids. These are found to be convenient even for trans-
sphenoidal surgeries. Contact lenses have also been used for stimulating
devices. In some devices, the LEDs are implanted into special contact
lenses and these are connected by a fine wire to a remote electrical source.
•• VEP is used in patients with a tumour or aneurysm pressing on the
optic nerve or chiasm also in pituitary tumours. Monitoring during trans-
sphenoidal surgery for pituitary tumours showed a drop in VEP amplitude
during infiltration of the nose (during which there is rise in BP), suggesting
that VEP is susceptible to cerebral blood flow changes.
•• Intra-operative monitoring of visual evoked potentials (VEPs) has been
regarded as having limited significance for the preservation of visual
function during neurosurgical procedures, mainly due to its poor spatial
resolution and signal-to-noise ratio.
BRAINSTEM-AUDITORY EVOKED POTENTIAL

•• Neurophysiologic intra-operative monitoring of brainstem auditory evoked
potentials (BAEPs) is a widely used method to assess the functional integrity
Chapter 6 • Intra-operative Monitoring
47
of the central auditory system, during surgery involving the brainstem or

the cranial nerves.
•• The stimulus is a brief click delivered through tubal insert earphones. The
stimulator is connected to silicone tubes, to which are attached disposable
polyurethane foam tips, which are inserted into the ear. For better recording
of wave one, gold TIPtrodes serve a dual purpose: They are used for
delivering the sound and as a recording electrode.
•• BAEP is useful in surgery for CP angle tumours, brainstem surgery, microvascular
decompression and in stereotactic biopsy of some brainstem tumours.
•• In these, the active electrode is placed on the CZ and the reference
electrodes are placed on the ear lobes. The rate of stimulation is 11.1/sec.
•• Brainstem auditory evoked potentials (BAEP) monitoring is a useful tool to
decrease the danger of hearing loss during cerebellopontine angle surgery,
particularly in microvascular decompression (MVD). Critical complications
during MVD surgery are the stretching of the VIII nerve—the main cause
of hearing loss—labyrinthine artery manipulation, direct trauma with instru-
ments or a nearby coagulation and at end of the surgery neocompression
of the cochlear nerve by the prosthesis positioned between the conflicting
vessel(s) and the VIIth-VIIIth nerve complex. All these dangers warrant the
use of BAEP monitoring during the surgical team’s training period.
SOMATOSENSORY EVOKED POTENTIAL

MONITORING
•• SEPs are used for spinal cord monitoring, in surgery for cortical masses
and cerebral aneurysms, cortical localisation of the central sulcus and in
surgeries in and around the brainstem. The stimulating electrodes can be
discs, bars or needles.
•• Depending on the location of the lesion and type of surgery, either the
median nerve at the wrist or the posterior tibial nerve at the ankle is
stimulated at a rate of 4.7/sec.
•• The principle cortical peaks for median nerve are N20 and P30 and for
tibial nerve are P37 and N45.
•• In some spinal cord surgeries epidural electrodes are used. Epidural
electrodes are not useful below the L1 level.
MOTOR EVOKED POTENTIAL

•• Intra-operative motor evoked potential (MEP) monitoring in patients with
spinal and cranial lesions is thought to be a valuable tool for prevention of
post-operative motor deficits.
•• MEPs provide the possibility for monitoring anterior and lateral spinal cord
tracts. Responses can be recorded directly from the motor tracts or muscle.
•• Recently, transcranial electrical stimulation (TES) and transcranial magnetic
stimulation (TMS) techniques were introduced for IOM of the corticospinal
pathways. For intra-operative monitoring TES is more convenient than TMS.
•• Sustained vascular dynamics (vasospasm, congestive oedema) may cause
delayed paresis which are missed or hardly reflected by intra-operative
MEP changes. Even minor MEP changes must therefore be observed to
prevent impending motor deficit.
•• MEP monitoring, as opposed to SEPs, is a valid indicator of corticospinal
function in brainstem related surgery, independent from the type of lesion
operated on.
48
Fig. 1: Photograph showing electrode placement for facial nerve monitor-

ing. Subdermal needle electrodes are placed in the (A) frontalis muscle;
(B) orbicularis oculi; (C) oris, with a common reference electrode in; (D) the
masseter; (E) ground electrode in the Fpz. Note how the cables are twisted
together to reduce artefacts. The electrode close to cleaning area is covered
with transparent adhesive
•• Intra-operative monitoring of facial nerve motor evoked potentials

(FNMEPs) elicited by transcranial electrical stimulation during skull base
tumour surgery is useful for predicting facial nerve function outcome Fig. 1.
•• Intra-operative neurophysiological monitoring (IONM) with motor-evoked
potentials (MEP), elicited by transc ranial electrical stimulation and
somatosensory-evoked potentials (SSEP) can be safely used in pregnant
women.
MOTOR NUCLEI AND NERVE STIMULATION

•• During brainstem surgery, it is important to identify various nuclei, so that
the surgeon can avoid manipulating or cause injury to them.
•• Identifying the facial nerve and mapping the course of the nerve fibres
during cerebellopontine angle (CP) tumour surgery is also very important.
It is useful particularly for CP angle tumours during drilling of the porus
acousticus, where the facial nerve is out of view and under the bone. The
electrode can be bent into a hook and the surgeon can “feel” for the nerve.
•• Starting current strength is 2.5 mA and usually go down to 0.2 mA, keeping
the rate of stimulation at 4.7/sec. The filters are set between 30 Hz and
3,000 Hz.
MAPPING OF ELOQUENT AREAS

•• Central sulcus mapping is done using somatosensory evoked potentials.
This is followed by cortical stimulation for further confirmation of the
eloquent areas under general anaesthesia. This technique is useful in
planning the course of surgery for subcortical lesions.
•• For a corticogram, subdural electrodes are used. The contralateral median
nerve is stimulated at 4.7/sec.
•• The sulcus, where a phase reversal occurs, is considered the central sulcus.
This is further confirmed by monopolar cortical stimulation.
•• In awake craniotomy, bipolar stimulation is used. The stimulus is a
monophasic square pulse of 1 msec duration stimulated at the rate of
49
50 Hz. Subdural strip electrodes are placed in the vicinity of the stimulating
area to record after discharge.
INTRACRANIAL MONITORING USING

ELECTROENCEPHALOGRAPHY
•• Intracranial monitoring using electroencephalography (IC-EEG) continues
to play a critical role in the assessment of patients with medically intractable
localisation-related epilepsy.
•• Intracranial monitoring using EEG allows detailed definition of the region
of ictal onset and defines the epileptogenic zone, particularly with regard
to adjacent potentially eloquent tissue.
•• Recent developments of IC-EEG include the co-registration of functional
imaging data, such as magneto-encephalography to the frameless
navigation systems.
•• IC-EEG remains the gold standard for localisation of the epileptogenic
cortex.
•• Intracranial electrodes take a variety of different forms and may be placed
either in the subdural (subdural strips and grids, depth electrodes) or
extradural spaces (sphenoidal, peg and epidural electrodes).
•• Each form has its own advantages and shortcomings, but extensive
subdural implantation of electrodes is most common and is most
comprehensively used.
INTRA-OPERATIVE ELECTROMYOGRAPHY
•• Intra-operative monitoring, by stimulated electromyography (EMG) of the
facial nerve to predict the completeness of microvascular decompression
(MVD) for hemifacial spasm (HFS), is useful.
•• The disappearance of an abnormal muscle response in the facial nerve
EMG indicates the completeness of MVD. Intra-operative facial nerve EMG
provides a real-time indicator of successful MVD during an operation, while
BAEP monitoring may provide an early warning of hearing disturbance
after MVD.
INTRA-OPERATIVE DOPPLER ULTRASONOGRAPHY AND

ULTRASOUND ANGIOGRAPHY
•• In treatment of brain arteriovenous malformations (AVMs), there is a
correlation between the change of resistive index (RI) of the feeding artery
and the completeness of resection of brain AVMs.
•• The resistive index (RI) of the feeding artery was recorded so as to identify
residual AVM.
•• Intra-operative Doppler ultrasonography is a reliable tool for intra-operative
localisation and complete resection of AVMs. Providing real-time flow
pattern of AVMs, intra-operative ultrasound angiography combined with RI
effectively indicates the completeness of resection of AVMs.
NEURONAVIGATION
•• Currently, neuronavigation is an indispensable part of neurosurgical
procedures in the majority of centres. The history of neuronavigation is
quite short (less than three decades).
50
•• The advent of neuronavigation would be unimaginable without the

development of imaging technology, electronics, robotics and space
technology.
•• Intra-operative neuromonitoring includes motor mapping by direct cortical
stimulation (CS) and subcortical stimulation (sCS) and localisation of the
central sulcus, by using cortical multipolar electrodes and the N20 wave
inversion technique.
•• Multimodal navigation allows integration and correlation among pre-
operative and intra-operative anatomical and functional data.
•• Cortical motor functional areas are anatomically and functionally located
pre-operatively, thanks to MR and fMR imaging and subcortical motor
pathways with DT imaging and tractography.
•• Frameless stereotactic neuronavigation provides tracking of surgical
instruments on radiographic images and orients the surgeon to tumour
margins at surgery.
•• Bipolar electrical stimulation mapping (ESM) delineates safe limits for
resection of brain tumours adjacent to eloquent cortex.
•• The presence of residual neoplasm is evaluated using iMR imaging;
resection is continued until eloquent areas are encountered or iMR imaging
confirms complete removal of any residual tumour.
•• A NY Tract Finder bipolar needle electrode, which enabled the identification
of motor pathways by inserting it into the white matter, was developed and
has been used. The scale on the needle indicates the approximate distance
from the tumour cavity wall to the pyramidal tract. This technique may be a
feasible method to detect and spare the motor pathways. However, further
studies are needed to determine reliability and limitations.
NAVIGATED BLOOD FLOW IMAGING

•• Blood flow imaging (BFI) is a new 2D ultrasound modality that offers angle-
independent visualisation of flow. When integrated with 3-dimensional (3D)
navigation technology, BFI can be considered as a first step toward the
ideal tool for surgical needs.
•• A real-time, high-resolution, 3D visualisation that properly portrays both
vessel geometry and flow direction.
•• The neurovascular flow direction is properly visualised in all cases using
BFI. Navigation technology allowed for identification of the vessels of
interest, despite the presence of brain shift.
•• BFI allows for quality control of sufficient flow in all distal arteries during
aneurysm surgery and makes it easier to discern between feeding arteries
and draining veins, during surgery for arteriovenous malformations.
FLUORESCENCE-GUIDED RESECTION
•• Fluorescence-guided resection (FGR) of brain tumours is an emerging
technology for visually delineating neoplastic tissue exposed intra-
operatively.
•• It detects surface fluorescence as a biomarker of the current surgical margin.
Implementation of deformation modelling for brain shift compensation in
protoporphyrin IX FGR and updated MR image information provide maximal
surgical benefit.
51
INTRA-OPERATIVE MAGNETIC RESONANCE

IMAGING IN NEUROSURGERY
•• Intra-operative MRI (iMRI) has been incorporated into modern neurosurgical
operating theatres as a guide for neurosurgical interventions.
•• This technology has been shown to be a useful modality in brain tumour
surgery and biopsy.
•• Its use in spine, vascular and epilepsy surgery has been evolving. It is
particularly useful in low-grade gliomas, pituitary adenomas and paediatric
tumours.
•• The addition of iMRI to the surgical armamentarium for treatment of patients
with GBM improves the degree of tumour resection while minimising
complications.
•• The intra-operative combination of an open magnetic resonance imaging
(MRI) system with neurophysiological localisation and continuous
monitoring techniques allows for the best available anatomic and
physiological orientation, as well as real-time functional monitoring.
•• MRI-compatible platinum/iridium electrodes for intra-operative neuromoni-
toring are attached to the patient’s head. Electrodes fixed to the head for
neurophysiological monitoring for evoked potentials should be of low
magnetic susceptibility to guarantee optimal imaging quality.
•• The combined use of an open ultra low-field MRI system and intra-operative
monitoring allows for resection control and continuous functional monitoring.
•• The use of the intra-operative ultra low-field MRI scanner helps to evaluate
the extent of resection in glioma surgery.
•• The technique of intra-operative diffusion-weighted imaging (iDWI) using
an intra-operative MR scanner of low magnetic field strength (0.3 T) has
been developed. iDWI is very useful for localisation of the pyramidal tract
and for clarification of its spatial relationships with the tumour.
•• The use of iDWI, in addition to structural iMRl and subcortical functional
mapping with electrical stimulation, can potentially result in a reduction of
the post-operative morbidity after aggressive surgical removal of lesions
located in the vicinity of the motor white matter tracts.
INTRA-OPERATIVE MONITORING OF CEREBRAL BLOOD

FLOW BY LASER SPECKLE CONTRAST ANALYSIS
•• Laser speckle contrast analysis (LASCA) is performed in patients
undergoing cerebral revascularisation procedures for the treatment of
haemodynamic compromise and complex aneurysms.
•• LASCA offers non-invasive and rapid intra-operative assessment of relative
CBF, which can be used for optimising neurovascular procedures.
•• LASCA allows immediate visualisation and measurement of relative CBF
in excellent spatiotemporal resolution.
WIRELESS INSTANTANEOUS NEUROTRANSMITTER

CONCENTRATION SYSTEM
•• Wireless instantaneous neurotransmitter concentration system (WINCS),
which couples digital telemetry with fast-scan cyclic voltametry (FSCV) is
used to measure extracellular concentrations of dopamine.
52
•• With the extended capability of the WINCS to use fixed potential

amperometry (FPA), it is possible to measure extracellular concentrations
of dopamine, as well as glutamate and adenosine.
•• The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-
fibre microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase
enzyme-linked electrode to measure glutamate and 3) a multiple enzyme-
linked electrode (adenosine deaminase, nucleoside phosphorylase and
xanthine oxidase) to measure adenosine.
•• Because many neurotransmitters are not electrochemically active, FPA in
combination with enzyme-linked microelectrodes represents a powerful
intra-operative tool for rapid and selective neurochemical sampling in
important anatomical targets during functional neurosurgery.
INTRA-OPERATIVE ELECTROCORTICOGRAPHY
•• Wilder penfield and Herbert jasper, in the 1950s, developed the technique
of intra-operative electrocorticography for localisation and surgical treatment
of epilepsy.
•• It has been used in the surgical management of medically refractory
epilepsy to localise anatomic areas of focal seizure onset, guide the extent
and completeness of resective epilepsy surgery, aid in functional mapping
of cortical anatomy and predict epilepsy surgery outcome.
•• The usefulness is often dependent on the underlying pathology and type
of resective surgery.
•• It seems to be valuable in the following circumstances:
–– Tailoring the extent of hippocampal resection during temporal lobec-
tomies.
–– Guiding resection of cortical brain malformations, low-grade tumours
and other neocortical lesions, especially those involving eloquent
cortex.
–– Monitoring for after discharges during functional cortical mapping.
•• Cortical stimulation can identify cortex with reorganised function secondary
to congenital lesions and cerebral plasticity. These lesions include brain
tumours, cortical dysplasia resulting in intractable epilepsy and cavernous
angioma causing epilepsy.
•• It has the disadvantage of being invasive but the advantage of being highly
accurate, allowing for surgical tailored resections.
•• Electrocorticography (ECoG) monitoring in the microsurgical treatment
of cavernous angiomas can direct the surgical procedure and control the
post-operative epileptic seizure.
7
CHAPTER
Conventional Radiology
Ravi Ramamurthi  Goutham Cugati
PLAIN X-RAY OF THE SKULL

•• Careful examination of well-exposed plain radiographs often helps to give a
clue to the possible diagnosis and points to the line of further investigations.
•• It is useful to have anteroposterior (AP) and lateral views.
•• Special views like posteroanterior (PA), Towne’s, perorbital, tangential or
stereoscopic are required for special indications.
•• An inspection of the plain radiograph of the skull includes the examination
of the vault with its outer table, the diploe, the inner table and the structures
at the base.
•• Anteriorly, the frontal sinuses extend into the frontal bone on both sides to
a varying extent. In some, the frontal sinuses extend high up into the frontal
bone and also laterally almost to the outer margin of the orbit. This is more
common in acromegaly and has to be taken note of when planning surgery.
•• Arterial markings in the skull are usually visible as thin wavy lines and may
become well marked when the external carotid branches supply a vascular
lesion like a meningioma or an arteriovenous malformation. The venous
channels of the skull are usually more prominent. The confluence of veins
in the parietal bone has been termed the “parietal spider”. At times, this
is strikingly prominent and should not be mistaken for a vascular lesion
of the skull.
•• The foramina of the emissary veins may be well visualised in some X-rays,
but this happens more often in patients with increased intracranial pressure.
•• In the base of the skull, the pituitary fossa is one of the most important
structures. In the lateral view, the anterior clinoid process, the planum
sphenoidale, the chiasmatic sulcus, the tuberculum sella and the posterior
clinoids are usually recognisable.
•• It is important to be aware of the normal variations in the shape and size
of the sella.
•• Zagga et al. found three types of sella namely oval, round and flat among
which oval shaped sella was seen in 83%.
•• Among the three types of sella floor namely the concave, flat and convex,
the concave type of sella floor was seen in 75% of the Nigerian population.
Occasionally, the pituitary fossa may be deep and extend more in the
vertical than in the AP direction. This has been termed “J-shaped sella”
and has no special pathological significance.
•• In the lateral view, it is also possible to visualise the floor of the middle
cranial fossa; a difference in the level of the floor on either side may indicate
hypoplasia or a space-occupying lesion dating from early childhood.
54
Posteroanterior View
•• The greater and lesser wings of the sphenoid bone and the anterior clinoid
processes are seen through the orbit in the PA view.
•• The anterior clinoids and the planum sphenoidale may be eroded by carotid
aneurysms or thickened by a meningioma.
Fronto-occipital View
•• In the AP view the frontal bone, frontal and ethmoid sinuses, crista galli,
ridge of the petrous bone, the posterior clinoid processes, the sides of the
sella turcica and the foramen magnum can be inspected.
Caldwell View (Perorbital View)

•• The petrous bones are projected through the orbits and along with it the
internal auditory canals are well visualised in this view.
Towne’s View
•• The occipital bone, petrous pyramids, foramen magnum, dorsum sellae
and posterior clinoids are seen well in this projection.
•• Normal variations in the thickness of the petrous ridge must be remembered
before diagnosing an erosion of the petrous bone or an enlargement of the
internal auditory canal in the Towne’s view.
Submento-vertical View
•• Lesions involving the base of the skull can be demonstrated by a special
basal view (submento-vertical view). The floor of the anterior, middle and
posterior cranial fossa may be outlined.
•• Erosion of the orbital roof, the lesser wings of the sphenoid, the floor of the
middle cranial fossa and the petrous bones are well seen.
•• Nasopharyngeal growths, chordomas and chondromas show appropriate
changes in the base of the skull.
•• The basal view is also used to visualise the foramen magnum and the
odontoid process.
•• Plain X-rays of the skull may also reveal signs of systemic disorders.
•• In hyperparathyroidism, there appears a peculiar but characteristic
granular demineralisation of the vault, along with accentuation of the
temporal line on frontal radiographs.
•• In Paget’s disease, thickening of the bone is characteristic.
•• In haemolytic anaemias, the diploic space widens with thinning of the
tables of the skull vault (especially the outer table) and a radial disposition of
the diploic trabeculae, giving rise to the so-called “hair-on end” appearance.
•• Multiple, rounded radiolucent areas suggest deposits of multiple myeloma
or osteolytic metastases.
•• Larger well-defined areas of radiolucency may indicate deposits occurring in
reticulosis which, in older children and adults, usually manifests as the solitary
“eosinophilic granuloma”. In very young patients, these areas may be confluent
as in the Letterer-Siew disease or the Hand-Schuller-Christian syndrome.
Intracranial Calcification
•• Calcification within the skull may be physiological or pathological.
•• The structures in the midline that calcify are the pineal body, the falx cerebri,
the habenular commissure and the Pachionian granules.
Chapter 7 • Conventional Radiology
55
•• The normal structures away from the midline that calcify are the choroid
plexus, the petroclinoid ligament, the lateral edge of the diaphragma
sellae and the carotid artery. The carotid siphon may show calcification in
arteriosclerosis and may simulate a suprasellar calcification and is identified
by its curvilinear shape and parallel streaks.
•• Calcification of the midline structures is of clinical importance as they may
be shifted to the opposite side by a space-occupying lesion in the supraten-
torial region, thus providing an important lateralising sign.
•• Of the three, pineal and habenular calcifications are of much greater
importance, as these structures shift readily, whereas the much more rigid
falx cerebri does not lend itself very easily to a shift.
•• Apart from a lateral shift, the pineal shadow may be shifted superiorly in
the lateral radiograph of the skull by a space-occupying lesion dorsal the
midbrain, e.g. a tentorial meningioma.
•• Abnormal calcification tends to be less dense in our patients, as compared to
patients from developed countries. Contrary to popular belief, tuberculomas
show radiologically visible calcification only in 6–7% of cases.
•• Dense irregular calcification is more often seen in healing brain infarcts
that result from vascular occlusion in tuberculous meningitis and should
not be mistaken for a tuberculoma.
•• In some instances of abnormal calcification, the shape and type of calcifica-
tion may be diagnostic, as in the case of the double-line wavy (“rail-road”)
calcification, seen in the Sturge-Weber-Dimitri syndrome.
•• Suprasellar oval or speckled calcification is seen characteristically in a
craniopharyngioma.
•• Other instances of abnormal calcification occur in tuberose sclerosis,
toxoplasmosis, oligodendroglioma, an aneurysmal sac, chronic subdural
haematoma and dermoids.
•• Of all brain tumours, oligodendrogliomas show the highest incidence of
calcification.
Increased Vascularity
•• An increase in vascularity, as indicated by increased and widened diploic
vascular markings, is of clinical significance only if found to be localised
or unilateral.
•• Such vascularity may point to an underlying vascular neoplasm such as
a meningioma, an arteriovenous malformation or a metastatic deposit.
Localised Areas of Bony Erosion or Sclerosis

•• Irregular areas of hyperdensity in the inner table of the frontal bone, as seen
in hyperostosis frontalis interna, are not of any pathological significance.
•• Erosion is associated with increased vascularity in the bone, whereas
sclerosis occurs with decreased blood supply or as a reaction to tumour
tissue infiltrating the bone.
•• Direct pressure may also expand or erode the bone, as happens at the internal
auditory meatus in an eighth nerve tumour or the tip of the petrous bone in
a trigeminal neurinoma or in the pituitary fossa due to an intrasellar tumour.
•• Local areas of bony erosion may be caused by an adjacent surface tumour
like a meningioma. The inner table is more widely affected and there may be
an associated increase in the local vascularity. A combination of sclerosis
and erosion or sclerosis alone may occur, e.g. reactive sclerosis produced
by a meningioma of the sphenoid ridge.
56
•• Fibrous dysplasia in the cranial vault present as cystic expansion of the

diploic space, usually in the direction of the outer table, with a coarsening
of the diploic pattern.
•• Lesions in the base of the skull, however, present as a diffuse fairly dense,
sclerotic thickening of the bone, which is often bilateral. The sclerosis
often extends to the infratemporal and maxillary regions, giving rise to
the condition described as “leontiasis ossea”. When unilateral, it may
closely mimic a meningioma of the sphenoidal ridge. It can be differentiated
from the latter by the more diffuse bone formation and associated cystic
expanding lesions, seen in other parts of the skeleton.
•• While viewing the skull X-rays the various cranial air spaces—the frontal,
ethmoidal, sphenoid, mastoid and maxillary sinuses should be seen for
evidence of thickening of mucosa, opacity, fluid level, etc.
Raised Intracranial Pressure

•• In infants and children, raised intracranial pressure is manifested by sepa-
ration of the sutures and increased convolutional markings with thinning
of the bone.
•• Although, the sutures in infants normally tend to be somewhat wide in the
neighbourhood of the fontanelles, any separation beyond 2 mm is indicative
of raised intracranial pressure.
•• Such sutural diastasis may also be seen in young adults, occasionally up
to the age of 20 years.
•• Prominent convolutional markings with premature fusion of the sutures
are seen in craniosynostosis. By contrast, the fully ossified skull of adults,
with sutures partly or completely fused, does not allow sutural separation.
Likewise, abnormal convolutional markings also fail to develop in adults
even with marked increase in intracranial pressure.
•• Under these circumstances, the changes occurring in the sella turcica
constitute by far the most important manifestation of raised intracranial
pressure.
•• In the earliest phase, there is demineralisation of the subcortical bone
leading to a loss of the normal “lamina dura” (white line) of the sellar floor.
•• This is followed by a thinning of the dorsum sellae and the posterior clinoid
processes. The dorsum sellae later becomes foreshortened and pointed,
resulting in a shallow sella turcica.
•• In extreme cases, the sella becomes very shallow and flattened with its
floor and anterior wall demineralised and the posterior clinoid processes
and the dorsum sellae destroyed.
•• The pituitary fossa may balloon-out in some cases of increased intracranial
pressure associated with hydrocephalus. In such cases, the infundibular
recess of the enlarging third ventricle acts like an expanding intrasellar
lesion and the X-ray appearances resemble those of a pituitary adenoma.
•• Another useful sign of increased pressure is the enlargement of the
emissary foramina of the occipital region. This is due to increased
intracranial venous pressure, which is transmitted to the exterior, through
the emissary and diploic veins.
•• Superficial expanding intracranial lesions like a congenital cyst or a chronic
subdural haematoma may cause a localised thinning and bulging of the
overlying bone.
57
Craniostenosis (syn. Craniosynostosis)

•• In craniostenosis, one or more sutures of the skull fuse prematurely during
infancy or early childhood. This requires early recognition and treatment.
•• Craniosynostosis is classified into the complete or partial types.
•• In the complete variety all the sutures are fused, the head assumes a
rounded (oxycephalic) or pointed or tower-like (turricephalic) shape. There
is a marked increase in the convolutional markings due to the pulsation
effect of the normal brain on the vault of the abnormally small skull.
•• Deformity resulting from a combination of complete craniostenosis and
hypertelorism, proptosis and hypoplasia of the maxillary antra is called
“craniofacial dysostosis” or Crouzon’s disease.
•• The growth at the fused sutures is arrested, whereas it continues normally
at the open sutures in partial craniostenosis.
•• When the sagittal suture is prematurely fused, the growth occurs at the
coronal and lambdoid sutures and the skull grows in an anteroposterior
direction, resulting in a dolicocephalic or scaphocephalic shaped skull.
•• If the coronal or lambdoid sutures fuse abnormally, the skull is foreshortened
in its AP diameter, resulting in brachycephaly. In another variety of
incomplete craniosynostosis, fusion of one half of the coronal or lambdoid
sutures results in an asymmetrical skull, i.e. plagiocephaly.
Microcephaly
•• The microcephalic skull is small due to an under-developed brain. The
sutures are normal and the fontanelles are closed. There are virtually no
convolutional markings on the skull vault. There is usually some degree of
“shelving” of the frontal bone.
•• In a few cases due to lack of growth stimulus, the sutures fuse prematurely
leading to “secondary craniosynostosis”. From the point of view of
treatment, early differentiation between the small skull due to primary
premature craniosynostosis and microcephaly with or without secondary
craniosynostosis is of vital importance.
•• The former needs surgical intervention, whereas surgery has no role for
true microcephaly.
•• An early decision is necessary, as the operation should be undertaken in
the first year of life when the brain has its maximum rate of growth.
•• The differentiation is easy if the sutures are normal, the small skull then
obviously being secondary to the underlying microcephaly. If, however,
secondary craniosynostosis has supervened, the absence of convolutional
impressions in microcephaly differentiates it from the characteristic
excessive convolutional markings seen in primary cranisynostosis.
“Hemiatrophy” of the Skull

•• In infantile hemiplegia when one cerebral hemisphere fails to develop fully,
the skull on the affected side appears smaller than the opposite side and
the bones are thicker. The crista galli is also shifted to the atrophic side.
•• In the AP view, the atrophy of one half of the skull is well seen and is
commonly known as “hemiatrophy of the skull”.
Platybasia and Basilar Invagination

•• Platybasia is the term applied to the condition in which the base of the
skull is flat.
58
•• This is assessed by measuring “Welcker’s angle”, i.e. an angle subtended

by the lines joining the nasion to the tuberculum sellae and that joining
the tuberculum sellae to the anterior margin of the foramen magnum. The
normal limit of the angle is 125 degrees. If the angle measures more than
140 degrees, platybasia is said to exist.
•• Basilar invagination and basilar impression are terms used to indicate
elevation of the median part of the floor of the posterior cranial fossa; this
condition may coexist with platybasia and developmental anomalies of the
craniovertebral junction, such as occipitalisation of the atlas and atlanto-
axial dislocation.
•• A number of radiological lines and measurements are available to determine
the presence and degree of basilar invagination.
•• A few of the more important ones are mentioned:
–– Chamberlain’s line extends from the posterior end of the hard palate
to the posterior lip of the foramen magnum. If more than one-third of
the odontoid process extends above this line, basilar invagination is
present.
–– McGregor’s line joins the posterior end of the hard palate to the
lower margin of the occipital squama. If the tip of the odontoid process
extends more than 5 mm above this line, basilar invagination is sug-
gested.
–– Bull’s angle is subtended between the line extending the hard palate
backwards and the line joining the centre of the anterior and posterior
arches of the atlas extended forwards. If this angle measures more
than 13 degrees, basilar invagination is indicated.
–– Clivus-canal line is a line which is extended along the plane of the
clivus into the spinal canal. The odontoid tip normally lies anterior and
inferior to this line and if the tip of the odontoid projects superior and
behind this line, basilar invagination is present. For all the above, a
strict lateral view of the skull is necessary.
–– Fischgold’s line or the interdigastric line joins the digastric grooves
of the two sides. In the AP projection, basilar invagination may be diag-
nosed, if the atlanto-occipital joint lies less than 7 mm below this line.
–– McRae’s line measures the sagittal diameter of the foramen magnum
from the opisthion (the posterior lip of the foramen magnum) to basion
(the anterior lip of the foramen magnum). If the tip of the odontoid is
above this line, BI is present.
Sellar and Parasellar Neoplasms

•• The size and dimensions of the sella are quite variable in the normal skull
X-ray.
•• The upper limits of normality are:
–– Anteroposterior diameter—17 mm
–– Depth—14 mm
–– Width—15 mm.
•• The dorsum sella is markedly thinned (but not destroyed) and is concave
forwards and the anterior clinoid processes are thinned and sharpened by
erosion from below (undercutting).
•• The sella is deepened; a depth of more than 15 mm and an AP diameter
of 20 mm are definitely abnormal. The floor may be so demineralised that
the tumour actually appears to project into the sphenoid sinus. Irregular
59
growth may cause a step to be visible in the floor of the sella, “Double floor”
in a “strict lateral” view.
•• The enlargement of the sella in some cases of raised intracranial pressure
may simulate a pituitary tumour due to the infundibular recess of the third
ventricle acting like an intrasellar lesion.
•• The X-ray changes in pituitary tumours have been graded by Hardy:
–– Grade I: The sella turcica is normal in size, although there may be a
lowering of the floor on one side as revealed by strict lateral X-rays of
the skull.
–– Grade II: The sella turcica is enlarged to various degrees but the floor
remains intact.
–– Grade III: When the erosion is well localised to an area of the floor of
the sella.
–– Grade IV: When all the boundaries are barely visible and the entire
floor of the sella is diffusely eroded or destroyed, having the aspect of
a ‘phantom’ sella.
•• In acromegaly, the paranasal sinuses are large, the skull bones are
thick and coarsely trabeculated and the bony prominences and ridges
accentuated. The skull vault is usually thick and the mandible is also
thick, with everted edges. There is fairly well-marked prognathism with
malocclusion of the teeth. There is also a ‘tufting’ of the terminal phalanges
of the fingers and toes.
•• Craniopharyngiomas are usually suprasellar and about two-thirds of them
show some calcification. Classically, the calcification is of the curvilinear
or “eggshell” variety situated just above the sella. More often one sees a
diffuse speckled calcification.
IMAGING OF THE SPINE

Plain X-rays
•• Special views are necessary to demonstrate changes in the atlas and the
odontoid process.
•• In the cervical region, in addition to the AP and lateral views, oblique views
are necessary to show clearly the intervertebral foramen.
•• Lateral views in flexion and extension help in determining minor subluxa-
tions between the cervical vertebrae and may also demonstrate abnormal
mobility. Obliteration of the cervical lordosis itself is a useful sign.
•• Proper visualisation of the lower most cervical and upper four thoracic
vertebrae is often difficult, especially in obese patients.
•• The structures to be examined are the upper and lower borders of the
body, the trabeculae in the body, the intervertebral disc space, the pedicles,
the inter-articular joints, the laminae, the transverse processes and the
spinous processes.
•• One should also look at the paravertebral shadow, the head, neck and
the body of the ribs and other shadows like that of the lateral border of
the aorta, etc.
•• The interpedicular distance varies from the cervical to the lumbar spine,
with an enlargement in the cervical and lumbar regions corresponding to
the origin of the brachial and lumbosacral plexuses. The interpedicular
distance increases from C2 to C6 and then narrows from C6 to T4, below
which there is a progressive increase.
8
CHAPTER Basic Principles of
CT Scan and MRI Scan
Veena Norhona
INTRODUCTION
•• The first computed tomography (CT) scanner was developed by Sir Godfrey
Hounsfield in 1972.
BASIC PHYSICS
•• Computed tomography uses X-rays to obtain cross-sectional, two-
dimensional (2D) images of the body.
•• The cross-sectional image is produced by 360° rotation of the X-ray tube
around the patient.
•• The transmitted radiation is measured by the detectors located inside the
gantry like a ring around the patient.
•• The final image is generated from these measurements. The gantry of the
CT machine houses the X-ray tube and the detectors.
TYPES OF SCANNING TECHNIQUES

Axial (Sequential) Scanning
•• In sequential scanning, a single slice is obtained with a single 360° rotation
of the tube.
•• The disadvantage is that the time taken for an individual study is long,
hence prone to motion artifacts and the quality of reformations is suboptimal.
Helical (Spiral) Scanning

•• With the advent of slip ring technology, the continuous rotation of the X-ray
tube around the patient is made possible during continuous patient table
movement. This led to the development of helical scanning.
•• The transmitted radiation thus, takes the form of a helix or spiral around
the patient acquiring a large volume of data. This allows larger anatomical
regions of the body to be imaged during a single breath hold, thereby
reducing the possibility of artifacts caused by patient movement. Faster
scanning also increases patient throughput.
•• Multislice or multidetector machines utilise the principles of the helical
scanner but incorporate multiple rows of detector rings. They can, therefore,
acquire multiple slices per tube rotation, thereby increasing the anatomical
coverage in a shorter time.
Chapter 8 • Basic Principles of CT Scan and MRI Scan
61
COMPUTED TOMOGRAPHY TERMINOLOGIES

Pixel and Voxel
•• Every CT image is made up of a square of picture elements called the pixel
and volume element called the voxel (Fig. 1).
•• The obtained CT image is subdivided into a matrix of up to 512 × 512 or
1024 × 1024 elements.
•• The pixel width is determined by the field of view (FOV) and matrix size,
i.e. FOV/matrix.
•• The voxel volume = pixel area × slice thickness.
Hounsfield Unit or Computed Tomography Number

•• Each pixel is assigned a numerical value (CT number), based on the
attenuation of X-rays by the tissue.
•• This number is compared to the attenuation value of water and displayed
on a scale of arbitrary units named HU after Sir Godfrey Hounsfield.
•• This scale assigns water an attenuation value (HU) of zero.
•• Each number represents a shade of grey with +1000 (white) and –1000
(black) at either end of the spectrum (Fig. 2).
•• The CT number of various tissues in the body is as follows:
Brain grey matter 35–40 HU
Brain white matter 30–35 HU
Blood—Flowing blood 40 HU
Acute haematoma 70–90 HU (depends on the Hb
concentration and coagulation profile)
Calcification + 80 HU and above
Fat – 100 HU
CSF 0–10 HU
Bone + 800–1000 HU (depends on the type of
bone).
Fig. 1: Pixel—represents the matrix and voxel represents the slice thickness
Fig. 2: Scale representing the range of Hounsfield numbers of the tissues

seen in the body
62
Window Level and Window Width

•• The term “window level” (WL) represents the central Hounsfield unit of all
the numbers within the window width (WW).
•• The WW covers the HU of all the tissues of interest and these are displayed
as various shades of grey.
•• Tissues with CT numbers outside this range are displayed as either black
or white.
Slice Thickness
•• The slice thickness can be varied depending on the anatomical region to
be covered by varying the beam collimation.
•• Orbit scanning is done using 2–3 mm slice thickness, posterior fossa
4–5 mm slice thickness and supratentorial brain parenchyma 10 mm slice
thickness.
Pitch
•• Pitch is the terminology used in helical scanning and denotes the distance
travelled by the table (in millimetres) during one complete rotation of the
X-ray tube, divided by the slice thickness (millimetres).
Table distance per 360° rotation (mm)
Pitch = –––––––––––––––––––––––––––––––––––
Slice thickness (mm)
IMAGE POSTPROCESSING
•• Multiplanar reformatting: With the current multi-slice CT scanner, it is
possible to obtain isotropic sagittal and coronal reconstructions. These
are useful in pediatric and trauma patients who cannot be positioned for
direct coronal scans.
•• Three-dimensional (3D) imaging: The acquired data can also be
postprocessed to obtain a 3D model to display spatial information or surface
characteristics (volume and surface rendering). This is useful in paediatric
craniofacial anomalies and maxillofacial injuries to guide the surgeon in
treatment planning.
•• CT angiography (CTA): This involves injection of 100–120 mL of contrast
medium, rapidly, using a pressure injector at a predetermined rate of
injection. Serial axial images are obtained. These images are then used
for reconstruction of the data using maximum intensity projection to get a
display of the vascular tree. By altering the time of image acquisition and
contrast injection, we can obtain only the arterial or venous phases.
COMPUTED TOMOGRAPHY CONTRAST MEDIA

•• These are iodine containing compounds.
•• Iodine absorbs X-rays within the CT range (120 KVp) since iodine has an
atomic number of 53 and atomic weight of 127.
•• There are two types of contrast agents used:
–– Ionic contrast: These are sodium or methylglucamine combined with
a tri-iodinated benzene ring to form soluble salts. These are hyperos-
molar and hence are likely to cause severe contrast reactions. These
are contraindicated intrathecally.
63
–– Nonionic contrast: These are near iso-osmolar and hence tend to

produce fewer side effects and considered relatively safe for patients.
•• Absolute contraindication for contrast:
–– History of previous contrast sensitivity
–– Abnormal renal parameters.
•• Diabetes and multiple myeloma patients are more likely to develop altered
renal function post IV contrast injection.
•• Patients with myasthenia gravis, sickle cell anaemia and pheochromocytoma
are at risk of developing contrast-induced symptoms.
ADVANTAGES AND CLINICAL USE OF

COMPUTED TOMOGRAPHY
•• CT is readily available in most hospitals and is cost- effective.
•• It is a rapid imaging modality with excellent image resolution, hence useful
in trauma, paediatric and uncooperative patients.
•• Patients in whom magnetic resonance imaging (MRI) is contraindicated.
DISADVANTAGES OF COMPUTED TOMOGRAPHY

•• Radiation—The effective doses from diagnostic CT procedures are typically
estimated to be in the range of 1–10 mSv.
PHYSICAL PRINCIPLES OF MAGNETIC

RESONANCE IMAGING
BASIC PRINCIPLES OF MAGNETIC
RESONANCE IMAGING
•• Magnetic resonance imaging (MRI) is based on the principles of nuclear
magnetic resonance (NMR).
•• Magnetic resonance imaging is based on the absorption and emission of
energy in the radiofrequency (RF) range of the electromagnetic spectrum.
•• The human body is primarily made up of fat and water, which have many
hydrogen atoms (almost 63%).
•• The hydrogen atom (1H) consists of a single positively charged proton that
spins around its axis. These charged particles create an electromagnetic
field, similar to that of a bar magnet.
•• The proton possesses a property, called spin, which has a small magnetic field.
•• These spinning particles have a net magnetic moment, which has both
magnitude and direction. In the absence of an external magnetic field,
these protons are randomly oriented.
•• When placed in a magnetic field of strength B, the protons align themselves
parallel or antiparallel to the external magnetic field.
•• There is a low energy state where the poles are aligned N-S-N-S and a
high-energy state N-N-S-S. This particle can undergo a transition between
the two energy states by the absorption of a photon.
•• A particle in the lower energy state absorbs a photon and ends up in the
upper energy state.
•• Application of a RF pulse of appropriate duration and amplitude excites
these protons from the lower energy state to the higher energy state.
64
•• The MRI signal results from the energy difference of the spins emitted
during transition from the higher energy state to the lower energy state. The
signal is thus proportional to the population difference between the states.
•• When the RF pulse is applied, the protons are tipped into the horizontal
or X-Y plane by an angle termed as the flip angle or tip angle depending
on the type of RF pulse.
•• The rate at which the protons precess is termed as frequency and the
angular position of the precessing spin is called the phase of the spin.
•• The frequency of precession (f) is called the Larmor frequency and is
characteristic of the specific nucleus and strength of the external magnetic
field.
•• Hydrogen has the highest gyromagnetic ratio and is the most abundant
body element, hence is the natural choice for H signal.
Radiofrequency Field
•• Every nucleus in the body precesses at its own Larmor frequency and will
produce an MR signal only when the RF energy is delivered at the correct
frequency.
•• The excitation RF pulses are delivered by coils that produce an RF field
perpendicular to the external magnetic field.
•• The RF is absorbed by the nuclei and the magnetic moment is tipped away
from the Z-axis, i.e. axis of the external magnetic field depending on the
duration and amplitude of the RF pulse.
Free Induction Decay

When the RF pulse is switched off, the magnetic momentum of the nuclei
begins to return to its original position, thereby transferring the absorbed energy
and inducing alternating current signal in the receiver coil. This is termed as
free induction decay (FID).
T1 and T2 Relaxation
•• When the RF pulse is switched off, two processes take place simultaneously
–– Recovery of the net magnetic moment in the Z axis—termed as
longitudinal or T1 relaxation. T1 is the time required for the build up of
63% of the original magnetisation along the Z axis.
–– Loss of phase coherence in the X–Y plane or transverse plane—
termed as T2 relaxation.
•• The nuclei while returning to the ground state dissipate their excess energy
to their surroundings, which is called the lattice. This process is named as
spin-lattice relaxation.
•• Smaller molecules reorient more rapidly than larger molecules. The
medium-sized molecules, such as lipids, relax faster as their frequency of
rotation is closer to the Larmor frequency than that associated with pure
water or larger molecules such as proteins.
•• Thus, T1 relaxation times depend on magnetic field strength because the
latter affects the Larmor frequency. Thus water has a long T1.
•• Anything that changes the magnetic field strength also changes the
precessional frequency and causes a loss of phase coherence (dephasing)
and shrinking of the transverse magnetisation. This is called T2 relaxation
or spin-spin relaxation.
65
Repetition Time
•• The time between two RF excitation pulses is called the repetition time (TR).
•• Longer values of TR allow more T1 relaxation to occur, and this property
can be exploited to manipulate the contrast between tissues with different
T1s or the signal-to-noise ratio in an image.
Echo Time
•• The time from the centre of the RF excitation pulse to the centre of the
echo is the echo time (TE).
•• The amplitude of the transverse magnetisation at the echo peak depends
on TE and T2 of the tissue.
•• As TE is prolonged, the transverse magnetisation becomes weaker.
Slice Orientation
•• The orientation of a slice, i.e. axial, coronal or sagittal, depends on which
of the three magnetic field gradients is activated during the RF pulse.
•• An RF pulse in the presence of the z gradient creates a transverse slice.
•• The x and y gradients select slices provide the sagittal and coronal
orientations, respectively.
•• Oblique slices are created by activating two or more gradients during an
RF pulse.
INSTRUMENTATION
•• The key components of an MR system:
–– Magnet
–– Gradient
–– RF subsystem
–– Computer.
The Magnet
•• The magnet is the main component of the MR system.
•• The higher the field strength the better is the signal-to-noise ratio.
•• The strength of the magnetic field is measured in Gauss (G) or Tesla (T)
units (10,000 G = 1 T).
•• Diagnostic MR systems usually employ magnets with operating field
strengths ranging from 0.02 to 3 T. Research systems operate above 3T
up to 9T.
•• There are three types of magnets in common use for MRI:
–– Superconducting electromagnets
–– Resistive electromagnets
–– Permanent magnets.
Superconducting Magnets
•• These are the most commonly used magnets and operate at field strength
above 0.5 T.
•• Some metals (e.g. Hg) and alloys (e.g. niobium/titanium, Nb/Ti; niobium/
tin, Nb3Sn; and vanadium/gallium, V3Ga) lose their electrical resistance
at very low temperatures and become superconductors.
•• The superconductor most widely used in the construction of clinical magnets
is Nb/Ti.
66
•• This alloy becomes superconducting at 10 K (Kelvin) in the absence of an

external magnetic field. This temperature is provided by a bath of liquid
helium (4 K).
Resistive Magnets
•• A resistive magnet is an electromagnet in which the magnetic field is
generated by the passage of electrical current through a wire.
•• The disadvantage is their high-power consumption, limiting field strength.
Permanent Magnets
•• It uses a horse-shoe magnet.
•• An advantage of these low field permanent magnet systems is that their
C-shaped design is patient friendly and therefore useful in claustrophobic
patients.
•• Their field strength is limited to 0.5 T.
Transmitter and Receiver Coils
•• The body part to be examined is placed inside a coil.
•• Separate coils can be used for transmitting and receiving or a single coil
can be used for both excitation and detection (transceiver coil).
•• A coil is a winding of low-resistance wire, usually made of copper.
•• Surface coils are used to study small regions such as the eye. The
advantage of surface coils is that their signal-to-noise ratio is better as the
part is close to the coil.
•• Surface coils can receive a good signal from the tissues within the depth
of half its diameter.
COMMONLY USED PULSE SEQUENCES

Spin-Echo Pulse Sequence
•• In a spin-echo pulse sequence two RF pulses, i.e. 90° and 180°, are applied
spaced by a time interval of TE/2.
•• After the nuclei are excited by a 90° pulse, the spins dephase in the x’-y’
plane and this is followed by a refocusing 180° pulse.
•• The 180° pulse results in reversal of the phase of each spin. The position of
the spins has not changed, so they will continue to rotate in the same direction.
•• However, the 180° pulse causes the spins to return towards their starting
point, rather than rotating further away from it. This 90°–180° pulse
sequence is called spin-echo sequence.
•• By altering the echo delay time, and the sequence TR, the spin-echo
sequence can be used to obtain T1, T2 or proton density images.
Gradient Echo Imaging

•• Gradient echo imaging is an imaging technique by which images can be
acquired in much shorter time than conventional pulse sequences.
•• The basic difference between spin-echo and gradient echo imaging is that
gradient echo uses gradient reversals to get an echo, and spin echo uses
180° rephrasing pulse and gradient echo uses flip angle less than 90°.
Inversion Recovery Imaging

•• The inversion recovery sequence uses a 180° inverting pulse, a 90° pulse
and a rephrasing 180° pulse.
67
•• The inversion time (TI) is determined by the TR and T1 of the tissue needed
to be suppressed.
•• Commonly used inversion recovery pulse sequence are:
–– Fluid attenuated inversion recovery (FLAIR) whereby the cerebro-
spinal fluid (CSF) bright signal is suppressed. It is now a routinely used
sequence in brain imaging and especially to image periventricular
plaques in multiple sclerosis.
–– Short tau inversion recovery (STIR) sequence is mainly used in
imaging the optic nerves. It suppresses the orbital fat and highlights
the lesion within the optic nerve, mainly in optic neuritis.
MAGNETIC RESONANCE CONTRAST

•• Most of the contrast agents in clinical use enhance tissue relaxation.
•• Gadolinium is a rare earth element and toxic by itself, hence it is chelated
with multidentate ligands for safety such as diethylenetriamine pentetate
(DTPA) and tetraazacyclododecane tetraacetic acid (DOTA).
•• It is a paramagnetic substance that shortens the T1 relaxation and hence
makes the tissues with contrast appear bright.
Safety
•• These contrast agents are considered safe with a rate of adverse reaction
such as nausea and vomiting (1–2%) and hives (1%). Severe anaphylactoid
reactions have been reported with an estimated rate of 1 in 200,000 and
1 in 400,000.
•• These contrast agents can be safely used in children above 2 years.
•• They should not be used in patients with compromised renal function. There
have been cases reported of nephrogenic systemic fibrosis in patients with
compromised renal function.
•• Should not be used in pregnancy as its bioeffect on the fetus has not been
established.
MAGNETIC RESONANCE ANGIOGRAPHY

Advantages of magnetic resonance angiography (MRA) versus catheter
angiogram are:
•• Non-invasive or minimally invasive
•• Three-dimensional information can be obtained
•• Can give surrounding soft tissue details.
Disadvantages include:
•• Flow dynamic information is lacking.
Techniques of Magnetic Resonance Angiography

The commonly used techniques in clinical practice are:
•• Time-of-flight (TOF) MR Angiogram:
–– Most widely used MR angiography technique for imaging the intracra-
nial circulation.
–– The basic principle involves suppression of the static background tis-
sue and retaining the signal from the flowing blood.
–– It gives reliable vascular information without the need for intravenous
contrast.
–– The TOF angiogram can be obtained using 2D or 3D sequences.
68
–– Two-dimensional angiograms are used to evaluate slow flowing blood,

but are susceptible to turbulent flow.
–– Three-dimensional angiograms have high spatial resolutions and are
less susceptible to turbulent flow.
•• Phase Contrast (PC) MR Angiogram
–– Moving spins undergo a phase shift in the presence of paired oppos-
ing gradients. This phenomenon is utilised in phase contrast magnetic
resonance angiogram (PC MRA).
–– Advantages: It gives flow quantification, flow direction, excellent back-
ground suppression and can be used for imaging areas of slow flow
–– Disadvantages: Long scan time.
Contrast-Enhanced Magnetic Resonance Angiography

•• It is now possible to obtain MRA images almost at par with conventional
angiogram.
•• The technique involves capturing of high magnetization strength during the
first pass of the vascular contrast, i.e. gadolinium, by appropriate timing
using 3D acquisition.
Advantages
•• Insensitive to saturation effects of the RF pulse as against TOF angiogram
and therefore can cover vessels over a larger FOV
•• Useful in large aneurysms where flow is complex.
NEWER ADVANCED MAGNETIC RESONANCE

IMAGING TECHNIQUES
Diffusion-Weighted Imaging
•• It is based on the principle of Brownian motion, which is dispersion or
random translation of a molecule in a liquid due to thermal agitation.
•• Neuronal tissue consists of tightly and coherently packed axons surrounded
by glial cells.
•• The movement of water molecules is hindered in a direction perpendicular to
the orientation of the axonal fibres. Thus, motion of molecules in biological
tissues is anisotropic.
•• The cell membranes are thought to be responsible for anisotropic diffusion
rather than myelin. The restricted diffusion appears as a bright signal on
diffusion-weighted images.
•• Lesions Bright on Diffusion Images: Acute infarct, bacterial abscess,
epidermoid cyst, tissue with high cellularity, subacute haemorrhage
•• Applications:
–– Stroke
–– Multiple sclerosis
–– Tumours
–– Trauma
–– Abscess.
Functional Imaging
•• It is the demonstration of brain activation secondary to a specific stimulus
based on the functional anatomy of the brain, e.g. the primary visual cortex
is activated using a flicker display or alternating checkerboard pattern as
a visual stimulus.
69
•• Once the brain is activated using a stimulus, there is change in the blood
flow to the particular region due to the increased demand for oxygen and
glucose.
•• This increase in oxygen, i.e. deoxyhaemoglobin concentration causes
local susceptibility effects, which are used to receive the signals using
appropriate pulse sequences. This is termed as blood oxygen level-
dependent (BOLD) contrast imaging.
Magnetic Resonance Spectroscopy

•• Magnetic resonance spectroscopy utilises the differences in the resonance
frequency of nuclei due to their different chemical bond. This is also termed
as chemical shift imaging.
•• The frequency difference varies with the magnetic field and is directly
proportional to the external magnetic field. It is expressed in parts per
million (ppm).
•• The advantages of higher field strength, while performing spectroscopy,
are that it provides better signal-to-noise ratio and better separation of
metabolite peaks.
•• Of all the atomic nuclei, 1H has the strongest response and is found in all
biochemicals. MR spectroscopy thus provides details of the brain chemistry.
•• The spectrum is read from right to left and the metabolites detected on
brain spectroscopy are:
–– Lipid 0.9–1.4 ppm
–– Lactate 1.3 ppm
–– N-acetyl aspartate (NAA) at 2 ppm
–– Creatine (Cr) 3.0 ppm
–– Choline (Cho) 3.2 ppm
–– Myo-inositol 3.5 ppm.
Ratio Normal Abnormal
NAA/Cr 2.0 < 1.6
NAA/Cho 1.6 < 1.2
Cho/Cr 1.2 > 1.5
Indications
•• Tumours
•• Radiation necrosis versus recurrence
•• Infections
•• Neurodegenerative disorders
•• Metabolic brain disorders
•• Stroke.
Magnetic resonance spectroscopy should be carefully interpreted and
correlated with MR images to make a final diagnosis.
9
CHAPTER Radiology:
Intracranial Tumours
Kesavdas
IMAGING MODALITIES
•• The role of imaging includes:
–– Localisation and assessment of the extent of abnormality
–– Characterisation of the abnormality
–– Distinction of neoplasms from non-neoplastic lesions
–– Assessment of the nature of tumour
–– Planning for surgery or other types of therapy
–– Intra-operative control of resection progress
–– Monitoring of response to therapy.
•• Computerised Tomography (CT)
–– CT is a good screening method for the demonstration of supratentorial
abnormalities, because it is accurate and the imaging method, most
often available.
–– It takes a much shorter time and is less costly.
–– It is superior in depicting the presence of calcification and bone abnor-
malities such as destruction, erosion, penetration and hyperostosis.
–– However, imaging of posterior fossa lesions is limited due to bone
artifacts.
–– The definition of the extent of oedema is poor and the neuroanatomical
depiction is poor in comparison to magnetic resonance imaging (MRI).
•• Magnetic Resonance Imaging
–– MRI has a higher sensitivity in the demonstration of oedema and is
better for earlier detection of tumours.
–– It gives a more accurate definition of the extent of surrounding oedema
and mass effect.
–– Brainstem structures are better identified.
–– It gives a better characterisation of brain tumours.
–– Along with the advanced techniques, MRI has become the most useful
pre-operative imaging tool.
•• Intra-operative Ultrasonography
–– It is useful in real-time update for the detection of brain and/or tumour
shift during surgery.
–– It is inexpensive compared to intra-operative magnetic resonance
(MR) imaging.
•• Positron Emission Tomography
–– PET imaging of brain tumours with F-18-fluorodeoxyglucose is helpful
in prognostic stratification of patients and detection of early tumour
recurrence following surgery and radiation/chemotherapy.
Chapter 9 • Radiology: Intracranial Tumours
71
APPROACH TO BRAIN TUMOURS

•• Approximately 15−20% of all intracranial tumours, mostly primary lesions,
occur in children below 15 years of age.
•• A higher proportion of paediatric intracranial tumours occur in the posterior
fossa.
•• A tumour in the cerebellum in the elderly is usually a metastasis.
•• First determine whether the mass arises from within the brain parenchyma
(intra-axial) or from outside the brain parenchyma (extra-axial, in which case
symptoms are usually due to compression of subjacent brain).
•• Intra-axial tumours are twice as common as extra-axial tumours.
•• Radiologic clues that a tumour is extra-axial include:
–– Widening of the ipsilateral subarachnoid space
–– Cerebrospinal fluid (CSF) cleft between the mass and the brain pa-
renchyma
–– Deviation of pial vessels between the mass and the brain tissue
–– Buckling of the grey matter (GM)/white matter (WM) junction
–– Broad base along the dural or calvarial surface
–– Adjacent bony changes such as hyperostosis in meningioma or ero-
sion in acoustic neurinoma.
•• T1 hyperintensity in MRI may represent haemorrhage (methaemoglobin),
melanin (in metastatic melanomas), fat, calcification or slow vascular flow.
Haemorrhage within a tumour is usually seen in:
–– Glioblastoma multiforme (GBM)
–– Anaplastic oligodendroglioma
–– Ependymoma
–– Metastases from renal cell carcinoma
¾¾ Choriocarcinoma
¾¾ Breast carcinoma
¾¾ Melanoma
¾¾ Lung carcinoma
¾¾ Thyroid carcinoma.
•• T2 hypointensity may represent haemorrhage (haemosiderin), calcification,
proteinaceous material or flow voids.
•• Cell composition and relative water content are suggested by imaging.
•• Tumours that show CT hyperdensity and T2 hypointensity often have high
nucleus-to-cytoplasm ratio with decreased relative water content.
•• This is suggestive of densely cellular tumours such as lymphoma, primitive
neuroectodermal tumour (PNET)/medulloblastoma, pinealoblastoma,
metastases from adenocarcinoma/prostate and, sometimes, meningioma.
•• Tumours such as GBM and higher grades of glioma, metastases and
lymphoma in an immunocompromised patient may show necrotic areas
within the tumour.
•• Hypervascular tumours, such as GBM, haemangioblastoma and metastases
from renal cell carcinoma, may show flow voids within the lesion.
•• Enhancement reflects the breakdown of the blood-brain barrier (BBB),
which is normally absent in structures such as the pituitary gland, pineal
gland, choroid plexus and meninges.
•• Several criteria are important for the differential diagnosis of brain tumours:
–– Signal contrast with normal brain
–– Tumour structure
–– The presence or absence of tumour margins
72
–– Extent of perifocal oedema

–– Indirect tumour signs
–– Relation of tumour to blood vessels
–– Richness of tumour blood supply
–– Degree of contrast enhancement.
ADVANCED NEUROIMAGING OF
BRAIN TUMOURS
Unlike conventional imaging, advanced MR techniques also provide physi-
ological information concerning metabolism and haemodynamics.
Perfusion Imaging
•• Brain tumours can induce angiogenesis or the formation of new blood
vessels. Hypoxia occurs as the tumour, which outgrows its blood supply,
can produce angiogenic cytokines; these cytokines are responsible for
angiogenesis.
•• Tumour vessels that are produced in this manner are histologically
abnormal and more permeable than normal. They are also disorganised and
tortuous. These vascular abnormalities and altered flow dynamics lead to
changes in blood volume and flow, which are seen in MR perfusion images.
•• The most frequently used measure of perfusion is the cerebral blood
volume (CBV).
•• The CBV (or the volume of blood passing through a portion of the brain) is
measured in millilitres of blood per 100 grams of brain tissue (mL/100 g).
•• The most common perfusion technique is T2 dynamic susceptibility imaging.
•• The change in signal intensity is plotted against time to form a signal
intensity time curve.
•• The CBV is estimated from the area encompassed by the curve, which is
inverted in this case, since there is signal loss.
•• The cases in which an arterial input function is not determined, only a
relative CBV (rCBV) can be calculated.
•• High permeability or leaks in regions of marked breakdown of the Blood-
brain barsier (BBB) results in intravascular gadolinium extravasating into
the interstitial space. Extravasation can significantly affect calculations
and alter CBV values.
•• Using T1-weighted dynamic perfusion imaging, one can eliminate the
problem with the breakdown of the BBB and permeability. In this technique,
tumour enhancement or transendothelial permeability is measured using
the Ktrans parameter.
•• In general, high-grade brain tumours have greater rCBV than low-grade
lesions.
Spectroscopy
•• In the spectroscopy literature, the most commonly used echo times are
144 milliseconds and 270 milliseconds.
•• At these long echo times, the spectrum is dominated by five different
metabolite peaks:
–– Choline (Cho)-containing compounds; creatine (Cr)
–– N-acetylaspartate (NAA)
–– Lactate and lipid.
•• The choline peak reflects cell membrane turnover.
73
•• Creatine is a good surrogate for energy synthesis.

•• NAA is a marker that is exclusive to neuronal cells.
•• Lactate results from anaerobic metabolism and is detected in necrotic
tumours and infarcted tissue.
•• Cellular and myelin breakdown products result in prominent lipid peaks.
•• In tumours, choline-containing compounds are increased, and NAA is
decreased relative to uninvolved or normal brain tissue. This pattern of
metabolic change is the spectroscopic hallmark of brain tumours.
•• Combined with MRI, MRS can aid in the evaluation of tumour type and grade.
•• The higher-grade gliomas tend to exhibit higher Cho/Cr and Cho/NAA
ratios. The high-grade gliomas also tend to have lipid and lactate as the
result of necrosis.
•• MR spectroscopy can non-invasively enable the distinction between a
solitary metastasis and high-grade gliomas, particularly when combined
with perfusion MR imaging.
Functional Magnetic Resonance Imaging

•• Functional MRI (fMRI) provides activation maps that reflect haemodynamic
variations related to neuronal activity and identify the eloquent cortex.
•• Blood oxygen level-dependent (BOLD) imaging examines changes in local
tissue oxygenation to exploit the magnetic property changes of haemoglobin
as an intrinsic contrast agent.
•• An increase in brain activity causes an increase in oxygen consumption
and an over-compensatory increase in regional cerebral blood flow (CBF),
with a net effect of increased diamagnetic oxyhaemoglobin and decreased
paramagnetic deoxyhaemoglobin.
•• Paradigms may be tailored for language, speech, comprehension, memory
and motor testing.
•• Pre-operative fMRI may be used to better determine the relationship
between tumour margins and the eloquent cortex, interrogate the sup-
plemental cortex or test bilateral haemispheres.
•• Another technique that is coming up for mapping the eloquent cortex is
magnetic source imaging where the information from magnetoencepha-
lography is combined with MRI.
Diffusion Weighted Imaging and

Diffusion Tensor Imaging
•• Diffusion weighted and diffusion tensor imaging is an MRI technique that
is sensitive to directional movement of water molecules and that allows the
identification of functional tracts in vivo.
•• Diffusion weighted imaging can give information about the cellularity of the
tumour and can also differentiate infective brain abscess from a necrotic
tumour.
•• Diffusion tensor imaging (DWI) has the potential to establish spatial
relationships between eloquent white matter and tumour borders.
•• In GBM, it is usually sufficient to characterise the diffusion characteristics
with a single apparent diffusion co-efficient (ADC).
•• A number of recent developments have led to a new application of DWI,
termed diffusion tractography. This application uses diffusion tensor data
to identify specific white matter tracts as opposed to white matter tracts
in general.
74
Susceptibility Weighted Imaging

•• Susceptibility weighted imaging (SWI) is a sequence that is sensitive to
T2 effects.
•• It uses magnitude or phase images, the combination of the two image sets,
obtained with a three-dimensional, fully velocity-compensated, gradient
echo sequence.
•• SWI has exquisite sensitivity to the venous vasculature, blood products
and changes in iron and calcium content.
•• In tumour imaging, it has a role in picking up micro-haemorrhages and the
venous vasculature within the tumour.
SPECIFIC TUMOURS
Glioma
•• Astrocytomas are the most common primary intra-axial masses in adults.
•• According to the World Health Organisation (WHO) three-tier classification
scheme:
–– Grade I tumours are pilocytic or fibrillary. These are diffusely infiltrative
tumours that may show CT hypodensity and very mild T1 hypointensity
with T2 hyperintensity in MRI and usually no enhancement.
–– Grade II tumours are anaplastic with evidence of vascular hyperplasia
and mitotic figures. They have an aggressive appearance with promi-
nent enhancement and mass effect.
–– Grade III tumours are GBM with areas of necrosis and haemorrhage.
These are highly aggressive tumours that have outgrown their own
blood supply. De-differentiation from lower to higher grade tumours is
usually associated with contrast enhancement.
•• Pilocytic Astrocytomas
–– These are histopathologically distinct from the more infiltrative low-
grade astrocytomas.
–– Patients usually present at less than 1 year of age (80% at less than
20 years).
–– Nearly two-thirds of these tumours arise from the cerebellar hemi-
sphere with a dominant cyst and avidly enhancing mural nodule.
–– Most of the remaining tumours occur in the hypothalamic-optic region.
–– On MRI, the solid component shows T1 isointensity to hypointensity
and T2 hyperintensity, while the cystic component shows T1 hyperin-
tensity relative to CSF.
–– Elevated protein in the cyst fluid may cause slight T1 hyperintensity
to CSF.
•• Brainstem Gliomas
–– Account for 1% of tumours in adults and 10−20% of tumours in children.
–– MR shows T2 hyperintensity with mass effect and variable enhance-
ment, which does not correlate with prognosis.
–– Diffuse brainstem gliomas are the most common, at 58−75%.
–– These are usually fibrillary astrocytomas that are centred at the pons
and show ill-defined margins, T2 hyperintensity and mass effect.
–– Focal tumours of the mid-brain, medulla and cervicomedullary junc-
tion have distinct margins, may be solid and/or cystic, and usually do
well after aggressive resection, which is easier to perform for dorsal or
lateral exophytic tumours.
75
Oligodendrogliomas
•• These tumours originate from the oligodendroglia.
•• CT demonstrates calcification in more than 80% of cases.
•• The tumours tend to be subcortical in location with T1 hypointensity and
T2 hyperintensity.
•• Similar to the more common astrocytomas, oligodendrogliomas vary from
low grade to high grade.
Gangliogliomas
•• Gangliogliomas are mixed tumours whose cells originate from both glial
and neuronal lines.
•• They tend to be of low grade and have a good prognosis, although some
may have more aggressive features and de-differentiation into higher-
grade lesions.
•• The lesion is usually cortical, especially in the temporal lobes.
•• These are slow-growing tumours with a longstanding course, which may
result in thinning of the overlying bony calvarium. Tumours may also present
in the brainstem.
•• They are commonly cystic well-delineated lesions which may also have a
solid component.
•• They appear homogeneously hyperintense on T2-weighted images.
•• CT in these tumours is of value in picking up calcification alone.
Meningioma
•• Meningioma is the most common extra-axial neoplasm of adults, represent-
ing 20% of all primary intracranial tumours.
•• These are twice as common in females and occur most often in middle-
aged patients.
•• Meningiomas originate from neoplastic meningothelial (arachnoid cap)
cells, and their distribution parallels that of the cap cells, which are most
abundant in arachnoid granulations.
•• Predispositions to meningioma development include neurofibromatosis type
2, familial susceptibility, hormonal factors and previous ionising radiation.
•• Common sites are the parasagittal and convexity dura, sphenoid ridge,
and parasellar and cerebellopontine angles.
•• Parasagittal meningiomas have a propensity to invade the dural venous
sinuses and cavernous sinus meningiomas cause encasement and
narrowing of the internal carotid arteries.
•• The majority of histopathological subtypes are benign (80−90%); atypical
(5−15%) and anaplastic/malignant (1−3%) grades are uncommon.
•• Recurrence is likely after incomplete surgical resection and with atypical
or anaplastic pathology.
•• Calcification can be detected by CT in roughly 20% of cases.
•• There may be a bony reaction in the adjacent skull, usually hyperostosis
due to stimulation of a bony reaction through growth into the Haversian
canals, and less frequently to bone destruction.
•• They show T1 and T2 isointensity relative to the cortex. Enhancement is
usually relatively homogeneous with occasional cystic components, areas
of necrosis or calcification.
76
•• Oedema in the brain adjacent to a meningioma is variable and more

frequent in larger lesions. Demonstration of indistinct tumour margins with
adjacent brain parenchyma should suggest more aggressive tumours.
•• Perfusion MRI shows hypervascular tumours with greater elevations of
the endothelial permeability constant K trans in atypical and anaplastic
meningiomas as compared to typical meningiomas.
Choroid Plexus Papillomas

•• Choroid plexus papillomas and carcinomas may be present at birth, and
the former is twice as common as the latter.
•• In children, these tumours are typically located in the trigone of the lateral
ventricles, usually on the left side.
•• In adults, they are more common in the fourth ventricle.
•• The tumours have fine, lobulated or papillary margins.
•• They are homogeneous with mild T2 hyperintensity, although they may
contain focal hypointensities from calcifications or enlarged flow voids from
branches of the anterior and posterior choroidal arteries.
•• Although hydrocephalus may occur due to tumour overproduction of CSF,
it more commonly occurs due to mass effect and mechanical obstruction,
similar to other intraventricular tumours.
Central Neurocytomas
•• These are heterogeneous masses with cystic areas, calcifications and
haemorrhage.
•• These tumours show neuronal differentiation and tend to occur in young
patients at the age of 20–30 years.
•• These tumours were previously mistaken for intraventricular oligodendro-
gliomas, and are characteristically attached to the septum pellucidum and
located in the body of the lateral ventricle.
•• They have a well-circumscribed smooth or lobulated margin with solid and
cystic components and heterogeneous enhancement.
Chordomas
•• Chordomas arise from remnants of the primitive notochord.
•• These tumours are most common in the sacrum (50%), with intracranial
tumours occurring almost exclusively in the clivus (35%).
•• They are benign, but locally aggressive tumours that destroy bone and
may grow into the nasopharynx, parasellar region, or pre-pontine cistern.
•• Imaging shows a lobulated enhancing soft-tissue mass centred on the
clivus exhibiting bone destruction and areas of calcification, which are
better seen on CT.
•• MRI shows marked T2 hyperintensity that reflects the high water content of
these tumours, and may exhibit internal reticulations or septations.
Craniopharyngiomas
•• Craniopharyngiomas arise from metaplasia of squamous epithelial
remnants of Rathke’s pouch, from which the anterior pituitary develops.
•• These tumours are usually centred in the suprasellar cistern and may
extend into the sella, retroclival region and third ventricle; 5% may be
purely intrasellar and rarely may be exclusively located in the third ventricle.
77
•• They have a bimodal distribution, with a larger peak at 5–15 years than
at 50–60 years.
•• They may be cystic, solid or mixed cystic and solid. Nearly half of paediatric
suprasellar tumours are craniopharyngiomas.
•• These tumours are of the adamantinous variety, with lobulated contours,
predominantly cystic or mixed cystic and solid with calcification, intensely
enhancing solid components, and encasement of the circle of Willis vessels.
•• The squamous papillary craniopharyngiomas tend to occur in older adults
and present with predominantly solid tumours.
•• Calcifications and recurrence are both less common in adults.
•• MR often shows heterogeneous signal intensity with T1 isointensity
to hyperintensity, fluid-attenuated inversion recovery (FLAIR) and T2
hyperintensity.
Dermoids and Epidermoids

•• These tumors represent non-neoplastic inclusion cysts that presumably
arise from ectodermal cell rests during embryogenesis.
•• Epidermoids:
–– Composed of desquamated cyst wall contents from an ectoderm-
derived epithelial lining.
–– They are most frequently found off the midline with insinuation into
cisternal spaces and fissures, most often in the cerebellopontine angle
(CPA), and less frequently around the sella.
–– Their hyperintensity on FLAIR and DWI allows them to be readily dis-
tinguished from arachnoid cysts.
•• Dermoids:
–– Similar to inclusion cysts, but they may also contain ectodermal-
derived appendages (e.g. hair, teeth and sweat glands).
–– They are more typically found near the midline and may be associated
with a dermal sinus.
–– The contents are oily with lipid metabolites that give rise to imaging
features similar to those of fat, while ectodermal appendages contrib-
ute to heterogeneity.
–– Fat characteristically results in chemical shift artifact, with spatial
misregistration shown as bright and dark bands along the frequency-
encoding direction.
–– Ruptured dermoids may simulate acute subarachnoid haemorrhage as
the oily contents are released into the subarachnoid space.
•• Other Non-neoplastic Extra-axial Lesions Include:
–– Arachnoid cyst (a CSF-filled cavity within the arachnoid membrane that
follows CSF intensity on all sequences).
–– Colloid cyst (anterior third ventricle at the foramen of Monro).
–– Neuroepithelial cyst (most likely intraventricular with choroidal origin).
–– Ependymal cyst and neurenteric cyst (cyst wall composed of gut/respira-
tory epithelium, remnant of the neurenteric canal during embryogenesis).
–– A tall peak at 2 ppm in MR spectroscopy will help diagnosing cysts
lined with ciliated columnar epithelium.
Ependymomas
•• Ependymomas are glial tumours derived from differentiated ependymal
cells along the ventricular system.
78
•• In 60−70% of cases, these tumours occur in the infratentorial compartment

and are intraventricular as they arise from the floor of the fourth ventricle.
•• Most occur in children below 10 years old, and characteristically exit through
the foramina of Luschka or Magendie.
•• The supratentorial tumours occur in patients 30−50 years old and may
be transependymal, intraventricular or more commonly intraparenchymal.
•• Extraventricular tumours are thought to arise from ependymal cell rests,
which are predominantly located at the angled margins of the ventricles.
•• The signal characteristics are non-specific, with T1 hypointensity and T2
isointensity to hyperintensity, cystic changes in 74%, and hemorrhage in
13−21%. The tumours show intense but heterogeneous enhancement with
little or no peri-tumoural oedema.
•• Calcifications occur in half of these tumours, as opposed to the Primitive
neuroectodermal tumours (PNET)/medulloblastomas, in which calcification
is uncommon.
Germ Cell Tumours

•• Germinomas are the most common intracranial germ cell tumours (GCTs),
accounting for 60% of pineal GCTs and 40% of pineal masses.
•• Around 90% of patients with GCTs are below 20 years of age.
•• Clinically, suprasellar germinomas often present with diabetes insipidus.
•• Germinomas are twice as common in the pineal region as in the suprasellar
region, although 5−10% involve both areas simultaneously. Other possible
midline locations include the thalamus, and fourth ventricle.
•• Suprasellar germinomas are more common in females, while pineal
germinomas have a marked male predominance (9:1).
•• CT demonstrates a hyperdense, vividly enhancing mass that can be
described as engulfing the pineal gland calcification.
•• MR shows T1 isointensity and slight T2 hypointensity similar to that of
GM because of the high nucleus-to-cytoplasm ratio. There is strong
enhancement.
•• Metastases may occur due to dissemination via the CSF or ependymal
surfaces.
•• MRI is highly sensitive for diagnosing pineal or suprasellar mass lesions,
but has limited specificity for distinguishing GCTs from other tumours. In
these situations, evaluation of the CSF for specific protein markers can help
establish the diagnosis and discriminate germinoma from non-germinoma
lines (i.e. teratoma, choriocarcinoma, mixed germ cell, endodermal sinus
and embryonal carcinoma).
Hemangioblastomas
•• Hemangioblastomas are the most common primary intraparenchymal
infratentorial tumours in adults.
•• These benign tumours represent 10% of all posterior fossa masses,
with 83% occurring in the cerebellar hemispheres and characteristically
contacting the pial surface.
•• Hemangioblastomas usually occur in young males. The principal
differentiating feature between these tumours and similar-appearing
juvenile pilocytic astrocytomas is age, [since the latter tend to occur in
children (5−15 years old)] and their vascularity.
•• They present as a cystic mass with a highly vascular, solid mural nodule
in 60% of patients.
79
•• Enlarged, serpentine flow voids representing feeding vessels may be seen

with MRI.
•• The tumours are well defined and may induce a minimal surrounding
parenchymal reaction. The cyst wall does not enhance, is not neoplastic,
and does not have to be resected at surgery.
•• Excision of the solid mural nodule is usually curative.
•• Up to 25% of hemangioblastomas are associated with von Hippel-Lindau
syndrome, in which case, the tumours present at a younger age and are
multiple, occurring in the cerebellum, brainstem and spinal cord.
Lymphoma
•• Lymphoma has increased in incidence over the past two decades, largely
due to an increased incidence in patients with acquired immunodeficiency
syndrome (AIDS).
•• A pre-operative diagnosis of primary cerebral lymphoma is of paramount
importance to the neurosurgeon. These tumours are exquisitely sensitive
to chemotherapy and radiation therapy.
•• Conventional images often show multiple enhancing masses that often
involve the deep GM, peri-ventricular white matter, subependymal region,
corpus callosum or are located adjacent to CSF spaces.
•• They show T1 hypointensity to isointensity and are hypointense on T2WI
with isointensity to mild hyperintensity because their dense cellularity leaves
little interstitial room for water accumulation.
•• Diffusion restriction with diffusion hyperintensity and apparent diffusion
coefficient (ADC) hypointensity may occasionally mimic an infarct.
•• Homogeneous enhancement is absent in AIDS patients, whose tumours
are more likely to have central necrosis.
•• Despite conventional imaging features that may suggest a highly malignant
neoplasm, perfusion MRI will often show only modest increases in perfusion
that are much less than expected for high grade glioma. This is because
neovascularity is not a prominent feature of lymphomas, since the tumour
cells instead grow around blood vessels in an angiocentric pattern.
Paragangliomas
•• Paragangliomas may arise at the jugular foramen (glomus jugulare) or in the
middle ear cavity (glomus tympanicum). These tumours arise from glomus
bodies (neural crest derivatives) and often present with pulsatile tinnitus.
Glomus jugulare tumours originate in the adventitia of the jugular foramen
and may occlude the jugular vein with growth. At the time of diagnosis,
there is usually infiltration of the tumour into the bony margins of the jugular
foramen with a pattern of permeative bone destruction that is best seen with
CT scan. MRI shows an enhancing soft-tissue mass centred on the jugular
foramen (jugulare) or inferior portion of the middle ear cavity (tympanicum),
or spanning both (jugulo-tympanicum). A soft-tissue component may grow
intracranially toward the cerebellopontine angle. These highly vascular
tumours are characterised by direct visualisation of prominent vessels within
a mass evidenced by MRI “flow voids” or a “salt and pepper” appearance.
Metastases
•• Metastases are the most common supratentorial and infratentorial
neoplasm in adults, accounting for more than 40% of all tumours.
80
•• About half of these lesions are reported to be solitary; however, with the
use of higher doses of gadolinium (as well as higher field strengths), the
number of lesions detected is increasing.
•• In decreasing order of numbers, metastases tend to arise from the lung (50%),
breast (15%, in women), melanoma (11%), kidney and gastrointestinal prima-
ries, although rarely metastases from primary CNS tumours may also occur.
•• They are often located at the germinal matrix (GM)/white matter (WM)
WM junction, reflecting the normally high perfusion of the cerebral cortex.
•• Lesions often have a fair amount of vasogenic oedema (recognised by the
sparing of the arcuate fibres along with its frond-like appearance).
•• Foci of T1 hyperintensity (seen in 3−14%) may represent blood products
(from melanoma, thyroid, renal, breast and lung primaries) or melanin
(in melanomas). These may be distinguished from benign haemorrhagic
lesions by their relatively delayed haemoglobin evolution and incomplete
haemosiderin periphery.
•• Mucinous metastases tend to show T2 hypointensity, especially in meta-
static colon adenocarcinomas.
•• Calcification typically occurs in lung or breast metastases.
•• Cystic lesions are associated with metastatic squamous cell carcinoma.
•• Leptomeningeal metastases are more commonly due to adenocarcino-
mas and melanoma than haematological malignancies. These are best
evaluated by both contrast T1-weighted images (T1WI) and contrast
FLAIR images which show curvilinear or nodular pial enhancement (35%),
hydrocephalus (13%) and cranial nerve deposits (11%).
Pituitary Adenomas
•• Pituitary adenomas represent 33−50% of all sellar and parasellar masses.
•• In 66−75% cases, the tumours are hormonally active and likely to present
earlier with endocrine dysfunction.
•• The hormones include growth hormone, adrenocorticotropin, prolactin
and thyrotropin.
•• Hormonally-inactive tumours present with larger sizes due to mass effect
on adjacent structures.
•• Adenomas usually demonstrate T1 hypointensity; however, variable signal
intensities may occur due to intratumoural haemorrhage, which is more
common after medical treatment with bromocriptine.
•• Complicated macroadenomas may present with cystic changes and
haemorrhage, including fluid-fluid levels.
•• There is avid, immediate enhancement of the normal anterior pituitary
tissue, infundibulum and cavernous sinuses due to the pituitary’s lack of a
BBB and the adjacent hypothalamo-hypophyseal venous plexus.
•• The adenoma shows delayed enhancement, with the differential most
apparent in the first minute after injection.
•• Secondary signs of a small, usually laterally located mass include increased
gland height, eccentric superior convexity, contralateral deviation of the
infundibulum and focal erosion of the sellar floor.
Medulloblastomas/Primitive Neuroectodermal Tumours

•• Medulloblastomas/PNET are the most common posterior fossa neoplasms
in children (more than 33%), although they may also occur in the
supratentorial compartment and have a second incidence peak in adults.
81
•• PNETs classically originate in the midline cerebellar vermis in children and

are more common in males, with a 2:1 ratio.
•• They represent a spectrum of disease with a varied degree of aggressive-
ness, the most aggressive being the atypical teratoid/rhabdoid tumour.
•• Desmoplastic medulloblastomas in adolescents and adults are often
eccentrically located, and arise from the cerebellar hemisphere rather
than the vermis.
•• CT shows homogeneously hyperdense vermian masses.
•• MRI reveals well-circumscribed T1 hypointense and T2 intermediate/
isointense tumours that distort the fourth ventricle, which is usually
displaced in an anterior-inferior direction. The site of origin may be obscured
by large tumours.
•• For distinction from fourth ventricle ependymomas, MRS of medulloblastoma
shows high choline, low NAA and no lactate peak.
•• Contrast MRI of the entire neuraxis must be performed because
subarachnoid drop metastases occur in 15−50% of cases.
•• Supratentorial PNETs are also aggressive malignancies with areas of
cystic change, calcification, haemorrhage, heterogeneous enhancement
and relatively little surrounding oedema. They have a similar propensity for
leptomeningeal and CSF dissemination, and a poor outcome.
Rathke’s Cleft Cysts

•• These originate from persistent remnants of Rathke’s pouch.
•• Forty percent of these cysts are intrasellar and intra-pituitary, and larger
cysts extend into the suprasellar cistern.
•• They are composed of a fibrous wall lined by a single layer of ciliated
cuboidal or columnar epithelium.
•• CT shows a hypodense cyst.
•• Depending on the fluid composition and concentrations of protein, choles-
terol and triglyceride, MR demonstrates variable T1 and T2 signal intensity.
•• The cyst wall should show no calcification and no enhancement; however,
an enhancing rim of compressed normal pituitary tissue or reactive
granulation tissue may be observed.
Schwannoma
•• Schwannoma is the most common type of neurogenic tumour, and
neurofibroma is much less common.
•• Schwannomas originate from Schwann cells whose myelin processes
surround axons of cranial nerves.
•• They are most frequently found at the transition zone between oligoden-
droglial and Schwann cell coverings of the axons.
•• The peak incidence occurs in patients 50−60 years old, and they are slightly
more common in females than in males.
•• They originate much more frequently from sensory than motor nerves, and
thus, identification of a nerve root signature can help improve diagnostic
certainty.
•• Since these tumours are well delineated and encapsulated, they affect the
cranial nerve of origin and adjacent brain by compression rather than invasion.
•• The vestibular division of the eighth cranial nerve (i.e. in the internal auditory
canal and CPA) is the most frequently affected, followed by the fifth and
seventh cranial nerves.
82
•• MR usually demonstrates a T1 isointense to hypointense and T2 hyperin-

tense extra-axial mass.
•• Even very small intra-canalicular vestibular schwannomas can easily be
seen with high-resolution (512 matrix) T2WI or 3D constructive interference
in the steady state (CISS) images.
•• The presence of microbleeds within the tumour in the T2 gradient sequence
or susceptibility weighted image helps in diagnosing schwannomas.
•• Schwannomas show intense enhancement that is usually homogeneous
in smaller tumours and more heterogeneous in larger tumours due to
necrosis or cyst formation.
TUMOUR-MIMICKING LESIONS
•• Some non-neoplastic entities may mimic malignancy due to overlapping
signal abnormalities, enhancement patterns and mass effect with conven-
tional imaging.
•• Advanced MRI, particularly perfusion MRI and MR spectroscopy, may be
very helpful in these situations.
•• Lack of angiogenesis should suggest a tumour-mimicking lesion.
•• A peripherally enhancing mass lesion that shows diffusion restriction and
surrounding T2 hyperintensity may represent a brain abscess or metastasis.
•• The abscess often shows a thin peripheral T2 hypointense rim, which is
thought to represent free radicals caused by the inflammatory process.
Perfusion MRI of the capsular portion of these lesions will show significantly
decreased perfusion for the abscess compared to the neoplasm.
•• Tumefactive Demyelinating Lesions:
–– These may present with enhancement, central necrotic change, mass
effect and surrounding T2 hyperintensity similar to brain tumour find-
ings based on conventional images.
–– Perfusion MRI of these lesions may show mild hyperperfusion, al-
though a conspicuous absence of hyperperfusion is more typical.
–– Blood vessels in the areas of demyelination are intrinsically normal in
comparison to the tumoural neovascularity.
–– An examination of the source T2 images often reveal the presence of
small venules streaming through the lesions without mass effect, which
is a highly specific sign.
•• Acute to subacute infarcts may occasionally present with an atypical
location or history and mimic a tumour, especially if there are DWI/ADC
discrepancies. Ischaemia should decrease to absent perfusion with
decreased CBV and CBF; however, the CBV may also be increased if
there are adequate collaterals or luxury perfusion.
POST-SURGICAL IMAGING
•• Imaging is performed after surgical resection to evaluate for residual tumour
and assess potential complications.
•• MRI is the preferred modality though most of the centres still perform CT.
•• The initial post-operative scan is obtained within 24 hours using
conventional sequences.
•• In this time frame, post-operative changes affecting the BBB are not
manifest, and any enhancement is thought to represent residual enhancing
tumour rather than post-operative changes in the tissue.
83
•• Non-contrast T1WI is essential because a fair amount of hyperintense

blood product may be present.
•• DWI is useful in the post-operative period for patients complicated by acute
neurologic deficits, since:
–– Cytotoxic oedema of acute infarction is characterised by restricted
diffusion (DWI hyperintensity and ADC hypointensity).
–– In contrast to vasogenic oedema of tumour, which has elevated diffu-
sion due to increased extracellular water (DWI hypointensity to slight
hyperintensity and ADC hyperintensity).
RADIATION NECROSIS VERSUS

TUMOUR RECURRENCE
•• Therapeutic necrosis (secondary to radiation therapy or chemotherapy)
cannot be distinguished from residual or recurrent tumour by conventional
imaging methods, which show enhancing mass lesion(s) in the radiation
bed due to disruption of the BBB with surrounding oedema and mass effect.
•• The contrast enhancement simply reflects a breakdown of the BBB, which
may occur in both tumoural disease and therapeutic necrosis. For this
common clinical scenario, advanced imaging can be very helpful.
•• Perfusion MRI will show significantly reduced or even absent capillary
volume in areas of therapeutic necrosis, which manifests as a “cold” region
on an rCBV map.
•• MR spectroscopy will reveal decreased metabolites manifested by reduced
Cho/Cr and NAA/Cr ratios and mild NAA increase are often seen with
successful therapy.
•• These techniques may be misleading, however, if inflammatory cells in the
areas of radiation necrosis are hypermetabolic, leading to false-positive
studies, and comparison with normal-appearing brain may be difficult due
to radiotherapy and/or chemotherapy-induced metabolic depression.
10
CHAPTER Radiology:
Intracranial Infections
Bejoy Thomas
INTRODUCTION
•• CNS infection can result from bacteria, viruses, fungi and parasites.
•• It can manifest as cerebritis, cerebral abscesses, meningitis, encephalitis,
subdural empyema and effusions, and ventriculitis.
•• The pathogen can reach the brain via the haematogenous route and rarely
by direct spread from an adjacent infective focus, e.g. infection in middle
ear or paranasal sinuses.
PYOGENIC INFECTIONS
Cerebritis
•• It is the earliest manifestation of a cerebral infection that may progress to
the formation of a brain abscess.
•• Usually, it occurs 2–3 days following pathogen inoculation.
•• Pathologically, localised yet poorly demarcated areas of parenchymal
softening with scattered coagulative necrosis, oedema, congestion,
petechial haemorrhages and perivascular inflammatory infiltrates can be
noted at this stage.
•• It results from direct spread of infection (head and neck infections/
meningitis) or from haematogenous spread.
•• Magnetic resonance (MR) is more sensitive and it shows an ill-defined area
of isointensity or hypointensity with subtle mass effect (sulcal effacement
or ventricular compression) on T1WI and contrast enhancement is absent
or minimal.
•• On fluid-attenuated inversion recovery (FLAIR) and T2WI, the infected
tissue is hyperintense.
•• In the absence of purulent fluid, DWI may show restricted diffusion in early
cerebritis.
•• Spectroscopy shows the presence of lactate which is non-specific.
Cerebral Abscesses
•• Evolution of an abscess is characterised by four stages:
–– Early cerebritis
–– Late cerebritis
–– Early capsule formation
–– Late capsule formation.
Chapter 10 • Radiology: Intracranial Infections
85
•• In the final stages, the surrounding area of cerebritis extends only minimally
beyond the capsule and the capsule is well formed on its cortical side than
on its ventricular side.
•• The length of time required for formation of a mature abscess varies from
a few weeks to several months.
•• In haematogenous spread, lesions are usually seen in the grey-white matter
junction of ACA and MCA territories.
•• Cerebellar abscesses constitute 2–14% of all cases.
•• The central liquefied portion is slightly hyperintense to cerebrospinal fluid
(CSF) on T1WI and would be isointense to CSF on T2WI.
•• The peripheral rim is hypointense to CSF on T2WI and hyperintense on
T1WI and shows peripheral contrast enhancement on contrast enhanced
T1 weighted sequences.
•• This property of the rim has been attributed to collagen, haemorrhage and
paramagnetic free radicals, within the macrophages which are peripherally
distributed.
•• This hypointense rim usually resolves with successful surgical and/or
medical treatment. So, the rim may be a better indicator of response to
treatment than the residual enhancement.
•• The differential diagnosis for ring enhancing lesions include primary brain
tumours (e.g. necrotic glioblastoma), metastases, resolving haematoma,
infarction and demyelinating diseases. DWI and MRS may help in the
differentiation.
•• Ring enhancement of an abscess is usually thin and smooth, thinner along
the medial margin.
•• Daughter abscesses appear as small adjacent rings, often along the medial
margin of the parent abscess. Oedema surrounding the abscess may be
greater in volume than the abscess itself.
•• If the abscess ruptures into the ventricles, it results in ventriculitis or
ependymitis, which carries a bad prognosis.
•• DWI shows restricted diffusion in the abscesses with calculated apparent
diffusion coefficient (ADC) values in the range of 0.21–0.31.
•• Magnetic resonance spectroscopy appears to be very useful in
differentiating and characterising cerebral abscesses. MRS shows acetate
(1.92 ppm), lactate (1.3 ppm), alanine (1.5 ppm), succinate (2.4 ppm)
and complex peak at 0.9 ppm indicating cytosolic amino-acids like valine,
leucine, isoleucine. They can show lactate/lipid peaks.
•• Acetate and pyruvate/succinate peaks were found to disappear within
1 week after instituting therapy for an abscess.
•• MRS also helps in differentiating aerobic and anaerobic abscesses.
•• DWI and MRS also may help in differentiating pyogenic abscesses from
tubercular and fungal abscesses.
Septic Embolism and Mycotic Abscesses
•• This can occur in patients with history of intravenous drug abuse, bacterial
endocarditis or children with congenital cyanotic heart disease.
•• It can result in major arterial branch infarction, as also multiple small
abscesses located at the grey-white matter junction.
•• Mycotic aneurysms involve intermediate to small branch arteries and are
usually located in more peripheral arterial branches.
•• They are usually small and are difficult to be detected with cross-sectional
imaging and often require digital subtraction angiography for detection.
86
Meningitis
•• Meningitis is acute or chronic inflammation of the leptomeninges.
•• It occurs either secondary to haematogenous spread, direct spread from
the adjacent focus of infection or from penetrating injury to the brain.
•• Pathologically, the affected region shows congestion and hyperaemia of
the pia-arachnoid and distension of the subarachnoid space by exudates.
•• Magnetic resonance imaging forms the most sensitive method for detecting
meningeal inflammation.
•• Unenhanced scans may be unremarkable in the acute stage. Post-
gadolinium images show leptomeningeal enhancement. Pre-magnetisation
and post-magnetisation transfer gadolinium (Gd) increases the sensitivity
of displaying leptomeningeal enhancement.
•• Magnetisation transfer ratios (MTRs) from the affected meninges may give
clues to the aetiological nature of meningeal inflammation.
•• Meningitis can result in several complications which include arterial and
venous infarcts, abscess and cerebritis, subdural collection and empyema.
Hydrocephalus and rarely ventriculitis may also follow meningitis.
•• Subdural collections: These could be subdural effusion or subdural
empyema. Subdural effusion secondary to H. influenzae meningitis is
usually bilateral and is seen as crescentic collections along the frontal
and parietal cortices. They are isointense to CSF in all sequences. The
underlying cerebral cortex does not show signal changes. Post-Gd images
usually do not show enhancement.
•• Hydrocephalus can be communicating or non-communicating, more
frequently seen in children than in adults. It occurs due to adhesions or
loculations secondary to meningitis. Ventricular dilatation with transependy-
mal periventricular CSF seepage (T2 hyperintensity) is seen especially on
FLAIR sequences.
Empyema
•• They represent purulent collection in the subdural and/or epidural space.
•• In 65–70% of cases, it is secondary to otorhinologic infections with a very
rapid clinical course.
•• In the remainder, it is due to previous head trauma, neurosurgical procedure
or secondary to bacteraemia or meningitis.
•• There can be either an epidural or a subdural empyema.
•• Epidural Empyema:
–– It shows lentiform collections, continuous across the midline with a
hypointense margin on both the T1WI and T2WI (medially displaced
dura).
•• Subdural Empyema:
–– These are crescentric or lentiform in shape, located on the cerebral
convexities and are frequently bilateral.
–– On T1WI, they appear hyperintense to CSF which become iso to
hyperintense on T2WI and PD (high protein content).
–– Abnormal signals in the underlying brain parenchyma can be noted.
–– Sulcal effacement and dural venous thrombosis may be associated.
Pyogenic Ventriculitis
•• Gram-negative bacteria, in particular, resistant to standard antibiotics are
the most common cause of infective ventriculitis.
87
•• Ventricular debris was the most characteristic finding which is irregular in

contour because of the high protein content and possibly, necrotic material.
•• Tufts of glial tissue projecting through areas of denuded ependyma into
the ventricular exudate also might contribute to the intraventricular debris.
•• Hydrocephalus has been documented in most cases.
•• Periventricular signal abnormality, detected in 78% of cases with MR
imaging, likely reflects the periventricular inflammatory change which
consists of swollen subependymal astrocytes and perivascular infiltration
with lymphocytes and plasma cells. Chronic infection might result in
subependymal astrocytic and microglial proliferation.
MYCOBACTERIUM TUBERCULOSIS INFECTION

•• Adult tuberculosis often results from post-primary infection and most cases
of childhood TB are due to primary infection.
•• Intracranial TB can present as meningitis, tuberculomas and abscess.
Tuberculous Meningitis
•• Tuberculous meningitis (TBM) usually manifests as enhancement of the
basal cisterns, meningeal enhancement, hydrocephalus and parenchymal
infarctions usually of the perforator territory (e.g. basal ganglia), both on
CT and MRI.
•• The basal meninges are involved early in the course of the disease with
thick gelatinous exudates.
•• Circle of Willis vessels may be involved resulting in arteritis, thrombosis
and infarction.
•• Hydrocephalus, usually communicating, occurs in most cases. Hydrocepha-
lus can be occasionally obstructive due to mass effect or obstruction of the
aqueduct or outlet foramina.
•• Chronic sequelae include mental retardation, paralysis, cranial nerve palsy,
seizures, and speech or visual deficits.
Tuberculomas
•• They may develop secondary to haematogenous spread or extension into
the adjacent parenchyma, via cortical veins or small penetrating arteries.
•• They can show various stages and are composed of central solid/liquid
caseation, surrounded by a capsule of collagenous tissue, epithelioid cells,
giant cells and phagocytes.
•• They usually occur in the grey-white junction, periventricular regions,
subarachnoid, subdural and epidural spaces.
•• On CT, the immature forms appear as small discs and rings with massive
oedema, while the mature forms appear as large rings or lobulated masses.
•• The large rings enclose a mass, whereas the lobulated masses represent
coalesced small discs and rings forming a large tuberculoma. Target sign
may be seen on CT scan.
•• MR imaging shows variable findings, depending on the stage of the
tuberculoma.
•• On T1WI, it is usually isointense to grey matter with a slightly hyperintense
rim.
•• T2WI shows signals iso to hypointense to brain parenchyma, due to
paramagnetic free radicals or high cellular density. If hyperintense on T2,
it is due to liquefactive necrosis of the centre.
88
•• Perilesional oedema is less compared to pyogenic abscess which can be

intense in the early stages.
•• Post-Gd images show intense nodular or ring-like enhancement. Healed
tuberculomas may show calcification. Healing time depends on the size
of the initial lesion.
•• Tuberculomas may have distinctive MRS with lipid peaks and phosphoserine
peaks.
Tuberculous Abscess
•• Tuberculous abscess may develop due to liquefactive breakdown of
caseated tuberculomas.
•• They are usually larger than a tuberculoma.
•• On CT, they appear hypodense with surrounding oedema and mass effect
and ring enhancement.
•• MRI shows central hyperintensity on T2WI with post-Gd ring enhancement.
•• DWI shows restricted diffusion with MRS, showing a strong lipid lactate
peak and sometimes a phosphoserine peak.
NEUROCYSTICERCOSIS
•• Neurocysticercosis is a common parasitic infection of the CNS.
•• This disease is prevalent in developing countries and particularly affects
the socially and economically deprived classes of society, where hygiene
is often poor.
•• Man gets afflicted by the parasite when he consumes infected pork or
vegetables contaminated with parasitic eggs.
•• NCC is caused by the larvae of Taenia solium; Cysticercosis cellulosae
and less frequently by Cysticercosis racemosae.
•• C. cellulosae is characterised by a small cyst of 5–15 mm, the cyst wall is
thin and transparent and the cyst contains clear fluid with a pearly white
invaginated scolex. C. racemosae are often large, measure 4–12 cm and
are devoid of a scolex.
•• Based on the location of the cysts, five forms are recognised: parenchymal;
spinal; arachnoid; ventricular and mixed.
•• The cysts can remain viable in the CNS for several years depending on
the immune status of the individual.
•• Morphologically, four stages of disease are identified:
–– Vesicular: The cyst is well defined, contains a scolex and is viable
–– Colloidal: Death and disintegration of the cyst, the cyst fluid becomes
turbid and there is an associated inflammatory process.
–– Granular nodular: The cyst wall retracts with thickening of the cap-
sule. Chronic inflammatory infiltrates are seen around the cyst with
moderate to intense fibrillary astrocytosis.
–– Calcific stages: The lesion retracts to a fraction of its initial size, fibro-
sis gradually replaces the lesion and often it gets calcified.
•• Epilepsy is the most common and often, the only symptom of parasitic
infestation. Other manifestations include headache, arachnoiditis, focal
neurological deficits, hydrocephalus, raised intracranial pressure and
rarely encephalitis.
•• MRI is the investigation of choice and can identify various stages of NCC
and this reflects evolution of the parasite through different pathological
changes.
89
•• In the acute phase of invasion, MR may show a focal non-enhancing

hyperintensity or small contrast enhancement, due to mild inflammatory
reaction.
•• In the vesicular stage, a typical 1–2 cm cyst is demonstrated, which
appears as a well defined hyperintense lesion on T2W and hypointense
on T1W sequences similar to CSF.
•• The larval scolex may be identified which is seen as a 1–2 mm mural
nodule which appears hyperintense on T1 and hypointense on T2W. The
demonstration of a scolex is pathognomonic of cysticercosis.
•• The colloidal stage cyst contents become turbid due to increased protein
content, which is seen as hyperintense on T1W and T2W. The cyst capsule
is thickened and appears hypointense on T2W images.
•• In the granular nodular stage, the cyst shows uniform ring enhancement
and there is reduction in the oedema and mass effect.
•• In the calcified stage, the cyst becomes calcified and may not be detected
with conventional MR.
•• The Cisternal Form of NCC:
–– Involves the subarachnoid spaces and basal meninges.
–– They are commonly located in the cisterna magna, cerebellopontine
angle cistern or sellar cisterns.
–– Cysts are usually large and may attain giant proportions.
–– These are racemose cysts and lack a scolex. Usually, these are single
cysts, but imaging may show these cysts to be multi-loculated, which
may be due to the infolding of the cyst wall or agglomeration of multiple
cysts presenting as a nodular mass.
–– FLAIR imaging with 100% supplemental oxygen improves the conspi-
cuity of cisternal cysts.
–– These cysts can provoke inflammatory reaction, resulting in severe
basal arachnoiditis, communicating hydrocephalus, vasculitis and
basal ganglia infarcts.
•• Intraventricular NCC:
–– Occurs in 20% of the cases.
–– This is most commonly detected in the fourth ventricle due to depend-
ant gravitation of the cysts. Other less common sites include the
aqueduct of sylvius and the third and lateral ventricles.
–– Early diagnosis is important as the mobile cysts can cause acute ob-
struction to the ventricular outflow, resulting in sudden death.
–– The cyst is often similar to CSF in all sequences; however, the iden-
tification of the cyst wall or scolex, if present, helps in the correct
diagnosis. These cysts often conform to the ventricular wall and may
be mistaken for a dilated ventricle.
–– Sometimes, the cyst can cause ependymal inflammation which may
be seen as a high intensity rim in FLAIR images or as thin contrast
enhancement of the ependymal wall.
–– O2 supplementation does not improve the conspicuity of these cysts.
–– 3D CISS has been shown to be more sensitive and specific than con-
ventional MR to detect the cyst wall and scolex of intraventricular cysts.
–– Intrathecal iodinated contrast administration and imaging with CT may
identify these cysts as filling defects.
•• Spinal Cord Involvement:
–– Reported in 2–5% of NCC.
90
–– Extramedullary cysts are more common than intramedullary forms,

and usually, these patients have the manifestations of this parasite
elsewhere in the body.
–– The cysts can be solitary or conglomerated, commonly located in the
thoracic cord and may show non-specific imaging findings.
–– Co-existant CNS infection or CSF analysis may resolve the issue.
•• MR spectroscopy of NCC may show lactate (1.3 ppm), acetate (1.98
ppm), cytosolic amino acids (0.9 ppm), alanine (1.47 ppm) and succinate
(2.4 ppm).
•• The presence of strong succinate with a smaller acetate peak may help in
differentiating NCC from pyogenic brain abscess.
•• The diagnostic criteria have been put forth based on clinical, radiological
and epidemiological parameters proposed by del Brutto et al.
•• Diagnostic Criteria and Degree of Certainty for Human Neurocysticer-
cosis:
Absolute criteria: 1. Histological demonstration of parasite
2. Direct visualisation of parasite by fundoscopy
3. Visualisation of scolex on CT/MR.
Major criteria: 1. Lesions suggestive of neurocysticercosis(NCC)
on CT/MR
2. Positive immunological studies
3. Plain X-ray shows calcifications in muscles.
Minor criteria: 1. Subcutaneous nodules
2. Soft tissue or intracranial calcifications
3. Clinical history suggestive of NCC
4. Disappearance of NCC with anti-helminthics.
Epidemiologic: 1. Living or hails from endemic regions
2. Frequent travel to endemic areas
3. Household contact with Taenia solium.
Definitive: (1) One absolute criterion; (2) two major criteria; (3) one major +
two minor + one epidemiologic.
Probable: (1) One major + two minor; (2) one major + one minor + one
epidemiologic; (3) three minor + one epidemiologic.
Possible: (1) One major; (2) two minor + one epidemiologic.
•• Differential diagnosis includes tuberculosis, brain abscess, cystic tumours
and hydatid cysts.
NEUROBRUCELLOSIS
•• It is a rare zoonotic disease with the primary hosts being camels, sheep
and goats, and humans act as the secondary host. This disease is usually
transmitted through consumption of uncooked meat or unpasteurised dairy
products.
•• Neurobrucellosis occurs in 5–10% of cases of brucellosis and affects both
the central and the peripheral nervous systems. It preferentially affects the
auditory system with occurrence of sensorineural hearing loss.
•• Three types of imaging abnormalities can be seen—inflammation, white
matter changes and vascular insults.
•• Inflammation may result from granulomas or enhancement of the meninges
(basal meningitis), perivascular space or lumbar nerve roots.
•• White matter changes manifest as hyperintense lesions on T2WI in the
form of diffuse involvement of the arcuate fibres or periventricular regions
(corpus callosum) or as focal demyelination.
91
•• Vascular insult is likely to be due to one of the two mechanisms:

(a) Inflammatory process (vasculitis) of the small vessels or venous system
causing lacunar infarcts, small haemorrhages, or venous thromboses
(b) A haemorrhagic stroke caused by rupture of a mycotic aneurysm, a
likely sequel of embolic stroke from brucellar endocarditis.
ANTHRAX MENINGOENCEPHALITIS
•• Infection with the Bacillus anthracis, a large gram-positive, spore-forming
bacillus is transmitted to humans by contact with infected animals or
contaminated animal products.
•• CT and MRI show multiple haemorrhagic lesions at the grey-white matter
junction of the cerebrum and diffuse meningeal enhancement.
•• Haemorrhage in the deep grey matter, ventricle, supra and infratentorial
subarachnoid spaces and diffuse meningeal enhancement can also be
seen.
VIRAL INFECTIONS OF THE BRAIN

•• Viral infections of the brain result usually in aseptic meningitis or viral
encephalitis.
•• Pathological features include neuronal degeneration and inflammation.
•• It can range from diffuse brain congestion and oedema to haemorrhage
and necrosis.
•• MRI shows scattered or confluent areas of hyperintensity on T2WI and
iso- to hypointense on T1WI.
•• Haemorrhage may be present. Localised or generalised atrophic changes
may be seen.
Herpes Simplex 1 Encephalitis

•• Herpes simplex 1 (HSV-1) encephalitis initially involves the cerebral cortex,
causing neuronal destruction and cytotoxic oedema.
•• A characteristic pattern of distribution is exhibited by the pathogen, with the
anterior and medial aspects of the temporal lobes and the inferior portion
of the frontal lobes initially being affected. The process may then extend
to include the insular cortex. The lentiform nucleus is typically spared.
•• Bilateral mesial temporal involvement is almost pathognomonic for HSV
encephalitis, particularly when asymmetric.
•• CT is usually normal during the early stages of infection and abnormal
parenchymal or meningeal enhancement is rarely detected before the 2nd
week of clinical symptoms.
•• MR imaging, especially DWI is more sensitive during the initial course. It
appears hypointense on T1WI and hyperintense on T2WI. DWI shows re-
stricted diffusion in the early course of the disease. The leptomeningeal and
gyral enhancement associated with HSV encephalitis typically occur along
the temporal lobes, insular cortex, subfrontal area and cingulate gyrus.
•• If the patient has HIV infection, the white matter is predominantly affected,
especially in the occipital lobe and exceptionally in the cerebellum. The
hippocampi, frontobasal, insular and temporal cortices are spared.
•• MRS shows reduced NAA between 7 weeks and 14 weeks after onset,
whereas choline can be elevated with the presence of lactate.
•• Glial proliferation in HIV-related herpes simplex encephalitis can be
associated with progressive myoinositol increase.
92
Japanese Encephalitis
•• The natural transmission cycle of the Japanese encephalitis (JE) group
involves infection of a mosquito vector alternating with viral amplification
in a variety of vertebrate hosts. Human disease is incidental to this cycle.
•• It presents after a brief, non-specific prodromal febrile illness. Seizures are
a prominent manifestation in children.
•• Adults usually present with more obviously encephalitic symptoms. Cranial
nerve palsies, particularly of the VII nerve, occur in 50% of cases. Movement
disorders are a major feature in 40% of patients and include choreiform
movements, Parkinsonism and other tremors.
•• Thalamic lesions are most frequently hypointense on T1-weighted images and
hyperintense on T2-weighted images, but high signal intensity on T1-weighted
images, consistent with subacute haemorrhage, has also been described.
•• The basal ganglia and midbrain are frequently involved by JE. These
lesions are more likely to be asymmetric than are those within the thalami.
Co-infection with NCC is also known in endemic areas.
Rabies Encephalitis
•• It is an acute infection involving the CNS in humans and other mammals
caused by an RNA virus of the rhabdovirus family.
•• Human rabies presents in two forms—encephalitic and paralytic.
•• The passage of the virus to the CNS occurs axonally through retrograde
axoplasmic flow of approximately 12–24 mm per day, until the virus reaches
the next neuronal cell body.
•• In paralytic rabies, the medulla and the spinal cord are mainly involved by
extensive neuronal damage and inflammation, whereas in the encephalitic
form, it is the brainstem and the cerebrum, particularly the limbic system.
•• CT scan shows focal or diffuse areas of decreased attenuation and
MRI show areas of hyperintensity on T1 and T2 in the basal ganglia,
periventricular white matter, hippocampus and brain stem.
•• Diffuse cerebral oedema may be seen in advanced stages.
Creutzfeldt-Jakob Disease
•• Creutzfeldt-Jakob Disease (CJD), a fatal neuro-degenerative disorder, is
diagnosed by the detection of an accumulation of an abnormal form of the
human prion protein (PrPSc) in the brain.
•• Brain biopsy or autopsy is required for a definitive diagnosis.
•• In sporadic CJD, MRI shows hyperintense signal-intensity on T2-weighted
and proton attenuation (PD)-weighted images. In addition, the cortical
ribbon can also show hyperintensity. DWI shows a decrease of the
ADC in the affected areas, most probably because of the characteristic
neuropathologic spongiform neuropil changes.
•• The disease has a fatal course.
Acute Disseminated Encephalomyelitis

•• It is a monophasic post-infectious (varicella, measles and rubella) or post-
vaccinial inflammatory disorder that is pathologically characterised by an
acute perivenous lymphocytic inflammation with confluent demyelination.
•• It presents with seizures, focal neurologic signs and alteration of conscious-
ness that develop days to weeks after the onset of presumed viral infection.
•• CSF analysis reveals mild pleocytosis.
93
•• MR imaging usually shows T1 and T2 prolongations, typically bilateral and

asymmetric, in the deep and subcortical white matter of the cerebrum,
cerebellum and brainstem with no mass effect.
•• The corpus callosum may be involved in acute disseminated encephalo
myelitis (ADEM) and these patients nearly always have asymmetric callosal
lesions and their white matter has lesions as well.
•• After contrast material infusion, the lesions in ADEM will show various
patterns of enhancement, depending on their acuity.
Subacute Sclerosing Panencephalitis

•• This is attributed to slow progressive infection by measles virus.
•• Children between the ages of 5 years and 12 years who had clinical measles
3 years before are affected.
•• Clinically, four stages are recognised from initial mental or behaviour
abnormalities to loss of cerebral cortical function.
•• Death usually occurs within 2–6 years.
•• White matter abnormality seen in the centrum semiovale is either patchy
or diffuse and there is minimal inflammation.
•• Gliosis can occur in the grey matter, basal ganglia, pons and thalamus.
•• MR shows bilateral periventricular white matter hyperintensities on T2WI.
No mass effect is seen. Frontal and/or occipital involvement can be more
extensive.
FUNGAL INFECTIONS
•• They are divided into those that predominantly infect the immuno-
compromised (Aspergillus, Candida, Mucormycosis) and those that infect
immuno-competent individuals.
•• Cryptococcus and Histoplasma spread haematogenously, reach the
microvasculature of the meninges, penetrate the vessel walls and result
in an acute or chronic leptomeningitis.
Cryptococcus Neoformans
•• It is the most common fungus to affect the CNS and to cause meningoen-
cephalitis and is usually associated with HIV infection or AIDS and rarely
seen in immuno-competent healthy persons.
•• It reaches the CNS through the haematogenous route from a peripheral
focus in the lung. It extends into the parenchyma, either through the choroid
plexus or through the Virchow-Robin spaces. Expansion of these spaces
forms the pseudocystic lesions, characteristic of this disease.
•• The avascular pseudocysts are seen as well circumscribed, round to oval
hypointensities on T1WI and hyperintensities on T2WI, which fail to enhance
after administration of contrast medium.
•• Granulomatous lesions enhance with contrast medium administration and
are hyperintense on T2WI. They are located preferentially on the ependyma
of the choroid plexus. Periventricular oedema appears to result from altered
CSF dynamics and seeping of the CSF into the interstitial space across
the subependymal gliotic layer.
Candidiasis
•• On T2WI, Candida abscess appears as an area of a well demarcated
hypointense signal surrounded by a larger area of high signal intensity.
•• Meningitis, meningoencephalitis and granuloma may also result.
94
Aspergillus Infection
•• Aspergillus infection occurs by direct extension from the nasal cavity or
paranasal sinuses or by the haematogenous route.
•• With direct spread, vascular invasion is often observed resulting in angiitis,
thrombosis and infarction. Meningitis can result with extension into the
subarachnoid spaces.
•• With haematogenous spread, the vessels get occluded, producing
infarction, septic infarction, cerebritis and cerebral abscess.
•• The presence of haemorrhage gives a clue to the diagnosis of aspergillosis.
Fungal organisms were detected in the encapsulated lesion, but they were
not commonly found in vessels or in the parenchyma outside the abscess.
•• Usually abscesses are hypointense on T1WI and hyperintense on T2WI with
or without mass effect. Hypointensity on T2WI also can be seen. DWI show
centrally restricted diffusion. The changes in diffusion are a likely reflection
of proteinaceous fluid and cellular infiltration in the lesions.
Mucormycosis
•• Mucormycosis occurs in uncontrolled diabetic or immunocompromised
patients.
•• It spreads from the PNS along perivascular and perineural channels,
through the cribriform plate into the frontal lobe or through the orbital apex
into the cavernous sinus.
•• It causes either infarction or fungal abscess and involves the base of the
brain and cerebellum after invasion of the infratemporal fossa or orbit.
•• It appears hypo or hyperintense on T2WI and hyperintense on T1WI and
may demonstrate peripheral post-Gd enhancement.
Section II: Congenital
11
CHAPTER Embryology: Skull and
Vertebral Column
Muthukumar N
DEVELOPMENT OF THE VERTEBRAL COLUMN

•• The vertebral column consists of 33 vertebrae, which include 7 cervical,
12 thoracic, 5 lumbar, 5 sacral and 4 coccygeal.
•• Each vertebra passes successively through three different stages of
development, which are as follows:
1. Blastemal or membranous
2. Cartilaginous
3. Bony.
•• As the notochord forms, the mesoderm condenses on either side of the
notochord as two parallel longitudinal columns known as the paraxial
mesoderm (Fig. 1).
•• Initially, this mesoderm exists as a pair of unsegmented, longitudinal strips
along the rostro-caudal axis. Later, the paraxial mesoderm begins to
undergo segmentation resulting in the formation of the somites.
•• The somite formation occurs first in the rostral end and then progresses
sequentially caudally. The rate of formation of the somites has been estimated
to be one pair every three hours. Initially, a cavity known as the somitocoele
(Fig. 2) is present within the somite which later disappears as the somites
mature.
•• Each somite differentiates into a ventromedial part known as the sclerotome
and a dorso-lateral part known as the dermomyotome (Fig. 3).
Fig. 1: Schematic representation of the development of the paraxial meso-

derm and its relationship to the notochord and the developing neural tube
Fig. 2: Schematic representation of the development of the somite and its

relationship to the notochord
Section II • Congenital
96
Fig. 3: Schematic representation of the differentiation of the somite into the

ventromedial part, sclerotome, and the dorsomedial part (dermomyotome) and
further differentiation of the dermomyotome into dermatome and myotome
•• The dermomyotome then forms the dermatome (forms dermis) and the
myotome (forms muscle).
•• The myotome differentiates to form two components, dorsally the epimere
and ventrally the hypomere.
•• The epimere gives rise to the epaxial muscles (dorsal skeletal muscles) and
the hypomere gives rise to the hypaxial muscles (ventral skeletal muscles
and the limb muscles) as shown in Figure 4.
•• During the 4th week of gestation, the polymorphous cells of the sclerotome
migrate ventromedially around the notochord and form the rudiment of the
centrum of the blastemal vertebra. Thereafter, the cells extend dorsally
around the developing neural tube.
•• These bilateral dorsal extensions meet in the midline dorsally to form the
neural arch.
•• The mesenchyme that intervenes between adjacent somites is related on
either side to an intersegmental artery.
•• Subsequently, each sclerotome is divided by a horizontal fissure known
as the sclerotomic fissure (also known as Von Ebner’s fissure) into a less
dense cranial half and a more dense caudal half (Fig. 5).
•• The caudal half of one sclerotomic segment fuses with the cranial half of
the subsequent sclerotomic segment to form the definitive centrum of the
vertebra.
•• The sclerotomic fissure and the mesenchymal condensation around it form
the perichordal disc which persists into adult life as the intervertebral disc
(Fig. 6).
•• The nucleus pulposus of the intervetebral disc is notochordal in origin
whereas, the annulus fibrosus is mesenchymal in origin.
•• The neural arches are related to that part of the centrum, which is derived
from the cephalic part of the sclerotome.
•• Thus, the vertebral body is derived from two adjacent sclerotomes. Close
to the neural arch, each centrum gives rise to a costal element that extends
laterally through the segmental myotomes.
•• The boundary of the head and neck corresponds to the boundary between
the 5th and 6th somites. The first true somite disappears and somites 2–5
(known as occipital somites 1–4) fuse to form the basioccipital bone.
•• The vertebrae are formed from the 6th somite onward caudally. C1 (atlas)
is formed by the fusion of the caudal half of the occipital somite 4 with the
cranial half of the cervical somite 1.
•• The shift of the somite number accounts for the production of seven cervical
vertebrae from eight cervical somites.
Chapter 11 • Embryology: Skull and Vertebral Column
97
Fig. 4: Schematic representation of the migration of the different components

of the somite to form the vertebra and its associated musculature. The sclero-
tomal cells migrate to surround the notochord and the neural tube to form the
vertebra. The myotome differentiates into the epimere, which gives rise to the
epaxial muscles and the hypomere, which gives rise to the hypaxial muscles
Fig. 5: Schematic representation of the division of the sclerotome, into cranial

and caudal halves, by the sclerotomic fissure and the relationship of the scler-
otome to the intersegmental artery and the developing myotome
Fig. 6: Schematic representation of the development of the vertebra and the

intervertebral disc
•• The 1st to 28th pair of somites is formed from the primitive streak by a
process known as primary gastrulation.
•• All the other caudal somites are formed from the tail bud by a process
known as secondary gastrulation.
•• It is believed that in humans, the boundary between primary and secondary
gastrulation lies at the level of the 5th lumbar vertebra.
•• During the 6th week, chondrification starts in the membranous vertebra.
•• Two cartilaginous centres appear in the centrum and fuse to form a single
mass.
•• Each neural arch is chondrified from one centre and fuses later with the
centrum.
•• Ossification begins in the 7th week. The vertebra is ossified from three
primary centres and five secondary ossification centres.
98
•• At puberty, five secondary ossification centres appear; one for the spinous
process, one each for the transverse processes, two ring-like epiphyseal
centres for the upper and lower surfaces of the centrum.
Molecular Basis of Vertebral Column Development

•• The morphogenetic specification of the vertebral phenotype is controlled
by a number of genes.
•• These genes involved in embryogenesis encode a set of instructions or
rules of assembly.
•• Implementation of these one-dimensional rules via gene expression
and protein interaction produces the three-dimensional structure, viz the
vertebral column.
•• Hox Genes:
–– These are also known as homeobox genes.
–– These genes were originally identified in the fruit fly, Drosophila mela-
nogaster.
–– Hox genes encode transcription factors which act as regulators of
downstream gene activity and are characterised by a highly conserved
180-base pair sequence called the homeobox.
–– The homeobox encodes a 60-amino acid helix-loop-helix DNA motif
within the encoded transcription factors.
–– The Hox genes play a fundamental role in the establishment of the
body plan, including specification of the axial skeleton.
–– All vertebrates, including human beings, contain 39 Hox genes that are
distributed on four linkage groups or clusters designated as Hox A, B,
C, and D on chromosomes 6, 11, 15 and 2, respectively.
•• Hox codes:
–– The complement of Hox gene is believed to form the Hox code that
specifies the position along the cephalocaudal axis.
•• Losing the function of a Hox gene, the first cervical vertebra is transformed
into a more rostral identity, which is termed as “anterior homeotic
transformation”.
•• Conversely, extension of an expression domain rostrally can transform
structures into a more caudal identity, a phenomenon known as “posterior
homeotic transformation”.
•• The common form of craniovertebral junction anomaly, assimilation of atlas,
is believed to be a form of anterior homeotic transformation.
•• Pax Genes:
–– These are also known as “paired-box” genes.
–– Two genes, Pax-1 and Pax-9, control segmentation of the somites and
sclerotomes to establish intervertebral boundaries.
•• The Sonic Hedgehog Gene: Acts as a signalling switch.
•• Msx1 and Msx2:
–– These genes are expressed by the sclerotomal cells that migrate dor-
sally around the neural tube to form the neural arch.
–– The expression of these genes is controlled by the roof plate of the
neural tube and the surface ectoderm via BMP4 signals [Bone Mor-
phogenic Protein (BMP)].
–– In experimental studies, it has been shown that interruption of the func-
tion of these genes result in spina bifida.
Chapter 11 • Embryology: Skull and Vertebral Column
99
Development of the Skull

•• The skull has two distinct portions: the one which surrounds the brain and
organs of special senses, viz the neurocranium and that which forms the
lower face and jaws, viz the viscerocranium.
•• The neurocranium consists of vault of the skull and the base of the skull.
•• The vault of the skull is membranous in origin and the base is cartilaginous
in origin.
•• Vault of the Skull:
–– The membranous neurocranium which goes to form the cranial vault
is mesenchymal in origin.
–– This mesenchyme is derived from the neural crest.
–– All the sutures of the calvarial bones are also derived from the neural
crest.
–– The bones that go to form the cranial vault are sometimes referred to
as dermal bones. These include the frontal bones, the parietals, the
squamous parts of the temporal bones and the upper (interparietal)
part of the occipital squama.
–– These bones first appear at about the 30th day of gestation when they
begin to form curved plates of mesenchyme at the sides of the devel-
oping brain and gradually extend cranially to blend with each other.
•• Base of the Skull:
–– With the exception of the orbital plate of the frontal bone and the lateral
parts of the greater wings of the sphenoid which are membranous in
origin, the rest of the base of the skull is preformed in cartilage.
–– Thus, the bones of the base of the skull that are preformed in cartilage
include: the occipital (except the interparietal part), the petromastoid
part of the temporal, the body, lesser wings and the roots of the greater
wings of sphenoid, and the ethmoid.
–– The formation of the cartilaginous base of the skull occurs in three
main regions, viz:
1. Caudally, in relation to the notochord known as the parachordal cartilage
2. Intermediately, in relation to the hypophysis known as the hypo
physeal cartilage
3. Rostrally, between the orbits and nasal cavities and known as the
interorbitonasal cartilage.
•• Molecular Biology of Skull Development:
–– This also has important implications for understanding the various
craniosynostosis syndromes and their treatment.
–– Fibroblast growth factor receptors:
¾¾ Fibroblast growth factor receptors (FGFRs) are cell surface recep-
tors for fibroblast growth factors (FGFs), which elicit a variety of
cellular functions in different cell types, including cell proliferation,
differentiation, migration, and pattern formation.
¾¾ FGFRs belong to a family of proteins known as transmembrane
tyrosine kinases.
¾¾ So far, four FGFRs (FGFR 1-4) have been identified. They all have
an extracellular ligand-binding domain, a transmembrane domain,
and an intracellular kinase domain.
¾¾ The importance of FGFR function in normal suture development is
amply demonstrated in molecular genetic studies of craniosynos-
tosis syndromes associated with FGFR mutations.
100
¾¾ For example, it has been shown that in Apert’s syndrome, muta-

tions of the FGFR2 have an effect on the phenotype of the calvarial
bone cell.
–– The Msx genes:
¾¾ Belong to a family of homeobox containing genes.
¾¾ The exact role of Msx genes in skull bone and suture development
has not been fully elucidated.
¾¾ It is believed that Msx2 gene product might influence suture devel-
opment by altering the apoptotic rate in suture cells or by interaction
between sutures and adjacent tissues or both.
–– TWIST gene:
¾¾ The protein product of the TWIST gene is a transcription factor.
¾¾ Mutations in the TWIST gene are responsible for the Saethre-
Chotzen syndrome (SCS), a form of autosomal dominant
craniosynostosis.
–– Transforming growth factors (TGFs):
¾¾ Transforming growth factor-beta (TGF-b), 1 to 3 belong to a family
of related heparin-binding peptides.
¾¾ They are involved in regulation of osteoblast and chondrocyte dif-
ferentiation, proliferation and matrix gene expression.
12
CHAPTER Embryology:
Brain and Spinal Cord
Muthukumar N
DEVELOPMENT OF THE CENTRAL

NERVOUS SYSTEM
The Embryonic Disc
•• The internal cell mass becomes the
flattened and circular embryonic disc
with two layers, the bilaminar embryo
(Fig. 1). The outer layer adjacent
to the amniotic cavity is called the
epiblast, which gives rise to all or
nearly all the cells of the embryo.
The inner layer adjacent to the yolk
sac is called the hypoblast.
•• At 13–15 days of development, the
hypoblastic cells near the future
rostral end of the embryo form a Fig. 1: Schematic representation
thickened circular area called the of the bilaminar embryonic disc
prochordal plate (future site of the with the epiblast related to the
mouth) and in the caudal end, the amniotic cavity and the hypoblast
cloacal membrane (future site of related to the yolk sac
anus).
Gastrulation and the Trilaminar Embryonic Disc

•• Gastrulation is the process by which the bilaminar embryonic disc is
converted into a trilaminar embryonic disc by the interposition of a
mesoblastic layer between the epiblast and hypoblast.
•• At about 15 days of development, a linear thickening called the primitive
streak appears in the caudal midline of the embryo. The primitive streak is
limited caudally by the cloacal membrane.
•• Progressively, the primitive streak increases in length and a thickening
forms at the rostral end of the primitive streak, known as the primitive knot
or Hensen’s node (Fig. 2).
•• A longitudinal groove then appears in the primitive streak and deepens at
the level of the Hensen’s node to form the primitive pit.
•• Cells from the epiblast migrate into the primitive streak and groove, separate
from the epiblast and migrate rostrally between the epiblast and hypoblast to
form the mesoblast, thus creating the earliest stage of the trilaminar embryo.
•• The epiblast (ectoderm) is destined to form the CNS (neurectoderm) and
the epidermis (cutaneous ectoderm).
102
Fig. 2: Schematic representation of the embryonic disc at the commence-

ment of gastrulation. Cells from the epiblast migrate into the primitive streak
and pass between the epiblast and hypoblast. Formation of the notochord is
also seen
•• The mesoblast (mesoderm) forms the skeleton, striated and smooth

muscles, connective tissues, blood vessels, blood cells and bone marrow
and the reproductive and excretory organs.
•• The hypoblast (endoderm) is the source of the epithelial linings of the
respiratory and digestive tracts and glandular cells of the liver and pancreas.
Development of the Notochord

•• At about 16–17 days of development, some of the mesoblastic cells migrate
in the midline rostral to the Hensen’s node between the ectoderm and
the endoderm, all the way to the prochordal plate to form a solid rod-like
structure known as the notochord.
•• The notochord is represented during life by the nucleus pulposus of the
intervertebral disc.
•• The notochord plays an important role as an embryonic inducer, which is
important for the formation of the neural plate from which the neural tube
develops.
•• As the notochord extends cranially toward the prochordal plate, the
intraembryonic mesoderm originating from the primitive streak forms two
parallel streaks on either side of the developing notochord, to form the
paraxial mesoderm (Figs 3A to C).
•• Initially, the notochord remains as a solid cord of cells known as the
notochordal process.
•• Subsequently, the primitive pit extends into the notochord and converts the
notochord into a tubular structure known as the notochordal canal (Fig. 4).
•• Later, the notochordal canal becomes incorporated with the underlying
endoderm by a process known as the intercalation of the notochord (Fig.
5A).
•• During this process, the amniotic cavity is transiently in communication
with the yolk sac through the neurenteric canal (Fig. 5B).
•• This is known as the excalation of the notochord (Fig. 5C). This process
of intercalation and excalation of the notochord is the period during which
three different types of occult spinal dysraphism are known to develop,
viz. neurenteric cyst, split cord malformation, and combined anterior and
posterior spina bifida.
Chapter 12 • Embryology: Brain and Spinal Cord
103
A B
Figs 3A to C: Formation of the neural groove: (A) Notochord. (B) Paraxial

mesoderm. (C) Neural crest
Fig. 4: Schematic representation of the formation of the notochordal pro-

cess and canal and its relationship to the ectoderm and endoderm
A C
Figs 5A to C: Schematic representation of the (A) Intercalation of notochord.

(B) Formation of the neurenteric canal which forms a transient communica-
tion between the yolk sac and amniotic cavity. (C) Excalation of the notochord
Formation of the Neural Tube

•• The neural tube is the primordium of the brain and the spinal cord. The
process by which the neural tube is formed is known as neurulation.
•• Primary neurulation is the process by which the brain and the spinal cord
up to L1 level are formed.
•• The portion of the spinal cord distal to L1 is formed by a process known
as secondary neurulation, which involves two stages, viz. canalisation
and regression.
•• Disorders of primary neurulation are responsible for the various forms of
open dysraphism and disorders of secondary neurulation are responsible
for the various forms of closed spinal dysraphism.
104
Neurulation
•• In response to the notochord, the overlying ectoderm begins to thicken
and forms the neural plate.
•• A longitudinal depression develops in the neural plate to form the neural
groove, the sides of which are elevated to form the neural folds.
•• The neural folds then fuse in the midline to form the neural tube.
•• With the formation of the neural tube, the cutaneous ectoderm once again
becomes continuous in the midline and the neural tube subsequently detaches
from the cutaneous ectoderm and comes to lie dorsal to the notochord
(Fig. 3).
•• The fully formed neural tube has two openings, the anterior and posterior
neuropores, which remain temporarily open at the cephalic and caudal
ends of the embryo.
•• Through these openings, the neural tube communicates with the amniotic
cavity. The amniotic fluid circulates through the neural tube and provides
nourishment to the neural tube.
•• The anterior neuropore closes by the middle of the 4th week at about the
20-somite stage and the posterior neuropore closes by the end of the 4th
week at about the 25-somite stage.
•• The position of the anterior neuropore is represented in the adult by the
lamina terminalis.
•• The posterior neuropore closes at the level of the spinal cord segments L1
or L2 with a range of error of two segments above or below (T11 or L4).
Development of the Brain

•• At the time of closure of the anterior neuropore, the rostral end of the neural
tube shows three dilatations known as brain vesicles.
•• The three early subdivisions are known as the “prosencephalon” or
forebrain, “mesencephalon” or midbrain, and the “rhombencephalon” or
hindbrain (Fig. 6).
•• These three vesicles are demarcated by two constrictions between
them. The constricted region between the mesencephalon and the
rhombencephalon is known as the isthmus.
•• The prosencephalon subsequently is subdivided into two parts: The
telencephalon or the cerebral hemispheres and the diencephalon or
thalamus.
•• The mesencephalon or the midbrain shows less change during development
than the other divisions.
•• The hindbrain vesicle is subdivided into two parts: The “metencephalon”
from which develop the pons and the cerebellum; and the “myelencephalon”
from which develops the medulla oblongata (Fig. 7).
•• The primitive cavities of the brain vesicles are the forerunners of the
ventricular system.
•• The cavities of the telencephalon become the lateral ventricles and the
cavity of the diencephalon persists as the third ventricle.
•• The cavity of the mesencephalon becomes progressively narrowed to
form the aqueduct of sylvius and the cavity of the hindbrain becomes the
fourth ventricle.
•• Flexures of the Brain:
–– Two prominent flexures occur in the rostral portion of the neural tube
at an early stage.
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Fig. 6: Schematic representation of the development of the three primary

brain vesicles and the formation of the cervical and cephalic flexures
Fig. 7: Schematic representation of the development of the brain vesicles

and the formation of the pontine flexure
–– The “cervical flexure” develops at the junction of the rhombencepha-

lon and the spinal cord, with its concavity directed ventrally and the
“cephalic flexure” occurs at the junction of the mesencephalon and
rhombencephalon (Fig. 6).
–– At about the 6th week of development, a third flexure, known as the
“pontine flexure”, develops in the rhombencephalon with its concavity
directed dorsally and divides the rhombencephalon into two segments,
viz. the metencephalon and the myelencephalon (Fig. 7).
–– It is believed that these flexures develop as a result of differences in
the rates of cell proliferation and cell movement.
–– At this stage, the developing brain has five different subdivisions:
(1) the telencephalon; (2) the diencephalon; (3) the mesencephalon;
(4) the metencephalon and (5) the myelencephalon.
–– The developing neural tube is divided into a dorsal “alar lamina” and
a ventral “basal lamina”. The alar lamina is sensory in function and
the basal lamina is motor in function, the two being separated by the
“sulcus limitans”.
Histogenesis of the Neural Tube

•• The lumen of the neural tube forms the ventricular system of the brain and
the central canal of the spinal cord. Initially, the neural tube is lined by a
single layer of undifferentiated neuroepithelial cells or stem cells.
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•• The continued proliferation of these neuroepithelial cells make the single-

layered neural tube into a multilayered neural tube with three distinct zones.
•• The innermost zone is called the germinal or ependymal zone, the
intermediate zone is called the mantle zone and the outer zone is the
marginal zone.
•• Some cells remain in the ependymal zone and eventually become the
ependymal cells that line the ventricles of the brain and the central canal
of the spinal cord.
•• In the mantle zone, further differentiation into spongioblasts and neuroblasts
occur. The spongioblasts differentiate into astrocytes and oligodendrocytes.
•• The microglia, however, are mesodermal in origin and appear in the mantle
zone and marginal zone from the blood histiocytes when the vascular
system grows around the neural tube.
Neural Crest and its Differentiation

•• The neural crest cells are derived from the neuroectoderm.
•• When the two neural folds fuse dorsally to form the neural tube, the neural
crest cells intervene in a wedge-shaped area between the surface ectoderm
and the neural tube (Fig. 3).
•• Neural crest cells extend from the region of the mesencephalon to the
caudal somites.
•• Neural crest cells are a highly pluripotent cell population that play a
significant role in the development of various structures.
•• Neural crest cells migrate extensively throughout the embryo in four
overlapping domains (cephalic, trunk, sacral and cardiac). The structures
that are derived from the cranial neural crest are summarised in Table 1.
Table 1: Derivatives of the cranial neural crest

Derivatives
Nervous system Sensory ganglia
Sympathetic ganglia (V, VII, IX, X)
Parasympathetic ganglia of the neck
Neuroglial cells
Schwann cells
Skeletal system Maxilla
Mandible
Palatine
Facial complex
Cranial vault
Connective tissues Cranial musculature
Adenohypophysis
Lingual glands
Thymus
Thyroid and parathyroids
Corneal endothelium and stroma
Vascular and dermal smooth muscles
Melanocytes and melanophores
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Development of the Spinal Cord

•• As can be understood from the preceding discussion on neurulation, the
portion of the spinal cord up to the lumbar segments is formed by a process
known as primary neurulation (discussed earlier).
•• The distal portion of the spinal cord is formed by a process known as
secondary neurulation.
•• This process of secondary neurulation consists of two stages (Figs 8A to C):
1. Canalisation of the tail bud and
2. Regression or retrogressive differentiation.
•• Canalisation of the tail bud:
–– Takes place during embryonic stages 13 through 20 (days 28 to 48).
–– Caudal to the posterior neuropore, the tail bud contains an undifferen-
tiated mass of cells known as the caudal cell mass, derived from the
primitive streak.
–– Under an intact covering of the cutaneous ectoderm, the caudal cell mass
develop vacuoles around which cells assume a neural appearance.
–– Subsequently, the vacuoles coalesce to form the neural tube, which
then fuses with the more proximally placed neural tube formed by
primary neurulation.
–– The ventriculus terminalis, which marks the level of the future conus
medullaris, becomes identifiable during days 43 to 48.
–– Certain forms of occult spinal dysraphism, such as lumbosacral lipoma
and lipomyelomeningocoele, are believed to have their origin during
this period.
•• Regression:
–– The process by which the filum terminale and cauda equina are formed
from that portion of the neural tube formed by canalisation and by
which the conus medullaris eventually comes to lie at its adult level is
termed as regression or retrogressive differentiation.
–– This process begins as early as 43–48 days of gestation and continues
throughout the foetal period and into the early post-natal period.
–– During the process of regression, the ventriculus terminalis “ascends”
both by regression of the caudal neural tube, as well as by the dispro-
portionate growth of the vertebral column, resulting in the formation of
the filum terminale.
A B C
Figs 8A to C: Schematic representation of the development of the caudal

spinal cord by secondary neurulation
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–– At birth, the conus lies opposite the third lumbar vertebral body and
eventually reaches its adult position at the L1-L2 interspace by the 3rd
month of life.
–– As a result of these changes, the lumbar and sacral nerve roots which
early in their development, exit directly opposite their segmental spinal
cord levels of origin become elongated as the conus “ascends”, thus
forming the cauda equina.
–– Abnormalities during this stage of development result in “tight filum ter-
minale”, one of the most common causes of tethered cord syndrome.
•• Like other parts of the central nervous system, the developing spinal cord
also has three layers: the germinal or ependymal layer, the mantle layer
and the marginal layer.
•• Cell proliferations in the mantle layer produce anterior and posterior
thickenings known as the basal lamina and the alar lamina (Fig. 9).
•• The basal lamina gives rise to the anterior horn of the spinal cord and the
alar lamina gives rise to the posterior horn of the spinal cord.
•• Neuroblasts of the basal lamina become the efferent peripheral neurons.
•• As development proceeds, the proliferation of the germinal cells of the
ependymal zone gradually decreases and ultimately stops altogether.
•• As more and more stem cells are transformed into neuroblasts, the germinal
zone progressively diminishes in size and ultimately is reduced to a single
layer of columnar epithelial cells lining the central canal of the spinal cord.
•• The mantle layer progressively increases in size and becomes the grey
matter of the spinal cord, which is surrounded by the marginal layer, which
contains the descending and ascending axons and ultimately becomes the
white matter of the spinal cord.
Development of the Meninges

•• The meningeal layers in the spine and in the cranium up to the midbrain
are derived from the paraxial mesenchyme.
•• The meninges overlying the cerebral hemispheres are derived from the
neural crest.
•• The dura mater constitutes the pachymeninges, and the pia and arachnoid,
together, constitute the leptomeninges.
•• All the three meningeal layers are derived from a loose mesenchyme known as
the meninx primitiva or primary meninx that surrounds the primitive neural tube.
Fig. 9: Schematic representation of the development of the basal and alar

lamina of the spinal cord
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Molecular Regulation of Neural Induction

•• Induction of neural plate formation is controlled by several factors.
•• Under the influence of BMP-4, the ectoderm becomes epidermis and the
mesoderm differentiates into intermediate and lateral plate mesoderm.
•• Ectoderm destined to become the future neural plate, the activity of BMP-4
is blocked by three molecules, viz. noggin, chordin and follistatin.
•• These molecules are secreted by the primitive node, notochord and the
paraxial mesoderm.
•• Induction of the neural plate regions that go to form the hindbrain and spinal
cord depends upon two proteins, Wnt3a and fibroblast growth factor (FGF).
•• In addition, retinoic acid and homeobox genes play an important role in
organising the craniocaudal axis of the developing nervous system.
13
CHAPTER Congenital
Malformations of Cerebrum
Venkatramana NK  Ravi Shankar S
•• The development of the central nervous system (CNS) is very complex.

•• Neurogenesis, apoptosis, neurulation, neural crest separation, cell
migration, axonal path finding, dendritic sprouting, synaptogenesis,
neurotransmitter biosynthesis and myelinisation are the various steps
involved.
•• Congenital malformations of the brain are common clinical conditions, which
are one of the leading causes of infant morbidity, mortality and foetal loss.
DEVELOPMENT AND PATHOGENESIS

•• During the 4th week of gestation, the neural plate will form and fold itself
along its long axis to form the neural tube which closes.
•• During this process, the surface of ectoderm gets separated and allowing
the interposition of mesenchyme. If the process of closure of the neural tube
fails, the resulting malformations belong to the group of open dysraphisms.
•• Failure of closure of the calvarium and anterior cerebrum results in cranial
encephalomeningocoele. Exencephaly is an extreme form and if the
herniated brain is destroyed by necrosis, it will lead to anencephaly.
•• The minor equivalent of this disorder is the atretic parietal encephalocoele.
•• At the forebrain level, lack of differentiation can result in a single prosence-
phalic vesicle leading to various forms of holoprosencephaly.
•• Embryonic period—First 8 weeks, post-fertilisation
Gastrulation and notochord formation— 2–3 weeks
Dorsal induction— 3–4 weeks
– Primary neurulation
– Secondary neurulation
Ventral induction— 5–6 weeks.
•• Foetal period 8 to 38 post-fertilisation weeks
Neuronal proliferation, differentiation and histogenesis— 2–4 months
Migration— 3–5 months
Myelination and organisation— 3rd trimester–post-natal.
Commissural Agenesis
•• There are three telencephalic interhemispheric commissures namely:
–– Paleocortical anterior commissure
–– Archicortical hippocampal commissure
–– Large neocortical corpus callosum connecting most of the neocortex.
•• The agenesis could be complete or partial with cysts including lipoma of
the corpus callosum or isolated agenesis of a single commissure.
Chapter 13 • Congenital Malformations of Cerebrum
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Malformation of Cortical Development

•• Malformation of cortical development includes all varieties of cortical
malformations previously described as cortical dysplasias or neuronal
migration disorders.
•• They can be classified based on the pattern of cortical formation as defects
of:
Cellular Multiplication
–– It starts as soon as the neural tube is completed in the periventricular
layer.
–– The faulty multiplication can result in an abnormal size of the brain.
Cellular Differentiation
–– When there is a defect in this process due to any mechanism, the cells
will have the characteristics of both neurons and glia, and they fail to
migrate and segregate properly.
–– They look abnormal, as giant dismorphic neurons or huge balloon
cells.
–– If this defect is localised, it leads to focal cortical dysplasias and if it is
large, it can lead to hemimegalencephaly.
Cellular Migration
–– The neuronal cells migrate from the periventricular region towards the
cortex in a radial pattern established by the radial glia, which act as a
guideline from the ventricle to the pial surface.
–– Defects in this process will lead to neurons in abnormal locations form-
ing masses called “grey matter heterotopias”
Cellular Organisation
–– Intrinsic organisation of the cortical layers occurs with the development
of the intracortical connections and then the extracortical connections
mediated by the transitory subplate during the 20th and 25th weeks
of gestation.
–– Disorders at this stage will result in abnormal folding of the cortex and
lead to microgyria, polymicrogyria, etc.
–– They are classified according to the histology of the membrane as
arachnoid cyst, neuroglial cyst and glioependymal cyst.
–– They are usually located in the suprasellar cistern, middle cranial fossa
or posterior fossa.
CNS Malformations are Classified as

–– Abnormal brain size (microcephaly/megalencephaly).
–– External form (holoprosencephaly/lissencephaly).
–– Internal configuration (hydrocephaly/agenesis of corpus callosum).
CONCEPTS, CAUSES AND CLASSIFICATION

There are many causes of congenital malformations (Table 1) which include,
chromosomal abnormalities, gene defects, foetal infection, exposure of the
foetus to harmful chemicals, radiation, foetal hypoxia and often more than one
of these factors may play a role and, therefore, the resultant malformation may
not follow a specific pattern.
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Table 1: Different causes of congenital malformations

Anomalies of dorsal induction Anomalies of ventral induction
Primary neurulation (neural tube defects)
Encephalocoeles Holoprosencephaly
Craniorachischisis totalis Septo-optic dysplasia
Anencephaly/exencephaly Agenesis of septum
Chiari malformation Diencephalic cyst
Anomalies of neuronal proliferation and Anomalies of neuronal migration
differentiation
Micro/megalencephaly Lissencephaly
Phakomatoses Pachygyria
Colpo/porencephaly Schizencephaly
Hydranencephaly Polymicrogyria
Cong tumours/vascular malformations Heterotopias
Dysgenesis of corpus callosum
•• Morphogenic Classification:
–– Defects in neural tube closure
–– Forebrain growth failure
–– Midbrain malformations
–– Hindbrain malformations
–– Abnormal cortical development
–– Miscellaneous.
•• Classification Based on Developmental Stages:
–– Weeks 1–3 – Early stages of layer formation
–– Weeks 4 – Neurulation
–– Weeks 5 – Disorders of the anterior neural plate, abnormal
diverticulation
–– Weeks 6–8 – Dandy-Walker spectrum, cystic mal-formation of
posterior fossa
•• Classification Based on Structural Process:
–– Commissural agenesis
–– Malformations of cortical development
–– Cellular multiplication symmetrical divisions
–– Cellular differentiation
–– Cellular migration
–– Cellular organisation
–– Extracerebral cysts
–– Vascular malformations
–– Uncertain process—schizencephaly.
STRUCTURAL IMAGING
•• Congenital cerebral malformations commonly manifest as epilepsy and
neurodevelopmental deficits.
•• MRI scan is superior to CT scanning in detecting the abnormality and
associated structural defects.
•• Gross abnormalities, such as lissencephaly or schizencephaly, may
be identified on CT scan, but are more clearly seen and also in greater
detail using MRI. Multiple techniques, like fat-suppression sequences and
113
magnetic resonance venography, give additional information required for

diagnosis and surgical planning.
•• The presence of cortical dysplasia is best established by application of the
following sequences:
–– Multiple sequences, including T1-weighted, T2-weighted, fast FLAIR
and proton density, help to confirm the nature of ectopic tissue, allow
good discrimination of grey and white matter and identification of foci
of T2 prolongation (seen typically with polymicrogyria and focal cortical
dysplasia).
–– Volumetric acquisition with thin (≤ 1.5 mm) partition enables complete
coverage and reformatting in any plane, for detailed visualisation of
data and 3-dimensional constructions.
–– The use of surface coils improves discrimination by increasing the
signal-to-noise ratio. Magnification techniques and phase-array coils
enable detection of subtle abnormalities.
FUNCTIONAL IMAGING
•• Functional imaging techniques include single photon emission computed
tomography (SPECT), positron emission tomography (PET) and functional
MRI (fMRI) techniques.
•• They provide information regarding the epileptic focus, functional status,
ictal activity, blood flow changes, metabolism and neuroreceptors, and also
delineates the function of abnormal ectopic grey matter, which is important
in surgical planning.
CLINICO-RADIOLOGICAL FEATURES
Microencephaly
•• It is a descriptive term for a small brain (weight and size less than three
standard deviations for age) which may or may not be associated with
microcephaly.
•• It is usually a silent familial trait or may be associated with mental retardation
or several syndromes with autosomal recessive inheritance.
•• It is relatively a common finding in chromosomal and metabolic diseases.
•• Abnormal brain growth, faulty neurogenesis, brain atrophy and abnormal
programmed cell death are the usual proposed causes.
•• Pathologically, there may be gyral retraction ranging from pachygyria to
agyria. Histology shows a four-layered cortex with chaotic polymicrogyria,
inverted cortical layering, heterotopias, neuroglial ectopia and lack of
maturation.
Megalencephaly
•• It is a large brain (by size and weight), which is above two standard
deviations for age.
•• It may affect a single hemisphere (hemimegalencephaly or may be
associated with ventriculomegaly), could be isolated or in association with
other developmental disorders like Soto’s syndrome or osteochrondral
dysplasia.
•• It could be silent or manifest with seizures and psychomotor impairment.
•• In hemimegalencephaly the large hemisphere usually shows an abnormal
gyral pattern with abnormal cortical plate organisation.
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•• In addition, abnormal angiogenesis may be seen in Klippel-Trenaunay

syndrome.
Hydrocephaly
•• It is ventricular enlargement caused by excessive production of CSF,
insufficient absorption or disturbance in the circulation.
•• Depending on the pathology, it could be monoventricular, biventricular,
triventricular or tetraventricular enlargement.
•• Aqueductal stenosis due to Bickers-Adams syndrome or atresia (forking)
is well known.
Lissencephaly
•• It describes the morphologically smooth brain. The term is also used for
agyria/pachygyria due to abnormal corticogenesis.
•• Total absence of convolutions leads to agyria (smooth brain).
•• Pachygyria is an intermediary form with less frequent broad gyri and
shallow sulci.
•• These two can coexist in the same brain.
•• More than 25 syndromes, associated with this anomaly presenting with
mental retardation, and epilepsy have been described.
•• Classical Lissencephaly or Type 1:
–– It is due to abnormality in two genes, namely LIS 1 gene mapping on
chromosome 17p 13.3 and DCX gene mapping on abnormal XQ 22.3.
–– Radiologically, there could be reversal of grey-white matter ratio.
–– Histologically, there is a four-layered cortical organisation made up of
the following:
¾¾ Superficial hypocellular layer
¾¾ Cellular zone of hypertrophic large pyramidal cells
¾¾ Underlying pachycellular layer
¾¾ Large rim of ectopic neurons.
•• Cobblestone Lissencephaly or Type 2:
–– It is a distinct cytoarchitectural disorder occurring in a group of auto-
somal recessive disorders like Walker-Warburg syndrome, Fukuyama
muscular dystrophy and muscle-eye-brain disease usually associated
with early hydrocephalus and agyric nodular brain surface.
–– “Cobblestoned” disorder is usually associated with cerebellar dys-
plasia, brain stem disorganisation, micro-ophthalmia and retinal
dysplasia. In addition, encephalocoeles and genital malformation in
males have also been reported.
•• Walnut Type Lissencephaly or Type 3:
–– It is described in relation to Neu-Laxova syndrome.
–– Severe microcephaly, joint deformities and skin abnormalities are the
usual features.
Holoprosencephaly
•• It morphologically refers to a spectrum of forebrain malformations
characterised by failure of the prosencephalon to form two lateral
telencephalic vesicles.
•• It is usually associated with a spectrum of craniofacial abnormalities.
•• Single calculi, atresia of the aqueduct, single medially fused cerebellar
115
hemispheres and spina bifida have also been described.

•• Septo-optic dysplasia (de Morsier syndrome) is also a midline developmental
field defect.
•• CNS malformations are characterised by an abnormal septum pellucidum,
dysplasia of the optic chiasm or optic nerves and pituitary abnormalities.
•• Based on the severity, it has been divided into three groups:
–– Lobar
–– Semi-lobar and
–– Lobar with numerous transitional forms.
Agenesis of Corpus Callosum

•• It may be total or partial due to failure of the cortico-cortical tracts to cross
the midline.
•• In total agenesis, the medial surface of the hemisphere shows the
characteristic absence of the cingulate gyrus and radial arrangement of
the convolutions with an abnormal callosal artery.
•• The callosal fibres that have failed to cross remain on either side of the
lamina terminalis and form anteroposterior bundles called “Probst bundles”
in association with the fornix.
•• In partial agenesis, the body and splenium will be missing.
•• Anterior agenesis is extremely rare.
•• In severe hydrocephalus, the roof of the third ventricle may bulge into the
interhemispheric region resembling the wall of a cyst.
•• Corpus callosum agenesis may be isolated or associated with an incredible
number of syndromes like golden hour syndrome, Aicardi syndrome, Apert
syndrome, etc.
•• The isolated ones are usually clinically asymptomatic.
•• The chromosomes 18 and 8 are the most commonly involved in this
condition, in addition to many metabolic diseases.
Schizencephaly
•• Schizencephaly is a developmental disorder of cortical migration that was
first described in 1946 by Yakovlev and Wadsworth.
•• Schizencephaly is a cerebrospinal fluid-filled cleft extending from the
ependymal surface of the brain to the pia.
•• The clefts are lined with thickened four-layered grey matter oriented
parallel to the major sulcus. Other cortical areas may also show disordered
migration with pachygyria, polymicrogyria and heterotopias.
•• There are two types of schizencephaly:
–– Closed-lip (type I) schizencephaly: These are grey matter lined
clefts which are in apposition to each other. Usually the ventricular
margin shows an outpouching at the site of closed-lip schizencephaly,
acting as an important clue.
–– Open-lip (type II) schizencephaly: These are larger, grey matter
lined clefts which are separated with an obvious defect in ventricular
margin.
•• Schizencephaly can be unilateral or bilateral.
•• Associated findings may include heterotopias, absence of septum
pellucidum, hippocampal abnormality, pituitary hypoplasia and callosal
dysgenesis.
116
•• Patients with schizencephaly may present with features resembling those

of polymicrogyria.
•• Patients can be divided into those with bilateral and unilateral schizencephaly.
•• Bilateral are less common than unilateral. Approximately 30−40% of
patients have bilateral schizencephaly.
•• Bilateral lesions are often asymmetric, with type I schizencephalic lesions
in one hemisphere and type II lesions in the opposite hemisphere.
•• The localisation of these lesions follows the vascular supply territory, with
the majority of clefts localised in the fronto-temporal regions.
•• Clinical observations have identified that patients with bilateral schizen-
cephaly often have moderate to severe motor dysfunction, characterised
as spastic quadriparesis, marked developmental delay, mental retardation
and language disorders.
•• The seizure disorder in the unilateral group of patients is focal motor, but
often sensory, as well as complex partial seizures.
Pachygyria
•• Pachygyria is a milder variant of lissencephaly characterised by broad gyri
and a thick cortex with an abnormal cytoarchitecture, although histologically
the pachygyric cortex may have a more organised cortical structure than
in lissencephaly.
•• Pachygyria is seen in metabolic CNS disorders, such as the Zellweger
syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and glutaric
aciduria IIA.
•• On MRI, the cortex appears thicker and the typical figure 8-shaped image
seen in lissencephaly is not present in pachygyria.
•• The clinical presentation includes developmental delay and seizures, and
half of the patients have microcephaly.
Polymicrogyria
•• The term “polymicrogyria” refers to an abnormal macroscopic appearance
of the brain gyration that is characterised by too many small, abnormal gyri.
•• In some cases, the gyri are shallow, small and are separated by shallow
sulci, whereas in other cases the gyri are wider.
•• Histologically, the cortex consists of the molecular and wide neuronal layer
(in some cases, there are three poorly defined neuronal layers).
•• These layers are irregularly over-folded and fused, eliminating the sulci
and there is evidence of midcortical ischemic laminar necrosis in layer 5.
•• Superficial to this cortical band, the cortex consists of normal layers 4, 3
and 2.
•• Polymicrogyria can be diffuse or focal, bilateral or unilateral, symmetric
or asymmetric.
•• It is diverse in its aetiology and pathogenesis. Although most of the
experimental and human foetal pathology data suggest that polymicrogyria
may be the result of a post-migratory ischaemic mechanism.
•• Clinically, patients with polymicrogyria have an extremely variable presenta-
tion, depending on the location, extent and whether there is involvement
of the contralateral hemisphere.
•• Diffuse polymicrogyria may present with severe developmental delay,
microcephaly and hypotonia.
•• Polymicrogyria can be localised to one hemisphere and may also be one
of the histologic changes in patients with hemimegalencephaly.
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•• MRI findings demonstrate a thick cortex that can be interpreted as

pachygyria.
•• However, cortical thickness is less than that observed in pachygyria.
•• The sulci are shallow and the underlying white matter may show an
abnormal T2 signal.
HETEROTOPIAS
•• Heterotopias are a collection of nerve cells in abnormal locations due to
an arrest in the migration process.
•• Band Heterotopias
–– This syndrome is prevalent in females.
–– Patients have mild to moderate developmental delay, pyramidal signs
and, in some cases, there may be associated dysarthria.
–– EEG demonstrates generalised spike-and-wave discharges or multi-
focal EEG abnormalities.
–– Classic MRI findings demonstrate a band of subcortical grey matter
heterotopia underlying the cortical mantle and separated from it by a
thin rim of white matter. This is usually more obvious over the fronto-
central-parietal region.
–– Pathologic specimens have demonstrated normal lamination in corti-
cal layers 1 through 4. Layers 5 and 6 cannot be seen, the layer 6 is
merged with the U-fibres of the white matter.
–– Functional MRI studies in double cortex have shown that these regions
may play a role in normal brain functioning.
–– Periventricular heterotopias may be seen in tuberous sclerosis, but
there the lesions are usually calcified and have a heterogeneous in-
tensity on MRI scanning.
•• Subependymal Heterotopias:
–– Heterotopias are defined as nodular grey matter masses that can be
diffuse, bilateral or unilateral.
–– Subependymal heterotopias comprise one of the most common forms
of developmental disorders.
–– These can range from a few nodular clusters of neurons to diffuse lin-
ing of the ependymal regions.
–– Clinically, patients with subependymal heterotopias have normal neu-
rologic development, unlike most other neuronal migration disorders.
–– Most patients with periventricular nodular heterotopia present with
epilepsy (80%).
–– Onset of epilepsy in the second decade of life, normal developmental
milestones and intelligence, and overwhelming female preponderance
differentiates subependymal heterotopia from other cortical dysgen-
eses.
–– The typical MRI features consist of multiple smooth nodules of cortical
grey matter in all sequences, protruding slightly into the ventricular lu-
men, resulting in an irregular ventricular outline and no enhancement
on contrast.
–– Subependymal nodules seen in patients with tuberous sclerosis may
be mistaken for that seen in heterotopias.
•• Focal Cortical Dysplasia:
–– Focal cortical dysplasia (FCD) is probably the most common form of
focal developmental disorder diagnosed in patients referred for intrac-
table epilepsy.
118
–– Pathologic characteristics are disruption of cortical lamination with

giant neurons and large astrocytes.
–– These changes range from mild cortical disruption without apparent
giant neurons to the most severe forms in which cortical dyslamination,
large bizarre cells and astrocytosis are present.
–– The most prominent histologic feature is the presence of a large num-
ber of abnormal cells with total loss of histologic architecture.
–– FCD can be classified into two types based on the presence of bal-
loon cells.
–– Type I is without balloon cells and type II is with balloon cells. Type II
is more severe and is characterised by the presence of increased cel-
lularity, giant cells and cortical chaos.
–– Seizures begin in the first decade of life, usually after the age of 2 or
3 years, but sometimes shortly after birth. In some patients, seizures
present in the second decade.
–– The seizures may be partial motor, partial complex with or without
secondary generalised. The majority of patients tend to have extratemporal
cortical dysplasias.
–– Temporal lobe developmental malformations with cortical dysplasia
and balloon cells may coexist with mesial temporal sclerosis (dual
pathology).
–– The most obvious MRI finding of FCD is abnormal signal intensity in
the white matter, resulting in a poor grey-white differentiation.
–– The presence of a radiated abnormal signal extending from the
ependymal surface of the ventricle to the overlying cortex, termed
“transcortical malformation” of cortical development, helps to distin-
guish FCD from neoplasms.
–– Immunocytochemical staining for tuberin, which is defective in tuber-
ous sclerosis, is effective for differentiation of the two conditions.
–– Though FCD is a major cause of medically intractable epilepsy, the
cellular mechanisms underlying the epileptogenicity of FCD remain
largely unknown.
MANAGEMENT
•• The management of patients with congenital malformations includes
establishing the cause of the malformation with genetic studies and
establishing the foci of epilepsy.
•• Once such information is gathered, the management includes physical
rehabilitation, pharmacotherapy to control seizures and spasticity, genetic
counselling, and appropriate surgical treatment.
•• Best results are obtained when complete or major excision of both the
MRI-visible lesion and the cortical areas displaying ictal electrographic
activity can be performed.
•• Multilobar resection or hemispherectomy for patients with infantile
spasms associated with cortical dysplastic lesions and for patients with
hemimegalencephaly are often associated with dramatic improvement in
seizure control.
•• Callosotomy can be performed in selected patients with diffuse cortical
dysplasia who have intractable drop attacks.
14
CHAPTER
Encephalocoeles
Ashok Kumar Mahapatra
INTRODUCTION
•• Encephalocoeles are a group of conditions in which there is protrusion of
the brain and/or meninges out of the cranial cavity through a skull defect.
•• Depending on the content of herniation, it may be a cranial meningocoele
or meningoencephalocoele.
•• When herniated brain contains part of the ventricle, the condition is named
as hydroencephaly. Thus, encephalocoele is a general term used for all
the above abnormalities.
•• Tandon in 1970, reported a comprehensive classification of all
encephalocoeles and provided the first large series of these lesions from
India.
INCIDENCE
•• Encephalocoeles occur less commonly than spinal dysraphism. The inci-
dence of encephalocoeles is reported to be 1 per 3,000−10,000 live births.
•• Overall, occipital encephalocoeles are more frequent than anterior
encephalocoeles (75% vs 15%).
•• In general, encephalocoeles are occipital in 75%, frontoethmoidal in
13−15% and parietal in 1−12% cases.
•• Basal encephalocoeles, such as transethmoid and trans-sphenoid
encephalocoeles are rare.
EMBRYOLOGY
•• There is no clear-cut explanation for maldevelopment of the neural tube at
the cephalic end, leading to encephalocoele.
•• The development of various neural tube defects has been attributed to
either primary failure of closure of the neural tube, or rupture of the neural
tube due to some unknown reasons after it has closed around the 27−28th
day of gestation.
•• The neuroschisis theory proposes the formation of a bleb over the neural
tube, which, on healing, gets adherent to cutaneous ectoderm resulting in
explain the formation of an encephalocoele.
•• Anterior encephalocoeles are due to failure of the anterior neuropore, which
lies in front of the foramen caecum in the floor of the anterior cranial fossa
just ahead of the crista galli, which marks the junction of the frontal bone
with the ethmoid bone.
120
CLASSIFICATION OF ENCEPHALOCOELES
•• A large number of classifications of encephalocoeles (Table 1) are available
depending on several aspects, such as site of cranial defect, whether or not
the encephalocoele is seen from outside and the size of the encephalocoele.
•• Encephalocoeles are classified as occipital, parietal, frontal, nasal and
nasopharyngeal type.
•• Heinecke, in 1882, classified anterior encephalocoeles as: (a) spheno-
pharyngeal, (b) spheno-orbital and spheno-maxillary types depending on
the hernial tract.
•• Mesterton, in 1885, classified anterior encephalocoeles as: (a) naso-frontal;
(b) naso-ethmoidal and (c) naso-orbital types.
•• Bumenfeld and Skolink, in 1965, named these encephalocoeles as:
(a) trans-ethmoidal; (b) trans-sphenoidal; (c) spheno-ethmoidal and (d)
spheno-maxillary.
Table 1: Classification of encephalocoeles

A. Congenital:
Acquired—post-traumatic, post-operative, post-irradiation
B. According to the locations:
1. Anterior encephalocoeles (frontoethmoidal or sincipital)
2. Occipital or sub-occipital encephalocoele
3. Basal:
• Trans-sphenoidal
• Transethmoidal
• Intranasal
• Spheno-oribital
• Transtemporal
4. Cranial vault:
• Frontal
• Parietal
• Temporal
• Through anterior or posterior fontanel
C. According to the size:
• Small encephalocoele
• Giant encephalocoele
D. According to the content:
• Cephalocoele
• Encephalocoele
• Meningoencephalocoele
• Cranial meningocoele
• Hydroencephalomeningocoele
E. Encephalocoele as a part of complex syndrome such as:
• Chiari III—Malformation
• Knobloch syndrome
• Morning glory syndrome
• Walker-Warburg-Syndrome (WWS)
F. Overt:
Occult
• Intranasal
• Intraorbital
• Intratemporal
• Intradiploic
Chapter 14 • Encephalocoeles
121
ASSOCIATED PATHOLOGY
•• A large number of systemic abnormalities have been reported along with
encephalocoeles (Table 2).
•• The musculoskeletal system is widely involved.
•• Rarely, the retina and vitreous can be abnormal.
•• Morika et al. had described progressive hormonal and visual disturbance,
which has been described as “morning glory syndrome”.
•• Associated anomalies can include many genetic syndromes, such as
Meckel-Gruber, Von Voss, Chemke, Roberts and Knobloch syndrome.
•• Other non-genetic anomalies may include cryptophthalmos, amniotic band,
spina bifida, agenesis of corpus callosum and Dandy-Walker syndrome.
•• The most common chromosomal abnormality is Trisomy.
CLINICAL PRESENTATION
•• Classically, patients with encephalocoeles are born with a swelling at birth.
The size and content of the encephalocoeles are variable.
•• In occipital encephalocoele, a globular swelling is noticed over the occipital
bone in the midline.
•• Encephalocoeles could be pedunculated or sessile.
•• The size of the encephalocoele is hardly ever indicative of its content. The
head may be smaller than the size of the encephalocoele.
•• Most encephalocoeles are brilliantly transilluminant on examination.
However, when a large amount of gliosed brain is present inside the sac,
there may be variability in the degree of transillumination.
•• Usually the head size is small. The larger the brain herniation, the smaller
is the head size.
•• Sometimes the encephalocoeles may be very large and are called giant
encephalocoeles.
•• The site of the encephalocoeles is frequently occipital or suboccipital.
Around 10% of the encephalocoeles could be anteriorly located. Rarely,
encephalocoeles could be temporal or parietal in location. They could
also be rarely intranasal transethmoidal or orbital in location. Very rarely
the encephalocoele can be located at the anterior or posterior fontanel.
•• Patients with frontoethmoid encephalocoele present with a swelling over
the root or the bridge of the nose at birth.
•• Patients with nasopharyngeal, sphenoethmoidal and trans-sphenoidal
encephalocoeles do not have an obvious external swelling and may present
with nasal obstruction or CSF rhinorrhoea.
Table 2: Systemic abnormalities associated with encephalocoeles

– Cleft lip cleft palate – Visual disturbances
– Micrognathia – Vitreoretinal degeneration
– Microcephaly – Retinal detachment, myopia
– Scalp defects – Dextrocardia
– Hair Collar sign – Septal defects
– Klipple–Feil deformities – Patent ductus arteriosus
– Vertebral abnormalities – Pulmonary hypoplasia
– Polydactyly – Renal hypoplasia
– Spina–bifida – Renal agenesis
– Diastematomyelia
122
•• Rarely, encephalocoeles may present in the mouth through a cleft palate

(trans-sphenoidal transpalatal encephalocoele).
•• Orbital encephalocoeles usually present with proptosis without
hypertelorism. The proptosis disappears on assuming the supine position.
ANTERIOR ENCEPHALOCOELES
Nasofrontal Type
•• This type is also called frontonasal or glabellar encephalocoele.
•• The internal bone defect is round or oval shaped and present in front of the
crista galli. The crista galli projects into the defect and forms the posterior
margin. The anterior cranial fossa is deep. The facial bone defect is at the
junction between the frontal and the nasal bones.
•• Hypertelorism may or may not be present.
•• However, the maxilla, nasal bone and nasal process of the maxilla are
normal. This type is relatively rare.
Nasoethmoid Type
•• This is the commonest type of sincipital encephalocoele and constitutes 85%
of anterior encephalocoeles. This type is called long nose encephalocoele.
•• The cranial defect lies in front of the crista galli in the floor of the anterior
cranial fossa. The outer or facial defect lies at the junction of the nasal
bone and nasal cartilage.
•• The neck of the encephalocoele is very long. The nasal bone and frontal
process of the maxilla form the antero-superior part of the sac. The nasal
cartilage and nasal septum form the postero-inferior wall. The lateral part
of the sac extends into the orbit and presents at the inner canthi.
•• Thus, the encephalocoele pushes the orbit and the eyeball laterally and
downwards, and produces a marked degree of hypertelorism.
•• The swelling widens the bridge of the nose and pushes the tip of the nose
downwards, thus elongating the nose considerably.
Naso-orbital Type
•• This is a rare form of fronto-ethmoidal encephalocoele.
•• The inner skull defect lies in front of the crista galli and the outer defect is
present between the frontal process of the maxilla and the lacrimal bone.
•• The frontal process of the maxilla forms the anteromedial boundary,
whereas the lacrimal bone forms the posterior-lateral part of the sac.
•• The outer swelling appears at the inner canthus of the eye and may be
unilateral or bilateral.
•• The eyeball and the inner canthus are pushed laterally and downwards.
•• Thus, in all these patients, some degree of hypertelorism is invariably
present. The nose and nasal bones are normal.
Trans-sphenoid Encephalocoeles
•• This is the rarest form of encephalocoele reported in the literature.
•• The bony defect is present over the roof of the sphenoid sinus.
•• Thus, the encephalocoele may come through the sella or through the
planum sphenoidale and enter into the sphenoid sinus and nasopharynx.
•• The patient may have a history of CSF rhinorrhoea.
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ASSOCIATED CLINICAL FEATURES

•• Hypertelorism is a common finding in anterior encephalocoeles.
•• Neurofibromatosis and 13-15 trisomy syndrome have been reported in
patients with encephalocoeles.
•• Mental retardation is reported depending upon the degree of brain damage.
•• Children with occipital encephalocoeles with cerebellum and brainstem
herniating into the sac may present with poor cry and suckling. Increased tone
in the limbs and defective temperature regulation indicate a poor prognosis.
•• In unilateral naso-orbital encephalocoeles with a paramedian anterior fossa
defect, smell is likely to be preserved on one side.
•• Visual abnormalities are due to a variety of reasons and may be due
to herniation of the occipital lobes into an occipital encephalocoele,
chiasmal abnormality in trans-sphenoidal encephalocoele or due to orbital
encephalocoele pressing on the optic nerve.
•• Few rare syndromes are associated with encephalocoeles.
–– “Knobloch syndrome” was described by Knobloch and Layer in
1971. This syndrome is transmitted by an autosomal recessive gene
and characterised by vitreoretinal degeneration with retinal detach-
ment, high myopia and encephalocoele.
–– “Morning glory syndrome” is a condition characterised by nasal
encephalocoeles associated with progressive hormonal and visual
problems. The basal encephalocoeles are either the trans-sphenoidal
or sphenoethmoidal type. Due to pituitary involvement, patients pre-
sent with dwarfism, polyurea and polydipsia. There is deficiency of
growth hormone and ADH.
–– “Von Voss-Cherstvoy syndrome” is another clinical entity first
described by Von Voss et al. in 1979. The syndrome is characterised
by an occipital encephalocoele along with phocomelia and cerebellar
anomalies and is transmitted by an autosomal recessive gene. The
other anomalies associated involve the face, heart, lungs, urogenital
system, gastrointestinal system and thrombocytopenia.
–– Walker-Warburg syndrome (WWS) is a lethal, complex syndrome
involving the CNS and the eyes, and is genetically transmitted by an
autosomal recessive gene. Martinez et al. reported nine children with
WWS out of whom eight had occipital encephalocoeles.
Investigations
•• Prenatal diagnosis is possible by ultrasound scanning earliest by 13 weeks
of gestation.
•• Chromosomal abnormalities have been recorded in 15−40% and, therefore,
karyotyping should be done in the mother.
•• Maternal serum alpha-fetoprotein levels are elevated in only 3% in the
mother, because most encephalocoeles are covered with skin.
•• In the 2nd trimester, ultrasound scanning is the mainstay of foetal imaging.
•• Foetal MRI is the investigation of choice. MRI is also far better in
resolving posterior fossa anatomy. The fluid and CSF filled cavities are
best demonstrated in MRI scan. The contents of the encephalocoele are
well-depicted on MR scan. MRI scanning helps in visualising associated
intracranial anomalies such as chiari malformation, Dandy-Walker
Syndrome, agenesis of corpus callosum and porencephalic cyst.
124
•• Large number of factors influence the treatment and ultimate outcome.

These include the presence of hydrocephalus, associated CNS anomalies,
facial deformity and associated systemic abnormalities. Assessment of
all the above factors needs proper investigations which may include the
radiological, genetic and hormonal assessment.
•• Plain X-ray:
–– Shows a soft tissue mass and a circular smooth bone defect in the
sub-occipital area, the skull vault or at the skull base depending on the
site of the encephalocoele.
–– In sincipital encephalocoeles, X-ray skull will show a deformity of the
orbits and increased interorbital distance in cases of hypertelorism.
–– Plain X-ray skull will show an enlarged orbit in case of intraorbital
encephalocoeles.
–– Plain X-ray may show hypoplasia of the anterior or middle fossa, skull
deformity, craniostenosis, etc.
•• CT scan and MRI scan:
–– Help in evaluation of the ventricular system. Hydrocephalus is com-
monly associated with posterior encephalocoeles.
–– The contents of the encephalocoele can be made out and the bony
defect in the skull base can be delineated with bone window settings.
–– CT scan can also detect associated anomalies like agenesis of the
corpus callosum, porencephalic cyst, Dandy-Walker malformation, etc.
In transethmoidal or trans-sphenoidal encephalocoeles, CT shows the
soft tissue density in the sinuses and the bone defect in the skull base.
–– In orbital encephalocoele, its relationship to the eyeball and optic nerve
can be evaluated by high resolution CT. The bone cut may show a
sphenoid wing defect.
–– Metrizamide CT cisternography is useful in cases of occult encepha-
locoele. Three dimensional CT scans are also used for the evaluation
of basal defects.
–– MRI helps in soft tissue delineation. It also helps in diagnosis of Chiari
malformation, syringomyelia and associated cortical dysplasia.
•• Isotope studies: Isotope cisternography confirms the cause of CSF
rhinorrhoea.
•• Recently, visual evoked potentials have been used to assess occipital lobe
and anterior visual pathway function.
MANAGEMENT
•• The principle behind the management of encephalocoeles is to excise
the encephalocoele and to repair the dural defect after putting back the
herniated brain inside the cranial cavity, if possible.
•• Sometimes, it may not be possible to push the brain into the cranial cavity.
Then, the choice is to either excise a part of the brain or to give support to
the brain in an extracranial space.
•• For a patient with a leaking encephalocoele associated with hydrocephalus,
shunt surgery may stop the CSF leak and allow the skin to heal.
•• Except for the situation with CSF leak, probably there is no indication for
emergency surgery. Fortunately, most of the encephalocoeles have a good
skin cover hence, emergency surgery is not required.
•• The surgery can be delayed for weeks and months depending on the
condition of the neonate.
125
•• Surgery is simple when an encephalocoele is small, has a narrow neck, a

small cranial defect and very little or no brain inside the sac.
Occipital Encephalocoele
–– An occipital encephalocoele without brain herniation can be operated
upon easily. However, when the sac contains cerebrum, cerebellum
and brainstem, surgery may be harmful and it is better to avoid an
operation.
–– Generally, patients with occipital encephalocoeles are operated upon
in the prone position, with controlled ventilation and closed tempera-
ture monitoring.
–– For patients with a large encephalocoele aspiration of CSF prior to
incision helps in dissecting out the sac. For a circular encephalocoele
with a small occipital bone defect, a transverse incision is ideal. The
sac is separated from the skin flap.
–– Patients in whom the encephalocoele extends above and below the
posterior fossa, a vertical incision is preferable.
–– Sometimes the brainstem and occipital lobe are present in the sac.
Care must be taken to identify the contents of the sac. Rarely, the
sagittal sinus, torcula and transverse sinus are in the vicinity of the sac
It is always preferable to preserve the neural tissue.
–– The dural defect can be repaired by using pericranium as a graft.
–– In neonates and infants, no attempt should be made to cover the bone
defect by a bone graft. In older children with a large cranial defect,
autogenous bone graft or acrylic plate may be used for closure of the
defect.
Anterior Encephalocoeles
–– The principle behind the management of anterior encephalocoeles
is to repair the dural defect and to correct the bony deformities.
Unfortunately, a large number of patients have facial abnormality due
to associated hypertelorism, and an elongated nose. Hence, the facial
deformity plays an important role in corrective surgery.
–– The cosmetic outcome depends upon the experience of the surgeon,
age of the patient, degree of deformity and the teamwork between the
neurosurgeon and the plastic or craniofacial surgeon
–– One stage correction of the craniofacial deformity is ideal. It involves
bifrontal craniotomy, fronto-orbital osteotomies and medial advance-
ment of the orbit, after excising the extra-bone in the midline to correct
the hypertelorism
–– One stage repair of encephalocoeles along with the correction of the
facio-orbital deformity is a long procedure and requires on an average
6−8 hours of surgery. Hence, the timing must be such that the child is
able to withstand a long procedure. Ideal to do the surgery when the
child is older than 8−10 months.
–– Early surgical repair is ideal, as the bones are thin and moulding of
the bones is easy. Early surgery also prevents CSF leak and the risk
of meningitis.
–– A ventriculoperitoneal shunt prior to corrective surgery prevents post-
operative CSF leak in patients with hydrocephalus.
–– The factors which influence the surgery are the type of encephalocoele,
degree of hypertelorism, degree of nasal deformity and associated
CSF leak or meningitis.
126
–– Reconstruction of the nose is an important step in correction of anterior

encephalocoeles.
–– Post-operatively, there may be a CSF leak or acute hydrocephalus
may develop. Patients in whom shunt is not performed prior to enceph-
alocoele repair may need ventriculoperitoneal shunt subsequently.
•• Encephalocoeles Through the Cranial Vault: These are rare may be
through the frontal, parietal or temporal bones. Encephalocoeles can occur
through the anterior or posterior fontanel.
•• Parietal or interparietal encephalocoeles are probably the most common
encephalocoeles of the cranial vault. Interparietal encephalocoeles are
difficult to treat and do have a poor prognosis.
•• Patients with large skull defects need cranioplasty.
•• Temporal and Parietal Encephalocoeles:
–– They constitute 1% of all cases of encephalocoeles. Rarely, a tempo-
ral encephalocoele may develop following radiation and present with
CSF otorrhoea. The surgical procedure is similar to that of occipital
encephalocoeles.
•• Trans-sphenoid Encephalocoele:
–– It is rare and only less than 50 cases are reported in the world literature.
–– Small children with a cleft palate may present with respiratory
obstruction or recurrent chest infection.
–– Management is difficult and they need early surgery. The surgical
approach can be transpalatal or transcranial. Repair the temporo
sphenoidal encephalocoele with a vascularised split calvarial graft.
Prognosis
•• Occipital Encephalocoeles:
–– Factors influence the outcome include site, size of the encephalocoele,
amount of brain herniated into the sac, the presence of brainstem,
occipital lobe with or without dural sinuses and the presence of
hydrocephalus.
–– One of the most important prognostic factors is the presence of
associated brain and systemic anomalies.
–– Overall, the outcome in occipital encephalocoele is not very good.
occipital encephalocoele with hydrocephalus carries a much poorer
prognosis
–– In giant encephalocoeles, the mortality and morbidity rates are high.
•• Anterior Encephalocoeles:
–– Generally, the prognosis in children with anterior encephalocoele is
better than occipital encephalocoele.
–– The intellectual function is good in patients with anterior encephalocoele.
The associated cosmetic problems can be corrected with appropriate
craniofacial surgery.
–– In the absence of hydrocephalus or meningitis, a large number of
children are likely to have normal intellectual development.
15
CHAPTER Intracranial
Arachnoid Cysts
Chidambaram Balasubramaniam  Vani Santosh
INTRODUCTION
•• Bright described these as, “serous cysts forming in connection with the
arachnoid and apparently lying between its layers”.
•• Arachnoid cysts (ACs) are “intra-arachnoidal” collections of cerebrospinal
fluid (CSF). These cysts are found within the arachnoid as isolated
collections of CSF.
•• AC may be found anywhere along the CSF axis; the intracranial cysts are all
intradural while those located in the spinal canal may be extradural or intradural.
•• Most of the ACs are discovered in the first two decades of life, 60−80%
being discovered by 16 years of age.
•• Although most of these cysts are usually congenital, they may follow trauma
or infection of the central nervous system (CNS). The congenital variety
accounts for 1% of all intracranial space occupying lesions.
•• These cysts may be associated with other developmental anomalies of the
brain and, by indenting and exerting pressure on the subjacent brain, they
may cause secondary local atrophy and gliosis.
•• Of the many theories proposed to explain their origin, abnormal splitting of
the arachnoid during embryogenesis is widely accepted. Their association
with the CSF cisterns lend support to this theory.
EMBRYOLOGY AND ANATOMY

•• Two theories have been proposed to explain the formation of AC.
•• One holds that sequestration of the CSF resulting from an aberration of
the flow of the CSF, results in the formation of AC.
•• The other postulates that an abnormal splitting of the primordial arachnoid
and the subsequent aberration in the formation of the CSF spaces leads
to the formation of the AC.
•• Suprasellar AC is considered to be an outpouching of the membrane of
Liliequist. If this membrane remains imperforated, it prevents the flow of
CSF from the infratentorial to the supratentorial compartment. This results
in the formation of a diverticulum and, over a period of time, the continued
dilatation results in the formation of a suprasellar AC.
•• ACs are thus congenital malformations, which are wholly intra-arachnoidal,
lying between the layers of the arachnoid, the outer and inner layers being
formed by the barrier cell layer and basal cell layer, respectively.
•• The causative factors of these cysts are quite varied. By and large, the
most common variety is the congenital form. The other causes include
trauma and inflammation.
128
•• Not all cysts which are initially diagnosed as congenital AC (based on

clinical, imaging or operative findings) are true AC. Some of them may be
glioependymal cysts, ependymal cysts or simple cysts lined by atrophic
brain.
•• True ACs are congenital and the evidence to support this is strong and
may be summarised as follows:
–– They occur predominantly in the paediatric age group—as much as
60–80% being discovered by the 16th year of life.
–– Most required treatment in the paediatric age group.
–– Associated expansion or bulging of the calvarium at the site of the cyst.
–– An acquired cause cannot explain the gross and microscopic pathol-
ogy.
–– The subarachnoid cisterns and spaces are not one continuous sea of
CSF. In addition, the cisterns are divided into discrete compartments
which communicate with one another. This indicates that these cysts
result from an abnormal splitting and loculation of CSF as a conse-
quence of an embryologic error. All cysts are related to a subarachnoid
cistern.
–– The walls of the AC are continuous with the arachnoid; the cyst thus is
an “island” in an “ocean” of CSF.
–– Presence of other congenital brain anomalies.
–– Normal structure of the brain as seen during surgery and the re-
expansion following surgery.
PATHOGENESIS OF CYST EXPANSION

•• The expansion of the cysts over time has been attributed to a variety of
causes.
•• These include flow of CSF into the cyst by a ball-valve action, secretion
of CSF by the cyst wall, secretion by a choroid-like structure in the wall or
osmotic gradient permitting ingress of CSF.
•• A slit valve mechanism was observed in a child with a suprasellar AC during
endoscopic surgery. The valve, formed by an arachnoid membrane, was
seen to open and close with pulsations.
•• Vascular pulsation is the force which propels the CSF into the cyst. The
fluid may gain entrance into the cyst during the various phases of the
cardiac cycle.
•• Secretion of CSF by the cyst wall has been postulated to be a mechanism
by which these cysts expand. Secretion from choroid-like structures present
in the cyst wall has also been postulated to be a cause for the increase in
the size of the cyst but this lacks proof.
•• Also, the ultracytochemical evidence of Na+–K+–ATPase and alkaline
phosphatase in the plasma membranes of the lining cells suggest a capacity
for fluid secretion. Although these indicate possible secretory activity, no
direct evidence for secretion exists. Until this is observed directly or definite
proof for this is available, this has to be accepted only as a hypothesis.
PATHOLOGY
Macroscopic Appearances
•• The most striking histological finding in the AC is the splitting of the
arachnoid membrane to enclose the cyst, while the pia-mater remains as
a separate intact membrane.
Chapter 15 • Intracranial Arachnoid Cysts
129
•• The normal arachnoid membrane seems to blend with the outer layer of
the cyst wall at the margin of the cyst.
•• The cyst is, therefore, intra-arachnoid with an inner and outer wall formed
by the arachnoid membrane.
•• Grossly, the cyst consists of a thin transparent wall. Its outer part is distinct
from the inner layer of the dura. On its inner aspect, it shows a plane of
cleavage from the underlying pia-mater.
•• The cyst is usually filled with clear, colourless fluid. The watery content of
an AC is readily seen through its delicate translucent wall.
•• When the wall is punctured, the contents spill to expose the flattened gyri
of the adjacent brain. Thereafter, the delicate membrane may be hard to
find, its thin substance being almost inapparent.
•• Occasionally, the cyst fluid may be xanthochromic and rich in protein and
can be mistaken for a subdural hygroma.
•• Vessels lie unsupported in the cyst and may rupture easily leading to
intracystic haemorrhage.
Microscopic Appearances
•• The light microscopic and ultrastructural features of ACs are comparable
to the normal arachnoid mater with a few differences.
Light Microscopic Features
•• The majority of cases exhibit features suggestive of splitting of the arachnoid
membrane. The cyst wall consists of a vascular collagenous membrane.
•• The collagen bundles in the adjacent normal arachnoid membrane and in
the superficial layers of the dome of the cyst are compact, while the collagen
fibres in the deeper layers of the dome and in the inner wall of the cyst are
more loosely arranged.
•• The inner wall of the cyst and pia mater are in direct contact with each
other. Here, the subarachnoid space is obliterated.
•• The light arachnoid cells are frequently seen lining the subarachnoid space
and these cells are also sparsely scattered in the connective tissue.
Transmission Electron Microscopic Features
•• The superficial dark arachnoid cells which form the outer tiers within the
dome of the cyst have condensed nuclei and cytoplasm.
•• The cytoplasm contains abundant filaments and a fair number of rough
endoplasmic reticulum, free ribosomes, mitochondria and golgi complexes.
•• The inner surface of the AC wall is lined by clear arachnoid cells. These
are hyperplastic, larger and appear as evenly hydrated cells, and resemble
foetal arachnoid cells.
Immunohistochemical Findings
•• The cysts are negative for markers found in other intracranial and intraspinal
cysts such as glial fibrillary acidic protein (GFAP), carcinoembryonic antigen
and transthyretin.
NATURAL HISTORY
•• These cysts are well known to expand over a period of time and manifest
as space-occupying lesions or haematomas often following a trivial trauma,
with features of increased intracranial pressure.
130
•• They are also known to disappear after a head injury or undergo spontaneous
rupture.
INTRACRANIAL CYSTS
Incidence and Distribution
•• These congenital lesions account for about 1% of all intracranial mass
lesions and in 0.5% of autopsies they are seen as incidental findings.
•• Arachnoidal cysts may be congenital (or primary) or acquired. Congenital
cysts may be an outpouching of the membrane of liliequist, while acquired
ones are result of trauma, hemorrhage or inflammation.
•• Males are affected more than females and the cysts occur more often on
the left side.
•• About 60−90% of patients are in the paediatric age group and the majority
manifest within the first 6 months of life. In 25% of the cases, it is diagnosed
at birth.
•• The cyst is single in 87.5% of patients.
•• 50% of the cysts are in Sylvian fissure, 20% in posterior fossa, 10% in
supracollicular area, 9% are found in the sellar and suprasellar areas.
Clinical Features—General
•• Sylvian fissure cysts usually cause fits, haemiplegia and headache;
suprasellar cysts result in hydrocephalus, endocrine problems and bobble-
head doll syndrome; posterior fossa cysts lead to ataxia, hydrocephalus
and features of posterior fossa neoplasm.
•• These cysts may remain asymptomatic even when large and may be
discovered only at the time of autopsy.
•• The aetiology of the symptoms can be classified into “fluid related
symptoms”, “epilepsy” and “deficiency syndromes”.
•• Headache is a fairly common feature, both in children and adults. Up to
70% of patients experience chronic headaches.
•• Enlargement of head size, tense or full anterior fontanelle and wide open
sutures are often seen in children.
•• The incidence of hydrocephalus varies from 30–100% depending on the
location of the cyst. Hydrocephalus is common in posterior cranial fossa
cysts, but it is seen in almost all midline cysts.
•• Seizures are common and form an important clinical feature in as many as
half the number of patients. This is so, especially in Sylvian fissure cysts.
•• Middle cranial fossa or Sylvian fissure cysts may cause global impairment
of brain function by interfering with the blood supply.
•• Following rupture, these may present as subdural hygromas or
haematomas.
Manifestations—Specific
•• Sylvian Fissure Cysts:
–– Included in this group are temporal cysts and cysts in the middle cra-
nial fossa. This is the commonest site of occurrence of AC.
–– The incidence ranges from 49%–68%.
–– Headache and seizures are the commonest presentation of AC in this
location.
–– In infants and children, the calvarium may exhibit a bulge, even pro-
duce an asymmetrical enlargement of the head.
131
–– The cranial deformity and the midline shift, which are often present,
result from the mass effect of the cyst.
–– Since these are located primarily within the Sylvian fissure or are
closely related to it, the Sylvian fissure is spread out resulting in a
“foreshortening” of the temporal lobe.
–– The Sylvian vessels are pushed posteromedially and lie deep to the
cyst.
–– These cysts are highly susceptible to trauma and bleeding.
–– These cysts have been classified into three types based on their
size, appearance and CT cisternographic findings by Galassi et al as
follows:
¾¾ Type I: These are small biconvex cysts which are located in the
anterior part of the Sylvian fissure. They do not exert any mass
effect or cause cranial deformity. CT cisternography discloses free
communication with the subarachnoid space.
¾¾ Type II: The cysts are medium sized and quadrangular or triangu-
lar in shape. They occupy the anterior and the middle part of the
Sylvian fissure. Early pooling of the contrast and partial communi-
cation with the subarachnoid space are found on cisternography.
¾¾ Type III: These cysts are large and oval or round in shape and
involve the whole of the Sylvian fissure. They exert considerable
mass effect on the brain with severe compression of the brain and
midline shift.
•• Suprasellar Cysts:
–– These cysts account for 9−15%, of all intracranial cysts.
–– These are considered to be an outpouching of the membrane of lil-
iequist.
–– Two varieties of suprasellar AC have been described, the communi
cating and the non-communicating variety.
–– Communicating cysts communicate with the pontine cistern and non-
communicating cysts are pinched off during development and are thus
true cysts.
–– As they grow, these tend to invaginate the third ventricle and in addition
exert pressure on the pituitary stalk. They may also bulge out through
the foramen of Monro.
–– A common presenting feature is hydrocephalus and the resulting fea-
tures of raised intracranial pressure like headache and vomiting may
also be present.
–– “Bobble-head doll syndrome” is considered diagnostic of suprasellar
AC. This syndrome is characterised by a rhythmic 2−3 per second
antero-posterior oscillation of the head and trunk.
–– The clinical features are due to the hydrocephalus or compression of
the adjacent structures.
–– These cysts may invaginate into the sella turcica and cause a bitempo-
ral field defect in addition to behaving as an intrasellar mass.
–– Precocious puberty, panhypopituitarism and diabetes insipidus can
be seen.
–– The list of differential diagnoses include craniopharyngioma, Rathke’s
cleft cyst, colloid cyst of III ventricle, epidermoid cyst, lipoma, ependy-
mal cyst, parasitic cyst and dilated III ventricle in hydrocephalus.
–– AC do not show calcification on CT and present with fewer endocrine
symptoms in comparison to craniopharyngioma or Rathke’s cleft cyst.
132
•• Posterior Cranial Fossa Cysts:

–– The common presenting features are headache, vomiting and cerebel-
lar signs.
–– Infants may be referred for evaluation of an enlarged head which
results from the mass in the posterior cranial fossa.
–– These cysts can be in the midline or laterally placed as in the cerebel-
lopontine angle. In the latter instance, all the features of a mass in the
cerebellopontine angle may be present, viz sensorineural hearing loss,
facial weakness, corneal anaesthesia, etc.
•• Parasagittal and Interhemispheric Cysts:
–– Parasagittal cysts are seen off the midline while interhemispheric cysts
straddle the midline.
–– An important differentiating feature is that the latter are associated with
agenesis of the corpus callosum.
–– In addition, parasagittal cysts are unilateral and hence may cause the
midline to be shifted to the contralateral side.
–– Parasagittal cysts are elongated while interhemispheric cysts take on
a butterfly shape. Compression of the adjacent cerebral tissue is often
a feature of parasagittal cysts.
•• Pineal and Quadrigeminal Cistern Region Cysts:
–– The commonest presenting symptom is hydrocephalus.
–– AC here mimics pineal tumours but unlike pineal tumours, Parinaud’s
syndrome may not be seen.
–– Incisural region cysts also invariably cause hydrocephalus and cortical
enhancement may be seen around the cyst.
•• Convexity Cysts:
–– Even when large, may not manifest many localising signs apart from
a local bulge.
–– In infants, these may be mistaken for a subdural hygroma, but ACs do
not have an enhancing membrane.
Radiology
•• Plain skiagrams:
–– Sylvian fissure cysts cause an asymmetry of the vault, as parasagittal
and convexity cysts, may elevate the sphenoid and cause the floor of
the middle fossa to be bowed downward.
–– If there is significant mass effect, the groove for the sagittal sinus may
also be displaced.
–– In cysts of the Sylvian fissure region, the lesser wing of sphenoid may
be displaced forward.
–– Convexity and parasagittal cysts cause a localised bulge in the calva-
rium or, if large, an asymmetry of the vault.
•• Sonography:
–– Done as a screening procedure when a neonate or infant presents with
a bulging fontanelle or increasing head size.
–– Sonography reveals ACs to be anechoic fluid-filled mass lesions with
sharp margins.
–– Mass effect may also be seen as well as other brain anomalies.
•• Computerised Tomography Scan:
–– The basic appearance of these lesions is a hypodense cystic lesion
without any calcification, but with well defined non-enhancing, smooth
and round borders.
133
–– Unless there has been a haemorrhage in the cyst, the contents have
the attenuation value of CSF.
–– If the cyst is adjacent to the calvarium, a bulge or asymmetry of the
cranium may be seen.
–– Although differentiation from other cystic lesions, like cystic gliomas,
Dandy-Walker malformation, porencephaly, dilated third ventricle,
craniopharyngiomas, Rathke’s cleft cysts, lipomas and epidermoids,
may be difficult on CT, it is possible in most instances.
–– Neoplasms exhibit enhancing borders and the presence of a mural
nodule is a give-away sign for these. The cerebellar vermis is absent
or attenuated in Dandy-Walker malformation unlike in AC of the pos-
terior fossa.
–– No areas of calcification or fat are present. These allow differentiation
from neoplasms, dermoids/epidermoids and lipomas.
–– On axial imaging studies, the suprasellar cyst has been described as
resembling a bunny’s head.
–– The presence of intracystic haemorrhage, varies depending on the
“age” of the blood in the cyst.
–– Water-soluble contrast studies have disclosed the following three kinds
of cysts:
¾¾ Those that communicate freely with the CSF space.
¾¾ Those that communicate slowly.
¾¾ Those that do not communicate.
•• Magnetic Resonance Imaging:
–– The basic appearance of these lesions on MR is the same as CT,
namely well demarcated non-enhancing CSF containing cystic lesions
without any calcification.
–– MR shows indirect evidence of bony changes, namely a bulge in the
bone and erosion of bone, if present.
–– The cyst is seen as a sharply demarcated hypodense (on T1 study)
non-enhancing lesion. The “low signal of cyst fluid on T1 images give
good contrast with adjacent brain and is useful for initial diagnosis and
definition”.
–– MRI is invaluable in evaluating the soft tissue abnormalities, haemor-
rhages, and in delineating the anatomy of the adjacent brain.
–– If the signal intensity is the same as CSF in T1 and T2 weighted im-
ages, then it is almost pathognomonic of AC.
–– Even if the features are the same as CSF, the presence of enhance-
ment of the cyst walls or mural nodule favours a neoplasm.
–– MR is also very useful in differentiating AC from other lesions.
–– Steady-state precession and fast imaging (PSIF) MR sequence with
cine gating helps in differentiating cysts from enlarged CSF spaces and
increases the certainty of establishing cyst communication with CSF
spaces.
–– In diffusion weighted images, abscesses, epidermoids and cholestea-
toma are hyperintense while ACs are hypointense.
Management
•• The best operative intervention for children with ACs remains a subject
of controversy.
•• The surgical treatment is as variable as the location of the cyst.
134
•• The “middle of the road” policy of not treating asymptomatic or accidentally

discovered cysts has also been advocated.
•• At the other end is the proposal to follow a “wait and watch” policy even
for large cysts until a causal relationship with the symptoms is proven.
•• The management of these lesions can be divided into the following groups:
–– Conservative approach for all cysts
–– Surgery for all lesions (even for asymptomatic lesions)
–– Craniotomy and fenestration
–– Shunt procedures
–– Endoscopic surgery
–– Other methods of management.
•• Surgery is indicated for large cysts, which exert a mass effect, or when there
is hydrocephalus, fits, features of raised intracranial pressure, a neurologic
deficit caused by the cyst or the presence of other symptoms like endocrine,
visual/ophthalmic deficits (as may be seen in suprasellar cysts).
•• Craniotomy and Fenestration:
–– Craniotomy and fenestration of the cyst into the ventricle or adjacent
subarachnoid cistern has been proposed as the definitive or curative
treatment for these lesions.
–– The successful outcome of the surgery hinges on the principle of re-
storing normalcy to CSF circulation.
–– Primary treatment is, therefore, resection of the cyst wall and opening
of the cyst into adjacent cisterns.
–– In the areas where the dura is adherent, dissection has to be done
carefully for two reasons:
¾¾ To prevent inadvertent rupture of the cyst
¾¾ To prevent rupture of the vessels which are either draped over the
dome of the cyst or those which course inside the cyst.
–– After opening the cyst, fenestrating the inner wall may be more physi-
ologic and may obviate the need for a shunt.
–– Suprasellar cysts can be approached through a transcallosal, trans-
ventricular or subfrontal approach.
–– Once the cyst is widely fenestrated, the dead space may be filled with
irrigating fluid to prevent pneumocephalus and also to allow a gradual
re-expansion of the brain.
–– Post-operative haemorrhage may result because of the sudden re-
expansion of the brain.
–– The complications include haemorrhage because of the dead space
or snapping of the unsupported veins, failure of the brain to re-expand,
aseptic meningitis, subdural collections and a neurologic deficit result-
ing from brain shift due to rapid decompression.
•• Shunting:
–– The fundamental idea is to divert the CSF to the peritoneum—as one
would in hydrocephalus—where it will get absorbed. The results of
shunting are best for middle cranial fossa cysts.
–– The standard technique ventriculoperitoneal shunt is used. The proxi-
mal end of the shunt is placed in the cyst cavity while the distal end is
in the peritoneum.
–– A straightforward ventriculoperitoneal shunt has been proposed as a
first line of treatment if contrast cisternography shows good communi-
cation of the cyst with the CSF pathways.
–– If the communication is not good, cysto-peritoneal shunt may be
needed.
135
–– The complications of shunting as a treatment modality for AC are the

same as shunting for hydrocephalus.
–– The common postoperative problems are shunt failure and infection.
In addition, “slit cyst syndrome” which is similar to the slit ventricle
syndrome has also been described.
Endoscopic Surgery
•• Endoscopic surgery may, in the future, become the standard way to treat
intracranial AC specially for deep seated cysts.
•• The basic principle here is the same as in craniotomy, viz establishing a
communication between the cyst and the normal CSF pathways.
•• Several holes are made in the cyst wall and these are enlarged with a
balloon catheter such as Fogarty catheter.
•• If the cyst is in close relation to the ventricle, in addition to cysto-
cisternostomy, cysto-ventriculostomy can also be performed for added
benefit.
•• Frameless stereotaxis has proved useful for endoscopic surgery of deep
seated cysts but it may not be needed for large lesions, or the surgery can
be started with an endoscope and then can be converted to a microsurgical
technique with endoscope assistance.
•• Endoscopic surgery for AC has been divided into various groups as
“endoscopic neurosurgery (EN), endoscope-assisted microneurosurgery
(EAM) and endoscope-controlled microneurosurgery (ECM)”.
•• The best success rates were achieved in patients with intraventricular cysts
(89%) and posterior fossa AC (78%).
•• It appears that endoscopic management has the advantages of craniotomy
combined with the less invasive nature of shunts.
•• Intraventricular cysts and suprasellar AC are easily approached using EN,
whereas posterior fossa and Sylvian AC may be more effectively treated
using a combined technique (EAM or ECM).
•• For intrasellar AC, trans-sphenoidal approach and excision has been
reported to give good results. This can be done for small intrasellar AC
but larger ones or those with suprasellar extension will need a craniotomy
for effective management.
•• Stereotactic intracavitary irradiation, using colloidal Phosphorus-32, has
been administered leading to good results.
•• Cyst aspiration as a treatment for AC has also been advocated, but simple
aspiration through a burr hole and cyst drainage leads to recurrence of
the cyst.
•• Cysto-subdural shunt has also been reported to give good results. Cysto-
ventriculostomy using stereotactic guidance has been used.
SPINAL CYSTS
Introduction
•• Many congenital and developmental cysts are seen in the spinal canal,
namely, ACs, neurenteric cysts, epithelial cysts and inclusion cysts.
•• Spinal ACs are not as common as the intracranial cysts.
•• A variety of names have been used to describe these lesions: “subdural
ACs, arachnoid diverticula, leptomeningeal cysts and meningeal hydrops”.
•• Unlike their intracranial counterparts, these may be intradural or extradural,
with the intradural variety being the commonest.
136
Embryology
•• The embryology of these lesions has not fully been elucidated.
•• The origin of these is more often than not congenital, although these “cysts”
may follow inflammation, haemorrhage, myelography or trauma.
•• Extradural cysts originate as small arachnoid diverticula through defects
in the dura.
•• Intradural cysts are thought to arise from the septum posticum which lies
on the dorsal aspect of the cord.
•• An alternate theory suggests that the variations in intraspinal CSF pressure
leads to the dilatation of the low resistance areas, resulting in the formation
of the cyst.
•• Another hypothesis suggests that all these “arachnoid diverticula result
from hypertrophy, proliferation and dilatation of arachnoid granulations”.
Clinical Features
•• Commonest cystic lesions in the spinal canal.
•• The commonest location is the mid-thoracic level on the dorsal aspect.
•• The common presenting feature is slowly evolving paraparesis.
•• The motor deficit is worse than the sensory or autonomic deficits.
•• In addition, the patients may have root pains and kyphosis.
•• An important differential diagnosis is multiple sclerosis since the symptoms
may fluctuate.
•• In addition, the symptoms in communicating AC may vary with posture.
•• Spinal meningeal cysts have been classified into three types:
–– Type I: Extradural meningeal cysts without involvement of spinal nerve
root fibres.
¾¾ Type IA: Extradural meningeal cyst (“extradural arachnoid cyst”).
¾¾ Type IB: Sacral meningocoele (“occult sacral meningocoele”).
–– Type II: Extradural meningeal cysts with involvement of spinal nerve
root fibres (Tarlov’s perineural cyst, spinal nerve root diverticulum).
–– Type III: Spinal intradural meningeal cysts (“intradural arachnoid
cyst”).
Radiology
•• Plain films show erosion of the pedicles at the level of the lesion.
•• Myelography shows, in addition to a filling defect, pooling of the contrast
medium inside the cyst if it is of the communicating variety.
•• MRI, however, is the investigation of choice. This shows a non-enhancing
cystic lesion with signals similar to CSF.
•• Cine MRI can demonstrate abnormal fluid flow and spinal cord compression
caused by a spinal intradural AC.”
Treatment
•• These lesions have to be managed surgically.
•• The outer wall is widely excised. If by doing this, a communication with the
CSF space cannot be established, a fenestration has to be done.
•• The results of surgery are often very good, particularly, if surgery is done
early.
•• Shunting may be useful in recurrent lesions.
16
CHAPTER Craniofacial Deformities
(Craniostenosis)
Uday Andar  Nitin Mokal
HISTORY
•• Many would consider Professor Paul Tessier as the father of modern
craniofacial surgery.
•• Historically, the first operation in India for craniofacial deformity secondary
to frontonasal encephalocele—a modified Tessier operation was carried
out at AIIMS.
NORMAL CALVARIAL GROWTH

•• The processes involved in normal growth of the craniofacial skeleton are
as follows:
–– Endochondral Ossification: Its growth mainly occurs in long bone
endochondral cartilage. In the skull, it occurs mainly at the synchon-
droses at the skull base.
–– Intramembranous Ossification and Sutural Growth:
¾¾ Most of the skull bones are membranous bones and their growth
is spurred on by the osteoblastic activity in the surrounding perios-
teum externally and the outer dura internally.
¾¾ This active bone formation may be maximum at the sutural inter-
faces. These sutural interfaces are under stress due to the growing
brain, growing facial musculature, the orbits and the teeth.
¾¾ This continuous stress stimulates bone deposition at these
junctions and craniosynostosis interferes with this process and
prevents growth.
–– Remodelling: It is the process by which deposition and resorption of
bone occurs in different areas of the skull vault.
–– Displacement: It occurs when the bone gets deposited over the suture
lines and the enlarging brain displaces the calvarial bones outward and
away to remodel.
INCIDENCE, AETIOLOGY AND PATHOGENESIS OF

PREMATURE CRANIOSYNOSTOSIS
•• Craniosynostosis occurs due to the premature fusion of a single suture or
multiple sutures.
•• The overall prevalence of craniosynostosis is around 1 in 2,500 live births.
•• The last decade of intensive research has linked many of the multiple suture
“syndromic synostosis” to a series of mutations in the fibroblast growth
factor receptor (FGFR) genes 1−3.
138
•• Common syndromic craniosynostosis like Apert and Crouzon, have a preva-

lence of about 1 in 65,000, each forming about 4–6% of all craniosynostosis.
•• There is evidence of FGFR2 mutation in Apert’s syndrome, FGFR3 in
Crouzon’s syndrome and FGFR1 in Pfeiffer’s syndrome.
•• There are chromosomal aberrations of which craniosynostosis may be a
feature.
•• There are teratogenic causes associated with anticonvulsants (valproate,
hydantoin), cytotoxic agents (methotrexate, cyclophosphamide, cytarabine),
abortifacients and other drugs (chlorpheniramine, nitrofurantoin,
chlordiazepoxide and fluconazole).
•• Isolated craniosynostosis is far more common than multiple syndromic
synostosis.
•• Sagittal synostosis seems to be the commonest, followed by coronal and
metopic synostosis.
•• Sagittal synostosis accounts for almost 55% of all craniosynostosis. It is
sporadic, commoner in twins and it is three times more common in males
than the females.
•• Coronal suture involvement accounts for about 20% of all craniosynostosis.
It is almost twice as common in females, and the unicoronal type is twice as
common as the bicoronal type. This type is associated with family history,
increased paternal age and FGFR3 mutation, especially when it is bicoronal.
•• Isolated metopic craniosynostosis has a wide range varying from
3%–50%. It can be associated with learning disability, without evidence of
high intracranial pressure (ICP). There can be associated chromosomal
aberrations. Foetal valproate exposure is increasingly recognised as a
cause of metopic synostosis with or without learning disability, behavioural
disturbances, limb and nail defects and neural tube defects.
•• Isolated lambdoid craniosynostosis is in the majority of cases deformational.
Contributing factors include intrauterine constraint, prematurity, complicated
delivery and laying the baby excessively on one side while sleeping. This
type is mostly managed conservatively.
CLASSIFICATION AND TERMINOLOGY

These deformities can be classified into three different varieties:
1. Secondary Craniosynostosis:
–– Occur as a result of twinning, amniotic bands or uterine abnormalities,
and is seen in preterm babies.
–– It can also occur in newborns with hyperthyroidism or maternal hyper-
thyroidism during pregnancy.
–– Pan-sutural synostosis is seen in children with microcephaly, where
the brain is small and underdeveloped.
2. Simple Anomalies: Include single suture or two suture involvement and
are named as:
–– Sagittal synostosis or scaphocephaly or dolichocephaly: It is so
called when the sagittal suture is singularly prematurely fused and
the head attains a long antero-posterior length with or without frontal
bossing.
–– Unicoronal synostosis: It is also called plagiocephaly, when there is
flattening of one side of the forehead and a mild facial scoliosis, due to
premature fusion of one coronal suture.
Chapter 16 • Craniofacial Deformities (Craniostenosis)
139
–– Metopic synostosis or trigonocephaly: This occurs when there is

premature fusion of the metopic suture, and the forehead assumes a
triangular shape like the keel of a boat.
–– Lambdoid synostosis: It is also called posterior plagiocephaly when
a single lambdoid suture fuses to produce asymmetric occipital flat-
tening.
–– Bicoronal synostosis or brachycephaly: This is a condition where
both coronal sutures fuse prematurely and the skull assumes a spheri-
cal shape.
–– Acrocephaly or turricephaly or oxycephaly: A condition where both
coronals and anterior sagittal sutures fuse and the skull assumes a
pointed tower like shape.
3. Complex Craniofacial Deformities: These are mainly associated with
syndromes and FGFR mutations and they are named as follows:
–– Crouzon syndrome: Apart from craniosynostosis, this condition
manifests maxillary hypoplasia, exorbitism with hyperteleorism and
type III dental malocclusion. There are no obvious skeletal anomalies.
There may be associated FGFR3 mutation and phenotypic variability
between generations is a common observation.
–– Apert syndrome: It is characterised by bicoronal and anterior sagittal
synostosis, midface retrusion and hypertelorism with orbital proptosis
and complex syndactyly of hands and feet. They can also have spo-
radic visceral malformations and skin abnormalities.
–– Saethre-Chotzen syndrome: The features here include bicoronal
synostosis with variable involvement of the metopic, sagittal and lamb-
doid sutures. There is associated proptosis, low set frontal hairline,
parrot beaked nose, strabismus and brachydactyly.
–– Pfeiffer syndrome: This syndrome has features of bicoronal synos-
tosis to pan-sutural synostosis and cloverleaf deformity of the skull. It
includes limb anomalies like thick broad thumb and toe, fusion between
thumb phalanges and soft tissue syndactyly of thumbs and fingers.
–– Cloverleaf or Kleeblattschadel deformity: This is an uncommon
and severe form of craniosynostosis resulting from the fusion of both
coronal and a combination of metopic, lambdoid and sagittal sutures.
The midface is retruded with ocular ectopia and dental malposition.
The posterior fossa is small and there is cerebellar tonsillar herniation.
There may be severe airway obstruction and the clinical prognosis is
often poor, without some very aggressive surgical management.
–– Carpenter syndrome: This is a rare syndrome where the cranial
deformity mainly involves the sagittal and lambdoid sutures asym-
metrically and severely. The affected person is usually short, obese
and neurodevelopmentally retarded.
–– Antley-Bixler syndrome: This is also a rare type of synostosis where
there is involvement of coronal and lambdoid sutures, with dysplastic
ears, radiohumeral synostosis, long tapering fingers and upper airway
abnormalities.
–– Jackson-Weiss syndrome: There is craniosynostosis with midfacial
hypoplasia and foot abnormalities.
–– Muenke syndrome: This syndrome is so described due to its molecular
abnormality. Here too, there is a coronal synostosis associated with
FGFR3 mutation.
140
RADIOLOGY
•• Plain X-ray of the skull is the most commonly used modality and is a good
investigation to assess the primary condition.
•• Skull X-ray AP and anterior posterior (AP) Towne’s with lateral view
is capable of showing sutural absence, parasutural sclerosis, sutural
narrowing and heaping or enostosis and also to confirm whether the entire
suture or only part of it is involved.
•• Computed tomography scan of the head and brain, with 3D reconstruction
of the skull bones and sutures along with the deformity of the sphenoid
plate and base of skull asymmetry.
•• MRI scan is helpful in children with syndromic anomalies to define the
airways, cranio-vertebral junction anomalies, hydrocephalus, venous sinus
anatomy and any other cerebral or cerebellar anomalies as also the upper
laryngo-pharyngeal airway.
TREATMENT OF CRANIOSYNOSTOSIS
•• Requires close co-ordination with specialists in neurosurgery, plastic
surgery, maxillofacial surgery, orthodontics, ophthalmologists, ENT
specialists and, of course, medical specialists including psychologists,
speech therapists, geneticist and trained nursing and paramedical staff.
•• The earliest times that surgery can be considered in the various regions
of the craniofacial skeleton are when that region completes its full growth
potential and this is approximately as follows:
Cranium: 1 year (6 months for sagittal)
Orbits: 5 years and above
Upper maxilla: 9−12 years
Lower maxilla: 17 years and above
Mandible: 17 years and above.
SURGICAL INCISIONS AND PROCEDURES

•• In almost all cranial exposures, a bicoronal incision extending from three
fingers above the mastoid and behind the ear, going all the way across to
a similar location via the vertex, is by far the best and gives the necessary
exposure anteriorly, posteriorly and in both temporal regions and the best
post-operative healed scar with minimally visible hair loss.
•• For facial and midfacial exposures, there are subconjunctival, infraorbital
and subciliary incisions as per the preference of the maxillofacial/plastic
surgeon.
•• In sagittal synostosis, where the shape of head is long with a bit of frontal
bossing and temporal hollowing, the attempt is to give it a rounded shape
as far as possible. This surgery is ideally carried out in the first 6 months
of life for the best results.
•• In anterior unilateral plagiocephaly, a plan for surgical repair can either
be a standard bifrontal craniofacial advancement or as many believe in
repairing the affected side only.
•• In trigonocephaly, brachycephaly and anterior plagiocephaly, the aim is
to remodel the fronto-orbital region by flattening the forehead and at the
same time pulling it in front. Thus, a bifrontal bone flap is raised in one
block and the supraorbital bar is taken separately, which includes the root
of the nose, part of the orbital roof and some part of the lateral orbital wall.
Chapter 16 • Craniofacial Deformities (Craniostenosis)
141
•• In the syndromic varieties, where there is need for repositioning of the

maxilla, a Le Fort III or Le Fort I corrective osteotomy is necessary.
•• The monobloc frontofacial osteotomy combines a transcranial frontal
advance and extracranial Le Fort III midfacial advance into a single
procedure, making use of external distraction frames.
COMPLICATIONS OF SURGICAL TREATMENT

Intra-operative Stage
•• Injury to the venous sinuses, severe bleeding and haemorrhagic shock.
•• Injury to the cerebral cortex.
•• Injury to the eyeball.
•• Acute brain swelling due to venous drainage compromise.
Early Post-operative Stage

•• Airway compromise due to local oedema.
•• Extra- and intra-parenchymal haematomas.
•• Fluid and electrolyte imbalance.
•• Visual compromise or ocular palsies.
•• CSF leak from the wound or rhinorrhoea, ottorrhoea.
•• Infection.
•• Failure of bony fixation.
Late Post-operative Stage

•• Exposure of miniplates and screws used for fixation.
•• Damage to roots of the teeth and devascularisation.
•• Soft tissue absorption and hollowing of temporalis muscle area.
•• Relapse of the bony fusion.
17
CHAPTER
Spinal Dysraphic States
Venkatramana NK
INTRODUCTION
•• Spina bifida literally means “spine in two parts” or “open spine”.
•• Spinal dysraphism involves a spectrum of congenital anomalies resulting
in a defective neural arch through which meninges and/or neural elements
herniate leading to a variety of clinical manifestations.
•• They are divided into aperta (visible lesion) and occulta (with no external
lesion).
•• Meningocele, myelomeningocele, lipomeningomyelocele, myeloschisis
and rachischisis are the usual names associated with these anomalies
depending on the pathological findings.
•• Meningocele by definition involves only the meninges with no neural
involvement. The other lesions will have a variable extent of neurological
involvement.
•• Spina bifida aperta is usually associated with a skin defect with an
impending risk of cerebrospinal fluid (CSF) leak constituting “open defects”,
whereas the occult forms will have full skin cover thickness.
•• Both forms demand different approaches in their management.
PREVALENCE
•• The estimated incidence of spinal dysraphism is about 1−3/1,000 live births.
•• The prevalence of spinal dysraphism has been on the decline world
over in the last few decades due to better nutrition for women, folic acid
supplementation, improved antenatal care and high resolution ultrasound
for prenatal screening and use of biochemical markers.
EMBRYOLOGY
•• Open defects occur when the caudal neuropore fails to close.
•• The secondary neurulation sets up the spinal cord formation. Defects at
this stage will result in occult dysraphism, connecting the epidermis and the
mesenchymal tissues leading to a variety of anomalies and tethered cord.
•• Failure of primary neurulation leads to open dysraphism posing the risks
of CSF leakage and exposure of the neural placode.
•• The higher the level usually, the worse is the prognosis.
•• A spectrum of neurological abnormalities like hydrocephalus, Chiari
malformation, syrinx, gyral malformations, skeletal malformations and
urovesical defects, can be associated.
Chapter 17 • Spinal Dysraphic States
143
•• In occult dysraphism, the overlying skin is intact but the spinal cord will be
anchored to various tissues starting either from skin, subcutaneous tissue,
adipose tissues or cartilage.
AETIOLOGY
•• The cause is multifactorial with both genetic and environmental factors.
•• Recent information has stressed on the importance of maternal nutrition
and folic acid supplementation.
SYMPTOMATOLOGY
•• Open dysraphism presents with a swelling over the back which is noticed
at birth.
•• Symptoms are primarily referred to as CSF leak or the exposed spinal
cord. Since the skin over the swelling is poorly developed, it usually gives
way during labour resulting in CSF leak, contamination and meningitis.
•• Defects predominantly involve the thoracolumbar, lumbosacral, lumbar,
thoracic, sacral and cervical in the order of occurrence.
•• Neurological deficits include motor, sensory and sphincter dysfunction
depending upon the severity and level of defect.
•• In severe cases, hypotonic flaccid limbs, sphincter atonia with rectal
prolapse may be seen.
•• Chiari malformation presents with lower brainstem and lower cranial nerve
dysfunction.
•• The presence of a large head usually indicates associated hydrocephalus.
•• The associated skeletal abnormalities are kyphosis, scoliosis and
deformities of the long bones and feet, hemivertebrae, defective ribs, etc.
ASSESSMENT
•• Assessment of head size, shape, skull bones and openness of fontanellae,
lacunar skull defects and the size of the posterior fossa.
•• Examination of the back needs assessment of the neural placode, level of the
lesion, condition of the skin, extent of skin defect and associated deformities.
•• Examination of the lower limbs for detection of the deformities of the foot
and abnormalities of long bones.
•• A detailed neurological examination to assess the level of motor weakness,
sensory level and sphincter dysfunction.
PRENATAL DIAGNOSIS
•• Prenatal screening is based on ultrasound performed routinely or by
maternal alpha fetoprotein (AFP) screening. It should be performed around
12, 22 and 32 weeks.
•• Maternal serum screen can detect up to 80% of spina bifida and 90% of
anencephaly.
•• Sonography may identify up to 90% of myelomeningoceles.
•• Gross lethal abnormalities nearly always require termination of pregnancy
depending on the regional legal system.
•• A growing number of more subtle abnormalities including midline or
posterior fossa abnormalities are being discovered. But their postnatal
outcome cannot always be predicted accurately, despite the use of foetal
magnetic resonance imaging (MRI).
144
•• Maternal serum screening for chromosomal abnormalities is also

increasingly being used. Only in selected situations, amniocentesis is
contributory.
RADIOLOGICAL ASSESSMENT
•• Plain X-rays will reveal skull defects, spine deformities and bony anomalies.
•• MRI is the investigation of choice to study the neural tissue abnormalities
and also to assess the severity of hydrocephalus and Chiari malformation.
•• Ultrasonography can be used to obtain quick information regarding
hydrocephalus.
MANAGEMENT
•• Management of these children needs multidisciplinary approaches.
•• Parents need to be counselled and informed regarding the immediate as
well as long-term management strategy.
•• The management of a pure meningocele involves a simple repair, while that
of a myelomeningocele or myelocele is prolonged, complicated and costly.
•• The total care of such a child requires collaboration between the neurosur-
geon, orthopaedic surgeon, plastic surgeon and the urologist.
SURGICAL TREATMENT
•• The aim of surgery is to free the placode from the surrounding abnormal
skin and to reposition it into the spinal canal with reconstruction of the dura
and coverings to prevent CSF leak and infection.
•• The surgical technique depends on the size and the level of the lesion.
•• The role of foetal surgery for myelomeningocele is yet to be proved.
PATIENT SELECTION
•• There is considerable controversy regarding selection of patients with
myelomeningocele for surgery, i.e. who should be offered surgery and
who should not.
•• Though there is no definite method of prognosticating outcome, certain
guidelines do exist.
•• Major associated congenital defects of other systems, megalencephaly at
birth, severe orthopaedic problems with gibbus at the site of dysraphism,
dislocated hips and poor general condition of the child are associated with
a poor outcome.
•• Complete flaccid paralysis of the bilateral lower extremities, observed after
adequate resuscitation of the newborn with myelomeningocele is generally
considered a contraindication for surgery.
•• In some patients, one may operate to make nursing care easier or to lessen
the social stigma.
•• Socioeconomic circumstances play an important part in the decision
regarding treatment, especially in the developing countries.
•• Timing of intervention primarily depends on the clinical condition of the
child, and the impending risks.
•• In case of suspected meningitis, CSF infection or colonisation of the wound,
prophylactic antibiotics and anti-convulsants will form the initial treatment.
•• Careful assessment of body weight is essential for intra-operative
management.
•• The newborn child with myelomeningocele should have saline dressings.
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SURGICAL TECHNIQUE
•• At the apex of the myelomeningocele usually, the flat neural placode is
located and from its edge the remnants of the arachnoid membrane gets
attached at the nerve root entry zone.
•• From this junction, the nerve roots emerge and exit through neural foramina
located ventrally.
•• They are seen through the transparent arachnoid membrane which is fused
with the skin at the lateral edges of the lesion.
•• The dura mater which is defective posteriorly is loosely adherent to the
underlying soft tissue of the back and densely adherent to the bony
structures underneath.
•• Rostrally, the dura forms a tube and the neural placode continues into it,
which leads to functional spinal cord.
•• The first step is to isolate the neural placode, while salvaging the nerve
roots as much as possible, irrespective of their functional status.
•• It is essential that no skin element becomes buried in the repair to prevent
the possibility of an implantation dermoid postoperatively.
•• In a circumferential fashion, the arachnoid is lifted and the nerve roots are
identified. This technique is continued all-round till the neural placode is
completely free. The neural placode can then be inverted and sutured.
•• The dura is dissected from the underlying soft tissue. The dural closure
needs to be made watertight with a graft, if necessary.
•• The overlying skin is dissected from the underlying fascia and musculature,
mobilised and approximated. If necessary, relaxing incisions or flaps may
be used to close larger defects.
•• Post-operative care is equally important. The child is nursed in the prone
position, and the wound is protected from faecal and urinary contamination.
A careful watch is maintained to detect development of hydrocephalus.
TETHERED CORD SYNDROME

•• Tethered cord syndrome has been defined as progressive neurological
deficits from the restraint of spinal cord movement and traction due to either
anatomical or physiological reasons.
•• The neurological deficits are insidious and progressive and may be motor,
sensory, urorectal associated with pain and/or scoliosis.
Embryogenesis
•• A diagnosis of tethered cord is made when the tip of the conus is below
the level of the lower border of the L1 vertebral body.
•• The ascent of the cord, which occurs throughout the embryonic, foetal
and postnatal period requires a well-formed cord and a smooth meningeal
covering.
•• During neurulation, the ectoderm on either side of the neural plate come
close together as the neural tube closes.
•• When neural tube fusion is complete, the ectoderm detaches on either
side in an event called dysjunction and fuses. If, however, the dysfunction
occurs before the neural tube closure is complete, or if the closure is faulty,
mesenchymal cells gain access to the central canal of the neural tube.
•• The mesenchymal cells then differentiate into fatty tissue to form a lipo-
myelomeningocele which is essentially a mass of fat extending from the
conus medullaris to the subcutaneous plane underlying an intact skin.
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All the manifestations of lipomyelomeningocele can be explained by this

mechanism of embryogenesis.
Pathogenesis
•• Tethered cord can result from a variety of conditions. This can broadly be
classified into the following points:
–– Anatomical: In anatomical condition, the conus is placed at a lower
level than normal.
–– Physiological: This is due to tight or thick filum. In this variety, the
conus may be at the normal level but the movement of spinal cord
is restrained resulting in neurological deficits and vesicle dysfunction
called “non-neurogenic bladder”.
–– Developmental: This could be secondary to a variety of conditions
like congenital anomalies, terminal lipoma, intra-spinal lipoma, lipomy-
elomeningocele, split cord malformations, sacral agenesis and other
occult dysraphic states.
–– Post-operative: Post-operative tethering that occurs after surgery for
myelomeningocele or dermoid or recurrent adhesions from previous
surgery, often termed retethering.
Clinical Features
•• During embryonic life, the spinal cord lies way down at the sacral segments
which in foetal life gradually ascends so that the conus reaches the adult
level to L1, as confirmed by ultrasonographic studies.
•• In this pathological situation, the spinal cord is tethered to anatomical
structures lower down, preventing the ascent of the conus in parallel to
the vertebral growth.
•• Normally, when a child bends forward, there is an ascent of the spinal cord
by one to two segments. The filum can be short and thick with a variable
quantity of fibrous tissue making it tight and preventing such movement.
•• Neurological deterioration in tethered cord syndrome due to stretching
central fibres are subjected to traction injury, resulting in structural damage.
•• Also the mechanical stretching of the cord during physical activity leads to
changes in intracellular respiration, reduction in cytochrome oxidase and
shift in redox curves.
•• Traction and elongation of the spinal cord can compress the radial
perforating vessels resulting in ischaemic damage. Once the neurological
deficit occurs, it is rarely reversible, therefore, it is important to treat such
defects prophylactically.
Symptoms
•• The predominant symptoms can be motor in the form of insidiously progres-
sive distal weakness and spasticity, and sensory ones like sensory loss,
paraesthesias and trophic ulcers.
•• Neurovesical dysfunction is one of the commonest presentations.
•• At times, pain can be the major symptom. It may be radicular or funicular,
low back or calf muscle pain.
•• The scoliosis due to tethering is a much debated issue, but there is enough
evidence to suggest that it is due to the tethering.
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Neurological Examination
•• Neurocutaneous markers like tuft of hair, nevus, dysplastic skin,
angiomatous patches, lipoma, dermal sinus, presence of human tail and
absence of gluteal folds are strong indicators.
•• Neurovesical dysfunction, leg pain, scoliosis, progressive motor or sensory
deficits, should prompt the clinician to look for possible tethering even in
the absence of cutaneous markers.
•• MRI is the investigation of choice to identify the anatomical location of the
conus and associated abnormalities.
•• The classical dorsal displacement of the conus with a large, ventral CSF
space is often suggestive of this lesion.
Indications for Treatment

•• Any child with progressive neurological deterioration of motor, sensory or
urinary function should be treated.
•• Pain, spasticity, gait abnormality, persistent or progressive scoliosis are
the other indications.
•• If the neurological deficit has already occurred, surgery should be done as
soon as the diagnosis is established.
The Principles of Surgery

•• Complete untethering of the spinal cord.
•• Proper dural reconstruction with adequate CSF space around the spinal
cord to prevent retethering.
Retethering
•• Precautions to prevent rethering includes complete untethering of all the
contributory structures, proper concealing of rough and possible adhesive
surfaces by pial sutures, laminectomy to accommodate the thickened cord
and to facilitate upward movement, duraplasty to create a reservoir of CSF
around the repaired structures and epidural fat grafts to prevent fibrosis.
•• At present, there is no foolproof investigation to demonstrate retethering.
MRI in the prone position to demonstrate CSF dorsal to the conus has
been suggested.
•• Serial electrophysiological and urodynamic studies seem to be indicative.
Till such time, clinical diagnosis remains the gold standard.
Lipomyelomeningocele
•• Lumbosacral lipomyelomeningocele is a subcutaneous fibro-fatty mass
that traverses the lumbodorsal fascia causing a spinal laminar defect,
penetrating the dura and tethering the spinal cord.
•• Lipomas are one of the important causes of spinal cord tethering, almost
all of them have a low lying conus.
•• The term lipomyelomeningocele is used despite the overlying skin being
normal. They arise from a disorder of embryogenesis.
•• They usually consist of a single cell type but may have fibrous tissue,
muscle cells, neural tissue and a variety of other cell types that arise from
all the embryonic layers.
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•• The incidence is approximately one in 4,000 births in the USA with a slight
female preponderance.
•• Symptoms and signs are mainly related to the traction on the lower
spinal cord, leading to motor deficits, sensory disturbances, spasticity,
urodynamic, urorectal dysfunctions and skeletal deformities.
•• The pathogenesis and natural history of these complex anomalies are not
clearly understood.
•• Surgical treatment is complex as it poses several challenges and there is
a risk of neurological deterioration postoperatively.
•• A variety of factors can influence the outcome. Anatomical features like size
of the lipoma, location (midline or paramedian), wide bony defect, defective
muscles and fascia and poor cleavage at the neurolipomatus junction.
•• Lumbosacral lipomyelomeningoceles have been classified by Chapman as
dorsal, transitional and terminal types and by Aris as of five types: dorsal,
caudal, combined, filar and lipomeningomyelocele.
•• In dorsal variety, the lipoma enters into the segment of spinal cord dorsally
through a fibro-fatty pedicle below which normal cord and dura exist.
•• Transitional variety is essentially a dorsal type which covers the entire conus
and extends up to the filum. Distally, no normal cord exists.
•• In terminal variety normal looking conus ends in the lipoma through a dural
defect and all the sacral roots will be cranial to the lipoma.
•• Diagnosis in 90% of children is made by the presence of a visible lipomatous
mass in the midline on the back with or without a cutaneous marker.
•• Associated hydrocephalus or cranial anomalies are extremely low, though
the other spinal anomalies can be associated.
•• MRI (craniospinal screening) is the choice of investigation for a
comprehensive assessment.
•• The surgical treatment is aimed at complete untethering and prevention
of retethering of the cord.
•• Based on the progressive irreversible worsening, prophylactic surgery has
been recommended.
Surgical Technique
•• Broad principles include vertical skin incision, dissection of subcutaneous
lipoma up to the fascia, excision of extraspinal component of lipoma,
identification of upper and lower intact laminae and performing laminectomy,
identification of normal dura above and below and separation of dural tube
from the thoracolumbar fascia all round.
•• Then dural opening (circumferential) around the fibro-fatty stalk, removal of
intradural lipoma, gentle dissection of the fibro-fatty pedicle up to the neural
structures over the dorsal surface of cord and removal of fibrous tissue up
to the neurofibrolipomatous junction, removal of other fibrous bands and
finally detachment of the filum.
•• The spinal cord should eventually be made free from five structures: skin,
subcutaneous tissue, thoracolumbar fascia, dura and filum terminale to
achieve complete untethering.
•• All known precautions to prevent retethering like pial, closure to cover the
raw dorsal surface of the cord and duraplasty to enlarge the subarachnoid
spaces and to facilitate free CSF circulation around the repaired surface
of the cord are to be adopted.
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•• Replacement of free fat over the dura will fill the dead space, protect the
soft tissue, prevent CSF leak and prevent skin edge necrosis.
Myelocystocele
•• It is an occult form of spinal dysraphism with a localised, cystic dilatation
of the central canal of the spinal cord herniated through a posterior spina
bifida.
•• Terminal myelocystocele truly is an anomaly of the caudal cell mass
associated with anomalies of the anorectal system, lower genito-urinary
system and vertebrae such as anal atresia, cloacal exstrophy, lordosis,
scoliosis and variable degree of sacral agenesis.
•• They constitute 4−8% of occult dysraphism and rarely occur in the lower
thoracic region.
•• The lesion consists of skin covered lumbosacral spina bifida, arachnoid
lined meningocele directly continuous with the subarachnoid space and a
low lying hydromyelic spinal cord that traverses the meningocele and forms
a distal sac which does not communicate with the subarachnoid space.
•• The MR appearance is distinctive and is characterised by trumpet like
flaring of the distal cord central canal into an ependyma lined terminal cyst.
•• Surgical correction cannot only release tethering but also prevent the
complications.
SPLIT CORD MALFORMATIONS

•• Split cord malformations (SCMs) are increasingly being recognised as one
of the causes of tethered cord syndrome.
•• They are defined as a form of occult spinal dysraphism, in which any part
or entire spinal cord, cauda equina and filum terminale are divided into two
lateral parts by a dorsal/ventral spur.
•• The pathogenesis of these complex anomalies still remains controversial.
•• The diagnosis has become easy and certain with the advent of MRI. It is
necessary to screen the entire spine in order to recognise all the associated
anomalies and to plan the management strategies.
•• Several terminologies were in vogue in literature like “diastematomyelia”
(Olivier) and “diplomyelia” (Bruce) with a poor distinction. Pang introduced
the term “split cord malformation”.
•• The most widely accepted theory about embryogenesis of this complex
malformation was originally proposed by Bremer and subsequently
modified by Pang et al as “Unified theory of embryogenesis”.
•• The basic error appears to be development and persistence of accessory
neurenteric canal (ANC).
•• The persistence of the anterior end of this canal will result in intestinal
malformations and of the posterior end in cutaneous malformations
like angiomas, hypertrichosis, dermal sinus or dermoid, whereas the
persistence of the intermediate part causes a split in the notocord and the
neural placode.
•• The division of the notocord then leads to the formation of hemiverterbrae,
bifid, hypertrophic, hyperplastic vertebrae or fusion of vertebral bodies or
posterior elements.
•• The division of the placode later on leads to the formation of two hemicords.
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•• If the mesenchyme surrounding the ANC contains precursor meningeal

cells, it will result in the formation of dural and bony spurs within, leading
to SCM type I.
•• If meningeal cells are not incorporated then it is not involved in the formation
of the dural sac and once the ANC disappears it will be transformed into an
intradural fibrous band situated between the two hemicords, thus leading
to SCM type II.
•• The original description diastematomyelia denotes splitting of the cord with
a bony spur extradurally. Spinal roots arise from the lateral aspect of the
hemicords with no medial roots.
•• Diplomyelia is supposed to represent true hemicords, and therefore,
harboured in a single dural tube, with medial roots from each hemicord.
•• SCM type I constitutes 40−50% of SCM.
–– The dural sac is always double with division of the spinal canal and
cords by an extradural bony or cartilaginous spur. The spur can be an-
teroposterior, usually attached to the posterior surface of the vertebral
body. Rarely, it can have a dorsal attachment to the spine.
–– The spur can divide the canal into two symmetrical halves or can be
slanting in the axial plane dividing the canal asymmetrically. In such
situations, one of the hemicords can be hypoplastic.
–– In the majority, the spur is located in the lumbar region and less frequent
in lower thoracic, cervical and upper thoracic regions, respectively.
•• SCM type II accounts for 50−60% of SCMs.
–– In this anomaly, the dural sac is single with one spinal canal and two
almost equal and symmetrical hemicords, between which an anter-
oposterior fibrous band tethering the cords to the dura.
Surgical Technique
•• Laminectomy is started at the normal level and continued on both sides
close to the pedicles in an encircling fashion, protecting the dura and
preserving the facet joints.
•• The central bony spur with its attachment to the lamina is isolated.
•• The two dural tubes are identified and protected.
•• The bony spur is gradually nibbled till its attachment after careful and
adequate separation from dura.
•• The dura is then opened in the midline at the normal level extending down
elliptically on either side of the sleeve of the spur joining in the midline caudally.
•• The arachnoid is also opened.
•• The dural sleeve over the spur is then completely excised. The cords are
inspected anteriorly and posteriorly and all the surrounding arachnoidal
and fibrous bands are removed.
•• Dura is closed posteriorly in the midline converting it into a single dural
tube. The anterior defect of dura need not be closed.
•• In type II malformations, posterior bony elements almost look normal and
hence a marker will be necessary. After laminectomy or laminotomy of the
required levels, the dura is opened in the midline.
•• The hemicords are inspected under magnification for the fibrous bands.
•• The fibrous band is usually located ventrally between the hemicords. The
band is released from its dural attachment. The filum is untethered and the
dura is closed in the midline.
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DERMAL SINUS
•• Congenital dermal sinuses are a unique form of occult dysraphism
presenting with meningitis, tethering or neurological compression with an
incidence of one in 1,500 births.
•• The dermal sinus tracts are lined by squamous epithelium and may present
anywhere in the midline from the lumbosacral region to the occiput or nasion.
•• The most common location is the lumbosacral area. Thoracic and cervical
dermal sinuses are present in 10%.
•• Dermoid and epidermoid nodules are frequently associated with these tracts.
•• The small sinus ostium is quite often overlooked, unless a discharge is
noted by the parents.
•• The neurological examination is nearly always intact, except in situations
where the dermoid or epidermoids lead to cord compression.
•• The MRI is diagnostic.
•• Embryologically, the formation of the dermal sinuses may reflect incomplete
dysjunction. Altered dysjunction can lead to dermal sinus terminating in the
subcutaneous tissues or may extend to an intramedullary location.
•• These are usually in the midline providing a portal for infection leading to
meningitis or intraspinal abscesses.
•• The most common organisms are Staphylococcus aureus and Escherichia
coli followed by Proteus species and anaerobes. Multiple organisms may
be cultured.
•• Recurrent meningitis is one of the classical presentations.
•• The treatment includes antibiotics and complete surgical excision of the
sinus tract and the associated lesions. Incomplete removal is the usual
cause for recurrences.
SYNDROMES OF THE TETHERED CORD

•• Tethered cord syndrome may occur with the conus in normal position with
or without associated neurocutaneous markers.
•• These children usually present with hyper-reflexic neurogenic bladder which
was earlier referred to as non-neurogenic bladder.
•• Urodynamic studies often reveal detrusor hyper-reflexia.
•• There is growing evidence that sectioning of the filum improves the bladder
function in 96% of the patients.
NEUROGENIC BLADDER WITH CONUS AT

NORMAL POSITION
•• These conditions were earlier coined by different names like non-neurogen-
ic−neurogenic bladder. It usually presents in children less than 10 years.
•• They do not have associated regional, neurological or vertebral anomalies.
•• Urodynamic studies are highly suggestive of the diagnosis.
•• Release of filum terminale has shown significant improvement, up to 96%
in their bladder control and also in the urodynamic abnormalities.
18
CHAPTER
Hydrocephalus
Venkatramana NK
INTRODUCTION
•• Hydrocephalus is a condition wherein excess of cerebral spinal fluid (CSF)
accumulates within the ventricular system of the brain, leading to increased
intracranial pressure (ICP).
•• This condition apparently can result from various conditions that can affect
a foetus, infant, child and adult.
•• Hydrocephalus is due to imbalance between the production of CSF and
its absorption.
•• Although overproduction of CSF as a cause of hydrocephalus is well
recognised in association with choroid plexus papillomas, these are rare
tumours in clinical practice.
EMBRYOLOGY
•• The ventricular system develops from the corresponding vesicles of the
developing neural tube.
•• The cavity of each telencephalic vesicle becomes the lateral ventricle and
that of the diencephalic becomes the third ventricle.
•• The cavity of the rhombencephalon forms the fourth ventricle.
•• Its continuation into the spinal cord is the central canal.
CEREBROSPINAL FLUID PRODUCTION AND

ABSORPTION
•• The majority of CSF production is by the choroid plexus, contributing
70–80% of the daily volume. A small proportion of CSF may be produced
from the ependyma and brain parenchyma.
•• CSF production occurs by a combination of filtration across the endothelium
and active secretion of sodium by the choroidal epithelia.
•• CSF, which is largely formed in the lateral ventricles, passes through the
foramen of Monroe into the third ventricle and reaches the fourth ventricle
through the aqueduct of Sylvius and then exits through median foramen
of Magendi and the lateral foramina of Luschka.
•• Cerebrospinal fluid is produced at the rate of 0.33 mL/min, approximately
500 mL/day.
•• The total volume of CSF varies with age and in adults is 100–150 mL, of
which 15–25 mL is contained within the ventricles.
•• The mechanism of absorption of CSF has been extensively investigated.
Direct absorption from the brain parenchyma, choroid plexus and by
Chapter 18 • Hydrocephalus
153
the lymphatic channels in the region of the cribriform plate has been
postulated.
•• The arachnoidal villi and granulations contribute to the maximum
absorption. They are the herniations of arachnoidal tissue into the dural
venous sinuses.
•• Two mechanisms have been proposed. The “closed“ mechanism, where
the villi are blindly diverticulated and absorption occurred by a process of
seepage across the endothelial covering. The open mechanism indicates
the presence of channels across the villi, opening and closing in a valve-
like manner, permitting unidirectional flow of CSF.
AETIOLOGY AND PATHOPHYSIOLOGY OF

HYDROCEPHALUS
•• The incidence of congenital hydrocephalus is about 0.2–0.5/1,000 live births.
•• A higher incidence has been reported in elderly primiparus mothers.
•• Traditionally, obstruction within the ventricular system is called non-
communicating hydrocephalus and when the impairment is in the circulation
through the subarachnoid space or absorption to the venous system, it is
called communicating hydrocephalus.
•• Wherever the aetiology is known, it is further divided into congenital
and acquired forms. The aetiology of congenital hydrocephalus remains
obscure. An inheritable form of aqueductal stenosis has been described in
males (X-linked hydrocephalus). The other mechanism of hydrocephalus
is overproduction, seen in papilloma of the choroid plexus.
•• Rekate has classified hydrocephalus based on CSF flow obstruction.
Impaired absorption is another mechanism where venous sinus
occlusions, vein of Galen malformations and developmental anomalies
like craniostenosis with malformations of the skull base can lead to the
development of hydrocephalus.
•• Absence or disease of the arachnoidal villi, resulting in disturbance of
absorption, can also result in hydrocephalus.
CLASSIFICATION
1. Hydrocephalus may be due to:
–– Overproduction of CSF (a rare entity)
–– Obstructive: wherein there is obstruction to the flow of CSF in the:
¾¾ Lateral ventricles through foramen of Monroe
¾¾ Third ventricle through Aqueduct of Sylvius
¾¾ Fourth ventricle through foramina of Luschka and Magendie
¾¾ Subarachnoid spaces
–– Absorption defect.
2. Based on the site of blockage to the CSF flow, the hydrocephalus may be:
–– Monoventricular or unilateral
–– Biventricular (both lateral ventricles)
–– Triventricular (third and both lateral ventricles)
–– Panventricular (fourth, third and both lateral ventricles).
3. Depending on the exact aetiology:
–– Congenital
–– Traumatic
–– Inflammatory
–– Neoplastic
–– Degenerative.
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CLINICAL FEATURES
•• Prior to closure of the cranial sutures and obliteration of the fontanelle,
hydrocephalus results in disproportionate head growth.
•• Thus, over the first 2–3 years of life, measurement of the occipito-frontal
circumference and plotting this on a centile chart provides a simple and
sensitive test.
•• Clinical symptoms are often subtle and include general irritability, poor
feeding and slow attainment of milestones.
•• In addition to head size, clinical signs include bulging of the fontanelle,
separation of the cranial sutures, prominent scalp veins and sun-setting
appearance of the eyes. This latter clinical sign is attributed to pressure on
the mid-brain tectum by CSF in the dilated supra-pineal recess.
•• Papilloedema can be difficult to diagnose in the infant and indeed is not
uncommonly absent in infantile hydrocephalus and so is an unreliable
sign in this context.
•• In older children and adults, the classical symptom complex of raised ICP,
headache, vomiting and drowsiness is seen.
•• Hydrocephalus developing insidiously causes cognitive impairment, poor
concentration and behavioural changes occur.
•• Visual obscurations and papilloedema are more common than in the
younger age group.
•• In both groups of patients, the presence of bradycardia, hypertension and
irregularities in breathing pattern imply critical elevation of ICP and should
be treated promptly.
INVESTIGATIONS
•• In the neonate, the supratentorial ventricular system can be reliably
evaluated using ultrasound. Ultrasound provides a non-invasive and readily
available tool for both diagnostic purposes and, by means of sequential
studies, a way of charting changes in ventricular size.
•• Plain X-rays of skull may give an indication. A large skull with different
shapes of the vault, sutural separation, cranio lacunae, flat anterior cranial
fossa and thinning of vault bones may be seen. Sellar changes and beaten
silver appearance may be seen as a sign of raised ICP.
•• A small posterior fossa is often associated with aqueductal stenosis and a
large one might suggest Dandy Walker cyst.
•• Multiple calcifications may be an indication of infectious aetiology.
•• Ventriculography was the gold standard during yesteryears and can
demonstrate the size of the ventricles and also the site of the obstruction.
It is still valuable in evaluating CSF dynamics.
•• Cerebral angiography is not an usual investigation except in vein of Galen
malformations and major venous anomalies. The venous angle seen in the
venous phase is an indicator of the degree of hydrocephalus.
Computerised Tomography (CT) and Magnetic

Resonance Imaging (MRI)
•• Enlargement of the temporal horns of the lateral ventricles and enlargement
of the third ventricle, commensurate with the enlargement of the rest of the
ventricular system, are findings in favour of hydrocephalus.
•• Obliteration of the basal cisterns and effacement of the cortical sulci further
support a diagnosis of hydrocephalus.
155
•• When the ventricles are under pressure, there may be transependymal

flux of CSF into the periventricular parenchyma, particularly at the tips of
the frontal, occipital and temporal horns. This appears as a low density on
CT scan or a rim of high signal intensity on the T2-weighted MRI scans.
Volumetric Measurements
•• Several methods have been used to calculate ventricular volumes right
from the days of pneumoencephalography.
•• Linear measurements, planimetric methods, direct calculation of volume
and CT planimetry were used in the past. These are not of much clinical use.
TREATMENT
Management
•• Osmotic diuretics and acetazolamide (inhibitor of carbonic anhydrase)
may be useful. Carbonic anhydrase is present in the choroid plexus and is
necessary for the formation of CSF.
•• However, the effects are not sustained and, hence, it is useful only in benign
intracranial hypertension or as a temporary measure in post-haemorrhagic
hydrocephalus.
•• Bypassing the site of obstruction to CSF flow by diverting the CSF, from
the ventricular cavity to a site where it is readily absorbed, is the basic
principle underlying the treatment of hydrocephalus.
•• Based on this, shunt procedures have become the mainstay of surgical
treatment even in severe hydrocephalus.
•• Shunts can alter the process dramatically in infantile hydrocephalus.
•• Neuroendoscopic third ventriculostomy is an important alternative in select
situations. Numerous shunt systems have been devised and marketed.
•• The list of procedures is mentioned here for the sake of historical importance
(John E Scarff).
Therapy based on physiological principles
a. Choroid plexectomy—Dandy 1918
b. Third ventriculostomy—Dandy 1922.
Intracranial shunts using tubes
a. Ventriculocisternostomy—Torkildsen 1939
b. Ventriculo-transcallosal shunt anterior—Lazorthes
c. Ventriculo-transcallosal posterior—Kleizer and Geuma
d. III to IV ventricular shunt—Leksel 1949
e. Ventriculo-ambiens shunts—Kluzer
f. Ventriculo-chiasmatic—Feld
g. Ventriculo-subdural—Forrest
h. Ventriculo-mastoid—Nosik
i. Aqueductoplasty or interventriculostomy using stent in aqueduct (Elvidge).
Extracranial shunts
a. Ventriculoatrial—Nusen, Spitz 1952, Pudenz 1953
b. Ventriculoperitoneal—Scot, Wyan 1958
c. Ventriculopleural—Heile.
Shunts into epithelialised ducts
a. Ventriculocholecystostomy—Snuth et al.
b. Ventriculosalpingostomy—Harsh
c. Ventriculoileostomy—Narmann
d. Ventricle to thoracic duct
156
e. Ventricle to Stensen’s duct—Parkinson

f. Ventriculoureteral shunt—Matson.
Lumbar SA to lumbar epidural—Hakim et al.
Theco-peritoneal shunt—Jackson, Snodgrass 1955
Miscellaneous
To vertebral body—Radvon Teimn
To Retroperitoneal space—Aboylker.
•• The shunt assembly comprises a proximal catheter located in the cerebral
ventricle and a distal catheter draining into the selected site of CSF
absorption, connected by a valve and reservoir incorporated into the shunt
system.
•• The proximal catheter has a blind-ended tube with multiple side holes to
facilitate CSF drainage.
•• A number of devices are available like stylet, endoscope and navigation
assistance to facilitate the placement of the catheter into the ventricle.
•• The valve designs are based on differential pressures, fixed and
programmable or flow control types.
•• Four types of differential pressure valves are commonly available:
–– Slit valves
–– Midtre valves
–– Ball and spring
–– Diaphragm walls.
•• The fixed-resistance valves, programmable valves have been developed,
whose operating pressure can be varied. An externally applied magnetic
field is used to alter the position of an internal rotor and, thus, vary the
pressure setting.
•• Anti-siphon device is a siphon controlled device and can be incorporated
with the valves. This device houses a mobile membrane which moves in
response to the pressure change.
•• The peritoneal cavity is the most common site of placement of the distal
catheter.
•• The alternate sites are the right atrium, pleural cavity and the gall bladder.
Indian Shunt Systems

•• These include: Upadhyaya shunt system, Chhabra shunt system and Sri
Chitra shunt system.
•• Chhabra shunt system includes “Slit N Spring”, “Z” Flow, Low Pressure,
Medium Pressure and High Pressure. These valves were evaluated and
compared with the Western systems and found to be equally effective. Low
cost of these shunts is of major advantage.
Endoscopic Treatment
•• Popular among them is the endoscopic third ventriculostomy for aqueductal
stenosis.
•• In addition, septostomy, extirpation of choroid plexus, removal of paracytic
cysts, removal of migrated shunts and arachnoid cysts can be treated
effectively through neuroendoscopy.
Complications of Shunts
•• They could be classified as mechanical, like shunt blockage, disconnection,
migration and shortening of length.
157
•• The flow-related complications are CSF overdrainage leading to

subdural haematoma, subdural hygroma, extradural haemorrhage, low
pressure headaches, secondary craniostenosis and cranial deformity
and asymmetrical drainage can lead to trapping or isolation of a part of a
ventricular system.
•• The slit ventricular syndrome can also occur.
•• Complications related to absorption are intra-abdominal fluid collections,
loculations and hydrocoele. Perforation of the stomach, large and small
bowel, gall bladder and vagina have been described.
•• Shunt Infection:
–– Most common cause accounting for significant morbidity and mortality,
incidence to range from 5 to15%.
–– Approximately 70% of shunt infections will present within 2 months
and the remaining by 6 months of the surgical procedure and rarely
beyond 6 months.
–– A high index of suspicion is maintained for symptoms like pyrexia,
meningismus, irritability and lack of well-being.
–– CSF examination is needed to confirm the diagnosis and it may be
obtained by the aspiration of the shunt reservoir or from the ventricle.
–– Appropriate antimicrobial therapy and management of the shunt sys-
tem is necessary for a good outcome.
–– The most common source of infection is coagulase negative Staphy-
lococci, particularly S. epidermidis. S. aureus is also well recognised.
Enterococci, micrococci and coryneforms account for a significant
proportion.
–– The most common strategy is to remove the shunt and insert an exter-
nal ventricular drain for the duration of antibiotic coverage and a fresh
shunt inserted once the CSF is sterile.
–– The role of prophylactic antibiotics, its type, duration and route of ad-
ministration are still controversial.
–– The more recent technique of antibiotic delivery has been to incorpo-
rate antibiotics into the silicon tubing, which gradually leaks out and
provides protection in the early postoperative period.
–– Antibiotic impregnated shunts are now available; however, the long-
term results need to be evaluated.
•• Miscellaneous complications: Seizures, metastasis, haemorrhage related
to catheters and silicone allergy.
SPECIAL TYPES OF HYDROCEPHALUS

Posthaemorrhagic
•• The blood vessels of the germinal matrix have immature connective tissue
and lack auto-regulatory capacity.
•• Due to these factors, premature infants born before 34 weeks have a high
incidence of intracranial haemorrhage.
•• Haemorrhage is reported in 40–45% of immature infants, whose birth
weight is less than 500 g and 20% of infants, who suffer intraventricular
haemorrhage, will develop hydrocephalus, requiring a shunt.
•• The majority occurs within the first few days of birth and the clinical
symptoms can be misleading due to prematurity.
•• Serial ultrasound examinations are helpful, especially when the head
circumference is increasing.
158
•• A ventricular catheter with a subcutaneous reservoir is much safer in

avoiding repeated cerebral punctures.
•• Intraventricular fibrinolytic therapy, instituted soon after the haemorrhage is
detected, may prevent chemical arachnoiditis and reduce shunt dependency.
Meningomyelocoele
•• Hydrocephalus complicates open spina bifida in 85–90% of patients.
•• This is usually associated with Chiari malformation; it is preferable to
treat hydrocephalus simultaneously to facilitate wound healing after
myelomeningocoele repair.
Aqueduct Stenosis
•• The growth of the tectum and tegmentum makes the lumen of the neural
tube narrow in the region of the mesencephalon, leading to narrowing of
the aqueduct of Sylvius.
•• Aqueductal stenosis occurs in approximately 10% of children.
•• Communicating hydrocephalus with external pressure on the mesencephalon
has been proposed as a cause for obliteration of the aqueduct secondarily.
•• Scaring, and gliosis following infection or haemorrhage, can cause acquired
stenosis.
•• Tumours from the surrounding structures may block the aqueduct.
Diagnosis is confirmed by MRI.
Dandy Walker Syndrome

•• This syndrome comprises of agenesis of the cerebellar vermis with cystic
dilation of the fourth ventricle, enlargement of the posterior fossa and
hydrocephalus.
•• The hydrocephalus manifests in the post-natal period.
•• Treatment with placement of proximal catheters in the lateral ventricle and
the fourth ventricle with a wide connector.
•• The idea is to treat the fourth ventricular hydrocephalus, and subsequently
the supratentorial hydrocephalus, by shunt or endoscopic method.
Postmeningitic
•• Organisation of the inflammatory exudate with scaring or gliosis of the
meninges can produce obstruction to CSF flow, both in the ventricular
system and in the basal cisterns, cortical subarachnoid space and may
also lead to occlusion of the arachnoidal villi, leading to either obstructive
or communicating hydrocephalus.
•• Bacterial, parasitic and granulomatous infections like tuberculosis and
fungal infections can lead to hydrocephalus.
•• Hydrocephalus can be acute, causing severe rise in the ICP and rapid
deterioration of the clinical condition.
•• The goals of treatment are early diagnosis, effective relief of raised ICP by
CSF diversion and treatment of the primary infection.
•• External ventricular drainage may be used as a temporary measure
till the infection is resolved, before implanting a shunt or doing third
ventriculostomy.
•• Endoscopic third ventriculostomy is gaining popularity with 50–60% success
rates in select cases.
159
Subarachnoid Haemorrhage
•• Hydrocephalus can occur in 10–15% of patients following subarachnoid
haemorrhage. The incidence increases with intraventricular haemorrhage.
The mechanism is impaired absorption due to blockage at multiple sites.
Normal Pressure Hydrocephalus

•• Usually seen in adulthood, it is characterised by gait deterioration, dementia
and urinary incontinence. Imaging usually shows enlarged ventricles.
•• The ICP-related symptoms may not be evident.
•• A number of investigations have been advocated in the selection of patients
for shunt therapy. These include isotope cisternography, infusion tests to
detect increased CSF resistance in flow, ICP monitoring and therapeutic
lumbar drainage.
Hydrocephalus and Venous Hypertension

•• The role of raised venous pressure as a cause of hydrocephalus has been
described long ago as otitic-hydrocephalus. Similar clinical situations have
also been described in anchondroplasia and syndromic craniostenosis.
•• The deformed skull base resulting in narrowing of the jugular foramen
leading to impaired intracranial venous drainage has been attributed.
•• The raised pressure within the cranial venous sinuses reduces the
pressure gradient across the arachnoid villi, leading to impaired absorption.
Hydrocephalus also accompanies vein of Galen aneurysms.
Arrested Hydrocephalus
•• Hydrocephalus may evolve into a chronic state in which persistent
ventricular enlargement with normal CSF pressures exists.
•• Although it is a controversial entity, it appears to be a compensated
hydrocephalus.
•• Treatment strategies should be weighed between the benefit versus
complications in individual situations.
•• Disproportionate head growth, progression of ventricular size and intel-
lectual decline are indications for intervention.
Multiloculated Hydrocephalus
•• It usually occurs after an initial episode of neonatal meningitis or a germinal
matrix haemorrhage.
•• CT scan or MRI is usually diagnostic. CT ventriculography has been advo-
cated to delineate the communication between the cysts.
•• Among the various treatment options available, placement of multiple
shunts, single shunt with multiple fenestrations of all the loculations, cra-
niotomy with lysis of intraventricular septations, stereotactic cyst aspiration
or endoscopic cysts fenestration with shunt insertion have been described.
•• After the perforations are made, the multiple cavities are communicated with
each other and a single shunt can be placed into one of the major cavities.
•• If the loculations are unilateral, they can be communicated to the opposite
ventricle through a septum pellucidotomy.
160
Hydrocephalus Ex-vacuo
•• This condition generally indicates enlargement of the ventricles second-
ary to cerebral parenchymal damage. The ex-vacuo of cerebral atrophy
can be associated with ageing, head trauma, severe infection, hypoxia or
ischaemic insults.
•• Following radiotherapy and chemotherapy, ventricular enlargement can occur.
•• They are usually associated with white matter loss and concomitant enlarge-
ment of the cortical sub-arachnoid spaces and basal cisterns.
•• Peri-ventricular lucency is absent.
•• A number of structural abnormalities of the brain, such as calpocephaly,
holoprosencephaly and agenesis of the corpus callosum may also be
associated with ventricular enlargement and do not necessarily require
any intervention.
19
CHAPTER Endoscopic Management of
Hydrocephalus
Aaron Mohanty
APPROACH
•• The majority of neuroendoscopic procedures are performed in the lateral
and the third ventricles.
•• The standard approach is a precoronal burr hole at Kocher’s point (3 cm
from the midline, just anterior to the coronal suture on the right side). This
point is ideal for reaching the foramen of Monro and the third ventricle.
•• However, in certain circumstances, where a more posterior visualisation
is required, a parietal burr hole may be placed.
•• For approaching a lesion in the temporal horn, a burr hole in the temporal
region may be considered.
•• Alternatively, the temporal horn can be approached through the dilated
atrium of the ipsilateral ventricle.
•• After the burr hole is made, the dura is coagulated and incised.
•• The trocar with the cannula is subsequently introduced into the ventricle.
The trocar is removed and the endoscope is introduced into the ventricle
through the cannula.
•• In patients with small ventricles, stereotactic guidance may be used for
cannulating the ventricles.
Lateral Ventricles
•• The most important landmark is the foramen of Monro.
•• In cases with developmental anomalies, the location of the foramen of
Monro can be identified by locating the choroid plexus and the formation
of the internal cerebral vein.
•• The choroid plexus is located at the floor of the lateral ventricles traversing
from the lateral to the medial side and enters the foramen of Monro.
•• Also seen are the thalamostriate and the septal veins which traverse from
the lateral and medial sides respectively and join at the foramen of Monro
to form the internal cerebral vein.
•• The medial and anterior border of the foramen of Monro is formed by the
fornices. In cases, where the septum is absent, the fornices can be seen
as two distinct bundles.
•• The central part of the lateral ventricle up to the ventricular trigone can
often be visualised by angling the endoscope posteriorly.
•• Visualisation of the temporal horn requires a flexible scope.
162
Third Ventricle
•• Through the foramen of Monro, the floor of the third ventricle can be
visualised.
•• In the floor of the third ventricle, the paired mammillary bodies can be
visualised. The thin membrane anterior to it is called the tuber cinereum,
which is often thinned out and translucent in chronic hydrocephalus.
•• The basilar artery pulsations can often be seen through the thinned out
membrane. Anterior to it is the infundibular recess and the optic chiasma.
•• The aqueductal inlet is located posterior to the mammillary bodies and often
requires a 30°-angled scope. The posterior commissures and the pineal
recess can be identified just superior to it.
•• Visualisation of the aqueduct for procedures, like aqueductoplasty, often
requires a fibreoptic endoscope. Often interthalamic adhesions of various
degrees are visualised and large adhesions may hinder the navigation of
the instrument.
Aqueduct and Fourth Ventricle

•• In obstructive hydrocephalus, the aqueduct may be obstructed by a thin
septum or gliosis or may be thinned out.
•• The fibreoptic scope can be navigated through the outlet foramina, and
the basal cisterns, foramen magnum region and upper cervical region can
be inspected.
INSTRUMENTATION
•• Three prototypes of neuroendoscopes are currently in use: the rigid Hopkins
Lens scope; flexible fibreoptic scope and the rigid fiberscope.
•• Rigid Endoscope:
–– Conventional rigid endoscopes have solid rod lenses and fibreoptic
illumination.
–– The recent endoscopes have an outer diameter ranging from 2.6 mm
to 6 mm.
–– The larger diameter endoscopes allow for larger working channels
and, hence, a variety of accessory instruments can be used.
–– Rigid endoscopes can have a viewing angle from 0° to 120°.
–– The 0° telescope is the most useful in routine practice; however, the
rest are required to inspect the inaccessible areas or to “look around
the corner”.
–– Rigid endoscopes have the advantage of better vision, better surgical
orientation and are easy to use.
–– They are also sturdier and have a longer life than fibreoptic scopes.
•• Fibreoptic Endoscope:
–– Significant technical advancements have resulted in the availability of
thinner fibreoptic scopes with diameters as small as 0.7 mm. However,
the quality of viewing of these thinner endoscopes is poor.
–– Fibreoptic endoscopes are advantageous for their flexibility and ability
to explore the areas where a conventional rigid endoscope cannot be
navigated.
–– Thin instruments can be passed through the endoscope for obtaining
a biopsy.
Chapter 19 • Endoscopic Management of Hydrocephalus
163
–– A poor picture quality, difficult orientation and a high maintenance cost

are the disadvantages of a fibreoptic endoscope.
•• Rigid Fibrescope:
–– In this third prototype, fibreoptic bundles are compactly arranged in a
rigid frame structure.
–– This architecture adds the advantage of easier orientation and smooth
passage of reasonably sized instruments while maintaining the thinner
diameter of the flexible scope.
STABILISATION AND GUIDING DEVICES

•• The endoscopes with camera attachments are heavy and, hence, devices
are essential to provide the necessary stabilisation during the operative
procedure, which frees the endoscopist from holding the instrument.
•• The Gaab’s rigid endoscope can be attached to the conventional Leyla
retractor by fixators.
Stereotactic Guidance
•• Stereotactic guidance is helpful for cannulation of small ventricles or for
planning to reach deep-seated targets. The endoscope can be attached
to the stereotactic guiding device.
•• Neuronavigation has especially been useful in planning the trajectory,
maintaining the trajectory during the procedure and avoiding injury to the
adjacent structures.
•• Image guidance is helpful in patients with anomalies of the ventricular
system and in patients with multiloculated hydrocephalus.
•• Other adjuncts which often have been used include ultrasound and robotic
assisted endoscopic third ventriculostomy (ETV).
ENDOSCOPIC PROCEDURES FOR OBSTRUCTIVE

HYDROCEPHALUS (TABLE 1)
Third Ventriculostomy
•• Though it was performed as early as in 1923 by Mixter, the procedure
did not gain widespread acceptance due to inadequate instrumentation.
•• Patient Selection:
–– Patients with acquired aqueductal stenosis are considered to be the
ideal candidates for third ventriculostomy.
–– Aqueductal obstruction due to posterior fossa tumours are also ben-
efited by a third ventriculostomy.
–– The role of third ventriculostomy in hydrocephalic children with my-
elomeningocoele has been controversial.
–– Patients with communicating hydrocephalus theoretically would not
benefit from the procedure, although evidence in this regard has been
lacking.
•• Complications:
–– A transient arrhythmia often occurs during the perforation of the floor
which usually settles by itself.
–– In case the perforation is performed away from the midline, hypotha-
lamic damage may result leading to water and electrolyte imbalance,
which, however, is usually transient.
164
Table 1: Endoscopic procedures for obstructive hydrocephalus

Pathological condition Endoscopic procedures performed
Aqueductal stenosis • Third ventriculostomy
• Aqueductoplasty (Aqueductal reconstruction)
• Aqueductal stenting
Posterior fossa tumour with • Third ventriculostomy
hydrocephalus
Fourth ventricular outlet • Third ventriculostomy
obstruction
Unilateral hydrocephalus • Septostomy
• Foraminoplasty
Multiloculated hydrocephalus • Membrane fenestrations with endoscopic ventriculoperito-
neal shunt insertion
Trapped fourth ventricle • Endoscopic third ventriculostomy with aqueductal stenting
Miscellaneous • Endoscopic shunt placement
• Removal of adherent ventricular catheter
• Removal of migrated ventricular catheter
• Choroid plexus coagulation
–– Transient pareses of the III and VI cranial nerves have also been
observed.
–– Bleeding from the edges of the perforation is usually self-limiting. How-
ever, damage to the basilar artery may occur and may be fatal during
the procedure or lead to the formation of a pseudoaneurysm.
–– Subdural effusions and subdural haematoma can occur due to sudden
release of cerebrospinal fluid (CSF).
•• Assessment of Effectiveness:
–– Improvement in the pre-operative downward bulging of the third ven-
tricular floor has also been noticed in the post-operative MRI scans.
–– The periventricular lucencies resolve, symptoms resolve and the head
size enlargement arrests.
–– The CSF cisterns become prominent, suggesting a patent third ven-
triculostomy.
–– Radiological studies can demonstrate patency of the fenestration.
Though contrast ventriculograms were initially performed with the ad-
vent of MRI, flow void through the floor can often be visualised.
–– T2-weighted fast spin echo images or 2D-phase contrast images have
been used to assess the flow through the third ventricular floor and
have been found to be equally effective in assessing the patency.
•• Age has been found to be the single most predictive factor in assessing
the prognosis of ETV. In large series, success rates of 70−81% in patients
older than 2 years and between 45% and 50% in children below 2 years
of age are reported.
•• The aetiology of hydrocephalus has also been found to be a significant
factor in determining the success rates.
•• Reduction in the absorption mechanism of the CSF at the arachnoid
granulations as in postinfectious and post-haemorrhagic hydrocephalus
has been associated with a lower success rate in this population.
•• The success rate has varied from 23% to 65% with the lower rates
associated with coexistence of haemorrhage and infection.
Chapter 19 • Endoscopic Management of Hydrocephalus
165
•• The degree of scarring in the basal cisterns has been found to be directly
related to the overall outcome in several recent studies.
•• ETV has also been found to be successful in the management of hydro-
cephalus associated with the chronic stages of tubercular meningitis.
•• Myelomeningocoele with Hydrocephalus:
–– The success rate of ETV in patients with myelomeningocoele depends
on the age of onset of hydrocephalus and any previous shunt inser-
tions.
–– The success rate has varied from 27% in patients who had ETV as
their initial procedure to 77% in patients where a previous shunt has
been inserted, and the ETV was performed as a subsequent proce-
dure.
–– An overall success rate of 72% was reported in a series of 69 patients
who had ETV performed for hydrocephalus associated with my-
elomeningocoele, though the success rate improved to 80% in patients
who were either over 6 months of age or had a previous shunt inserted.
–– Poor absorptive capacity in the initial neonatal period was considered
to be the deciding factor for the lower success rate in the early infantile
period.
•• Chiari Malformation and Hydrocephalus: The obstruction to the CSF flow
occurs in the region of the foramen magnum and the outlets of the fourth
ventricle. The success of the ETV relates to diverting the fluid away from
the obstruction site into the basal cisterns. Shrinkage of the associated
syrinx has also been well demonstrated.
•• Fourth Ventricular Outlet Obstruction: Commonly due to an inflammatory
process, this can be due to either infectious or post-haemorrhagic aetiology.
ETV has been found useful in 65% of patients, who had outlet obstruction,
resulting in obstructive hydrocephalus.
•• Obstructive Hydrocephalus Due to Tumours:
–– Endoscopic procedures have been found to be useful in three areas in
patients with intraventricular or paraventricular tumours with hydroceph-
alus. Associated obstructive hydrocephalus caused by tumours located
at or distal to the posterior third ventricle can be treated with ETV.
–– Third ventriculostomy has been found to be effective in posterior third
ventricular and tectal plate tumours as an alternative to ventriculoperi-
toneal (VP) shunt placement.
–– It has also been used as a CSF diversion procedure in fourth ventricu-
lar tumours.
–– It can be used to biopsy the lesions during the same sitting while per-
forming the third ventriculostomy. In patients with highly radiosensitive
tumours (germinoma), a subsequent second procedure can, thus, be
avoided.
–– In selected intraventricular tumours complete tumour excision can be
performed endoscopically.
•• Dandy-Walker Malformation:
–– In patients with Dandy-Walker malformation with an open aqueduct, a
third ventriculostomy should suffice in diverting the CSF from the site
of obstruction.
–– Considering the above, it is apparent that adult patients with obstruc-
tive triventricular hydrocephalus, due to aqueductal stenosis, tectal
plate tumours and posterior fossa tumours, are excellent candidates
for the procedure.
166
Aqueductal Reconstruction
•• Aqueductoplasty and aqueductal stenting have emerged as exciting options
for a selected group of patients with obstructive hydrocephalus.
•• Aqueductal stenosis is classified as long segment stenosis, short segment
stenosis and aqueductal web.
•• A long segment aqueductal stenosis with the length of the stenosis
exceeding 5 mm is not suitable for an aqueductal reconstruction procedure
as attempting a reconstruction would lead to periaqueductal region damage.
•• On the other hand, fenestrating the thin web that often blocks the aqueduct
or dilating or stenting a segment of stenosis less than 5 mm in length is
often not difficult.
•• Such cases are ideal candidates for aqueductoplasty or aqueductal
stenting.
•• Aqueductal stenting in conjunction with ETV or VP shunt has also been
considered for the management of an isolated fourth ventricle.
•• Complications: Injury to the cranial nerve nuclei in the region of the upper
brainstem can cause dysconjugate eye movements and upward gaze
paresis. Transient loss of consciousness has also been reported due to
injury to the periaqueductal grey.
Multiloculated Hydrocephalus
•• Multiloculated hydrocephalus usually occurs after an initial episode of
neonatal meningitis or a germinal matrix haemorrhage.
•• Among the various treatment options available are placement of multiple
shunts, single shunt with multiple perforations traversing all the loculations
or craniotomy with lysis of intraventricular septations.
•• Stereotactic cyst aspiration or endoscopic cyst fenestrations with shunt
insertion have been described.
•• The endoscopic option appears the most ideal and can be performed
through a single burr hole with the aid of a steerable endoscope.
•• A large fenestration is usually performed to prevent recurrent cyst formation.
•• Intra-operative ultrasound or navigational systems can be of considerable
help in identifying the loculations.
•• After the perforations are made, the multiple cavities are communicated
with each other and a single shunt can be placed into one of the major
cavities with endoscopic guidance.
Septum Pellucidotomy
•• In unilateral hydrocephalus due to tumours or adhesions at the foramen
of Monro, the septum pellucidum can be perforated endoscopically. Also
in cases of triventricular hydrocephalus due to cysts and tumours at the
foramen of Monro, the septum can be perforated and a lateral ventricular
shunt may be avoided.
•• Successful endoscopic fenestration of congenitally occluded foramen of
Monro has been described.
20
CHAPTER Normal Pressure
Hydrocephalus
Sanjay Behari  Das NK  Vimal Kumar V
INTRODUCTION
•• Normal pressure hydrocephalus (NPH) is a clinical syndrome characterised
by a triad of altered mentation, gait difficulties and sphincter disturbances,
together with ventriculomegaly and normal cerebrospinal fluid (CSF)
pressure.
•• The term “normal pressure hydrocephalus” was introduced by Hakim in
his thesis paper in 1964.
•• NPH has been classified into two groups:
–– The first group is secondary NPH with a known cause, which includes
patients with a past medical history of meningeal inflammation (e.g. trau-
ma, meningitis, subarachnoid haemorrhage and subdural haematoma).
–– The second group is idiopathic normal pressure hydrocephalus (iNPH),
which includes patients in whom no apparent cause is detectable.
•• Patients with iNPH bear a close resemblance to dementia associated with
Alzheimer’s disease or the movement disorders associated with Parkinson’s
disease, or NPH may co-exist with these diseases.
INCIDENCE
•• In adults, NPH may occur at any age.
•• The children with NPH may manifest poor scholastic performance, gait
retardation in infants or repeated falling spells in older children and delayed
bladder control.
•• The sex distribution reported in the literature has a male predominance
in nearly every series with the male-female ratio being approximately 2:1.
AETIOLOGY
•• Still not known and various theories have been proposed to account for
the progressive ventricular dilatation associated with near-normal CSF
pressures as well as the regional cerebrovascular changes. These include:
1. Increased Venous Resistance: Decreased CSF resorption occurs
at the level of the arachnoidal villi and granulations (probably due to
leptomeningeal fibrosis) as well as the brain parenchyma (i.e. tran-
scapillary and transvenular increased vascular resistance). Decreased
CSF absorption increases the transmantle pressure (i.e. the pressure
difference between the ventricles and the subarachnoid space) caus-
ing ventricular enlargement. Thus, often, the ventricles may be dilated
out of proportion to any sulcal enlargement, which distinguishes it from
cortical atrophy.
168
2. Tissue Distortion: Distortion and stretching of the periventricular tis-

sues including blood vessels increase cerebrovascular resistance and
cause ischaemia. In the early stages, the mechanical strain of the brain
parenchyma and the interstitial pressure are more pronounced in the
periventricular region. Later, the periventricular tissue yields the brain
parenchyma shrinks, and CSF pressure returns to normal, creating the
NPH state.
3. Interstitial Fluid Pressure Increase: Suffusion of CSF into the peri
ventricular tissues and the reversal of interstitial fluid flow compress
local vessels and accumulation of toxic/vasoactive substances causes
border-zone ischaemia and tissue damage of white matter even with
modest systemic hypotension or rise of intracranial pressure (ICP).
4. Watershed Ischaemia: Watershed ischaemia within the corona
radiata may occur in the boundary zone between the middle cerebral
artery perforators and the medullary branches from the pial arteries.
The corona radiata is vulnerable to reductions in the cerebral perfusion
pressure even within the conventionally defined autoregulatory range
when accompanied by impairment of CBF pressure autoregulation.
5. Vasoactive Metabolites: Interstitial/extracellular oedema pre-
dominantly in the periventricular tissue leads to accumulation of
inappropriate vasoactive metabolites in this oedema. These me-
tabolites may interfere with intrinsic mechanisms (e.g. nitric oxide)
subserving cerebrovascular reactivity. The accumulation of amyloid
protein may also damage tissues including vessels. These lead to
failure of autoregulation in iNPH.
6. Vascular Disease: In NPH patients, there is a high incidence of
periventricular white matter hyperintensities representative of small
vessel ischaemic changes. These multiple areas of infarction reduce
the elasticity of the periventricular tissue leading to enlargement of the
ventricles provoked by intraventricular CSF pressure pulsations, which
are also increased in the case of systemic hypertension.
CRITERIA FOR DIAGNOSIS

•• “Probable INPH”: The guidelines for the diagnosis and management
of iNPH published in the supplement of “Neurosurgery” in 2005 have
suggested the following criteria:
–– The onset should be insidious, usually in a patient above the age of 40
years, with a minimum duration of at least 3−6 months and be slowly
progressive over time.
–– There should not be evidence of an antecedent event, like head
trauma, intracerebral haemorrhage, meningitis or any known causes
of secondary hydrocephalus, nor any other neurological, psychiatric or
general medical conditions that may explain the syndrome.
–– The clinical features must be in the form of gait/balance disturbance
with at least one other area of impairment in cognition, urinary symp-
toms or both.
•• Gait/balance: At least two of the following should be present. These include
decreased step, height and length; decreased speed and increased trunk
swaying during walking; widened standing base with toes turned outwards
during walking; spontaneous or provoked retropulsion; en bloc turning or
impaired walking balance.
Chapter 20 • Normal Pressure Hydrocephalus
169
•• Cognition impairment may be in the form of increased response latency,

decreased fine motor speed and accuracy, difficulty in maintaining attention,
and impaired recent recall, impaired insight, abstraction, multi-step
procedures, working memory and behavioural or personality changes.
•• Urinary incontinence in the absence of any primary urological disorders
may be episodic or persistent urinary urgency (frequent perception of a
pressing need to void), frequency (>6 voiding episodes in an average 12
hours’ period despite normal intake) and/or nocturia (need to urinate >2
times in an average night).
•• The computed tomography (CT)/MRI must show:
–– Ventricular enlargement that is not entirely due to cerebral atrophy or
congenital enlargement (Evan’s index >0.3)
–– No macroscopic obstruction to CSF flow
–– Callosal angle of > 40 degrees on coronal magnetic resonance imag-
ing (MRI)
–– Decrease in the diameter of the corpus callosum on sagittal MRI as
the dorsal surface of the ventricle domes upwards and evidence of
periventricular lucency
–– Radionuclide cisternogram showing delayed clearance of radiotracer
over the cerebral convexity over 48−72 hours
–– Cine MRI study showing increased ventricular flow rate and a single
photon emission computed tomography (SPECT)-acetazolamide chal-
lenge showing decreased periventricular perfusion that is not altered
by acetazolamide.
•• On lumbar puncture (LP), the CSF opening pressure should be in the range
of 5−18 mmHg (or 70−245 mm H2O).
•• “Possible”: If patients do not meet all of the above criteria, but are
still suspected of having iNPH, certain exceptions are permissible for a
designation of the clinical presentation and history may include any of the
following six exceptions:
1. Symptoms have a subacute or indeterminant mode of onset.
2. Symptoms begin at any age following childhood.
3. Symptoms have less than 3 months or indeterminant duration.
4. Symptoms remotely follow events, such as mild head trauma, intrac-
erebral haemorrhage, childhood and adolescent meningitis or other
conditions, that the clinician judges unlikely to be immediately causally
related.
5. Symptoms coexist with other neurologic, psychiatric or general medi-
cal disorders that the clinician judges not to be entirely attributable to
these conditions.
6. Symptoms are non-progressive or not clearly progressive; if either
incontinence and/or cognitive impairment is present in the absence
of gait or balance disturbance or if gait disturbance or dementia occur
alone.
•• Idiopathic normal pressure hydrocephalus occurs due to insufficient CSF
absorption. It may lead to symptoms due to vascular ischaemic effects,
elevated transmantle pressure, axonal stretching of the periventricular white
matter and deformation of the brain parenchyma.
•• It has been suggested that ventricular enlargement leads to vascular
stretching, decreased compliance and high pulse pressure, leading to local
barotrauma or tangential shear stress.
170
Gait Abnormality
•• Gait impairment is the commonest and often the first symptom in patients
with NPH.
•• Initially, there may be slowing with difficulty in turning and a mild instability,
which may not be distinguishable from the senile gait or very early
Parkinsonism gait.
•• On progression of the disease, stride length shortens and gait speed slows
and there is decreased floor clearance and difficulty in turning.
•• In late phases of the disease, the gait becomes a “magnetic gait”, and
the patients appear to have forgotten how to take a step or even to stand.
•• The posture in these patients is known as “hydrocephalic astasia-abasia”
and is forward leaning with a wider sway and imbalance accentuated by
eye closure.
•• In iNPH, gait disturbances may arise due to compression of upper motor
neuron fibres passing through the medial portion of the corona radiata as
a consequence of ventricular dilatation.
•• Electromyography suggests contraction of the antagonistic muscle groups
and increased activity in the antigravity muscles acting on the hip and knee
joints. This disorder of phased activation of muscle groups points towards
subcortical motor control indicative of premotor pathway involvement.
•• With the progression of the disease, and extensive subcortical white matter
changes, the pyramidal tracts also become involved manifesting with
extensor plantar response.
•• Subcortical dopaminergic nigrostriatal pathway impairment may also
contribute to gait and movement disturbances by leading to a disturbance
in motor planning.
•• Impaired input from the sensorimotor cortex, the superior frontal cortex, and
the anterior cingulate gyrus to the reticular formation in the tegmentum of
the brainstem may also contribute to the gait and stance disorder.
Cognitive Deficits
•• NPH is the cause of less than 1% of all dementias.
•• Initially, there is slowing of mental processing, reduced organisational and
problem-solving skills and a reduction in prior interests.
•• Patients with NPH exhibit subcortical type of mental deficits including
forgetfulness, decreased attention, inertia and mental slowness with a
pattern of memory impairment that differs from the cortical dementias as
seen in Alzheimer’s disease.
•• NPH is also not associated with “aphasia-apraxia-agnosia syndrome”, which
characteristically occurs in cortical dementias. Significant hippocampal
atrophy on MRI studies is an important neuroimaging criterion for the
diagnosis of Alzheimer’s disease.
•• Various psychiatric disorders in association with iNPH are depression,
mania, aggression, obsessive compulsive disorder, psychosis and
disturbance of impulse control.
Urinary Incontinence
•• Disturbances of bladder control range from urinary frequency to inconti-
nence.
•• Urinary incontinence may be present in about half of the patients diagnosed
with NPH.
171
•• Incontinence typically signifies a late stage of NPH, although some degree

of urgency is often present even in the early stages.
•• Bladder symptoms may not improve or resolve following CSF diversion.
•• Patients with more advanced iNPH may show indifference to the episodes
of incontinence due to an associated frontal lobe syndrome.
•• The problems in urinary function may initially be due to the involvement of
sacral fibres of the corticospinal tract and later may be a feature of dementia.
Differential Diagnosis of Normal

Pressure Hydrocephalus
•• These include neurodegenerative disorders, like Alzheimer’s disease,
Parkinson’s disease, Huntington’s disease, frontotemporal dementia,
progressive supranuclear palsy, amyotropic lateral sclerosis and
multisystem atrophy.
•• Vascular dementias including cerebrovascular disease, stroke, multi-infarct
state, Binswanger’s disease, leukoencephalopathy and vertebrobasilar
insufficiency.
•• Hydrocephalic disorders, like aqueductal stenosis, arrested hydrocephalus,
long-standing overt ventriculomegaly syndrome and non-communicating
hydrocephalus.
•• Infectious diseases, like Lyme, HIV and syphilis and urological disorders,
like urinary tract infections, bladder or prostate cancer and benign prostatic
enlargement.
•• Miscellaneous disorders include B12 deficiency, collagen vascular disorders,
epilepsy, depression, traumatic brain injury, spinal stenosis, Chiari I
malformation, post-subarachnoid haemorrhage hydrocephalus, spinal
cord tumours and carcinomatous meningitis among several other causes.
Diagnosis
Computed Tomography
•• The CT scan shows the presence and
extent of hydrocephalus as well as the
degree of existing cortical atrophy.
•• The CT diagnosis of NPH (Fig. 1) relies
on the enlargement of the lateral and
third ventricles, enlargement of the tem-
poral horns, prominent basilar cisterns,
enlarged suprasellar cisterns, non-visu-
alisation of the high cerebral convexity
sulci, and possible enlargement of the
fourth ventricle.
•• The temporal horn dilatation is thought
to be more specific for the diagnosis of
NPH and correlates with positive findings Fig. 1: Calculation of Evans
on radionuclide cisternography. ratio
•• Evans Index (or Frontal Horn Ratio):
–– It is the ratio of the maximum width of the frontal horns to the maximum
width of the inner table of the cranium.
–– Ratio greater than 0.32 is consistent with the diagnosis of NPH.
–– It cannot differentiate NPH from cortical atrophy or obstructive hydro-
cephalus as the ratio may increase in all the three entities.
172
–– Higher preoperative Evans ratio (e.g. > 0.40) does not correlate with
clinical improvement.
Nuclear or Computed Tomography Cisternography

•• Cisternography, originally described with radionuclides, has also been
performed with iodinated contrast agents. In both the techniques, the CSF
kinetics are similar.
•• Radionuclide cisternography is performed by injecting an isotope iodine
labelled serum albumin or indium111 via an LP. A two-dimensional gamma
imaging is done intermittently over 24−48 hours.
•• In hydrocephalic patients, both the ventricular reflux and delayed ascent and
prolonged activity of the tracer over the cerebral convexity are evaluated.
•• Nuclear or CT cisternography may show ventricular reflux with a slow
cortical uptake.
•• The advantages of the CT technique include direct visualisation of intrathe-
cal injection under fluoroscopy and improved spatial resolution, possibly for
quantitative analysis. However, this poorly evaluates flow over the cerebral
convexities, which is more easily seen with the radionuclide technique.
•• Overall, there is no greater advantage of CT cisternography over the
radionuclide technique.
•• The recent recommendation is that cisternography is not very helpful in
identifying patients with iNPH and should not be included as an option.
Magnetic Resonance Imaging

•• The periventricular white matter has been studied in patients having NPH
using an MR imaging technique called magnetisation transfer (MT).
•• This technique measures the interaction between the pool of unbound water
protons in tissues and the pool of water protons bound to macromolecules
such as proteins and membranes.
•• White matter changes with a high rate of MT are considered abnormal.
These are detected much earlier on MT sequences than on routine T2
weighted imaging.
•• MR has also been used to study the pathophysiology of NPH by evaluating
the presence of decreased vascular compliance in the superior sagittal
sinus and straight sinus in NPH patients.
Magnetic Resonance Cerebrospinal Fluid Flow Studies

•• On MR imaging, a signal void (Jet sign) is seen in the region of the cerebral
aqueduct. This is because the velocity of fluid motion increases when larger
volumes move through passages with decreasing cross-sectional areas.
•• Patients with iNPH have a pathological cerebral compliance and a majority
of them suffer from hypertension.
•• These patients may have a hyperdynamic CSF motion that appears as CSF
flow void. This is recognised as a signal loss within the ventricular system
on T2 weighted MR scans and may be due to dephasing of protons that
move along a gradient that is perpendicular to the imaging plane.
Cerebral Perfusion
•• Cerebral perfusion studies showed decreased CBF in iNPH. However, as
CBF is also decreased in patients with cerebral atrophy, it may be difficult
to distinguish between the two conditions using this technique.
173
•• Normalisation or near normalisation of CBF after LP in patients having

iNPH has prognostic importance as this subset of patients may improve
after shunting.
•• The acetazolamide challenge test (i.e. a vasomotor response to carbonic
anhydrase inhibitors) or inhaled CO2, which normally increases CBF, often
fails to do so in iNPH patients, particularly in the periventricular white matter.
Cerebral Metabolism
• 18F-fluoro-deoxy-glucose positron emission tomographic (PET) scans of
the brain have demonstrated globally decreased brain metabolism and
CBF in patients with iNPH.
•• Enlargement of the subcortical low cerebral flow region taken from slices
through the midbrain or basal ganglia as demonstrated on SPECT using
either 99mTc hexamethylpropyleneamine or 123I-isopropylamphetamine may
also be useful in identifying candidates for shunt surgery.
Transcranial Doppler Ultrasonography

•• Transcranial Doppler (TCD) ultrasonography has been used to study the
preoperative and postoperative cerebral haemodynamics in iNPH.
•• Measurement of the preoperative end diastolic velocities also has
prognostic significance. When CBF velocity is maximum at the diastolic
phase of the cardiac cycle, it indicates that the patient may be benefited
by CSF shunting.
•• TCD has not been used to diagnose or plan treatment of patients with
iNPH routinely.
Tap Test
•• The tap test is one of the commonly used tests to determine the clinical
response to installation of a shunt in iNPH.
•• It is easy to perform and is inexpensive.
•• It has been documented that if after CSF (40−50 cc) drainage through an
LP, the patient improves clinically, it indicates that he/she may be shunt
responsive.
•• The sensitivity and specificity of the test increases when more fluid is
tapped. A positive predictive value of more than 70% has been reported.
•• When combined with SPECT measurements of CBF before and after the
tap test, higher predictive rates of shunt responsiveness are obtained.
Measurement of Cerebrospinal Fluid Opening Pressure

•• Manometric measurement of CSF opening pressure on LP is also used for
determining shunt responsiveness in patients with iNPH.
•• In normal individuals, the CSF opening pressure averages 122 ± 34 mm
H2O (8.8 ± 0.9 mmHg).
•• In patients with iNPH, the CSF opening pressure averages 11 ± 3.3 mmHg
(150 ± 45 mm H2O) but may fall between 4.4 mmHg and 17.6 mmHg
(60−240 mm H2O).
•• Thus, in iNPH, the mean CSF opening pressure is slightly higher than
normal but is still within the normal range.
•• In iNPH, there may be transient high pressure waves (B waves) during
prolonged intraventricular pressure monitoring, but these waves are not
sustained.
174
•• CSF opening pressures in the range of 105−190 mm H2O may indicate

probable iNPH.
•• At the extremes of the expected range (60−104 mm H2O or 191−240 mm
H2O), iNPH may be possible.
•• Pressures outside this range would make the diagnosis of iNPH unlikely.
•• Thus, iNPH may be distinguished from secondary forms of hydrocephalus
where the CSF pressure is usually high (usually above 18 mm Hg; 245 mm
H2O) and the increased CSF pressures are sustained.
Continuous Intracranial Pressure Monitoring

•• A normal or slightly elevated ICP (> 15 mm Hg) and an increased frequency
of B waves (occupying more than 50% of the monitoring period) may be
indicative of a lower compliance.
•• However, there is a lack of normal age-matched control data in the literature.
Both A and B waves often poorly predict which patients will respond to
shunt surgery.
Controlled Continuous Lumbar Drainage

•• Controlled continuous lumbar drainage consists of draining 10 cc of CSF
per hour for a period of 72 hours.
•• However, the potential risks and disadvantages (hospitalisation and costs)
prevent this test from being routinely used in clinical practise.
Impedance of Flow Offered by Cerebrospinal

Fluid Absorption Pathways
•• This resistance offered by CSF absorption pathways may be measured
by several methods.
–– In the Katzman test, a pump introduces artificial CSF or saline into the
lumbar subarachnoid space at a known constant rate. The resistance
is the difference in the final steady-state pressure reached and the
initial pressure divided by the infused flow rate.
–– In the bolus method, about 4 mL fluid is injected into the lumbar sub-
arachnoid space at the rate of 1 mL/sec. This method measures both
the resistance offered by the CSF absorption pathways as well as the
brain compliance (defined by the pressure-volume index).
–– A third method calculates the resistance and compliance during
ascending pressure curves in response to a known infusion rate.
•• A problem with measuring impedence of CSF flow is that it increases with
age even in normal individuals.
•• Headache and meningismus may occur following fluid infusion.
•• The predictors of good surgical candidates for shunting in iNPH are
summarised in Table 1.
SURGICAL MANAGEMENT OF IDIOPATHIC

NORMAL PRESSURE HYDROCEPHALUS
Patient Selection
•• Patients with severe cerebrovascular disease do not respond as well to
shunting but may still derive some benefit from the procedure.
•• The neurological decline in spite of shunt placement in iNPH may be related
to the progression of comorbid conditions rather than as sequelae of iNPH.
175
Table 1: Predictors of good surgical candidates for shunting in iNPH

Evaluation parameter Positive predictor
Clinical examination Presence of classic triad, especially gait disturbance as the
primary symptom
Lumbar puncture Opening pressure >100 mm water
Cisternogram Typical NPH pattern, especially persistent ventricular activity at
48 hours
Continuous CSF CSF recording pressure >180 mm monitoring water; frequent
beta waves
Cranial CT scan Enlarged ventricles; periventricular hypodensities; flattened corti-
cal sulci; small or absent perihippocampal fissures
MRI All of the above, specially small or absent perihippocampal
fissures
Transcranial Doppler Reactivity above 25% with pathologic readings on pressure
studies with carbon recordings
dioxide reactivity
•• The CSF shunt improves the symptomatology of patients with iNPH due
to its dual action, i.e. the diversion of a greater proportion of CSF as well
as the provision of additional capacitance.
•• The latter is because, with the modulation of pulse pressure, the interstitial
oedema and pressure also decrease, improving perfusion and decreasing
ischaemia. This may be the reason why third ventriculostomy is also
effective in some patients of iNPH.
•• Surgical diversion of CSF is recommended for iNPH patients in whom there
is a favourable risk-to-benefit ratio.
•• Factors such as coagulation status, immune incompetence, comorbidity,
functional status and advanced age should be taken into account while
considering surgical intervention.
•• The medical treatment of NPH consists of acetazolamide and repeated
LPs, which have occasionally yielded prolonged clinical improvement.
Current Guidelines for iNPH Diagnosis and

Use of Supplemental Prognostic Tests for
Identifying Shunt Responsive Patients
•• On the basis of clinical examination and neuroimaging (CT/MR), the patient
may be categorised as “probable”, “possible” or “unlikely”.
•• Improvement following shunt placement for “possible” or “probable” iNPH
ranges from approximately 61% to slightly less than 50%.
•• Thus, if the classical triad is present and no other illness accounts for
the clinical presentation, then one may proceed directly to CSF diversion
without supplemental tests. In the unlikely NPH category, a shunt placement
is usually deferred.
CSF Tap Test
•• Resistance to flow of CSF determination and/or external lumbar drainage.
•• This may be done in order to increase the certainty of positive shunt
response beyond 50 to 61%.
•• A favourable clinical response to a 40−50 mL CSF tap test indicates that
the patient is likely to be benefited from CSF diversion surgery.
176
•• This may be performed for three consecutive days and clinical assessment
made.
•• If the tap test does not elicit a favourable clinical response, however, it
cannot be used as an exclusionary test due to its low sensitivity (26−61%).
•• Thus, if a negative tap test is obtained, supplemental tests should be
performed. If the opening pressure during tap test exceeds 18 mmHg,
a diagnostic work up for secondary causes of hydrocephalus should be
initiated.
Type of Shunt
•• Various shunt diversion procedures have been described: VP and ventri
culoatrial (VA) shunts, the lumboperitoneal shunt and the ventriculopleural
shunt.
•• The most commonly used CSF diversion procedures in iNPH are the VP
and lumboperitoneal shunts.
•• However, patients who have a history of peritonitis or multiple abdominal
operations may not have adequate CSF drainage due to decreased
absorptive capacity of the peritoneal cavity. In these patients, a VA shunt
may be preferred.
•• Endoscopic third vetriculostomy has also been advocated as a therapeutic
option in selected patients. ETV reduces the intraventricular pressure
(with a consequent increase of the CBF) and also restores the normal
CSF dynamics.
Valve Selection
•• The shunt valve selection may have a bearing on the outcome of iNPH since
it maintains a balance between an efficient CSF drainage and prevention
of overdrainage-related complications.
•• The valve designs may be of different types:
–– Differential pressure valves (e.g. Chhabra shunt):
¾¾ A spring-loaded ball check valve or the opposed leaves of a slit
valve will open, if the pressure differential across the valve mecha-
nism exceeds a set value.
¾¾ They may be categorised into low pressure (approximately 20−40
mm H2O); medium pressure (approximately 50−90 mm H2O) and
high pressure (approximately 100−140 mm H2O).
–– Flow-limiting valves: These may either:
¾¾ Have a differential pressure valve that in conditions of normal CSF,
flow limits CSF flow rate by narrowing the aperture of the valve
mechanism and in conditions of high ICP, switches to a high flow
rate (e.g. NMT Orbis-Sigma and Phoenix shunts)
¾¾ Incorporate a high flow resistance tube without a differential pres-
sure mechanism in series to an adjustable differential pressure
valve that prevents gravitydependent overdrainage by selectively
reducing high CSF flow rates when the patient is in an upright posi-
tion (e.g. Codman FloGuard valve)
¾¾ Incorporate a dual stage differential pressure valve (containing tan-
talum spheres that move within the valves in response to gravity)
which has a low pressure in the supine position and a high pressure
in the upright position (e.g. Miethke dual switch valve).
177
–– Programmable valves (e.g. Sophy and Codman-Medos valves):

These permit the opening pressures of the differential pressure valve
mechanisms to be changed non-invasively. The valve adjustments
may be made depending upon whether or not overdrainage, underd-
rainage or a subdural fluid accumulation is occurring.
Clinical Scales for Assessing Outcome

•• The various scales used for assessing clinical outcome at follow-up after
shunt placement are as follows:
–– The Stein and Langfitt scale
–– The Black scale
–– The modified Rankins’ scale
–– Boon’s Dutch NPH scale
–– Folstein Mini-mental state examination.
21
CHAPTER Bony Anomalies of the
Craniovertebral Junction
Sanjay Behari  Rabi N Sahu  Vijendra Kumar Jain
INTRODUCTION
•• The term ‘craniovertebral junction” (CVJ) refers to the occipital bone that
encircles the foramen magnum, the atlas and the axis cervical vertebrae.
•• The medulla oblongata, cervicomedullay junction and upper cervical spinal
cord pass through the bony canal formed by these structures.
•• The CVJ has a predilection for a variety of congenital anomalies due to its
complex embryological development.
•• Any bony abnormality that affects this complex can result in neural
compression along the entire circumference, vascular compromise and
abnormal cerebrospinal fluid (CSF) dynamics.
EMBRYOLOGICAL ANATOMY OF
CRANIOVERTEBRAL JUNCTION
•• During the 4th week of gestation, somites are formed, of which four
occipital somites and the upper two cervical somites are involved in the
development of CVJ.
•• The first two occipital sclerotomes ultimately form the basiocciput.
•• The third sclerotome is responsible for the exoccipital center and forms
the jugular tubercle.
•• The fourth occipital sclerotome is called the proatlas and has three divisions:
–– Hypocentrum that forms the anterior tubercle of the clivus
–– Centrum that forms the apical ligament and the apex of the dens
–– The neural arch of the proatlas that has further two subdivisions:
¾¾ The ventral rostral part forms the occipital condyles, the anterior
portion of the foramen magnum and the alar and cruciate ligaments
¾¾ The dorsal caudal portion forms the posterior arch of atlas and
its lateral masses.
•• The hypocentrum of the first cervical (C1) sclerotome forms the anterior
arch of atlas, the centrum forms the dens and the neural arch of C1 forms
the posterior-inferior arch of atlas.
•• The 2nd cervical spinal segment has three similar divisions: (1) hypocen-
trum, which disappears; (2) centrum, which forms the body of the axis and
(3) neural arch, which forms the facets and posterior arch of axis.
•• The odontoid process fuses with the base of the axis by the age of 8 years.
•• Wide varieties of congenital anomalies are possible because of this complex
developmental sequence.
•• More often, multiple abnormalities are present in a single individual, which
may involve both osseous and neural structures.
Chapter 21 • Bony Anomalies of the Craniovertebral Junction
179
•• This maldevelopment usually occurs between the fourth and the seventh
months of intrauterine life. CVJ anomalies can be classified into the
following types:
–– Failure of segmentation
–– Failure of fusion of different bony components
–– Hypoplasia
–– Ankylosis.
•• Various genetic associations have been found with CVJ anomalies:
–– Methylenetetrahydrofolate reductase (MTHFR) gene 677C
–– Hox gene
–– PAX regulatory genes control segmentation of the somites and
sclerotomes to establish vertebral boundaries. During chondrification
of the vertebrae, the PAX gene is strongly expressed in the developing
vertebrae and, therefore, its expression may underlie vertebral fusion
and may be responsible for the Klippel-Feil anomaly (bony fusion of
adjacent vertebrae).
–– There is increased incidence of occipitocervical instability and CVJ
abnormalities associated with Down’s syndrome.
CLASSIFICATION
•• The congenital CVJ anomalies may be divided into the following:
–– Malformations of Occipital Bone:
¾¾ Manifestations of occipital vertebrae, i.e. clivus segmentations,
remnants around foramen magnum, proatlas remnants
¾¾ Basilar invagination
¾¾ Condylar hypoplasia
¾¾ Assimilation of atlas
–– Malformations of Atlas:
¾¾ Atlas assimilation
¾¾ Atlantoaxial fusion
¾¾ Hypoplasia of atlas arches
–– Malformations of Axis:
¾¾ Segmentation defects of C1-C2 or C2-C3 vertebrae
¾¾ Dens dysplasia
Hypoplasia of the dens
Ossiculum terminale
Os odontoideum
¾¾ Irregular odontoid segmentation
–– Syndromic atlantoaxial instability
¾¾ Inborn errors of metabolism (Morquio syndrome)
¾¾ Down’s syndrome
¾¾ Grisel’s syndrome.
Syndromic Abnormalities of Craniovertebral Junction

•• Mucopolysaccharidoses (MPS):
–– Mucopolysaccharidoses are primary metabolic abnormalities of
carbohydrate metabolism.
–– These diseases are inheritable storage disorders manifested by mental
retardation, macrocephaly, corneal clouding, small stature, dwarfism and
skeletal dysplasia.
–– Generalised ligamentous laxity causes the development of atlantoaxial
dislocation.
180
–– In some patients, radiographic evidence of hypoplasia, absence of

odontoid process or even os odontoideum has been found.
–– Death is common in Morquio syndrome (Mucopolysaccharidosis type IV)
by the age of 7 years.
–– Other described syndromes with similar manifestations are type VI
mucopolysaccharidosis (Maroteaux-Lamy syndrome), mucopolysac-
charidosis (MPS) Type VII (Sly disease) and Hurler’s syndrome.
–– Spinal cord compression due to atlantoaxial subluxation at the CVJ is
a major cause of disability and death in these patients.
•• Down’s Syndrome:
–– This is the most commonly occurring chromosomal anomaly described
in humans occurring in about 1.4/1000 live births.
–– Atlantoaxial instability due to ligamentous laxity occurs in 15−20% of
Down’s syndrome patients.
–– Other bony abnormalities, like os odontoideum, hypoplastic odontoid
process and rotatory atlantoaxial subluxation, have also been found.
–– The most common clinical complaints include neck pain and torticollis.
–– Cervicomedullary compression associated with hyper-reflexia, ataxia
and progressive weakness are also documented in a majority of
patients.
–– Atlantoaxial fusion is required in the symptomatic group with instability
limited to the atlas and axis.
•• Grisel’s Syndrome:
–– This is a unilateral or bilateral atlantoaxial subluxation occurring as a
result of parapharyngeal infections.
–– The pathophysiology involves metastasic inflammation causing
ligamentous stretching and subluxation, muscle spasm and regional
hyperaemia with decalcification of ligamentous structures.
–– The management of such lesions requires precise visualisation of the
area by means of MRI. Elimination of the source of infection is the
mainstay of treatment.
–– The CVJ region must be stabilised with a Halo brace during the phase
of active treatment.
–– Most cases do well with conservative measures.
Clinical Symptomatology
•• The symptoms and signs of craniovertebral anomalies are diverse owing
to compression of the medulla, spinal cord, cranial nerves, spinal roots as
well as vascular compromise secondary to various bony malformations.
•• The signs of myelopathy are variable both in severity and in symmetry.
•• Similarly, the sensory disturbances are also diverse and may include
posterior column as well as bladder symptoms.
•• Various brainstem signs are common when there is compression of the
cervicomedullary region, which include horizontal and down beat nystagmus,
dysmetria, vertigo, internuclear ophthalmoplegia and sleep apnoea.
•• Cranial nerve dysfunctions of trigeminal, vestibulocochlear, glossopharyn-
geal, vagus, accessory and hypoglossal nerves have also been reported.
•• Symptoms related to vascular compromise are rare, but include syncope, vertigo,
episodic hemiparesis, altered consciousness and transient impairment of vision.
•• The stigmata specific to CVJ anomalies include a small stature, short and
webbed neck, low hairline, facial asymmetry, mirror movements of the
hands and high arched palate.
Chapter 21 • Bony Anomalies of the Craniovertebral Junction
181
Investigations
•• The radiological investigations of CVJ anomalies must start with a good
quality X-ray of the CVJ with active flexion, extension and transoral views.
•• Numerous craniometrical reference lines were used to describe the
atlantoaxial instability before the advent of CT and MRI scan.
•• These measurements are meant to analyse the degree of medullary
cord compression and other skull deformities associated with these bony
anomalies.
•• The basal angle is the angle formed by the line joining the nasion to the
tuberculum sellae and the line joining the tuberculum sellae to the anterior
lip of the foramen magnum. Normally, this angle should be about 132
degrees. When it exceeds 142 degrees, platybasia is present. For further
detail see page 58 in chapter 7.
Surgical Management
•• The surgical treatment of symptomatic CVJ anomalies requires a precise
identification of the underlying pathophysiological conditions.
•• The operative treatments include the anterior, posterior as well as the
combination of both these approaches.
•• Symptomatic patients with CVJ anomalies are divided into two groups:
–– Reducible deformity
–– Irreducible deformity.
•• Some of the irreducible variety may be reducible with application of
skeletal traction, especially under cover of muscle relaxants and general
anaesthesia and in such situations these patients are grouped under the
reducible variety.
•• The principle of surgery in the reducible group is to fix the deformity in a
perfectly reduced position by a posterior construct and bone grafts.
•• In the irreducible group, the aim should be to attain a neural decompression
if necessary with resections of misaligned fixed bony tissue using the
anterior transoral approach and to stabilise the CVJ that is rendered
unstable by the extensive osteoligamentous excision.
•• There are various procedures available for stabilisation of the CVJ like
stabilisation with custom countered rods, various bone grafting techniques
with plates and screws as well as wires or cables.
22
CHAPTER
Syringomyelia
Suresh Nair  Girish Menon  BRM Rao
TERMINOLOGY AND CLASSIFICATION

•• Syringomyelia is defined as “tubular cavitations” (i.e. cyst) of the spinal
cord extending over many segments.
•• Many issues are controversial, especially the distinction between
(a) Hydromyelia and syringomyelia
(b) The terms communicating and non-communicating syringomyelia.
•• Milhorat classified syringomyelia into three types:
1. Communicating syrinx occurring with hydrocephalus and anatomically
continuous with the fourth ventricle.
2. Non-communicating syrinx, which is separated from the fourth
ventricle by a syrinx free segment of spinal cord and occurs with
Chiari malformation, extramedullary compressive lesions, spinal cord
trauma, intramedullary tumours, infections, etc.
3. Atrophic syrinx occurring following myelomalacia.
•• Batzdorf’s classification:
1. Syringomyelia related to anomalies at the craniovertebral junction (CV).
2. Syringomyelia related to abnormalities at the spinal level.
AETIOPATHOGENESIS
•• Syringomyelia is associated with many different pathologic conditions.
•• The numerous causes of syringomyelia are listed in Table 1.
•• The majority of cases are due to hindbrain descent of the Chiari
malformation and the syrinx is usually in the cervical spinal cord.
•• Traumatic syrinx usually develops in the vicinity of the spinal injury and is
most frequently located in the thoracic spine.
•• Syrinx associated with occult spinal dysraphism usually occurs just rostral
to the lipoma and is located in the lower thoracic and lumbar levels.
•• Myelomenigocoeles are associated with Chiari type II malformations and
the syrinx is mostly in the cervical and thoracic levels.
•• Although neoplasms, trauma, inflammation and displaced cerebellar tonsils
are the most common causes of cyst formation within the spinal cord, most
intramedullary tumour associated cysts are an entirely different condition,
in which protein rich cyst fluid is generated by the neoplasm itself.
Mechanism of Syrinx Formation

•• Syringomyelia Associated with CV Junction Anomaly:
–– The most common CV junction anomaly associated with syringomyelia
is Chiari malformation.
Chapter 22 • Syringomyelia
183
Table 1: Aetiology of syringomyelia

Abnormalities at Craniovertebral Junction
• Bone abnormalities
– Basilar invagination
– Platybasia
– Bone tumours
• Arachnoid scarring
– Trauma
– Infection
– Inflammation
• Subarachnoid space compression (hindbrain impaction)
• Fourth ventricular cyst
– Dandy- Walker malformation
• Tumours
– Intrinsic
– Extrinsic
Abnormalities at the Spinal Level
• Arachnoid scarring
– Trauma
– Surgery
– Infection
– Inflammation
• Subarachnoid space compression
– Tumour (intrinsic or extrinsic)
– Spondylosis
–– Chiari malformation represents a hind brain herniation from the

posterior fossa into the cervical spinal canal.
–– In Chiari type II malformation, in addition to the herniation of the tonsils
and vermis, there may be buckling of the medulla because of the
caudal herniation of the brainstem.
–– The exact mechanism of entry of the cyst fluid in most cases of
syringomyelia is not known.
–– Chiari believed that the fluid was present in the cord due to the
persistence of an embryonal state (hydromyelia) associated with
hydrocephalus the syrinx in his model would be of the communicating
variety.
–– Gardner proposed the hydrodynamic theory to explain the association
of hydrosyringomyelia with Chiari malformation. He postulated that
arterial pulsations of the choroid plexus induced pulse waves of
cerebrospinal fluid (CSF) that forced open and progressively distended
the central canal, because of impaired outflow from the fourth ventricle.
In Chiari malformations, the caudally displaced tonsils obstruct the
foramen of Magendie and continue to direct the pulse wave into the
central canal.
–– Williams proposed a modification of the hydrodynamic theory, in which
venous pressure changes were thought to be responsible for the
formation of hydrosyringomyelia.
–– These theories suggested that the syrinx developed and progressed
from expansion of the central canal of the spinal cord, by CSF pulse
184
pressure waves or craniospinal pressure differentials transmitted from

the fourth ventricle to the syrinx.
–– Stoodely et al. proposed two distinct mechanisms for the normal migra-
tion of fluid through the perivascular spaces: (a) systolic expansion of
the arteries in the perivascular space may force fluid through the sur-
rounding basement membranes, while in diastole, fluid may enter the
perivascular spaces from the subarachnoid space and (b) pulsation in
the subarachnoid space transmitted through perivascular spaces acts
as an impetus for flow.
–– Milhorat proposed that CSF was continually produced by the ependy-
mal cells lining the central canal and the expansion of the central canal
occurred in segments isolated by occlusion or stenosis at each end,
such as occurs with viral ependymitis.
–– Ball and Dayan proposed that the subarachnoid fluid dissects into the
spinal cord parenchyma along the Virchow Robin space, when tonsillar
impaction prevented the upward escape of CSF. The intramedullary
fluid in this theory would gradually enter the central canal.
–– Aboulker proposed a similar theory with fluid entering along the dorsal
nerve roots.
•• Syringomyelia Related to Primary Spinal Abnormalities:
–– The mechanism proposed for the development of post-traumatic
syringomyelia is that the necrotic tissue and the haematoma within the
injured spinal cord are resorbed and replaced by a cystic cavity.
–– A proposed mechanism related to scar formation is the “spinal-spinal
pressure dissociation” model, where rapid pressure equilibrium in the
subarachnoid space proximal and distal to the scar, which causes the
CSF to move into the lower pressure environment of the central canal
region of the spinal cord.
–– Spinal syringomyelic cavities may develop and fluctuate in multiple
sclerosis. Plaques are frequently found in areas adjacent to CSF path-
ways. These plaques can undergo degenerative change with resultant
syrinx formation, involving areas of plaque and spinal cord rostral and
caudal to the plaque.
–– Alternatively, a syrinx like lesion can develop, following atrophy of the
swollen spinal cord which has undergone demyelination.
–– The predilection of inflammatory lesions of the spinal cord to produce
secondary necrosis and subsequently syrinx may be a consequence
of the tight investment of the cord by pia.
Mechanism of Syrinx Propagation

•• Gardner proposed that the high pressure waves from the fourth ventricle
passing through the opening at the rostral end of the central canal produced
progressive enlargement of the fluid collection.
•• Ball and Dayan and Aboulker proposed that the fluid entering the spinal
cord parenchyma, driven by the arterial pulsations, would coalesce and
rupture into and therefore enlarge the central canal.
•• Williams proposed that the pressure differentials initiated by epidural venous
distension after normal physiologic events, such as coughing and straining
caused to and fro fluid dissection within the spinal cord referred to as slosh.
•• Oldfield proposed that the systolic pressure wave of the subarachnoid CSF
applied against the surface of the spinal cord forces the syrinx fluid to move
caudally within the cyst.
185
SYMPTOMATOLOGY
•• Most patients with hind brain anomaly related syringomyelia become
symptomatic in young adulthood.
•• The mean age at onset of symptoms was third decade.
•• Syringomyelia is generally more common in males.
•• Syringomyelia usually progresses slowly and the course may extend over
many years.
•• The condition may have a more acute course, especially when the
brainstem is affected.
•• Syringomyelia usually involves the cervical area.
•• Symptomatic presentation depends primarily on the location of the lesion
within the neuraxis.
•• The majority of cases of syringomyelia are associated with Chiari malfor-
mation. Therefore, it is essential to differentiate symptoms predominantly
due to central spinal cord cavitations from those due to hindbrain descent.
•• Symptoms Predominantly Due to Central Spinal Cord Cavitation:
–– The classic symptoms of a syrinx within the spinal cord include
dissociated sensory loss, amyotrophy and spastic paraparesis (upper
motor neuron symptoms in the lower extremities and lower motor
neuron symptoms in the upper extremities).
–– In later stages, with a larger syrinx, the symptoms may become bilateral.
–– The dissociated sensory deficit is due to damage of the spinothalamic
fibres (conveying pain and temperature sensation) in the anterior
commissure.
–– The ascending sensory fibres involved with light touch and
proprioception are usually spared.
–– The anterior commissure is damaged at the levels of the syrinx but
remains intact rostrally and caudally.
–– The resulting sensory deficit has been described as “cape like” or as a
“suspended sensory level of cuirasse” because it typically involves the
breast-plate distribution.
–– When the cavity enlarges to involve the posterior columns, position
and vibration sense in the feet are lost and astereognosis may be
noted in the hands.
–– Amyotrophy of the muscles is due to damage of the anterior horn cells.
It usually begins in the hands and extends into the proximal upper
extremities.
–– Lower extremity motor symptoms are due to destruction or compression
of the corticospinal tracts in the lateral columns. Typically, this results
in asymmetric spastic paraparesis with absent superficial reflexes,
increased deep tendon reflexes and extensor plantar responses.
–– Respiratory insufficiency, which usually is related to changes in pos-
ture, may occur. Sphincter disturbance may occur as a late finding.
–– Syringomyelic patients can develop complex regional pain syndrome
(CRPS), formerly known as reflex sympathetic dystrophy.
–– CRPS is a pain syndrome that develops after an irritating noxious event.
Typically, evidence of oedema, changes in skin blood flow, abnormal
pseudomotor activity in the region of the pain, and allodynia or hyperalgesia
is observed. The site is usually the distal aspect of an affected extremity.
–– If the syrinx extends into the medulla, syringobulbia develops, with
symmetric limb weakness, palatal weakness, wasting of the tongue,
dissociated trigeminal sensory loss and nystagmus.
186
–– Lower cranial nerve signs and symptoms are seen particularly with
basilar invagination.
–– Rarely, the syrinx cavity can extend beyond the medulla in the
brainstem into the centrum semiovale (syringocephalus).
–– Clinical symptoms associated with Chiari malformation include
headache, neck pain, cerebellar dysfunction, nystagmus, spasticity,
ataxia, diplopia and bulbar palsies (dysphagia). These symptoms tend
to develop in adolescence and early adulthood.
IMAGING
•• Magnetic resonance imaging is the best imaging modality for diagnosis
of syringomyelia.
•• It is able to demonstrate the extent of syrinx along with associated soft
tissue abnormalities of the craniovertebral junction, neoplasms, stenosis
and arachnoid scarring.
•• Imaging of the entire rostrocaudal extension of the cyst or cysts is important.
•• It also helps to see the flow and septations inside the syrinx.
•• Gadolinium enhanced images are indicated if a tumour is suspected.
•• Magnetic resonance angiography may be helpful in cases of syringomyelia
associated with vascular lesions.
•• Myelography with delayed CT performed after 4–12 hours may be used
in patients who are unable to tolerate MRI and may demonstrate contrast
accumulation in the cyst.
•• More recently, cardiac gated cine mode T2 weighted MRI has been used
to demonstrate CSF flow patterns and it has been proposed that less
pulsatile flow within the syrinx is associated with a decreased likelihood
of benefit from surgery. This modality may also be useful in distinguishing
patients with asymptomatic tonsillar descent from those with abnormal flow
dynamics who are more likely to benefit from surgery.
•• Real-time ultrasonography is rarely used for imaging syringomyelia. It is
technically more feasible in young children or in thin patients.
•• Routine radiographs may demonstrate a widened cervical canal, bony
abnormalities of the skull and CV junction, platybasia, midline keel and
assimilation of the atlas.
NATURAL HISTORY
•• The natural history of syringomyelia varies from spontaneous and complete
regression to progressive devastating neurologic deficits.
•• In spite of this lack of information on the disease’s course, it is usually
viewed, as Lord Brain described it, “relentlessly progressive”.
•• The unpredictable clinical course of syringomyelia causes difficulties and
controversies regarding management.
•• The possibility that a syrinx may spontaneously disappear may warrant a
more conservative approach in certain instances.
•• It is noted that patients with a nearly normal sized spinal cord were more
likely to have a benign clinical course and if significant spinal cord dilation
was seen, the symptoms tended to progress.
MANAGEMENT
•• Syringomyelia is caused by many different conditions and thus may require
different treatments.
187
•• Another problem, encountered in interpreting the available information,

is that a fairly long follow-up is needed because syrinx progression may
occur slowly over time.
SELECTION OF PATIENTS FOR SURGERY

•• Operative management of syringomyelia should be considered when there
are progressive neurological deficits by clinical criteria or when sequential
imaging techniques show progressive enlargement of the syrinx.
•• With the availability of high resolution MR images more and more non-
distended intramedullary cavities are detected.
•• Patients with little or no neurologic impairment and non-distended syrinx
cavities should be followed-up with serial neurological examination and
imaging before surgery is recommended.
•• Size of the syrinx cavity alone should not be used as an indication for surgery.
•• The likelihood of improvement of a symptom or symptoms following surgery
should influence the decision to recommend surgery.
•• It is known that not all the clinical manifestations of syrinx, which occur, with
abnormalities of the CV junction, respond equally to surgery.
•• The main goal of surgery is to arrest progression of neurological deficits.
•• Suboccipital headache caused by tonsillar impaction responds well to
adequate decompressive therapy.
•• Pyramidal tract manifestations and spinothalamic sensory loss improve,
as the pressure of the cyst on these pathways is reduced.
•• Weakness and atrophy of the hands show little improvement because of
destruction of corresponding anterior horn cells.
•• Similarly, dysaesthetic pain, which is a form of denervation dysaesthesia
due to destruction of ascending spinal pathways with a thalamic projection,
responds poorly to decompressive therapy.
•• Each patient must be judged individually, keeping in mind that progression
of symptoms can sometimes occur rather abruptly.
•• Because some of the neurologic deficits tend to become fixed once they
develop, most patients with Chiari malformation and a distended syrinx
should be candidates for surgery.
•• Chiari malformation presenting with lower cranial nerve involvement or
symptoms of direct brainstem compression should also be candidates
for surgery.
Surgical Management of Syringomyelia Associated with

Craniovertebral Junction Anomalies
•• The management strategy follows a “top down” rule.
•• Treatment always begins by addressing hydrocephalus, if it is present. A
VP shunt placed in patients with hydrocephalus may relieve both cerebellar
ectopia and dilatation of the central canal as well.
•• Early surgical techniques attempted to address syrinx and Chiari
malformation separately with a decompressive procedure directed at
the foramen magnum for Chiari and a myelotomy or shunting procedure
directed at the syrinx.
•• Most patients with Chiari malformation and syringomyelia are treated with a
sub-occipital decompressive craniectomy, as well as cervical laminectomy
to the distal tips of the cerebellar tonsils.
•• The goal of the surgery is to relieve cord compression and to re-establish
adequate CSF flow.
188
•• The simple bony decompression without intradural exploration alone

relieves the ball valve effect of Chiari malformation. There is controversy
regarding the extent of decompression required to alleviate symptoms.
•• Dural bands and arachnoid adhesions maybe freed, although several
surgeons have stressed the importance of avoiding undue manipulation
of the subarachnoid space. Manipulation of the tonsil has also become a
matter of considerable debate.
•• If the tonsils cannot be mobilised, a tube or silastic wick is placed to maintain
the patency of the fourth ventricle outlet in the midline.
•• In the presence of dense arachnoid adhesions, a shunt tube is placed
between the fourth ventricle and the intact subarachnoid space around
the spinal cord.
•• The opened dura is reconstructed capaciously using a graft.
•• In and patients who underwent decompression with and without duraplasty
and no reduction of hydromyelia, patients without duraplasty had a
significantly worse outcome compared to those with duraplasty.
•• In patients in whom there is no neurological improvement without
radiological collapse of the syrinx cavity, 3–6 months after foramen magnum
decompression, a syringoperitoneal shunt is inserted.
Management of Syringomyelia Related to

Primary Spinal Abnormalities
•• The indications for surgery in patients with primary spinal syringomyelia
are debatable.
•• As a rule, relatively rapid loss of neurological function facilitates the decision
for surgery.
•• The various management options for primary syringomyelia include:
–– Syringostomy
–– Shunting to the subarachnoid, pleural or peritoneal spaces
–– Endoscopic release of septations.
•• Syringostomy:
–– Is the oldest and simplest surgical procedure.
–– It involves a laminectomy at the appropriate level and a dorsal
longitudinal incision through the thinned out spinal cord into the syrinx
cavity.
–– Incisions are usually made in the midline or just posterior to the dorsal
root entry zone.
–– Intra-operative real-time ultrasonography is useful in locating the
largest section of the syrinx and where it is most superficial and in
guiding the drainage/shunt catheter into the optimal position.
–– Problems with syringostomy include locating the optimal myelotomy
site, minimising the risk of tissue damage and keeping the stoma patent.
–– Myringostomy tube can be introduced through a small 3 mm midline
myelotomy at the level of the maximum syrinx enlargement, to
maintain the syringo-subarachnoid communication.
•• Shunting:
–– May achieve syrinx drainage into the pleural, peritoneal or subarachnoid
spaces.
–– A small myelotomy is performed, either in the midline or at the dorsal
root entry zone.
–– A variety of valveless silastic catheters have been used.
189
–– The catheter may be inserted cephalad or caudal, depending on the

neurosurgeon’s preference. The distal end of the catheter may then
be placed in the subarachnoid space or tunnelled into the pleural or
peritoneal space.
–– Another procedure which was tried in the past is terminal ventricu-
lostomy. The terminal ventricle is the dilated portion of the central
canal that extends below the tip of the conus medullaris into the filum
terminale. This procedure is suitable only in patients with symptoms of
syrinx without Chiari malformation.
•• Endoscopic Release of Septations:
–– At the spinal level it involves open or endoscopic dissection of sub-
arachnoid adhesions and the enlargement of the local subarachnoid
space by expansile duroplasty or creation of a pseudomeningocoele.
–– As microsurgical skills progress lysis of local adhesions may prove to
be an excellent treatment option for syringomyelia that can prevent the
need for implantation of a foreign body. More minimally invasive treat-
ments for syringomyelia have been evolving.
•• Abe have classified syringomyelia into five types and have suggested the
most appropriate treatment for each type.
•• Type I Syringomyelia:
–– Associated Chiari malformation and MRI, shows wedge shaped herni-
ated tonsils to be occupying the cisterna magna with the rostral end of
the syrinx looking conical and there is no obliteration of the caudal part
of the fourth ventricle.
–– As these findings suggest the herniated tonsils to be compressing the
brainstem and spinal cord and mechanically obstructing the CSF flow
at the foramen magnum, a foramen magnum decompression with or
without duraplasty alone is required.
•• Type II Syringomyelia:
–– There is basal arachnoiditis, usually with a history of difficult labour.
–– MRI of these patients reveals the cisterna magna to be narrowed by
scar tissue or by herniated tonsils. However, the tip of the tonsils is
rounded and a cavity resembling the subarachnoid space may be seen
in the region of the cisterna magna.
–– In addition, the upper end of the syrinx is rounded and the lower part
of the fourth ventricle will be well visualised.
–– These MRI findings suggest that the foramen magnum is not mechani-
cally obstructed by herniated tonsils but rather by arachnoid scarring
due to arachnoiditis.
–– The treatment consists of foramen magnum decompression followed
by placement of a shunt tube from the fourth ventricle to the ventral
cervical subarachnoid space to prevent reobstruction of the foramen
of Magendie.
•• Type III Syringomyelia:
–– MRI reveals a direct communication of the syrinx with the fourth ven-
tricle via a patent central canal and is associated with hydrocephalus.
–– The treatment suggested is foramen magnum decompression followed
by opening of the membrane obstructing the foramen of Magendie,
which will equalise the pressure between the ventricular system and
the subarachnoid space.
190
•• Type IV Syringomyelia:
–– Have obliteration of the subarachnoid space around the spinal cord
due to arachnoid scarring with a normal craniovertebral junction.
–– There is extension of the syrinx both rostrally and caudally from the
site of scarring.
–– When scarring is localised, a syringosubarachnoid shunt rostrally from
the site of scarring is advised.
–– When the scarring is not localised a syringoperitoneal shunt is the
treatment recommended.
•• Type V Syringomyelia:
–– Patients in whom no associated lesions could be found on MRI or with
cine MRI, either a syringosubarachnoid shunt or a lumboperitoneal
shunt is suggested as the most effective treatment.
Results of Surgery
•• The five most common clinical manifestations of syringomyelic patient
are sensory deficit, motor weakness, sub-occipital pain, dysaesthetic pain
and spasticity.
•• Of these, headache and spinal pain responded best to surgery, presumably
because pressure and distension of the dura were relieved.
•• Weakness of lower limbs and spasticity improvement can be seen in two
thirds of patients but weakness and atrophy of hands often failed to improve.
CAUSES OF SURGICAL FAILURE AND

THEIR PREVENTION
•• Patient prognosis and long-term response to surgery remain highly variable,
which reflects the wide divergence in clinical presentation and surgical
management.
•• Many patients who initially improve with surgery frequently return to their
pre-surgical state or sometimes even become worse and continue to
deteriorate.
•• Whether this denotes the natural course of the disease in a subset of this
patient population is not known.
•• Because the natural history of this condition is poorly understood, the true
benefits of surgery over what may be the natural history of this condition
are poorly understood.
•• Progressive neurological deficits after the initial operation should lead one
to suspect post-operative cerebellar ptosis with tethering and scarring of
the cervical spinal cord and recurrent syringomyelia.
•• The herniated tonsils and vermis become adherent to the duraplasty,
leading again to obstruction of CSF flow and reappearance of syringomyelia.
•• These patients present severe headache due to stretching of an inad-
equately supported duramater of the posterior fossa, which is innervated
by nociceptive fibres, which has contribution from the trigeminal nerve.
•• Apart from an oversized craniectomy, there are other possible causes
for scar formation between the dural graft and the cord. Post-operative
arachnoid scarring can be caused by insufficient haemostasis, obex plugging
with muscle or autologous graft material or a large pseudomeningocoele.
•• Blood and its breakdown products or muscle proteins may cause severe
arachnoiditis.
•• This may be provoked by William’s technique of leaving the dura open
after decompression.
191
•• Treatment of post-operative tethering at the level of the foramen magnum is

possible, but can be extremely dangerous and can lead to life-threatening
complications.
•• Post-operative adhesions of artificial graft material to underlying structures
and adhesions related to pseudomeningocoele can be released by sharp
dissection.
•• Patients with a history of meningitis or with dense adhesions of autologous
grafts are poor candidates for re-operation.
•• Shunting procedures for syringomyelia are associated with potential
complications. The tube may become kinked or displaced. It may be blocked
internally by arachnoid scar, proteinaceous fluid or tissue debris.
Section III: Head Injuries
23
CHAPTER Biomechanics of
Head Injury
Deepak Agrawal  Ashok Kumar Mahapatra
INTRODUCTION
•• Head injuries are very common and, apart from treatment, a very important
area to which attention must be given is prevention.
•• Prevention has three stages:
–– To stop the accident from occurring
–– To reduce the injuries on impact
–– To minimise the risk of subsequent complications.
TYPES OF MECHANICAL FORCES

•• Mechanical forces leading to head injury can be categorised as static or
dynamic (Flow chart. 1).
•• Dynamic Loading: Dynamic loading is more commonly seen and is defined
as input force applied to the cranium over a very short period of time (usually
less than 50 ms). Dynamic loading may further be subclassified as “impact
loading” and “impulsive loading”.
Flow chart. 1: Types of mechanical forces involved in head injury
Chapter 23 • Biomechanics of Head Injury
193
•• Impact Loading: Impact loading, which is the more common type, is a

combination of contact and inertial forces.
•• Contact injuries:
–– Contact injuries result from forces that occur during direct impact.
–– The impact results in complex mechanical events that occur both near
and distant from the point of contact (contact phenomenon).
–– Contact injuries typically cause focal injuries, but they do not cause
diffuse brain injury.
–– Neural brain damage by this mechanism is typically superficial and
localised to the immediate vicinity of the skull injury.
•• Local effects of contact injuries:
–– These include depressed fractures, linear fractures, basilar skull frac-
tures, extradural haematomas and coup contusions.
–– Depressed skull fractures are a result of a concentrated force immedi-
ately beneath the impacting object.
–– The apex of the bone which is formed by the inner table breaks first
and results in a linear fracture.
–– In children, sutural diastasis may occur.
–– Direct impact to the face, mastoid or occiput, results in basilar skull
fractures.
–– Local bending of bone also results in tearing of dural vessels, leading
to epidural haematomas.
–– When the in-bent skull recoils back to its position, negative pressure
is created which results in tensile strain on the underlying pial vessels
and brain resulting in a focal contusion (Table 1).
•• Remote effects of contact injuries:
–– These are due to skull distortion and stress waves.
–– Stress waves may also account for the remote contact effects such as
basilar fractures, potential haemorrhages and intracerebral haematomas.
•• Inertial injuries:
–– These are commonly called acceleration and deceleration injuries.
–– Acceleration injury of the head causes either a functional or a structural
failure of neural and vascular structures, where the severity and extent
of disruption are linked to the magnitude, rate, duration and type of
inertial loading.
–– Three types of acceleration may occur in inertial injuries:
1. Translational acceleration occurs when the brain moves in a
straight line at its centre of gravity, i.e. pineal gland.
Table 1: Clinical classification of head injuries

Skull fractures Focal brain injuries Diffuse brain injuries
Vault Contusion Concussion
Linear Coup Mild
Depressed Contrecoup Classic
Intermediate
Basilar injury Haemorrhagic Diffuse axonal
Extradural
Subdural
Intracerebral
Petechial
Other
Section III • Head Injuries
194
2. Rotational acceleration occurs when brain tissue moves around

its static centre of gravity.
3. Angular acceleration occurs when there is movement of the
centre of gravity in an angular manner. Angular acceleration is
a combination of both translational and rotational acceleration.
Angular acceleration is most commonly encountered clinically
and the centre of angulation is usually the mid-cervical and lower-
cervical regions.
•• Three zones of the brain (e.g. surface, intermediate and deep) can be
affected differentially as the duration of acceleration increases.
•• Structural damage to superficial vascular tissue (bridging veins and pial
vessels) occurs in short acceleration duration with a large acceleration
magnitude, whereas deeper brain tissue injury occurs in longer duration
acceleration with lesser acceleration magnitude.
•• Impulsive Loading:
–– Impulsive loading occurs when the head is put into motion or when the
motion of a moving head is suddenly arrested without the head itself
being struck or impacted.
–– A blow to the thorax or face can set the head into violent motion without
direct impact on the skull. Other examples include fall from a height or
being thrown off a moving vehicle.
•• Static Loading:
–– Static loading is uncommon and is defined as input force applied to the
load relatively slowly (over 200 ms).
–– Typical examples of static loading are injuries from slowly m oving vehi-
cles or earthquakes that trap the head against rigid structures resulting
in slow crushing of the skull.
–– Static loading causes multiple comminuted fractures of the vault or
base of skull.
MECHANISM OF SPECIFIC INJURIES

Concussion and Sports Injuries
•• Concussion, or mild traumatic brain injury (TBI), occurs in many activities,
mostly as a result of the head being accelerated.
•• Angular or rotational head motions cause transient electrophysiologic
dysfunction of the reticular activating system in the upper midbrain, caused
by rotation of the cerebral hemispheres on a relatively fixed brainstem.
•• In this type of injury, most of the strain is insufficient to cause structural
damage, but results in biochemical and ultrastructural changes, such as
mitochondrial ATP depletion.
Contrecoup Contusions
•• The predominant mechanism for contrecoup contusions is head accelera-
tion (inertial effects).
•• The term is a misnomer, as actual impact is not necessary.
•• In situations where the head undergoes impulsive loading, contrecoup
lesions occur solely due to acceleration effects.
Chapter 23 • Biomechanics of Head Injury
195
Subdural Haematoma
•• Acute subdural haematoma is due to disruption of surface vessels, usually
bridging veins.
•• Disruption of bridging veins mostly occurs from inertial force and not from
contact force.
•• The acceleration is of short duration with a high strain ratio loading. Hence,
acute subdural haematomas are usually associated with diffuse axonal
injury (DAI) and cerebral contusion.
Diffuse Axonal Injury

•• Diffuse axonal injury is considered as an extreme form of concussional injury
and may be caused by long duration rotational or angular acceleration.
•• The extent of axonal damage depends upon the magnitude, duration and
rate of angular acceleration.
•• Neuronal damage occurs in a centripetal fashion, from the cortex inwards
to the brainstem, as the force of injury increases.
•• The direction of acceleration is important in the production of DAI.
•• Pure sagittal acceleration may result in a milder DAI, whereas angular
acceleration in the coronal plane is associated with a higher incidence of
severe DAI.
Shaken Baby Syndrome

•• Shaken baby syndrome (SBS) is characterised by a constellation of clinical
findings, including subdural bleeds, retinal haemorrhages and fractures
of the extremities and ribs, with no external evidence of cranial trauma.
•• Injury biomechanics analysis of the reported SBS levels of rotational velocity
and acceleration of the head for their injury effects on the infant head-neck.
Resulting forces were compared with experimental data on the structural
failure limits of the cervical spine in several animal models as well as human
neonate cadaver models.
•• These studies clearly showed that cervical cord and brainstem damage
would occur prior to and, more importantly, at lower levels of rotational
velocity and acceleration then purported in SBS.
•• The very basis of SBS therefore remains controversial.
FUTURE RESEARCH
•• At the cellular level, plasma membrane disruption may be the earliest
cellular outcome from a mechanical trauma.
•• The increase in membrane permeability due to such disruptions may
therefore play an important role in the initiation of deleterious cascades
following brain injury.
•• Spontaneous electrophysiological activity of injured cultures can then be
monitored to get an insight into the neuronal effects of TBI.
•• The outcome from such ongoing research may help in our knowledge of the
pathophysiology and biomechanics of head injury leading to improvement
in preventive measures.
24
CHAPTER
Pathology
Sankar SK  Anita Mahadevan
INTRODUCTION
•• Road traffic accidents and falls are the major cause of traumatic injuries in
62% and 22% respectively, followed by violence in 10% of cases.
•• People in their prime and in the productive age group of 20–30 years are
affected maximally, men being at greater risk.
•• Alcohol has been a major risk factor for traffic injuries, falls, violence, work
related accidents and others (Table 1).
CAUSES OF BRAIN DAMAGE—TRAUMATIC

BRAIN INJURY
•• The different causes of TBI are listed in Table 2.
Focal Brain Injury

•• Brain damage in non-missile head injury is classified as “focal” or “diffuse”.
•• The focal damage includes contusion and lacerations on the surface of
the brain and intracranial haematoma and raised ICP as a secondary
phenomenon.
•• Focal injuries result from localised damage, found in nearly 58% of patients
with severe head injuries and 66% of deaths associated with head injury.
•• Contusions:
–– Contusions are caused by blunt contact of the brain with various bony
surfaces of the skull.
–– The pia arachnoid is intact over a contusion, but is torn in a laceration.
–– Recent contusions are haemorrhagic and when superficial, are charac-
teristically restricted to the crests of the gyri, but often extend into the
sulci and the underlying white matter.
Table 1: Factors modulating primary brain injury

a. Precise type, location, extent (size) of injury
b. Type → Moving vehicle
→ Missile—gun shot, stone throw
→ Fall or assault (blunt/sharp/size of impact)
Blunt Injury → Wide damage, long-term psychological impairment, poor recovery
c. Biological factors in victim – Pre-existing disease
– Psychological status
– Nutritional status prior to injury
– Consumption of sedative, alcohol, psychoactive drugs
Chapter 24 • Pathology
197
Table 2: Causes of brain damage—traumatic brain injury

A. Focal lesions:
• Scalp laceration
• Fracture of the skull
• Surface contusions/lacerations of the brain
• Intracranial haemorrhage - Extradural
- Subdural
- Subarachnoid
- Intracerebral
• Damage secondary to raised intracranial pressure (ICP)
• Damage to vessels due to trauma → dissection → thrombosis → large territory infarction
B. Diffuse lesions:
• Diffuse axonal injury (DAI) (secondary to stretching/rupture of axons)
• Diffuse brain swelling (secondary to vasomotor paralysis → vasodilatation → vaso-
genic oedema)
• Diffuse small vessel injury—(secondary to acceleration/deceleration → rupture of small
vessels)
C. Sequelae of head injury:
DAI + hypoxic brain damage → Severe disability, vegetative state.
(Traumatic injury to the scalp and skull are not dealt with in this chapter)
–– Healed contusions are commonly found in chronic epileptics, with

repeated history of falls and are of medico legal importance.
–– Unlike in all other age groups, the contusion in infancy (battered baby
syndrome) results in tears in the sub-cortical white matter and inner
layers of the cortex, particularly in the frontal and temporal lobes and
the cortex above and below the Sylvian fissures.
–– The most common sites of contusion in closed head injuries are the
under surface, and polar regions of the frontal and temporal lobes
followed by their lateral surfaces.
–– Various forms of contusions provide clues about their evolution:
–– Fracture contusion: It is related to the site of fracture, common in the
frontal lobe.
–– Herniation contusion: Parahippocampal gyrus and cerebellar tonsils
impacting against the tentorium and foramen magnum, respectively,
follow blunt impact on the vortex.
–– Gliding contusions: Adjacent to the superior sagittal sinus, (Para
sagittal contusions) haemorrhages in the superficial cortex and white
matter, caused by anteroposterior gliding movement of the brain with
respect to the dura and falx cerebri. The parasagittal bridging veins
entering the sinus may be torn resulting in haemorrhage. They are
usually bilateral and asymmetric, and associated with diffuse brain
damage and DAI.
–– Coup contusion: It occurs at the site of impact in the absence of
fracture. The extent depends on the size of contact between the skull
and the striking object and the accelerating force transmitted to the
underlying brain.
–– Contrecoup contusion: It occurs in the brain away from the site of
impact, usually in a diagonally opposite anatomical area, caused by
deceleration of the moving head against bone.
–– Contusion index: For an objective evaluation of the extent of con-
tusion and for clinical correlation, Adams developed a quantitative
198
approach. The index is the product of the extent and depth of contu-
sional damage.
•• Intracranial haemorrhage:
–– It is a common complication of severe forms of blunt head injury where
the patient deteriorates after a period of lucid interval.
–– In traumatic intracranial haemorrhage, there may be bleeding into the
extradural, subdural or subarachnoid space, the brain parenchyma
and into the ventricles.
•• Extradural haematoma:
–– EDH occurs in approximately 2% of all forms of head injury and in
5–15% of fatal head injuries.
–– In the majority, there is associated skull fracture. It usually follows a fall or
road accident, but, in children, it can occur in the absence of a fracture.
–– The haemorrhage originates from the ruptured meningeal vessels and
enlarge by stripping the endosteum and dura from the skull.
–– Nearly 50% of EDHs occur in the region of the squamous part of the
temporal bone, which is thin and easily fractured by blunt impact, tear-
ing the middle meningeal artery.
–– Posterior fossa EDH can also occur and follows injury to the middle
meningeal vein, diploic vein, dural sinuses or tear of the carotid artery
before it enters the intracranial dura along the base of the skull.
–– The size of the EDH can increase by up to 50% till the end of the 2nd
week following the injury, after which it starts shrinking by organisation,
and if small, may resolve completely by 6–8 weeks after injury.
However, most patients with significant EDH deteriorate rapidly and
require early surgical intervention.
–– These haematomas have a pink spongy appearance like “cooked
meat”, indicative of thermal injury, unlike the usual dark colour. For it
to develop the victim needs to be alive and the EDH follows the pattern
of external charring.
•• Subdural haematoma:
–– Acute SDHs are found in approximately 10–30% of all patients with
head injuries.
–– Subdural haematoma (SDH) is caused by rupture of bridging veins,
connecting the superior surface of the brain to the sagittal sinus.
–– These types of lesions are common in adults and the elderly following
even trivial trauma or whiplash movement of the head.
–– Some SDHs are of arterial origin.
–– It may occur in combination with intracerebral haemorrhage, and the two
can communicate with each other, when it is referred to as “burst lobe”.
–– Unlike EDH, SDH tends to spread diffusely to cover the entire hemi-
sphere. In young adults, they are common following falls, assaults and
vehicular accidents.
–– Occasionally, clear or xanthochromic fluid may accumulate in the
subarachnoid space resulting in hygroma and compression of the
underlying brain. This is considered to be due to a valve like arachnoid
tear causing unidirectional flow of CSF into the subdural space that
mixes with liquefied blood.
•• Intracerebral haemorrhages:
–– They are often multiple and most frequent in the white matter of the
frontal and temporal lobes and, occasionally, the cerebellum.
199
–– The commonest sites of intracerebral haematoma are temporal,

followed by the frontal lobe, the same sites where contusions occur
most frequently.
–– Histological examination of the brain with basal ganglionic haemorrhage
(BGH) resembles those noted following DAI, although both these
pathological entities can coexist.
–– Vascular damage and microhaemorrhages predominate, the area
bordered by zones of axonal pathology. These suggest that the
haematomas in the deep cerebral parenchyma are caused by rupture
of cerebral blood vessels at the time of impact.
–– The frequent coexistence of DAI and BGH suggests that the bio-
mechanics of the evolution of the two lesions is essentially similar,
requiring angular acceleration of the head as in the case of a road
traffic accident than in a free fall.
•• Intraventricular haemorrhages:
–– Intraventricular haemorrhages (IVH) are also usually associated with
DAI.
–– Subependymal haemorrhages due to rupture of veins with a breach
of the ependyma and corpus callosal haemorrhages related to DAI
extending to the fornix and septum and rupturing into the ventricle
were common.
–– In cases of IVH, the axonal bulbs are particularly observed in the sub-
ependymal area.
Diffuse (Multifocal) Brain Damage

•• This diffuse pathology is the cardinal mechanism for prolonged uncon-
sciousness in nearly 50% of patients with no expanding intracranial mass.
•• These diffuse lesions are seen in nearly one-third of all head injury deaths.
•• Four types of diffuse cerebral injury that follow trauma are:
1. Diffuse vascular injury
2. Diffuse brain swelling
3. Diffuse ischaemic brain damage
4. DAI.
Diffuse Vascular Injury
•• Diffuse vascular injury, which is most serious and is found in patients who
succumb soon after head injury.
•• Multiple small haemorrhages are frequently seen soon after a head injury,
especially in those who die instantaneously after impact.
•• These haemorrhages are likely to be mechanical in origin caused by
mechanical stretching and shearing of small blood vessels.
•• As they are usually seen in the brainstem, they are indicative of brain
damage that is incompatible with life.
•• They are usually conspicuous in the white matter of the anterior frontal
and temporal lobes, periventricular white matter, thalamus and brainstem.
•• These microscopic haemorrhages are, especially, present around small
arterioles and venules with disruption of the vessel wall.
•• The perivascular distribution of axonal retraction bulbs suggest shearing
and stretching of the axons by the mechanical forces, though vessels
themselves were not torn, because of the differential threshold of reaction
to acceleration deceleration impulses.
200
•• Damage to blood vessels following injury:

–– The main vessels that show evidence of tear are the vertebral and the
internal carotid arteries.
–– The internal carotid artery can get traumatised in its sigmoid portion as
it traverses the bony canal in the base of the skull following a fracture. It
can manifest as a pseudoaneurysm, the blood accumulating between
the media and the adventitial sheath or dissecting the media, into two
layers.
–– Carotico-cavernous fistula is another rare sequel of head injury.
Features of Raised Intracranial Pressure and Brain Swelling
•• Following TBI, three types of brain swelling are observed:
1. Swelling adjacent to a contusion and intracerebral haemorrhage
2. Diffuse swelling of the unilateral cerebral hemisphere
3. Bilateral diffuse brain swelling.
•• The essential mechanism for all the types appear to be vasogenic, due to
deranged vasotonicity or vasoparalysis, mediated by neurotransmitters,
ionic imbalance and physical injury.
•• Consequent to contusion and haemorrhage, the breakdown in the blood
brain barrier (BBB) causes localised vasogenic oedema.
•• Diffuse swelling of one side of the hemisphere is usually seen in relation
to an ipsilateral acute subdural haematoma.
•• An epileptic seizure alone or a large supratentorial tumour pre-existing
alters the BBB further, aggravates the oedema and herniation.
•• The supratentorial-expanding lesion, with raised ICP, causes downward
displacement of the brain, the parahippocampal gyrus and uncal herniating
down the tentorial opening resulting in pressure necrosis.
•• If the ICP is due to an expanding lesion infratentorially, there is upward
herniation of the vermis, the tentorial margin producing a groove.
•• The other neuropathological features of raised ICP include supracallosal
transfalcine cingulate gyrus herniation, contralateral grooving of the cerebral
peduncle (Kernohan’s notch), due to compression against the sharp
tentorial margin, infarction in the territories of the anterior and posterior
cerebral arteries, anterior choroidal artery and superior cerebellar arteries.
•• Some of the lesions can be haemorrhagic due to pressure on the veins
around the brainstem, resembling a venous infarct.
•• Rapid downward displacement of the cerebellum and brainstem manifests
as cerebellar tonsillar herniation through the foramen magnum resulting in
compression of the medulla and death.
Ischaemic Brain Damage
•• Ischaemic damage to the brain is common in fatal head injuries.
•• The lesions are more common in the hippocampus and basal ganglia than
in the cerebral cortex and cerebellum.
•• Episodes of hypoxaemia, raised ICP, transient failure of cerebral perfusion
pressure due to fall in cerebral blood flow (CBF), associated cardiac arrest
and status epilepticus at the time of injury contribute to the ischaemic insult
and form an important cause for mortality and morbidity.
•• The hippocampus is selectively vulnerable to a variety of hypoxic events
like cardiac arrest, status epilepticus and hypoglycaemia and is involved
in nearly 84% of cases.
•• A post-traumatic electrical storm, flood of excitatory neurotransmitters
like glutamate and vascular leak are some of the events contributing to
the ischaemia.
201
•• Using transcranial Doppler ultrasonography, vasospasm has been demon-

strated in severely head injured patients, which contributes to post-traumatic
hypotension.
•• These events of hypotension, and reduced CBF cause ischaemic lesions
in the cerebral arterial territories, especially at the watershed zones of the
anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior
cerebral artery (PCA) territories.
•• Gross examination of the brain may look normal, but histological examina-
tion reveals laminar necrosis.
•• These patients have relatively normal CT features, but the recovery is poor
and they may become vegetative.
•• As the axonal damage can be identified on postmortem, by microscopy,
the term DAI is better used as a histological entity as defined by Adams
reserving the term, diffuse brain injury (DBI) to connote the clinical state.
•• Sahuquillo also advocated the use of the term DBI to describe patients
rendered immediately unconscious on impact and do not show any mass
lesion on the admission to CT scan.
•• DAI is now defined as the occurrence of diffuse damage to the axons in
the cerebral hemispheres, in the corpus callosum, in the brainstem and,
occasionally, in the cerebellum resulting from head injury.
•• Three distinct structural abnormalities are recognised in the pathology of DAI:
1. Focal lesions in the corpus callosum.
2. Focal lesions in one or both dorsolateral quadrants of the rostral brain-
stem adjacent to the superior cerebellar peduncle.
3. Diffuse damage to axons, especially in the corona radiata and other
long fibre tracts.
•• It is conceivable that DAI encompasses a spectrum of pathological changes,
correlating with severity of injury, beginning with the concussive syndrome
leading to minor cerebral injury to severe forms of brain impairment, which
include immediate coma with decerebrate posturing, prolonged coma and
incomplete recovery.
•• These observations have led to grading of DAI for clinical correlation
(Tables 3 and 4).
•• In the initial stages after injury, the focal lesions in the corpus callosum
and dorsal brainstem are haemorrhagic, usually unilateral and asymmetric
when bilateral.
•• From the corpus callosum, they may extend down to involve the septum
and fornix.
•• With progression of time, the lesions become brown leading to gliotic scars
and tiny pale infarcts.
•• On histological examination, the initial haemorrhage is perivascular, later
extending to the surrounding tissue.
•• Silver impregnation and immunohistochemical stain using antibody to
neurofilament (NF) reveals numerous axonal swellings adjacent to the
focal lesion 15–18 hours after injury.
•• At 6 hours post-injury, the axons were only swollen and varicose without
disconnection while, at 24 hours, they appeared grossly swollen and formed
bulbs/spheroids, indicating disruption and interrupted axoplasmic flow.
•• The axonal pathology in those surviving less than 8 hours could be
identified only by immunohistochemical staining with NF antibodies, but
not by silver stains.
202
Table 3: Grading of diffuse axonal injury

Grade I Only histological evidence of axonal damage in white matter without focal
lesions in corpus callosum, brainstem. Complete or partial lucid interval
Grade II Widely distributed axonal injury along with focal lesions in corpus callosum.
Partial lucid interval
Grade III Diffuse axonal damage with focal lesions in corpus callosum and brainstem.
Did not talk—No lucid interval
Identification: Survival for 18–20 hours: visible axonal pathology—Silver stain (30%).
Survival for 2–3 hours: visible axonal pathology by antibody to b-APP (92%
cases)
Pathogenesis: Primary axotomy—shearing of axolemma and resealing in 60 minutes after
acceleration/deceleration injury at Node of Ranvier
Secondary axotomy—Multiple foci of axonal injury
→ At Node of Ranvier form Nodal bulbs
→ At Internodes form axonal swelling 15 minutes after injury
Table 4: Diffuse axonal injury

Evolution: Early—Haemorrhagic 3 days—Pale, rarefied
Weeks-Months—Residual haemosiderin
Axonal injury: Disruption of axolemma (in the absence of infarcts and axonal swelling
other lesions)
Survival days: Multiple axonal swellings and oval/round bulbs at the end
Survival weeks: Clusters of microglial cells in white matter.
Survival months: In vegetative state—Wallerian degeneration in white matter
• Lower incidence of lucid interval
• Skull fracture, surface contusions, basal ganglia haematomas—common
•• Recent studies highlighted the utility of immuno-histochemistry using anti-

bodies to ubiquitin and beta-amyloid precursor protein (b-APP).
•• Frequent involvement of the brainstem in cases of DAI indicates that this
lesion is probably the common structural basis for persistent disability or
the vegetative state so often seen in severe DAI.
•• The involvement of the brainstem is almost always accompanied by similar
lesions in the corpus callosum and deep cerebral white matter and less
frequently related to haemorrhagic areas.
•• The medulla oblongata is relatively spared in DAI.
•• The other pathological hallmark of DAI is diffuse microglial cells proliferation,
at places forming clusters that resemble the early encephalitic process.
Cytokines secreted by these cells further aggravate tissue damage through
Ca++ ion influx. This feature may persist for a few days to assist in scaveng-
ing the tissue breakdown products.
•• The most characteristic findings on EM study of human DAI were separation
of the myelin sheath and detachment of the axolemma from myelin,
swelling of axons filled with cytoskeletal components and mitochondria,
and extrusion of axonal contents through the tear to the exterior.
Fat embolism (small haemorrhages):
•• Fat embolism is a well-recognised, though relatively uncommon cause
of progressive neurological deterioration without an acute intracranial
expanding lesion.
203
Table 5: Pathophysiology of head injury

Early traumatic process (not an event):
Traumatic brain injury → Acute perturbation → Mechanoporation in neurons lasting from min-
utes to 3–4 hours
Transient separation of cell membrane lipid layer from protein:
Components—receptors, channel proteins
↓
Sonic influx of K+ inside and Na+, Ca++, Cl– to outside
↓
Closure of defect by Ca++ activated lysolecithin patching and membrane fusion
Mild injury: Return to normal after few seconds to a few minutes (mild contusion)
Severe injury: Ca++ → severe cell toxicity
•• Usually one finds multiple petechial haemorrhages in the white matter.

•• Occasionally, the classical petechial haemorrhages may be absent in spite
of extensive fat embolism.
•• In patients with multiple injuries with fracture, the brain needs to be scruti-
nised for fat embolism by staining a frozen section of the suspected area
with Oil Red O. The intravascular fat stains bright red. In pregnant women,
amniotic fluid embolism needs to be suspected.
•• In addition, multiple haemorrhages may be found due to thrombocytopaenia
secondary to drug reaction, sepsis and small vessel diseases.
PATHOLOGY OF TRAUMATIC
HEAD INJURY IN CHILDREN (TABLE 5)
•• The pattern of intracerebral injury in infancy differs from that described in
adults due to:
–– Increased elasticity and moldability of the infant’s skull due to suture
patency
–– Softer consistency of brain due to incomplete myelination
–– Shallow cranial vault.
•• In children, fracture of the skull is not uncommon as the skull is thin and
breaks easily with impact.
•• The finding of a subdural haematoma suggests “shaken baby syndrome”,
a form of child abuse, though perinatal trauma needs to be kept in mind.
•• Subdural haematoma can occur due to rupture of bridging superficial
cerebral veins, tentorial laceration with rupture of the straight sinus, trans-
verse sinus, vein of Galen and laceration of falx with rupture of the inferior
sagittal sinus.
•• Occipital osteodiastasis due to traumatic separation of the cartilagenous
joint between the squamous and lateral aspects of the occipital bone (com-
mon with breech delivery) results in posterior fossa subdural haematoma.
•• Other causes of subdural haematoma in children include birth trauma,
bleeding diathesis, meningitis (Haemophilus influenzae) and shunt surgery.
•• Epidural haematomas are infrequent in infants, possibly due to the intrad-
iploic course of the middle meningeal artery until the skull is fully ossified
and the fontanelle are closed.
•• Head trauma in infants is characterised by haemorrhagic tears in the
cerebral white matter, unlike in adults who develop surface cortical lesions
only following contusion.
204
•• Epilepsy has long been established as a late consequence of head injury

and is related to the severity and type of injury. Depressed skull fracture,
cortical laceration and parenchymal haematoma contribute to increased
risk of post-traumatic epilepsy.
OTHER AREAS
Brainstem
•• The clinical features of altered sensorium, hypertonicity, decerebrate
rigidity, bilateral dilatation of pupils and absence of cold caloric response
following traumatic injury indicate the anatomical localisation of damage
to the brainstem.
•• Deteriorating state of consciousness, decerebration and depression of vital
signs represent significant caudal displacement of the upper brainstem
towards the tentorial hiatus.
•• Shearing of the brainstem is maximal in the region of the aqueduct with
the fibres of the medial longitudinal fasciculus being vulnerable resulting
in internuclear ophthalmoplegia.
•• Oculomotor nerve palsy is common with brainstem injury due to damage
either at its exit from the midbrain or fascicular injury in the midbrain.
•• “Locked in syndrome” due to traumatic basilar artery dissection or direct
impact following clival fracture has been reported.
•• In the midbrain, the haemorrhagic lesions are in the dorsolateral part, almost
always involving the superior cerebellar peduncle.
•• The brainstem can be involved by any one of the following mechanisms:
–– Primary brainstem injury—not so rare as considered.
–– As a part of DAI.
–– Secondary brainstem injury—due to downwards herniation, torsion,
lateral displacement.
Hypothalamus
•• Hypothalamic dysfunction following head injury may lead to aberrations in
homeostatic functions including appetite and satiety mechanism and the
thermoregulatory process.
•• Injury to the hypothalamus produces dissociated adrenocorticotropic
hormone (ACTH) cortisol levels with no response to insulin-induced
hypoglycaemia, hypothyroxaemia with preserved TSH response to TRH,
low gonadotropin levels with normal response to gonadotropin releasing
hormone, variable GH levels with paradoxical rise of ADH secretion,
disturbed glucose metabolism, loss of thermoregulation, etc.
•• Most severe injuries involving the skull base are sufficient to damage both
the hypothalamus and pituitary causing a mixed endocrine picture.
Pituitary
•• Although an array of potential neuroendocrine problems can occur after
TBI, most of the commonly encountered problems are transient in nature.
•• Panhypopituitarism is actually a rare post-traumatic phenomenon, but
may be responsible for significant alterations in the level of the patient’s
consciousness.
•• Most frequently seen are anterior lobe infarction, posterior lobe haemor-
rhage and destruction of the pituitary stalk.
205
•• Post-traumatic haemorrhage into the neural lobe occurs, but extensive

infarction is rare and, thus, post-traumatic diabetes insipidus is transient.
•• Permanent diabetes insipidus indicates damage at a higher level; either at
the infundibulum or at the hypothalamus. However, most of the damage to
the pituitary is secondary to raised ICP, resultant ischaemic events reflecting
multifocal brain damage.
Cranial Nerves
•• Following gliding contusion of the orbitofrontal area or fracture involving
the anterior cranial fossa, loss of olfactory sense is common.
•• The most vulnerable part of the optic nerve is the portion traversing the
optic canal.
•• Following traumatic SAH, the blood extends into the orbital portion of the
optic nerve causing vasospasm.
•• Severe trauma to the apex of the orbit or fracture in the middle cranial fossa
extending medially can cause injury to the III, IV and VI cranial nerves and,
occasionally, the Gasserian ganglion.
•• Injury to the petrous temporal bone by lateral impact can cause facial and
VIII cranial nerve injuries of varying degrees.
•• Damage to the lower cranial nerves is common following gunshot wounds
or severe angular injury to the occipital bone and impact against the clivus.
CELLULAR/MOLECULAR RESPONSE TO
BRAIN INJURY
•• A wide range of pathological insults to the brain, including mechanical
injury, ischaemia and seizures induce the immediate early genes (IEGs);
C-fos, C-jun and jun B.
•• Inflammation and Cytokines:
–– Recapitulating the acute inflammatory process following acute focal
brain injury like contusions, polymorphonuclear leucocytes accumulate
in the damaged tissue temporarily coinciding with cerebral oedema.
–– The macrophages replace the polymorphs to initiate the repair process
and scavenging of the necrotic debris.
–– These macrophages secrete cytokines like 1L-1β, 1L-6 and TNF-α,
that initiate an excitotoxic neurodegenerative process with upregula-
tion of their receptors to find their way into the CSF. Thus, CNS derived
cytokines may play a role in the pathophysiology of TBI.
•• Hypersensitivity of Traumatised Brain to Secondary Cerebral
Ischaemia (Tables 6 and 7):
–– Secondary insults like hypertension, hypoxia and global ischaemia
worsen the bioenergetic, electrophysiologic and behavioural status
subjected to TBI.
•• Ionic Events and Role of Exitatory Amino Acids in TBI:
–– One major event that occurs at the moment of impact in neuronal cells
is the sudden and massive ionic influxes across the cell membrane of
Na+, Ca++ and Cl1 and efflux of K+.
–– As the magnitude of trauma crosses a threshold, an abrupt efflux of K+
occurs with membrane electrical changes and traumatic depolarisa-
tion (TD).
–– Localised mechanical or K+ ionic membrane stimulation induces other
ionic events called spreading depression (SD).
206
Table 6: Pathobiological changes caused by traumatic brain injury

Post-traumatic brain hypersensitivity to ischaemic and chemical insults
Injury → Vasospasm → Primary ischaemia
Physical shaking of neurons Neurotransmitter storm
discharge Neuronal excitation
[receptor mediated]
Intracranial Vasospasm Seizure
Reactive hypertension Sec. Ischaemia
Neurons more sensitive
Large areas of damage
Electrophysiological changes
Non-traumatised brain—Tolerates same degree of ischaemia
better
• Secondary ischaemia—starts 1 hour post-trauma → Brain hypersensitivty lasts for 24
hours post-trauma
• Secondary ischaemia starts → Beyond 24 hours post-trauma → Brain hyposensitive
Table 7: Neurochemical/neurotransmitter changes

Traumatic brain injury
• Injury induced membrane depolarisation
• Activation of voltage dependant channels
• Acetyl choline↑↑↑—brain, cerebrospinal fluid
• Reduced binding or low affinity → Cholinergic receptors (muscarinic)
→ In Hippocampus, brainstem, for 2 weeks
• Acetyl choline excitation → Behavioural abnormalities and cognitive deficits
(RX: Anticholinergic drugs useful !!!)
• Catecholamine/monoamine—alterations proportional to degree of injury
• Levels and receptor binding:
Vasomotor changes
• 5HT levels ↑↑↑↑— cerebral hemisphere—same side of injury
↓
Glucose internalisation reduced
↓
Anoxic injury
• Dopamine levels (transporter ↑↑↑↑)
– Down regulation of dopamine receptor (↓↓)
• Excitatory amino acids ↑↑↑ (hippocampus, neocortex)
– Immediate lasts for 4–6 days
• Fall in Mg++ levels → secondary damage via neurochemical
path and influx of Ca++
• Rise in Ca++ levels → lasts for 2–4 days
↓
Cytoskeletal damage (within 24 hours)
• Accumulation of amyloid precursor protein (within 24 hours) for repair
–– Following injury, energy failure and anoxia, abrupt and rapid ionic fluxes
occur with a short latent period of a minute, called anoxic depolarisation
(AD).
–– The three events TD, SD and AD, either in tandem or in various
combinations, can disrupt the powerful mechanisms maintaining ionic
homeostasis.
207
•• Role of Apolipoprotein E in the Outcome of Head Injury:

–– Following injury, there is a coordinated increase in the expression of
ApoE by astrocytes and low-density lipoprotein (LDL) receptors by
neurons, facilitating the transport.
Ethanol Potentiation of Central

Nervous System Trauma
•• Alcohol consumption has been a major risk factor in occurrence of
neurotrauma.
•• Ethanol and its principal metabolite acetaldehyde, because of their lipophilic
nature, get intercalated into the cell membrane, altering the biochemical
and biophysical properties.
•• In addition, the free radicals generated damage the cell membrane and
other structures like mitochondria, depleting the energy system.
•• Altered platelet function, acetaldehyde induced mitochondrial damage and
deranged adrenergic vasotonic activity following alcohol administration
could be responsible for haemorrhagic lesions and oedema.
•• Free radical induced inhibition of Na+/K+—ATPase activity in the membrane
could contribute to depressed evoked potentials.
IMAGING IN TRAUMATIC BRAIN INJURY

•• Prediction of the outcome by imaging is dominated by a few variables like
intracranial haemorrhages, brain swelling and DAI.
•• CT may show petechial haemorrhages, but these punctuate lesions may
resolve quickly.
•• Small lesions and non-haemorrhagic lesions in the lobar white matter,
corpus callosum and brainstem are detected in the MRI due to its excellent
resolution.
•• TBI is associated with delayed T1 and T2 weighted signal abnormalities in
the frontotemporal area and poorer outcome beyond 6 months after injury
and some remain in persistent vegetative state.
•• It appears that atrophy and compensatory hydrocephalus may be associ-
ated with bad outcome and long-term sequelae detected on MRI, especially
the frontal horn and III ventricle.
•• During the acute phase, MRI image hypodensities noted in the deep
dorsal brainstem indicate a poorer prognosis than those in the ventral and
superficial brainstem.
•• Diffusion weighted imaging sensitive to random movement of water
molecules show initially restricted diffusion (representing cytotoxic oedema)
followed by unrestricted diffusion (vasogenic oedema) highlighting the
evolution of dynamic events in the acute phase.
•• Perfusion weighted imaging shows regional reduction in CBF and is
sensitive to microscopic tissue level blood volume changes.
•• Bosnell studied the application of diffusion tensor imaging in recovery from
TBI and summarised its uses as below:
–– Monitoring pathological change
–– Predicting recovery
–– Identifying individual targets of therapy
–– Providing outcome measures
–– Providing measures of potentially compensatory structural changes
208
–– Understanding of normal brain anatomy to aid in interpretation of the

consequences of localised damage.
•• Proton magnetic resonance spectroscopy (MRS) in clinical studies has
revealed reduction in N-acetyl aspartate in the white matter, reflecting DAI
and poorer clinical outcome.
•• Functional MRI, sensitive to the oxidative state of haemoglobin, reflecting
oxygen extraction and regional activation, has not been widely used to
study TBI.
Neuropathology of Post-Traumatic Sequelae

•• Severe disability after head injury is usually associated with abnormalities
in the rostral brainstem, intracranial haematoma (SDH and intracerebral),
cerebral oedema, circulatory and respiratory disturbance—thus, indicating
the role of secondary events in the evolution during the first 1 month.
•• In patients with persistent vegetative state, widespread bilateral neocortical
and white matter lesions are seen, some of them are cavitatory.
•• Neurologic diseases with possible connection with head injury include
Alzheimer’s disease, Parkinson’s disease and motor neuron disease.
•• A large number of concussive or subconcussive blows, as common in
boxers, induce the development of progressive dementia. The pathological
features noted were cavum septum pellucidum, fenestration of the septum,
thinning of the fornix and corpus callosum, neuronal loss in the cerebellum
and loss of pigmented neurons in the substantia nigra.
•• The brains of boxers and those subjected to prolonged domestic violence
have numerous non-neuritic diffuse plaques not identifiable by congo-red
or silver stains, but labelled by antibody to β-amyloid protein.
PATHOLOGY AND PATHOGENESIS OF

SPINAL CORD INJURY
INTRODUCTION
•• The annual incidence of SCI in various countries range from 15 cases to
40 cases per million population.
•• In civilian life, the most common causes are road traffic accidents, sports
and recreational activities, accidents at work, falls and violence.
CLASSIFICATION OF SPINAL CORD INJURIES

•• SCI can be classified as “open” and “closed” injuries depending on the
dynamics of the force, the separation into the respective categories being
dependant on the integrity of the dura.
•• In general, open injuries result from sharp or penetrating injuries while blunt
force causes indirect or closed injuries by transmission of the mechanical
impact to the cord without injury to the spine.
•• A combination of the two may also occur as in fracture dislocation
resulting from blunt force, wherein the dislocated bony spicules can cause
penetrating injury and tear of arachnoid/dura.
209
Mechanisms of Closed Injuries

•• The mechanism of injury and the anatomical lesion that results is best
described by indicating the direction of the resultant vector and the axis
of rotation.
•• Unlike the moveable head, the spinal cord is rarely submitted to acceleration
injury.
•• Accordingly, SCI are most often classified into four groups according to the
most predominant factor at the time of injury as:
1. Flexion and deflexion injuries
2. Vertical compression
3. Rotational injuries
4. Combination of forces.
•• All these mechanisms, except vertical compression, are associated with
crushing of the cord. Vertical compression injuries often produce incomplete
cord lesions.
•• Flexion and Deflexion Injuries:
–– Ventroflexion and dorsiflexion forces produce deformities of the spine
with or without accompanying cord injury.
–– In this form of trauma, three types of forces come into play: (1) trans-
verse shear; (2) longitudinal shear and (3) torsion. Among these,
transverse shear is the most important.
–– Flexion and deflexion injury is the most common mechanism of neck
injuries (e.g. whiplash injuries) and results in anterior and posterior
longitudinal ligament tears.
–– The cord gets stretched diagonally upwards resulting in a transverse
tear if there is a fracture dislocation or protrusion of the disc just above
the fulcrum in both types of injuries.
•• Flexion (anteroflexion/hyperflexion) injuries:
–– Extreme hyperflexion injuries result in severe spine deformities leading
to fracture, fracture dislocation of vertebral bodies, prolapse of discs,
dislocation of articular processes, and is associated with severe local
damage to the cord causing central necrosis and haemorrhage.
–– Acute anterohyperflexion of the neck in infants cause fatal central cer-
ebral haemorrhage or haemorrhagic necrosis of the medulla or upper
cervical cord.
•• Hyperextension injuries:
–– The term “hyperextension injuries” encompasses retroflexion or dor-
siflexion forces, and fracture dislocations caused by facial or frontal
injuries.
–– Such forms happen with excessive skull traction, which causes frac-
tures of the neural arches and, rarely, cord damage.
–– But the majority of injuries to the cervical cord result from facial or
frontal trauma as in a blow to the forehead or diving into shallow water
and, in this form of injury, there is retrohyperflexion of the head and
neck with or without rotation.
•• In elderly persons with cervical spondylosis, dorsiflexion causes significant
cord damage by tearing of the intervertebral disc and angulation of the cord
already narrowed by ankylosing spondylitis.
•• Retroflexion of the head and neck causes central cord injury which can
take the following forms:
210
–– Small intramedullary haemorrhages with oedema (focal haematomyelia,

representing butterfly-like central haemorrhage or haemorrhagic
necrosis in the grey matter)
–– Direct contusion of the cord (ischaemic malacia caused by squeezing
of the cord)
–– Central concussion with surrounding oedema and central ischaemic
infarct due to vascular insufficiency caused by compression of the
vertebral arteries.
•• Compression Injuries:
–– The vertebral body absorbs compression injuries caused by vertical
impact and cause vertebral fractures while the ligaments are intact.
–– Such injuries follow a fall on the head or neck, car accidents, etc.
resulting in flattening of the vertebral body, fracture of end plates and
rupture of the nucleus pulposus.
–– Such injuries affect the thoracolumbar junction (most moveable part of
the thoracolumbar spine) or lower cervical spine.
–– Protrusion of the fractured vertebral body (posteriorly more often than
anteriorly) or the intervertebral disc (acute retropulsion) in the trans-
verse plane causes compression of the spinal cord.
•• Rotation Injuries:
–– This can affect any part of the vertebral body, its articulations and
the ligamentous complex to cause fracture dislocations (unilateral/
bilateral, stable/unstable) and displacement of the intervertebral discs.
–– This most often involves the thoracolumbar junction and the upper
lumbar spine.
–– Compression leads to cord injury and this type of injury is also associ-
ated with lesions in the cord and roots in the region of the cauda equina.
•• Combined Mechanisms:
–– Pure extension or flexion injuries do not produce ligamentous rupture,
disc destruction or fracture dislocations which requires coexisting
rotational forces.
–– Dislocations are the most common in the cervical spine due to its marked
mobility, followed by the lower thoracic and thoracolumbar spine.
–– Flexion-rotation injuries produce unstable fracture dislocations that are
associated with rupture of the posterior longitudinal ligaments, separa-
tion of spinous processes and unilateral or bilateral facet dislocations.
–– Bilateral dislocations are more often associated with compression or
crush injury of the cord.
–– In hyperextension (retroflexion) injuries of the neck, the anterior lon-
gitudinal ligament ruptures with posterior dislocation of the vertebral
body that compresses the cord.
–– In patients with cervical spondylosis, even minor injuries can cause
subluxation without rupture of the anterior longitudinal ligament.
–– In the so-called “whiplash injuries”, there is ventro/dorsiflexion of the
cervical spine with rotation, compression and anteroposterior angular
acceleration. This causes excessive distortion with soft tissue damage,
in addition to damage to both anterior and posterior ligaments, the
nerve roots and disc with or without cord injury.
211
Types of Cord Lesions in Closed Injury

1. Primary traumatic lesions
2. Secondary traumatic lesions—That develop from non-traumatic second-
ary sequelae resulting from the circulatory alterations, oedema, etc.
3. Late sequelae of both primary and secondary lesions—That include
repair, regeneration and secondary tract degeneration. Late complications
and delayed progression (myelopathies) that occur at various intervals.
Primary Traumatic Lesions
•• These are the immediate result of direct trauma on the cord.
•• This includes all local lesions at or adjacent to the site of impact caused by
direct trauma as in laceration of the cord coverings, extradural, intradural
and subarachnoid haemorrhages.
•• The damage to the cord ranges from petechial haemorrhage and oedema
to central necrosis, and damage to the vasculature or nerve roots.
•• Extramedullary haemorrhages:
–– Subarachnoid and extradural haematomas are more common follow-
ing birth injury and perinatal distress.
–– Spinal subdural haematomas, similarly, are rare in adults except if
there is associated bleeding tendency and more common in neonates
following obstetric trauma.
–– This is an important cause of perinatal paraplegia.
•• Concussion of the cord:
–– Concussion is by definition a functional disorder, which is reversible
and is produced by blunt direct injury without anatomically discernible
damage to the cord.
–– Like its cranial counterpart, it is associated with transitory changes
in the nerve cells (neuronal chromatolysis and necrosis), fibre tracts,
focal myelin and axonal breakdown, small haemorrhages, oedema and
microscopic foci of ischaemic necrosis.
–– The pathological events in concussion of the cord is focused in the
grey matter, and results in haemorrhagic necrosis. Hypoperfusion of
the grey matter, which is the initiating factor along with increase in
intracellular calcium and reperfusion injury, plays a key role in cellular
injury.
•• Compression:
–– This may result from fracture dislocation of the vertebra, prolapsed
disc, exostosis and spondylitic changes and, rarely, from extensive
extramedullary haemorrhage more often in the cervical region.
–– The pathological changes caused by compression include necrosis
with or without haemorrhage or non-necrotic changes depending on
the duration.
•• Contusion of the cord:
–– The term connotes all primary injuries to the spinal cord and its cover-
ings caused by indirect blunt violence transmitted to the cord.
–– It ranges from small petechial haemorrhages and oedema to extensive
crush injuries wherein the cord tissue is pulped, but complete tears
are rare.
–– The pathology, similar to cerebral contusions, evolve over three con-
secutive stages:
1. An early phase of haemorrhage and necrosis
2. An intermediate stage wherein the process of resorption and or-
ganisation begins
3. The final stage of scarring or syringomyelia.
212
•• The acute lesion is also characterised by traumatic changes of demyelina-

tion and Wallerian degeneration of the axis cylinders, which have escaped
total disruption.
•• Immediately following injury, there is complete disruption of a proportion
of nerve fibres and partial injury to others. In the former, the damage is
permanent, while in the latter, it is still reversible.
•• Axonal damage can be detected within hours of injury by immunohis-
tochemical methods using antibodies to the bA4 moiety of the amyloid
precursor protein.
•• This highlights two types of axonal damage:
–– Irregular varicosities appear within 30 minutes of injury and indicate a
failure of the rapid anterograde axonal transport.
–– The axonal spheroids (“retraction bulbs”) become apparent within
24 hours of injury suggesting that varicosities may progress to total
axotomy and spheroid formation.
•• Intermediate “repair” phase:
–– Within 24−48 hours post-trauma, the transverse progression of acute
haemorrhagic necrosis, extravasation of RBCs and local blockage of
blood flow begins to subside, but the oedema reaches a peak within
3−6 days after the injury.
–– Within 2−3 days following the contusion, the haemorrhagic necrosis is
gradually resorbed and a reparative process begins.
–– The central necrotic area progressively undergoes cystic dissolution.
–– Along the margins, vessels proliferate and the resolving central necrotic
area is soon surrounded by a zone of highly vascularised granulation
tissue (“proliferation zone”).
•• Late stage:
–– Months to years after the injury, damaged parts of the cord are totally
replaced by connective tissue. The zones above and below develop
dense isomorphic gliosis, which replaces the lost neurons and nerve
fibres.
–– Wallerian degeneration of tracts also progresses with subsequent gliosis.
–– Changes in the vasculature of the cord in the late stages include
organisation and recanalisation of occluded intramedullary and pial
vessels, an obliterative vasculopathy.
•• Late sequelae (Post-traumatic syringomyelia):
–– A nidus of traumatic haematomyelia or myelomalacia followed by
liquefaction and cavitation, instead of solid scar formation is the initiating
lesion.
–– Further, a communication between the syringomyelic cavity and the
subarachnoid space can act as a valve-like promoter, once the original
cavity has been established.
–– Histologically, post-traumatic syrinx is not any different from an idi-
opathic syrinx.
•• A less common type termed “microcystic myelomalacia” (marshy cord
syndrome) described by MacDonald and his co-workers is post-traumatic
central degeneration without frank syringomyelia. Arachnoiditis has been
seen with this condition. This may play a role in the progression of both
post-traumatic syringomyelia and cystic myelomalacia.
213
PATHOPHYSIOLOGY OF ACUTE SPINAL

CORD INJURIES
Systemic Effects
Neurogenic Shock
•• Spinal cord injury is one of the common causes for neurogenic shock, which
results from a combination of decreased sympathetic tone, unopposed
vagotonia and possible secondary changes in the heart.
•• The magnitude of the shock is directly related to the level (more common
in complete cervical injuries) and the severity of the injury.
•• The peripheral resistance and cardiac output can remain depressed for
long periods of time following the injury.
Local Effects
Damage to the Microcirculation
•• A common feature of SCI is the development of central haematomyelia.
This is attributed to the mechanical disruption of the capillaries, arterioles
and venules due to the mechanical force of injury and distortion by impact,
compression or laceration.
Biochemical Changes
•• The key event is damage caused by the excitatory neurotransmitter
glutamate that mediates injury through elevation of intracellular calcium.
•• Increased levels of intracellular calcium sets into motion a chain of events, all
of which acting via different pathways cause cell death and tissue necrosis.
•• These processes include activation of proteases that degrade neurofilament
proteins; lipases that cause dissolution of cell membranes, and release of
free radicals that cause lipid peroxidation.
•• Lipases also cause release of prostaglandins and eicosanoids from
damaged neuronal membranes that can, in turn, induce vasospasm.
Electrolyte Shifts
•• The most important is increase in intracellular calcium that plays an
important role in pathogenesis in acute SCI similar to ischaemic injuries
and head trauma.
•• Calcium enters either through disrupted cell membranes or through voltage
gated calcium channels following depolarisation or via receptors activated
by glutamate.
•• Increase in calcium within the vascular smooth muscle can result in tetanic
contraction or vasospasm causing ischaemic damage.
STRATEGIES FOR TREATMENT OF

SPINAL CORD INJURY
•• Spinal cord injury (SCI) is one of the most physically, psychologically, as
well as, socially devastating afflictions.
The approaches vary from:
•• Arresting the immediate effects of injury so that secondary damage to the
cord is prevented or arrested.
214
•• Induce axonal regeneration to re-establish pathways so that functional

restoration is possible.
•• Reconstruct the injured segment by transplantation or grafting.
–– Initial interest was focused on developing pharmacological regimens
that can protect the cord at the time of the acute injury.
–– These operate by suppressing some of the secondary processes that
are activated following the trauma.
–– Methyl prednisolone and the ganglioside GM-1 inhibit the inflammatory
reaction and generation of free radicals.
–– The GABA inhibitors, such as riluzole or gabapentin, may be useful in
limiting the damage caused by excitotoxicity.
–– Regeneration of the CNS axons is the prime target for treatment of
end stage lesions.
–– Numerous methods of achieving the primary goal of promoting regen-
eration by transplantation have been tried out. Peripheral nerve grafts,
grafting of embryonic tissues or Schwann cells, olfactory ensheathing
cells and cells genetically engineered to produce neurotrophins and
even inert substances, like polyethylene glycol have produced exciting
results with remyelination.
–– Whether foetal tissue transplant will ever be applicable to human SCI
is debatable given the ethical and procedural problems that arise with
procurement of foetal tissue, non-invasive monitoring of the graft site,
assessment of outcome, etc. but this is an important stepping stone in
the treatment of chronic SCI.
–– Neural Stem Cells:
¾¾ Neural stem cells have been the focus of intense research in recent
times aimed at developing transplantation strategies to promote
neural recovery in the injured nervous system.
¾¾ Neural stem cells have the capacity of self-renewal to generate
progeny that are capable of differentiating into both neurons and
glia.
¾¾ Transplantation of human neural stem cells obtained from embry-
onic tissue has shown both neuronal and astrocytic differentiation.
¾¾ Remyelination and recovery of impulse conduction has also been
demonstrated following transplantation into demyelinated rat spinal
cords.
¾¾ But relative inaccessibility of these cells for autologous therapy,
the ethical and practical problems in obtaining embryonic tissues
with their inherent problems of host incompatibility, and rigorous
testing for viral screens make this an unpopular choice of therapy,
forcing investigators to look further for alternate sources of neural
precursors.
25
CHAPTER
Concussion Brain
Sandeep Vaishya  Khan Z
INTRODUCTION
•• Concussion, derived from the Latin concutere (“to shake violently”) or the
Latin concusses (“action of striking together”) is the most common type of
traumatic brain injury.
•• Concussion is frequently defined as a head injury with a transient loss of
brain function and is known to cause a variety of physical, cognitive and
emotional symptoms.
•• The most widely accepted definition is the one proffered by The Committee
on Head Injury Nomenclature of Neurological Surgeons in 1966 and defines
it as “a clinical syndrome characterised by immediate and transient post-
traumatic impairment of neural function such as alteration of consciousness,
disturbance of vision or equilibrium, etc. due to brainstem dysfunction”.
•• The more recent description, as given by The American Academy of
Neurology, states that “concussion is the trauma induced alteration in
mental status that may or may not include loss of consciousness”.
MECHANISM
•• The brain is anatomically designed to prevent damage from light trauma,
as the surrounding cerebrospinal fluid acts as a cushion.
•• Concussion may be caused by impact forces, in which the head strikes
or is struck by something or impulsive forces, in which the head moves
without itself being subjected to blunt trauma.
•• Forces may cause linear, rotational or angular movement of the brain or a
combination of these types of motion.
•• Amongst all these forces, the amount of rotational force is considered the major
type of force to cause concussion and the largest component in its severity.
•• Rotational forces primarily affect the midbrain and diencephalon and the
subsequent injury is thought to disrupt the normal cellular activities in
the reticular activating system located in these areas, which eventually
produces the loss of consciousness often seen in concussion.
•• Other areas of the brain that may be affected include the upper part of
the brainstem, the fornix, the corpus callosum, the temporal lobe and the
frontal lobe.
PATHOGENESIS AND PROPOSED THEORIES

•• Most of the theories proposed to explain the genesis of concussion rely on
the understanding of the post-traumatic responses of the various parts of
the brain, towards different types of forces employed for causing the injury.
216
•• Ricker suggested that concussion could be due to extreme vascular

dilatation followed by constriction.
•• Duret proposed that it could be due to the forces of CSF impinging on
the floor of the fourth ventricle and sudden compression of the cerebral
hemispheres.
•• Trotter suggested that it could be the result of a momentary cerebral
anaemia, due to compression or indentation of the skull.
•• Scott suggested that temporary rise of intracranial pressure above the
systolic pressure with sudden cerebral anaemia could be one of the causes.
•• Denny Brown and Russell suggested acceleration to be responsible for
concussion.
•• Walker proposed that the underlying reason for concussion could be
the presence of pressure waves which cause primary intense neuronal
stimulation followed by a temporary paralytic phase.
•• Bronstien suggested the role of acetyl choline, which is normally absent in
CSF and was present in large quantities in experimental and clinical head
injuries. Acetylcholine in high quantities can block synaptic transmission by
depolarisation of the post-synaptic membrane. This remains the basis of the
hypothesis regarding changes in the reticular system during concussion.
•• Foltz and Schmidt proposed that concussion was due to reversible blocking
of the functional integrity of the brainstem reticular system.
•• Dott suggested that stretching of perforators cause vasospasm, resulting
in brainstem anoxaemia.
•• Symonds proposed that the instantaneous loss of cerebral function was
the result of sudden direct damage, either by stretching or by compression
of the nerve cells or fibres in the brain.
•• Rowbotham believed that less force might cause temporary derangement
of fibre conduction or synaptic transmission, without actual anatomical
disruption of fibres.
•• Ommaya and colleagues found slowing of circulation and disruption of blood
brain barrier as perhaps the primary cause of concussion.
•• Kaplan divided the entity into two subdivisions, as physiological concussion
with reversible changes and pathological concussion with irreversible
changes and permanent neuronal cell damage.
•• Kristiansen and Tandon considered the latter to represent a transitional
stage between concussion and contusion.
PATHOPHYSIOLOGY
•• Most of the clinical studies proposed that concussion is caused by
acceleration and deceleration forces.
•• It may be considered as the mild end of the traumatic brain injury continuum
with loss of consciousness and post-traumatic amnesia being brief in
duration and with minimal axonal stretch.
•• Limited stretch of axons lead to initiation of a pathophysiological process
that leads to very limited cell death, depending upon the morphology of
the cell.
•• The majority of these changes are a reversible series of metabolic events.
•• The primary mechanism includes ionic shifts, abnormal energy metabolism,
diminished cerebral blood flow and impaired neurotransmission.
Chapter 25 • Concussion Brain
217
CLINICAL PICTURE
•• Immediately after the injury, the patient may experience brief loss of
consciousness.
•• The muscles become hypotonic and the respiration is slowed with an
imperceptible pulse and fall of blood pressure which starts returning to
normal within a few seconds or a minute.
•• The stage of confusion may last for a few minutes and the patient often
complains of severe headache.
•• Amnesia is emerging as perhaps the most important sign for careful
assessment after concussion.
•• It may present as retrograde amnesia or anterograde amnesia. The pres-
ence and duration of amnesia, disorientation or mental disturbance has
been associated with an immediate good outcome or slower recovery. The
period of amnesia shrinks over time with recovery.
•• The most common symptom associated with concussion is headache or
dizziness which may last for few hours to seven days.
•• The patient may also complain of blurring of vision and increased fatigue
or feeling sluggish.
•• There may be cognitive changes with problems of attention, concentration,
short-term memory, learning and multitasking.
•• Another commonly reported symptom is that of emotional changes which
may present as irritability, sadness/depression, nervousness/anxiety or
silliness and euphoria.
STRUCTURAL AND FUNCTIONAL IMAGING

•• Concussion presents itself largely as a metabolic event and not a structural
injury, therefore limiting the role of conventional neuro-imaging techniques,
like CT and MRI which are almost always unremarkable following simple
concussion.
•• Recently, functional MRI and Blood Oxygen Level Dependent (BOLD)
activity have been used to study the functional changes after concussion
injury. They showed decreased activity in the mid dorsolateral prefrontal
cortex. Increased activity was seen in the temporal and parietal lobes after
concussion, as compared to controls.
•• Positron emission tomography (PET)/single photon emission computed
tomography (SPECT) studies done in concussed patients showed a pattern
of frontal hypoactivity.
•• Electroencephalography done in post-concussion patients revealed amplitude
reduction in all standard frequency bands, especially during standing.
•• N2/P3 or P300 responses have been used in cognitive event related
potentials for evaluation of patients with concussion.
•• Auditory P3 paradigm showed mixed results with decreased P3 amplitudes.
SECOND IMPACT SYNDROME

•• Second impact syndrome is related to an extraordinarily rare cascade of
events in which a patient experiences a catastrophic brain injury, following
a seemingly mild concussion. Sustaining a second brain injury during the
period of recovery from first concussion has been linked to second impact
syndrome.
218
Table 1: Comparison of concussion grading scales

Grade I Grade II Grade III
Cantu guidelines Post-traumatic amne- Loss of conscious- Loss of conscious-
sia <30 minutes, no ness <5 minutes or ness >5 minutes or
loss of consciousness amnesia lasting 30 amnesia >24
minutes–24 hours
hours
Colorado medical Any loss of Confusion, no loss of Confusion, post-
society guidelines consciousness amnesia, no loss of traumatic
consciousness
American academy Confusion, symptoms Symptoms last >15 Loss of conscious-
of neurology guide- last <15 minutes, no minutes, no loss of ness (IIIa, coma lasts
lines loss of consciousness consciousness seconds, IIIb for
minutes)
•• The pathophysiological basis of this syndrome is cerebrovascular

congestion or loss of cerebral auto-regulation, leading to brain swelling
and oedema.
•• If a second injury is inflicted within 24 hours, there is a marked breakdown
of the blood-brain barrier, which may be the possible mechanism for the
rapid swelling and oedema.
RECOVERY TIME
•• Single concussion typically resolves in less than two weeks.
GRADING SCALES
•• Three grading systems are followed most widely: One was developed
by Robert Cantu, one by the Colorado Medical Society and the third by
the American Academy of Neurology. Each divides concussion into three
grades, as summarised in the Table 1.
TREATMENT
•• Pure concussion, being a self-limiting and an extremely short-lived
phenomenon, does not need any treatment.
•• When concussion merges with traumatic unconsciousness, which is a
phenomenon of longer duration, investigation with CT is necessary and
the appropriate treatment may be given.
•• All patients must be kept under observation.
•• Post-concussion syndromes like giddiness, light-headedness or difficulty
in concentration may require symptomatic treatment and reassurance.
26
CHAPTER
Cerebral Contusions
INTRODUCTION
•• Cerebral contusion (in Latin, contusio cerebri) is a bruise of the brain
parenchyma.
•• Cerebral contusion is the most frequently encountered lesion following
head injury, occurring in 20−30% of severe head injuries.
•• Contusions are wedge shaped, with the apex pointing towards the white
matter.
•• In a contusion, the pia is intact and, if the pia is torn, it becomes a laceration.
•• Contusions can occur without laceration, but a laceration is always
associated with contusion.
•• Based on the mechanism of injury, McCormick divided contusions into
various types:
–– Coup
–– Contrecoup
–– Intermediate coup
–– Gliding
–– Herniation
–– Fracture contusion.
•• Coup contusion occurs beneath the area of impact.
•• Contrecoup contusion occurs in remote areas, particularly in the area
diagonally opposite to the site of impact.
•• Intermediate coup occurs within the brain and is located between coup
and contrecoup contusions.
•• Gliding contusions occur on the vertex due to the rostrocaudal movement
of the brain. These contusions involve the deeper layers of the cortex more
than the surface gyrus, with extension into the convolutional white matter.
•• Herniation contusions occur at the site of subfalcine, tentorial or tonsillar
herniations. Medial temporal and hippocampal contusions are commonly
associated with tentorial herniation.
•• Fracture contusions are coup contusions that lie under the fracture line.
•• Extensive contusion associated with subdural haematoma is called burst
lobe.
•• A burst frontal or temporal lobe is associated with high mortality and
morbidity.
PATHOLOGY
•• The gross appearance of a contusion is an area of haemorrhage beneath
the pia extending usually through the cortex, into the convolutional white
matter.
220
•• The pathogenesis underlying such a rapid progression of mass effect

cannot be fully explained by vasogenic and cytotoxic brain oedema.
•• Kawamata and Katayama proposed that the high osmolality within the
contused brain tissue generates an osmotic potential across the central and
peripheral areas, causing the brain to accumulate a large amount of water.
•• Hypoxia and hypotension still cause a substantial proportion of secondary
injuries and many reports associate secondary brain injury with neuroin-
flammatory responses.
•• Chemokines have been found in the cerebrospinal fluid but not in the brain
tissue of patients following head injuries.
•• Just as in subcutaneous bruises, in brain contusion also, breakdown of
erythrocytes takes place and haemosiderin pigments are released. Phago-
cytosis of the haemosiderin granules occur.
•• Macrophage activity is intense, as also the activity of compound granular
corpuscles.
•• Reactive gliosis occurs at the edges.
•• Thus, over a period of 48 hours to several months, healing takes place in
a graded manner and the contused area begins to look almost like normal
tissue, yet some scarring and gliosis remain.
•• Secondary degenerative changes following cerebral trauma include axonal
disruptions, reorganisation of neuronal circuits and new growth of viable
connections.
CLINICAL FEATURES
•• Contusion can present with limb weakness, lack of motor co-ordination,
numbness, aphasia, and memory and cognitive problems, depending on
the contusion’s location in the brain.
•• It must, however, be emphasised that there is no consistent diagnostic
feature of a contusion.
•• It may produce no clinical deficit, depending upon its size, location, extent
of associated oedema and haemorrhage and it may result in a rapidly
deteriorating clinical course indistinguishable from an expanding intracranial
haematoma.
•• Large or multiple contusions involving the frontal and temporal lobes may
produce raised intracranial pressure (ICP), midline shift and associated
coma.
•• Also, when the level of consciousness is depressed, the clinician has to
rule out an expanding intracranial haematoma.
•• Contusions of the frontal lobe, temporal lobe, sensorimotor cortex, cerebellar
hemisphere and hypothalamus can clinically be made out as characteristic
syndromes.
Frontal Lobe Injury

•• Prolonged post-traumatic confusion or a state of delirium in the earlier
stages and a Korsakoff-like state in the later stages may result from
contusions and laceration of the frontal lobe.
•• The patient may be disoriented and may have a memory disturbance and
confabulation.
•• Persistent nocturnal and occasional diurnal incontinence, as well as
euphoria and disinhibition may closely resemble the clinical picture seen
in frontal tumours.
•• Focal motor or adversive fits with or without generalisation may occur.
Chapter 26 • Cerebral Contusions
221
Sensorimotor Contusion
•• Some form of pyramidal deficit is a common accompaniment of moderately
severe head injuries.
•• Upper motor neuron type of facial weakness, fall of the outstretched hand,
weakness of handgrip, dragging of the foot while walking and an extensor
plantar response may often be seen on one side.
•• Special tests may be required to bring out associated parietal lobe
dysfunction.
Cerebellar Injury
•• Contusions of the cerebellum or of the cerebellar peduncles are not
common.
•• Occasionally, following a blow to the back of the head and in association
with an occipital fracture, obvious unilateral cerebellar signs like hypotonia,
nystagmus and inco-ordination are observed.
•• When these signs occur without any impairment of consciousness or
evidence of increased ICP, a space occupying posterior fossa haematoma
is unlikely.
•• Cerebellar dysarthria and an ataxic broad-based gait may also be seen.
•• Recovery is spontaneous, early and generally almost complete.
Hypothalamic Injury
•• Hyperpnoea and excessive pulmonary secretions indicate associated
hypothalamic damage.
•• Unexplained severe and irreversible shock may indicate primary
hypothalamic damage, but is very rare.
•• Persistent hypothermia has been noted following widespread damage to
the periventricular grey matter around the third ventricle.
•• Diabetes insipidus may follow bilateral infarction of the supraoptic nuclei and
hypernatraemia may result from bilateral damage to the ventromedial nuclei.
•• Treatment of these manifestations is purely symptomatic until spontaneous
recovery occurs, but severe hypothalamic damage almost always leads
to a fatal outcome.
Radiology
•• CT scanning is the imaging modality of choice for traumatic brain injury. To
standardise the imaging procedure, 5-mm slices should be obtained from
the foramen magnum to the sella and 10-mm slices should be obtained
above the sella, parallel to the orbitomeatal line.
•• The CT scan appearance in cerebral contusion depends on the presence
of oedema and haemorrhages in the contused region and hence, presents
a variable appearance depending on the predominance of either factor.
•• There is a combination of high attenuation and low attenuation areas,
described as ‘salt and pepper appearance’ by French and Dublin.
•• There is enhancement with contrast in an area of contusion due to vascular
disruption.
•• The high attenuation areas due to haemorrhage are short lasting while the
low attenuation due to oedema may persist for a long time.
•• In large contusions, ventricular displacement or compression may be seen.
•• Chesnut et al. found the following early CT scan findings to correlate with
the outcome:
222
–– Status of the basal cisterns

–– Midline shift
–– Subarachnoid haemorrhage in the basal cisterns.
•• Perfusion CT (PCT) has been found to be better in the evaluation of tissue
viability than non-contrast CT.
•• In the MR, there is a combination of different signal intensities. In non-
haemorrhagic contusions, hypointense signals on T1 and hyperintense
signals on T2 are observed. Haemorrhagic contusions show marked
variability in signals depending on the age of the contusion.
•• More often than not a significant contusion is associated with other lesions
like subdural haematoma, or intracerebral haematoma, subarachnoid
haemorrhage which complicate the clinical and radiological findings and
influence the management.
MANAGEMENT
•• The management of patients with cerebral contusion depends on the
location and extent of the contusion. The severity of associated lesions
and the neurological status of the patient.
•• Patients with small or deep seated contusions can be managed without
surgery, and can be followed with frequent assessment of their neurologic
status.
•• The ICP should be monitored and, if raised, should be treated accordingly.
However, ICP monitoring is not mandatory in all cases.
•• Since contusions tend to evolve, the timing of surgery with respect to the
occurrence of neurological deterioration clearly affects the outcome.
•• Patients with GCS scores 6−8 with frontal or temporal contusions greater
than 20 cm3 in volume with midline shift of at least 5 mm and/or cisternal
compression on CT scan, and patients with any lesion greater than 50 cm3
in volume should be treated surgically, as an emergency.
•• There is reluctance in operating on contusions involving a dominant lobe,
and medical therapy along with frequent assessment of the neurological
status can be tried in an attempt to tide the patient over the period of
maximum oedema.
•• Large decompressive craniectomy with opening of the dura mater without
resecting the contused brain has been performed as a treatment for
cerebral contusion.
•• Decompressive procedures, including subtemporal decompression, and
temporal lobectomy are other surgical options for patients with refractory
intracranial hypertension and diffuse parenchymal injury with clinical and
radiographic evidence for impending transtentorial herniation has been
advocated by Tandon et al.
PROGNOSTIC FACTORS
•• These include age, admission or post-resuscitation GCS, presence of
pupillary response/brainstem reflexes, respiratory insufficiency, raised ICP
and the status of the basal cisterns or third ventricle on CT scan.
•• Other variables include location of the lesion, ICH volume, GCS at time
of follow-up CT, lowest recorded GCS, severity of surrounding oedema,
timing of surgery, occurrence of pre-operative neurological deterioration,
and presence of acute hemispheric swelling or concomitant subdural
haematoma.
Chapter 26 • Cerebral Contusions
223
TEMPORAL LOBE CONTUSION

•• Contusion of the temporal lobe is seen in 70% of fatal head injuries.
•• The pulped necrotic brain in temporal lobe contusion swells and is capable
of producing a fatal increase in ICP.
•• Focal oedema and contusion of the temporal lobe may also be so severe
as to compress the blood vessels in the middle fossa and lead to extensive
secondary ischaemia.
•• The majority of temporal lobe injuries are associated with injuries to the
frontobasal region, brainstem and other parts of the brain.
•• Temporal lobe contusion may mimic the clinical picture of an extracerebral
haematoma and may present acutely or subacutely.
•• It is frequently associated with a varying degree of subdural haemorrhage.
•• It is difficult to draw a clear-cut line between a lesion which could be called
cerebral contusion with haemorrhage and a real intracerebral haematoma.
•• This explains the variety of names given to these lesions like traumatic
intracerebral haemorrhage, pulped temporal lobe, intradural haematomas,
exploded temporal lobe, traumatic encephalomalacia or simply temporal
lobe lesions in head injury.
•• In subacute and chronic cases, the clinical manifestations are slow in
evolving.
•• There is usually a history of a blow to the side or back of the head.
•• The patient shows rapid improvement from the initial unconsciousness but
does not progress to complete recovery.
•• He may continue to be mildly restless, but co-operative. Often he is mute
or just able to say a few words and obey simple commands.
•• The level of consciousness may remain stationary at this stage for several
days or may deteriorate following any respiratory complication or after the
administration of excessive fluids.
•• In the initial stages, the pupils are equal and reacting, but later there
may be a little transient dilatation and sluggish reaction on one side, or
alternatively, on both sides.
•• A mild hemiparesis, with central weakness of the face, may become slowly
evident.
•• Dysphasia may be present if the dominant hemisphere has been affected.
These findings suggest a mass lesion in the cranium.
•• CT scan helps to exclude extracerebral haematomas and confirm
haemorrhagic contusion with local oedema. CT reveals the age and extent
of the contusion, the presence of necrosis and oedema and any shift of
the midline structures.
•• In mild cases of contusion, when the clinical condition is satisfactory, one
is justified in using anti-oedema measures and keeping the patient under
observation. These measures are not useful in laceration with oedema
or with an intracerebral haematoma. In such cases, if the neurological
condition worsens and if the CT shows a large lesion, craniotomy is
indicated to decompress the temporal lobe or to remove any associated
haematoma.
•• It should be stressed that temporal lobe haematomas and contusions are
potentially dangerous due to the possibility of rapid herniation into the
tentorial hiatus.
•• If the swelling is marked and the affected side is non-dominant, sometimes
one may be justified in doing partial anterior temporal lobectomy, as a
method of internal decompression.
•• Old age and alcoholism influenced the ultimate recovery adversely.
Recovery is quite slow. Profound disturbance of recent memory is seen out
of proportion to other mental changes. Dysphasia may recover only partly.
27
CHAPTER
Rajkumar  Vivek Kumar Vaid  Ashok Kumar Mahapatra
INTRODUCTION
•• Diffuse brain injury is defined as the pathology of head-injured patients
who are unconscious from the moment of impact without any evidence of
space occupying intracranial lesions on computed tomography (CT) scan
or magnetic resonance imaging (MRI).
•• Diffuse brain injury can exist in four principle forms, viz.
1. Diffuse axonal brain injury
2. Diffuse hypoxic/anoxic/ischaemic injury
3. Diffuse swelling
4. Diffuse vascular injury.
•• Of these four forms, diffuse axonal injury (DAI) is the one that is gaining
the most attention particularly because of its relationship in its less severe
forms to the sequelae of subtle brain injury.
•• A number of terms have been used to describe Traumatic DAI(TDAI) and
include “shearing injury”, “diffuse white matter shearing injury” and “inner
cerebral trauma”.
•• The current definition includes severely head-injured patients with
normal scans, tissue tear haemorrhages, traumatic subarachnoid and
intraventricular haemorrhages, diffuse brain swelling and unilateral swelling
with midline shifts.
PATHOPHYSIOLOGY
•• It is caused by angular or rotational acceleration and deceleration inertial
effects and not by contact phenomena.
•• The severity of axonal damage is related to
the magnitude, duration and onset rate of the
angular acceleration.
•• Sudden acceleration-deceleration impact
can produce rotational forces that affect
the brain.
•• The injury to tissue is the greatest in those
areas where the density difference is the
greatest. For this reason, approximately Fig. 1: Shear injury great-
two-third of the DAI lesions occur at the grey- est in areas where the
white matter junction (Fig. 1). density difference is the
•• When shearing forces occur in areas of greatest such as the grey-
greater density differential, the axons white matter junction
Chapter 27 • Diffuse Axonal Injury
225
suffer trauma (Fig. 2); this results in

oedema and in axoplasmic leakage
(which is most severe during the first
2 weeks following injury).
•• The exact location of the shear-
strain injury depends on the plane
of rotation and is independent of the
distance from the centre of rotation.
Conversely, the magnitude of injury
depends on the following three
factors:
–– The distance from the centre of
Fig. 2: Shear injury causing primary
rotation.
injury (axotomy) to the neuron
–– The arc of rotation.
–– The duration and intensity of the force.
•• On the microscopic level, the axon may not completely be torn by the initial
force, but the trauma still can produce focal alteration of the axoplasmic
membrane, resulting in impairment of axoplasmic transport.
•• This would lead to axoplasmic swelling, with the axon subsequently splitting
into two pieces and forming a retraction ball—a pathologic hallmark of
shearing injury (Fig. 3).
•• The axon would then undergo Wallerian degeneration.
•• Dendritic restructuring might occur, with some regeneration possible in
mild-to-moderate injury.
•• Within the basal ganglia, the effect of DAI produces parenchymal atrophy
brought on by shrinkage of astrocytes in the lateral and ventral nuclei,
with sparing of the anterior and dorsomedial nuclei, the pulvinar, the
centromedian nuclei and the lateral geniculate bodies.
•• Cholinergic neurons have been found to be slightly more susceptible to
trauma than are neurons belonging to other neurotransmitters.
•• Peripheral lesions usually are smaller than central lesions.
•• The lesions typically are ovoid or elliptical, with the long axis parallel to the
direction of the involved axonal tracts. A high association is seen between
thalamic injury and DAI.
•• Remaining surviving axons may be vulnerable due to secondary events
leading to hypoxia, ischaemia and subsequent release of excitatory amino
acids and free radicals.
•• The ultimate event in neuronal death appears to be the influx of calcium ions.
•• Both silver staining and beta-amyloid precursor protein immunohistochemical
staining have proven useful in the pathologic identification of DAI lesions.
Fig. 3: Shear injury causing focal alteration of the axoplasmic membrane,

leading to impaired axonal transport, axoplasmic swelling, with the axon sub-
sequently splitting into two pieces and formation of a retraction ball
226
PATHOLOGY OF TRAUMATIC DIFFUSE

AXONAL INJURY
•• McCormick described three “classic” lesions which characterise severe TDAI.
–– Reactive axonal “retraction” balls.
–– Haemorrhagic necrosis in the dorsolateral quadrant of the rostral
brainstem.
–– Haemorrhagic necrosis in the corpus callosum.
•• The axonal swellings are the microscopic hallmark of TDAI.
•• They become apparent within hours after injury and may persist for a year or more.
•• Typically, the process is diffuse and bilateral, involving the lobar white
matter at the grey-white matter interface.
•• The most commonly involved area is the frontal and temporal white matter.
•• Microglial stars develop in these damaged sites and may eventually replace
the swollen axon.
•• Degeneration of long tracts will evolve and ventricular dilatation will follow.
•• The lesion in the dorsolateral quadrant of the rostral brainstem is usually
haemorrhagic and involves the dorsolateral/lateral part of the midbrain and
the rostral pons, almost always involving the superior cerebellar peduncle.
•• The lesion in the corpus callosum usually lies lateral to the midline and
affects the inferior and posterior part of the corpus callosum. The callosal
injury may be focal, segmental or may extend from the genu to the splenium.
•• Other sites of involvement are the caudate nuclei, thalamus, tegmentum
and internal capsule.
•• Adams et al described the stages of involvement according to the anatomic
location of the lesions:
–– Stage I—This involves the parasagittal regions of the frontal lobes, the
periventricular temporal lobes, and less likely, the parietal and occipital
lobes, internal and external capsules, and cerebellum.
–– Stage II—This involves the corpus callosum in addition to the white-
matter areas of stage I.
–– Stage III—This involves the areas associated with stage II, with the
addition of brainstem involvement.
INCIDENCE OF TRAUMATIC DIFFUSE

AXONAL INJURY
•• The incidence of TDAI will be higher at autopsy than would be obvious on
radiographic (e.g. CT and MRI) examination.
•• Diffuse axonal injury represents approximately one-half of all intra-axial
traumatic lesions.
•• No racial or sex predilection exists.
•• DAI can occur at any age.
•• Patients with severe TDAI present in an unconscious state from the onset of
trauma, with the majority of severely injured patients showing a combination
of generalised extensor posture or flexion.
•• About one-third of TDAI patients may recover sufficiently from the initial
head injury to talk before lapsing into coma.
•• Classically, DAI has been considered a primary-type injury, with damage
occurring at the time of the accident.
•• Research has shown that another component of the injury comprises the
secondary factors (or delayed component), since the axons are injured,
secondary swelling occurs, and retraction bulbs form.
Chapter 27 • Diffuse Axonal Injury
227
•• Of patients with DAI, 80% demonstrate multiple areas of injury on CT scans.

•• DAI is suggested in any patient who demonstrates clinical symptoms
disproportionate to his or her CT scan findings.
•• DAI results in instantaneous loss of consciousness and most patients
(> 90%) remain in a persistent vegetative state, since brainstem function
typically remains unaffected. DAI rarely causes death.
•• The chance that a patient will remain in a persistent vegetative state is
greater when lesions are observed in the supratentorial white matter, corpus
callosum and corona radiata.
DIAGNOSTIC STUDIES
Conventional Radiography
•• No specific findings related to DAI can be detected using conventional
radiography; however, other signs of head trauma can be appreciated,
such as facial bone fractures or fluid levels within the paranasal sinuses.
Computed Tomography Scan

•• Among patients eventually proven to have DAI, 50−80% have a normal
CT scan upon presentation.
•• Small petechial haemorrhages located at the grey-white matter junction,
as well as in the corpus callosum and brainstem are characteristic of CT
scan findings in the acute setting.
•• The following CT scan criteria have been suggested by Wang et al:
–– One or more small intraparenchymal haemorrhages less than 2 cm in
diameter, located in the cerebral hemispheres
–– Intraventricular haemorrhage
–– Haemorrhage in the corpus callosum
–– Small focal areas of haemorrhage less than 2 cm in diameter, adjacent
to the third ventricle
–– Brainstem haemorrhage.

•• Recommended sequences include T1-weighted, T2- weighted, T2-gradient-
echo, proton density-weighted and diffusion-weighted images.
•• T1-weighted images are helpful for anatomic localisation; however, non-
haemorrhagic lesions may be isointense to surrounding tissue.
•• Haemorrhagic lesions appear hyperintense on T1-weighted images. Non-
haemorrhagic lesions appear hyperintense on T2-weighted sequences.
•• Diffusion-weighted sequences can reveal hyperintensities in areas of
axonal injury.
•• Gradient-echo sequences are particularly useful in demonstrating the
paramagnetic effects of petechial haemorrhages. Gradient-echo imaging
can often demonstrate signal abnormality in areas that appear normal in
T1-weighted and T2-weighted spin-echo sequences.
•• For this reason, gradient-echo imaging has become the mainstay of MRI
examination for patients with suspected shearing-type injuries.
•• The most common MRI finding is the presence of multi-focal areas of
abnormal signal (bright on T2-weighted images) in the white matter in the
temporal or parietal corticomedullary junction or in the splenium of the
corpus callosum.
228
Fig. 4: Method for intracranial pressure monitoring; also helpful to drain

cerebrospinal fluid so as to lower intracranial pressure
•• A novel MRI technique, diffusion tensor imaging (DTI), permits the

examination of white matter integrity in vivo through observing the amount
of water diffusion within biological tissues.
•• Single-photon emission CT (SPECT) imaging demonstrates areas of
hypoperfusion in regions of known injury and reveals additional areas of
injury not visualised with MRI.
DIFFERENTIAL DIAGNOSIS
•• In a patient with history of head-injury, the only differential diagnosis is
traumatic fat embolism.
MANAGEMENT OF TRAUMATIC DIFFUSE

AXONAL INJURY
•• The following basic principles are applicable for managing patients with DAIs:
–– Immediate establishment of ventilation and circulation at the site of accident.
–– Aggressive monitoring and control of intracranial pressure (ICP).
–– Intensive care to achieve neuronal recovery.
–– Endotracheal intubation is often necessary to protect the airway and
maintain ventilation.
–– Cerebral perfusion pressure (CPP) defined as mean arterial pressure
(MAP) minus ICP is critical for minimising secondary brain damage.
–– The initial approach is to maintain MAP (hence CPP) by establishment
and maintenance of circulatory volume by administering an adequate
volume of crystalloids, colloids or blood products, as appropriate.
–– Risk factors which can predict intracranial hypertension are presence
of subarachnoid haemorrhage, midline shift, abnormal mesencephalic
cistern.
–– Severe head-injured patients with a normal CT scan have a 10−15%
chance of developing intracranial hypertension after 72 hours, hence
serial follow-up CT scans are necessary.
–– ICP may be measured from intraventricular, intraparenchymal, subdural
and extradural sites (Fig. 4) [See chapter 2].
–– Various medical methods for controlling increased ICP are position of
the patient’s head, osmotherapy and diuretics, hyperventilation, barbi-
turates, cerebrospinal fluid drainage.
28
CHAPTER
Fat Embolism
Krishna Reddy A
INTRODUCTION
•• Fat embolism is a pathological entity characterised by occlusion of multiple
blood vessels with fat globules, which presents clinically with manifestations
of diffuse pulmonary insufficiency causing hypoxia, neurological
dysfunction, pyrexia, tachycardia, tachypnoea and petechiae occurring
12–48 hours after trauma.
•• The incidence of fat embolism presenting clinically varies between 0.5%
and 2% of patients with long bone fractures and 5–10% of patients with
multiple fractures.
•• Subclinically, it is present in almost all cases of long bone fractures.
AETIOLOGY
•• The causes of fat embolism syndrome (FES) are as follows:
Traumatic Factors
•• Fractures
–– Long bone
–– Pelvis.
•• Burns and subcutaneous adipose tissue injuries.
•• Surgery
–– Intramedullary (IM) nailing
–– Total hip and knee arthroplasty.
Non-traumatic Factors
•• Procedures
–– Cardiopulmonary resuscitation (CPR)
–– Cryosurgery of bone
–– Intraosseous fluid and drug administration
–– Liposuction
–– Intra-operative autotransfusion
–– Lymphangiography
–– Hysterosalpingography.
Diseases
•• Sickle cell anaemia
•• Acute pancreatitis
230
•• Fatty liver
•• Diabetes
•• Immunosuppression.
Drugs
•• Lipid emulsions
•• Intra-arterial cisplatin
•• Long-term steroid administration.
PATHOPHYSIOLOGY
•• Two theories have been proposed to explain the pathophysiological basis
of the FES:
1. Mechanical theory of Gauss
2. Biochemical theory of Lehman and Moore.
•• Mechanical Theory:
–– FES results because of the physical obstruction of pulmonary and
systemic vasculature by the embolised fat which is liberated into the
circulation from the bone marrow at the site of a fracture.
–– This theory basically explains the FES of traumatic origin.
–– The presence of cardiac septal defects will increase the incidence of
systemic embolism.
•• Biochemical Theory:
–– Explains the non-traumatic origin of FES, fat globules in the pulmonary
or systemic circulation originate from the lipids normally present in the
blood.
–– Physiochemical alterations of these compounds can lead to FES by
two mechanisms: toxic and obstructive.
–– Circulating free fatty acids (FFAs) are directly toxic to the pneumocytes
and the capillary endothelium.
–– FFAs are usually cleared by the liver and in the presence of shock
and associated hypovolaemia and sepsis, the blood flow to the liver is
reduced, which leads to the exacerbation of the toxic effects of the FFAs.
–– The obstructive mechanism attributes to the development of FES to
the coalescence of chylomicrons into fat globules, which is triggered
by the mediators released at the site of a fracture.
•• Additional mechanisms appear to contribute to the pathophysiology of
FES. These include activation of the platelets, coagulative and fibrinolytic
cascades.
•• Pathological examination revealed alveolar oedema and haemorrhage with
multiple fat droplet depositions and fibrin thrombi.
•• Fat droplets were also found in the arterioles and/or capillaries in the lung,
kidney and brain.
•• Immunohistochemical staining identified inducible nitric oxide synthase
(iNOS) in alveolar macrophages.
CLINICAL FEATURES OF FAT EMBOLISM

SYNDROME
•• Fat embolism syndrome is a serious manifestation of fat embolism that
involves a cascade of clinical signs such as petechial haemorrhages,
deteriorating mental status and progressive respiratory insufficiency, usually
occurring within 24 hours of an injury, particularly a fracture of the long bones.
Chapter 28 • Fat Embolism
231
•• Clinically, FES consists of a triad of hypoxia, confusion and petechiae

appearing in a patient with fracture, 1–2 days after the trauma.
NEUROLOGICAL ABNORMALITIES
•• Neurological impairment occurs in about 85% of cases who die of FES.
•• It begins as an acute confusional state and then progresses to stupor and
coma.
•• Seizures have been reported.
•• Focal neurological deficits can be identified, including anisocoria, hemiplegia,
scotomata, apraxia, aphasia and conjugate eye deviation.
•• Focal neurological findings typically follow the encephalopathy.
•• Cerebral oedema and decorticate posturing have been reported in severe
cases and are reversible, suggesting that in certain cases, intracranial
pressure monitoring may be beneficial.
•• Pathologically, diffuse petechial haemorrhages are present, predominantly
in the white matter of the cerebral cortex.
•• Ischaemic lesions are present and fat globules are demonstrated in the
micro-vessels.
DIAGNOSIS
•• Diagnosis of this syndrome is mainly a clinical one, that requires accumu-
lation of clinical and laboratory findings and exclusion of other diagnostic
possibilities.
•• Several diagnostic criteria have been reported in the literature, of which,
two have found wide acceptance:
•• Gurd and Wilson’s Criteria:
–– Major clinical features: petechial rash, respiratory insufficiency and
cerebral involvement.
–– Minor clinical features: pyrexia, tachycardia, retinal changes, jaundice
and renal changes.
–– Fat macroglobulinaemia.
–– Presence of one major clinical feature, four minor clinical features and
fat macroglobulinaemia, gives a positive diagnosis.
•• Lindeque et al. Criteria:
–– PaO2 < 60 mmHg on room air respiration.
–– PaCO2 > 55 mmHg or pHa < 7.3.
–– Spontaneous respiratory rate > 35 breaths/min (even after adequate
sedation).
–– Clinical signs of increased work of breathing (dyspnoea, accessory
muscle use) and tachycardia.
–– The presence of at least one of these findings in a patient with long
bone fracture(s) establishes the diagnosis of FES.
Laboratory Tests
•• Cytological examination of urine, blood and sputum after Sudan or Oil
Red O staining may permit detection of fat globules, either free or in
macrophages within 2–3 hours after collection of the specimen.
•• Examination of the blood for fat globules by cryostat test helps in the
diagnosis when it is performed on the blood obtained from the pulmonary
vasculature, where a large amount of fat globules are trapped.
232
•• Quantification of the cells containing fat droplets in broncho-alveolar lavage

material is helpful in diagnosing clinical fat embolism.
•• The lavage done with the help of a fibreoptic bronchoscope that is wedged
in a sub-segmental bronchus, preferably in the one with maximal infiltrates
on the chest radiograph.
•• Other laboratory tests like measurement of blood lipids, activated
complement levels and coagulation parameters will not help in the diagnosis
of the FES.
•• Chest radiograph shows distributed fleck-like shadows and increased
interstitial and alveolar densities are the typical findings, and give the
radiograph a snow-storm appearance.
•• Ventilation/perfusion scans show sub-segmental perfusion defects, a
finding highly suggestive of FES.
•• CT scan of the brain in cases of cerebral fat embolism may demonstrate
diffuse oedema and low density areas with haemorrhages.
•• MRI is indicated in any patient with orthopaedic injuries who manifests an
unexplained acute alteration in mental status, despite a normal head CT.
•• MRI of the brain may show hypointense signals on T1-weighted images
and hyperintense signals on T2-weighted images.
•• On the diffusion-weighted scans, areas of fat embolism are revealed as
bright spots on a dark background (“starfield” pattern).
•• High-intensity lesions in the brain on diffusion-weighted images may serve
as an early-appearing and more sensitive indicator of the diagnosis of fat
embolism, in the clinical context of long bone injury without head trauma.
•• Single photon emission computed tomography may demonstrate hypop-
erfusion in areas of fat embolism.
•• Transcranial Doppler was found to be useful for monitoring of the micro-
emboli moving in the cerebral vessels.
MANAGEMENT
Prevention
•• Most authors recommend early fixation of all fractures after stabilisation of
the systemic complications, although this approach has neither decreased
nor worsened the incidence of FES in these patients.
•• Surgery can best be carried out after the patient has been fully resuscitated.
Treatment of Established Fat Embolism Syndrome

•• Treatment is largely symptomatic with therapy for respiratory failure similar
to that used in the management of acute respiratory distress syndrome.
•• Corticosteroids have not been found to be of significant benefit.
•• The mainstay of treatment of FES is supportive.
•• Administration of adequate humidified oxygen (titrated against the
patient’s needs by monitoring the arterial blood gas levels) together with
fluid replacement and physiotherapy to the chest, minimises the risk of
secondary infection.
•• Mechanical ventilation is advocated wherever there is an indication.
•• The hypoxaemia is addressed by manipulating the concentration of inspired
oxygen and using positive end expiratory pressures.
•• Antibiotics may be required for secondary infection, and tracheostomy and
nutritional support may be needed if prolonged ventilation is necessary.
29
CHAPTER
Paediatric Head Injuries
Chidambaram Balasubramaniam  Ramachandran B
GROWTH AND DEVELOPMENT

•• The child, and in particular the brain, undergoes constant and dynamic
changes from birth to adulthood.
•• These changes have serious implications when the brain suffers a traumatic
injury.
•• The changes are seen in body weight, head size, blood volume, tracheal
size, etc. These have direct implications on the management of the child
who has sustained a polytrauma or head injury.
•• Neuronal plasticity which, in simple terms, is the process by which the
CNS develops and recovers from an insult is active till growth is complete.
•• In spite of neuronal plasticity coming into play in the recovery process,
the outcome depends on the age at the time of injury, severity and the
location of the injury.
•• The two other important factors which have a direct influence on the
outcome are the increased water content in the child’s brain and the process
of myelination which continues past the second year.
•• The consumption rate of oxygen in children is twice that of adults. In a
state of shock, the infant heart can increase the output, only by increasing
the heart rate and not the stroke volume. Hence, the child may go into
irreversible hypovolaemic shock without manifesting hypotension.
•• The relative surface area of children is greater than adults. So, hypothermia
is a real danger when the clothes are removed in a cold environment to
evaluate the injuries in a child who has sustained polytrauma. Reverse is
also true, the child may develop hypothermia if kept in a hot environment,
so common in tropical climate.
CLINICAL ASPECTS
Evaluation and Management of the Injured Child
•• The steps in assessing and evaluating a child who has suffered a traumatic
injury are as follows: (a) airway, (b) breathing, (c) circulation, (d) disability
(neurologic) evaluation, (e) exposing and evaluating all injuries and (f) fluid
therapy for resuscitation.
•• Hypoxia and hypotension have been shown to be associated with increased
morbidity and mortality and should, therefore, be treated aggressively as
far as possible at the site of injury and during transport to the hospital.
•• The airway should be cleared by a “jaw thrust” technique, rather than a
“head tilt−chin lift” manoeuvre.
234
•• A hard cervical collar of the appropriate size should be applied and,

whenever this is removed, the cervical spine must be stabilised manually
by an assistant till a cervical spine fracture has been ruled out.
•• The guidelines in Table 1 can be used to decide which patients should
receive assisted ventilation with an endotracheal tube.
•• In suspected anterior skull base or facial fractures, an orogastric rather
than a nasogastric tube is passed lest the latter enter the intracranial cavity
through the fracture site.
•• Endotracheal intubation is a noxious stimulus that results in increased
intracranial pressure (ICP). Unless the patient is in a state of cardiopulmonary
arrest, he should always be prepared with adequate pre-oxygenation,
sedation and neuromuscular blockade.
•• The drugs used should be chosen after considering the haemodynamic
stability of the patient, since some will cause or exacerbate hypotension.
These have been elaborated in Table 2.
•• Breathing is best evaluated by observing the chest movement.
•• Patients with isolated head injuries seldom are in shock except in certain
special situations. Therefore, if a child with head injury is in shock, other
sources of blood loss, such as intra-abdominal injuries, should be searched
for.
•• The primary objective in the patient with shock is to restore the intravascular
volume as quickly as possible. Fluids should not be withheld in the patient
in shock due to the concerns of worsening cerebral oedema.
•• Clinical signs of increased ICP, such as unilateral or bilateral pupillary
dilatation, asymmetric pupillary reaction, posturing or other evidence of
neurological deterioration, should be treated aggressively.
Table 1: Guidelines for intubation

• A GCS of 8 or less
• A decrease in the GCS >2, irrespective of the initial GCS
• Anisocoria >1 mm
• Cervical spine injury compromising ventilation
• Apnoea
• Loss of the cough and/or gag reflexes
• Inability to clear upper airway secretions
• Uncontrollable seizures
• Associated chest injuries
Table 2: Drugs for intubation of the head-injured child

• Haemodynamically unstable Fentanyl 2−4 mcg/kg
Lidocaine 1 mg/kg
Vecuronium 0.2−0.3 mg/kg
• Haemodynamically stable Fentanyl 2−4 mcg/kg
Lidocaine 1 mg/kg
Midazolam 0.1−0.2 mg/kg
• Raised ICP Fentanyl 2−4 mcg/kg
Lidocaine 1 mg/kg
Thiopentone sodium 4 mg/kg
Chapter 29 • Paediatric Head Injuries
235
•• It is important to avoid hypothermia when doing this, since hypothermia is

tolerated poorly. The relatively large surface area in children predisposes
not only to hypothermia but also to increased insensible water loss.
•• After resuscitation, basic investigations should be done, including
estimation of electrolytes, glucose, haematocrit and blood gases.
•• After the initial resuscitation, a detailed neurological examination is carried
out and the patient is transported to the nearest available CT scanner.
•• A detailed history of the cause and nature of injury should be obtained after
the child has been stabilised.
•• The AVPU scoring is as follows: A—Alert; V—Responds to verbal com-
mands; P—Responds to pain; and U—Unresponsive.
•• The GCS is more popular and more comprehensive. The adult scoring
system has been modified for use in children. The adult and the paediatric
scores are as indicated in Table 3.
•• Additional points to be noted in the examination are palpation of the
fontanelles and sutures. The former may be bulging or tense in the presence
of raised ICP while the latter may be splayed.
•• Vomiting is very common after head injuries in children. Although vomiting
is a hallmark of raised ICP in adults who have sustained a head injury, it
may follow even trivial injuries in children.
•• Seizures too are common in the head-injured child and like vomiting may
follow even trivial injuries.
•• The following group of children are at increased risk for post-traumatic
seizures: “those with diffuse cerebral oedema, acute subdural haematoma,
compound depressed skull fracture with parenchymal damage, or severe
head injury (GCS ≤8)”.
•• The blood loss resulting from scalp injury can be severe enough in children
to precipitate hypovolaemic shock. Even subgaleal haematomas can be
large enough to cause significant blood loss.
Table 3: Glasgow coma score in adults and children

Score Adults Children
Eye opening:
4 Spontaneous Spontaneous
3 To command To sound/speech
2 To pain To pain
1 None None
Motor response:
6 Obeys spontaneous Spontaneous/obeys
5 Localises Localises
4 Withdraws Withdraws
3 Abnormal flexion Abnormal flexion
2 Abnormal extension Abnormal extension
1 None None
Verbal response:
5 Oriented Appropriate for age
4 Confused Crying but consolable
3 Inappropriate words Irritable/Restless
2 Incomprehensible sounds Lethargic
1 None None
236
Injuries in the Various Age Groups

•• Injuries in neonates are due to two factors:
1. Those caused by the natural forces of labour and
2. Those produced by obstetric intervention.
•• Closed depressed fractures referred to as “ping pong” or “pond” fractures
are seen in the parietal region usually at the parietal eminence. These
fractures may result from the soft cranium being pressed against the sacral
promontory or ischial tuberosity of the mother. This injury may also be
seen when forceps have been applied. Although plain skiagrams reveal
the amount of depression, a CT scan is needed to evaluate the degree of
underlying brain damage.
•• Parenchymal injuries or bleeds are uncommon in neonates.
•• Epidural, subdural and subarachnoid haemorrhages again are not very
common.
•• Intraventricular haemorrhage from germinal matrix haemorrhage is seen
in premature infants but not in term infants.
•• The other cause for intracranial bleeds is clotting disorders.
•• Posterior fossa haemorrhage can occur in neonates as a result of birth
trauma. During the process of labour, the skull is compressed in the
anteroposterior direction. This results in stretching of the falx and also com-
pression of the cerebellum. The result is rupture at the falcotentorial junction
and consequent bleeding from the venous sinuses and bridging veins.
•• Shaken baby syndrome refers to the infants with acute subdural haematoma
and subarachnoid haemorrhage, retinal haemorrhages and periosteal new
bone formation at epiphyseal regions of long bones resulting from to and
fro shaking of a child’s body producing a whiplash motion of the child’s
head on the neck.
•• Injuries in toddlers result from a variety of causes. Fall from a cot and
stumbling and falling when learning to walk are the commonest causes.
•• The common symptoms which prompt the parents to seek medical attention
are vomiting, seizures and the appearance of subgaleal haematoma after
a fall.
•• Falls, minor or major (like from the first floor balcony), may not cause
significant intracranial problems, but a skull fracture may be seen in many
instances. These fractures may be extensive and may extend bilaterally.
•• Epidural haematomas may occur in this age group without any skull fracture
or only an insignificant fracture.
•• Rotational acceleration in children due to blunt trauma to the ear may
result in “tin ear syndrome” which comprises of unilateral ear bruising,
radiographic evidence of ipisilateral cerebral oedema with obliteration of
the basilar cisterns, and haemorrhagic retinopathy.
•• Subdural haematomas (SDH) usually follow a severe injury like falls from
the first or second floor, traffic accidents, etc. The presentation is more
acute and these children deteriorate faster.
•• Injuries in older children and teenagers are usually the result of falls
from balconies, injuries sustained when playing and traffic accidents on
the way to and from school.
•• The major cause of serious injuries in this age group is acceleration-
deceleration injury. Hence, diffuse injuries are commonest in this age group.
237
SPECIFIC INJURIES AND PROBLEMS

•• Scalp injuries are seen commonly in all age groups and are a part of almost
all traumatic injuries involving the head and neck.
•• A certain amount of scalp haematoma is seen even at the time of birth—
caput succedaneum—which resolves over a few days.
•• Fractures are seen in all paediatric age groups. They are present in up to
20% of children admitted for the management of head injuries. Despite this
high prevalence many of the fractures do not need any treatment.
•• In adolescents, the presence of a skull fracture is the only significant risk
factor for predicting an ICH.
•• Linear fractures are the commonest variety of skull fractures in children.
•• Growing fractures:
–– A rare complication of fractures, is also peculiar to the paediatric age
group, generally between 2 and 5 years.
–– These are also referred to as enlarging/expanding skull fractures, lep-
tomeningeal cysts and post-traumatic meningocoeles.
–– A dural laceration beneath the fracture is mandatory for this to occur.
–– The dural laceration and the fracture result in the “amplification of the
ICP pulse wave”, which in turn results in herniation of the arachnoid
and brain.
–– Over a period of time, due to the transmitted pulsations of the brain, the
edges of the fracture separate and the fracture “grows”.
–– These manifest clinically as a pulsatile swelling at the site of injury, a
few weeks or months after the injury.
–– In addition, hemiparesis and seizures may be present.
–– Since this entity is associated with a severe injury, a meningocerebral
cicatrix is usually seen at the site of injury.
–– The treatment is surgical. The fracture margins are exposed and the
dura and arachnoid are exposed. These are separated from the site of
incarceration. Watertight dural repair is mandatory to prevent further
incarceration and growth of the fracture. The calvarium is then recon-
structed preferably using autogenous bone grafts.
•• Depressed fractures in the paediatric age group are usually green stick
fractures unlike those in adults. This is because the skull of children is
softer than the skull of adults.
•• In neonates the skull is “soft” and membranous, hence it does not fracture
so easily.
•• Small fractures do not need any specific treatment since the growing brain
“pushes” the depressed segment out.
•• The indications for surgical elevation are similar to those for other closed
depressed fractures, namely large diameter of the depression (>3−4 cm),
significant depression, pressure on or deformation of subjacent brain, focal
deficit, seizures or cosmetic disfigurement.
•• Surgery, if it is to be performed, is best done within the first week. This
will make elevation easier since the depressed segments would not have
fused. A vacuum device (i.e. obstetric vacuum extractor) has also been
used to elevate these fractures.
•• Basal fractures and those involving the frontal air sinuses are commoner in
adults. If there are clinical indicators of basal fractures or fractures involving
the frontal air sinus (like raccoon eyes or Battle’s sign), the presence of
these fractures must be assumed to be present until proved otherwise and
all precautions must be taken during management.
238
•• Contusions of the brain in children as in adults may be a cause for delayed

deterioration.
•• Cortical blindness is an entity peculiar to children. Immediately, or soon after
a fall, the child complains of loss of vision. The pupils will be reacting normally
to light. The blindness recovers without any treatment. Associated features
are headache, nausea, vomiting and irritability. The etiology has been
attributed to concussion of the occipital lobe and transient “kinking” of the
posterior cerebral arteries. Vasospasm has also been proposed as a cause.
•• This condition has to be differentiated from post-traumatic optic neuropathy
where the blindness is unilateral and recovery is poor.
•• Diffuse brain swelling is a condition seen in children, more commonly than
in adults.
•• Even though the child may be clinically normal, the initial CT may show
changes like compression of the perimesencephalic cisterns, absent third
ventricle and diffuse cerebral swelling.
•• Extradural haematomas in infants are venous in origin unlike those in
older children in whom it is arterial. The other sources of bleeding are the
fractured edge of the bone and from venous sinuses. The latter is often
the source in posterior fossa haematomas.
•• In older children, the aetiology is as in adults, bleeding from the middle
meningeal artery.
•• For nonsurgical treatment, the indications are conscious children with no
neurologic deficit but with mild to moderate headache, nausea, infrequent
vomiting.
•• Conservative treatment is terminated, if the patient develops a focal
deficit, the level of consciousness deteriorates, pupillary changes develop,
headache, or vomiting persists or rebleeding occurs.
•• Delayed epidural haematoma is usually seen following a severe head
injury. The diagnosis is based on a high index of suspicion in the absence
of neurologic deficit. The outcome is good if timely intervention is carried
out, even in delayed extradural haemorrhage (EDH).
•• The source of bleeding in a posterior fossa EDH is usually venous—from
a venous sinus. An associated fracture of the occipital bone is seen in a
significant number of these children. At times, the clot can extend to the
supratentorial compartment as well. Rapid deterioration is a hall mark of
this condition.
•• Subdural haematoma (SDH) in older children generally present as they do
in adults—as an acute event following trauma.
•• In neonates, due to enlarged subarachnoid spaces, the bridging veins snap
easily and may lead to a subdural collection.
•• ICH occurring in childhood has certain features which are not encountered
in adults. Since the aetiopathogenesis, clinical features and management
of germinal matrix haemorrhage are completely different.
•• These include bleeding as a result of coagulopathies, vascular malformation
or tumour (Table 4).
CRITICAL CARE
Indications for Admission to the ICU
Neurosurgical Indications
Seriously head-injured children—even if the child is neurologically intact, i.e.
child with multiple contusions as seen in CT.
239
Table 4: Spontaneous intracranial haemorrhage: Causes

Structural causes:
• Bleed into a tumour or an infarction
• Vascular malformations: AVM; aneurysms; cavernomas
• Vasculopathies: Inflammatory; moyamoya syndrome
• Dural sinus thrombosis
• Venous infarcts
Non-structural causes:
• Coagulopathies: Haemophilia; vitamin K deficiency
• Liver disorders
• Anticoagulation therapy
• Disseminated intravascular coagulation: Due to any cause
• Platelet disorders
• Fulminant sepsis
• Unknown aetiology: Germinal matrix haemorrhage
Children with impending neurologic deterioration.

Children with proved or suspected raised ICP.
Children with more than one episode of seizure even if the seizures are mild.
Post-operative patients.
Non-neurosurgical Indications
Intubated children—intubated for any reason whatsoever.
Polytrauma victims.
Children with compromised cardiopulmonary status.
Care in the ICU

•• Intensive care management of children should be a combined effort
between the neurosurgeon and the paediatric intensivist.
•• There are two aspects to the care of the child in the ICU: (1) Monitoring
and (2) Managing.
•• Monitoring in ICU: There are two parameters which are routinely monitored
in the ICU.
–– The non-neurologic monitoring, i.e. haemodynamic and other param-
eters like fluid and electrolyte therapy.
–– The other is the neurologic part which consists of clinical examination
and ICP monitoring.
•• Haemodynamic: In addition to routine PICU monitoring (heart rate,
respiration, pulse oximetry and non-invasive blood pressure), all patients
with serious head injuries should have invasive monitoring of the central
venous and arterial blood pressures.
•• Fluids and electrolytes: The aim of fluid therapy should be to maintain
euvolaemia. It is important to maintain an adequate preload so that the
cardiac output and blood pressure are sufficient to maintain optimal cerebral
perfusion.
•• Patients with head injury are at risk of developing the syndrome of
inappropriate antidiuretic hormone secretion (SIADH). This manifests
as a decreased urine output, despite adequate filling pressures and
hyponatraemia, and is managed by fluid restriction.
•• An important differential diagnosis for hyponatraemia in head injury is
the CSW, which is caused by an excess of atrial natriuretic peptide and
240
Table 5: Differential diagnosis of SIADH and CSW

Parameter SIADH CSW
Volume depletion No Yes
Plasma volume Isovolumic or ↑ ↓
Serum sodium ↓ ↓
Serum osmolarity ↓ Normal or ↑
Serum uric acid ↓ Normal
Serum ADH ↑ ↓
Urine sodium ↑ ↑
Sodium loss Normal Very high
Urine output Low Very high
results in massive urinary losses of sodium and water, resulting in severe

hyponatraemia and volume depletion.
•• It is vital to differentiate between the two conditions since the therapy is
different (Table 5).
•• Nutrition: Early nutritional support is extremely important. Head-injured
patients, like all trauma victims, have a hypermetabolic state with increased
nitrogen excretion that can last for several weeks.
•• Current adult recommendations are to provide 140% of the resting
metabolic expenditure in non-paralysed patients and 100% of the resting
metabolic expenditure in paralysed patients, with at least 15% of the calories
as nitrogen, upto the seventh day following head injury.
•• ICP monitoring has come to stay in the management of a head-injured
patient, but the use of ICP monitoring in adults has only been recommended
as a guideline.
•• Indications for ICP monitoring: ICP monitoring is also recommended
for patients with severe head injury and a normal head CT scan if they
have hypotension or unilateral or bilateral motor posturing. Severe head
injury is defined as a GCS of 3−8 after cardiopulmonary resuscitation. An
abnormal head CT is one that shows a haematoma, oedema, contusion
or compressed basal cisterns.
•• Using ICP to guide therapy:
–– Normal ICP in adults is 0−10 mmHg.
–– In the absence of good data for children, these adult baselines are
often used.
–– However, more important than the actual ICP is the blood flow to the
brain. This is reflected by the cerebral perfusion pressure (CPP), which
is the difference between the mean arterial pressure and the ICP (CPP
= MAP – ICP).
–– Therefore, even if the ICP is elevated, it may be possible to maintain
adequate blood supply by increasing the MAP.
–– Although the exact level at which one should intervene is being
debated, most centres intervene when the ICP is greater than 15−20
mmHg.
–– A CPP target of 70 mmHg is often used in adults.
–– Good guidelines are not available for children, but a CPP target of
40−50 mmHg in infants and toddlers and 50−60 mmHg in older chil-
dren are recommended.
•• Techniques of ICP monitoring:
–– A ventricular catheter connected to a standard pressure transducer is
the gold standard.
241
–– The other devices used commonly are fibre optic catheters with a
pressure transducer at the tip.
–– Subarachnoid, subdural and epidural devices are not accurate and
should not be used.
•• Monitoring cerebral metabolism: Various techniques, including jugular
venous saturation, near-infrared spectroscopy, cerebral parenchymal pO2
monitoring, cerebral microdialysis and positron emission tomography have
been used to monitor the cerebral metabolism.
•• Monitoring cerebral blood flow: Cerebral blood flow (CBF) can be
measured by techniques such as: (1) stable Xenon-enhanced CT; (2)
radioactive 133Xenon scanning; (3) transcranial Doppler and (4) cerebral
thermal perfusion.
•• Of the three, stable Xenon-enhanced CT is the simplest and can be
performed using almost any of the recently introduced CT scanners with
slight modifications.
•• Radioactive 133Xenon scans can be performed at the bedside and gives
information about regional blood flow.
•• Managing in the ICU: As in monitoring, there are two broad divisions:
(1) raised ICP and (2) associated problems (like seizures) and each one
influences the overall outcome.
•• The strategies may be divided as follows:
–– General: Head positioning: Elevation of the head to 30° lowers the
ICP; haemodynamic (regulating CPP); sedation and paralysis.
–– Barbiturate: Barbiturates are effective in lowering raised ICP by their
effect on altering the vascular tone, lowering cerebral metabolism and
inhibition of free radical peroxidation.
–– Diuretic:
¾¾ Both loop and osmotic diuretics have been used in the manage-
ment of head injury.
¾¾ The exact mechanism of action of mannitol is still unclear, but it
probably has two separate actions:
1. Through its rheological properties, it reduces blood viscosity
and produces an increase in the CBF and also oxygen
delivery to the brain. The increase in plasma volume after the
administration of mannitol may raise the blood pressure and
increase the CPP.
2. Its osmotic effect occurs in about 15−30 minutes after ad-
ministration. Mannitol creates an osmotic gradient across the
blood-brain barrier, which results in dehydration of the brain and
thus reduces the ICP.
¾¾ There is a risk of acute renal failure due to acute tubular necrosis,
especially when mannitol is used in large doses or the serum os-
molality is allowed to exceed 320 mOsm/L.
¾¾ Mannitol should not be used when there is pre-existing renal failure.
¾¾ The initial dose is usually 0.5−1 g/kg body weight given intrave-
nously. The child is then given mannitol at a dose of 0.25−1g/kg.
Intermittent bolus doses (administered 4−6 hourly) are thought to
be safer and more effective than a continuous infusion.
–– Ventilatory Support:
¾¾ The concept of hyperventilation was built on the foundation of the
response of the cerebral vasculature to CO2.
¾¾ Hyperventilation, however, is a double edged sword.
242
¾¾ It reduces the ICP by vasoconstriction but this vasoconstriction also

worsens the already existing cerebral ischaemia which is almost an
inevitable occurrence of severe head injury.
¾¾ So the use of hyperventilation is limited to brief periods when there
is an acute deterioration or “for longer periods if there is intracranial
hypertension refractory to sedation, paralysis, CSF drainage and
osmotic diuretics”.
•• The use of chronic prolonged or prophylactic hyperventilation should be
avoided.
Surgical Measures
•• Surgical measures include CSF drainage, removal of mass lesions and
decompressive craniectomy.
•• CSF Drainage:
–– Monitoring ICP through an indwelling ventriculostomy catheter is prob-
ably the best.
–– The CSF can be removed manually every time the pressure rises be-
yond a set level or the drainage chamber can be positioned in such a
way that the CSF drains automatically when the pressure goes above
the set level.
•• Controlled lumbar cerebrospinal fluid drainage significantly reduces
refractory intracranial hypertension.
•• The danger of transtentorial or tonsillar herniation is minimised by consid-
ering lumbar drainage in the presence of discernible basilar cisterns only.
•• Removal of mass lesions, e.g. haematomas if they are responsible for
raised ICP, should be done promptly.
•• Decompressive Craniectomy: Which was initially described by Cushing,
is now staging a resurgence, but it is mired in debate and controversy.
–– It is used in cases of refractory intracranial hypertension where con-
ventional therapies have failed.
–– The technique involves removal of a large bone flap and opening the dura.
–– The dura may be left open as it is or a graft may used to “enlarge” the
volume of the dural compartment.
–– Once the period of intracranial hypertension has settled and the patient
has improved, cranioplasty is done.
–– The decompression may be bifrontal or temporoparietal.
•• There is a large volume of literature regarding the use of corticosteroids
in head-injured patients, both adults and children. However, none have
shown conclusively that the administration of steroids is beneficial or has
any adverse effects. Therefore, steroids are not recommended in the
treatment of head injuries at this time.
Complications
•• Disseminated intravascular coagulation (DIC): Brain tissue is a rich source
of tissue thromboplastin. Following a severe traumatic brain injury, there
may be a significant outpouring of thromboplastin from the injured brain. The
released thromboplastin initiates the coagulation cascade which results in
the scenario of a “runaway” consumptive coagulopathy or DIC.
•• Neurogenic pulmonary oedema (NPE): Generally occurs 2−12 hours
after injury, although its onset may delayed further.
–– It manifests as hypoxia, hyperventilation and hypercarbia, with bilateral
fluffy infiltrates on the chest X-ray.
243
Table 6: Different treatment therapies

Treatments Monitoring
Basic level therapy:
• Elevation of head end of bed • Systemic BP and oxygenation
• Keep head in neutral position • Intracranial pressure
• Sedation ± paralysis • PaO2; PaCO2; pH
• Mechanical ventilation to keep PaCO2 • Intake/output; pulse; pulse pressure;
between 35 and 40 mmHg weight
• Maintain euvolaemia to slight hypervolae- • Haemogram; serum electrolytes; blood
mia and normal blood urea nitrogen glucose
• Maintain normal fluid and electrolyte • Monitor for sepsis/fever and if present
status; No fluid restriction; avoid anaemia treat aggressively
and hyperglycaemia
• Temperature: maintain euthermia; treat • CT scan
hyperthermia
Escalated therapy:
• Ventricular CSF drainage • Ventricular catheter
• Mannitol • Central venous pressure
• Maintain PaCO2 between 30−35 mmHg • Serum osmolality
Intensive therapy (for refractory raised ICP):
• High dose barbiturate therapy • Continuous EEG, serum level of barbitu-
rates
• Lumbar CSF drainage • Jugular venous O2 saturation, CBF
• Decompressive craniectomy
• Hyperventilation for acute rise in ICP
(Source: Modified from Leurssen)
–– This oedema is non-cardiogenic and is due to increased pulmonary

permeability.
–– Medullary ischaemia causes a sudden massive surge in sympathetic
activity, which leads to increased pulmonary vascular pressures and
shifts blood from the systemic into the pulmonary circulation.
–– There is increased permeability in the lungs, which allows the transu-
dation of fluid into the alveoli.
–– NPE generally resolves spontaneously if the patient survives. The
presence of NPE in any head injured or polytrauma victim results in a
poor prognosis.
SUMMARY
•• Treatment has been divided into basic, escalated and intensive tires
(Table 6).
•• Two rules are to be observed in following these guidelines before
“escalating therapy to any higher level”:
–– “One must confirm that the current therapy is being correctly applied”
–– “Prior to any escalation of therapy, escalation of systemic and neuro-
logic monitoring must occur.”
30
CHAPTER Clinical Assessment of a
Head Injured Patient
Rajkumar  Samir Kumar Kalra  Ashok Kumar Mahapatra
INTRODUCTION
•• The major goals of assessment are:
–– To have a baseline evaluation of clinical parameters for future com-
parison.
–– To determine the presence of an intracranial mass lesion requiring
operative removal.
–– To define an abnormal intracranial mass lesion for institution of ap-
propriate operative or non-operative therapy.
–– To diagnose associated injuries.
–– To carry out necessary investigations.
–– To prognosticate patients and apprise them or relatives of the possible
course of illness.
–– To allow statistical analysis and comparative studies.
CONSCIOUS LEVEL
•• It must be pointed out that the single most important parameter for
evaluation of a head-injured patient is the state of consciousness and its
evolution during the period of observation till full recovery.
•• The initial evaluation should be as thorough as possible whether the patient
presents in a conscious or an unconscious state.
•• The anatomical, as well as physiological parameters are assessed on
examination.
•• The anatomical parameters are assessed by the abbreviated injury scale
and the injury severity score.
•• The Glasgow Coma Scale (GCS) and the Revised Trauma Score (RTS)
are commonly used to measure the physiological derangements.
•• The RTS provides an assessment of the physiological state by including
respiratory rate, systolic blood pressure and GCS.
GENERAL EXAMINATION
•• The first concern of the physician after having assessed the level of
consciousness is to assess the respiration and insure a clear airway and
oxygenation.
•• Endotracheal intubation is often necessary to protect the airway and
maintain the ventilation. As a rule, intubation requires ventilation.
•• The vital parameters including the pulse rate, blood pressure and respiration
should be assessed.
Chapter 30 • Clinical Assessment of a Head Injured Patient
245
CLINICAL HISTORY
•• The feedback from the attendants, relatives, police or any eye witness
who brought the patient should also be obtained regarding the scene of
the accident and the course of events following injury.
•• Post-traumatic amnesia is an index of the severity of injury and should be
ascertained.
•• A history of seizures should be inquired into and recorded. The seizures
occurring following trauma, may be of three types:
–– Immediate seizures; occurring within 24 hours.
–– Early seizures; occurring within 7 days.
–– Late seizures; occurring later than 7 days.
GENERAL PHYSICAL EXAMINATION

•• The chest, abdomen, pelvis, spine and long bones should also be
assessed for associated injuries and an effort should be made to have a
comprehensive whole-body examination.
•• All scalp wounds, lacerations and avulsions should be inspected.
•• The forehead should be palpated for signs of a depressed fracture or
frontal sinus injury.
•• Associated CSF rhinorrhoea or otorrhoea are usually secondary to basal
skull fractures and should be sought.
•• Bilateral periorbital haematomas (raccoon eyes) result from fractures of
the orbital roof.
•• Associated bleeding beneath the pericranium over the mastoid (Battle’s
sign) usually appears after 2−3 days. This indicates presence of base of
skull fracture.
•• A high index of suspicion should be kept for an associated cervical injury.
•• The auscultation of carotid arteries and the eyes should be done to rule out
an associated carotid dissection and traumatic carotid cavernous fistula,
respectively.
NEUROLOGICAL ASSESSMENT
•• The single most important parameter of neurological examination is the
state of consciousness.
•• This should be recorded meticulously as per the GCS as already discussed.
The score was first introduced in 1974 and then revised in 1977 by the
addition of another motor response. The score includes eye opening, best
motor response and best verbal response.
•• The GCS has been adopted by neurosurgical units all over the world to
evaluate head-injured patients. The score also helps to classify the types
of head injury into three categories namely:
–– Mild head injury; GCS 13−15.
–– Moderate head injury; GCS 9−12.
–– Severe head injury; GCS 8 or less.
•• The score, however, has a few pitfalls despite its wide acceptance. They
are:
–– Eye movements and other brainstem reflexes are not taken into account.
–– Patients with dysphasia or with bilateral ecchymosis have inaccurate
recording.
–– GCS does not take into account the pupillary status and vital para-
meters.
246
–– Facial fractures or lip and tongue injuries may impede patients from
talking.
–– The usefulness in children is limited and a modified scale called the
“children coma scale” is used for them.
•• The children coma scale has the same three parameters as used in the
GCS and only the verbal response is different from the GCS. This is best
used in children below 4 years of age.
Pupillary Status and Optic Nerve Function

•• The pupillary status constitutes an important part of the neurological
examination and the size, shape, position, reaction to light and the pupillary
reflexes should be recorded in all cases.
•• An attempt to see the fundus is also made at this time along with the
observation of the iris margins and evidence of local injury to the eye.
•• The pupillary size depends upon a balance of tonic forces constituted by
pupilloconstrictor parasympathetic and pupillodilator sympathetic controls.
•• The pupillary status and their changes are related to the brainstem and
both II and III nerve activity.
•• In an unconscious patient, the direct and consensual reflexes are most
important aids to assess optic nerve function.
•• The direct and consensual reflexes should both be elicited as they help to
distinguish between II and III nerve injuries.
•• In patients having hemianopias, the signs are elicited from the blind side
of the visual field.
•• A unilateral dilated and non-reactive pupil with absent consensual reflex
points towards an underlying optic nerve injury.
•• The interruption of oculo-sympathetic neurons may result in Horner’s
syndrome. This syndrome is characterised by unilateral miosis, facial
anhidrosis, ptosis, pseudoenophthalmos and loss of ciliospinal reflex.
•• Bilaterally dilated pupils are indicators of a poor prognosis and are early
harbingers of brain death.
•• There are certain conditions like bilateral glaucoma with blindness, drugs
like atropine, dhatura and glutethimide poisoning which can lead to bilateral
pupillary dilatation and such entities should be kept in mind when one sees
a patient with bilaterally dilated and non-reactive pupils.
•• The patients with accidental or post-surgical aphakia may have irregular
pupils.
•• Colobomas of the iris may lead to irregular pupils as well.
•• Opiate and barbiturate poisoning lead to small-sized pupils.
Eye Movements
•• For unconscious patients, the “Doll’s head ocular movement” and oculo-
vestibular reflex (caloric response) can be elicited. These are amongst
the most important signs for assessment of brainstem function in an
unconscious patients.
•• The presence of nystagmus in the same direction as the warm saline and
in the opposite direction to the cold saline (well-known mnemonic: COWS)
is indicative of the integrity of the brainstem.
•• It also helps to evaluate abnormalities of the ocular nerves or gaze paresis.
•• Patients with head injury can also have upward or downward gaze palsies.
247
•• The upward gaze palsies occur in compressive or destructive lesions

involving the pretectal area of the midbrain, posterior commissure and
dorsal midbrain tegmentum.
•• Lesions in the pons involving the pontine paramedian reticular formation
(PPRF) produce conjugate deviation of the eyes toward the opposite side.
•• Internuclear ophthalmoplegia is due to a lesion in the medial longitudinal
fasciculus (MLF) of the midbrain. In this condition, there is impaired
adduction of the ipsilateral eye with nystagmus of the abducting opposite
eye during attempted lateral gaze to the opposite side.
•• The so-called “one and a half syndrome” is due to a lesion involving both
the PPRF and the MLF on the same side and is associated with ipsilateral
gaze paresis with impaired adduction of the ipsilateral eye and nystagmus
on abduction of the opposite side. It is possible to ascertain these deficits by
using the cold-caloric (vestibulo-ocular reflex) test in unconscious patients.
•• Skew deviation in which one eye is directed upward and the other eye is
directed downward may also be noted. This is indicative of lesions of the
brachium pontis or dorsolateral medulla and point toward a grave prognosis.
Other Cranial Nerves

•• It is impossible to examine the olfactory nerve in unconscious patients.
•• Fractures of the anterior cranial fossa may be associated with loss of smell
and, so, the sense of smell should be examined in all conscious patients.
•• The V cranial nerve may be injured in fractures of the middle cranial fossa.
The corneal reflex tests the integrity of the V and VII cranial nerves and is
done with a moist light cotton wisp.
•• The VII and VIII cranial nerves may also be affected in fractures of the
petrous pyramid.
•• The more common longitudinal fracture of the petrous bone is due to a
lateral blow to the head and may result in facial nerve injury and CSF leak.
•• The less common transverse fracture results from occipital blows and
is associated with a higher incidence of facial nerve injury and other
complications. There may be associated CSF otorrhoea, deafness or
vertigo.
•• Patients may also have vertigo on account of micro-haemorrhages in the
vestibular system. It is impossible to test the auditory component of the
VIII nerve directly in the unconscious patient (except by evoked potential
using audiometric inputs). The vestibular component is tested using the
caloric test.
•• Posterior fossa fractures involve the lower cranial nerves. A haematoma
below the mastoid is seen as a skin discolouration.
•• The assessment of vocal cord function, gag and swallowing evaluates
glossopharyngeal and vagus nerve functions.
•• The endotracheal tube in an unconscious patient can be manipulated to
elicit these responses.
Motor Examination and Reflexes

•• In conscious and alert patients, muscle tone can be evaluated by passive
range of movement and muscle power by assessing voluntary movement.
•• The Medical Research Council Grading is used to grade muscle function.
248
•• The assessment of motor power in an unconscious or uncooperative

patient is done by observing the characteristics and strength of response
to painful stimuli.
•• The painful stimulus used is pressure applied with the thumb in the
supraorbital groove thereby pressing on the supraorbital nerve. The
responses of the two sides are compared.
•• Mass effect on one side produces pupillary dilatation on the same side
with hemiplegia of the opposite side. This is the usual situation and is due
to the involvement of the III nerve, and the pyramidal tracts in the cerebral
peduncle.
•• There are exceptions to this axiom and the dilated and non-reactive pupil
may be associated with ipsilateral hemiplegia due to the indentation of
the contralateral cerebral peduncle by the edge of the tentorium cerebelli
(Kernohan’s notch).
•• The “decorticate posture” indicates severe supratentorial damage. This
is represented by patients in abnormal flexion with adduction and internal
rotation of the shoulders, slow flexion of elbow, wrist and fingers with flexion
or extension of the lower limbs.
•• The “decerebrate posture” indicates a lesion in the midbrain between the
superior and the inferior colliculi. There is extensor motor response with the
head extended backward and extension of all limbs and internal rotation
of the arms and opisthotonus position.
•• The common tendon reflexes include biceps, supinator, triceps, knee and
ankle jerks.
•• The abnormal reflexes may be exaggerated, diminished or absent.
•• The superficial reflexes include the plantar reflex and the superficial
abdominal reflex.
•• Patients with corticospinal tract involvement have an extensor plantar
response.
•• In patients with suspected spinal cord injury, anal wink and bulbocavernous
reflexes are also checked.
•• The tests for co-ordination, involuntary movements and gait should be
included as a part of the examination whenever feasible.
SENSORY AND LOCAL EXAMINATION

•• The local examination should include looking for any external swelling,
laceration or avulsion of the scalp.
•• A simple depressed fracture can often be seen and palpated, except when
covered by a scalp haematoma.
•• Local deformity and tenderness should be sought.
•• The examination of the neck for tenderness and stiffness should be
performed as a routine and there should be a high index of suspicion of
an associated cervical injury in all cases of head injury.
•• The sensory examination should include tests for pain, touch, temperature,
vibration and sense of position.
BRAIN DEATH
•• The crucial point in determining brain death is the cessation of all brainstem
functions.
•• The aim of neurological examination is to prove death of the whole
brainstem and to detect any evidence of persisting function.
249
•• The causes of brainstem death can be either related to primary damage

of the brainstem itself or secondary damage resulting from increased
intracranial pressure with compromised blood supply.
•• A better understanding of brainstem death has clearly increased the number
of patients in whom mechanical ventilation has electively been stopped,
avoiding both an excessively long and tragic waiting period for the family
and the enormous costs of intensive care.
•• The concept of brain death became a legal issue and, in India, it was defined
in 1995 in “The Transplantation of Human Organ Act, 1995”.
•• There are various criteria used differently all around the world to define
brain death.
•• Each brain dead patient is a potential donor for organs and all neurosur-
geons must be well aware of the rules, regulations and the essential criteria
required for such a diagnosis.
31
CHAPTER Fluid and Electrolyte
Balance in Head Injury
Sharma RR
INTRODUCTION
•• The incidence of significant fluid and electrolyte imbalance increases with
the severity of injury.
•• Though it is very rare in minor head injury (1−2%) and infrequent in
moderate head injury (5−8%), it is very frequent in severely head-injured
patients (8−25%).
•• Principally, polytrauma patients with severe head injury, especially central
neuraxis damage and hypothalamic insult, usually develop fluid and
electrolyte disturbances.
•• Minor fluid and electrolyte disturbances are self-correctable, moderate
disturbances get corrected with routine therapy, whereas the management
of severe disturbances may be extremely challenging even in neuro-
intensive care units (NICUs).
GENERAL CONSIDERATIONS
Head Injury Patients
•• In head injury patients, maintenance of precise fluid balance is of paramount
importance in preventing hypovolaemia, electrolyte imbalance and
intravascular coagulation.
•• Inadequate fluid therapy results in hypotension and underperfusion of the
vital organs, whereas excessive fluid therapy results in cerebral, pulmonary
and peripheral oedema.
•• The body’s mechanisms are usually adequate for correction/compensation
of fluid imbalance of minor and moderate severity, but in the severely or
critically ill patients, the mechanisms are usually compromised.
Normal Homeostatic Mechanisms

•• Normal homeostatic mechanisms maintain intracellular fluid (ICF) and
extracellular fluid (ECF) volume, tonicity and composition in healthy
individuals (Table 1).
•• However, in patients with acute head injury, alterations in fluid volume,
tonicity and composition occur due to an emergent neuroendocrine surge
[antidiuretic hormone (ADH) to retain water, renin-angiotensinogen II-
aldosterone to retain sodium, and catecholamines to support the vascular
system], which is mainly aimed at maintaining an effective intravascular
volume for adequate cerebral blood flow at the expense of ICF and ECF
fluid tonicity and composition [Na+, K+, HCO3– and H+].
Chapter 31 • Fluid and Electrolyte Balance in Head Injury
251
Table 1: Composition of ECF and ICF compartments (mmol/L)

Sl. No. Ions ECF (plasma) ECF (ISS) ICF
Cations:
1. Na+ 135−145 135−140 5−10
2. K+ 4.5−5.5 4.5−5.5 156−160
3. Others 2−3 2−3 14
Anions:
1. Cl– 101−105 115−120 3−4
2. HCO3– 26−28 26−28 10
3. PO4– & Others 1 1 106
(non-diffusible)
4. Protein 15−17 0 64−66
(non-diffusible)
Total 292 302 368
•• Disturbances of ICF/ECF tonicity and composition are often associated

with a worsening neurological status.
•• Excessive capillary leakage in the brain is well recognised as a cause of
acute cerebral swelling and its association with high morbidity and mortality.
BASIC PHYSIOPATHOLOGICAL FACTS

Water Distribution in the Body
•• A 70 kg person has 42 litres of body water; 28 litres (66%) in the intracellular
space (ICF) and 14 litres in the extracellular space (ECF): 10.5 litres in
interstitial space and 3.5 litres in plasma.
•• Water is obtained from the diet (1.5−2.1 litres/day) and oxidative metabolism
(400 mL/day) and is lost (2−2.5 litres/day) through the kidneys (sensible loss
of 1.5 litres/day), lungs, gut and skin (sum total insensible loss of 1 litre/day).
•• Its distribution in ICF and ECF is determined by the osmolalities of these
compartments.
•• Osmolality is the sum of the total solute particles in the solution and is
expressed as the molar concentration of all solutes in water (mOsm/kg).
The normal serum osmolality ranges from 280 mOsm/kg to 295 mOsm/kg.
•• Normally, ICF and ECF are isotonic. Any change in osmolality of a
compartment results in the net to and fro movement of water between the
ECF and the ICF to restore isotonicity.
•• The minimum volume of urine necessary for normal excretion of metabolic
waste products is about 500 mL/day (20 mL/h), and minimum daily dietary
water intake is about 1100 mL.
•• Free-water deficit = (0.6 × body weight in kgs) × current serum
sodium/1.40−1.
Sodium Distribution in the Body

•• The majority of exchangeable sodium is extracellular:
•• The normal ECF sodium concentration is 135−145 mmol/L while that of
the ICF is only 4−10 mmol/L.
252
•• Most cell membranes are permeable to sodium and the gradient is

maintained by active pumping of sodium from ICF to ECF by Na+/K+-
ATPase pump.
•• The normal daily intake of sodium is about 100−200 mmols, but the daily
obligatory loss is less than 10 mmols.
•• Sodium balance is maintained by regulation of its renal excretion; 70% of
glomerular filtrate is absorbed in the proximal convoluted tubules, 25% in the
loop of Henle and nearly 5% in the distal convoluted tubules and collecting
ducts (Renin-Angiotensinogen II-Aldosterone mechanism).
•• Na+ requirement is usually calculated by the following equation:
–– 0.6 × body weight × serum Na+ deficit = mmol of sodium × 0.05 = gm
of salt required.
–– 1 gm of NaCl gives 44 mmol of Na+.
–– Na+ deficit in mmols × 2 = mL of 3% saline.
–– 1 mL of 3% saline provides 0.5 mmol of Na+.
Osmolarity of the ECF

•• The osmolarity of the ECF is normally maintained in the range of 280−295
mmol/L of water.
•• Increase in ECF osmolarity in comparison to ICF osmolarity causes three
main effects:
–– Stimulation of the hypothalamic thirst centre promoting dietary water
intake.
–– Movement of water from ICF to ECF in order to maintain isotonicity,
and
–– Stimulation of hypothalamic osmoreceptors causing the release of
ADH for effective renal water reabsorption and minimising urinary
water output and, therefore, resulting in a concentrated (low water-high
solute) urine.
Osmoreceptors
•• Osmoreceptors are highly sensitive to the increased ECF osmolarity even
by 1% more than the ICF osmolarity and, therefore, stimulation of these
osmoreceptors results in immediate release of ADH in the circulation.
•• They are located outside the blood-brain barrier in the anteroventral region
of the third ventricle of the hypothalamus.
•• If the ECF osmolarity falls, then there is no sensation of thirst; ADH secretion
is inhibited (and a dilute urine is produced) allowing increase in renal water
loss to restore ECF osmolarity (by raising it) to a normal level.
•• If an increase in ECF osmolarity occurs as a result of a solute, such as
urea, which readily diffuses across cell membranes, the ICF osmolarity is
also increased. In such cases, the ECF and the ICF remain isotonic and,
therefore, osmoreceptors are not stimulated.
Hypovolaemia
•• Significant hypovolaemia (10%) is a powerful stimulus (via angiotensinogen,
arterial and venous baroreceptors and volume receptors) to ADH release
to restore effective ECF volume, even though there is a decrease in
osmolarity.
•• Maintenance of volume takes precedence over the maintenance of serum
osmolarity.
253
•• ADH is synthesised in the supraoptic nuclei of the hypothalamus and

passes down the nerve axons into the posterior pituitary from where it is
released into the circulation.
•• ADH plays a vital role in the control of the tonicity of the ECF and indirectly
of the ICF and, therefore, overall control of water balance in the body.
•• Excessive ADH secretion results in dilutional hyponatraemia (SIADH)
with a risk of water intoxication while decreased ADH secretion results in
excessive renal water loss (diabetes insipidus—DI) causing hypernatraemia
with a risk of severe dehydration (Table 2).
•• In general, patients with brain damage with preservation of the hypothalamo-
pituitary axis develop SIADH, whereas DI is due to hypothalamo-pituitary
axis disturbance/damage. Damage to the posterior pituitary gland may also
cause temporary failure of ADH secretion/release.
Atrial Natriuretic Peptide (ANP) and

Brain Natriuretic Peptide (BNP)
•• Brain natriuretic peptide (largely of cardiac ventricular origin) has biological
effects on the control of blood volume, blood pressure and electrolyte
composition.
•• ANP/BNP induce natriuresis through direct tubular effects or by inhibition
of the rennin-angiotensinogen II-aldosterone mechanism.
Serum Osmolality and Osmolarity

•• In clinical practice, serum osmolality and osmolarity are routinely measured
using the following equations:
–– Osmolality (mOsm/kg) = 2 x [Na+] + Glucose/18 + BUN/2.8.
–– Osmolality is a measure of solute concentrate per kilogram of solvent.
–– Osmolarity (mmol/L) = 2 x [Na+] + [Urea] + [Glucose]
–– Osmolarity is a measure of solute concentrate per litre of solution.
•• In clinical practice, the difference between osmolality and osmolarity is
negligible (Table 3).
•• In head injury patients, abnormalities of serum sodium (<125 or >150 mEq/L
or <150 or >300 mmol/L) and serum osmolality (<260 or >320 mOsm/kg)
should be avoided.
Table 2: Clinical manifestations of Na+ imbalance

Sl. No. Organic systems/ Hyponatraemia Hypernatraemia
clinical state
1. Neurological Cerebral oedema, Cerebral dehydration,
disorientation, lethargy, restlessness, irritability,
apathy, impairment of disorientation, ataxia, sei-
consciousness, seizures, zures, coma, intracranial
coma, Cheyne-Stokes haemorrhage
respiration, hypothermia
2. Muscular Cramps, hypotonic weak- Increased muscle tone,
ness, depressed reflexes, hyperreflexia
rhabdomyolysis
3. Renal Oliguria, concentrated Polyuria, diluted urine or
urine or hypertonic urine hypotonic urine
4. Gastrointestinal Loss of appetite, nausea, Thirst
vomiting
254
Table 3: Characteristics of parenteral fluid therapy

Sl. Name Concentration Na+ Cl– K+ HCO3– Ca2+ Calculated
No.
1. Normal saline NaCl 0.9% 150 150 – – – 300
2. Hartman’s solution Saline + K+ + 131 111 5 29 – 280
(Ringer Lactate) HCO3–
3. 5% Glucose 5% dextrose – – – – – 280
4. Dextrose saline 4% glucose, 30 30 – – – 286
0.18% saline
5. Half normal saline NaCl 0.45% 75 75 – – – 150
6. Human plasma HPPF mol. wt 150 150 5 – 2 314 or
protein fraction 69000 more
7. Haemaccel poly- Degraded gelatin 145 145 5 – 6.25 310 or
geline mol. wt. 24,500 more
8. Succinylated Gelofusin mol. 154 154 0.4 – 0.4 310
gelatin wt. 22,600
9. Hetastarch Hydroxyethyl 154 154 – – – 310 or
starch 6% in more
saline mol. wt.
70,000
10. Blood Whole blood 140 102 4 26 2.4 285
constituents
Loss of Fluid and Electrolytes

•• Loss of fluid and electrolytes without protein loss will raise the haematocrit
and plasma protein concentration. These two parameters provide a good
guide to ECF losses.
•• Haematocrit and plasma protein (albumin) are, therefore, more useful in the
assessment of plasma volume and ECF fluid losses as compared to the Na+
measurements where, although the Na+ is being lost, it does not change
in its serum concentration or in cerebral salt wasting syndrome (CSWS).
•• By invasive haemodynamic monitoring, a low pulmonary capillary wedge
pressure (<18 mmHg) or low CVP (<6 mmHg) implies volume depletion.
Clinical evidence of dehydration, weight loss, orthostatic hypotension, CVP
<6 mmHg and negative water balance are noted in CSWS.
•• Moreover, elevation of haematocrit, the serum creatinine and serum protein
concentration point to dehydration in CSWS.
•• Increased natriuresis and elevated serum K+ also suggest CSWS.
•• It is essential that appropriate fluid and electrolyte studies be done early in
the course of management of the head-injured patient.
•• Therapy is directed primarily towards the underlying cause of the fluid and
electrolyte abnormality.
•• In the potentially salvageable patients, optimal correction may occur
spontaneously or may require cautious use of medical therapy to achieve
a good outcome (Table 4).
MAIN CLINICOPATHOLOGICAL CATEGORIES

•• There are two main types of clinicopathological categories:
1. Hyponatraemia
2. Hypernatraemia
Table 4: Clinical characteristics of common causes of Na+ imbalance in head injuries
Sr. No. Clinical features Hyponatraemia Hyponatraemia SIADH Hypernatraemia CSWS Hypernatraemia DI solute
diuresis
1. Intravascular volume Hypervolaemia Hypovolaemia Hypervolaemia Hypovolaemia
2. Dehydration features Absent Present Absent Present
3. Body weight Increased Decreased Increased Decreased
4. CVP Increased Decreased Increased Decreased
5. Haematology:
i. PCWP Decreased Increased or normal Variable Increased
ii. Haematocrit Decreased Increased Decreased Increased
6. Biochemical parameters:
i. S. osmolarity Decreased Increased/ normal Increased Increased
ii. S. protein conc. Decreased/normal Increased Variable Increased
iii. BUN/Creatinine Decreased Increased/normal Variable Increased/normal
iv. S. uric acid Decreased Normal Decreased/normal Normal
v. S. Na+ Decreased Decreased Increased Increased
vi. Urine Na+ Incrreased/normal Increased Increased Decreased
vii. Urine osmolarity Increased Increased Increased Decreased
7. Management Fluid restriction, salt replace- Fluid replacement with isotonic Fluid replacement hypotonic Fluid replacement with hypotonic
ment, loop diuretics, phenytoin, fluid with therapy, blood trans- fluid, treatment of cause fluids, vasopressin, chlorpropa-
deme clocycline, lithium, fludro- fusions, fludrocortisone mide clofibrate, thiazide diuretics,
cortisone, haemodialysis carbamazepine, steroids haemo-
filtration
255
256
HYPONATRAEMIA
Maintenance of Volume in Hyponatraemic States
•• Hyponatraemia (a low serum-sodium concentration) is a common finding
in the intensive care unit. It is due to disturbance of the hypothalamo-
hypophysial axis, a metabolic response to trauma or a sick cell syndrome
requiring principally management of the underlying cause.
•• It is commonly due to water excess than to sodium loss.
•• The severity of hyponatraemia is divided into three categories: mild (Na+
<135 to 125 mEq/L); moderate (Na+ 120−124 mEq/L) and severe (Na+
<120 mEq/L).
Aetiopathogenesis
•• The risk of developing significant hyponatraemia increases in cases of
moderate and severe head injuries, fracture base of the skull and acute
subdural haematoma.
•• Following acute injury, the body retains water and sodium as a consequence
of an acute neuroendocrine surge in an attempt to maintain an effective
extracellular volume and, thereby, intravascular volume.
•• The water content of ECF increases as compared to its solute concentration,
which results in dilutional hyponatraemia.
•• Hyponatraemia lowers the seizure threshold, exacerbates cerebral oedema
and causes impairment of the level of consciousness.
•• However, the degree of cerebral disturbances usually depends upon the
rapidity of the development of hyponatraemia; a serum sodium level of 115
mmol/L may be asymptomatic if it develops slowly over a long period of
time, whereas a rapidly developing serum sodium level of 120−130 mmol/L
may have severe neurological consequences.
•• In the setting of hypervolaemia with hyponatraemia, initially the brain cells
(e.g. glia and neurons) swell due to the increase in cellular volume following
the movement of ECF water to the ICF compartment.
•• The water movement from ECF to ICF compartment is due to the low ECF
osmolarity as compared to the ICF osmolarity. Later, a gradually adaptive
but down regulatory volume reduction is achieved mainly by the loss of
intracellular ions, such as K+, Cl–, taurine, phosphocreatine and amino
acids including excitatory neurotransmitters (e.g. glutamine and glutamate).
•• This consequently causes neurologic impairment.
•• Hyponatraemia ultimately leads to cerebral oedema and raised ICP with
deleterious consequences.
•• Water retention (not natriuresis) is a marked feature of ADH excess,
whereas natriuresis (not water retention) is a prominent feature of ANP
excess.
•• Clinically, the intravascular volume expansion due to ADH excess is an
important feature of SIADH.
•• The intravascular volume depletion with natriuresis due to ANP and BNP
excess is a marked feature of CSWS.
•• Interestingly, ANP can suppress ADH secretion while ADH may itself
stimulate ANP secretion.
•• In SIADH, water retention (hyponatraemic hypervolaemia) inhibits aldos-
terone secretion and, therefore, relative natriuresis continues.
•• CSWS causes high natriuresis due to high ANP/BNP and low aldosterone
activity.
257
Hyperosmotic Hyponatraemia
•• Head injury patients with hyperglycaemia, uraemia and prolonged mannitol
therapy are more prone to develop hyponatraemia.
•• When plasma solute concentrations (e.g. glucose, mannitol, urea, etc.) are
increased, a shift of water from the ICF to the ECF causes cellular dehy-
dration and intravascular volume expansion with dilutional hyponatraemia.
•• Because of water shift from ICF to ECF, it is also called translocational
hyponatraemia.
•• In addition, increased serum osmolarity causes direct stimulation of
osmoreceptors and ADH release.
•• This leads to renal water retention and further worsens the dilutional
hyponatraemia.
•• Moreover, such an increase in ECF volume inhibits volume receptors,
thereby decreasing aldosterone secretion. This, in turn, leads to renal loss
of sodium (natriuresis).
•• Mannitol is an osmotic diuretic which increases ECF volume and reduces
ICF volume to treat cerebral oedema.
•• Following mannitol infusion in high dose with low renal output, hyponatrae-
mia may occur via the aforementioned mechanisms and may lead to
pulmonary oedema due to rapid volume expansion, metabolic acidosis
and hyperkalaemia.
•• In hyperglycaemic hyponatraemia with high renal output, patients may have
gastrointestinal symptoms such as dryness of mouth, nausea, vomiting
and abdominal pain besides dry skin and low jugular venous pressure.
•• Intensive management of hyperglycaemia is, therefore, of paramount
importance in such clinical settings.
Isosmotic Hyponatraemia
•• Pseudohyponatraemia may result due to decreased fractional water content
of the plasma in cases of hyperproteinaemia (two times the normal values)
and hyperlipidaemia.
•• An increase in positively charged paraproteins or a decrease in negatively
charged albumin concentrations in plasma can displace Na+ from the
plasma or ECF to the ICF compartment causing hyponatraemia.
•• Fractitious hyponatraemia with normal serum osmolality, therefore, requires
special attention to correct the responsible conditions.
•• Hypotonic fluid therapy with dextrose saline, half strength saline or
5% dextrose in head injury patients may result in isosmotic dilutional
hyponatraemia, which may, in turn cause cerebral oedema.
•• These patients may develop nausea, disorientation, confusion, convulsions
and gastrointestinal disturbances.
•• These solutions are better avoided; however, if needed, they should be
used judiciously in head trauma patients.
Hyposmotic Hyponatraemia
•• Excessive water intake and/or water retention are responsible for hypos-
motic (dilutional) hyponatraemia. This condition must be assessed and
treated differently in different clinical settings.
•• In low dietary intake, depletion of both ICF and ECF solutes can lead to
hyponatraemia.
258
•• In true sodium depletion, due to nutritional neglect, hyponatraemia is

accompanied by an evidence of a contracted blood volume (low blood
pressure, decreased skin turgor and elevated haematocrit).
•• In dilutional hyponatraemia, due to excessive hypotonic fluid infusion,
peripheral oedema is a prominent feature and, in addition, there may be an
evidence of cerebral oedema, congestive heart failure or hepatic disease.
•• Urinary sodium concentration will be less than 10 mmol/L in both the
aforementioned conditions: chronic dietary salt depletion and dilutional
hyponatraemia due to excessive hypotonic fluid therapy using dextrose
saline, half strength saline or 5% dextrose.
•• The persistence of dilutional hyponatraemia implies either SIADH or renal
impairment (acute tubular necrosis).
•• Dilutional hyponatraemia with low serum proteins and low serum urea
indicates SIADH.
•• In normal subjects, osmolarity of the maximally dilute urine is about
50 mmol/L. In SIADH, osmolarity of urine is more than 50 mmol/L,
and peripheral oedema is not a prominent feature, whereas dilutional
hyponatraemia with a dilute urine with peripheral oedema indicates renal
impairment.
•• Hyponatraemia is common after infusion of hypotonic fluids (5% dextrose or
dextrose saline), when the ability of the body to excrete water is depressed.
Common Hyponatraemic States in Head Injury Patients

•• The majority of head injury patients with hyponatraemia present with SIADH
or CSWS. In a few cases, both the conditions may coexist.
•• CSWS and SIADH are characterised by hyponatraemia, hyperosmolar
urine and hypernatriuresis in patients with normal renal, suprarenal and
thyroid functions.
•• The major distinction between these two conditions is the volume status
of the patient.
•• In CSWS, the ECF volume is contracted and the patient appears
dehydrated; whereas, in SIADH, the ECF volume is expanded and a clinical
picture of fluid overload is often seen.
•• Patients with CSWS respond to fluid and sodium administration while those
with SIADH respond to fluid restriction. In neurosurgical patients, CSWS
is more common than SIADH.
Syndrome of Inappropriate ADH Secretion
•• Syndrome of inappropriate ADH (SIADH) secretion usually begins in the
first or second week following head injury and with appropriate therapy
lasts no more than one to two weeks.
•• In SIADH, there is a continuous secretion of ADH even in the presence
of conditions such as hyponatraemia, hypo-osmolar serum and
hypervolaemia, which normally inhibits ADH secretion.
•• The typical clinical features of SIADH are hyponatraemia, with concomitant
hypervolaemic hyposmolar ECF, relative hypernatriuresis with hyperosmolar
urine and absence of clinical evidence of volume depletion (normal skin
turgor and blood pressure).
•• The clinical symptoms include anorexia, nausea, vomiting, irritability,
personality changes and neurological manifestations including seizures
(bulbar or pseudobulbar palsy, stupor, muscular weakness, loss of reflexes,
positive Babinski sign and convulsions).
259
Cerebral Salt Wasting Syndrome

•• Cerebral salt wasting syndrome (CSWS) is due to an inappropriate/
unregulated release of atrial natriuretic peptide.
•• It presents with hyponatraemia, hypovolaemic hypo-osmolar ECF,
hypernatriuresis with hyperosmolar urine and volume depletion (contracted
intravascular volume).
•• Persistence of high salt loss in the urine despite fluid restriction differentiates
this condition from SIADH, where salt loss depends on a liberal fluid intake.
•• The estimation of intravascular volume (by CVP) and urinary sodium usually
differentiates salt retaining state (SIADH) from salt losing state (CSWS).
•• The main diagnostic criteria of SIADH and CSWS are outlined in Table 4.
Management
•• Hyponatraemia is basically treated according to the underlying disease
process, serum osmolarity/osmolality and clinical estimates of total body
sodium.
•• The cornerstone of therapy in SIADH is fluid restriction, whereas in CSWS,
it is volume replacement and correction of the haematocrit.
SIADH
•• Patients with SIADH are basically treated with fluid restriction usually
below one litre/day until serum Na+ returns to normal levels with some salt
supplement or replacements.
•• The free-water restriction should be sufficient to decrease total body water
by 0.5−1.0 litre/day.
•• The resultant reduction in glomerular filtration rate enhances proximal tubu-
lar absorption of salt and water as well as stimulates aldosterone secretion.
•• Mild cases (Na+ >125 mEq/L) are best treated with fluid restriction, whereas
moderate cases (Na+ <125 mEq/L to 120 mEq/L) with water restriction to
600−800 mL 5% dextrose in 0.45% saline per 24 hours, with or without
normal saline; diuresis usually occurs in 36−48 hours.
•• Patients with severe hyponatraemia (Na+ <120 mEq/L) or in coma or with
seizures may require hypertonic saline, with furosemide; 20−40 mg.
•• The end-point of hypertonic saline therapy is generally a serum Na+ level
of 120 mEq/L or absence of overt symptoms.
•• Initially, plasma Na+ may be increased by 1−2 mEq/L/hr.
•• Care should be taken to avoid hypernatraemia by cautious correction so that
the plasma Na+ should not be increased more than 12 mEq/L in 24 hours
or 25 mEq/L in 48 hours, or to a concentration greater than 130 mEq/L.
•• Demeclocycline (anti-ADH synthetic hormone) antagonises the action of
ADH on the renal collecting ducts and, therefore, may be used (600−1200
mg/day) to induce nephrogenic resistance to ADH.
•• Phenytoin is used as an antiepileptic drug with an added benefit as an
anti-ADH agent.
•• Fluorocortisone (0.3−3 mg/day) is mainly used to inhibit action of ADH
on the aldosterone mechanism, and to help in raising serum Na+ levels.
Cerebral Salt Wasting Syndrome
•• The principles of managing hyponatraemia associated with CSWS consist
of the treatment of an underlying cause, restriction of intravascular
volume, isotonic fluid (e.g. normal saline, plasma and blood) infusion and
fludrocortisone.
260
•• CSWS is best managed with salt containing fluid orally, enterally or

intravenously to maintain CVP around 10−12 mmHg.
•• The patient’s haemoglobin and haematocrit levels are measured daily
and, if needed, packed cells with isotonic fluid or whole blood are given
as per requirements.
•• Rapid correction of chronic hyponatraemia using hypertonic saline has
been associated with fatal central pontine and extrapontine myelinolysis;
on the other hand, severe acute hyponatraemia can cause fatal cerebral
oedema (tentorial herniation) and status epilepticus.
•• Despite such concerns, the management of hyponatraemia with diuretic
therapy (furosemide) and supervised saline infusion (isotonic/hypertonic)
is safe.
HYPERNATRAEMIA
Common Hypernatraemic States
•• Clinically significant hypernatraemia (a high serum sodium concentration) is
much less frequent in head-injured patients than hyponatraemia. It is either
caused by the loss of water or an excess intake of sodium.
Aetiopathogenesis
•• In hypernatraemic states, especially in head injured patients, water
depletion mainly occurs due to an increased water loss as in DI (lack of
ADH), renal DI (ADH insensitivity), mannitol therapy (osmotic diuresis),
glycosuria (osmotic diuresis), prolonged hyperpyrexia (increased sweating),
hyperventilation (increased insensible loss) and antibiotics related diarrhoea
and, less commonly, due to reduced intake of dietary water.
•• The neurological causes of hypernatraemia include cerebral trauma,
cerebral tumours (craniopharyngioma, pituitary tumours), vascular disorders
(Sheehan’s syndrome, SAH-cerebral aneurysm), meningoencephalitis,
surgery in the sellar-suprasellar-third ventricular region and an idiopathic
variety.
•• Despite the frequent pathological demonstration of pituitary and
hypothalamic damage in head injury, the incidence of DI is relatively less
common. However, DI is a mortal sign in patients with massive brain injuries
and uncontrollable intracranial hypertension.
Differential Diagnosis
•• Serum hyperosmolarity, polydipsia (thirst leading to increased intake)
and polyuria following hypothalamo-hypophysial trauma are the hallmarks
of DI.
•• The differential diagnosis includes other conditions causing polyuria
and polydipsia, i.e. renal DI, diabetes mellitus, chronic renal failure,
hypercalcaemia, hypokalaemia and psychogenic polydipsia.
Diabetes Insipidus
•• Diabetes insipidus (DI) is a common condition after cranio-facial trauma,
skull base fractures and hypothalamo-pituitary injuries.
•• It can be permanent or transient, disappearing in a few days to a few weeks.
Polytrauma, cerebral hypoxia, cerebral ischaemia in haemorrhagic shock,
neurosurgery in the suprasellar region, fat embolism, drug overdose, etc.
may cause DI.
261
•• Hypothalamo-hypophyseal injury poses a particular risk of developing

transient or permanent DI.
•• It is transient in the majority of patients, lasting for 3−5 days; however, in
one-fourth to one-third of cases, it may be permanent.
•• Some patients show a triphasic response manifested by early transient
DI, followed by return of normal urinary functions for 1−3 weeks and then
relapse, leading to permanent DI.
Clinical Manifestations
•• Clinical manifestations of DI: Polyuria, (>2−3 litres/day), polydipsia,
hypernatraemia with hypovolaemia, high serum osmolality (320−330
mOsm/kg), low urine osmolality and a dilute urine (specific gravity less than
1005), and a urine to serum osmolality ratio of less than one, implying a
negative water balance are characteristic features of DI.
Diagnostic Tests
•• Serum and urine ADH assays and/or a water deprivation test are performed.
•• A normal person on water deprivation for 8 hours will have urine output
0.5 mL/mt and will concentrate urine to preserve water. Urine osmolality
will rise and become greater than 500 mOsm/kg.
•• Patients with DI fail to concentrate their urine and the water loss continues
as dilute urine.
•• Measurement of ADH levels in urine and serum in relation to plasma
osmolarity is far more desirable than the water deprivation test in acute
head injury patients as the latter may be highly inappropriate in many of
these patients.
•• If the ADH assays are not available, then a therapeutic trial with
desmopressin is highly indicated to resolve the diagnostic dilemma.
Management
•• Daily measurements of body weight, fluid intake/output, haemoglobin,
haematocrit, renal function tests (e.g. serum creatinine, BUN, electrolytes,
etc.), serum sugar, serum osmolarity, urine-specific gravity and urine
osmolarity are performed.
•• Treatment of hypernatraemia basically consists of water and electrolyte
replacement.
•• Hypernatraemia is corrected slowly because of the risk of neurologic
sequelae such as seizures and cerebral oedema.
•• The water deficit is corrected over 24−48 hours and plasma Na+ is gradually
reduced by 1−2 mEq/L/hr.
•• The aim of the fluid therapy is to replace hourly urine output along with the
usual estimate for the insensible loss, with hypotonic fluids.
•• The volume depletion may lead to reduction in the mean systemic arterial
pressure and subsequently a reduction in the CPP and, therefore, needs
cautious correction.
•• Regardless of its cause, hypernatraemia should initially be treated by
administration of hypotonic fluids such as water (orally) or 5% dextrose
(parenterally). Urine output in DI may exceed 10 L/day, although less than
this is more usual.
•• Adequate fluid replacement, desmopressin [Desmopressin (1-desamino-
D-arginine vasopressin) is a synthetic analogue of ADH] for severe
cases and chlorpropamide (oral hypoglycemic agent) 50−200 mg/day or
262
carbamazepine (antiepileptic agent 600 mg/day) for mild cases of DI may

be used.
•• Desmopressin is indicated if urine output exceeds 6−7 L/day, or urinary
output remains more than 250 mL/h for consecutive 2−4 hours or the patient
is unable to maintain fluid balance and the normal intravascular volume.
•• There are many preparations of vasopressin, which are highly effective:
–– Aqueous vasopressin (5−10 IU IM/IV, 4−6 hourly)
–– Vasopressin tannate-in-oil (5 IU IM daily as the initial therapy once in
2−3 days)
–– Lysine vasopressin nasal spray (2 IU/spray, 6−8 hourly)
–– DDAVP (l-deamino-8-D-arginine vasopressin): 10−20 mg intranasally
on OD or BD basis.
32
CHAPTER
Scalp Injuries
Krishna Reddy A
ANATOMY
•• The scalp extends from the supraorbital ridges anteriorly to the inferior
nuchal line posteriorly and to the auriculocephalic angle laterally.
•• Apart from the forehead, the scalp is completely covered with hair in most
individuals.
•• The thickness of the scalp varies from 3 to 8 mm, being thick over the
occipital region and thinner over the frontal and temporal areas.
•• The skin is the first layer of the five-layered scalp.
•• The septa of the superficial fascia lie in the connective tissue layer.
Numerous blood vessels and nerves course through this layer.
•• The galea aponeurotica, the third layer, is characterised by a flat central
tendon, attached between the frontalis and occipitalis muscles. The galea
offers tensile strength to the scalp, failure of closure of which leads to
contracture of attached muscles and a depressed appearance of a scalp
wound.
•• The subepicranium, containing loose areolar tissue and small vessels,
provides scalp mobility. It is the usual plane of scalp avulsion, haematoma
or infection.
•• The pericranium is adherent to the skull, contains many small capillaries
that pass through the underlying bone and has an outer layer of fibrous
connective tissue and an inner layer of elastic fibres.
DESCRIPTION OF SCALP INJURIES

Caput Succedaenum
•• It is due to scalp oedema, which occurs in the newborn following trauma
during prolonged engagement of the head at the pelvic outlet.
•• It presents as a boggy swelling seen at birth and usually subsides
spontaneously within 2–3 days.
Cephal-Haematoma
•• It is a subperiosteal haematoma occurring almost exclusively as a result of
birth trauma. It is seen usually following forceps delivery.
•• Since the pericranium meets the endocranium at the suture lines, this
haematoma takes the shape of the underlying bone.
•• It usually gets absorbed within a period of 2 weeks, failing which it may need
aspiration. It may occasionally calcify and may require surgical excision.
264
Abrasion
•• It is a destruction of the skin, usually involving the superficial layers of the
epidermis only.
•• It is caused by a lateral rubbing action by a blow, a fall on a rough surface,
by being dragged in a vehicular accident, by fingernails, thorns or teeth bite.
•• The spectrum of injury may range from flattening of epidermal cells and
elongation of nuclei to partial or complete removal of the epithelium and
damage of the superficial layer of dermis.
•• The exposed raw surface is covered by exudation of lymph and blood,
which produces a protective covering known as a scab or crust.
•• Abrasions vary in size, depending on the extent of the body surface exposed
to the abrading force.
•• They are simple injuries, bleed slightly, heal rapidly and scar is not formed.
Large abrasions can cause severe pain and bleeding.
•• The main types of abrasions are:
–– Scratches: These are caused by a sharp or pointed object. The sur-
face layers of the skin are collected in front of the object, which leaves
a clean area at the start and tags at the end.
–– Grazes (sliding, scraping or grinding abrasion): These occur when
there is movement between the skin and some rough surface in con-
tact with it. These show uneven, longitudinal parallel lines (grooves
or furrows) with the epithelium heaped up at the ends of these lines,
which indicate the direction in which the force was applied.
–– Pressure abrasions (crushing or friction abrasions): They are
caused by crushing of the superficial layers of the epidermis and are
associated with a bruise of the surrounding area. It occurs if the move-
ment of the instrument is around 90° to the skin.
–– Impact abrasions (contact or imprint abrasions): They are caused
by impact with a rough object, when the force is applied at or near
a right angle to the skin surface. The abrasion is slightly depressed
below the surface, unless there is bulging due to underlying contusion
or local oedema.
–– Impact abrasions and pressure abrasions reproduce the pattern of the
object causing it and are called patterned abrasions.
Age of the Abrasion
•• The exact age cannot be determined, but a fair estimate may be done.
–– Fresh: Bright red
–– 12–24 hours: Lymph and blood dries up leaving a bright scar
–– 2–3 days: Reddish brown scab
–– 4–7 days: Epithelium grows and covers defect under the scab
–– After 7 days: Scab dries, shrinks and falls off.
Contusion (Bruise)
•• A contusion is an effusion of blood into the tissues due to the rupture of
blood vessels (venules and arterioles) caused by blunt trauma.
•• The extravasated blood is diffusely distributed through the tissue spaces
and the margins are blurred.
Age of the Contusion
Immediately: Red
Few hours to 3 days: Blue
Chapter 32 • Scalp Injuries
265
4th day: Bluish-black to brown (haemosiderin)

5–6 days: Greenish (haematoidin)
7–12 days: Yellow (bilirubin)
2 weeks: Normal.
Lacerations
•• Lacerations are tears or splits of the skin. These are usually caused by
sharp objects.
•• In a laceration caused by a blunt object, localised portions of tissue are
displaced by the impact of the blunt force, which sets up traction forces
and results in tearing of the tissues.
•• Split Lacerations: Splitting occurs by crushing of the skin between two hard
objects. Scalp lacerations occur due to the tissues being crushed between
the skull and some hard object, such as the ground or a blunt instrument.
•• Stretch Lacerations:
–– Overstretching of the skin, if it is fixed, will cause a laceration.
–– There is localised pressure with pull which increases until tearing
occurs and produces a flap of skin, which is peeled off the underlying
bone or deep fascia.
–– This is seen in the running over by a motor vehicle and the flap may
indicate the direction of the vehicle.
•• Scalp lacerations are primarily troublesome because of bleeding.
•• Infection is extremely rare because of the rich blood supply.
Thermal Injury
•• Thermal injury may be caused by dry heat (burns), hot liquids (scalds)
and steam.
•• The depth of injury is directly proportional to the burning temperature and
the time of exposure, and inversely proportional to the depth of the skin.
•• As the hair follicles are in the subcutaneous space, re-epithelialization of
deep second-degree injuries also is rapid; provided there is no infection.
•• Hence, conservative treatment is indicated where the injury is superficial
or depth is questionable.
Electrical Burns
•• Luce and Hoopes showed that the non-infected burnt skull can act as an
in situ bone graft and regenerate, if covered by tissue of good vascularity.
•• The therapy for electrical burns, therefore, should consist of excision of the
burnt scalp and pericranium, once the margins of the burn are established
and before infection occurs (1–3 days) and immediate coverage with
vascularised flaps, either local or distant.
•• The burnt skull should be left intact, unless it is infected or underlying
damage to the dura or brain is suspected.
•• Grading of Electrical Burns:
First degree Superficial redness
Second degree Partial thickness
Blistering
Regenerate spontaneously
Third degree Full thickness
Leathery skin
Does not heal spontaneously
Requires excision and grafting.
266
Chemical Burns
•• Injury by chemical agents can be accidental (more common, especially in
children), homicidal (due to an assault) and suicidal (rare).
•• Alkali burns are more common than acid burns.
•• The damage caused to the scalp is determined by the duration of contact,
the concentration, penetrance, quantity and the mechanism of action of
the chemical compound.
•• Copious irrigation of the injured part with sterile water helps in minimising
the duration of contact.
•• Neutralisation is the next step and is done by dilute acetic acid for alkali
burns and with dilute sodium bicarbonate for acid wounds.
•• Extensive debridement should be avoided, particularly when the depth is
difficult to determine.
Radiation Injury
•• Ionising radiation may cause radiodermatitis or radionecrotic ulcer by
microvascular damage and reduced cell turnover.
•• Wound healing is also significantly affected in such scalps.
•• The radionecrotic ulcer may further worsen the matter by undergoing
malignant transformation.
•• Treatment includes excision followed by grafting with fresh, uninvolved,
vascularised tissue.
•• Free flaps have the greatest success rate in the long run.
MANAGEMENT
Resuscitation
•• Stabilise the patient’s vital signs, tetanus prophylaxis, administer a broad-
spectrum antibiotic and analgesics.
•• Preparation for blood transfusion should also be made.
•• The exposed cranium should be covered with saline moistened gauze.
•• In case of scalp avulsion, the amputated scalp should be placed in a plastic
bag and the bag placed in ice chips, awaiting replantation.
Initial Evaluation of Scalp Injury

•• Detailed history
•• Detailed physical examination
•• Assessment of mechanism of injury
•• Evaluation of intracranial injury
•• Evaluation of cervical spine injury, if any
•• Appropriate neuro-imaging
•• Additional history—male pattern baldness, Previous scalp trauma,
Radiation injury.
Aims of Management of Scalp Injury

•• Rapid and safe coverage of underlying structures
•• Minimising the risk of infection
•• Transforming a dirty wound into a clean wound
•• Transforming an open wound into a closed wound
267
•• Providing a durable tissue cover

•• Restoring normal contour and function
•• Achieving an acceptable aesthetic result.
Assessment
Assessment of the Scalp Injury includes the following:
•• Duration since injury
•• Environment of injury
•• Wound characteristics:
–– Size
–– Shape
–– Depth
–– Margins
–– Presence of haematoma
–– Presence of foreign body
–– Necrosis
•• Vascularity of local tissue:
–– Abundant
–– Poor
•• Nature of the defect in the bed:
–– Pericranium
–– Cortical bone
•• Character and abundance of the local tissue
•• Potential for simple camouflage.
•• Duration since injury is an important determinant of wound viability and the
outcome after surgical repair.
•• It is now accepted that a wound exposed to the exterior for more than
6 hours has a four-fold increased risk of infection, compared to the one
exposed for a lesser duration.
Surgical Principles in Treating Scalp Injuries

•• Large subgaleal haematomas should be evacuated early.
•• Meticulous haemostasis and approximation of wound margins is essential.
•• Local debridement to be done wherever necessary, to remove non-viable
tissue and re-orient the wound.
•• Galea has to be closed with absorbable sutures for protection and retention
of skin edges.
•• The flap should be taken from the scalp wherever feasible (“replace like
with like”).
•• Take the scalp flap from the areas of relative excess (lateral and posterior),
and place in areas of relative deficiency (anterior and medial).
•• Axial scalp flaps permit significant increase in length-base ratio, compared
to the conventional random flaps.
•• During scalp replantation anastomosis should be done between two normal
vessels.
•• The scalp can survive on one superficial temporal artery. But anastomosis of
as many arteries or veins as possible has to be done during scalp replantation.
•• Veins should be anastomosed first during scalp replantation, unless there is
significant ischaemia, in which case anastomosis of arteries first is a priority.
268
Surgical Planning and Execution

Reconstructive Ladder: Options for
Covering the Scalp Defect
•• Primary closure
•• Delayed primary closure
•• Secondary intention healing
•• Local transposition flaps – random axial
•• Distant flaps – split thickness skin graft island pedicle flaps (trapezium,
latissimus dorsi, temporalis)
•• Free autogenous tissue transplantation (skin, muscle, omentum).
•• The reconstructive techniques for scalp defects are mentioned in general
order of decreasing indications. These are:
–– Split thickness grafts: These are partial thickness of skin containing
epidermis and variable thickness of dermis.
–– Full-thickness skin grafts: These consist of a complete thickness of
skin with epidermis and dermis but without subcutaneous fat.
–– Local attached flaps: These flaps contain skin and subcutaneous
tissue and carry their own circulation during transfer.
–– Distant detached flaps: Skin and subcutaneous tissue from a non-
contiguous area is used that carries its own circulation during the
transfer process until circulation is established in the recipient area.
–– Distant re-attached flaps: Tissue is harvested from a distant donor
site with its vascular supply included and revascularised by microsur-
gical anastomosis at the recipient site. Such flaps include skin and
subcutaneous tissue, musculocutaneous flaps, muscle flaps with skin
grafts and omentum with an overlying skin graft.
–– Scalp expansion: Gradual expansion of adjacent scalp with subse-
quent advancement into the defect.
Free Skin Grafts

•• Free grafts in scalp reconstruction:
–– Scalp
–– Temporalis fascia
–– Latissimus dorsi
–– Parascapular
–– Omentum
–– Skin over scapular region
–– Rectus abdominis
–– Internal oblique
–– Skin from the groin region
–– Radial aspect of the forearm.
•• Use of the superficial temporal artery and vein for scalp and face reconstruc-
tion is reliable and safe. The superficial temporal artery and vein should be
considered as primary recipient vessels in microsurgical reconstruction of
the upper two-thirds of the face and/or scalp.
Pericranial Flaps and Overlying Skin Grafts

or Local Flaps
•• Pericranial flaps are endowed with a rich vascular network that allows
them to be used as pedicled flaps to cover denuded bone and act as a
bed for skin grafting.
269
•• They should be designed larger than the recipient site because of their
elastic properties.
•• Muscular Flaps: These flaps are unsatisfactory from an aesthetic
standpoint and do not restore hair-bearing tissue to the scalp.
•• Rotation Flaps: Planning a rotation flap requires an understanding of a
simple geometric concept. “Tissue is added to the defect subtracting from
the flap donor area and this is achieved by changing the defect shape from
non-closable to closable.”
Calvarial Reconstruction
Materials Used for Calvarial Reconstruction
Autogenous material Alloplastic material
Split rib grafts Acrylic
Calvarial bone grafts Hydroxyapatite cement
Bone paste Vitallium
Stainless steel
Tantalum
Titanium
Postoperative Assessment of Replanted Scalp
1. Clinical examination Colour
Capillary refill
Temperature
Capillary bleeding
2. Doppler
3. Thermocouples
4. Fluorescein staining
5. Transcutaneous oxygen measurements
6. Impedance techniques.
Complications of Scalp Injuries

•• Infection
•• Wound necrosis
•• Calvarial, dural and brain injury
•• Graft rejection
•• Wound contracture
•• Poor cosmetic result.
33
CHAPTER Acute Subdural
Haematomas
Sanjay Behari  Anuj Chaitley  Manish Singh Sharma  Ashok Kumar Mahapatra
INTRODUCTION
•• Acute subdural haematomas (SDHs) are haematomas accumulating within
the subdural space of the brain to become clinically symptomatic within
24−72 hours of injury.
•• They are extracerebral, hyperdense, crescentic collections between the
dura and the brain parenchyma.
•• They are usually located over the cerebral convexities conforming to the
convex brain surface.
•• When extending along the tentorium or falx cerebri, their extent is contained
by dural reflections.
•• There is a wide variation in the incidence of acute SDH (5−29%) as the
primary lesion in patients admitted with head injury.
•• Editorial comment: Acute subdural haematoma seldom occurs without
associated injury to the brain parenchyma; more often it represents a thin
layer of blood clot overlying a contused/lacerated brain.
•• Men are twice to four times more likely to be affected than women.
AETIOPATHOGENESIS
•• Acute SDH is frequently due to falls, assaults or vehicular accidents.
•• Rotational acceleration of the head, as occurs in boxing, may also produce
these injuries.
•• Avulsion of parasagittal and Sylvian bridging veins is often accompanied
by a degree of diffuse axonal injury and polar contusion.
•• The low pressure venous bleeding accumulates to form a haematoma of
sufficient size to compress the brain by two mechanisms.
•• Episodes of coughing, straining or vomiting may cause sufficient bleeding
to prevent progressive tamponade by the brain.
•• The avulsion of veins directly attached to the sagittal sinus may be
held open because of the high venous sinus pressure, rather than be
compressed by the haematoma.
•• Cortical contusion with haemorrhage from a small cortical artery rupture
is also a common cause of acute SDH. This results in a characteristic
“burst lobe” injury with SDH, polar contusion, cerebral haematoma and
hemispheric swelling.
•• Occasionally, coalescence and rupture of parenchymal small vessel
bleeding from a contusion may also cause an acute SDH. This may occur
especially when consumption coagulopathy develops or in patients on
anticoagulant therapy.
Chapter 33 • Acute Subdural Haematomas
271
CLINICAL SPECTRUM
•• The clinical presentation is non-specific and occurs due to mass effect
produced by the acute SDH as well as associated parenchymatous injury.
•• It depends upon the severity of the primary injury, the associated
parenchymal injuries and the rapidity of accumulation of the acute SDH.
•• About 40−50% of patients are unconscious at the time of their primary
injury and remain comatose for prolonged periods.
•• Pupillary asymmetry ipsilateral to the side of haematoma with contralateral
hemiparesis may be due to transtentorial herniation.
•• However, false localising pupillary dilatation contralateral to the lesion
may occur due to direct optic nerve, oculomotor nerve or brainstem injury
on that side.
•• Ipsilateral hemiparesis may be due to associated brain injury or due to
Kernohan’s notching produced by compression of the contralateral cerebral
peduncle against the tentorial edge.
•• The incidence of associated seizures varies from 6 to 22%.
•• Posterior fossa acute SDH is rare and occurs due to tearing of bridging
veins, laceration of the tentorium, contusion of the cerebellum or injury to
venous sinuses.
•• Cerebellar signs, neck stiffness and pain or symptoms of raised intracranial
pressure due to the size of the lesion or the development of hydrocephalus
may be the presenting features. Despite urgent surgical evacuation, the
mortality ranges from 5 to 75%.
IMAGING FEATURES
•• On CT scans, an acute SDH appears as crescentric, hyperdense collection
that lies between the arachnoid and the inner meningeal layer of the dura
that conform to and often exert a mass effect on the surface of the brain.
•• It extends across sutural lines, but does not cross the falx or the tentorium.
•• In contrast to this, an extradural haematoma is biconvex, less likely to cross
the sutural lines and may cross the falx or tentorium.
•• An acute SDH may occasionally be biconvex due to adhesions between
the brain and the dura mater, or when it is thick.
•• The exact thickness of the crescentric SDH should be measured by taking
the CT images with a wide window to distinguish the hyperdense clot from
the bone.
•• Magnetic resonance (MR) scan is a sensitive investigation for diagnosing
an acute SDH.
•• Patients with ferromagnetic foreign bodies or electronic implants need to
be excluded. Thus, MR is less preferred in the clinical setting in patients
with head injury as compared to a CT scan.
•• On MR imaging, the hyperacute stage, lasting from minutes to a few hours,
due to the oxyhaemoglobin content, the haematoma is dark on T1-weighted
images and bright on T2-weighted images.
•• In the acute stage, lasting for the next 1−12 hours, the presence of
deoxyhaemoglobin causes the haematoma to be isointense on T1-weighted
images and dark on T2-weighted images.
•• The subacute stage that starts as early as 3 days and is established from
a week may be divided into the early and late stages. In the early subacute
stage, the methaemoglobin appears bright on T1-weighted and dark on
T2-weighted images. In the late subacute stage, signals are bright on T1-
weighted and T2-weighted images.
272
•• As the SDH become chronic (21−30 days), these signals become

hypointense on T1-weighted and T2-weighted images.
•• Fresh haemorrhage within a subacute SDH may give rise to the layering
effect of the high and low attenuation clot.
•• Occasionally, the presence of bilateral acute SDH may cause no midline
shift despite the mass effect.
•• The effacement of frontal horns, obliteration of sulci and gyri and
compression of third ventricles points towards mass effect in these cases.
•• An extradural haematoma may be distinguished from an acute SDH by
the sharply delineated, low intensity dura between the haematoma and
the displaced brain in the former.
•• Acute SDH is often associated with displaced cortical pial veins demarcated
by flow voids.
•• Radionuclide tracers, such as 99mTc hexamethyl propylene amine oxime
(99mTc-HMPAO) and xenon-enhanced CT cerebral blood flow studies, may
also give an idea about the regional cerebral blood flow and hypoperfusion
below an acute SDH.
•• Loss of autoregulation may cause the hypoperfused area in the subacute
phase to appear hyperperfused.
SURGICAL MANAGEMENT
•• The aim of surgery is to evacuate the haematoma and any associated
underlying lesions in order to relieve the mass effect and improve the focal
neurological deficits.
•• The size of the haematoma that should definitely be removed has not
been ascertained.
•• Removal of a very thin acute SDH may not be indicated as the clinical
deterioration is usually due to associated lesions in this case and is not
likely to improve with acute SDH evacuation.
•• Non-operative therapy should only be considered in patients who are fully
conscious, when the extra-axial mass is the single dominant lesion, that
is, there are no multiple contusions or potentially significant contralateral
mass lesions (which may be preventing midline shift), and when there are
no features of mass effect such as a midline shift greater than 3 mm, or
basal cisternal effacement.
•• In such cases, and especially, if the lesion is less than 10 mm at its thickest
point, conservative therapy may be successful in most instances.
•• The SDH will usually resorb within 1 month, although there are occasional
instances of chronic SDH formation.
•• Similarly, a deep-seated interhemispheric or tentorial SDH in a stable
conscious patient may not need surgical evacuation.
•• The guidelines for selecting patients for conservative management of the
SDH proposed by Mathew et al. include:
1. GCS score greater than or equal to 13 since injury
2. Absence of other intracranial haematomas or oedema on CT scan
3. Midline shift of less than 10 mm
4. Absence of basal cisternal effacement.
•• All patients with acute SDH in coma (GCS score less than 9) should undergo
intracranial pressure monitoring.
•• A comatose patient (GCS score less than 9) with an SDH less than 10 mm
thick and a midline shift less than 5 mm should undergo surgical evacuation
Chapter 33 • Acute Subdural Haematomas
273
of the lesion if the GCS score decreased between the time of injury and
hospital admission by 2 or more points on the GCS and/or the patient
presents with asymmetric or fixed and dilated pupils and/or the intracranial
pressure exceeds 20 mmHg.
•• An increase in haematoma size on CT scan with increasing intracranial
pressure and decline in neurological status is also an indication for surgical
removal of the lesion.
•• Regarding the timing of surgery, it is recommended that in patients with
acute SDH and with indications for surgery, surgical evacuation should be
performed as early as possible.
•• If surgical evacuation of an acute SDH is indicated in a comatose patient
(GCS < 9), it should be performed using a craniotomy with or without bone
flap removal and a duraplasty.
•• A wide decompressive haemicraniectomy/craniotomy with duraplasty
may be useful in obtunded patients with intact brainstem function, who
subsequently deteriorate due to increased hemispheric oedema or the SDH.
•• Burr-hole drainage of an acute SDH is usually unsuccessful because the
underlying clot is solid. It may, however, be used to localise the site of clot
in case imaging facilities are not available, following which the burr hole
may be enlarged to a craniectomy.
OUTCOME
•• The factors determining outcome include:
–– The neurological status: This forms the most significant factor in
determining outcome.
–– Age: Younger patients have a better outcome than older patients due
to less comorbid conditions in the former.
–– CT parameters: CT parameters such as clot thickness, haematoma
volume, midline shift and patency of the basal cisterns.
–– Timing of surgery: In comatose patients, however, there was a sig-
nificant decrease in mortality and increase in functional recovery in
patients who underwent surgery within 4 hours of injury as compared
to those in whom surgery was delayed beyond 4 hours of injury.
–– Intracranial pressure: Persistently elevated (> 20 mm Hg) post-
operative intracranial pressure is associated with a poorer prognosis.
–– Associated lesions: An associated intracerebral haematoma or
contusion did not influence mortality but the functional outcome was
significantly better in patients without contusions.
–– Comorbid conditions: Lung infections, septicaemia, meningitis,
shock, cardiac arrhythmias, upper gastrointestinal haemorrhage or
cirrhosis may all influence outcome.
34
CHAPTER Extradural
Haematomas
Ashok Kumar Mahapatra  Vivek Kumar Vaid  Rajkumar
INTRODUCTION
•• Extradural haematoma (EDH) is a collection of blood in the potential space
that exists between the inner table of the skull and the dura (periosteal
layer).
•• Extension of the haematoma is usually limited by suture lines owing to the
tight attachment of the dura at these locations (continuation of periosteal
layer of the dura with the pericranium at the sutures).
EPIDEMIOLOGY
•• Extradural haematoma occurs in approximately 2% of all patients with head
injuries and 5−15% of patients with fatal head injuries.
•• EDH is considered to be one of the most serious complications of head
injury, requiring immediate diagnosis and surgical intervention.
•• EDH may be acute (58%), subacute (31%) or chronic (11%).
•• It usually occurs in young adults and is rare in children below 2 years of age
(due to the plasticity of the immature calvarium) or after age 60 (because
the dura is adherent to the overlying bone).
•• The incidence of delayed extradural haematoma (DEDH) following an
initially negative CT scan is reported in 10−30%.
PATHOPHYSIOLOGY
•• Extradural haematoma usually results from a brief linear contact force to
the calvarium that causes separation of the periosteal dura from the bone
and disruption of interposed vessels due to shearing stress.
•• Skull fractures are found in 85−95% of adult cases.
•• Arterial or venous structures may be compromised, causing rapid expansion
of the haematoma.
•• However, chronic or delayed manifestations may occur when venous
sources are involved.
•• The haematoma arises from injury to the middle meningeal artery or it
branch in over one half of the patients, from the middle meningeal vein
in one-third and from diploic veins or a torn dural venous sinus in the
remainder.
•• The temporoparietal region and the middle meningeal artery are most
commonly involved, although the anterior ethmoidal artery may be involved
in frontal injuries, the transverse or sigmoid sinus in occipital injuries and
the superior sagittal sinus in trauma to the vertex.
Chapter 34 • Extradural Haematomas
275
•• Bilateral EDHs account for 2−10% of all acute epidural haematomas in

adults but are exceedingly rare in children.
•• Posterior fossa EDHs account for 5% of all cases of EDH.
•• This classification was first described by Kristiansen and Tandon in 1960.
•• Patients with EDH may have the following five clinical presentations:
–– Conscious throughout (8−24%)
–– Unconscious throughout (23−24%)
–– Initially conscious and subsequently unconscious (20−28%)
–– Initially unconscious and subsequently lucid (14−21%)
–– The “Textbook” presentation consisting of brief post-traumatic loss of
consciousness (LOC), followed by a “lucid interval” for several hours
and then obtundation, contralateral hemiparesis and ipsilateral pupil-
lary dilatation occurs in less than 10−27% of the patients.
•• A lucid interval is not pathognomonic for EDH; other post-traumatic mass
lesions can also present in a similar manner.
•• There are no definite symptoms of EDHs.
•• The triad of head injury with lucid interval, mydriasis on the side of the
haematoma and contralateral hemiparesis occurs in only 18% of the cases
and mainly when the EDH is localised to the temporoparietal region.
•• The dilated and non-reactive pupil can be associated with ipsilateral
hemiplegia. This is due to indentation of the contralateral cerebral peduncle
by the edge of the tentorium cerebelli (Kernohan’s notch).
•• Initially, the pupil on the side of EDH contracts due to irritation of the
oculomotor nerve and the opposite pupil will be normal in size. In the next
stage, the ipsilateral pupil dilates due to paralysis of the oculomotor nerve.
Finally, the pupils of both the sides become dilated and fixed (Hutchinson’s
pupil). However, this clinical evolution is seldom seen in practice.
•• Treatment of EDH should be carried out prior to the pupil becoming dilated
and fixed.
•• Paralysis of extraocular muscles supplied by the oculomotor nerve occurs
a little after pupillary changes as the pupillary fibres are more sensitive
to pressure due to their peripheral arrangement in the oculomotor nerve.
•• A post-traumatic disorder (a form of vagal syncope), described by Denny-
Brown, consisting of “lucid interval” followed by bradycardia, brief episodes
of restlessness and vomiting, without intracranial hypertension or mass,
must be considered in the differential diagnosis.
DIAGNOSIS
•• The diagnosis of EDH must be considered when the plain skull X-rays show
a fracture and it must obviously be clinically correlated.
•• The “Classic” CT appearance consists of a hyperdense, biconvex
(lenticular) mass adjacent to the skull. Fracture lines will further be evident
and mass effect appreciated.
•• Magnetic resonance imaging (MRI) can also be done, but is time-consuming
and in no way superior to CT.
•• Another diagnostic modality now under development is near infrared
spectroscopy, which can be used with reasonable sensitivity and specificity
for detection of intracranial lesions in a short time and could be informative
when the patient is herniating, and urgent surgical intervention is required.
276
•• Cervical spine evaluation usually is necessary because of the risk of neck

injury associated with EDH.
MANAGEMENT
•• Non-surgical management may be attempted when:
–– Small EDH (≤1 cm maximal thickness)
–– Subacute or chronic EDH
–– Minimal neurological signs and symptoms.
•• Surgery should be done for most posterior fossa EDHs.
•• In a rapidly deteriorating patient with suspected EDH, a CT scan is in-
appropriate.
•• The clinical triad of altered mental status, unilateral pupillary dilatation with
loss of light reflex and contralateral hemiparesis is most often due to upper
brainstem compression by uncal herniation, which, in the majority of trauma
cases, is due to EDH. In such patients, exploratory burr holes are indicated.
•• The choices of the site for initial burr hole placement are (Fig. 1) as follows:
–– Start with temporal burr hole on the side ipsilateral to the dilated pupil
(will be correct side in >85% of EDHs and other intra-axial mass
lesions.
–– If both the pupils are dilated, use the side of the first dilating pupil (if
known) or on the side of the skull fracture.
–– If the pupils are equal, or it is not known which side is dilated first, place
on the side of obvious external trauma. For example, bruising and/or
scalp haematoma.
–– If there are no localising clues, place holes on the left side (to evaluate
and decompress the dominant hemisphere).
–– If no epidural haematoma is found, the dura is opened if it has bluish
discolouration (suggests subdural haematoma), or if there is a strong
suspicion of a mass lesion on that side.
–– If completely negative, usually perform temporal burr holes on the
contralateral side.
Fig. 1: Order of placement of exploratory burr holes: (1) temporal burr hole
on the side of initial dilatation of pupil; (2) temporal burr hole on the opposite
side; (3) frontal burr hole on the side of initial dilatation of pupil; (4) parietal
burr hole on the side of initial dilatation of pupil and (5) occipital burr hole on
the side of initial dilatation of pupil
Chapter 34 • Extradural Haematomas
277
–– If negative, further burr holes should be undertaken if CT scan can still

not be done.
–– Proceed to ipsilateral frontal burr hole.
–– Subsequent burr holes may be placed at the parietal region and lastly
in the posterior fossa.
•• If EDH is confirmed by CT scan, then the indications for surgical
management are given as follows:
–– Any symptomatic EDH.
–– An acute asymptomatic EDH >1 cm (containing more than 40 mL of
blood) in its thickest measurement.
–– EDH in paediatric patients (low threshold for sudden deterioration as
there is less room for the clot to accumulate).
–– Failure of non-surgical (conservative) management.
•• There are mainly three surgical objectives. These are as follows:
–– To remove the clot, thus reducing the ICP and eliminating the focal
mass effect.
–– Achieve absolute haemostasis.
–– Prevent reaccumulation by placing dural hitch sutures (tack-up
sutures).
–– A central tack-up suture (Poppen’s suture) in the middle of the crani-
otomy flap is always advisable.
35
CHAPTER Traumatic Intracerebral
Haematomas
CLASSIFICATION
•• Traumatic intracranial haemorrhage may be classified:
–– On the basis of the anatomical location of the bleed as subarachnoid,
extradural, subdural or intracerebral
–– On the basis of the time factor as acute, subacute and chronic.
•• Intracerebral haemorrhage can be either in the form of a haematoma or
a contusion.
•• Intracerebral haematomas are more common, occurring as the primary
lesion in 10% of severe closed head injuries in the Traumatic Coma Bank
(TCB) data study series.
•• It is difficult to distinguish between intracerebral haematomas occurring
primarily and those secondary to brain contusion.
INTRACEREBRAL HAEMORRHAGE
•• Most severe head injuries have some degree of intracerebral haemorrhage
which may be classified as follows:
–– Immediate
¾¾ Cortical and subcortical haemorrhage (local or diffuse) in associa-
tion with brain laceration and contusion.
¾¾ Petechial haemorrhages – small, medium or widespread in the
brain substance.
¾¾ Massive intracerebral haemorrhage.
–– Delayed intracerebral haemorrhage.
Immediate Intracerebral Haemorrhages

Cortical and Subcortical Haemorrhage
•• All lacerations or contusions of the brain, either due to direct injury as in
a depressed fracture and penetrating injury or in a closed head injury due
to an acceleration-deceleration type of trauma are associated with some
amount of subpial and subcortical extravasation of blood.
•• In the closed type of trauma, such lacerations are most marked in the frontal,
temporal and occipital poles and their undersurfaces.
•• These areas of the brain are more vulnerable as they strike the irregular
inner surface of the skull and also because they impinge over the sphenoidal
and petrous ridges of the base of the skull.
•• The damaged capillaries in the surrounding area give rise to a number of small
haemorrhages and the area of laceration is surrounded by an area of oedema.
Chapter 35 • Traumatic Intracerebral Haematomas
279
•• When extensive, this oedema may result in raised intracranial pressure

(ICP).
•• Traumatic basal ganglia haematomas are due to acceleration and decel-
eration injuries.
•• A contusion index has been developed that grades contusions based on
the depth of injury (1-superficial cortex, 2-full thickness of cortex, 3-cortex
white matter junction) and extent of contusion (1-localised, 2-moderately
extensive, 3-extensive).
Petechial Haemorrhages
•• In many cases of acute brain injury, autopsy studies reveal small or
moderate foci of haemorrhage in the white matter, basal ganglia, brainstem,
corpus callosum and the cerebellum.
•• Impairment of respiratory function due to any cause following a head injury
leads to anoxia of the brain, which also results in petechiae.
•• These haemorrhages are also caused by distortion of the brain occurring
at the time of the accident with consequent damage to the capillaries.
•• The shearing strain of the injury causes friction between the fixed vessel
and the deformed brain substance—“neurovascular friction”.
•• Small haemorrhages of this type attain clinical significance in critical areas
like the pons or the midbrain.
•• These small haematomas rarely require operative removal.
•• After absorption some of them may coalesce and form cavities resulting
ultimately in post-traumatic porencephalic cysts, which may or may not
communicate with the ventricular system or the subarachnoid space.
Massive Traumatic Intracerebral Haematoma
•• Traumatic intracerebral haematoma as an isolated lesion is not common.
However, those associated with contusion and laceration and acting as a
significant mass lesion constitute one of the most common lesions requiring
surgical relief.
•• More frequent in the older age group, they are situated mainly in the
temporal and frontal lobes, due to the brain impacting against the rigid skull.
•• Parietal and occipital lobe haematomas are much less common and are
usually due to direct impact, as seen in assaults.
•• They rarely occur in the cerebellum.
•• Multiple haematomas involving the brainstem and basal ganglia may occur.
•• Most intracerebral haematomas are visualised as hyperdense mass lesions
and can be detected by computed tomography (CT) immediately after the
trauma. However, some may evolve over the next 24–48 hours.
•• Intracerebral haematomas may co-exist with compound depressed
fractures and may be revealed while the fracture is being treated.
•• In subacute cases, CT scan is of great help in the diagnosis and localisation,
as well as in detecting associated surface haematomas.
•• When encapsulated, the haematomas can be evacuated with benefit,
through suitably placed burrholes. Stereotactic evacuation can be done.
•• In surface haematomas, if burrhole aspiration is not effective, the localised
haematoma can be removed by a craniotomy.
•• It is recommended that all patients with sizeable intracerebral haematoma
require a large trephine or a formal craniotomy to achieve satisfactory
evacuation and decompression.
280
•• Small haematomas do not need surgical relief.

•• Endoscopic evacuation of the intracerebral hematoma can also be done.
Delayed Intracerebral Haemorrhage

•• A delayed haematoma is one that is seen on a repeat CT scan within 24–48
hours of the injury, and was not present on the initial scan.
•• A circumscribed haematoma may occur some time after the original
accident during the process of repair of the lacerated brain. This is due to
bleeding from the necrosed blood vessels into the lacerated area.
•• Its pathogenesis is not clear.
•• The fact that these cases occur usually in the older age group may indicate
that this may be a complication of a pre-existing vascular pathology such
as atherosclerosis.
•• A probable explanation seems to be that the bleeding occurs slowly into a
softened area of traumatized brain, the “apoplexy” occurring when a critical
point is reached. During the intervening period, the patient appears well and
presents a picture resembling a chronic subdural haematoma.
•• The diagnosis is difficult as the symptoms and signs, both focal and general,
tend to wax and wane, and then, all of a sudden, the patient gets into the
final state of coma.
•• Clinical awareness of this possibility is important and when patients do
not rapidly improve or continue to be ill, CT studies are to be repeated.
•• The prognosis is poor even when the haematoma is evacuated by aspiration
through a burrhole.
•• In the course of an acutely enlarging space-occupying lesion, such as an
intracerebral haematoma/contusion in the human or an extradural inflated
balloon (a simulated lesion) in the experimental animal, four stages of
evolution may be distinguished:
1. Stage of initial compression
2. Stage of venous congestion, oedema, anoxia and neuronal irritation
3. Stage of arterial obstruction, anaemia and neuronal paralysis
4. Stage of irreversible neuronal failure and death.
Stage of Initial Compression
•• Initially, the rise in ICP due to an increasing mass lesion is compensated
by the displacement of CSF, blood and brain itself.
•• However, once these mechanisms prove to be inadequate, venous
congestion leads to stasis of blood and an increase in tissue CO2 and
oedema.
•• Clinically, the signs are those of neuronal irritation, epileptic fits, constricted
pupils and general irritability, with headache of increasing severity and vomiting.
•• The deformed and displaced brain irritates the ipsilateral third nerve and
then the contralateral third nerve followed by their paralysis resulting in
sequential changes in the pupils. These changes herald temporal lobe
herniation into the tentorial hiatus and compression of the upper brainstem.
•• Compression of the long tracts results in contralateral hemiplegia.
•• With rapidly collecting haematomas, the brainstem is pushed and the
contralateral cerebral peduncle is compressed against the free margin of
the tentorium (Kernohan’s notch) leading to an ipsilateral hemiplegia. Thus,
the haematoma may be on the same side as the hemiplegia (Kernohan’s
phenomenon).
281
Stage of Anaemia and Neuronal Paralysis

•• At this stage, the ICP is raised high enough to cause a critical reduction
in cerebral blood flow.
•• This leads to abolition of vasomotor tone and further autoregulation of the
cerebral circulation is not possible.
•• The vasoparalysis results in the volume of the blood in the vessels passively
following the changes in the arterial blood pressure, and haemorrhages
may occur in the brain.
•• The patient drifts into unconsciousness, the pulse pressure rises and the
respiratory rate first becomes slow and then rapid.
•• When both the cerebral peduncles get compressed, the patient goes into
extensor rigidity that comes on as extensor spasms spontaneously or on
stimulation.
•• At this stage, both the pupils are dilated and non-reacting.
•• As the ICP rises further, the lower brainstem begins to suffer. The patient
may hyperventilate washing out the CO2 and manifest Cheyne-Stokes
periodic breathing.
•• The respiratory centre gets deafferented and induces apneustic type of
breathing.
•• The autonomic nervous system is in disarray and there could be excessive
secretions from the salivary and other glands, which trickle down the throat,
making the respiration gurgling and noisy.
Stage of Irreversible Neuronal Failure
•• The blood pressure begins to fall and respiratory arrest and death
supervene.
•• Irreversibility sets in between the second and the third stages, a transition
which is marked by the onset of unconsciousness.
Note:
In this era of prompt transfer of the patient to the hospital and efficient
emergency service, one is unlikely to see the above-mentioned clinical
evolution prior to prompt diagnosis and necessary treatment.
CLINICAL FEATURES
Conscious Level
•• With the exception of penetrating injuries, like gunshot wounds, it is almost
impossible for severe brain damage to occur without an alteration in the
level of consciousness.
•• No one dies of a damaged brain in a conscious state; a period of
coma always precedes a fatal outcome. Thus, alteration in the level of
consciousness is an important clinical parameter.
•• During the first two or three hours after a non-fatal head injury, the primary
neuronal injury is the main, if not the only active, lesion.
•• Unconsciousness, which supervenes immediately after the injury but clears
in a few minutes, is usually explained as concussional.
•• If such unconsciousness persists, it indicates the severity of the underlying
primary neuronal damage.
•• On the contrary, if the loss of consciousness occurs some time after the
accident, the obvious conclusion is that the primary neuronal injury was not
severe enough to render the victim unconscious and that this delayed loss
after the “lucid interval” is due to the onset of the epiphenomena.
282
•• The state of consciousness at the time of onset of the epiphenomena has

a definite significance. The greater the depth of unconsciousness at the
onset, the grosser is the primary neuronal damage.
Early Detection
•• In patients with intracerebral haematomas, perilesional swelling and
enlargement of bleeding is the rule rather than the exception.
•• Thereby, to achieve a low mortality rate, the development of the classical
picture of severe compression has to be prevented by early recognition of
rising ICP and prompt intervention.
•• In this context, apart from guidance from CT findings, many neurosurgeons
advocate routine ICP monitoring to detect a rise in ICP before clinical signs
become obvious.
•• Headache, which does not subside on routine analgesic administration,
persistent vomiting and convulsions, especially in non-epileptics, must
arouse suspicion.
•• The earliest alterations in consciousness are subtle and must be looked for;
inattention, lack of the usual alertness, and a delayed response to routine
demands are extremely suggestive.
•• There is no clinical feature really pathognomonic of extradural, subdural
or intracerebral haemorrhage.
•• A direct injury, a fracture line across the vascular markings and a boggy
swelling of the scalp indicate the possibility of extradural haemorrhage.
•• Careful neurological examination reveals subtle signs like an extensor
plantar response and hyperreflexia on one side or diplopia.
•• Involuntary micturition in a conscious adult with head injury is always a
definite indication of raised ICP.
•• Restlessness not subsiding easily may indicate the onset of cerebral
compression.
•• These various features either singly or in combination constitute grounds
enough to get a CT done or repeated.
•• The most frequent clinical event that prompts the surgeon to operate is
the deterioration in the level of consciousness. This may be with or without
a lucid interval.
•• Pupillary asymmetry and onset of hemiplegia and convulsions are events
that appear later.
Volumetric Measurement of Intracerebral Haematoma

•• Volumetric measurement on traumatic brain injury is calculated by the
ellipsoid method (ABC method) (previously described for AVM) or by the
direct estimation method using a grid as described by Cavalieri.
•• The ABC method described by Kothari has been proposed as a means of
measuring ICH volume.
•• The first step is to identify the CT slice with the largest area of haemorrhage.
•• The variables are given as follows:
A. The largest diameter
B. Largest diameter perpendicular to A on the same slice
C. The total number of 10 mm slices.
•• Compare each slice with the first slice.
•• The haemorrhage is scored as follows: If it is more than 75% compared
with slice 1, the slice is counted as 1, if the ICH is 25–75% of the maximum
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size, count the slice as 0.5 and if the slice is less than 25%, the slice is not
counted. The total gives the value of the variable C.
•• The volume is then calculated by the formula ABC/2.
REGIONAL CEREBRAL BLOOD FLOW (RCBF)

MEASUREMENT
•• Regional cerebral blood flow (rCBF), evaluated by means of Xenon-
enhanced computerised tomography (XeCT) in patients with severe head
injury [Glasgow coma scale (GCS) < or = 8], provides valuable information
for management.
•• The rCBF is measured in three different regions of interest: The
haemorrhagic core, the peri-haematoma oedematous low-density area, and
a 1-cm rim of peri-haematoma normal appearing brain tissue, surrounding
the oedematous low-density area.
•• Findings suggest that the only area with persistent ischaemic values was
the haemorrhagic core, and the low rCBF levels seen in the peri-haematoma
low-density area can be ascribed partially to ischaemia, which can possibly
recover over time.
•• These results could encourage a surgical approach based on an early
evacuation of the haemorrhagic core with preservation of the surrounding
oedematous tissue.
GUIDELINES FOR THE TREATMENT OF

TRAUMATIC INTRACEREBRAL HAEMATOMAS
1. Patients with parenchymal mass lesions and signs of progressive neurologi-
cal deterioration with reference to the lesion, those who develop medically
refractory-raised ICP or those who show signs of significant mass effect
on CT have to be managed surgically.
2. Patients with GCS 6–8 with frontal or temporal contusions more than 20
cc in volume associated with a midline shift of 5 mm or more, with cisternal
compression on CT scan and with a lesional volume more than 50 cc are
to be managed surgically.
3. Patients with parenchymal mass lesions, who do not show signs of neu-
rological compromise, who have a controlled ICP and with no significant
mass effect on CT scan, may be managed conservatively with intensive
care unit (ICU) monitoring and serial imaging.
Treatment Strategies—Timing and Methods

•• Intracerebral haematomas generally do not require surgical evacuation
unless there is significant mass effect or intracranial hypertension resulting
in a poor GCS.
•• They resorb in about 4–6 weeks by macrophage phagocytosis and gliosis.
•• Craniotomy and evacuation of the mass lesion are recommended for
patients with the surgical indications listed above.
•• A bifrontal craniotomy sometimes may have to be performed in cases
of bifrontal haematoma as the procedure provides a larger area
of decompression, through which the underlying haematoma and
haemorrhagic tissue can be easily visualised and evacuated.
•• For temporal lobe lesions, one requires temporal craniotomy. Ventricular
drainage may be necessary when there is associated intraventricular
haemorrhage causing hydrocephalus.
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•• For temporal lobe lesions—contusion, laceration, haematomas, a temporal

craniotomy and removal of the damaged tissue is the treatment of choice.
In case the haematoma is circumscribed, it could be removed through a
cortical incision. In cases with a more diffuse lesion, an anterior temporal
lobectomy may be required.
•• Bifrontal decompressive craniectomy within 48 hours of injury is a treatment
option for patients with diffuse, medically refractive post-traumatic cerebral
oedema and the resultant intracranial hypertension.
•• Decompressive procedures, including subtemporal decompression, tempo-
ral lobectomy and hemispheric decompressive craniectomy, are treatment
options for patients with refractory intracranial hypertension with diffuse
parenchymal injury with clinical and radiological evidence of impending
transtentorial herniation.
•• To summarise, traumatic ICH of volume more than 50 cc or in any patient
with traumatic ICH in whom there is progressive neurological deterioration,
mass effect on CT, refractory raised ICP and with a shift of more than
5 mm, surgery is recommended.
36
CHAPTER Traumatic Brainstem
Haemorrhage
Ashok Kumar Mahapatra  Deepak Agrawal
INCIDENCE
•• The incidence of brainstem haemorrhage (BSH) is difficult to determine.
•• Zuccarello in 1983 reported primary brainstem haemorrhage in 36 patients
among 1,000 cases of head injury in whom CT scans were performed.
•• Kalyanaraman and Ramamurthi reported brainstem haematomas in 4.6%
of all head-injured patients.
MECHANISM OF INJURY
•• Since Duret first described this condition in 1878, there are several
pathological studies describing the details of mechanism, location and
pathogenesis of BSH.
•• Acceleration and deceleration injuries involve the brainstem to varying
degrees, depending upon several factors.
•• Mechanical effects of stretching and distortion further aggravate the damage
due to vascular injury.
•• Involvement of the brainstem can occur due to several mechanisms:
a. Damage to the brainstem by direct force of impact
b. Due to flexion and distortion
c. Vascular involvement.
•• Primary damage is also possible due to brain movement when the
brainstem gets lacerated or contused by the tentorial edge. While acute
flexion is the most frequent cause, rarely hyperextension injury to the head
can also give rise to brainstem damage.
•• Generally, primary brainstem injury can be in the form of: (a) laceration;
(b) contusion, and (c) BSH (Table 1).
•• Secondary damage to the brainstem occurs more frequently as compared
to primary damage. Transtentorial herniation is the most frequent cause of
brainstem damage. Secondary brainstem haemorrhage is more frequent
in the tegmentum of the midbrain and the pons.
•• Multiple subependymal punctate haemorrhages may also occur secondary
to transtentorial herniation. Secondary haemorrhages are often bilateral
and paramedian in location.
•• Necrosis may occur in the distorted areas. Secondary medullary lesions
are also seen due to longitudinal buckling of the medulla.
•• Frequently, both primary and secondary damage in the brainstem might
coexist.
•• Lesions, like ischaemic necrosis, small haemorrhages, microhaemorrhages
and degeneration of axons, showing retraction bulbs can also be seen.
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Table 1: Pathology of traumatic brainstem lesions

(A) Primary pathology
(i) Laceration
(ii) Contusion
(iii) Primary brainstem haematoma
(iv) Transection of brainstem
(B) Secondary pathology
(i) Oedema
(ii) Ischaemia
(iii) Infarction
(iv) Secondary haemorrhage
(C) Combination of primary and secondary pathology
•• Subthalamic lesions are prone to microhaemorrhages and necrosis. Primary

lesions are less common in the tegmentum. In the medulla, there is selective
necrosis of the inferior olivary nucleus and vestibular nuclei.
•• All the clinical features observed in patients with BSH can be observed
without any discernible structural lesion due to functional disturbances
(Tandon 1964).
•• Patients with BSH are usually unconscious or in altered sensorium. However,
only on the basis of unconsciousness, a clinical diagnosis cannot be made.
•• Rarely, patients may have GCS more than nine.
•• Decerebrate rigidity is commonly observed in patients with BSH.
•• However, decerebrate rigidity can occur in the absence of a brainstem
lesion. Rarely, patients present with hypotonicity.
•• Other clinical findings which are typical of brainstem lesions are respiratory
abnormalities, pupillary changes and temperature changes.
•• Varieties of respiratory abnormalities have been reported depending
on the site of the lesion. It could be classical Cheyne-Stokes breathing,
hyperventilation or shallow breathing.
•• Disturbances of temperature regulation lead to hyperpyrexia.
•• Pupillary abnormalities are well described in brainstem haemorrhage. Fixed
bilateral non-reacting dilated pupils is the classical presentation. ‘Pin-point
pupils’ are very rarely observed in patients with traumatic BSH. Thus,
pupillary changes are non-specific and not diagnostic of brainstem injury.
•• Disturbance of conjugated eye movement is more frequent. This is
basically due to involvement of the medial longitudinal fasciculus (MLF).
The disconjugate movement and abnormal oculocephalic or doll’s eye
movement are characteristic findings of brainstem damage.
•• Some patients rapidly deteriorate to brain death with respiratory arrest.
Cold Caloric Response (Vestibulo-ocular Reflex)

•• Cold caloric response is an important test for assessing brainstem integrity.
•• Its utility in predicting the outcome in severe head injury is well established.
•• It is a simple bedside test.
•• The head is raised by 30 degrees and the external auditory meatus is irrigated
with ice-cold saline or water which stimulates the semicircular canals. The
stimulus is carried by the vestibular nerve to the vestibular nuclei, which
are connected to the MLF, and 3rd and 6th nerve nuclei in the brainstem.
Chapter 36 • Traumatic Brainstem Haemorrhage
287
•• Thus, by stimulating the vestibular nuclei, there is conjugate deviation of

the eyes with nystagmus in normal individuals.
•• Depending upon the site of brainstem involvement and the degree of
damage, there may be absent or abnormal response of varying degrees.
•• A complete absence of caloric response is indicative of a grave prognosis,
and is one of the diagnostic criteria for brain-death.
Brainstem Auditory Evoked Response

•• Brainstem auditory evoked response (BAER) is a reliable study assessing
auditory nerve and brainstem function.
•• BAER is frequently used as a prognostic test in severe head injury.
•• Patients with normal BAER have a good prognosis and, on the contrary,
patients with repeatedly absent BAER either die or remain vegetative.
•• BAER normalised following surgery and preceded clinical improvement.
•• Improvement in BAER findings or normal BAER were associated with a
favourable outcome.
RADIOLOGY
•• CT scan is a reliable imaging modality for post-traumatic intracranial
pathology, because of its ability to demonstrate the extent, sites and nature
of injury. Hence, today CT is the primary diagnostic method in patients
with head injuries.
•• CT scan not only shows the haematoma but it also shows the obliteration
of the basal cisterns and the presence of blood in the prepontine or
perimesencephalic cistern.
•• The haematomas may be hyperdense, isodense or hypodense, depending
on the extent of haemorrhage and oedema.
TREATMENT
•• There is no specific treatment for BSH. However, associated pathology may
need surgery depending on the size of the haematoma and the mass effect.
•• Overall, 20% of patients with brainstem haemorrhage may have sizable
haematomas elsewhere in the brain needing surgery.
•• As the patients with BSH are very sick and remain unconscious for long
periods, they need longer intensive care management and ventilatory support.
•• Nursing care, management of pulmonary problems and tracheostomy care
need special mention.
•• Moderate hypothermia and control of hyperpyrexia, if present, are important
factors in survival. Hypothermia may enhance the chance of survival.
CONCLUSION
•• Traumatic BSH is not as rare a condition as was believed earlier. With
the availability of CT scan more cases are being diagnosed to have BSH.
•• The common sites for BSH are the pons or midbrain.
•• Around 25% of patients are conscious at admission and 50% of patients
are admitted in a decerebrating state. In more than 30% of patients, there
are associated haematomas elsewhere in the brain.
•• Caloric responses and BAER are two good prognostic tests.
•• Repeated normal cold caloric response or BAER is indicative of a good
prognosis.
•• Survival ranges from 30 to 50%, and 25% may have good outcome.
37
CHAPTER Complications and
Sequelae of Head Injuries
Khosla VK  Gupta SK  Mukherjee KK  Chhabra R
INTRODUCTION
•• Head injury (HI) can account for a great deal of chronic disability.
•• Common physical defects after HI include cranial nerve palsies, such as
anosmia, oculomotor paresis, visual field defects, and motor disorders,
resulting from cortical or brainstem lesions.
•• Post-traumatic sequelae include:
–– Post-traumatic amnesia
–– Post-concussion syndrome
–– Neurobehavioural sequelae
–– Post-traumatic epilepsy
–– Infections: Meningitis, osteomyelitis, abscess
–– Post-traumatic CSF fistulae and pneumocephalus
–– Normal pressure hydrocephalus
–– Metabolic abnormalities
–– Vascular abnormalities like coagulopathies, carotid cavernous fistula,
delayed intracerebral haematomas and others.
POST-TRAUMATIC AMNESIA
•• The length of post-traumatic amnesia (PTA) is defined as the time from the
moment of injury to the time of resumption of normal continuous memory.
•• When the duration of PTA is noted, there may be two end-points—the first
recollection after the accident or the first recollection after which the patient
has continuous memory. The latter is the accepted end-point for PTA.
•• Usually, the termination is abrupt, except in patients with severe head
injuries where memory impairment is likely to persist.
•• The amnesic phase may last from several minutes to several weeks, yet
finally ends sharply with the return of normal continuous memory.
•• Behaviour during the PTA period varies from apparent normality to impaired
memory and mental confusion.
•• PTA includes any period of unconsciousness or overt confusion and, in
addition, a further period during which outward behaviour has appeared
to return to normal.
•• In the majority of cases, the purely amnesic phase follows the clearing
of overt signs of confusion or impairment of consciousness, but it may
occasionally follow immediately after the injury and may be the only deficit.
•• The duration of retrograde amnesia (RA) is measured as the time between
the moment of injury and the last clear memory from before the injury,
which the patient can recall.
Chapter 37 • Complications and Sequelae of Head Injuries
289
•• Usually, RA is much shorter than PTA, although, the reverse may occasion-
ally be seen. Mostly, RA lasts for only a few seconds or minutes.
•• Longer RA is usually seen in severe injuries and may be of many days or
weeks duration.
•• In mild injuries, there may be no RA and full details of the injury can be
recalled up to the moment of loss of consciousness. With long RA, the
amnesia is most dense for events immediately preceding the injury.
•• The duration of amnesia is taken as a guide to the severity of injury and
prognosis. PTA is more valid and useful than RA in this regard.
•• The duration of PTA shows close correlation with objective evidence of
damage to brain tissue, such as motor disorder, dysphasia, anosmia or
memory impairment.
Evaluation of Posttraumatic Amnesia

•• Anterograde amnesia is evaluated by testing of impaired episodic memory
for events that occur within a specific spatio-temporal context, which is
reflected by difficulty in recalling events in the hospital environment and
recount events in the news or in the patient’s life.
•• Traditional methods of assessing retrograde amnesia asked the patient to
describe and date the last event in memory before the injury.
•• More recently, lists of information in the public domain or an autobiographical
memory questionnaire are used to assess retrograde memory loss.
•• The sequence of recovery of orientation is for persons, place and time in
about 70% of patients.
•• Serial administration of a brief bedside test, such as the Galveston
Orientation and Amnesia Test (GOAT) can depict an early cognitive
recovery curve that is related to long-term neurobehavioural outcome.
•• Monitoring the resolution of PTA is useful for acute clinical management.
(POST-TRAUMATIC) POST-CONCUSSION
SYNDROME
•• The post-traumatic syndrome is a constellation of symptoms that usually
occurs after a mild head injury.
•• The incidence of post-traumatic syndrome varies from 24 to 84%, and its
duration is usually 1–6 months.
•• Head injury patients at 6 weeks and 1 year after injury and found that
several factors are associated with a higher incidence of symptoms: (1)
female sex; (2) headaches or abnormal central nervous system signs at
24 hours and (3) fall from a height.
Pathophysiology
•• Post-concussion syndrome is generally attributed to diffuse axonal injury.
However, a significant element of psycho-social factors cannot be ruled out.
•• Traditionally, diffuse axonal injury was believed to occur at the moment
of impact and that this led to physical disruption and permanent damage;
however, studies indicate that a sequence of events occur that culminates
in axonal fragmentation.
•• Many secondary injury events, which include damage to the blood-brain
barrier, release of factors that cause inflammation, free radical overload,
excessive release of the neurotransmitters like glutamate (excitotoxicity),
influx of calcium and sodium ions into neurons and dysfunction of
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mitochondria occur, which injure the brain’s white matter axons, which may
separate from their cell bodies and lead to cell death.
•• There is, in addition, some early evidence of volume transmission through
the extracellular space that may occur in combination with the usual
synaptic transmission of information. For example, a mismatch between
the location of the transmitter release and receptors frequently occurs.
•• Volume transmission alterations may also be associated with neuronal
damage with potassium ion or glutamate release into the extracellular fluid.
Clinical Profile and Evaluation

•• The usual clinical profile of a patient with post-traumatic syndrome is that
of mild head injury, minor or no significant abnormalities on neurological
examination, and one or more of the following subjective complaints: Head-
ache, dizziness, emotional lability, sleep abnormalities, poor concentration,
memory difficulties, personality changes, anxiety or depression.
•• Evaluation of pre-existing conditions, such as alcohol or drug dependency,
psychiatric illness or endocrinological disorders, should be undertaken.
•• A thorough neurological evaluation should be performed by a neurosurgeon;
cranial nerve examination should include testing for anosmia, visual acuity
and field testing and a hearing evaluation.
•• The neck and suboccipital area should be examined for muscle spasm,
which may be responsible for the complaint of headache.
•• Follow-up computed tomography may show such lesions as chronic
subdural haematoma, cortical atrophy (particularly in the frontal lobes) or
hydrocephalus.
•• Magnetic resonance imaging expands the diagnostic possibilities by
demonstrating oedema, resolving contusions, effusions or evidence of
diffuse axonal injury.
•• PET scans showed reduction in glucose use by the brain and changes in
cerebral blood flow have been found to exist for as long as 3 years after a
concussion in studies using single photon emission computed tomography
(SPECT).
•• Electroencephalography may be indicated, particularly in patients who have
had seizure activity at some point in their clinical course.
•• Evoked potential studies, such as brainstem auditory evoked response
analysis or visual evoked response analysis, afford yet another method for
demonstrating evidence of underlying organic dysfunction.
•• Vestibular function tests may be required if dizziness is a dominant
syndrome.
•• Psychological testing is added to assess whether a patient has experienced
memory alterations, personality changes, task-oriented difficulties or similar
dysfunction. It is important to rule out the medicolegal motives underlying
the syndrome.
•• The Stroop Colour Test and the 2 and 7 Processing Speed Test (which both
detect deficits in speed of mental processing) can predict the development
of cognitive problems from PCS.
•• The Minnesota Multiphasic Personality Inventory profile can identify
characteristics of anxiety, somatisation and conversion mechanisms.
•• Other tests like Rivermead Postconcussion Symptoms Questionnaire,
Hopkins Verbal Learning A test and the Digit Span Forward examination
are also helpful in assessing the psychological status of the patient.
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Treatment
•• Treatment of post-traumatic syndrome mandates recognition of the interplay
of both organic and psychological factors.
•• Rehabilitation is intended to help the patient develop a sequence of adaptive
behaviours that increase personal independence. This includes learning
behavioural skills appropriate for independent daily living, such as use of
public amenities, food, shopping and driving.
•• Many of the rehabilitative efforts for post-traumatic syndrome patients are
directed at improving memory and attention.
•• Both physical and psychological factors are important in persistent post-
traumatic headache and dizziness.
•• Mild analgesics, medicines for vertigo and dizziness, antidepressants or
anti-anxiety drugs may be helpful.
•• Fortunately, the post-concussion syndrome almost always resolves with
the passage of time. In some cases, cessation of symptoms occur only
after the settlement of litigation.
NEUROBEHAVIOURAL SEQUELAE
•• Neurobehavioural sequelae refer to the cognitive and behavioural effects
of brain injury. The range of mental sequelae is very broad and embraces
most that can be found in psychiatric symptomatology.
•• There are a number of aetiological factors, which may contribute to post-
traumatic neurobehavioural sequelae.These are listed below:
–– Mental constitution
–– Pre-morbid personality specially history of alcohol or drug abuse
–– Emotional impact of injury
–– Circumstances, setting and repercussions of injury
–– Iatrogenic factors
–– Environmental factors
–– Compensation and litigation
–– Response to intellectual impairment
–– Epilepsy after injury.
•• Amount and location of brain damage.
•• The different post-traumatic psychiatric sequelae are:
–– Cognitive impairment
–– Personality change
–– Psychosis
–– Neurotic disability
–– Memory impairment.
Cognitive Impairment
•• The severity of post-traumatic cognitive disturbance depends on the degree
of diffuse axonal injury, as well as the volume and location of focal injuries.
•• These cognitive impairments are due to cholinergic deficits following head
injury.
•• Generalised Intellectual Impairment: After a closed head injury, the
impairment of intellect is usually global. Marked dementia is usually
accompanied by severe neurological disability and the patient may be in
a persistent vegetative state.
•• Focal Cognitive Impairment: This is more likely to develop following
penetrating head injury. Psychometric tests reveal disorders of memory,
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language and visuospatial competence. Localised damage to the

diencephalon or medial temporal lobe may result in a post-traumatic
Korsakoff’s syndrome.
•• Dominant hemisphere injury may cause language difficulties such as
impaired comprehension, speech production, reading, writing or spelling.
There may be reduced verbal fluency, impaired arithmetical function or
dyspraxia.
•• Non-dominant hemisphere damage may result in visuospatial agnostic
defects and disturbances of topographical orientation.
•• Disturbances of body image, dressing apraxia and anosognosia may
be marked in the early stages, but rarely persist in the absence of gross
intellectual derangement.
•• Recovery of Intellectual Function: Even after severe head injuries, most
patients may slowly show improvement over time, so that a firm prognosis
should not be attempted until 2–3 years after the trauma.
Personality Change
•• This implies an alteration in the patient’s habitual attitudes and patterns of
behaviour, so that his reactions to events and to the people are different
from what they were before.
•• Head injured patients are particularly prone to damage of the neocortical
portions of the limbic system; frontopolar, orbitofrontal and temporal regions.
•• Personality Change with Brain Damage: The personality changes, which
accompany intellectual impairment, may be only a loss of refinement or
lessened vitality of behaviour. With more severe dementia, there will be
slowing, impairment in motivation, loss of libido and withdrawal of interest
in surrounding events and people.
•• Frontal lobe lesions remain the best known examples of effects of regional
cerebral damage on personality. These include lack of foresight, tact and
concern, inability to plan ahead or judge the consequences of actions
and a euphoric disposition. Bilateral frontal lobe lesions, especially of the
orbital parts, lead to the most severe changes. A combination of disabling
euphoria and disinhibition associated with intense irritability is termed as
“fronto-limbic dementia”.
•• Hypothalamic and basal brain injuries may be characterised by sluggish-
ness and apathy, fluctuations of mood, sudden outbursts of irritability,
disturbances of appetite, thirst and sleep rhythm, and varied sexual pa-
thologies.
•• Personality Change without Brain Damage: These include fluctuating
depression, morbid anxiety, obsessional traits and persistent irritability.
Psychosis
•• Psychotic episodes may develop later in association with post-traumatic
epilepsy (PTE).
•• The problem is more complex when schizophrenic, paranoid or affective
psychosis develops in head-injured patients.
•• The generally accepted view is that a constitutional predisposition to the
psychosis is a major factor in most cases of schizophrenia or affective
psychosis, following head injury.
•• All forms of schizophrenia have been reported following head injury—
hebephrenic, paranoid and catatonic.
293
•• The various factors which help in distinguishing TBI psychosis from

schizophrenia include a later age of onset, less premorbid psychiatric
disturbance, brief duration, a less common family history, better response to
neuroleptics, less need for maintenance medication and a better prognosis.
Neuroses/Neurotic Disability
•• The post-traumatic neuroses represent the most common of the psychiatric
sequelae of head injury.
•• These include a number of emotional disorders: minor depression, states
of tension and anxiety, neurasthenic reactions, conversion hysteria and
obsessional neurosis.
•• Depression in these patients is characteristic of neurotic depression.
Anorexia, insomnia and early morning waking are rarely marked.
•• Complaints of difficulty in concentration, lack of normal interest and minor
forgetfulness may be marked. Anxiety may coexist with depression or
occur alone. Persistent states of anxiety and tension tend to be seen after
accidents of especially frightening nature.
•• Irritability is among the most common of the emotional consequences of
injury. The patient is short-tempered, snappy and stricter in matters of
discipline.
•• The dissociative states include fits, fugues, amnesia, motor paralysis,
anaesthesia, disturbances of speech, sight or hearing.
•• Obsessive compulsive symptoms may emerge in susceptible individuals.
Memory Impairment
•• About one-half of survivors of severe closed head injury exhibit residual
antero-grade memory deficit, as reflected by impaired learning and retention
of new information.
•• Episodic memory for events with a specific spatiotemporal context is the
most intensively studied form of memory in head-injured patients.
•• Tests involving verbal memory for word lists revealed that head-injured
patients recalled about 50% fewer words.
•• Improvement in memory after severe closed head injury occurs primarily
during the first 6 months on measures of verbal learning and memory and
on visual recognition memory.
Boxing Injuries
•• Serious sequelae appear to follow repeated mild head injuries, each in
itself leading to no more than brief concussion.
•• The mechanisms of such a cumulative effect are unknown, although the
findings of beta-amyloid deposition in the brain may be a pointer towards
the pathophysiologic process.
•• The picture of “punch-drunkenness” in retired boxers is widely recognised.
•• In its fully developed form, the syndrome consists of cerebellar, pyramidal
and extrapyramidal features, along with a varying degree of intellectual
deterioration.
•• In mild examples, there is dysarthria, facial immobility, poverty and slowness
of movement.
•• At its most severe, there is disabling ataxia, dysequilibrium, festinant gait,
tremors of the hands and head, and spasticity or rigidity of the limbs.
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•• Cerebral atrophy has been found to antedate the development of overt

signs of brain damage; and sometimes show association with the number
of bouts fought rather than with the number of knockouts, suggesting a
cumulative effect of multiple sub-concussive blows to the head.
•• Cerebral atrophy is commonly revealed on CT scanning, with dilatation of
the ventricles, sulcal shrinkage, and sometimes, obvious cerebellar atrophy.
•• A characteristic finding is perforation of the septum pellucidum.
•• The EEG may be abnormal with flattening of the record, diminution of the
alpha rhythm or diffuse slow waves.
•• At autopsy, cerebral atrophy and ventricular enlargement are obvious and
ragged holes may be seen in the septum pellucidum. The most obvious
abnormalities are in the deep midline structures, with tearing of the septal
region and atrophy of the fornices. Severe gliosis is seen in these regions
and also in the hypothalamus and thalamus. The cerebellum also shows
gliosis and loss of Purkinje cells. In the substantia nigra, there is loss of
pigmented neurons, similar to that seen in Parkinson’s disease.
•• The cerebral cortex shows extensive loss of neurons, many of those
surviving show neurofibrillary degeneration of the Alzheimer’s type. The
clinical features are probably related to damage to two main areas of the
brain—the upper brainstem and the hippocampal-limbic system.
POST-TRAUMATIC EPILEPSY
Definition
•• Post-traumatic epilepsy can be of two types:
–– One occurring within 7 days after injury is labelled as early PTE and
–– Seizures occurring more than 1 week after head trauma are
categorised as late PTE.
•• Within the early epilepsy group, seizures occurring within the first 24 hours
are labelled as immediate seizures.
Incidence
•• The incidence of early epilepsy varies from 2.5 to 7%.
•• Late PTE ranges from 5 to 7%, being much higher in soldiers with missile
wounds (34–53%). Young children are more prone to early seizure, and
adolescents and adults to late seizures.
Pathophysiology
•• The cascade of structural and physiological changes leading to PTE is still
not well understood.
•• The following different mechanisms may be responsible at different time
intervals:
–– Direct neuronal impact
–– Membrane depolarisation
–– Acetylcholine release
–– Temporary loss of inhibitory control from the mesencephalic reticular
system
–– Cerebral contusion and oedema with interference in cation transport
–– Hyperexcitability of recovering neurons
–– Meningocerebral cicatrix and glial scar
–– Dendritic depolarisation and post-synaptic hypersensitivity
–– Genetic factors.
295
•• The histopathological examination of brain tissue after trauma reveals

reactive gliosis, neuronal and oligodendroglial loss, axonal retraction
balls, Wallerian degeneration, neuroglial scar formation and cystic white
matter changes.
•• The deposition of iron liberated from haemoglobin may be an important
causative factor.
•• Iron and other compounds have been found to affect intracellular calcium
oscillation.
•• The activation of the arachidonic acid cascade leads to the formation of dia-
cylglycerol and inositol triphosphate. This leads to elevation of intracellular
calcium, which appears to be involved in excitotoxic damage to neurons.
•• Neuronal death and reactive gliosis can lead to the formation of a glial scar,
which becomes the epicentre of the hyperexcitable focus.
•• The epileptogenic focus has been demonstrated to have biochemical
defects in metabolism of acetylcholine, glutamic acid, gamma-aminobutyric
acid and potassium.
•• The epileptogenesis after chronic cortical injury could result from alterations
of intrinsic membrane properties of pyramidal neurons, together with
enhanced N-methyl-D-aspartate (NMDA) synaptic conductances.
Early Post-traumatic Epilepsy

•• The risk of early PTE is related to the type and severity of brain injury.
•• It is much higher in patients with more severe injuries.
•• Subdural haematomas and depressed skull fractures are the major
independent predictors of early seizures.
•• About one-third of early PTE occurs within the first hour, one-third between
1 and 24 hours, and the rest between 1 and 7 days after injury, with adults
having their first seizures somewhat later than children.
•• Focal seizures account for most of all early seizures (from 50 to 80%), with
the remaining being primarily generalised tonic clonic (25–50%).
•• Most early focal seizures are focal motor seizures; being more frequent
after missile injuries.
•• A generalised seizure occurring within a few moments of trauma is called
immediate epilepsy. This usually follows a mild injury.
•• Immediate concussive convulsions are thought to be a brief traumatic
functional decerebration that results from loss of cortical inhibition. It
requires no specific therapy and anti-epileptic medication is not indicated.
•• The main significance of early PTE is an indication of an increased risk for
development of late PTE, being approximately 25%.
Late Post-traumatic Epilepsy

•• The highest risk factor for late PTE is missile wounds.
•• In blunt head injury, the main risk factors are haematomas, depressed
fractures, focal signs and early seizures. Low GCS, subdural haematomas
and cortical contusion, each provide independent additional risk of late
seizures.
Prophylaxis and Treatment

•• Natural cessation of PTE is likely to occur in patients with a low frequency
of seizures, those in whom fits started early and in those who have an early
remission for more than a year.
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•• An attack of seizures occurring within a few minutes after a head injury

(immediate epilepsy) may not require any anticonvulsant medication.
•• There is a lack of consensus on the usefulness of prophylaxis with
anticonvulsants for the prevention of late PTE.
•• Considering the data available, prophylactic administration of phenytoin to
prevent either early or late PTE is not recommended.
•• However, there are many reports which conclude that phenytoin reduces
the risk of early seizures by 67–73%.
•• If an early seizure occurs, intravenous phenytoin should be given with a
loading dose of 18 mg/kg/min, followed by a maintenance dose of 5–7 mg/
kg/day. Prophylactic phenytoin can be stopped after about 1–2 weeks.
•• No prophylaxis should be given for late PTE. If a late seizure occurs, an
anti-epileptic drug (e.g. phenytoin, carbamezapine or valproate) may be
administered. The duration of treatment for late PTE follows the principles
of treatment of all late seizures and is usually 2 years.
•• Resection of the epileptogenic focus may be required to control post-
traumatic seizure intractable to medical management.
•• Late PTE tends to diminish with time and surgery should not be performed
for at least 2 years after the injury.
•• When there are multiple epileptic foci or the focus cannot be localised and
drug therapy is not effective, vagus nerve stimulation is another option for
treating PTE.
38
CHAPTER
Cranioplasty
Ramesh Kumar Sharma  Mathuriya SN
INTRODUCTION
•• Cranioplasty is defined as the restoration of a defect in the cranium or
correction of a deformity of the bone that may happen after trauma as in
depressed fracture or due to developmental anomalies.
•• The replacement of a bone flap after a craniotomy would also be a cranio-
plasty.
•• The technique of cranioplasty is a fine mix of art and surgical science.
•• The cranium has a well-defined topography and regions with specific
contours. Some areas are hidden under the hair and some areas, like the
frontal regions, are easily seen.
AETIOLOGY OF THE CRANIAL DEFECT

•• The main cause of defects of the cranial and facial bones is trauma.
•• Penetrating head injuries at times necessitate removal of bone (craniecto-
my). At times, it may not be possible to replace the osteoplastic craniotomy
flap due to either brain oedema or infection. The replaced bone flap may
become infected and may need to be removed.
•• Other causes are surgical bone excision for tumours (osteomas, meningi-
omas, haemangiomas, eosinophilic granulomas, epidermoids, metastases,
fibrous dysplasia, chondromas, sarcomas, aneurysmal bone cysts); for
infections (osteomyelitis, infected cranial flaps); for radionecrosis and
electrical lesions of the skull; and for congenital cranial and craniofacial
anomalies (encephalocoeles, congenital parietal defects).
CRANIOPLASTIC MATERIAL
•• An enormous range of materials have been employed for the repair of
cranial defects.
•• These have included an autograft from the same individual, allograft from
another individual of the same species, xenograft from other species and
bone substitutes from outside the realm of living tissues.
•• Whenever possible, the use of autografts is the most preferable, although,
this is sometimes impractical because of insufficient amount or their
unmalleable property.
•• The ideal substitute material should be strong, lightweight, malleable,
thermally non-conductive, sterilisable, easily secured, inert, radiolucent,
non-magnetic, aesthetically good, readily available and inexpensive.
298
PRESERVATION OF AUTOGRAFTS
•• There are times when the surgeon cannot replace the bone flap after
craniotomy.
•• Various methods have been used in an effort to preserve the bone and
maintain its sterility without losing its osteogenic potential.
•• Boiling of the bone, but this results in increased tendency for infection and
bone resorption. Other older preservation methods have included storing
in alcohol or formalin and then boiling before implantation. It has become
clear that boiling lessens the osteogenic potential of the flap and makes it
prone to bone resorption and infection.
•• Autoclaving bone flaps may also predispose them to similar complications,
but this has not been a uniform experience.
•• Storing the bone flap in the abdominal wall until it was required for the
cranioplasty was first described by Kreider (1920).
•• This technique is not widely used today, because it necessitates another
operation and produces an unsightly scar and there is little evidence for
better osteogenic potential of the bone. It is known that bone removed from
its blood supply and replaced in fresh tissue dies, with the exception of a
layer of superficial cells less than a millimetre in depth. Nevertheless, this
method has its contemporary proponents.
NEED FOR RECONSTRUCTION

•• Reconstruction of the cranial vault is often needed for protective and
cosmetic reasons.
•• The goals are to protect the brain and restore the normal contour of the
skull with as few complications as possible.
•• Other controversial goals are eliminating headache and apprehension and
avoiding cerebral palsy, decreasing vibration and motion intolerance, and
overcoming fatigue, insecurity and post-traumatic epilepsy.
CRITICAL SIZE OF DEFECT THAT REQUIRES

CRANIOPLASTY
•• It is commonly accepted that the fundamental indications for cranioplasty
are bone defects larger than 2 cm situated on the cerebral convexity and
bone defects of the glabrous frontal region.
•• Defects under the temporal and occipital muscles and those in very elderly
patients are not usually considered to require repair.
•• In children under 6 years of age in whom the dura is not damaged, regen-
eration of a portion of the skull may be observed. Thus, it is necessary to
wait at least a year after craniectomy in a child before deciding whether
reconstruction is necessary.
ANATOMY OF THE DEFECT

•• The defect may either be very small or be quite extensive.
•• These may be classified into Type I, where the size may be less than
5 cm2 or Type IV, where the size may be greater than 50 cm2.
•• Very small defects may not be reconstructed as far as protective function
is concerned, but may need reconstruction if these are situated in frontal
areas, especially the supraorbital and non-hair bearing forehead region.
Chapter 38 • Cranioplasty
299
•• The frontal region has been divided into three regions:

1. Supraorbital
2. Prehairline
3. Within the hairline
•• Even small defects in zone 1 and 2 look unaesthetic and should be
corrected but those in zone 3 may be left alone.
•• Parietal area defects of less than 5 cm2 may not require any reconstruction.
•• In the occipital area, defects of moderate size may also not need any
reconstruction as the thick musculature provides protection.
•• In short, the need for reconstruction is dictated both by the size of the defect
and the location of the defect.
TIMING OF RECONSTRUCTION
•• A significant reduction in incidence of infection has been noted when
sometime is allowed to elapse between the initial injury or infection and
the subsequent reconstruction.
•• It is generally believed that the interval between complex or contaminated
wounds and definitive cranioplasty should be between 3 months and
6 months.
•• If the frontal sinus has been opened, it may be prudent to perform cranio-
plasty after about a year.
•• Similarly, in the presence of an infected open wound, one should allow the
wound to heal and then embark on cranioplasty after about a year or so.
•• However, if adequate vascularised tissue is available, immediate recon-
struction is possible.
•• It is important to separate the aerodigestive tract from the extradural space
by the use of a vascularised flap like front-galeal flap. If the conditions are
favourable, a primary cranioplasty is advisable.
IMPORTANCE OF ADEQUATE SKIN COVER

•• Before undertaking cranioplasty, it is important to ascertain that there are
no compromised areas in the scalp.
•• The cranioplasty can be accomplished through existing scars and, if need
be, additional incisions can also be made.
•• It is very important to ascertain that there is sufficient skin available in the
scalp; it is more so in large defects of long-standing duration.
•• The scalp tends to sag inside the defect and might be stretched once
cranioplasty is done. This tight envelop can lead to exposure of the grafts/
implants in the post-operative period.
•• If there is deficiency of scalp tissues, it should be corrected before
cranioplasty is contemplated.
•• Smaller defects can be adjusted with local flaps, but larger defects will
necessitate import of tissue from distant areas. Very large defects may
require free-tissue transfer.
CHOICE OF MATERIAL FOR CRANIOPLASTY

•• Calvarial autograft is the most “natural” material of all because not only
does it possess all the ideal qualities for cranioplasty but it is also vital and
has excellent biological properties.
•• It has good growth potential and resistance to infection.
300
•• There can be no doubt that fresh autologous bone is the most suitable
material for reconstruction of cranial defects in view of its perfect
histocompatibility, optimal mechanical properties and good integration of
the graft with the adjacent bone, as well as the possibility of partial or total
revitalisation of the graft itself.
•• Autologous bone also ensures the best possible physiologic and cosmetic
results (in theory at least).
•• In fact, autologous bone grafts usually display bone regeneration processes
and there is a low incidence of infection.
•• The source of autologous bone can be the calvarium itself, ribs or iliac bone.
•• The cranium is the preferred donor site for harvesting bone graft for
cranioplasty.
•• The donor area is in the vicinity of the defect and a large amount of bone
can be harvested.
•• The patient experiences much less pain at the donor site as compared to
other donor sites like ribs and iliac bone.
•• The cranium provides a large area for bone grafting. The bone can be
harvested from an area which matches with the contour requirement of
the defect.
•• It requires training to obtain a cranial bone graft; however, the skill is easily
acquired. This may be done with a hammer and osteotome or even with
a Gigli saw.
•• The bone is generally, harvested from the non-dominant parietal area as it
is technically easy and the thickness of the bone is adequate.
•• It may be difficult to harvest split bone graft in very old and young patients
as the dipole in them is not well-developed. However, with a little practise,
a split cranial bone graft can be harvested even in children as young as
6 months to 1 year-old.
•• A full thickness cranial bone graft may be harvested from the skull, and it
can be split on a side table. More commonly, the bone is harvested as a
split graft in situ.
•• The graft may be oriented in any direction as dictated by the reconstructive
need.
•• The split graft can be harvested across the midline and suture areas.
•• The template of the defect can be made and placed in an appropriate area
of the calvarium to provide matching grafts.
•• If the need for bone graft is more than 50 cm2 additional bone may be
procured from other sources like ribs and iliac bone.
•• The rib may be split into two for increasing the surface area. The volume
loss in membranous bone like the cranium is much less as compared to
endochondral bone.
•• Autologous bone grafts from other sites can cause significant donor site
morbidity, can prolong operative time, are limited in the quantity available
for reconstruction and are difficult to contour.
ALLOPLASTIC MATERIAL
•• Alloplastic material has the advantage of malleability, easy accessibility
and durability.
•• However, it has many inherent disadvantages. These include high-risk
of infection, foreign body reaction, fibrous and capsular contracture of
surrounding tissue and lack of incorporation in the cranium.
Chapter 38 • Cranioplasty
301
•• There is also the danger of deeper migration of the implants.

•• The use of alloplastic implants for cranial reconstruction has a long history
with numerous materials used with varying degrees of success.
•• Currently, three different alloplastic alternatives are widely used:
1. Polymethylmethacrylate (PMMA)
2. Hydroxyapatite (HA)
3. Metal.
•• PMMA offers an inexpensive method. It is easily adapted and contoured
intra-operatively to cover a defect of any size and provides great impact
resistance. It does not integrate into the surrounding tissues and is reserved
for use in adult and older patients.
•• Methyl methacrylate is non-porous, and no bone in-growth is expected.
Cement paste implants tend to contain micropores, and experimental and
clinical evidence indicates that there is less long-term bone in-growth into
these biomaterials than in implants with macroporous architecture.
•• Custom made hard tissue replacement (HTR) implants, a modified porous
PMMA material, provide a very accurate and rapid method for large full-
thickness cranial defects. It requires pre-operative preparation utilising a
3D craniofacial model.
•• Hydroxyl apatite has excellent tissue compatibility and the advantage
of being osteoactive, radiolucent and readily available. In addition, it is
biocompatible and does not produce a chronic inflammatory response.
•• Unlike most other alloplasts that are inert, these materials are bioactive
(capable of osteoconduction) and have the potential to develop tissue in-
growth and integration into the recipient site after placement.
•• These materials are not osteoinductive by themselves but they do provide
a physical substrate onto which new bone from adjacent surfaces may
be deposited and potentially guided into areas occupied by the material.
•• Nova Bone (Porex Surgical, College Park, GA) is a synthetic bioactive
glass particulate consisting of 45% silica dioxide, 45% sodium oxide, 5%
calcium and 5% phosphate, which is believed to be bioactive towards the
production of new bone within the biomaterial.
•• Porous polyethylene (Medpor; Porex Surgical, College Park, GA) is
commonly used for facial augmentation and to restore continuity to
craniofacial skeletal defects. Unlike bone grafts, porous polyethylene shows
little evidence of implant degradation.
•• Demineralised bone is another alternative for reconstruction of the
craniofacial skeleton.
•• The most commonly used biomaterial in cranioplasty is HAs especially for
contour irregularities and touch up surgeries following cranioplasty.
•• Metal (Ti) mesh is an historic method of cranioplasty that provides a rapid
method for re-establishing an outer cranial cover. Its role today is more
limited but is still selectively used in the older cranial defect patients where
implantation times are shorter.
FIXATION
•• It is mandatory to properly fix the bone flap after bone flap craniotomy; an
improperly fixed flap has a tendency to drift downwards because of the
effect of gravity and pull of the temporalis muscle and leads to significant
cosmetic and functional disability.
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•• A variety of techniques are available for fixation of the bone grafts. The
edges of the cranial defect should be refashioned and the bone grafts
should firmly be in contact with the defect edges. The fixation can be
achieved quite satisfactorily with plates and screws or stainless steel wire.
•• The bone graft could also be pegged into the potential space between the
outer and the inner table.
•• The use of currently available absorbable plates may come in handy in
future.
39
CHAPTER
Maxillofacial Injuries
Arun Kumar Singh  DN Upadhyay
GENERAL PRINCIPLES
•• A vast majority of facial injuries occur due to automobile accidents,
assault and fall from a height, bringing these patients under the purview of
polytrauma. These are often associated with head-injury.
•• The patient has to be evaluated in toto, ruling out major and life-threatening
injuries.
•• Undiagnosed head injuries, blunt abdominal trauma and open chest
wounds/haemo/pnuemothorax wounds and spinal injuries are the major
causes of fatality in polytrauma patients.
•• Facial injuries, however grotesque, they may look, are not life threatening,
except if the airway is compromised due to bleeding in the air passages,
oedema or aspiration.
•• Evaluation of the polytraumatised patient should include a quick recording
of the vital parameters, a systematic survey of the other organ systems
and ensuring proper ventilatory and circulatory support.
•• A rapid haemogram and plain X-rays of the chest, abdomen and cervical
spine will avert many a diagnostic disaster and save many lives.
•• Continued blood loss is indicated by a labile blood pressure, a thready
pulse and a dyspnoeic, irritable patient.
•• A Glasgow coma scale (GCS) score should be established, cervical spine
injury excluded, and the chest and abdomen examined thoroughly to rule
out injuries in these areas.
•• Continued nasopharyngeal bleed cannot only exsanguinate the patient
but can also lead to respiratory compromise. A nasal pack or interdental
stabilisation of the facial fractures can often arrest the bleeding at a
dramatic speed.
•• Continued bleeding even after these measures should force one to think
of embolisation/ligation of the external carotid vessels and/or superficial
temporal vessels.
•• These injuries often require co-operation of a dental, maxillofacial, ENT
or plastic surgeon.
CLINICAL EVALUATION OF FACIAL INJURIES

•• Facial injury presentation can range from superficial lacerations to very
ghastly wounds with skeletal disruption.
•• Minor cuts, abrasions or contusions should not be taken lightly and as much
time should be devoted to their examination as to other injuries.
304
•• Bone injuries are often suggested by overlying soft tissue swelling and
distortion of facial features.
•• A haematoma in the region of the eye should prompt one to think of a
fracture in the region of the orbit or the zygoma.
•• A blunting of the cheek bone prominence is a clear indicator of fractured
zygoma.
•• Nasal bleed may be the only indicator of a fracture of the maxilla, while
fracture of the mandible may be indicated by an inability to clench the teeth
or open the jaw.
IMAGING
•• Most patients who present to the emergency department with facial injury
will be required to undergo a “Facial trauma series”, which consists of plain
X-rays (PA view, lateral view, caldwell view and Water’s view).
•• In all patients with severe facial trauma a CT scan must be performed.
A 3D reconstruction should be done to show the fracture line and their
displacements in great detail, which is helpful in planning the surgery.
•• A panoramic view of the mandible supplements the information got on a CT
and, therefore, must be requested. With newer CT software it is possible
to image great details of the mandibular and dental anatomy (DentaScan).
SOFT TISSUE INJURIES

•• The face is blessed with a very good vascularity of the soft tissues and
bones ensuring very good results if proper attention to certain details is
paid during the primary care.
•• The maxim—“first chance is the best chance”—holds especially true for
the management of facial soft tissue injuries.
•• There are certain fundamental principles of facial wound management
which, if adhered to, give highly gratifying results.
•• Thumb rules in facial soft tissue injuries are:
–– Debride conservatively
–– Clean thoroughly
–– Reposition nicely
–– Wait patiently.
•• A word of caution—seemingly harmless facial injuries—can have concomi-
tant bony injury or injury to the facial nerve or the duct of the parotid gland.
Be sure to rule them out before embarking on any definitive treatment.
FRACTURE OF THE MANDIBLE

•• The mandible is one of the most common bones to be fractured in the face,
due to its prominence in the face. The mandible is injured most commonly
due to direct trauma to the face.
•• Symptoms of fracture mandible are: Malocclusion, pain, swelling, bleeding
from the oral cavity,trismus.
•• Signs of fracture mandible are: Crepitus, intraoral haematoma, gingival
tear, anaesthesia/hypoaesthesia lower lip, deviation of jaw on opening the
mouth, loose teeth, difficulty in opening or closing of the jaws, open bite,
abnormal mobility.
•• Mandibular fractures typically result in some degree of malocclusion;
therefore, a complaint by the patient of a change in their occlusal status
after injury is a reliable indicator of fracture mandible.
Chapter 39 • Maxillofacial Injuries
305
•• Mandibular fractures are almost always compound into the mouth as the
mucoperiosteum on the inner aspect of the mandible is closely adherent
and gets torn during any fracture leading to the compounding of the fracture
into the oral cavity.
•• The goal of treatment of mandibular fractures is to not only restore the
aesthetics of the face but also to restore the occlusion.
•• Mandibular fracture can occur in the subcondylar area (commonest),
body, angle, parasymphysis area, symphyseal area, alveolar process and
coronoid process.
•• Again, depending on the direction of the fracture line, a mandibular fracture
can be either favourable or unfavourable.
•• An unfavourable fracture is one in which the action of muscles acting on
the mandible is such that it pulls the fracture fragments apart.
•• A favourable fracture, on the other hand, is pulled together by the action of
the local muscles. The fracture can be favourable or unfavourable either
in the vertical plane or in the horizontal plane.
Investigations
•• Plain X-rays mandible AP and oblique views
•• Ortho pantomogram
•• CT scan.
Management
•• Fracture mandible can be managed in a number of ways, both operative
and non-operative.
•• Non-operative treatment is preferred in patients at extremes of age
(edentulous arch and high-operative risk) or in co-operative patients with
stable fracture or in polytrauma patients with other life-threatening injuries,
which must be attended to first.
•• Non-operative treatments include:
–– Soft diet only
–– Interdental fixation with dental wires
–– Maxillomandibular fixation with arch bars
–– Splints for fracture stabilisation (Cap splint, Gunning splint).
•• Operative treatment includes open reduction of the fracture fragment and
either internal or external fixation. Internal fixation can be achieved by
means of dental wires or mini-plates and screws.
•• External fixation can be achieved by means of rigid pin and frame devices,
which come in various shapes and sizes.
MAXILLARY FRACTURES
•• In a patient with multiple injuries the maxilla is almost invariably involved
along with the mandible.
•• The maxilla occupies an important position in the mid-face and articulates
with the nasal bones anteriorly, the frontal bone superiorly, the pterygoid
plates posteriorly, the temporal bone laterally, and also forms part of the
floor of the orbit superiorly.
•• It houses the all important antrum of the maxillary sinus, which is the biggest
of all the sinuses and the most prone to trauma and infection.
•• Maxillary fracture, like the mandibular fractures, almost always leads to
malocclusion, the maxilla being part of the upper, tooth bearing arch.
306
•• Entrapment of the infraorbital nerve in the fracture fragments may lead

to loss of sensation or hypoaesthesia in the upper lip and lateral nose
(compare Mental N. entrapment in mandible fracture).
•• Maxillary fractures have classically been classified along the Le Fort lines
(Le Fort I, II and III).
•• Le Fort lines are the lines of inherent weakness in the maxilla along which
fracture lines run.
•• The Le Fort fractures are those which tend to separate the maxilla from the
skull base and they are classified according to their position.
•• The Le Fort fractures must extend up to the pterygoid plates for them to
be complete and cause a complete dysjunction.
•• The Le Fort I fracture classically passes through the maxilla transversely
between the tooth apices and the infraorbital rim.
•• The Le Fort II (or the Pyramidal fracture) extends through the nose and
the infraorbital rim in a pyramidal fashion, separating a triangular segment
of the face from the skull base.
•• The Le Fort III fracture is also called craniofacial dysjunction and in this
type the fracture line passes through the nasal bones, zygomaticofrontal
suture and zygomatic arch and results in the face being separated from
the skull (hence the name!).
•• Maxillary injuries can be treated in a variety of ways including interdental
wiring, arch bar fixation with maxillary mandibular fixation, transpalatal
wiring and mini-plate and screw fixation.
•• The surgical approach to the fractures can also be many.
•• The Le Fort I injury is best approached through an intraoral, upper buccal
sulcus incision.
•• The Le Fort II fracture can be approached through a lower eyelid incision,
a transconjunctival incision, and upper buccal sulcus incision or a local
laceration.
•• The Le Fort III fracture can be approached via a combination of incisions—
upper buccal sulcus and coronal.
•• While fixing the maxillary fractures it is important to keep in mind to fix the
nasofrontal, zygomaticomaxillary and zygomaticofrontal buttresses.
FRACTURES OF THE ZYGOMA

•• The zygoma, also known as the cheek bone, is a pyramidal structure and
articulates with the maxilla, the frontal bone and the temporal bone and
also forms part of the floor of the orbit.
•• Swelling in the malar area and hypoaesthesia in the distribution of the
infraorbital nerve are prime indicators of fracture of the zygoma, although
the swelling in the malar area often masks the zygomatic displacement
except to the careful eye.
•• Injuries to the zygoma are often associated with injuries to the orbital area
as the zygoma itself forms part of the lateral part of the orbital floor. These
injuries are often together known as orbitozygomatic injuries.
•• These may be associated with ophthalmologic symptoms like diplopia and
a downward tilt to the lateral canthus and merit a careful ophthalmologic
examination.
•• Solitary, undisplaced fractures of the zygoma may be treated conservatively
with rest and soft diet, but fracture of two of the three major articulations
of the zygoma (to the maxilla, frontal bone and temporal bone) along with
Chapter 39 • Maxillofacial Injuries
307
complicating factors, like displacement or rotation, are indications for

operative treatment.
•• The signs and symptoms indicating an injury to the zygoma have been
tabulated as under:
–– Swelling and ecchymosis in the malar area
–– Conjunctival haematoma
–– Pain/anaesthesia over cheek/upper lip
–– Nasal bleed
–– Difficulty in opening of the mouth/trismus
–– Diplopia
–– Downward tilt to the lateral canthal area.
•• Fractures of the zygoma have been classified by Knight and North according
to their displacement and the presence or absence of comminution.
•• As already alluded to zygomatic fractures (solitary, undisplaced) and
undisplaced arch fractures are treated conservatively.
•• Displaced zygomatic fractures, fractures with disruption of two or more
buttresses, rotated fractures, fractures of the arch impinging on the coronoid
and fractures with an orbital component leading to diplopia are indications
for operative treatment with closed or open reduction and fixation of the
fracture.
•• The zygomatic fracture lines can be approached through a variety of
approaches including the intraoral, lower eyelid and temporal approach
(Gillies). Fixation of two out of three buttresses ensures prevention of re-
rotation of the injured zygoma.
NASAL FRACTURES
•• Nasal fractures occur as a result of direct violence to the nose (frontal or
lateral).
•• The diagnosis of a nasal fracture is usually straight-forward and is mainly
clinical.
•• History of trauma to the nose along with a deviated nose and/or oedema
and nasal bleed are indicators of nasal fracture.
•• X-rays are needed only for confirming the diagnosis and for documentation
purposes and usually consist of a plain X-ray lateral view of the face (soft-
tissue).
•• Nasal fractures are classified according to the extent of injury to the bony-
cartilaginous pyramid (Stranc classification).
•• Emergency treatment of nasal fractures is usually straight-forward and
consists of reduction of the fractured fragments and splintage (internal
and external).
NASO-ORBITO-ETHMOID/FRONTO-
ORBITO-ETHMOID FRACTURES
•• The naso-orbito-ethmoid region includes the medial part of the orbits, the
nasal bones and the nasofrontal area.
•• The typical findings in case of a naso-orbito-ethmoidal (NOE) fracture are
a depressed nasal area with loss of nasal support and telecanthus due to
fracture of the bone bearing the medial canthi.
•• A depressed middle third of the face (dish face or pan face) is a diagnostic
sign of a middle third fracture involving the nasoethmoidal area.
308
•• The orbits are almost always involved in any frontal trauma involving the
nasoethmoidal region and leading to a dish face.
•• The supraorbital margins, owing to their prominence, are especially prone
to frontal trauma. Besides fracture of the orbital margins, there can occur,
fractures of the orbital walls, most commonly the floor.
•• A frontal impact over the globe can also cause immense pressure to build up
within the bony orbit in a short span of time leading to fracture of the weak
areas of the orbit namely the medial wall (the lamina papyracea) or the floor.
•• A CT scan of the face is the best radiological tool for visualising the floor
of the orbit and the medial wall and also for calculating the loss of orbital
volume and for documentation of herniated fat for medical records.
•• The orbital floor can be approached via a number of routes, the most
common of them being the ‘Subciliary stair-step’ incision which has the
least incidence of post-operative ectropion and gives adequate exposure
of the bony orbit.
•• Another approach is the transconjunctival approach, which uses an incision
4−6 mm below the lid margin.
PAN-FACIAL FRACTURES
•• Pan-facial fractures are particularly tricky as most of the bones of the face
are involved in the trauma.
•• The face is conveniently divided into upper, middle and lower thirds.
•• Any injury encompassing two or more of these regions may be classified
as a pan-facial injury.
•• Typically, in a pan-facial injury, the major bones of the face are fractured
leaving one with no stable platform to reduce the bones onto. These are
usually the result of high speed frontal collisions or assault.
•• Such patients have to be closely evaluated for other life-threatening injuries
such as head injuries, major vessel ruptures, thoracic injuries, tracheal
fractures, abdominal trauma and spinal injuries.
•• Pan-facial fractures look particularly ghastly but are amenable to treatment
and give good results, if the general principles mentioned earlier are kept
in mind.
•• One must remember to proceed either from above, below or vice versa
reducing the unstable fragments over a stable bone which can serve as
the reference or scaffolding to build the facial skeleton on.
•• Comminuted fractures may require wide exposure and interfragmentary
wiring or external fixation in major trauma.
40
CHAPTER Traumatic Cerebrospinal
Fluid Fistulae
Ravi Ramamurthi  Amit Kapoor
CEREBROSPINAL FLUID RHINORRHOEA

•• Leakage of cerebrospinal fluid (CSF) through the nose following trauma
has been reported to occur in 1−2% of head injuries admitted to hospital.
•• In 70% cases, the leak occurs within 48 hours of the injury.
•• The leak will clinically be obvious in 98% within 3 months.
•• The leak ceases spontaneously in 70% during the first 7 days.
•• In most cases the leak will stop within 6 months.
•• In a small group, after the initial arrest, the rhinorrhoea may recur a few
weeks, months or even years after the original trauma.
•• In such cases, the dural defect gets temporarily sealed by blood clot,
brain, or a spicule of bone or by direct adherence of the sinus mucosa to
the arachnoid.
•• When such local factors resolve, or when there is an increase in intracranial
pressure (ICP) due to post-traumatic hydrocephalus, a free pathway is
opened up from the subarachnoid space to the exterior and a delayed
CSF leak occurs.
•• The interposition of a piece of dura and arachnoid and possibly a bit of brain
tissue trapped into the bony gap is the primary defect. If such interposition
of the meninges into the bony gap does not occur in the immediate post-
trauma period, the fistula heals spontaneously.
•• The pulsations of the brain enlarge the bony and dural defects leading to
a recurrence of the leak.
•• CSF fistulas may also be classified as low pressure or high pressure. This
distinction is relevant for management, as when the CSF pressure is high
as in patients with associated hydrocephalus, the ICP has to be reduced
by appropriate surgical intervention.
Pathophysiology
•• The CSF rhinorrhoea may be unilateral or bilateral.
•• When unilateral, it need not necessarily be on the same side as the fracture
and dural tear.
•• The severity of the leak is also not always proportional to the size of the
dural tear.
•• Usually the leak is through a dural tear, which is associated with a fracture
of the anterior cranial fossa involving a paranasal air sinus or the cribriform
plate of the ethmoid.
310
•• The next common sites for the fistula are fractures of the posterior wall of
the frontal sinus and those involving the sphenoid sinus (tuberculum sella
and anterior wall of the sella rather than the planum sphenoidale).
•• Rarely, fluid leaking through a fracture of the middle cranial fossa into the
eustachian tube may flow into the nose during forward bending of the head,
i.e. paradoxical CSF rhinorrhoea.
•• A minor injury causing profuse rhinorrhoea through a large fistulous tract
is due to the rupture of an associated encephalocoele projecting through
a congenital defect in the cribriform plate.
Diagnosis
•• A detailed history should be obtained in patients who do not have an
obvious profuse leak.
•• A salty taste in the back of the throat and salty fluid running down the back
of the throat should be asked for.
•• When the fluid is blood tinged, the fluid should be allowed to drip onto a
piece of cloth. A ring of blood with an outer ring of fluid suggests the pres-
ence of CSF (ring sign).
•• The fluid should be collected and sent for glucose and B2 transferrin
estimation. B2 transferrin is present in CSF and vitreous fluid. It is absent
in tears, nasal discharge, saliva and serum.
•• Glucose levels above 30 mg% are indicative of CSF though it may be lower
when there is meningitis. This test is more useful when it is negative as it
may rule out CSF rhinorrhoea.
•• Allergic rhinitis with sudden leak of clear fluid from the nostrils can be
differentiated by:
–– The use of sterile cotton pledgets in the nose and soaking them later
in water which is examined for glucose
–– Application of decongestant nasal drops and then attempting to pro-
voke the rhinorrhoea by changes in the position of the head
–– Failure of nasal fluid to stain or stiffen a handkerchief
–– The presence of eosinophils in the nasal discharge of allergic rhinitis.
•• Headache may be complained of and may be due to high or low ICP.
•• Low pressure occurs when there is a profuse leak of CSF.
•• High pressure headache is often relieved when there is fresh leak of CSF
brought about by the high pressure.
•• Meningitis may be the presenting symptom in about 20% of patients in
the acute stage.
•• The risk of meningitis in delayed cases is 57%.
•• The most common organism is Pneumococcus and the mortality is around
10%.
•• Anosmia would indicate a fistula near the cribriform plate, whereas a leak
through the sphenoid sinus may be suspected if there are signs of injury to
the neighbouring structures, viz. visual field disturbance, diabetes insipidus
or a carotid cavernous fistula.
•• Retention of the sense of smell, demonstration of an ipsilateral middle
fossa fracture and the absence of an anterior fossa fracture would throw
strong suspicion on the Eustachian tube being involved in the rhinorrhoea.
Chapter 40 • Traumatic Cerebrospinal Fluid Fistulae
311
Investigations
•• Searching for the site of the fistula during surgery can at times be time
consuming and frustrating and every effort must be made to locate the site
by clinical and radiological means preoperatively.
•• Plain X-rays of the skull, lateral, AP, basal and paranasal sinus views may
be helpful in diagnosis, but may not always demonstrate the defect.
•• Tomograms are useful in confirming suspected fracture sites.
•• Radiological demonstration of a fracture involving a paranasal air sinus is
strong supporting evidence that the nasal discharge is CSF.
•• Occasionally, plain X-rays of the skull may show pneumocephalus, the air
having gained access into the cranium through a fistula.
•• Plain lateral films of the skull in the sitting position may show air in the
chiasmatic cistern and a fluid level in the sphenoid sinus.
Computerised Tomography Scan
•• Fine 1−1.5 mm cuts in the coronal and axial planes should be done from
the anterior cranial fossa base up to the sella and a fracture can be made
out in about 50%.
•• On intravenous contrast administration there may be enhancement of the
adjacent brain. Hydrocephalus can also be made out.
•• When the fracture site is not obvious on the plain CT scan, cisternography
using water soluble non-ionic contrast, like iohexol or metrizamide, has
to be done.
•• When there is an active leak the site of leak can be made out 76–100%
of the time.
•• In inactive leaks the site of leak can be made out in 60%.
•• CT cisternography cannot differentiate between small ethmoid bones and
leaking contrast as they both appear white. Bone can be separated from
the contrast medium by using dual energy CT scanning.
Radionuclide Cisternography
•• Isotope studies are useful especially when the leak is minimal or intermittent.
•• The isotopes in common use are technetium-99 and DTPA.
•• Cotton pledgets are placed in the appropriate areas of suspected leak like
the roof of the anterior and posterior nares, sphenoethmoidal recess, the
posterior floor of the nose and the middle meatus.
•• The isotope is then injected by a lumbar puncture and counts are taken at
various time intervals from the different cotton pledgets.
•• In active rhinorrhoea, the site of leak can be located in 70% and in only
28% in inactive leaks.
•• The usefulness of magnetic resonance imaging in finding the site of leak
better than the other methods has been doubted.
•• MR cisternography was done using T2-weighted sequences, a 3D PSIF
(time-inversed fast imaging with steady-state precession, FISP) and a 3D
constructive interference steady-state sequence.
•• The sensitivity in detecting the site of leak was 92% as compared to 72%
with CT cisternography.
312
Treatment
•• The usefulness of prophylactic antibiotics has been questioned. There
was found to be no difference in incidence or morbidity of meningitis when
antibiotics were not given. Therefore, the routine use of prophylactic
antibiotics in patients with CSF fistulae in closed head injuries is not
recommended.
•• The nose or ear may be covered with a light dressing, but the orifice should
not be plugged tightly.
•• A course of acetazolamide and oral glycerol for a week may be helpful.
•• A period of one or two weeks is allowed to give a chance for the fistula to
close on its own.
•• In the presence of associated fractures of the face and extensive facial soft
tissue, injury operative intervention cannot be delayed for too long. Repair
of the CSF fistula, if required in such cases, should be performed after any
surgical manipulations needed to correct mandibular or facial fractures.
Indications for Surgery
•• A persistent CSF fistula needs surgical closure because of the ever present
risk of meningitis and brain abscess.
•• The accepted indications for surgery are:
–– Profuse rhinorrhoea
–– Delayed onset or recurrence of rhinorrhoea
–– The presence of an intracranial aerocoele
–– Associated faciomaxillary injuries
–– Radiological demonstration of a spicule of bone projecting into the
brain
–– History of an attack of meningitis.
•• Operative Technique: The operative repair of CSF fistulae may be
performed through an intracranial or extracranial approach.
•• Intracranial Approach:
–– The defect may be approached intradurally, extradurally or both ways.
–– The most suitable plan is to look for the fistulous tract intradurally first.
–– The protrusion through or adherence of the brain to the dural margins
of the tract indicates the site of the fistula. After releasing this, the
fistula is approached extradurally.
–– A probe inserted into the fistula from inside the dura helps in identifica-
tion of the tract extradurally.
–– The site of the leak, along with a minimum margin of 1 cm of dura all
round, is fully exposed.
–– Fascia lata or pericranium may be used to close the dural defect.
–– It is advisable to place two flaps of fascia lata over the defect, one
extra-durally and the other intradurally. Fibrin glue can be used to
promote adhesion of the graft.
–– The use of cyanoacrylate adhesive for the dural defect and methyl
methacrylate for the bone defect has been advocated.
–– If the site is still unidentifiable it is recommended to cover the cribriform
area and packing the sphenoid sinus.
•• The disadvantages of the intracranial route include: (a) difficulty in reaching
and dealing with sphenoidal sinus fistulas and (b) the risk of anosmia
following the procedure.
Chapter 40 • Traumatic Cerebrospinal Fluid Fistulae
313
•• Extracranial Approach:
–– The endoscopic approach has become universally accepted and is the
method of choice.
–– The approaches use mucoperiosteal or mucosal flaps, fascia lata or
abdominal fat and fascia.
–– The advantages of the extracranial approach are: (a) it does not
generally result in anosmia; (b) it produces the best exposure of the
sphenoid, parasellar and posterior ethmoid regions, the posterior wall
of the frontal sinus, cribriform plate and fovea ethmoidalis and (c) it
produces less morbidity than the intracranial procedure.
–– The disadvantages of the extracranial approach are: (1) it does not
allow visualisation of the associated cerebral injury and (2) in the
presence of comminuted fractures of the skull base, the extracranial
approach does not allow sufficient debridement to delineate the exten-
sive dural tears which may be present.
–– A CSF diversionary procedure (lumboperitoneal shunt) is necessary
when there is raised ICP without hydrocephalus, as measured by
lumbar manometry or intracranial ICP monitoring.
–– A ventriculoperitoneal shunt should be done when there is hydro-
cephalus.
–– It is wise to do the diversionary procedure after the CSF leak site has
been identified and repaired. If the shunt is done first, the site of leak
may be difficult to locate.
CEREBROSPINAL FLUID OTORRHOEA

–– This is rarer than rhinorrhoea and occurs when there is a fracture of the
petrous temporal bone along with injury to the tympanic membrane.
–– The fracture can be longitudinal or transverse to the long axis.
–– The incidence in longitudinal fractures is 29% and in transverse frac-
tures 44%.
–– The dural tear in these cases is usually found on the anterior surface
of the petrous ridge in relation to the tegmen tympani.
–– The CSF leaks through the external auditory meatus only if there is an
injury or a perforation of the tympanum. Otherwise, the fluid reaches
the pharynx through the ear.
–– Such patients complain of deafness after the injury and examination
with an auroscope shows a fluid level behind the tympanic membrane.
–– The leak in CSF otorrhoea is usually more profuse than in rhinorrhoea,
but has a much greater tendency to cease spontaneously.
–– The tear tends to heal permanently and surgical repair is required
rarely.
–– The leak can surgically be repaired by a mastoidectomy. If necessary,
the mastoid cavity, middle ear cleft and the Eustachian tube may be
obliterated.
–– A limited craniotomy may also be done along with the mastoidectomy.
–– The dural defect after definition can be packed with fat and fascia.
–– A pedicled temporalis muscle flap can be rotated.
–– Sudden arrest of CSF otorrhoea may be an indication of natural
healing but may also be the first sign of the onset of meningitis.
314
TRAUMATIC PNEUMOCEPHALUS
•• Following a head injury, air may enter the cranial cavity through a tear in
the dura and a fracture of the skull.
•• This is most often preceded by a CSF leak which may be missed if heavily
bloodstained.
•• Occasionally, pneumocephalus may also occur in well-established CSF
rhinorrhoea.
•• Air may enter the cranial cavity immediately after the head injury or after a
few days, and may be found in the ventricles, in the subarachnoid space
or subdurally.
•• In the usual course of events, the air gets absorbed without producing
any symptoms.
•• However, if there is a ball valve action which allows the entry of air,
but prevents its exit, a condition of tension pneumocephalus may
develop.
•• Some patients present with no symptoms, the pneumocephalus being
diagnosed accidentally during routine imaging.
•• In other cases the patients may report with headache and irritability.
•• There may also be vomiting and convulsions. This clinical picture may
appear immediately after the head injury or some time later. Infection may
occur, leading to meningitis or brain abscess.
•• Treatment:
–– In most cases the air gets absorbed by itself.
–– If it persists or recurs or is accompanied by a CSF fistula, then a repair
of the fistulous tract is indicated after careful assessment of the patient
and after accurate localisation of the tract.
–– If there is a tension, pneumocephalus or a trapped subdural aerocoele
causing headache and vomiting, tapping and release of the air is
essential.
41
CHAPTER Missile Injuries of
the Brain
Harjinder S Bhatoe
INTRODUCTION
•• Missile injuries of the brain have traditionally been viewed with pessimism
due to their supposedly poor outcome.
•• While their incidence is rising all over the world, due to rise in ethnic armed
struggle and militancy and terrorist related violence, civilian injuries are also
showing a rise due to easy availability of firearms.
•• Missile ballistics is now understood better and CT has revolutionised the
evaluation and prognostication of these injuries.
APPLIED BALLISTICS
Missiles
•• Projectiles travelling at less than 2,000 ft/sec fall into the category of low
velocity missiles, while those travelling above this speed are high velocity
missiles.
•• There is a distinct difference in the pattern of injury and the outcome of low
velocity missile injuries (LVMIs) and of high velocity missile injuries (HVMIs).
•• Most handguns and revolvers use heavy bullets weighing about 0.5 oz and
have muzzle velocities ranging from 550 ft/sec to 900 ft/sec.
•• In contrast, most rifles and small arms (rifles, stenguns, machine-guns,
etc.) used in war, use light bullets, having muzzle velocities averaging
3,000 ft/sec.
•• High velocity missiles, as they reach the limit of their range become low
velocity (spent bullet) and may inflict less severe wounds, as compared to
that within their effective range.
•• Fragments of exploding devices: The variety of exploding devices reflects
the ingenuity of the minds that assemble them, often in innocuous looking
forms.
•• A domestic LPG cylinder placed on its top often makes an innocuous looking
but deadly combination for explosion.
Energy Transfer
•• Injury to the tissues by a missile is a function of energy release over time
and of the volume and location of tissue disruption.
•• The amount of kinetic energy (KE) contained in the missile is defined by the
formula E = –1/2 mv2, where m is the mass of the missile and v its velocity.
Since energy contained in the missile varies directly with the square of its
velocity, the latter is relatively more important in determining the energy
transfer by the missile than the mass.
316
Figs 1A to D: Passage of low and high velocity missiles through animal tissues
•• The amount of tissue damage caused by a missile may be correlated with

the amount of energy deposited within the tissues by the missile.
•• The energy transferred can be expressed by the equation: Et = Een – Eex,
where Et = missile energy transferred, Een = energy of entry at the time
of impact, and Eex = energy contained in the missile at the time of its exit
from the tissues.
•• The amount of energy transfer to the brain is the difference of the energies
of the missiles at entry into and exit from the skull. If the missile does not
exit from the skull, the energy transferred is the energy contained in the
missile at the moment of impact. Thus, lower the residual velocity, greater
the energy liberated.
•• The extent and degree of damage in wounds are proportional to the amount
of KE of the missile dissipated in the wound.
•• Transfer of energy is greatest in dense tissues with high water content.
Thus, wounds of the brain (and those of liver, kidney, muscle and bone)
are more destructive than wounds of less dense tissue, such as lung or fat.
PHYSICAL EFFECTS OF MISSILE WOUNDING

•• Missile wounding can be understood in terms of physical interactions
between the missile and the tissues through which it passes. The primary
destructive effects of a missile interacting with tissues are caused by two
mechanisms:
–– Crushing action of the missile: There is fracture of the skull, laceration
and fragmentation of brain tissue and injury to vascular structures.
–– Pressure waves and cavitation (Figs 1A to D): Besides the direct
crushing action, a missile moving in water or tissue medium generates
distinctive types of pressure waves within the medium it transits:
¾¾ Juxta-missile pressure
¾¾ Longitudinal shock wave
¾¾ Pressure waves from KE transfer (Cavitation).
PATHOPHYSIOLOGY
•• The pathophysiology of CMI remains a complicated and poorly understood
aspect of neurotrauma, although some deductions arrived at from head
injury management can be applied to it.
•• Absence of specific data and scant literature on experimental studies
(unlike that seen in closed head injuries) are major limiting factors in further
understanding of the pathophysiology of CMI.
Chapter 41 • Missile Injuries of the Brain
317
Effect on ICP and Cerebral Perfusion

•• Experimental studies have revealed an instantaneous rise in ICP
immediately after tissue penetration, due to shock waves lasting 15–25
microseconds; the magnitude of rise is determined by the amount of KE
of the missile and can reach up to 80 kg/cm2.
•• Such a rise in ICP may produce instant brainstem compression and internal
brain herniations, resulting in death or decerebration, while there may be
no demonstrable significant mass effect.
•• Such acutely raised ICP may be the cause of instant death in humans
following CMI.
•• Experimental studies have demonstrated a second rise in ICP to
60–100 mm Hg within two to five minutes of injury and a rapid rise in
mean arterial blood pressure (MABP)
•• MABP shows a subsequent fall and a low MABP with persistently raised
ICP, results in poor cerebral perfusion, decerebration and higher mortality.
•• Transcranial Doppler studies in patients with CMI have shown vasospasm
in 37% cases; these patients have poor survival, as compared to those
without vasospasm.
Mechanism of Brain Injury

•• Immediate rise of ICP due to a shock wave lasting 15–25 microseconds
may be transmitted to the brainstem and this factor along with internal brain
herniations may lead to instantaneous death, especially, if the missile is
a high-velocity one.
•• As the missile penetrates the brain, cerebral parenchyma in its path is
crushed and spread apart, creating a permanent cavity that is slightly larger
than the diameter of the missile.
•• Contusion and haemorrhage may occur in areas distant from the missile track.
•• Laceration of major vessels may produce large parenchymal haematomas,
extending considerable distances from the site of the track.
•• Patients who have no intracranial missile penetration may develop
neurological deficit as a result of blast wave.
•• They may suffer fracture of the skull as well.
•• White matter oedema has been observed in experimental animals.
•• The blood flow in the microvessels may increase progressively in the areas
of concussion, contusion and laceration, induce reperfusion injury following
ischaemia and hypoxia of the brain tissue resulting from a microcirculation
disorder caused by the wound.
EVALUATION AND INITIAL MANAGEMENT

•• Rapid neurological deterioration after missile injury to the brain can occur
due to primary and secondary factors.
•• Because the morbidity and mortality are significantly influenced by the
patient’s neurological status before reaching neurosurgical care, efforts
should be made to minimise the time taken for transportation to a well-
equipped neurosurgical centre.
•• Upon arrival in the emergency room, the patient is completely evaluated
after ensuring an adequate airway and haemodynamic stability.
•• All external bleeding should be controlled and a search for abdominal,
thoracic and extremity injury is made and their appropriate treatment is
planned.
318
•• The head is shaven completely and, extruded brain matter or CSF leak,
boggy scalp swelling, eye injury (indicating oculocerebral injury), bleeding
or CSF leak from nose or ears, subcutaneous emphysema over the face
and neck and pulsations in the carotids in the neck are carefully looked for.
•• The mouth and oropharynx are cleared by suction and examined for bone
fragments, splinters and brain matter.
•• Rapid examination of sensorium by Glasgow Coma Scale (GCS) is done.
•• Pupils and visual status and ocular movements are noted and facial paresis,
focal motor deficit, etc. are looked for.
•• An enlarging intracranial mass lesion should be suspected when there
is progressive loss of brainstem function in a pattern consistent with
herniation or if the brainstem examination is dramatically better than the
overall GCS score.
Imaging
Skull Radiograph
•• Skull radiographs are done routinely in all the patients.
•• The most common finding is the presence of intracranial radio-opaque
foreign bodies.
•• Their location and distribution can give an idea about the direction of the
missile track and the structures likely to have been injured.
•• Communited fractures, depressed fractures, stellate and linear fractures
can be observed.
•• Skull radiographs are superior to CT in delineating certain fractures, such
as horizontal linear fractures and fractures in the same plane as axial CT
slices that can be missed on CT.
•• Another important finding is the presence of pneumocephalus and rarely
an air ventriculogram, if the ventricle has been entered.
Computed Tomography
•• CT is the imaging procedure of choice for evaluation of these injuries. It
can diagnose as well as prognosticate the injuries.
•• Usually, a depressed comminuted fracture within driven fragments is seen
in LVMIs.
•• On the other hand, HVMIs may result in extensive skull fracturing remote
from the impact site.
•• The parenchymal laceration is seen as a conical track with the base of the
cone at the entrance site. Haemorrhage into the track outlines it as a high
attenuating track.
•• CT will also show the ricocheted missile tract, intracranial haemorrhage,
in driven radio-opaque material, pneumocephalus, cerebral oedema and
brain contusion.
•• Patients with multilobar injury, subarachnoid haemorrhage and cerebral
infarction carry a worse prognosis, as compared to those with localised
damage.
Carotid Angiography
•• Angiography is, however, valuable in evaluation of certain sequelae of CMI
like traumatic aneurysms, arteriovenous fistulae, etc.
Chapter 41 • Missile Injuries of the Brain
319
OPERATIVE MANAGEMENT
•• The aim of surgical management of missile injuries of the brain is to improve
the quality of survival by reducing the raised intracranial pressure and
prevention of infection in as many patients as possible.
•• The principles of surgery are:
–– The mass lesion consisting of intracranial haematoma and non-viable
brain tissue along the path of the missile must be evacuated.
–– The missile and bone fragments, wherever feasible, must be removed,
but without enhancing the pre-existing neurological deficit. The brain
is usually swollen and retraction can be hazardous. Therefore, one
should avoid digging into the brain to retrieve the elusive missile.
–– Dura and scalp must be closed over the brain in a watertight fashion.
–– Post-operative elevation of intracranial pressure should be minimised
and adjunctive therapy (vide infra) should be instituted aggressively.
–– Availability of adequate anaesthesia support during and after surgery,
good fibreoptic illumination, suction and bipolar cautery are mandatory
prerequisites for optimum management.
•• The choice of approach is between debridement via small craniotomies
and large bone flaps centred over the wound of entrance. The latter allows
greater control of haemorrhage and better decompression and lower
infection rate.
•• Craniectomy should be wide enough to allow access to normal dura from
all sides.
•• Recent military data indicate that an aggressive approach is not always
necessary and efforts should be made to preserve as much neural tissue
as possible.
•• After debridement, missile and bone fragments should be retrieved, only
if they are accessible without producing any further neurological damage.
•• Exit wounds, if present, are also debrided and the dura is closed with
pericranial graft, temporalis fascia or fascia lata.
•• Orbito-cranial injuries and fronto-orbito-maxillary injuries are usually
associated with compound fracture of the skull base, resulting in profuse
CSF rhinorrhoea and orbitorrhoea. These injuries have to be recognised
and repair of the dural defect (usually by bifrontal craniotomy) to stop the
CSF leak should be carried out at the earliest. Pericranial flaps, mashed
muscle and fascia lata are extremely useful in dealing with these CSF leaks.
PROBLEMS DUE TO RETAINED INTRACRANIAL

FRAGMENTS
•• It may not be possible to extricate all the metallic fragments lodged within the
brain, due to the unpredictable trajectory of the missile and accompanying
factors like brain swelling. Attempts to aggressively remove these missiles
may aggravate neurological injury due to retraction, haemorrhage, etc. The
problems to be kept in mind while dealing with retained fragments are:
–– Infection
–– Epilepsy
–– Migration.
320
ADJUNCTS TO OPERATIVE MANAGEMENT

Anticonvulsants
•• The exact role of prophylactic anticonvulsants in CMI is not yet settled,
although what is clear is that there is a higher incidence of post-traumatic
epilepsy after CMI, as compared to that seen after closed head injury.
•• Thus, it would be reasonable to believe that all penetrating brain injuries
must have anticonvulsant prophylaxis, since the true incidence of epilepsy
in such injuries may be as high as 35%.
Management of Raised Intracranial Pressure

•• Head elevation by 30 degrees in euvolaemic patients can significantly
reduce ICP without altering CPP.
•• Judicious debridement of injured cerebral tissue and evacuation of
intraparenchymal and extra-axial haematomas can minimise ICP elevations.
•• Medical management of raised ICP consists of proper positioning, ensuring
adequate oxygenation and administration of osmotic and loop diuretics.
•• Hyperventilation can be valuable in selected patients.
•• ICP monitoring is a valuable adjunct in the post-operative management.
Antibiotics
•• Antibiotics that cross into the CSF should be administered in antimeningitic
doses for 4–6 weeks.
•• Previously, a combination of chloramphenicol and penicillin was widely
used; at present, one of the third generation cephalosporins (cefotaxime,
ceftazidime, ceftriaxome) along with an aminoglycoside (netilmicin,
amikacin) are favoured.
•• Metronidazole may be added, especially in the presence of extensive soft
tissue injury.
CONCLUSION
•• Initial GCS is the single most important prognostic factor in predicting the
outcome in missile injuries of the brain.
•• Rapid evacuation of these patients to a neurosurgical centre, aggressive
resuscitation in both the field and during transit and prompt correction of
physiologic abnormalities are of paramount importance to clinical outcome.
•• CT is the cornerstone in the diagnostic evaluation of these patients.
•• The surgical principles of aggressive treatment of mass lesions, limited
brain debridement, watertight dural closure and tension free scalp closure
should be applied to all situations.
•• Post-operative management of raised ICP, administration of antibiotics
and anticonvulsants are required for optimising the outcome of victims of
missile brain injuries.
42
CHAPTER
Endocrine Abnormalities
Following Traumatic
Brain Injuries
Deepak Kumar Gupta  Ashok Kumar Mahapatra
INTRODUCTION
•• TBI poses a significant risk to hypothalamic and pituitary functions.
•• Structural abnormalities in the hypothalamus and the pituitary are commonly,
anterior lobe necrosis, posterior lobe haemorrhage or stalk laceration.
•• Pituitary function is at particular risk because of the vulnerable physiologic
location of the gland within the sella turcica as well as its delicate
infundibular hypothalamic structure and its fragile vascular supply.
•• Growth hormone deficiency (GHD) is most often seen in patients with TBI
because the growth hormone-secreting somatotrope cells are located in
the wings of the pituitary gland, and the vascular supply and oxygen they
receive comes from the hypothalamo-pituitary portal vessels.
Screening
•• The first step in diagnosing hypopituitarism is recording of a detailed patient
and family history.
•• A patient history can also reveal possible risk factors for hypopituitarism
[age, sex, acute diabetes insipidus (DI)].
•• Additional risk factors may include abnormal pupillary reactivity, presence
of hypotension or hypoxia within 24 hours after injury, presence of major
pathological findings and/or diffuse brain swelling on the first two CT scans
obtained.
•• Although, the incidence of TBI-induced hypopituitarism is likely to be under-
diagnosed, not all patients will have deficits and not all of those with deficits
will benefit from therapy.
•• In general, patients in a permanent vegetative state should be evaluated
for DI, inappropriate ADH syndrome, hypoadrenalism and thyroid deficits
if indicated, but excluded from further endocrinological testing.
CANDIDATES FOR IMMEDIATE HORMONAL

REPLACEMENT
•• There is considerable controversy within the medical community over the
potential ramifications of HRT.
•• Class I studies are yet to be conducted on hormone replacement in the
treatment of patients with TBI-induced hypopituitarism.
•• Physicians who manage patients with TBI should carefully examine the
natural history of each individual patient’s endocrinological abnormalities,
and try to determine if the disorder is permanent or transient.
322
•• HRT should be instituted for patients with isolated hypopituitarism in the cases
of: Diabetes insipidus (DI), secondary adrenal insufficiency and secondary
thyroid insufficiency (just after adrenal replacement has been started).
•• All patients with proved TBI-induced hypopituitarism who are already
receiving HRT should undergo periodic follow-up testing by an
endocrinologist.
PATHOGENESIS OF ENDOCRINAL
ABNORMALITIES
•• The endocrinal problems following TBI could result from either due to
damage to the pituitary or hypothalamus.
•• The pituitary is highly vulnerable due to its location in the sella turcica, its
vulnerable blood supply and delicate infundibular hypothalamic structures.
•• It is generally believed that pituitary dysfunction following head injury is
by and large due to diffuse brain swelling, hypotension or hypoxic insult.
•• Necrosis is another important finding. The common site of necrosis is the
anterior lobe followed by the pituitary stalk (Table 1).
•• Necrosis patterns always correspond to the blood supply of the long
hypophyseal portal veins. Long portal veins pass through the diaphragma
sella, where they are vulnerable to mechanical compression from swollen
brain and a swollen pituitary gland.
•• Hypothalamic injury can also lead to hypopituitarism following severe
head injury.
•• Severe catabolic response with marked tissue wasting seen in head injury
patients is attributed to higher ACTH levels.
•• A paradoxical growth hormone response is seen in traumatised patients
(GH increases post glucose administration in severe head injury with
normal GH response in less severely injured patients).
•• Basal prolactin increases following head injury and suggests hypothalamic
damage.
CLINICAL SIGNS AND SYMPTOMS OF

HYPOPITUITARISM
•• Hypopituitarism is associated with a number of non-specific signs and
symptoms.
•• Fatigue is a major symptom and it is also a major symptom of TBI.
Table 1: Pathology in pituitary gland following head injury

Primary Haemorrhage Capsular 50–55%
Posterior lobe 30
Stalk 15
Necrosis Anterior pituitary 20
Posterior pituitary 0
Stalk 3
Secondary – – Hypoxia
– Oedema
Direct stalk injury Rupture of stalk
Transection of stalk
Stalk haemorrhage
Chapter 42 • Endocrine Abnormalities Following Traumatic Brain Injuries
323
•• Examples of other signs, symptoms and laboratory abnormalities indicating

hypothalamic-pituitary impairment include decreased lean body mass with
increased body fat and dyslipidaemia; reduced exercise tolerance and
muscle strength, DI, decreased TSH and FT4 levels and adrenal insufficiency,
amenorrhoea/infertility, erectile dysfunction and hyperprolactinaemia,
diminished cardiovascular function, impaired cognitive function, memory
loss, decreased concentration, mood disturbances, increased anxiety and
depression, irritability, insomnia and a greater sense of social isolation.
•• Clinical manifestations of TBI widely vary depending on the type, location
and severity of the injury.
Endocrinological Symptoms of
Hypopituitarism in Traumatic Brain Injury
•• In the acute stage, there is likely to be cortisol and ADH deficiency which can
manifest with persistent hypotension in the absence of any obvious cause
as patients cannot withstand stress in the presence of acute pituitary failure.
•• Failure of the posterior pituitary leads to fall of plasma ADH resulting in DI.
This can be diagnosed as patients pass a large volume of urine, which is
of low specific gravity, of high serum osmolality and low urinary osmolality.
•• The syndrome of inappropriate ADH (SIADH) in severe head injury is not
rare and can be diagnosed on the basis of biochemical parameters of
serum and urine.
INVESTIGATIONS
Routine Baseline Screening Tests (Table 2)
•• These investigations been carried out after the cardio-respiratory status
is stabilised and the life-threatening intracranial pathology has been
satisfactorily attended to.
•• Both anterior and posterior pituitary functions are tested, when there is a
high degree of suspicion of hypopituitarism.
•• Insulin tolerance test (ITT) is a simple test to find out corticotropin and
somatotroph secretion by measuring GH and cortisol level.
•• TRH stimulation test is important to assess the level of TSH and prolactin.
GnRH stimulation test is necessary to assess gonadotrop function.
•• Derangement of posterior pituitary function is no less important, as it may
lead to fluid and electrolyte imbalance, DI and SIADH. Hence, measurement
Table 2: Hormonal assessment in pituitary dysfunction diagnosis

Hormone Test Method Adult hormone levels
GH Insulin tolerance RIA 0–5 ng/mL
test
ACTH Insulin tolerance RIA 9–50 ng/mL
test
TSH TRH stimulation lmmunochemilumi- 0.4–4.2 mg/L
noscence assay
Free thyroxin RIA 5.5–11.5 µg/dL
FSH GnRH stimulation fluoro-immuno- FHS-20–250 pg/dL
test metric
Testosterone GnRH stimulation RIA 298–1043 ng/dL
test
324
of serum sodium, blood urea nitrogen, creatinine and osmolatity of plasma

and urine are important.
•• In addition, a regular check of urinary specific gravity and 24 hour urinary
sodium excretion is also carried out to differentiate DI from SIADH.
•• Basal hormonal evaluations are an essential means of detecting
hypopituitarism—including deficits of the adrenal, thyroid and gonadal
axis—without the need for provocative testing.
•• Regarding the diagnosis of GHD, there is a growing body of evidence
indicating that IGF-1 levels are the best markers of GH status as these
levels provide an integrated measure of GH secretion.
Provocative Testing
•• Patients should be referred to an endocrinologist for provocative testing if
results of their basal evaluations are abnormal or unclear.
•• For instance, a low IGF-1 level in the absence of malnutrition is highly
suggestive of severe GHD and calls for provocative testing.
•• The ITT is considered the gold standard for the diagnosis of GHD as well
as for ACTH deficiency.
•• In fact, hypoglycaemia represents a potent stimulus of both somatotrophic
and corticotrophic functions. However, the ITT is generally contraindicated in
patients who have central nervous system pathologies and hypoglycaemia-
induced side-effects are known to be potentially hazardous.
•• Among classical provocative tests, glucagon is considered a good alterna-
tive to ITT for investigation of either GH or ACTH and cortisol secretion.
•• Other available provocative tests used to further investigate the existence
of deficiencies of other anterior pituitary hormones include GnRH, TRH,
CRH, ACTH and metyrapone tests.
TREATMENT OF HYPOPITUITARISM
•• Endocrinal abnormality, be it in the acute phase of head injury or chronic
state, requires careful evaluation and replacement therapy.
•• In the acute stage, patients with DI, or SIADH or CSW, need treatment to
correct the deficiency.
•• CSW occurs due to unregulated release of natriuretic peptide. Patients
present with persistent hyponatraemia, hypernatriuresis with hyperosmolar
urine. In CSW, volume is depleted, hence volume is replaced with Na-
containing fluids and deranged haematocrit should be restored. Infusion
of saline, plasma and blood is necessary depending on the need.
Fludrocortisone acetate is the specific treatment for CSW, which helps in
sodium retention with fluid and corrects hyponatraemia.
•• The treatment may be long-term or short-term depending on the need of
an individual patient.
•• DDAVP nasal spray, arginine vasopressin and pitressin injections are
widely used.
•• GH deficient patients showed the beneficial role of GH replacement, which
included improved memory, attention, comprehension and vocabulary.
Improvement also included general well-being of mood and reduction in
depression and anxiety state. GH also helps in increasing muscle mass.
•• Testosterone replacement in men helps in normalisation of libido and
sexual function, helps in bone formation and increases the muscle mass.
•• Sex hormone deficiency in women is adequately treated with oestrogen
therapy, which improves their neurobehavioural and cognitive functions.
43
CHAPTER
Optic Nerve Injury
Ashok Kumar Mahapatra  Deepak Kumar Gupta
INTRODUCTION
•• Optic nerve injury is a rare condition; nevertheless, it is important as it can
cause significant visual loss and even blindness after blunt or penetrating injury.
•• While projectiles or other sharp objects injure the optic nerve directly, the most
common form of traumatic optic neuropathy (TON) is indirect, as a result of a
concussive force to the head, particularly the forehead.
•• This impact is thought to transmit a shock wave to the optic canal, damaging
the optic nerve.
•• The pathogenesis of optic nerve injuries till date is unclear and, while the
diagnosis of indirect TON can usually be made with the aid of a careful
history and examination, its optimal management is far less well defined.
ANATOMICAL CONSIDERATIONS
•• The visual pathway is divided into anterior and posterior parts.
•• The anterior visual pathway includes the optic nerves and chiasma.
•• The posterior visual pathway includes the rest of the visual system distal
to the chiasma.
•• The most important pathology in optic pathway injury is optic nerve
involvement.
•• The optic nerve extends from the globe to the chiasma and is approximately
5 cm long.
•• The optic nerve is divided into four parts:
1. Intraocular part
2. Intraorbital part, which is the longest measuring 25−30 mm in length
3. Intracanalicular part, 4−10 mm long and lies in the optic canal, where
the nerve is fixed to the periosteum, and
4. Intracranial part, 10–15 mm long.
PATHOLOGY
•• Visual problems following head injury can involve (a) anterior, or
(b) posterior visual pathways.
•• According to the site of injury, the lesion can be at various places.
Optic Nerve Injury

•• Optic nerve injury is reported to occur in 0.6−3% of all head injuries.
•• The most frequent site of the injury is the optic canal.
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Table 1: Hughes classification of optic nerve injury based on the site of injury
Anterior visual pathway injury Posterior visual pathway injury
Optic nerve injury Optic tract and geniculate lesion
• Anterior marginal tear
• Intraorbital optic nerve injury
• Intracanalicular injury
• Intracranial optic nerve injury Optic radiation and calcarine lesion
Chiasmal injury
•• Hughes, in 1962, described the various types of optic nerve injuries, depend-
ing on the site: (a) anterior marginal tear; (b) anterior optic nerve injury, and
(c) posterior optic nerve injury, which can be intraorbital, intracanalicular and
intracranial (Table 1).
Anterior Marginal Tear
•• It occurs at the optic nerve head in the retina.
•• Hughes reported an incidence of 13.3% of anterior marginal tear in his
patients with optic nerve injury.
•• This type is also associated with retinal and choroidal injury. Ophthalmoscopy
reveals haemorrhage and irregular disc margins.
Anterior Optic Nerve Injury
•• It involves the optic nerve behind the globe till the entry of the central
artery of the retina.
•• It was observed in 12.3% of cases reported by Hughes.
•• Retinal vessel spasm occurs in 30−35% of cases.
Posterior Optic Nerve Injury
•• It is relatively more frequently seen.
•• Traumatic orbital apex syndrome is a rare condition, occurring in the
muscle cone.
•• In this situation, the optic nerve is involved and there is associated proptosis
and III, IV and VI cranial nerve palsy.
•• Intracranial optic nerve injury occurs in the optic canal, where the nerve is
relatively fixed and the nerve sheath is firmly adherent to the periosteum.
This type of injury can occur following anterior cranial fossa fracture and
in patients with LeFort type III fractures.
PATHOPHYSIOLOGY OF OPTIC NERVE INJURY

•• The exact mechanism of optic nerve damage is not understood. However,
a large number of hypotheses have been put forward.
•• Walsh and Lindenberg, in 1963, classified optic nerve injury into primary
and secondary type depending on the nature of the pathology as observed
at autopsy (Table 2).
•• Concussion, oedema and ischaemia, leading to infarction of the nerve, as
a result of microvascular thrombosis.
•• Microvascular thrombosis is probably due to shearing strain on the nerve
as a result of acceleration and deceleration injury to the orbit.
•• The shearing and stretching forces can lead to rupture of optic nerve axons.
•• One of the most favoured mechanisms of optic nerve damage in head injury
is vascular insufficiency.
Chapter 43 • Optic Nerve Injury
327
Table 2: Walsh and Lindenberg classification of optic nerve injury based

on pathology
Primary pathology Secondary pathology
Concussion Oedema
Avulsion or tear: partial/complete Ischaemia
Contusion Microvascular thrombosis
Haemorrhage: intraneural/ extraneural Infarction of the nerve
•• The vascular injury is generally to the pial vessels, which could be immediate.
•• Delayed onset of visual involvement is due to oedema and ischaemia. In
patients with irreversible visual loss, the most important cause is probably
optic nerve infarction.
•• Fracture of the anterior cranial fossa, orbital roof, anterior clinoid process
and the optic canal can produce optic nerve injury. These fractures can
produce tear or compression of the nerve.
•• Pathological entities, such as degeneration of myelin, loss of axons
and chronic inflammation with phagocytosis, are found on microscopic
examination. Vascular involvement in the form of thrombosis, ischaemia
and infarction are also seen.
PATHOLOGICAL ANATOMY
•• The intraocular and intraorbital portions are typically damaged by direct
ocular injuries; however, occasionally, indirect trauma may result in either
an intrasheath or orbital haematoma.
•• These haematomas may compromise the blood supply to the optic nerve
via compression, and subsequently result in loss of vision.
•• The intracranial portion of the optic nerve is most frequently injured by
blunt trauma, and tears of the optic nerve itself or of the optic chiasm are
occasionally seen.
•• The dural covering of the optic nerve consists of two layers, the outer layer
arising at the orbital apex where the central nervous system dura splits to
form the periorbita and the optic nerve sheath, and the arachnoid attached
to the inner portion of the dural sheath.
•• This anatomical arrangement has clinical implications, because theoretically
during optic nerve decompression, it should be possible to incise only the
outer layer of the dural sheath and not enter the subarachnoid space, thus,
avoiding a potential cerebrospinal fluid leak.
CLINICAL FEATURES
•• A history of unilateral visual loss or, rarely, bilateral visual loss is the main
complaint.
•• The visual loss could be immediate or delayed.
•• In 90% of cases, patients do have a history of loss of consciousness.
•• Typically, the retina and optic disc initially appear normal, and the only
objective finding is the presence of a relative afferent pupillary defect.
•• Optic atrophy does not become apparent for 3−4 weeks.
•• In severe head injury, when a patient is unconscious, unilateral fixed dilated
pupil with retained consensual light reflex should raise the possibility of
unilateral optic nerve injury (Marcus Gunn pupil).
328
•• Examination usually reveals a normal cornea, lens and vitreous. In anterior

marginal tear, ophthalmoscopy may show retinal haemorrhage.
•• In the vast majority of cases, the fundus reveals no abnormality.
Fundus Finding
•• Fundus findings vary according to the site of the injury and the degree of
damage to the nerve.
•• In anterior marginal tear, fundus examination a few hours later, usually
shows oedema and haemorrhage.
•• In anterior optic nerve injury, when the site of damage is nearer to the
eyeball, fundus changes occur earlier than distal optic nerve injury.
Generally, optic atrophy sets in 3−6 weeks time.
Field Defects in Optic Nerve Injury

•• Mahapatra et al noted all possible field defects including nasal field.
•• However, the temporal field was most frequently involved, possibly resulting
from selective involvement of nasal fibres as the bone in the medial side
of the orbit is thin and is likely to fracture more frequently.
•• Central or paracentral scotoma and altitudinal field cut, inferior field cuts
are observed.
INVESTIGATIONS
•• X-rays of the skull, paranasal sinus view and optic canal view are important
radiological investigations.
•• Skull fractures are reported in 50−80% of patients.
•• High resolution CT is the investigation of choice. CT frequently shows a
fracture in the anterior cranial fossa and opacity in the ethmoid and sphenoid
sinuses. Rarely, CT scan may show optic sheath haematoma.
•• MRI scans show nerve swelling and contusions very well.
•• Orbital ultrasound is also useful; it can show thickening of the nerve, orbital
haematoma or a bony fragment.
Role of Visual Evoked Potentials

•• Visual evoked potentials (VEPs) provide a good indication of the integrity
of the visual pathway.
•• VEPs must be recorded in every case of suspected optic nerve injury to
assess the integrity of the anterior visual pathways.
•• VEPs are performed within 48 hours of initial evaluation, and the test is
repeated within 7−10 days to assess the electrophysiological improvement.
•• VEPs are categorised as normal, abnormal or absent depending upon their
wave formation and latencies.
•• Latencies longer than 2 SD of the control value are considered as abnormal.
Flash Visual Evoked Potential (FVEP)

•• Flash visual evoked recordings are done as per the technical guidelines
developed by the American Clinical Neurophysiology Society.
•• Visual flashes are delivered by means of light-emitting diode goggles placed
over the eyes. These goggles are covered by a clear plastic bandage.
329
•• The presence of FVEPs has been considered to reflect at least some

functional integrity of visual pathways.
•• Patients with TON fall in two distinct groups:
1. Those who eventually have good-to-excellent visual outcome and
2. Those who have very poor to no visual recovery.
TREATMENT OF OPTIC NERVE INJURY

•• Although traumatic optic neuropathy (TON) has been known for long, the
best treatment methods remain controversial.
•• Spontaneous visual improvement has been noted with a frequency of
20−38%.
Medical Management
•• The use of megadose intravenous corticosteroids is based on laboratory
studies demonstrating that timely use of corticosteroids can reduce the
oedema and tissue damage resulting from ischaemic and traumatic injuries.
•• Mahapatra et al observed overall improvements in 53−58% patients and
recommended steroid treatment (dexamethasone or methylprednisolone)
for 3−4 weeks duration.

•• Earlier, conservative management was the treatment option followed in
the majority with surgery being indicated in only a few subset of patients.
•• Every patient is offered 3 weeks corticosteroid treatment initially.
•• VEPs are monitored and patients are closely followed.
•• Patients progressively improving or not showing any improvement are not
subjected to surgery.
•• A group of patients who show minimal improvement and then remain static
are subjected to surgery.
•• This situation only suggests that the optic nerve is not completely damaged
and given a chance, further improvement may occur.
•• Clinically, it is reasonable to decide to treat or not to treat on an individual
patient basis (Table 3).
•• Optic Nerve Decompression: Traditional surgical approaches to OND
are neurosurgical or craniotomy approach, extranasal transethmoidal
approach, transorbital approach, transantral approach and intranasal
microscopic approach.
Table 3: Author’s criterion for optic nerve injury management

1. All the patients are put on corticosteroids.
2. VEP and clinical examination repeated every 2–3 days for the first 3 weeks.
3. Patients showing good visual recovery do not need surgery.
4. Patients in whom visual acuity remains PL negative, in spite of corticosteroid at the end of 3
weeks, do not need surgery.
5. Surgery is beneficial in those patients in whom visual improvement is marginal and then
remains static.
6. One emergency indication for surgery is delayed onset optic nerve injury, when vision rapidly
deteriorates in spite of corticosteroids.
330
•• Endoscopic Optic Nerve Decompression:

–– Recent advances in instrumentation and surgical techniques have
made an endoscopic approach to OND possible.
–– The endoscopic method offers many advantages over the traditional
approaches.
–– Decreased morbidity, preservation of olfaction, rapid recovery time,
more acceptable cosmetic results with no external scars, no risk of
injury to developing teeth in children and less operative stress in a
patient who may have multi-system trauma are some of the benefits
associated with endoscopic OND.
–– In the endoscopic technique of OND, the optic nerve is approached
from its medial aspect.
CHIASMAL INJURY
Pathological Types of Chiasmal Injuries
•• Primary:
1. Sagittal split or tear
2. Transverse split
3. Contusion
4. Laceration.
•• Secondary:
1. Oedema
2. Ischaemia
3. Necrosis (infarction).
Pathogenesis
•• The pathogenesis of chiasmal injury is not clear.
•• However, chiasmal injury can be primary or secondary as observed at
operation or at autopsy.
•• Primary involvement could be in the form of a tear, laceration or contusion.
•• In most of these patients, there is evidence of fracture in the anterior
cranial fossa.
•• In closed head injury, due to forehead impact, there is anterior-posterior
distortion of the skull, which leads to midline chiasmal tear.
•• The usual site of the chiasmal necrosis is at the site of decussation.
•• Contusion and chiasmal necrosis of the central part are seen most
commonly in primary chiasmal injuries.
•• The chiasm can also get involved secondary to oedema and ischaemia
leading to infarction.
Clinical Findings
•• Patients are usually adult vehicular accident victims.
•• History of unconsciousness is available in over 90% of cases, and the head
injury is usually severe in such cases.
•• Chiasmal injury is also described as traumatic bitemporal hemianopia,
indirect chiasmal injury or post-traumatic chiasmal syndrome.
•• Bleeding from the nose and CSF rhinorrhoea are commonly seen in these
patients.
•• Bitemporal hemianopia is the most common field defect seen.
331
•• Temporal field cut in one eye and no perception of light in the other eye
suggest optochiasmal injury.
•• Other unusual symptoms associated with chiasmal injury are anosmia,
pituitary insufficiency and diabetes insipidus.
•• Rarely, there may be other cranial nerve deficit, traumatic aneurysm of ICA
and carotid-cavernous fistula (CCF).
Diagnosis
•• Clinical diagnosis is difficult in unconscious patients.
•• However, when a patient is conscious, diagnosis is made by the history of
bilateral temporal defect, confirmed by field charting.
•• CT and MRI have made the diagnosis easy.
Treatment
•• There is no specific treatment for chiasmal injury.
•• As secondary involvement of the chiasma can occur due to oedema, it is
probably rational to prescribe corticosteroids.
•• The role of surgery in chiasmal injury remains unproven.
Visual Outcome in Chiasmal Injury

•• Almost all patients develop varying grades of optic atrophy over a period of time.
•• As the central field is retained, daily activities of the patient are mostly
unaffected.
•• Recovery occurs over several weeks and depth perception is regained.
Injury to Posterior Visual Pathway

•• Posterior visual pathway is the portion distal to the optic chiasma.
•• Direct injury to these structures could result due to penetrating injury, either
due to bullet or by splinters.
•• Injury to the posterior visual pathway occurs in patients with severe head
injury.
•• In closed head injury, the optic tract and optic radiation can get involved
in contusion or intracerebral haematoma involving the temporal or parietal
lobes.
•• Patients with compression of the posterior cerebral artery due to
transtentorial herniation may not survive.
•• Damage to the optic tract, optic radiation or geniculate body is difficult to
diagnose in unconscious patients.
•• Cortical blindness does occur with head injury, and the outcome is
unpredictable.
Section IV: Spinal Injuries
44
CHAPTER
Assessment and
Emergency Management
of Acute Spinal Injuries
Anil Pande  Pradeep Kumar Jain N
INTRODUCTION
•• Most studies have shown road traffic accidents as the leading cause of
spinal trauma followed by falls, diving into shallow water and sports injuries.
•• In an agricultural country like India, injuries due to fall from trees, unpro-
tected terraces and fall into uncovered wells and specific injuries caused
by fall of a coconut on the head are common.
•• Males are more prone to spinal cord injury.
•• In the elderly, the incidence of fractures of C1 and C2 is more frequent
due to the relatively high occurrence of odontoid fractures, whereas the
incidence of injuries to the subaxial spine is less.
INITIAL TRAUMA EVALUATION

Suspicion of Injury to the Spine
•• It is mandatory to assume spinal injury in all patients who have significant
trauma, with loss of consciousness, altered mental status, evidence
of intoxication, spine pain, tenderness or deformity, neurological signs
and symptoms of radiculopathy/myelopathy or instability and suspected
extremity fractures.
•• Spinal cord injury occurs due to primary and secondary events and
surprisingly 3−25% of spinal cord damage occurs after the initial trauma,
due to faulty and delayed transportation and inadequate initial management
(the golden hour). In addition, the primary injury sets off a cascade of cellular
molecular events that cause further cell injury and death.
•• Secondary spinal cord injury can also occur due to factors like hypoxia,
hypothermia, hyperthermia, hypotension and cardiovascular and respiratory
instability.
•• Clearing the spine is a very important neurosurgical responsibility and must
follow stringent criteria.
•• Patients with spinal injuries may die due to shock and aspiration.
•• The advanced trauma life support (ATLS) protocol specifies; first take
care of the airway, followed by assessment of breathing effort, followed by
circulation and haemorrhage control (“ABC”s), and thereafter, an urgent
transfer to a regional spine injury centre, if available.
•• The patients are seen and evaluated as they are found (as they lie) and
the mechanism of injury can be understood from a well taken history and
studying the scene of trauma.
Chapter 44 • Assessment and Emergency Management
333
PREADMISSION SPINE IMMOBILISATION

•• All patients suspected to have spinal injury should be managed with
spinal column immobilisation till an injury has been definitely ruled out and
appropriate treatment has been initiated.
•• Spine immobilisation can reduce the possibility of secondary neurological
damage and pain in patients with an unstable spine.
•• Spine immobilisation consists of a cervical collar, supports on both sides of
the head and long and short backboards with associated straps to attach
and immobilise the body.
•• Any associated limb fracture is also strapped and immobilised.
TRANSPORT OF SPINAL INJURED PATIENT

•• The transport vehicle should be equipped with respiratory and vascular
support measures, and the most rapid mode of transport is chosen.
•• Rural areas account for 70% of serious accidents and the mortality rates
are 4−5 times higher.
•• The distance to the spinal injury centre and extent of the patient’s injuries
are the best determinants of the mode of transportation.
•• An ideal situation demands an on-board anaesthetist who can provide
respiratory, cardiac and haemodynamic monitoring, resuscitation and
intubation if necessary, thereby reducing morbidity and mortality. It
is unfortunate that such facilities are infrequently available in except
metropolitan cities.
EVALUATION AND TRIAGE

•• Once the patient reaches the centre, the initial evaluation and triage of
the patient is done by the anaesthetist, neurosurgeon, general or trauma
surgeon, orthopaedic surgeon, and if necessary, a vascular surgeon.
•• An urgent initial general evaluation is done to decide on what is to be
done first.
CLINICAL EVALUATION
•• Evaluation of suspected cervical spine injury includes taking a careful and
detailed history with attention to mechanism of injury and whether the
patient had any neurological symptoms immediately after the event and/
or loss of consciousness, seizures and ENT bleed, which should alert the
neurosurgeon about an associated head injury.
•• The clinical examination and radiographic evaluation follows and is used
to ascertain the presence of local tenderness deformity instability, identify
neurological deficits, to guide management and predict the outcome.
•• During the course of initial assessment, patients are kept in the supine
position with rigid collar immobilisation of the neck, while standard ATLS
protocols are followed.
•• Clinical examination of spinal injury patients is very important and should
be very thorough, but has been found to have a sensitivity of only 77% in
blunt trauma patients.
•• For a complete assessment, the patient must be awake, alert, non-
intoxicated and without any serious systemic injuries.
•• The attending neurosurgeon must get a very careful history about the
injury mechanism and its injury severity score (ISS) is calculated (Tables
1A and B).
Section IV • Spinal Injuries
334
•• Clinical protocols for determining the need for radiography have been
developed, such as the NEXUS low risk criteria [(NLC), Table 2] and the
Canadian C-spine (CCS) rule, which are used to aid in emergency room
triage.
•• The clinical examination includes inspection and palpation of the spine,
and a complete neurological examination, and a general examination is
mandatory to rule out polytrauma.
•• Systemic examination to look for bruises, ecchymosis and abrasions will
point towards the possible region of spinal injury.
•• The motor, sensory and autonomic nervous system is rapidly assessed
using the American Spinal Injury Association (ASIA) score.
•• Cranial nerve (CN) involvement (VI, VII, IX, X, XI and XII) can occur in
association with upper cervical spine injuries or these may be due to
associated cranial trauma.
•• Priapism indicates a loss of sympathetic tone and is an indicator of poor
prognosis in spinal injuries.
Table 1A: Injury severity score

Region Injury description AIS Square only the top three
Head and neck
Face
Chest
Abdomen
Extremity
External
The injury severity score (ISS) is an anatomical scoring system that provides an overall score for patients with
multiple injuries. Each injury is assigned an abbreviated injury score [(AIS) Table 1B] and is allocated to one of six
body regions [head, face, chest, abdomen, extremities (including pelvis), external]. Only the highest AIS score in
each body region is used. The three most severely injured body regions have their score squared and added together
to produce the ISS score. The ISS score takes values from 0–75. If an injury is assigned an AIS of 6 (unsurvivable
injury), the ISS score is automatically assigned to 75
Table 1B: Abbreviated injury score (AIS)

AIS Score Injury
1. Mild
2. Moderate
3. Serious
4. Severe
5. Critical
6. Unsurvivable
Table 2: The NEXUS low-risk criteria

Cervical-spine radiography is indicated for patients with trauma unless they meet all of the fol-
lowing criteria:
1. No posterior midline cervical-spine tenderness
2. No evidence of intoxication
3. A normal level of alertness
4. No focal neurologic deficit
5. No painful distracting injuries
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•• Bulbocavernosus reflex is elicited by gently squeezing the glans penis

or tugging an indwelling Foley’s catheter. A normal response in the form
of contraction of the anal sphincter is noted. This reflex is lost if there is
injury to the conus medullaris or cauda equina. A negative response in
the absence of injury to the conus or cauda equina is suggestive of spinal
shock. This is the first reflex to return after spinal shock.
•• Beevor’s sign: The patient is asked to lift the head with the examiner
gently pressing on the forehead and, if the lower abdominal muscles are
weaker (below T-9), the umbilicus moves upward.
SPINAL INJURY GRADING SYSTEMS

Frankel Grading System
Frankel divided spinal injuries into five grades with decreasing neurological
deficits:
Grade A: Complete loss of motor and sensory function below the level of lesion.
Grade B: Complete motor paralysis with some sensory preservation (e.g.
sacral sparing)
Grade C: Retained motor function but useless
Grade D: Useful motor function
Grade E: Free from neurological symptoms.
ASIA Score
•• This is a point score and is used in the initial evaluation, and the assessment
includes motor and sensory neurological level, completeness of the injury
and zone of partial preservation.
•• The motor and sensory levels are the most caudal segment of the spinal
cord with normal function on both sides of the body.
•• The most caudal muscle must have grade III power.
•• The assessment of sacral sensations is very important because it may be
the only evidence of neurologic function distal to the injury.
•• It is important to distinguish between complete and incomplete injuries as
complete injury has a poor prognosis.
SPINAL SHOCK
•• It is the transient loss of all neurologic functions including segmental and
polysynaptic reflex activity and autonomic functions which cause flaccid
paralysis and areflexia; which can be of variable duration (1−2 weeks),
rarely months and sometimes can be permanent below the level of injury.
•• Complete and incomplete injuries can be discriminated only after the spinal
shock has recovered.
SPINAL CORD NEUROPRAXIA

•• Transient neurological deterioration that occurs during sport activity, and
found that the narrowing of the sagittal diameter of the cervical canal in
the adult spine was the main causative factor.
•• It was not associated with permanent neurological injury and no permanent
morbidity occurred in patients who returned to contact activities.
•• But some of the patients returning to contact activities, experienced a
recurrent episode.
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WHIPLASH INJURIES
•• An injury caused to the muscles, ligaments, discs and facet joints of the
neck by hyperextension, hyperflexion or rotational excessive forces, with
no fracture, fracture dislocation or disc herniation is called a whiplash injury.
•• Occipital neuralgia, headaches, cognitive impairment and lumbago are
commonly associated symptoms.
Incomplete Injury
•• It implies the presence of motor and sensory function more than three
segments below the injury.
•• The term “sacral sparing” is used to indicate preserved perianal sensation,
voluntary rectal sphincter contraction or voluntary toe flexion.
Complete Injury
•• Complete injury of the spinal cord is the loss of all motor, sensory and
autonomic function more than three segments below the level of injury.
SPINAL INJURY SYNDROMES

BELL’S CRUCIATE PARALYSIS SYNDROME
•• This syndrome is characterised by weakness and paralysis of the hands
and arms and relative sparing of the lower limbs.
•• It is seen usually in patients with cervicomedullary injuries; most common
are C2 fractures.
•• The upper limb fibres of the corticospinal tract decussate at a higher and
more central level, and thereby, the lower limb weakness is less.
ANTERIOR CORD SYNDROME

•• This is characterised as a syndrome involving the anterior and lateral
motor corticospinal tracts (motor level) and spinothalamic tracts (pain
and temperature) and the sparing of posterior column function (two point
discrimination, position sense and deep pressure sense).
•• In trauma, this can result due to injury of the anterior spinal artery or anterior
cord pressure by a prolapsed disc, dislocated bone or osteophytes.
POSTERIOR CORD SYNDROME

•• Injury to the posterior part of the spinal cord by a depressed laminar fracture
or contusion has minimal motor signs but is characterised by pain and
burning paraesthesias.
BROWN SEQUARD SYNDROME

•• This syndrome is not frequent and is seen in only 2−4% of traumatic
injuries and consists of unilateral involvement of the corticospinal tracts,
and posterior column tracts.
•• On the contralateral side of the lesion, the spinothalamic tract is involved
causing dissociated sensory loss, i.e. loss of pain and temperature
(lateral spinothalamic tract) and preserved light or crude touch (anterior
spinothalamic tract).
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CONUS MEDULLARIS SYNDROME

•• The conus medullaris is located between D11-L1, 2 and thoracolumbar
fractures can cause injury to the conus and this is characterised by
symmetrical weakness of the lower limbs, flaccid rectal tone and bladder
involvement.
CAUDA EQUINA SYNDROME

•• Cauda equina syndrome occurs as a result of a traumatic lesion below L2
that occurs at the level of the cauda equina roots presenting as asymmetric
pain, sensory loss and bowel and bladder disturbances.
CENTRAL CORD SYNDROME

•• Central cord syndrome, described by Schneider is the most common type
of incomplete spinal cord injury.
•• This usually occurs in a patient who has a primary or secondary canal
stenosis and when an extension injury occurs in the presence of large
osteophytes.
•• There is greater motor involvement of the upper limbs with relative sparing
of the lower limbs with bladder dysfunction and variable sensory disturbance
(“man in a barrel” syndrome, burning hands syndrome).
•• Spinal cord injury here is due to compression between the disc-osteophyte
complex and an in-buckling ligamentum flavum.
•• The long tract fibres of the upper limb are located in the central region of
the cord, hence, when an injury is more in the centre, the upper limbs are
more involved.
SPINAL INSTABILITY
•• Stability of the spine has been defined by White and Panjabi as “the
ability of the spine under physiologic loads to maintain an association
between vertebral segments in such a way that there is neither damage
nor subsequent irritation of the spinal cord or nerve roots and, in addition,
there is no development of incapacitating deformity or pain due to structural
changes”.
•• White and Panjabi have provided a scoring system that has been widely
adopted in predicting the presence of instability on cervical radiographs
that have segmental kyphosis greater than 11 degrees and anterolisthesis
greater than 3.5 mm of one vertebral body on another.
Degrees of Instability
1. First degree is mechanical.
2. Second degree is neurological.
3. Third degree instability is a combination of both.
RADIOLOGICAL ASSESSMENT
X-Rays
•• Plain X-rays are still the initial investigation and are used in the initial
evaluation of spine injuries and doing a cross table lateral, AP and open
mouth odontoid views are standard.
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•• Cross table lateral view:

–– The radiographic features which are looked for in a lateral view are
the presence of soft tissue swelling anterior to the vertebral bodies;
a loss of the normal smooth cervical lordosis with special attention to
the normal lordotic lines; disc space narrowing; segmental kyphosis;
antero- or retrolisthesis of one vertebral body relative to another and
spreading apart of the spinous processes, chip and tear drop fractures
and opening of the anterior disc space.
–– In elderly people and in patients with DISH and ankylosing spondylosis
careful evaluation of the fracture of the anterior osteophyte may help
to localise the injury.
•• Anteroposterior view: X-ray is studied for alignment, canal encroachment,
and pedicle morphology. Foreign bodies like nails and bullets, are also
visualised well on these X-rays.
•• Oblique view: X-rays demonstrate the uncinate process, pedicles, superior
and inferior facets and the laminae, and will show the neural foramina which
may be blocked by a unilateral locked facet. The articular facets and laminar
alignment can also be studied.
•• The swimmer’s view: Is also called the “twining view” and while taking
this view, the X-ray tube is positioned above the opposite shoulder and the
film is placed centred on the axilla with the arm raised above the head, the
tube angled 10–25 degrees towards the head and this is used to visualise
the cervicothoracic junction.
•• Oblique pillar view: The view of the dens is used to visualise the articular
masses and C2 fractures.
•• Pseudospread of the atlas is due to a normal but disproportionate growth
of the atlas on the axis and can be misdiagnosed as a Jefferson’s fracture.
More than 2 mm of total overlap of the C1 lateral masses on C2 on the AP
view is common in children aged 2−5 years.
•• Pseudosubluxation is seen in children in the presence of spasm and when
the X-ray is not taken in a true neutral position. This is usually seen at C2-3,
C4-5 and C5-6 in children older than 10 years.
•• Missed diagnosis of a spinal injury is usually attributed to:
–– Not taking an X-ray
–– Radiological misinterpretation
–– Incomplete sets of radiographs
–– Inadequate poorly taken radiographs (which do not show the level of
the injury), and finally, failure of the treating surgeon to see and prop-
erly interpret the X-rays.
Computerised Tomography
•• The CT remains the most valuable modality to assess cranial trauma,
visualising bone, blood and contusions very well.
•• Spine CT had 98% sensitivity and detected 45% additional injuries in
cervical spine X-ray positive patients.
•• The advantages of CT are its easy availability, rapidity of the latest
generation scans and the “One Stop” ability to rule out polytrauma, thus
making it a good screening tool.
•• The CT can miss ligamental and soft tissue injuries.
•• Thin cuts (1.5−3 mm) CT followed by 2D, 3D sagittal reconstruction is done
in regions where an injury is suspected. The body, posterior arch fractures,
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facet fractures, dislocations of facets, C1-C2 injuries and intracanal

fragments are best seen on a CT.
•• Spiral CT has been found to have a sensitivity of 99% and specificity of
100%, and the risk of missed spine injury is minimal.
•• The CT scan of the chest and abdomen should be done immediately if
blunt visceral trauma is suspected and chest X-ray or ultrasound abdomen
show signs of injury.
•• CT Myelogram is done where MRI is not available or is contraindicated in
patients with a pacemaker or metallic implants.
•• CT Angiogram may be required for studying vertebral artery injuries or to
rule out an anomalous vertebral artery course, especially when planning
transarticular screw fixations.

•• Magnetic resonance imaging (MRI) is currently the investigation of choice
for imaging the traumatic spine.
•• The MRI visualises ligamentous injuries, disc injuries and herniations,
compression of the neural elements, cord oedema, contusion, haematomas
(EDH, SDH, SAH) and haematomyelia, and provides information which
helps in neurological prognostication.
•• Signal intensity changes in the cord may be due to repetitive cord trauma
as seen in chronic segmental instability of cervical spondylotic myelopathy.
•• Ligamentous injury is seen as increased signal on T2-weighted images
due to oedema and disrupted ligaments demonstrate a discontinuity in the
normal low signal intensity of the ligament. This is very useful in studying
craniovertebral junction injuries where a disrupted ligament may be the
only sign of instability. Vertebral artery injuries can be visualised on the
MRI and MR angiography will give more details.
Dynamic Imaging
•• Dynamic X-rays, dynamic fluoroscopy, dynamic CT and MRI flexion and
extension are useful to assess instability.
•• These should be done very cautiously and in patients who are conscious
and oriented. They are avoided if instability is apparent or is clinically
obvious.
SPINAL SCREENING
•• A new tool total, imaging modality (TIM) is very useful in picking up a second
non-contiguous injury.
•• If this is not available, CT screening or X-ray screening of the whole spine is
mandatory in high-risk cases, e.g. fall from significant height or polytrauma.
CLASSIFICATION AND A BRIEF OVERVEIW OF

SPINAL TRAUMA
OCCIPITOCERVICAL DISLOCATION
•• Occipitocervical dislocation is uncommon and has high mortality.
•• These injuries are more common in children and may be asymptomatic or
with cranial nerve (CN) involvement and cord injury.
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•• Classification of these injuries is based upon the displacement of the

occiput:
–– Type I injuries are anterior subluxations and are the most common.
–– Type II injuries have vertical distraction greater than 2 mm of the
atlanto-occipital joint.
–– Type III injuries are posterior dislocations and are rarely reported.
•• Traction is contraindicated. Treatment options are immobilisation, but an
occiput to C2 fusion is usually required to provide long-term stability.
OCCIPITAL CONDYLE FRACTURES

•• Occipital condyle fractures have been reported to occur in 3−15% of
trauma patients.
•• These present with lower CN deficits and cord injury.
•• Anderson and Montesano have classified them into different types.
–– Type I fracture, which is a result of axial loading and lateral bending,
and there is no instability.
–– Type II is a skull base fracture that extends into the occipital condyle.
This is also a stable injury, because the alar ligaments and the tectorial
membrane are not injured.
–– Type III is an avulsion injury of the occipital condyle. If there is disrup-
tion of the alar ligaments and tectorial membrane, then potential for
instability exists.
•• Traction should be avoided as it is associated with a risk of neurological
deterioration.
•• Type I and II fractures are typically treated conservatively with immobilisation
in a rigid cervical collar for 6−8 weeks.
•• Type III may require occiput to C2 fusion.
ATLAS FRACTURES
•• Atlas fractures comprise 1−3% of all spinal injuries and 3−13% of cervical
spine fractures.
•• The common mechanism of injury is axial loading.
•• Atlas fractures are classified as:
–– Type-I fractures involving a single arch.
–– Type-II burst fracture of C1 (Jefferson’s fracture),
–– Type-III lateral mass fractures.
•• Fractures without injury of the transverse ligament or associated with bony
avulsion of the transverse ligament can be treated with halo brace immo-
bilisation and instability may be excluded with flexion-extension imaging.
•• Surgical fixation is recommended for injury of the transverse ligament with
instability.
•• Posterior arch fractures are the most common and are typically bilateral,
and these are stable.
•• Lateral mass fractures are usually unilateral and may be unstable if there
is associated ligamentous injury.
AXIS (C-2) FRACTURES

•• The fractures of C-2 are:
1. Odontoid fracture
2. Hangman’s fracture
3. Miscellaneous C-2 fractures.
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Odontoid Fractures
•• Odontoid fractures are common cervical spine fractures, representing up
to 10−20% of all cervical spine fractures and are often missed.
•• They have a bimodal incidence, with the first peak in young patients in
association with high-velocity trauma; and the second peak occurring in
elderly patients.
•• The Anderson and D’Alonzo classification is based upon the location of
the fracture line.
–– Type I fracture is the least common. The fracture line occurs at the tip
of the odontoid. These are usually stable injuries and have a high union
rate, and are treated conservatively.
–– Type II fractures are the most common. The fracture line is at the od-
ontoid base and these have a high incidence of nonunion.
–– Type II(a) are comminuted fractures involving the base of the dens
with associated free fracture fragments and these form 5% of type II
fracture. These are very unstable and managed by posterior fusion of
C1 and C2.
–– Type III fractures are fractures of the odontoid which extend into the
body of C2. These have a much higher union rate, with only 8% going
on to nonunion.
•• Factors associated with higher rates of nonunion are age greater than 65
years, smoking and displacement greater than 5 mm or angulation greater
than 10 degrees.
•• Anterior odontoid screw fixation or a posterior fusion may be necessary.
Traumatic Spondylolisthesis of the Axis

•• Traumatic spondylolisthesis of the axis called, “Hangman’s fracture” is a
bilateral pars interarticularis fracture of C-2 with a C2-3 subluxation.
•• The Effendi classification modified by Levine is in current use.
–– Type I is a bilateral pars fracture with a vertical fracture line, less than
3 mm of displacement and no angulation.
–– Type I(a) has an “atypical” fracture pattern and the fracture runs
through the posterior body of C2.
–– Type II injuries have a vertical fracture line with displacement of great-
er than 3 mm and significant angulation, and with associated fracture
of the anterior and superior endplate of C3.
–– Type II(a) fractures, representing 10% of “Hangman’s” fractures differ
from Type II fractures and have an undisplaced oblique fracture of the
pars, but with angulation which is greater than 15 degrees. They are
associated with severe disc and posterior longitudinal ligament (PLL)
injury caused by a flexion-distraction injury force.
–– Type III fracture is a type I fracture with bilateral C2-3 facet disloca-
tion.
Miscellaneous C-2 Fracture

•• These include fractures of C-2 lamina, spinous process facets and lateral
mass, and these may require external immobilisation or Halo immobilisation,
if unstable.
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ATLANTOAXIAL DISLOCATION
•• It occurs due to ligamental injury involving C-1, C-2 and rarely due to Os
odontoideum.
Atlantoaxial Rotatory Instability

•• It is an uncommon injury in the adult patient population and may be
associated with other upper cervical spine fractures.
•• Fielding and Hawkins classification:
–– Type I—Rotatory fixation without anterior displacement of the atlas.
–– Type II—Rotatory fixation with anterior displacement of the atlas of
3−5 mm.
–– Type III—Rotatory fixation with anterior displacement greater than
5 mm.
–– Type IV—Rotatory fixation with posterior displacement.
Atlanto-Dens Instability
•• Atlanto-dens instability is usually a result of injury of the transverse ligament
and occasionally the alar ligaments and tectorial membrane.
•• It is usually due to a flexion injury and is assessed by a measurement of
the anterior atlanto-dens interval.
•• In adults up to 3 mm is considered normal.
OS ODONTOIDEUM
•• It is an ossicle with smooth circumferential cortical margins representing
the odontoid process that is separate from the body of C2.
•• It is of two types:
1. Orthotopic type—an ossicle that moves with the anterior arch of C1
2. Dystopic type—an ossicle that is fused functionally with the basion
and can sublux anterior to the arch of the atlas.
•• Patients who develop instability and have neurological deficits are surgically
fused.
•• Transoral decompression may be considered in patients with os odontoi-
deum who have irreducible ventral cervicomedullary compression.
COMBINATION FRACTURES OF C1-C2

•• Treatment of atlas-axis combination fractures is based on the specific
characteristics of the axis fracture.
•• External immobilisation of most C1-C2 combination fractures is recom-
mended.
•• C1-Type II odontoid combination fractures with an atlanto-dens interval
of 5 mm or more and C1—Hangman’s combination fractures with
C2-C3 angulation of 11 degrees or more should be considered for surgical
stabilisation and fusion.
•• In some cases, the surgical technique must be modified as a result of loss
of integrity of the ring of the atlas.
SUBAXIAL CERVICAL SPINE TRAUMA (C3-T1)

•• Subaxial spine traumatic lesions are classified according to Allen and
Ferguson’s classification into six groups based on the initial force of injury
and the position of the spine at the time of injury.
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Flexion Injuries
•• These are caused by vehicular accidents, falls and diving into shallow water
and constitute 15% of all cervical trauma.
•• Flexion-compression injuries: Posterior element fractures occur in 50%
of compression flexion injuries.
•• Flexion-distraction injuries: These type of injuries are the most common
injury patterns in Allen and Ferguson’s classification and range from mild pos-
terior ligamentous sprains, subluxations and severe bilateral facet dislocations.
•• Vertical compression injuries: These type of injuries result in examples
of cervical burst fractures and are the most severe injury. The C6 and C7
bodies are exposed to greater axial compression and flexion loads and are
prone to develop burst fractures.
Extension Injuries
•• A stage I lesion is manifested by abnormal widening of the disc space due
to disruption of the ALL and disc.
•• In the stage II lesion, the posterior ligaments are also disrupted and the
upper vertebrae retropulse into the canal.
Thoracolumbar Injuries
•• These are common and are usually associated with severe abdominal
and vascular injuries.
•• The McAfee classification based on CT scans describe six types and uses
the Denis three column model of stability:
–– Wedge compression fractures are failures of the anterior column.
–– Burst fracture is a combined anterior and middle column injury.
Surgery is indicated when there is neurological deficit, an angular de-
formity of more than 20 degrees, 50% canal compromise and reduction
of anterior body height by 50%.
–– Seat belt fractures are severe injuries and involve flexion compression
of the anterior column associated with distraction and failure of the
middle and posterior columns.
–– Fracture dislocation is a three column injury.
Sacral Injuries
•• Sacral fractures are caused by fall from a height and seen in association
with pelvic fractures.
•• The neurologic deficits in pelvic fracture are due to associated sacral
fractures. These have been classified into three zones:
–– Zone I: Fracture involving the ala and sparing the central canal.
–– Zone II: Fracture involves the sacral foramina on one side causing L5,
S1 and S2 involvement with sciatic pain.
–– Zone III: These fractures involve the canal and cause sphincter dis-
turbance and saddle anaesthesia. Zone III fractures are divided into
vertical and transverse types; vertical associated with pelvic fractures,
while transverse are associated with severe deficits.
Intensive Care Management of Spinal Injuries

•• In the emergency department, the “Trauma Team” comprises of an
anaesthetist, intensivist, general surgeon, orthopaedic surgeon and the
neurosurgeon.
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•• Potentially life threatening cardiac and respiratory events occur within

the first 2 weeks after the injury and patients with severe injuries (ASIA
grades A, B) benefit the most when initially they are kept in the ICU for
7−14 days after injury.
•• Use of cardiac, haemodynamic and respiratory monitoring devices to detect
cardiovascular dysfunction and respiratory insufficiency in patients after
acute cervical spinal cord injury is routine.
Cardiovascular
•• This intensive care management is critical to prevent life threatening
cardiovascular instability and respiratory insufficiency and to maintain mean
arterial pressure at 85−90 mm Hg for the first 7 days after injury, which may
improve spinal cord perfusion and neurological function.
•• Induced hypertension after severe spinal cord injury was not found to
be beneficial in improving spinal cord blood flow at the injury site, while
potentially increasing the risk of haemorrhage and oedema.
•• Measures are taken to control bleeding. Intravenous (IV) access and fluid
resuscitation must be started with 0.9% saline or ringer lactate solution.
Fluids are replaced with colloids, crystalloids and, if required, with blood.
•• If a pressor is necessary, dopamine is the drug of choice and phenylephrine
is avoided. Atropine and vagolytics, like glycopyrolate, are used for
preventing bradycardia associated with hypotension.
RESPIRATION
•• Prophylactic intubation in conscious patients is not done.
•• When there is a need for respiratory support, “chin lift” instead of “jaw thrust”
is used, with great care taken not to extend the neck.
•• Endotracheal intubation should be performed with inline traction of the
spine. Awake blind nasal intubation is another option, but the safest option
is awake fibreoptic intubation.
•• Cricothyroidectomy and tracheostomy are the other options to secure
airway and should be done early when indicated.
•• Neurogenic pulmonary oedema is rare and can lead to adult respiratory
distress syndrome if not recognised and treated. It is managed
pharmacologically and by ventilation.
AUTONOMIC SYSTEM MANAGEMENT

•• Spinal shock is the complete loss of motor, sensory and autonomic function
of the spinal cord and may last for a few hours to weeks.
•• This can cause haemodynamic instability due to loss of vasomotor tone
attributable to injury of the spinal cord.
•• Spinal shock has to be differentiated from vascular shock which may coexist.
•• Ryle’s tube insertion is required to prevent vomiting and aspiration as
paralytic ileus is common.
•• Decreased sweating can cause hyperthermia in tropical countries like India.
•• Prevention of decubitus ulcers is very important and can be done by
frequent turning of the patients, proper skin care and nursing the patient
on air or water beds.
•• Bladder and bowel care are of great importance and most patients with
spinal injuries may have retention and should be catheterised with proper
precautions.
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NUTRITION IN SPINAL INJURY PATIENTS

•• The hypermetabolic, catabolic injury cascade occurs immediately after both
traumatic brain and SCI, leading to depletion of whole body energy store,
loss of lean muscle mass, reduced protein synthesis and finally loss of
gastrointestinal mucosal integrity and compromise of immune competence.
•• This prolonged nitrogen loss and severe malnourishment occurs within
2−3 weeks of injury; therefore, nutritional support of patients with SCI is
done expeditiously.
•• Energy expenditure is best determined by indirect calorimetry in these
patients, because equation estimates of energy expenditure and
subsequent caloric need tend to be inaccurate.
•• Due to poor nutrition, spinal injury patients have poor wound healing and
increased susceptibility to infections.
MEDICAL AND PHARMACOLOGIC

•• Injury to the spinal cord involves mechanical forces like compression,
penetration, laceration, shear and distraction.
•• The secondary mechanisms include reduced blood flow, loss of autoregula-
tion, loss of microcirculation, vasospasm, thrombosis and haemorrhage.
•• Other events are electrolyte shifts, permeability changes, loss of cellular
membranous integrity, oedema and loss of energy metabolism.
•• The pathological cascade also includes neurotransmitter accumulation,
arachidonic acid release, free radicals and prostaglandin production and
lipid peroxidation. All these lead to axonal disruption and cell death.
•• Pharmacotherapy has been very ineffective in the management of these
cascades, and research into compounds like tirilazad mesylate, naloxone,
methylprednisolone, GM-1, is still ongoing and results are awaited.
Methylprednisolone
•• Giving methylprednisolone after spinal injury is an option that can be
undertaken with the knowledge that side-effects are very common.
•• The benefits of methylprednisolone are only seen when the drug is given
within 8 hours of the injury, and when given later the outcomes are worse.
•• The initial bolus is given as 30 mg/kg/IV over 15 minutes and the
maintenance infusion is started 45 minutes after the bolus, and is at a rate
of 5.4 mg/kg/hour for 23 hours if therapy was started within 3 hours of injury
and 47 hours if begun 3−8 hours after injury.
TRACTION
•• Traction, which earlier was the only modality of treatment of spinal injuries
has a limited stand alone application in the modern era of spinal surgery.
•• It is absolutely contraindicated in the management of atlanto-occipital
dislocation, Type II(A) and III Hangman’s fractures, in children below
3 years, in patients with a distraction injury and in any patient who develops
severe local pain, radiculopathy, myelopathy or autonomic dysfunction.
•• It should not be used in patients with impaired sensorium.
•• In patients with a locked facet, it is a safe option to get an MRI and exclude
a sequestered disc which can cause neurological deterioration when
traction is applied.
•• Today, most neurosurgeons practicing spine surgery would put in a 3 pin
fixator and reduce a dislocation with controlled traction under fluoroscopic
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control and maintain reduction with different anterior or posterior instru-

mentation.
•• Most fracture dislocations can be easily reduced by careful positioning
of the neck in extension. Over-distraction may occur due to excessive
weight, nature of injury and poor muscle tone, and due to the use of muscle
relaxants during anaesthesia.
Applying Traction
•• The Gardner-Wells tongs are the ones in current use and many Indian
variations of the same are available.
•• The site of application is usually 1.5−3 cm above the pinna and below the
equator of the skull.
•• Placement of pins is avoided beyond 1 cm anterior to the meatal line as
risk of pin perforation in the thinner squamous temporal bone increases,
and temporalis muscle injury can cause pain.
Extension Traction
•• The pins are placed 3 cm above and 2−3 cm in front of the external auditory
meatus.
•• This is rarely used because retroluxations are very rare.
Neutral Traction
•• The pins are placed 3 cm above and in line with the external acoustic meatus.
Flexion Traction
•• The pins are placed 3 cm above the pinna and 3 cm behind the external
auditory meatus and above the mastoid process.
•• This is the position used for reduction of locked facets.
ORTHOTIC DEVICES IN SPINE TRAUMA

Halo
•• The 4 pin halo can also be used for immediate immobilisation for acute
subaxial spine injuries.
•• Traction can be applied using the halo and after the fixation, if necessary,
the halo can be continued for immobilisation.
•• The halo provides relative immobilisation of the upper cervical spine, but
the lower cervical spine is not immobilised well.
Minerva Jacket
•• This is still used occasionally, and new thermoplastic Minerva jackets limit
cervical “snaking” better than the halo.
Soft Cervical Collar

•• This is used only in the treatment of pain caused by muscle spasm and
provides very little immobilisation and should not be used in patients with
bony and disco-ligamental injuries.
347
Philadelphia Collar
•• It is used postoperatively to limit flexion and extension.
Yale Brace
•• It is characterised by extended support to the sternum and upper thoracic
spine, and is better at immobilisation than the Philadelphia collar.
SURGERY
•• Surgery is usually indicated in incomplete cord lesions, unstable injuries
and in patients with a radiculopathy or myelopathy due to pressure on the
spinal cord or roots.
•• Surgery in complete injuries may be necessary to optimise recovery,
prevent deformity and allow for early mobilisation.
•• Early surgery: Timing of surgery in trauma is controversial, and many
surgeons prefer earlier cord and root compression.
PAEDIATRIC SPINE INJURIES

•• These are infrequent and most paediatric spine injuries can be treated by
immobilising in Halo and rarely Minerva jackets.
•• Anatomical reduction of deformity, stabilisation of unstable injuries and
decompression of the spinal cord, and isolated ligamental injuries associated
with deformity are indications for surgical management.
Spinal Cord Injury without Radiographic Abnormality

•• Pang and Wilberger described spinal cord injury without radiographic
abnormality (SCIWORA) in 1982.
•• Patients are usually children and this is seen rarely in adults.
•• Patients present with signs of myelopathy as a result of trauma, and no
evidence of fracture or ligamental instability on plain X-rays and CT. This
can appear as late as 4 days after injury.
•• The spinal column in children is more flexible and elastic and in the absence
of bony or ligamental injury, the MR images can show a spectrum of injuries
including cord contusion, vascular injury, traumatic disc prolapse, traction
injuries, meningeal rupture and even cord transection.
•• SCIWORA is more common in patients with asymptomatic Chiari 1
malformation.
•• Patients with SCIWORA have a 20% rate of repeat injury within 10 weeks
of the original injury and so patients are recommended immobilisation for
3 weeks to 3 months.
•• Contact and non-contact sports are prohibited for 3 months before allowing
these children to go back to their normal routine.
•• Dynamic imaging is done to rule out occult asymptomatic instability.
Geriatric Spine Injuries

•• The elderly population is at a higher risk of spine injuries after even minor
falls due to the loss of the normal spine biomechanics and flexibility,
osteoporosis, cervical spondylotic myelopathy, cord ischaemia and
secondary canal stenosis.
348
•• Abnormal ossification, ossification of posterior longitudinal ligament (OPLL),

diffuse idiopathic skeletal hyperostosis (DISH), flurosis and ankylosing
spondylitis are other factors that complicate spine injury in the elderly.
•• Patients with ankylosing spondylotis are highly susceptible to extensive
neurological injury and spinal deformity after sustaining cervical fractures
from even minor traumatic forces.
Deep Vein Thrombosis
•• Thromboembolism leading to complications is very high in spinal injured
patients and the incidence of a thromboembolic event ranges 7–100%.
•• This is diagnosed clinically by observing signs of inflammation and
confirmed by duplex Doppler, ultrasound, impedance plethysmography
and venography.
•• The prophylactic measures advocated are low molecular weight heparin
and rotating beds.
•• Heparin is given as a titrating dose to achieve a PTT of 1.5 times the control.
•• Low dose heparin with pneumatic compression stockings or electrical
stimulation is another option.
•• Vena cava filters are used for patients who do not respond to anticoagulation,
and in whom anticoagulants are contraindicated. The prophylaxis therapy
is given for 6−12 weeks.
Vertebral Artery Injury

•• Cervical spine translation injuries and transverse foramen fractures are the
most common injuries associated with vertebral artery injuries.
•• Wallenberg’s syndrome, which is characterised by V, IX, X and XI CN
deficits, Horner’s syndrome, ataxia, dysmetria and contralateral pain and
temperature loss is a frequent clinical presentation.
•• Digital subtraction angiography is the most sensitive imaging study.
CT angiography has sensitivity and specificity close to that of catheter
angiography.
•• Anticoagulation is recommended in patients with evidence of posterior
circulation stroke, either observation or anticoagulation in patients with
evidence of posterior circulation ischaemia, and observation of patients
with no evidence of posterior circulation ischaemia.
OUTCOME SCORES
•• The functional independence measure and the Modified Barthel index are
recommended as the functional outcome assessment tool for clinicians
involved in the assessment and care of the patients with acute SCI.
45
CHAPTER Biomechanics of
the Spine
Anil Pande  Goutham Cugati
INTRODUCTION
•• Biomechanics is the study of the functional anatomy of the spinal column.
•• This includes the study of its normal structure, curves, attachments of
ligaments and muscles and intrinsic biological tissue characteristics. The
dynamic character of the vertebral column, intervertebral disc and a large
number of variables make this subject difficult and forbidding.
•• With the increasing use of artificial device, screws, plates, cages for
a variety of spinal lesions, it is essential that the neurosurgeons are
knowledgeable about the principles of biomechanics of the spine.
BIOMECHANICAL TERMINOLOGY
Cartesian Co-ordinate System
•• This consists of X, Y and Z axis.
•• This can have both rotational and translation movements along these axis,
which can be positive or negative.
•• The right handed cartesian system is used in biomechanics (Fig. 1).
Deformation
•• Deformation results when force is applied to a non-rigid body.
•• The forces that can act can be rotational or translational and deformation
results in strain.
Fig. 1: Diagrammatic representation of cartesian co-ordinates of individual

vertebrae and the whole spine
350
Strain
•• This is the change in unit length or angle in a body subjected to a force.
•• Shear strain is the change in the right angle.
•• Normal strain is the change in the length divided by the original length.
Stiffness
•• It is the ratio of force to the deformation.
Instantaneous Axis of Rotation (IAR)

•• This is the axis perpendicular to the plane of motion of the body and this
passes through a point within the confines of the body.
•• It is also the central point about which the vertebra rotates.
•• This is not a static point but is dynamic and changes with position, posture
and direction of movement.
•• Each segment has a unique instantaneous axis of rotation (IAR) for every
movement and is influenced by spine alignment, anatomy, muscles and
loads exerted.
•• According to White and Punjabi, the IAR is located in the ventral portion
of the vertebral body.
•• The human body’s centre of gravity is located approximately 4 cm ventral
to the sacrum.
Range of Movement
•• They are the limits of rotational and linear motion.
•• The spinal cord has six degree of freedom with three angles and three
displacements of a chosen point along a coordinate axis.
•• Extension is a backward bending moment.
•• Flexion is a forward bending moment.
•• Subluxation is an anteroposterior or postero-anterior shear.
•• Rotation is an axial turning or torsion.
•• Distraction is stretch or tension.
Kyphosis
•• This is an excessive sagittal angular deformity that is beyond the estab-
lished normal range.
•• Thoracic spine curvature is 25–40 degree with a transitional zone of 40–55
degree.
•• Kyphosis greater than 60 degree in the thoracic spine is abnormal.
•• In the thoracolumbar junction, the normal kyphosis is 0 degree, and the
lumbar spine is normally lordotic.
•• A post-traumatic deformity of greater than 30 degree at the thoracolumbar
junction and a kyphosis of greater than 5 degree in the lumbar spine are
considered abnormal.
Junghans Motion Segment

•• Junghans defined the basic functional unit of the spine.
•• This consists of two vertebral bodies and an intervening disc with the
ligaments and joints (Fig. 2).
•• The basic structure of a spine functional segment is an anterior column,
mechanically supported by a hydraulic cushion and posterior secondary
joints, resulting in a strong load-bearing and flexible structure.
Chapter 45 • Biomechanics of the Spine
351
•• Thus, the motion segment is the

smallest structure for performing
biomechanical tests of the human
spinal column.
•• The human spine has 24 motion
segments.
Bending Moment
•• The bending moment (M) is the
product of the force (F) applied
Fig. 2: Diagrammatic representation
to the lever arm and length of the
of Junghans motion segment
lever arm (D).
M=F×D
BIOMECHANICAL TESTING METHODS

In vivo Testing
•• These may be in vivo in animals and rarely in human beings where
intradiscal pressure measurements or instrumentation that has sensors
has been used to give information about biomechanics.
In vitro Testing
•• This is usually of complete or part preparations of human cadavers and
animal specimens, (e.g. sheep, porcine spine functional unit).
Biomechanical Tests can be Dynamic and Static
•• Strength test: This is a static test where load is applied till failure occurs.
•• Stability test: The load is applied, avoiding permanent deformation and the
specimen is only tested on the elastic segment of the stress versus strain
curve. It studies stiffness, creep and viscoelastic properties of the material.
•• Fatigue or cyclic load tests: These tests involve cyclical loading with
subfailure loads till failure occurs and a fatigue curve is plotted out.
ROLE OF IMAGING IN BIOMECHANICS

Radiography
•• Plain dynamic radiography is useful in diagnosing instability, classifying
injuries and fractures, evaluating surgical results and follow-up. Dynamic
radiographs have been used to study the characteristics of sagittal vertebral
alignment.
Computed Tomography
•• It has been used to study the bony anatomy, especially in the craniovertebral
junction and can give great information about various anomalies and
abnormal biomechanics and guide surgical restoration of the column.
•• CT myelography can be a valuable tool to study dynamic canal stenosis,
abnormal disc response and CT angiography can give an idea about safety
of the instrumentation.
•• CT studies are also used to study structural dimensions and morphology
of the spine, and this data is then used for the computer models and finite
analysis.
•• Computer assisted anatomic study to evaluate canal size.
352

•• It has allowed three-dimensional imaging of the spine for accurate
assessment of anatomy, sagittal balance, pathology, deformity and
kinematics.
•• Pathology of the ligaments at the craniovertebral junction is very well
visualised.
•• In trauma, the role of MRI is invaluable and when combined with whole
neuraxis screening is very comprehensive.
•• Soft tissue and ligament injuries, including tears of the ligaments of the
craniovertebral junction are well seen.
•• The area of signal intensity change in the cord can help in localising
segmental instability.
•• Dynamic MRI and MRI that can image while a patient is standing have
been in clinical use.
BRIEF NORMAL ANATOMY OF THE SPINE

Curvatures of the Vertebral Column
•• The spinal column in utero has a thoracic and lumbosacral kyphosis and
when the child starts raising the head post-natally, the cervical and lumbar
curvatures begin to form.
•• The adult vertebral column has a cervical and lumbar lordosis and a thoracic
and lumbosacral kyphosis.
•• The thoracic and lumbosacral kyphosis are called primary curves.
•• The centre of gravity of the spinal column passes from the dens of C2
through the body of the vertebrae to the promontory of the sacrum.
•• Abnormal curves may be congenital or acquired.
•• Iatrogenic flat back syndrome is a well recognised condition where the loss
of the normal curve causes severe symptoms.
Vertebral Body
•• The vertebral body is a box-like structure with a central spongy and can-
cellous core, surrounded by a hard cortical shell and the upper and lower
endplates.
•• The endplates support the nucleus pulposus and provide points of
attachment for the annulus fibrosus.
•• The cervical vertebrae are smaller and cylindrical and their spinous
processes are short and bifid. The transverse processes have a foramen
for the vertebral artery. The pars interarticularis is also called the lateral
mass. The facets from C2 to C7 are oriented at 45 degree and aligned in
a coronal orientation.
•• The atlas is a bony ring with two lateral masses and anterior and posterior
arches. The axis has a body unlike the atlas and odontoid process at its
superior anterior surface. It has two superior facets on the lateral aspects.
•• Thoracic vertebrae are heart-shaped and have special costal facets on
the body and transverse processes and these articulate with the ribs. T1
to T4 have cervical features and T9 to T12 have lumbar features.
•• The lumbar vertebrae are large and wider in the transverse diameter and
their facets are aligned in a sagittal plane. The sacrum is a fused triangular
structure. The coccyx is the terminal part of the column.
•• The vertebral bodies and the intervertebral discs support 80% of the spinal
loading and 20% is by the facet joints and the posterior elements.
353
Facet Joints
•• The cervical facet joints have a coronal orientation, the thoracic ones are
of intermediate orientation and the lumbar have a sagittal orientation.
•• The orientation of the facet joints in the lumbar area makes the lumbar spine
weak to flexion and translational forces, but is able to resist rotational forces.
•• The cervical spine facets do not resist flexion, extension, lateral bending
and rotation, and thus, the cervical spine is very mobile.
Pedicles
•• The morphology of the cervical, dorsal and lumbar pedicles has been
studied because it allows for a single trajectory to stabilise all three columns
via a posterior approach, using pedicular screws.
Intervertebral Discs
•• The human vertebral column has 33 vertebrae and 23 intervertebral discs.
•• The discs vary in size and constitute 1/3rd to 1/5th of the total height of
the column.
•• The lumbar disc is the largest avascular structure in the body and the disc
consists of three zones; the outer annulus fibrosus, the central nucleus
pulposus and the intermediate transition zone.
•• Three types of macromolecules, collagen, proteoglycans and glycoproteins
constitute the disc parts.
Spinal Canal
•• The spinal canal varies in size from the craniovertebral junction to the
sacrum and the dorsal canal has the smallest diameter.
•• The canal size may be reduced due to osteophytes, disc, ligamental
hypertrophy or Ossification posterior longitudinal higament (OPLL).
Ligaments
•• These are composed of elastin and collagen and connect the vertebrae.
•• They may be short, connecting adjacent segments or long. They are the
anterior longitudinal ligament (ALL), posterior longitudinal ligament (PLL),
ligamentum flavum, interspinous ligament, intertransverse ligament,
capsular ligament and supraspinous ligament (Fig. 3).
•• The upper cervical spine and CV junction ligaments include the atlanto-
occipital capsule, cruciate ligament, tectorial membrane, atlanto-axial
capsule, ligamentum flavum, apical ligament, alar ligament and posterior
atlanto-occipital membrane.
Fig. 3: Diagrammatic representation showing attachment of various

ligaments to the spine
354
•• These ligaments respond to tensile forces and their effectiveness depends

on the morphology and movement arm through which it acts.
•• Anterior Longitudinal Ligament: This begins as the anterior occipito-
atlantal membrane at the occiput and ends at the sacrum. It is multilayered,
with the deep layer binding to the adjacent intervertebral discs. The
middle layer binds to the discs and vertebral bodies over three levels. The
superficial layer extends to 4 to 5 vertebral bodies. ALL maximally resists
extension loads. ALL disruption allows hyperextension.
•• Posterior Longitudinal Ligament: This begins as the tectorial membrane
and extends down to the sacrum, the fibres being spread out at the disc
level and narrowing at the body level. It has several layers with the deep
layers attached to adjacent bodies and superficial layer spanning several
levels. PLL prevents mainly flexion and lateral bending. PLL disruption
allows hyperflexion.
•• Ligamentum Flavum: Extending from C1-C2 level to L5-S1 level, these
have very high elastin content and are the most elastic tissues in the human
body and are distinctively yellow. These begin from the ventral surface of
the lower lamina and attach to the dorsal surface of the upper border of the
superior lamina. They are absent in the mid vertebral region and have a gap
at the midline. Laterally, they blend with the ligament of the joint capsule.
•• Capsular Ligaments: These ligaments surround the facet joints and
are attached to the bone outside the synovial joint with the fibres running
perpendicular to the plane of the joint. They resist lateral bending, axial
rotation and flexion.
•• Interspinous and Supraspinous Ligaments: These attach from the
base to the tip of each spinous process and begin at C2-3 and end at
L5-S1 levels. The supraspinous ligaments connect the spinous processes
at the tips.
SPINAL STABILITY AND INSTABILITY

•• Instability of the vertebral column is excessive motion beyond physiological
limits of one vertebra upon another in at least one of the three motion planes;
X-axis (flexion-extension), Y-axis (rotation) and Z-axis (lateral bending).
•• The most common cause of instability is trauma. The other causes are
degenerative, metabolic, neoplastic, congenital and iatrogenic.
•• The central nervous system, an osteoligamentous system and a muscle
system combine to maintain spine stability.
NEURAL CONTROL
•• The fine tuned multiple spinal segmental loops involving the alpha and
gamma motor neurons and the proprioception system are responsible for
the normal muscle tone which maintains the axial and transverse stability.
•• Axial stability is maintained along vertical columns: This consists of two
columns at the C1–C2 level and three columns from C2 to the sacrum.
•• Transverse stability at the motion segment levels is produced by the
coupling of joints and ligaments.
ROLE OF THE MUSCULATURE

•• Spinal column instability and injury is caused by overload.
•• Motor control is a key component in injury prevention and muscles, and
their role in spinal stability is being recognised.
355
Table 1: Benzel point system for quantification of acute instability in the

sub-axial, cervical, thoracic and lumbar spine
Loss of integrity of anterior (and middle) column 2
Loss of integrity of posterior column(s) 2
Acute resting translational deformity 2
Acute resting angulation deformity 2
Acute dynamic translation deformity exaggeration 2
Acute dynamic angulation deformity exaggeration 2
Neural element injury 3
Acute disc narrowing at level of suspected pathology 1
Dangerous loading anticipated 1
A score of 5 points or more implies the presence of instability.
A score of 2 to 4 implies the presence of limited instability.
From clinical or radiographic evaluation; one point if incomplete evidence exists.
Three points for cauda equina injuries, 2 points for cord injuries and 1 for isolated root injuries
Adapted from: Edward CB. Biomechanics of Spine Stabilization. Philadelphia: Lippincott.
DEFINITION OF CLINICAL INSTABILITY OF SPINE

•• White and Panjabi defined instability as “the loss of the ability of the spine
under physiologic loads to maintain its pattern of displacement, so that
there is no initial or additional neurological deficit, no major deformity, and
no incapacitating pain”.
•• Benzel has categorised four subcategories of instability of the spine.
•• Current quantification of instability of the sub-axial cervical, thoracic and
lumbar region based on a point system, suggested previously by White
and Panjabi, was modified by Benzel, so that the point system could be
applied uniformly to the complete spine (Table 1).
•• Instability also can vary in magnitude: first degree (mechanical), second
degree (neurological) and third degree (mechanical and neurological).
THEORY OF LOUIS
•• The spine bears weight principally by sustaining axial loads along the
vertebral body, intervertebral disc and two facet joint complexes at each
segmental level.
TWO COLUMN THEORY OF HOLDSWORTH

•• In the ‘two column theory’, he defined the anterior column as consisting
of the anterior vertebral bodies, the anterior longitudinal ligament, the
disc and the posterior longitudinal
ligament (Fig. 4).
•• The posterior column consists of
everything posterior to the posterior lon-
gitudinal ligament, including the capsular
ligaments, the facet joints, ligamentum
flavum and the interspinous and supras-
pinous ligaments.
•• Holdsworth believed that the stability of
the spine depends on the integrity of the Fig. 4: Two column theory of
dorsal ligament complex. Holdsworth
356
THREE COLUMN THEORY OF DENIS

•• Posterior column disruption did not lead
to instability, and Denis then divided the
anterior column into the anterior and
middle column, the anterior part of the
disc, annulus and anterior longitudinal
ligament, forming the middle column
and the posterior disc, annulus and the
posterior longitudinal ligament forming
the posterior column (Fig. 5).
•• This theory helps in evaluating bony
collapse associated with axial loading
and the effects of distraction, flexion Fig. 5: Three column theory of
and extension injuries. Denis
•• Of the three columns, the anterior and posterior columns are the principle
support structures.
•• The anterior column resists compression and axial loading and the posterior
column maintains the tension.
•• To maintain the correct posture, all forces and movements must be
balanced about the IAR.
•• The IAR is located dorsal to the annulus fibrosis in the intact spine.
EVANS FLAGPOLE CONCEPT

•• The stability of the spine is not
dependent solely on the integrity
of the spinal column but also
on the functional capabilities of
the paraspinal muscles and the
ligaments of the spine, which
participate in the “flagpole” concept
of spinal stability (Fig. 6).
•• Evans uses the flagpole model
to describe the biomechanical
advantages of posterior lumbar
interbody fusion (PLIF).
•• The central graft placement repre- Fig. 6: Evans Fagpole concept
sents the flagpole with the facets remaining annulus anteriorly and posterior
ligamentous restraints representing the surrounding guy wires.
•• This construction, according to Evans, balances both compressional and
torsional forces.
BIOMECHANICS AND AXIAL TRACTION

•• Currently, MRI should be performed to exclude the presence of a traumatic
disc before traction is applied and closed reduction is attempted.
•• Traction is contraindicated in Hangman’s type 2A fractures, where traction
can worsen the translation and cause stretch injury to the spinal cord.
•• The neutral zone (NZ) is a region of intervertebral motion around the neutral
posture where little resistance is offered by the passive spinal column.
•• The NZ appears to be a clinically important measure of spinal stability
function.
357
•• Its size may increase with injury to the spinal column, which in turn, may
result in spinal instability or low-back pain.
BIOMECHANICS OF TRAUMA
•• In the AO classification, the ‘A’ type injuries are axial injuries (compression
and burst fractures).
•• The ‘B’ injuries are the distraction injuries (flexion, distraction and chance
injuries).
•• The ‘C’ injuries are rotational injuries (fracture dislocation, shear injuries).
•• The key factor is the integrity of the ligaments. The knowledge about the
causative mechanism of injury may hold a key to its treatment, as exempli-
fied by the management of locked facets by ventral reduction and fusion.
BIOMECHANICS OF SPINE DEFORMITY

•• The normal curves of the spine are the major factor in maintaining the
normal biomechanics of the spine.
•• Pathological spinal deformation is usually a result of one unstable motion
segment.
•• The goals of spinal deformity surgery are reasonable correction of deformity,
prevention of further deformity, restoration of sagittal and coronal balance,
cosmetic optimisation and improved neurological function.
BIOMECHANICS OF CORD INJURY

•• The presence of cervical spine mobility, instability and kyphosis is strongly
predictive of clinical progression in patients with cervical spondylotic
myelopathy.
•• There is a decreased cross-sectional area of the spinal canal due to the
dorsal bulging of the annulus as well as the in-folding of the ligamentum
flavum and the scaffolding of the lamina leading to a pincer-like action on
the cord.
BIOMECHANICS OF BONE GRAFTS

•• Sir William Macewen introduced bone grafting to replace missing bone and
induce new bone formation.
•• Instrumentation without structural bone grafts generally fails, and a strong
structural graft is required to resist axial loading and flexion.
•• Tricorticate illium, fibular graft and titanium cages packed with autogenous
graft provide good anterior column support.
•• Single rib graft may not provide adequate structural support, but multiple
rib grafts stacked together and tied provide excellent support and oste-
oinduction.
•• The instrumentation causes stress shielding, but generally rigid fixations
result in better fusion rates.
BIOMECHANICS OF SPINAL IMPLANTS

•• It is a rapidly expanding field and the biomechanical properties of screws,
plates, wires, cages and newer disc arthroplasty and dynamic implants are
tested along with the associated vertebral column.
•• Dynamic systems, semi-rigid countoured plates and implants that are lighter
and stronger and more similar to biological tissues (titanium, carbon fibre,
358
polyetheretherketone (PEEK), ceramic and bioabsorbable implants) are

undergoing biomechanical testing.
FUTURE OF BIOMECHANICS
•• Fernstrom, in the 60s, implanted stainless steel spheres and began the
modern era of applied biomechanics.
•• This was followed by the AcroFlex artificial disc, the Charite artificial disc,
disc nucleus replacement, posterior dynamic stabilisation systems, inter-
spinous devices and facet joint arthroplasty.
•• Non-fusion surgery using artificial ligament stabilisation, dynamic stabili-
sation and the use of image guidance and dynamic imaging has become
routine.
•• The micro-electro-mechanical system (MEMS) technology uses nano
machines and integrates them on a chip. These are then used to measure,
transmit and modify biomechanical properties and functions.
•• The combination of minimally invasive and image guided neurosurgery
and restoration of normal biomechanics will lead to better outcomes in
spine surgery.
46
CHAPTER
Injuries of the
and Upper Cervical Spine
Sarat Chandra P  Vamsi Yerramani
SURGICAL ANATOMY
•• The craniocervical ligamentous structures may be divided into intrinsic and
extrinsic ligaments.
•• The extrinsic ligaments include the ligamentum nuchae, which extends
from the external occipital protuberance to the posterior aspect of the atlas
and all the cervical spinous processes. Fibroelastic membranes replace
the anterior longitudinal ligament, intervertebral disks, and ligamentum
flavum between the occiput and atlas and between the atlas and axis.
The atlanto-occipital and atlantoaxial joint capsules also contribute to the
extrinsic stability.
•• The intrinsic ligaments located within the spinal canal provide most of the
stability for the spine. These ligaments form three layers anterior to the
dura (Fig. 1). From dorsal to ventral, they include the tectorial membrane,
the cruciate ligament and the odontoid ligaments.
•• The tectorial membrane connects the posterior body of the axis to the
anterior foramen magnum and is the cephalad continuation of the posterior
longitudinal ligament.
•• The cruciate ligament lies anterior to the tectorial membrane, behind the
odontoid process.
•• The transverse atlantal ligament is the strongest component, connecting
the posterior odontoid to the anterior atlas arch, inserting laterally on
bony tubercles. Vertical bands extend from the transverse ligament to the
foramen magnum and body of the axis.
Fig. 1: Schematic diagram of the anatomical structures constituting the

craniovertebral junction: (A) Apical ligament of dens. (B) Superior longitudinal
band of cruciate ligament. (C) Anterior arch of C1. (D) Transverse ligament.
(E) Anterior longitudinal ligament. (F) Posterior longitudinal ligament. (G)
Odontoid process. (H) Vertebral artery. (I) Tectorial membrane. (J) Posterior
C1 arch. (K) Ligamentum flavum. (L) Alar ligament. (M) Transverse ligament
360
•• The odontoid ligaments (alar and apical ligaments) are the most ventral
ligamentous structures.
•• The paired alar ligaments connect the odontoid to the occipital condyles.
•• They measure 5–6 mm in diameter and are relatively strong, in contrast
with the small apical ligament that runs vertically between the odontoid
and foramen magnum.
CLINICAL FEATURES
•• Patients with an upper cervical injury may have an associated head injury,
which can alter their level of consciousness and complicate obtaining an
accurate history and physical examination.
•• In history, it is important to find out the mechanism of injury (including
potential forces imparted by the injury), whether the patient was restrained,
and whether transient motor or sensory deficits occurred at the scene of
the accident.
•• A careful, complete physical examination of the entire spine should follow—
inspection, palpation and neurologic evaluation while the head and neck
are stabilised in neutral alignment.
•• Neurologic examination should include testing of the cranial nerves as
well as motor function, sensory perception and reflexes in the extremities.
•• Results of neurologic examination may range from normal sensorimotor
functions to variable sensorimotor impairment, including incomplete to
complete spinal cord injury. Cranial nerve injury—including of nerves VI,
VII, IX, XI and XII—may result from upper cervical injuries and should not
be overlooked.
•• The screening radiography should include anteroposterior (AP), lateral
and open-mouth views.
•• With a normal atlanto-occipital relationship, the clivus on lateral radiograph
should point towards the tip of the odontoid, and the basion (tip of the clivus)
should be within 5 mm of the odontoid vertically.
•• Retropharyngeal soft-tissue swelling greater than 5 mm at C3 is abnormal
and should raise suspicion for the presence of an anterior arch fracture
of the atlas.
•• A diastasis greater than 2 mm between the occiput and atlas is also
abnormal.
•• Harris et al described the rule of 12, which is superior to the powers ratio
for identifying occipitocervical dissociation. The rule of 12 uses three
landmarks:
–– The basion
–– The rostral tip of the odontoid
–– The rostral extension of the
posterior cortical margin of the
axis (posterior axial line).
•• The basion-axial interval is the
distance between the basion and
the posterior axial line; the basion-
dental interval is the distance
between the basion and the tip
of the odontoid. The method is Fig. 2: Occipitocervical dissociation
applicable to adults and to children older than 13 years. Both intervals
should be less than 12 mm in normal individuals (Fig. 2).
Chapter 46 • Injuries of the Craniovertebral Junction
361
•• An open-mouth radiograph allows visualisation of the atlas, odontoid

process and lateral masses of the axis.
•• Computerised tomography (CT) is a very sensitive method for evaluating
craniocervical relationships and is the preferred method of investigation for
evaluating most suspected injuries in the upper cervical spine.
•• Magnetic resonance tomography (MRI) is useful in patients with neural
deficit or with suspected ligamentous injury (especially, the transverse
atlantal ligament).
OCCIPITOCERVICAL DISSOCIATION
•• Occipitocervical ligamentous injuries have a high mortality rate and often
do not reach the hospital. In autopsy studies, they represent 5–12% of
identified cervical injuries; the most common mechanism is pedestrians
struck by motor vehicles. Prompt recognition, high index of suspicion and
immobilisation are essential. Children are predisposed to these injuries
because of their inherent ligamentous laxity; immature occipitocervical
joints; and larger ratio of head to body size than in adults.
OCCIPITOCERVICAL INSTABILITY
•• This injury may occur due to several different mechanisms and can be
classified according to the direction of occipital displacement (Figs 3A to E):
–– Type I injuries are most common and have anterior occipital displace-
ment
–– Type II injuries have vertical displacement greater than 2 mm between
the occiput and C1 (Type IIA). Vertical instability also can occur at
C1-2 (Type IIB) because the same ligamentous structures, the tectorial
membrane and alar ligaments, resist distractive forces at both levels
–– Type III injuries are rare and have posterior occipital displacement.
•• Early diagnosis and treatment are critical because patients are at high risk
for neurologic injury or even sudden death.
•• Once occipitocervical instability has been diagnosed, reduction of
displacement should be performed carefully under fluoroscopic guidance by
carefully positioning the head with a bolster behind the thorax (for anterior
displacement) or the occiput (for posterior displacement).
A B C
D E
Figs 3A to E: Schematic diagram showing various types of occipitocervical

instabilities. (A) Normal relationship of occiput, C1 and C2 bodies. (B) Type I:
anterior—the occiput has translated anteriorly. (C) Type IIa: vertical—vertical
occipito C1 distraction. (D) Type IIb: vertical—vertical C1-C2 distraction. (E)
Type III: posterior—posterior dislocation of occiput in relation to the C1
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•• “Traction and collar immobilisation can precipitate axial displacement,

precipitating neurologic injury and accordingly should be avoided”.
•• For vertical displacement, reduction can be performed by providing gentle
downward pressure or by elevating the head of the bed.
•• A halo vest can provide temporary immobilisation, but surgical stabilisation
is necessary.
•• Occipitocervical fixation and arthrodesis, using plates with C2 fixation
obtained with C1-2 transarticular screws or C2 pedicle screws, is preferable
to wire and graft techniques.
•• Fixation with plates and screws remove the need for a post-operative halo
vest and more accurately maintain reduction.
CONDYLAR FRACTURES
•• Occipital condyle fractures are commonly caused by an axial compression
mechanism and are frequently diagnosed as a concurrent finding on head
CT scan done for trauma.
•• The classification system described by Anderson and Montesano was
based on CT pattern and evaluates the potential for instability.
•• A type I injury is a comminuted (impaction) fracture of the condyle and
is generally stable.
•• A type II fracture is a condyle fracture with associated basilar skull fracture.
This injury is stable except when the entire condyle is separated from the
occiput.
•• A type III injury is an avulsion fracture of the attachment of the alar
ligaments. This injury can be bilateral and occurs in 30–50% of patients
with atlanto-occipital dislocations.
•• Stable type I and II fractures should be treated in a collar for 6–8 weeks.
•• Displaced type II injuries should be treated in a halo vest for 8–12 weeks.
•• Type III injuries are treated based on stability; stable undisplaced injuries
are treated using a collar with a chin support, and minimally displaced
injuries are treated in a halo vest.
•• Any evidence of AP displacement, joint incongruity, or abnormal diastasis
makes the injury unstable, necessitating an occiput-C2 fusion.
ATLAS FRACTURES
•• The atlas acts as a transitional structure between the occiput and cervical
spine.
•• In various adult series, fractures of the C1 vertebra have accounted for 25%
of craniocervical injuries, 3–13% of cervical spine injuries, and 1.3–2% of
all spinal injuries.
•• The most common causes are motor vehicle accidents and falls.
•• The most common mechanism is axial loading.
•• Atlas fractures are commonly associated with other injuries of the cervical
spine.
•• Axis fractures are associated with 40–44% of atlas fractures.
•• Isolated fractures of the anterior or posterior arches are the commonest
with isolated burst fractures next in line.
•• Other associated injuries include subluxation, rupture of the transverse
ligament, non-contiguous cervical spine fractures and closed head injuries.
363
Fig. 4: Jefferson’s classification for atlas
Classification of Atlas Fractures

•• Sir Geoffrey Jefferson, a British neurosurgeon, presented a series of 42
patients with atlas fractures in addition to four of his own patients with the
injury (Fig. 4).
–– Type I fractures involve the posterior arch alone.
–– Type II fractures involve the anterior arch alone.
–– Type III fractures are bilateral posterior arch fractures associated with
a unilateral or bilateral anterior arch fracture.
–– Type IV fractures involve the lateral mass.
–– Type V fractures are transverse fractures of the anterior arch.
•• The classic Jefferson fracture is the burst type III fracture associated with
lateral displacement of the lateral masses.
•• Based on Jefferson’s classification, the most common fracture types seen
in various clinical series are type I followed by type III.
•• The transverse ligament plays a crucial role in determining atlantoaxial
stability. Atlas fractures have often been defined as stable or unstable
based on the inferred integrity of the transverse ligament.
•• According to the Spence rule, if the sum of the displacement of lateral
masses exceeds 6.9 mm after an atlas burst fracture, the transverse
ligament is probably torn.
Clinical Presentation
•• Patients with upper cervical spine fractures frequently present with neck
pain, spasms of the cervical muscles and limited neck motion.
•• Neuralgia and paraesthesias related to compression of or injury to the C2
nerve are common.
•• Retropharyngeal swelling may cause difficulty in swallowing.
•• Dissecting injuries of the vertebral artery and neuropathies of the lower
cranial nerves are some of the uncommon presentations.
•• Isolated burst fractures of the atlas, usually are not associated with
neurological deficits, as they cause the spinal canal to expand.
Diagnosis
•• To evaluate atlas fractures using plain X-rays, it is essential to obtain open-
mouth odontoid, lateral and flexion-extension views.
•• An open-mouth odontoid view will show overlapping of the C1 and C2
facets.
364
•• Any displacement of the C1 lateral mass over C2 facets is suggestive of

an atlas burst fracture. In a normal variant (pseudo-spread of the atlas) in
children younger than 7 years old, the ossified lateral masses of the atlas
may project beyond the ossified articular processes of C2, giving a false
sign of a Jefferson fracture in children.
•• In lateral views, an atlantodental interval (ADI) greater than 3 mm in
adults and greater than 5 mm in children is highly suggestive of a ruptured
transverse ligament.
•• The MRI is the modality of choice for assessing the transverse ligament
integrity.
•• Posterior atlanto-dental interval (PADI) is measured from the posterior
border of the dens to the anterior border of the posterior tubercle. This
index may be more important because it more directly assesses the space
available to the spinal cord.
•• The degree of neurologic deficits has been demonstrated to correlate with
the PADI. A PADI of less than 13 mm is considered significant.
•• Posterior arch fractures can be assessed on lateral or 60 degrees oblique
X-rays.
•• Anterior arch fractures are often difficult to diagnose from plain X-rays.
•• To rule out pseudo-spread of the atlas, thin-slice CT with cuts parallel to
the C1 arch is the optimal imaging modality and is recommended for all
children suspected of harbouring a Jefferson fracture.
Treatment and Results

•• Treatment of atlas fractures depend on whether they occur in isolation or
in conjunction with other cervical spine fractures.
•• Treatment recommendations are based on several case series (class III
evidence), which are summarised below:
–– Isolated atlas fractures can be treated by external immobilisation of the
craniocervical junction for 8–12 weeks. Late instability must be ruled
out by using dynamic imaging studies such as flexion-extension X-rays
–– Instability persisting after external immobilisation should be treated by
an occiput–C2 fusion or a C1-C2 fusion, whatever suits the given case
–– There are no established standards or guidelines for the treatment of
combined C1-C2 fractures. The treatment strategy is based on the
nature of the C2 fracture and the integrity of the transverse ligament.
–– Presence of an occipitoatlantal dislocation warrants occipitocervical
fusion.
RUPTURE OF TRANSVERSE LIGAMENT

•• Rupture of the transverse atlantal ligament is generally caused by a flexion
force and often affects not only the transverse ligament but also the alar
and apical ligaments.
•• With an intact ligament, the maximal ADI is 3 mm in an adult and 5 mm
in a child.
•• Displacement greater than 7 mm was associated with loss of integrity of
the alar ligament and tectorial membrane.
•• Complete ligamentous disruption can be accompanied by a significant
incidence of neurologic injury.
•• In addition, headache, nausea, visual abnormalities and sensorimotor
deficits may result from vertebral artery compression.
365
•• Disruption may occur in isolation or in association with other upper cervical

injuries.
•• Using thin-section CT or MRI, Dickman classified disruptions of the mid
substance of the ligament as type I injuries and avulsions of the ligament
from the C1 lateral mass as type II injuries.
•• Treatment depends on the degree of initial displacement and identification
of any coexistent fractures.
•• If the ADI is less than or equal to 5 mm in a neurologically intact patient,
collar immobilisation is sufficient initially.
•• For an ADI greater than 5 mm, non-surgical treatment including halo
immobilisation has generally yielded poor results, except in selected cases
when a bony avulsion can be documented on CT.
•• The method used for C1-C2 arthrodesis in patients with this injury need to
be carefully selected; some wire techniques, even with halo immobilisation
can result in post-operative displacement.
•• C1-C2 transarticular screw fixation for arthrodesis may be indicated.
ODONTOID FRACTURES
•• The first description of the surgical management of an odontoid fracture
was in 1910 and is credited to Mixter and Osgood.
•• Odontoid fractures constitute 8–18% of all cervical fractures, with neurologic
deficits occurring in 10–20% of cases.
•• They represent 75% of childhood cervical spine fractures as a result of
the large ratio of head to body size. High-velocity trauma, such as motor
vehicle accidents, accounts for most of these injuries in young adults, while
low-velocity injuries, such as falls, account for the majority of injuries in the
elderly and children.
•• The classification system of Anderson and D’Alonzo is based on the
anatomic level of the fracture, which has been shown to have a correlation
to prognosis for fracture healing.
–– Type I fractures occur at the tip of the odontoid process cephalad to
the transverse atlantal ligament. They are the least common odontoid
injury and generally are stable. They may also represent an avulsion
of the alar ligaments, which can occur in atlanto-occipital distraction
injuries.
–– Type II fractures occur at the junction of the base of the odontoid and
body of the axis. They are the most common fracture type and are
least likely to heal with non-surgical treatment and are unstable. These
fractures were subdivided into three types by Hadley et al:
¾¾ Type IIA: The fracture line is transverse, and with less than 1.0
mm of displacement. Both surgery and external immobilisation
have good success rates. The treatment strategy has to be decided
based on the individual merits of the case.
¾¾ Type IIB: The fracture line is from antero-superior to postero-
inferior or a transverse fracture with displacement greater than 1.0
mm. Surgical fixation is the treatment of choice.
¾¾ Type IIC: The fracture line passes from antero-inferior to postero-
superior or a fracture with significant comminuted segments of the
dens. This subtype is best treated with posterior atlantoaxial fixa-
tion. The fractured odontoid process may be displaced anteriorly or
posteriorly relative to the body of C2. Odontoid screw placement in
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these fractures is technically difficult and also the non-union rates

are high. Posterior fixation is a good option in this group of patients.
–– Type III fractures extend into the body of the axis. They may be more
stable than type II fractures and have a higher union rate with non-
surgical treatment.
Treatment
•• There have been many treatment strategies proposed for odontoid
fractures.
•• These strategies are based on fracture type, the degree of initial dens
displacement, the angle of the fracture line with respect to the body of the
axis, the integrity of the transverse ligament and the age of the patient.
•• Treatment options include both non-operative and surgical strategies.
•• There are several external immobilisation orthoses available for non-
operative management of odontoid fractures, each with variable results.
•• Surgical options include both anterior and posterior approaches.
•• Anterior approaches include odontoid screw fixation and a rarely used
salvage technique of anterior transarticular screw fixation.
•• Posterior arthrodesis approaches include the use of wiring techniques,
Halifax clamps, screw and rod constructs, and posterior transarticular
screw fixation.
TRAUMATIC SPONDYLOLISTHESIS
(HANGMAN’S FRACTURE)
•• Traumatic spondylolisthesis of the axis, most often occurs as a result of
either motor vehicle accidents or falls, and represents approximately 15%
of all cervical spine fractures.
•• Although the fracture pattern may resemble that resulting from judicial
hanging, the causative injuries are quite different.
•• A properly accomplished judicial hanging results in a violent hyperextension
injury to the spine with distraction, severing the spinal cord.
•• Traumatic spondylolisthesis, however, results from hyperextension with
axial load.
•• The hyperextension and axial load mechanisms result in fractures of the
pars interarticularis.
•• Neurologic injury is uncommon because the fracture fragments separate,
decompressing the spinal canal.
•• With increasing severity of injury, the rebound flexion or flexion/distraction
mechanism results in disruption of the C2-3 disc and posterior longitudinal
ligament.
•• Additionally, the anterior longitudinal ligament may be stripped from its
bony attachment.
•• The most severe and complex injuries most likely occur as a result of
flexion, causing dislocation of the C2-3 facets, followed by hyperextension
with axial load, producing the pars fractures secondarily.
•• The classification system for this injury was first described by Effendi in
1981 and was later expanded by Levine and Edwards, who described four
fracture patterns. Others have added a fifth type.
•• The classification is based on translation and angulation between C2 and
C3.
367
–– Type I injuries are bilateral pars fractures with translation less than
3 mm and no angulation. The C2-3 disc and ligamentous structures
remain intact because the major injury is bony.
¾¾ Type IA is an atypical fracture and is the most recently recognised.
There is minimal translation and little or no angulation. Elongation
of the C2 body is often seen radiographically. The CT will reveal
extension of one fracture line into the body and often through the
foramen transversarium. As a result, injury of the vertebral artery
may occur.
–– In Type II fractures, the C2-3 disc and posterior longitudinal ligament
are disrupted, resulting in translation greater than 3 mm and marked
angulation. The anterior longitudinal ligament generally remains intact,
but is stripped from its bony attachment.
¾¾ Type IIA fractures are less common. In contrast with type II, the
fracture line is more oblique than vertical. There is little or no trans-
lation, but there is significant angulation. Traction will cause further
fracture displacement and should be avoided.
–– Type III injuries are a combination of pars fracture with dislocation
of the C2-3 facet joints. This injury is very unstable with free-floating
inferior articular processes. This is the most common injury to be as-
sociated with neurologic deficit and requires surgery; it is irreducible
by closed means.
•• Type I and IA fractures can be treated by collar immobilisation, both initially
and definitively.
•• Type II and IIA fractures require gentle reduction.
•• Type II fractures require light traction and extension by placing a bolster
under the shoulders to achieve reduction.
•• Type IIA fractures require extension and gentle axial load to achieve
reduction.
•• Type III fractures are irreducible because the dislocated inferior facets of C2
are not connected to any other bony structure as a result of the bipedicular
fracture lying just anterior to them.
•• Closed traction is, therefore, unable to provide reduction, and open
reduction is required.
•• Once reduction is verified radiographically, type II fractures are immobilised
in a halo vest for 6–8 weeks.
•• For type II fractures with displacement greater than 5 mm and/or angulation
greater than 10 degree, traction is performed to reduce the displacement,
followed by halo immobilisation for an additional 6–8 weeks.
•• Alternatively, surgical stabilisation with transpedicular lag screws may be
considered if anatomic alignment can be achieved.
•• Type III fractures require open reduction followed by internal fixation with
a wiring or plating technique, based on the integrity of the facets and/or
lamina. Anterior C2-C3 plating also has been used.
•• Alternatively, more recently, surgical treatment is the preferred option as it
has a low-risk and up to 98% fusion rates with transpedicular screw fixation.
OPTIONS OF SURGICAL PROCEDURES FOR

CRANIOVERTEBRAL JUNCTION TRAUMA
Posterior Fusion Techniques
•• Historically, posterior cervical fusion was the primary operative alternative
when external immobilisation failed or was considered unsuitable.
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Wiring Techniques
•• Over time, wiring techniques have evolved to the use of braided cables
instead of monofilament wire.
•• Braided cables have the advantage of being flexible, strong, and resistant
to distortion and fatigue.
•• Braided cables also are not susceptible to over twisting, because a crimping
mechanism is used to securely lock and fix the construct.
Gallie’s Technique
•• Gallie described his method of C1-C2 arthrodesis in 1939.
•• A superior notch in the spinous process of C2 holds the H-shaped onlay
graft more securely in place, and the graft is secured with a wire that is
only sublaminar at C1.
•• The drawback of his technique is that it is a solitary, midline fixation and
fusion construct is susceptible to rotational forces.
Brook’s and Jenkin’s Technique
•• It involves two wedge bone grafts secured between C1 and C2 with
sublaminar wiring.
•• They designed it to overcome the rotational deficiencies of the Gallie’s
method.
Dickman and Sonntag
•• Dickman and Sonntag described an atlantoaxial arthrodesis secured with
a sublaminar wire at C1 that incorporated an iliac crest strut-graft between
the posterior arches of C1 and C2 secured with wire around the base of
the spinous process of the axis.
Interlaminar Clamps
•• Halifax clamps were initially described by Tucker.
•• Several problems were observed with these clamps, and they ultimately
fell out of favour. One problem was that in tightening the clamps, the
odontoid could be angulated dorsally, causing ventral encroachment up
on the spinal cord.
Jeanneret and Magerl Transarticular Screw Technique
•• Transarticular screw fixation of C1 and C2 was first described by Magerl
and Seeman.
•• The entry point on C2 is 2 mm lateral from the medial edge of the facet
and 3 mm superior to the caudal edge.
•• The trajectory is straight up across the C1 and C2 articular surfaces and
into the lateral mass of C1.
•• The drill is aimed at the superior portion of the C1 anterior arch.
•• Transarticular screws offer good biomechanical stability in all directions of
motion compared to the wiring techniques.
•• Bone fusion rates range between 98% and 100%.
•• When the anatomy is favourable, this is the preferred method of posterior
fixation.
•• Transarticular screws combined with C1-C2 wiring techniques have
achieved 100% fusion rates.
•• Posterior fusion may be preferred in patients who have a comminuted type
II or III fracture or an associated unstable Jefferson’s fracture.
369
•• C1-2 joint fusion eliminates 50% of the rotation of the head, a significant
loss of motion. Consequently, a technique for treating odontoid fractures,
anterior odontoid screw fixation, has been developed to preserve the normal
motion of the C1-2 joint.
Goel and Laheri/Harms and Melcher Fixation
•• The use of lateral mass screws in C1 and pedicle screws in C2 with plate
fixation was first described by Goel and Laheri in 1994 and later with
polyaxial screws and rods in 2001 by Harms and Melcher.
•• A point of difference between the two methods is that Goel and Laheri
described distraction of the C1-C2 joint space with spacers.
•• Resnick and Benzel described a C1-C2 fixation method similar to the Harms
and Melcher method using C1 and C2 pedicle screws.
•• This method of atlantoaxial fixation is the procedure of choice for patients
with C1-C2 fixed (irreducible) subluxation or an aberrant vertebral artery
that may make transarticular screws difficult and/or dangerous.
Crossed C2 Intralaminar Screws
•• In 2004, Wright described the most recent technique for screw fixation of
the axis.
•• This technique involves the use of polyaxial screws inserted into the lamina
of C2 in a bilateral crossing fashion.
Occipitocervical Lateral Mass Polyaxial Rod and
Screw Placement
•• This technique has become very widely accepted due to rigid long segment
immobilisation and distraction forces provided along with the ease, safety
and strength of the lateral mass screws.
•• Lateral mass screws are available as 12, 14 and 16 mm polyaxial screws
of diameter 3.5 mm.
•• They are placed about 1 mm medial to the centre of the lateral mass (C3-
C6) and directed lateral and superiorly at an angle of 25 degree. However,
before performing the procedure, it is essential that the adequacy of the
lateral mass of the cervical vertebrae is confirmed on CT scan bone
windows.
•• If all the techniques are compared, Magrel’s (C2-C1 transarticular) provides
maximum strength against axial rotation, followed by Brook’s, Halifax, the
least being Gallie’s technique.
•• Likewise, if other movements like flexion, extension and lateral bending are
assessed, Brook’s has the most stability followed by Magrel’s, Halifax and
again least by Gallie’s procedure.
•• Not surprisingly, bone fusion is least for Gallie’s (60–80%) and Magrel’s has
the highest incidence of bone fusion (95–100%).
Anterior Fusion Techniques

Odontoid Screw Fixation
•• Odontoid screw fixation allows the surgeon to directly reduce and fixate the
fracture itself, while maintaining atlantoaxial rotational mobility.
•• Disruption of the transverse ligament is an absolute contraindication to
odontoid screw fixation.
370
•• Displacement of more than 6 mm, age greater than 50 years, fractures

more than 6 months old and poor patient habits are associated with high
rates of non-union.
Anterior Atlantoaxial Facet Screw Fixation
•• This is a rarely used technique described by Feiz-Erfan for failed posterior
atlantoaxial fusion or for C1-C2 instability with destruction of the posterior
elements of C1 and C2.
•• The approach for this procedure is the same as that for odontoid
screw fixation.
•• The C1-C2 joint is identified bilaterally, and screws are placed in the
anterior cortex of C2 and through the C1-C2 joint space at a 90-degree
angle.
47
CHAPTER Injuries of Subaxial
Cervical Spine
Anil Pande  Ravindranath Kapu
INTRODUCTION
•• The subaxial cervical spine, also called the middle and lower cervical spine,
includes the cervical spine from C3 to C7 and the craniovertebral junction
is excluded, as the anatomy and biomechanics of these two regions are
quite different.
•• The cervical region is the most vulnerable part of the spinal column due to
increased mobility, small vertebral bodies, oblique articular facets and the
mobility of the heavy skull on the cervical spine.
•• Subaxial spine injuries include musculoligamentous sprains, whiplash
injuries, traumatic disc prolapse, fracture dislocations, burst fractures,
locked facets, posterior element fractures, cord contusions and, rarely,
extradural haematoma and subdural haematoma.
•• Spinal cord injury without radiological abnormality (SCIWORA) is seen in
children who have a more elastic spine.
•• Patients with congenitally narrow canals (<13 mm) are more predisposed
to neural injury. Patients who have connective tissue abnormalities,
e.g. Down’s syndrome, collagen disorders, diffuse idiopathic skeletal
hyperostosis (DISH) and fluorosis have more serious injuries.
ANATOMICAL CORRELATES OF THE

SUBAXIAL CERVICAL SPINE
•• The subaxial cervical spine includes the vertebral bodies, upper and lower
articular processes, pedicles, lamina, a bifid spinous process, transverse
processes and a uncinate process which forms the uncovertebral joint.
•• The vertebral body height increases from C3 to C7 with a slight reversal
of this relationship at C6.
•• Each body has an uncus; laterally is the ventral ramus of the transverse
process and dorsolaterally the pedicle.
•• The uncovertebral joints prevent excess lateral translation and allow for
coupled lateral bending and rotation of the cervical spine.
•• The lateral surface of the pedicle, the dorsal surface of the anterior
tubercle and the ventral surface of the posterior tubercle form the foramen
transversarium, which transmits the vertebral artery.
•• The lower subaxial spine, especially the C6-7 vertebrae, is exposed to great
axial compression and flexion loads due to its location, and the transition
between a very mobile cervical and a rigid thoracic spine.
•• The longus colli muscles diverge laterally, whereas the sympathetic trunks
converge medially at C6.
372
•• As the transverse foramen or uncovertebral joint is exposed with dissection

or transverse severance of the longus colli muscle at the lower cervical
levels, the sympathetic trunk should be identified and protected.
•• The intervertebral foramen contains the exiting nerve root and is related
anteriorly to the lateral portion of the intervertebral disc and the uncover-
tebral joints, superiorly and inferiorly to the pedicles and posteriorly to the
lateral masses.
•• The exiting root corresponds to the lower vertebra (C6 root exits the C5-6)
foramen.
•• The ligamentum nuchae is attached to the external occipital protuberance
and ends at the spinous process of C7; it limits excessive flexion of the
cervical spine.
•• The flexion-extension movements have a range of 65–75 degree and
translation is restricted to 2–3 mm.
•• The cervical disc has an average height of 4 mm anteriorly and this reduces
to 2.5–3 mm posteriorly.
MECHANISMS AND TYPES OF INJURY

•• Subaxial cervical spine injuries are common and range in severity from
minor ligamentous strain to complete fracture dislocation with osseous and
ligament injury, and severe spinal cord injury (SCI).
•• Pre-existing lesions like haemangiomas of the bone, osteoporotic or
sclerotic spine due to ageing, spondylotic myelopathy, DISH, ossification
of the posterior longitudinal ligament (OPLL) and ankylosing spondylosis
(AS) cause a spectrum of injuries.
•• A whiplash injury is commonly seen in motor vehicle accidents and presents
with nagging neck pain, radiculopathy, and rarely, myelopathy, and also
a non-specific post-traumatic concussional syndrome is often associated.
•• AS, DISH, OPLL and fluorosis are disorders characterised by abnormal
ossification of the spinal column which predisposes these patients to spinal
injuries with potentially devastating consequences.
•• Subaxial cervical spine injuries are divided into stable or unstable injuries.
•• Instability exists, if there is greater than 3.5 mm of translation or greater than
11 degree of angulation changes as compared to other segments.
•• The degree of ligamentous injury on magnetic resonance imaging (MRI)
correlates with instability in patients with lateral mass facet fractures, with
rupture of multiple ligaments including the anterior longitudinal ligament,
posterior longitudinal ligament, interspinous ligament, or facet capsule.
•• Patients with congenitally narrow canals and those with less than 13 mm length
of the sagittal canal are predisposed to neurological injury.
CLASSIFICATION OF SUBAXIAL
CERVICAL SPINE INJURIES
•• Allen, et al in 1982, put forward a mechanistic classification of middle and
lower cervical spine injuries and subdivided them into eight groups based
on a force vector (initial dominant force) and resultant injury based on the
three-dimensional position of the spine at the instance of failure.
•• Patel reviewed the subaxial injury classification (SLIC) and severity score
SLIC system, which identify three major injury characteristics to describe
subaxial cervical injuries:
–– Injury morphology
Chapter 47 • Injuries of Subaxial Cervical Spine
373
–– Discoligamentous complex integrity

–– Neurological status.
•• The common injuries of the subaxial spine are compression flexion, com-
pression extension and distraction flexion injuries.
•• Vertical compressions are of intermediate frequency and lateral flexions
are the least frequent.
Flexion Injuries
•• These form about 15% of injuries of the subaxial cervical spine and usually
result due to fall from a height, diving into shallow water or empty pools
and road traffic accidents.
•• Flexion-Compression Injuries:
–– These represent a spectrum of spinal injuries with simple vertebral
body compression fractures and injuries that result in the triangular
“teardrop” fracture or a “quadrangular” fracture with posterior ligamen-
tous disruption.
–– The most severe injury is posterior subluxation of the posterior verte-
bral body into the canal, causing acute kyphosis and disruption of the
ALL, PLL and posterior ligaments.
–– The SCI in these compressive flexion injuries range from 0 to 91% in
the most severe cases.
–– Posterior element fractures occur in up to 50% of these cases and pure
ligamental injury is usually rare.
•• Tear drop fractures are serious injuries and patients are seen with complete
spinal injury or central cord syndrome.
•• There is a fracture of the vertebral body in the sagittal plane and retrolisthesis
of the vertebrae and these require to be differentiated from simple avulsion
fractures. These have associated facet joint and discoligamental injuries.
•• Quadrangular fractures are characterised by oblique vertebral body fracture,
subluxation, angular kyphosis and discoligamental injury, and are unstable.
•• Flexion-Distraction Injuries:
–– These injuries represent a spectrum of pathologies from mild posterior
ligamentous sprains to bilateral facet dislocations (locked or jumped
facets).
–– These are the most common injury patterns in Allen and Ferguson’s
classification (Table. 1).
–– They include subluxation injuries and dislocation injuries.
•• Beatson classified facet dislocation injuries into four stages of progression:
–– Posterior ligament strain with facet subluxation and interspinous
widening and rounding of the anterior-superior aspect of the caudal
vertebral body.
–– Unilateral facet dislocation, with varying degrees of posterior
ligamentous injury.
Table 1: Allen and Ferguson’s subaxial cervical spine classification

Compression injuries I. Anterior II. Comminuted III. Tear drop fracture
compression fracture
Flexion-extension- I. Moderate sprain II. Severe sprain III. Bilateral fracture
distraction injuries dislocation
Rotation injuries I. Unifacet fracture II. Fracture separation III. Unilateral disloca-
(UFF) of the articular pil- tion (UD)
lar (FSAP)
374
–– Bilateral facet dislocations.

–– Complete anterior subluxation of the rostral vertebral body.
•• Dislocation injuries: These include unilateral and bilateral facet
dislocations.
–– Unilateral facet dislocations: These are caused when there is flexion
and a rotational vector acting together and facet fracture dislocations
represent the next pattern seen in the spectrum of injury.
–– They typically present with translation of 25% of one vertebral body on
another and have a pathognomonic “sail” or “bow tie” sign on lateral
X-rays.
–– The C6-7 is the level most commonly involved, and patients present
with radiculopathy and SCI.
–– Bilateral facet dislocations: These dislocations have a higher in-
cidence of neurological injury. These injuries require reduction with
traction or internal reduction and may have associated large anterior
disc prolapse.
Vertical Compression Injuries

•• Vertical compression injury to the subaxial cervical spine results in the
cervical burst fracture.
•• These burst fractures are subdivided into three categories of severity.
•• They are classified as the most severe pattern in the Allen and Ferguson’s
vertical compression phylogeny and are classified as A3 lesions in the
AO classification; they represent about 10% of all subaxial cervical spine
fractures.
•• Axial loading of the cervical spine causes compression of the vertebral
body and the posterior wall retropulses into the canal causing neural injury.
•• These can be associated with posterior ligamentous injury when there is
an associated flexion component of the injury force.
Extension Injuries
•• These were described by Taylor and Blackwood.
•• These represent approximately 8% of all subaxial cervical spine injuries
and two stages have been described:
1. Stage I injury is disruption of the anterior longitudinal ligament without
posterior displacement and is seen on imaging as abnormal widening
of the disc space due to the ALL and disc injury.
2. Stage II injury is when both the posterior ligaments and the anterior
ligaments are injured and the superior vertebra is retropulsed into the
spinal canal.
MANAGEMENT
Intensive Care and Initial Management
•• Management of spinal injuries is begun by taking an accurate clinical
history, and doing a complete general and neurological examination
including motor, sensory and autonomic systems using the American Spinal
Injury Association (ASIA) score.
•• The clinical evaluation then guides an appropriate radiological evaluation
protocol.
375
•• All trauma patients should be immobilised at the scene of accident and

during transport with a combination of a rigid cervical collar and supportive
blocks on a backboard with straps.
•• Use of cardiac, haemodynamic and respiratory monitoring devices, to
detect cardiovascular dysfunction and respiratory insufficiency in patients
after acute cervical SCI, is essential.
•• Hypotension (systolic blood pressure <90 mmHg) should be avoided, if
possible, or corrected as soon as possible after acute SCI.
•• Maintenance of mean arterial blood pressure at 85–90 mmHg for the first
7 days after acute SCI is required to improve spinal cord perfusion.
Steroids
•• Treatment with methylprednisolone for either 24 hours or 48 hours
immediate post-trauma is recommended as an option in the treatment of
patients with acute spinal cord injuries that should be undertaken only with
the knowledge that the evidence suggesting harmful side-effects is more
consistent than any suggestion of clinical benefit.
Venous Thromboprophylaxis
•• Low molecular weight heparin was more effective in the prevention of deep
vein thrombosis, with fewer bleeding complications, than un-fractionated
heparin.
•• The use of vitamin K antagonists appeared to be effective for the prevention
of pulmonary embolism.
EXAMINATION
•• The instability of the cervical spine is picked up by the clinical signs of
radiculopathy, neck pain or myelopathy.
•• In clinical practice, the presence of instability can be inferred from an
abnormal position of the neck, injury signs, like bruises and rope marks,
and spinal deformity and tenderness are obvious pointers to an occult injury
to the subaxial cervical spine.
INVESTIGATIONS
•• Usually static X-rays, computed tomography (CT) scans, MRI scans or,
very rarely, a myelogram is done.
•• In patients with cervical pain and those who do not have any radiculopathy
or myelopathy, instability can be confirmed by dynamic imaging (flexion
and extension views).
•• Bono et al have attempted consensus in techniques of measurement of
kyphosis (Cobb angle and posterior vertebral body tangent methods);
vertebral body translation; vertebral body height loss; maximal spinal canal
compromise and spinal cord compression; facet fracture fragment size and
percentage of facet subluxation.
•• Digital X-rays are taken with the shoulders pulled down to visualise up to C7.
•• A swimmers view may be necessary, if there is suspicion of injury to the
C7-T1 region, clinical signs of progression or development of radiculopathy
or myelopathy.
•• This is followed, if necessary, with CT to define areas that are suspicious
or not well-visualised on the plain cervical X-rays.
376
•• Immobilisation in awake/conscious patients can be discontinued after either:

a. normal X-ray or adequate dynamic flexion/extension radiographs with
no evidence of movement or
b. a normal MRI study which is obtained within 48 hours of injury.
•• Cervical spine immobilisation in obtunded patients may be discontinued
if there is:
–– Normal cervical spine X-rays (including supple mental CT as neces-
sary)
–– Normal dynamic flexion/extension studies performed under fluoro-
scopic guidance
–– After a normal MRI study is obtained within 48 hours of injury
–– At the discretion of the treating physicians.
•• Static X-Rays: Proper interpretation of lateral cervical spine X-rays is very
important and it remains an essential diagnostic.
•• Dynamic X-Rays: Flexion-Extension Views: Flexion/extension cervical
X-rays or fluoroscopy may be considered to exclude gross ligamentous
instability when there is a suspicion of cervical spine instability after static
X-rays are obtained.
•• Computerised Tomography:
–– Cervical CT scan is a very efficient imaging modality in picking up bony
injuries, having a sensitivity of 100%.
–– CT scans are useful in studying and measuring kyphosis (Cobb angle
and posterior vertebral body tangent methods), vertebral body transla-
tion, vertebral body height loss, maximal spinal canal compromise and
spinal cord compression, facet fracture fragment size and percentage
of facet subluxation.
•• Magnetic Resonance Imaging:
–– MRI of the cervical spine may also be considered to exclude cord or
nerve root compression, evaluate ligamentous integrity, or provide
information regarding neurological prognosis.
–– The presence of injury to at least three ligaments, like those of the facet
capsule, interspinous ligament and either of the longitudinal ligaments,
may be related to instability in unilateral facet fractures.
–– The MRI was superior to CT for assessment of the extent of soft-tissue
injury and for identification of spinal cord injuries and intracanalicular
haemorrhage in patients with more severe trauma.
–– The MRI is an excellent means of assessing ligamentous disruption,
disc herniation and compression of the neural elements.
–– The vertebral arteries are seen as regions of signal voids, and MR
angiography and CT angiography may aid in picking up vertebral artery
injuries and carotid injuries.
TREATMENT
Conservative
•• Many injuries of the subaxial cervical spine without significant discoligamental
injury, fracture or dislocation can be managed conservatively using orthoses
like the soft cervical collar, Philadelphia collar, Guilford brace, sternal
occipital mandibular immobiliser (SOMI) brace and the Yale brace.
•• But these patients must be followed up with great caution, and patients with
SCIWORA and sports related injuries, like spinal concussion, spinal cord
neuropraxia and burning hands syndrome, may be advised avoidance of
high-risk activities for up to 6 months after the injury event.
377
Axial Controlled Traction

•• Traction can be used with caution to re-align and maintain the alignment,
usually following an MRI prior to this, as nearly 80% of bilateral locked
facets will have an associated post-traumatic disc prolapse.
•• Early closed reduction of cervical spine fracture dislocation injuries with
craniocervical traction is recommended to restore anatomic alignment of
the cervical spine in conscious/awake patients.
•• Closed reduction in patients with an additional rostral injury is not
recommended.
•• The presence of a significant disc herniation in this setting is a relative
indication for a ventral decompression before reduction.
•• MRI study of patients who fail attempts at closed reduction is also
recommended.
Halo
•• The use of the halo has been increasingly questioned as an immobilisation
technique in cervical trauma due to reports of high complication rates and
unacceptable treatment results.
•• Their use is associated with several complications like infection, pin
loosening, dysphasia, skull and dural penetration, and pressure ulcers.
Guidelines for Surgery

Subaxial Cervical Facet Dislocation Injuries
•• Closed or open reduction of subaxial cervical facet dislocation injuries is
recommended.
•• Treatment of subaxial cervical facet dislocation injuries with rigid external
immobilisation, anterior arthrodesis with plate fixation, or posterior
arthrodesis with plate or rod or interlaminar clamp fixation is recommended.
•• Treatment of subaxial cervical facet dislocation injuries with prolonged bed
rest in traction is recommended, if more contemporary treatment options
are not available.
Subaxial Cervical Injuries Excluding

Facet Dislocation Injuries
•• Treatment of subaxial cervical spinal injuries with external immobilisation,
anterior arthrodesis with plate fixation, or posterior arthrodesis with plate
or rod fixation is recommended for patients with fracture dislocation without
facet dislocation.
•• Closed reduction is successful for most patients with subaxial cervical spine
fracture dislocation injuries.
•• Closed reduction is usually not successful with facet dislocation injuries
and may be injurious when there is a large disc prolapse.
LATERAL MASS FRACTURES

•• Lateral mass fractures are divided into the following four subtypes by
Kotani et al:
–– Separation
–– Comminution
–– Split
–– Traumatic spondylolysis.
378
Burst Fractures
•• Burst fractures of the subaxial cervical spine are common as described
earlier and usually involve the C6-7 vertebrae depending upon the amount
of canal compromise and reduction in vertebral body height.
•• These are usually operated upon by an anterior cervical approach and
median vertebrectomy is done to decompress the cord followed by iliac
crest graft and anterior plate fusion.
•• These may be associated with injury to the vertebral arteries.
Laminar Fractures
•• Laminar fractures are rare and, unless causing cord pressure, are managed
conservatively.
•• These may also be associated with posterior ligamental injury and, if there
is evidence of instability, posterior single stage decompression, and lateral
mass screw and rod fixation can be done.
Management
•• There are four general indications for spinal stabilisation as outlined by
White and Panjabi:
–– To restore clinical stability to a spine in which the structural integrity
has been compromised
–– To maintain alignment after correction of a deformity
–– To prevent progression of a deformity
–– To alleviate pain.
•• A patient was considered to have an unstable injury, if he had five points
or more in the White and Panjabi instability checklist.
•• Surgery may consist of:
–– Anterior instrumentation
–– Posterior instrumentation
–– Combined anterior and posterior approaches
–– Circumferential fusion.
OUTCOME
•• Radiographic outcomes include fusion scores and sagittal alignment
measurements.
•• Outcome scores with respect to neck pain, satisfaction with surgery and
function are recorded for each patient (Table. 2), according to analog pain
and satisfaction scales and the neck disability index.
Functional Outcome Assessment

•• The functional independence measure and modified Barthel index are
recommended as the functional outcome assessment tool for clinicians
involved in the assessment and care of patients with acute spinal cord injuries.
Table 2: Odom’s criteria of scoring

Excellent: All preoperative symptoms relieved; abnormal finding improved
Good: Minimal persistence of preoperative symptoms; abnormal findings unchanged or improved
Fair: Definite relief of some preoperative symptoms; other symptoms unchanged or slightly improved
Poor: Symptoms and signs unchanged or exacerbated

379
COMPLICATIONS
•• Complications in subaxial cervical spine trauma can be classified as both
intra-operative and post-operative, and both the patient and surgeon can
be the variables involved.
•• Other complications commonly encountered are implant failure like screw
back-out, poor purchase due to the screws being in the disc space rather
than the body and, rarely, screw breakage.
•• Post-operative haematoma, misplaced implant and retraction injury can
cause dysphagia and, rarely, respiratory distress.
•• Others include carotid artery injury, vertebral artery injury, injury to the
spinal cord and roots, injury to the recurrent laryngeal nerve, Injury to the
sympathetic trunk.
48
CHAPTER
Whiplash Injury
Harjinder S Bhatoe
INTRODUCTION
•• Acceleration injury or whiplash injury of the neck refers to the cluster of
symptoms following application of a propulsive force to the head and neck
complex.
•• Acceleration injury on the other hand is called neck sprain, whiplash or
soft tissue neck injury.
•• The mechanism is universally similar—rear-end impact to the body in
motion as the neck is unsupported.
MECHANISM AND PATHOLOGY

•• Whiplash injury has been simulated in several experimental studies.
•• McNab suspended anaesthetised monkeys with their head and neck
unsupported and dropped them from a height; the drop was arrested short
of ground impact, simulating neck hyperextension.
•• In a similar study, Clemens and Burrows, studied the mechanics using
embalmed cadavers subjected to rear-end impacts producing 13−16 G
forces.
•• Both these studies reported minor injuries to the sternocleidomastoid, partial
avulsion of the longus colli and retropharyngeal haematomas.
•• The most common findings were intervertebral disc failure and tears of the
anterior longitudinal ligament, found in nearly 90% of cases. These findings
have been confirmed on autopsy studies.
•• Taylor et al identified three patterns of injury to the intervertebral disc:
1. Anterior rim lesion—There are linear clefts in the peripheral cartilage
plate in the region where this cartilage is continuous with the fibrous
annulus. The anterior longitudinal ligament is intact and cervical spine
alignment is normal on radiographs.
2. Posterior contusions and herniation of intervertebral discs.
3. Partial or complete avulsion along the disc-vertebral interface—Usu-
ally seen in children. MRI shows high signal intensity on T2-weighted
images. It is important to recognise ligamentous injury, since there is
potential for segmental instability.
•• Initially, the upper cervical spine as well as the lower cervical spine
hyperextends converting the cervical spine to an ‘S’. Milliseconds later,
this is followed by hyperextension of the entire cervical spine. Injury is
sustained in the first phase (Fig. 1).
Chapter 48 • Whiplash Injury
381
Fig. 1: Diagrammatic representation of pathology of cervical spine accelera-

tion injury. (A) Fracture involving the epiphyseal surface. (B) Avulsion of epi-
physeal plate. (C) Anterior annular tear. (D) Transverse rupture of interver-
tebral disc. (E) Fracture of apophyseal joint. (F) Articular pillar fracture. (G)
Zygapophyseal joint capsule injury and (H) Posterior disc herniation.
CLINICAL PROFILE
•• The clinical picture of acceleration injury is dominated by neck pain, which
is accentuated on movement.
•• This is accompanied by other symptoms (Table 1), many of which are
poorly explained.
•• Clinical examination reveals restriction of neck movements, spasm of
paraspinal neck muscles and tenderness over the posterior neck muscles.
•• Neurological examination is normal.
•• Cervical spine radiographs are usually normal, except for loss of
physiological lordosis.
•• The symptoms persist for more than 1 year in about 88%, and more than
2 years in 64% of patients.
•• A severe injury in the elderly may rarely be complicated by oesophageal
rupture and mediastinitis.
•• Cognitive dysfunctions are the least understood aspect of cervical spine
acceleration injury. Broadly, these dysfunctions fall in two categories:
1. Cervicocephalic syndrome: There is demonstrable abnormality of
auditory and visual information processing, mood changes, sleep
disturbances, psychoneurotic reaction, depression and “litigation
neurosis.
2. Lower cervical spine syndrome: In addition to painful symptoms
pertaining to the cervical spine, there is disturbance in visual informa-
tion processing.
Table 1: Complex symptoms in whiplash injury

Neck and shoulder pain
Occipital headache
Arm pain/dysaesthesiae
Vertigo
Tinnitus
Temporomandibular joint pain
Depression
Anxiety
382
IMAGING
Cervical Spine Radiographs
•• Dynamic radiographs of the cervical spine show restriction of motion at
one level, and loss of the normal lordotic curve.
•• Prevertebral swelling is variable.
•• Degenerative changes pre-existing at the time of initial presentation are
likely to be associated with persistence of symptoms.

•• Many of the changes produced by acceleration injury can only be revealed
by MRI.
•• These changes affect the anterior column, and are seen as disruption of
the anterior longitudinal ligament, anterior annular tears, occult vertebral
end-plate fractures, acute cervical disc herniation, zygoapophyseal joint
injury, etc.
MANAGEMENT
•• Management depends upon the severity of the problem, and patients with
intense symptoms may require hospitalisation.
•• Usual treatment consists of analgesics, cervical collar, rest, muscle relaxant
and anti-inflammatory medication.
•• Narcotic analgesics may be required to interrupt the “pain-spasm” cycle.
•• Trigger point injections and epidural blocks may be required in refractory
cases.
•• Surgery is reserved for those with disc avulsion, especially with pre-existing
degenerative disc disease. These patients require discectomy with fusion.
49
CHAPTER Thoracic and
Thoracolumbar Injuries
EPIDEMIOLOGY AND AETIOLOGY

•• Thoracic and lumbar injuries accounted for 75% of all spine injuries.
•• The most commonly fractured level in the whole spine is L1, followed by
T12.
•• The vulnerability of the T12-L1 region is ascribed to the change from a
kyphotic curve of the relatively immobile thoracic spine to a lordotic one in
the mobile lumbar spine.
•• Spinal trauma is, world over, commoner in males and the gender bias is
more pronounced in India.
•• The mean age of occurrence is 35 years and the median age group 20−29
years.
•• A second peak is seen in the elderly due to osteoporotic vertebral fracture.
•• Fall from height is commoner cause than road traffic accidents in most
Indian series. Falling from trees, electric poles, staircases, ladder, upper
storeys of houses and construction sites account for about 50% of all
spine injuries.
•• Sporting activities associated with spine injury in India include wrestling
and bull fighting.
•• Diving, horse riding, skiing, pole vaulting, gymnastics, motor sports and
altitude sports are common causes in other nations.
CLASSIFICATION
•• The major classification systems are presented in Table 1.
•• Kelly and Whitesides introduced the two-column model in 1968 (Fig. 1).
•• The concept of stable and unstable fracture was better defined.
•• The introduction of axial CT made it possible to see burst fractures and
sagittal body fractures.
•• Denis brought out the importance of the osteoligamentous middle column
made up of the posterior wall of the vertebral body, the posterior longitudinal
ligament and posterior annulus fibrosus (Fig. 1).
•• He classified wedge compression fractures into anterior and lateral types.
•• The burst fractures are divided into five subtypes in the Denis system,
based on the additional force involved, apart from the axial load that is
common to all burst fractures.
–– Type A—Involves both endplates (pure axial load)
–– Type B—Only the superior endplate
–– Type C—Only the inferior endplate (axial load plus flexion in B and C)
Table 1: Classification schemes of thoracic and lumbar spine injuries
384
Holdsworth 1953 Kelly & Whitesides 1968 Denis 1983 McAfee 1983 Magerl 1994 TLICS 2005
Flexion-compression Two column concept Three column concept Wedge compression Type A-Compression Morphology
Flexion-dislocation Stable fractures Minor injuries (isolated AC flexion A1 Compression
(disc and posterior fractures of the transverse pro-
igaments ruptured) cess, spinous process, facets,
pars interarticularis, lamina)
Wedging fractures Stable burst fracture A2 Translation-rotation
AC & MC compression A3 distraction
Flexion-torsion Anterior wedging (flexion injuries) Unstable burst fracture Type B-Distraction Integrity of PLC***
(fracture-dislocation)
Lateral wedging AC & MC compression B1 Intact
Stable burst injuries Major injuries PC compression, lateral B2 Disrupted
Unstable injuries Compression: AC** flexion and rotation B3 Indeterminate
Flexion dislocation (Fracture usually present) Burst fractures: AC, MC Chance fracture Type C-Rotation Neurological state
Flexion-rotation Seat belt injury: MC, PC All 3 columns flexion C1 Intact
Cauda equina injury Fracture dislocations: but axis anterior to AC C2 Nerve root injury
(Fracture-dislocation/ “Slice” injuries) (all 3 columns) Flexion-distraction injury C3

Unstable burst See text for details of AC compression, MC & PC flexion (see Fig. 3 for Incomplete cord
subtypes details) injury
Translational injury Complete cord in-
jury
All 3 columns and lateral displace-
ment (see Fig. 2 for examples)
Note:
*TLICS = Thoracolumbar Injury Classification System of Spine Trauma Study Group
** AC = Anterior Column, MC = Middle Column, PC = Posterior Column
***PLC = Posterior Ligament Complex
Chapter 49 • Thoracic and Thoracolumbar Injuries
385
–– Type D—Additional rotation

–– Type E—Additional lateral flexion.
•• The Magerl scheme follows the general principles of Arbeitsgemeinschaft
für Osteosynthesefragen (AO) nomenclature.
•• There are three basic types of injuries:
1. Vertebral body compression
2. Anterior or posterior element distraction
3. Rotation plus type A injury (C1), rotation plus type B injury (C2) and
rotation with shear (C3).
•• These are illustrated in Figure 2. Magerl’s system is widely used in
Europe.
Fig. 1: Diagram showing the Kelly and Whitesides two-column model on the
left and the Denis three-column model on the right
Fig. 2: Magerl’s AO classification of thoracolumbar fractures

(modified from Cassar-Pullicino and Imhof)
386
ASSOCIATED INJURIES
•• Thoracic and lumbar spinal injuries may be associated with another spinal
injury such as an upper cervical spine injury.
•• Rib fractures, haemothorax and lung contusions are common with severe
thoracic spine injuries and they may be missed or picked up only after a
delay in a paraplegic patient.
•• Splenic, hepatic and renal injuries associated with spine fracture are
commoner with motor vehicle accidents than with falls.
PREDISPOSING FACTORS
•• Conditions that weaken the bone, increase the fracture risk.
•• The most important predisposing factor for thoracic and lumbar fractures
is osteoporosis.
•• Pathological fractures are also seen associated with myeloma, metastasis
or tuberculosis.
•• These patients may present with sudden paraplegia after trivial trauma.
•• Conditions that cause narrowing of the spinal canal include congenital or
degenerative thoracic canal stenosis, achondroplasia, ossification of the
posterior longitudinal ligament and ossification of the ligamentum flavum.
CLINICAL FEATURES AND ASSESSMENT

•• Pain is the commonest presenting symptom of thoracic or lumbar spine
injury.
•• Young children, patients with obtundation due to head trauma or ethanol
effect and those with minor fractures may not complain of spinal pain in
the casualty department.
•• A bruise over the back, a fluctuant haematoma or a tender gibbus may be
palpable, but only on turning the patient over—a manoeuvre that is often
sadly missed by doctors in the emergency room.
•• Conus and cauda injuries might present with isolated inability to void urine
in a patient who comes walking in.
•• Neurogenic shock, manifested by the triad of hypotension, bradycardia
and hypothermia may be seen in injuries above T6. It is due to disruption
of the thoracolumbar sympathetic outflow and unopposed vagal action.
•• Neurological syndromes seen are root injury, cauda equina syndrome,
incomplete cord lesion and complete cord injury.
•• Note that the American Spinal Injury Association (ASIA) guidelines
(International Standards for Neurological Classification of Spinal Cord
Injury—ISNCSCI) define complete cord injury as absence of sensory and
motor functions in the lowest sacral segments.
•• The completeness of the cord injury can be confirmed only after spinal
shock passes off.
•• Spinal shock can be taken to have passed when the anal or bulbocavernosus
reflexes reappear.
•• Anterior and central cord syndromes, seen commonly with cervical spinal
trauma, are not generally seen in thoracic trauma.
•• Brown-Sequard like syndrome might be seen in non-missile penetrating
trauma.
•• It is well to remember that the spinal fracture may be anywhere above the
highest neurological level of involvement in incomplete cord injury.
387
Table 2: Modified Frankel scale

A No neurological function, complete paralysis
B Preservation of sensory function below injury level
C Inadequate motor function below injury level
Da Allowing ambulation with assistance
Db Self ambulation with minor difficulty
E Normal neurological status
•• With complete injury, the rule of minus 2 in the upper thoracic and minus
3 in the lower thoracic spine holds. For example, if the patient has the
highest neurological level of impairment at T6, the vertebral lesion is likely
to be at T4; neurological impairment at T12 indicates T9 vertebral injury.
•• Though the modified Frankel scale (Table 2) is the most widely used one
for assessment because of its simplicity, it has its demerits.
IMAGING
Plain Radiography
•• A normal looking radiograph does not exclude spinal injury particularly in
children and so further studies are warranted, if there is clinical suspicion
of spinal injury.
•• Spinal cord injury without radiographic abnormality (SCIWORA) in the thoracic
region is mainly seen in the paediatric spine that bends but does not break.
•• Thoracic SCIWORA may be due to high-speed direct impact, distraction
from seat belts and run-over when the child is in the prone position.
•• Conversely, one occasionally sees a patient with a gross thoracic fracture
dislocation without any neurological impairment. Such a phenomenon has
been ascribed to the decompressive laminar fractures, but a congenitally roomy
canal and absorption of the impact energy by bone and ligaments might also
protect the cord. The situation may be analogous to a vehicle crash, where the
front of the car is badly crushed but the occupants escape unhurt.
COMPUTERISED TOMOGRAPHY SCANNING

•• CT is the best method of identifying canal compromise.
•• The axial transverse canal area might correlate better with neurological
state than the mid-sagittal diameter or percentage patency in thoracolumbar
burst fractures.
•• The Spine Trauma Study Group suggests measuring the sagittal-to-
transverse canal diameter ratio, canal total cross-sectional area and the
per cent canal occlusion, to assess canal dimensions.
•• Generally, less than 30% canal narrowing is not associated with neurologi-
cal deficit but more than 50% is almost invariably accompanied by deficit,
at least at the L1 level.

•• The prevertebral and paravertebral soft tissues, discs, ligaments and spinal
cord are best assessed by MRI.
•• Minor fractures missed on radiographs may be suspected from MR by the
associated marrow oedema and ‘bone bruise’.
388
•• Acute Schmorl’s nodes form due to endplate fracture that allows the disc
material to herniate into the vertebral body. These are common in the
T8-L1 region and are well imaged by MR.
•• Rupture of the anterior and posterior longitudinal ligaments, disc disruption
and shearing of the subepiphyseal growth zone of the vertebral endplates
are demonstrable by MRI in paediatric patients with SCIWORA. These
are markers for occult instability and indicate the need for spinal bracing.
•• The ‘sandwich sign’ of linear haemorrhage in the posterior neural arch
framed by marrow oedema has been observed in Chance fractures.
These flexion-distraction injuries are also associated with a severe soft
tissue injury.
•• The spinal cord abnormalities seen in MRI are complete transaction, major
or minor haematomyelia and oedema.
•• A vascular aetiology has been proposed to explain the delayed ascending
myelopathy.
•• Post-traumatic syringomyelia is seen months or years after trauma. T2
hyperintense signal around the cranial border of the post-traumatic syrinx
indicates progression.
CONCEPT OF INSTABILITY
•• Instability is defined as the inability to limit excessive spinal displacement.
•• Acute instability that results from trauma may be overt or limited.
•• Overt instability is the circumferential loss of spinal integrity resulting in the
inability to support the torso during all normal activities.
•• Limited instability is the loss of either ventral or dorsal integrity with the
preservation of the other.
•• Denis described three degrees of instability:
1. Mechanical (first degree) instability that results in progressive kyphotic
deformity
2. Neurological (second degree) instability that carries the risk of neuro-
logical compression
3. Combined (third degree) instability that has both the above components.
•• Table 3 gives a simple method of quantifying the instability, so as to clarify
the situation in the grey areas mentioned above.
•• The Spine Trauma Study group advocates the measurement of the Cobb
angle (to assess sagittal alignment), vertebral body translation percentage
(to assess traumatic anterolisthesis) and anterior vertebral body compres-
sion percentage as indicators of instability.
•• Loss of vertebral body height by more than 50% and kyphotic deformity of
20° or more are considered signs of instability.
Table 3: Quantifying thoracolumbar instability. If the score is > 5, overt insta-

bility and if it is 2−4, limited instability exists (modified from White & Panjabi)
Factors taken into account Points
Loss of integrity of the anterior (and middle) column 2
Loss of integrity of the posterior column 2
Resting sagittal or coronal plane translation 2
Resting sagittal plane rotation (angulation) 2
Cauda equina (3), spinal cord (2) or root (1) injury 3
Dangerous loading anticipated 1
389
MANAGEMENT
Triage Care
•• The initial goals of resuscitating polytrauma patients must vigorously be
pursued in the spine-injured patient.
•• It is necessary to have appropriate oxygenation and perfusion pressures
to prevent a secondary damage to the injured cord.
•• A major chest or abdominal injury takes precedence over spine injury.
•• Methylprednisolone use is recommended by the National adult social care
intelligence service (NASCIS) 3 guidelines as a standard of care but niggling
doubts remain over the study.
Non-surgical Management
•• Most minor fractures require nothing more than rest and analgesics.
•• The duration of bed rest has come down over the decades, from months
to days.
•• Spinal bracing is popular but its utility remains unproved.
•• Anterior (hyperextension) braces are preferred for thoracolumbar junction
fractures.
•• Isolated fractures of the transverse process or spinous process and most
stable wedge compression fractures can be treated thus.
•• Non-operative treatment of burst fractures can be attempted only if the
patient is neurologically well preserved, the alignment is acceptable (initial
or after postural reduction) and there is no PLC disruption.
•• Conservative treatment is also indicated for those in whom spine surgery
is contraindicated (haemodynamic instability, severe head injury, sepsis
or medical comorbidities).
Surgical Management
Goals of Surgery
•• The twin goals of surgery in thoracolumbar fractures are neural decompres-
sion and restoration/maintenance of spinal alignment.
•• Instrumented fixation and bone fusion are the techniques used to achieve
the latter aim.
•• Logically, achieving these twin goals should lead to greater neurological
recovery, prevent neural damage, permit earlier ambulation with a painless
spine and should prevent delayed deformity.
Decompression and Timing of Surgery in
Patients with Neurological Deficits
•• Decompression of the cord can be done directly (removing the bone pieces
in the canal) or indirectly through ligamentotaxis (by reducing the fracture,
the intact posterior longitudinal ligament pushes the fragments away from
the canal).
•• Table 4 presents the routes of decompression of the neural canal.
•• The proponents of decompression argue that continuing compression adds
to the cord damage. They hold that faster and greater neural recovery
results when the cord is decompressed.
•• They also contend that decompression reduces the incidence of delayed
pain.
390
Table 4: Methods of decompression and fusion for thoracolumbar injuries

Method Rationale and technique
Indirect Using ligamentotaxis to force the fragments out of the canal, on
reducing the fracture by postural methods or by long or short
segment posterior fixation
Direct Entails surgical removal of the bone pieces in the canal
Anterior This approach is anterior to the cord and exposes the anterolat-
eral part of the vertebral body. Safest for the cord.
Extended costo-extracavitary Same as ‘anterolateral decompression’ popular for transver-
approach sectomy or lateral spinal TB. Done through arched paramedian
incision, 7 cm of the rib and entire transverse process removed.
Through extrapleural space, the posterolateral part of the body
is exposed
Transpedicular Aims at creating a cavity in the mid-portion of the vertebral
body through bipedicular route, into which the retropulsed
fragments in the canal anterior to the cord can be pushed with
angled probes from either side and retrieved
Laminectomy Not to be used as a stand-alone procedure in trauma, especially
if there is anterior column injury
•• The main argument against decompression has been that there is no

large prospective randomised trial showing the benefit of decompression
in general and early decompression in particular.
•• Those against decompression feel that paralysis occurs at the moment of
injury and is not related to the position of the fragments of the fracture on
subsequent imaging.
•• The only consensus now is that patients who are progressively worsening
in their deficit, must be offered emergency surgery.
Treatment of Burst Fractures without Neurological Deficit
•• Burst fractures without neurological deficits pose three problems:
1. Pain at the fracture site that might continue unabated for months or
years
2. Delayed kyphosis and
3. Delayed neurological deficits due to stretch of the cord over an internal
gibbus.
•• Hence, several surgeons have advocated anterior and/or posterior surgery
for such lesions.
Available Options for Surgery
•• The types of available procedures for surgical stabilisation of thoracic and
lumbar fractures can broadly be categorised into long segment posterior
fixations, short segment posterior fixations or anterior fixations.
•• These are summarised in Table 5.
Posterior procedures:
•• It is likely that reducing the kyphosis by posterior instrumentation causes
the intact posterior longitudinal ligament to stretch and push the retropulsed
fragments into the body, thereby, effecting canal decompression without
direct surgical handling of the fragments.
•• CT has proved that this phenomenon of ligamentotaxis increases the
narrowed canal diameter in the short-as well as the long-term.
391
Table 5: Instrumented fixation for thoracic and lumbar fractures

Hook-rod systems
Harrington distraction
Wires-rod (Luque ‘L’/Hartshill rectangle) systems
Sublaminar wires
Spinous process wires— Drummond (Wisconsin)
Harrington distraction with sublaminar wires
Cotrel-Dubousset (CD) systems
Short segment posterior fixation
Pedicle screw-plate systems
Pedicle screw-rod systems
Screw-plate systems
Screw-rod systems
•• Generally, the posterior procedures are most effective in the acute stage
(within 72 hours) after trauma.
•• Though multiple segments are incorporated in long segment instrumentation,
the fusion is performed only at the level of the fracture.
•• Long segment instrumentation ultimately fails when bony union (by
spontaneous or surgical fusion) does not occur.
•• Short segment procedures are based on pedicle screw systems that can
theoretically provide three-column support to the spine.
•• Short segment instrumentation immobilises fewer segments, and hence,
causes less interference with whole spinal motion.
•• The pedicle screw used must be of the largest diameter that the pedicle
can take. A recent paper suggests that short segment fixation using pedicle
screws, 2 levels above and 1 below the thoracolumbar junction injury pre-
vents re-kyphosis and hardware failure while retaining the lumbar mobility.
Anterior procedures:
•• Anterior procedures offer the advantage of reconstructing and instrumenting
the anterior and middle columns.
•• They also offer the advantage of clearing the retropulsed fragments of bone
and disc without stressing the cord.
•• The flip side is that the procedure is more serious, involves more blood loss/
operating time and often needs the help of a thoracic or abdominal surgeon.
•• The complications of lung collapse/consolidation, pleural collection, ileus due to
retroperitoneal dissection, wound dehiscence and wound pain are significant.
•• The routes of anterior approach preferred are outlined in Table 6.
•• Anterior reconstruction began with strut bone grafts and went on to
incorporate anterior instrumentation.
•• Cages are substituting grafts.
Combined procedures:
•• Anterior and posterior procedures are considered for three-column injuries
so as to affect 360° fusion/stabilisation.
•• Anterior surgery can also be combined with posterior long segment fixation.
•• The two procedures can be done in a single session in a fit patient, but it
is prudent to stage the procedures 3−7 days apart.
•• Anterior augmentation with polymethylmethacrylate vertebroplasty after
short segment posterior fixation has recently been reported to be suc-
cessful for non-osteoporotic burst fractures.
392
Table 6: Routes of anterior approach to thoracic and lumbar spine injuries

Level of injury Approach of choice Comments
C7 toT2 Low anterior cervical for patients of Left side approach avoids recurrent
asthenic build Transmanubrioclav- laryngeal nerve injury, but carries
icular for corpulent patients risk of thoracic duct injury
T2 to T3 or T4 Right third intercostal space thora- Right side approach avoids the arch
cotomy of aorta and its branches that hinder
left side approach
T4 or T5 to T10 Left thoracotomy Approach through the intercostal
space that is in line with the targeted
vertebra at the midaxillary line
T11 to L1 Left thoracotomy, transdiaphragmat- Retroperitoneal space can be opened
ic retroperitoneal by either splitting the costal carti-
lage or by sweeping off the perito-
neum from the under surface of the
diaphragm after thoracotomy. Dia-
phragm is cut and repaired circum-
ferentially
L2 to L4 Left flank incision, retroperitoneal The lower the level, the more anterior
the incision extends
L5, S1 Midline transperitoneal ALIF retractors are very useful to
keep the abdominal
Paramedian retroperitoneal (mini- contents away and to increase space
ALIF approach) between iliac vessels
Decision Making
•• The questions to be answered while treating a thoracolumbar fracture are:
1. Whether to operate or not
2. When to operate (emergency/early/delayed) and
3. How to operate (route/level/decompression/fusion/instrumentation).
•• In order to answer these questions, the surgeon must take into account
several factors.
•• Age, general medical status, body weight and time since injury must be
factored in.
•• Associated injuries might impact the treatment plan.
•• The extent and evolution of neurological deficit matter much.
•• The level of the injury, the classification of injury, the scores and the load
sharing score profoundly influence the operative approach.
•• Finally, the experience of the surgeon and the availability/affordability of
instrumentation are germane issues.
•• Demonstrable neural compression with progressing deficit is the strongest
indication for decompression.
•• Canal compromise with incomplete cord injury, cauda equina syndrome or
severe pain is the next best indication.
•• In the face of complete SCI, issues of stability decide the surgery rather
than the canal compromise.
•• Since decompression procedures add to the instability, they are almost
invariably done along with an instrumentation/fusion procedure.
•• It must be emphasised that the decision has to be tailor-made to the
individual patient and type of injury.
50
CHAPTER Lumbar and
Lumbosacral Injuries
INCIDENCE
•• Sacral fractures are rare, accounting only for 1% of all spinal traumas.
•• In pedestrians struck by motor vehicles, spinal injuries are seen in 8%.
•• These spinal injuries are more or less evenly distributed in the spinal column
and 27% of these injuries affect the sacrum.
•• The sacrum completes the pelvic ring and sacral fractures are present in
about 45% of pelvic fractures.
CLASSIFICATION
•• The sacral fracture classification scheme of Schmidek, the sacral zones
of Denis and a morphological classification of transverse fractures are
given in Table 1.
•• A direct blow to the coccyx causes the low transverse fracture at S3 or
below, whereas the high transverse fracture at S1-2 level is due to indirect
trauma, transmitted through the pelvis.
•• Since most sacral fractures are vertically oriented and as the line of the
sacral foramina form a weak area, it is logical to divide the sacrum into
vertical zones:
–– Zone 1 fractures that are lateral to the foramina are caused by lateral
compression of the pelvis
–– Zone 2 fractures in the foramina by vertical shear and
–– Zone 3 fractures affect the sacral canal and are the least common, and
have the highest incidence of neurological damage.
•• The transverse fractures (5−15% of all sacral fractures) may affect all the
three zones.
•• Based on sagittal CT and lateral radiographs, the transverse fractures have
been classified into four types by Roy-Camille (Table 1).
•• Lumbosacral fracture dislocation follows one of the five types described
by Aihara.
•• The type 4 lumbosacral dislocation in the scheme (Table 1) has previously
been described as ‘acute traumatic spondylolisthesis’, but the former name
is more apt, considering the amount of anterior and posterior ligament
damage in this unstable injury.
CLINICAL FEATURES
•• Sacral fractures are missed or only detected after a delay in 30% of patients.
•• This is especially true for sacral insufficiency fracture that occurs in the
osteoporotic elderly patients after a trivial fall.
394
Table 1: Schemes of classification of sacral fractures

Schmidek (1984) Denis (1988)3 Root damage
classification classification
Direct trauma Zone 1 (alar zone) L5 partial in 6%
Penetrating Zone 2 (foraminal zone) Sciatica in 28%
Comminuted Zone 3 (sacral canal zone) Saddle anaesthesia and
sphincter dysfunction in
57%
Low transverse
Indirect trauma
High transverse
Type I
Type II Morphological
classification of
transverse fractures
Type III H shaped
Vertical U shaped
Lateral mass T shaped
Juxta-articular l shaped
Cleaving
Avulsion
Roy Camille (1985) classification of sacral transverse fractures
1. Kyphotic angulation
2. Partial anterior translation
3. Complete anterior translation
4. Burst fracture
Aihara (1998) classification of lumbosacral dislocation
Type 1: Unilateral L5-S1 facet dislocation with or without facet fracture
Type 2: Bilateral L5-S1 facet dislocation with or without facet fracture
Type 3: Unilateral L5-S1 facet dislocation with contralateral facet fracture
Type 4: Bilateral L5 pars interarticularis fracture with dislocation of L5 body
Type 5: Fracture of L5 body or pedicle with dislocation of L5 body
•• Sacral stress fractures also occur in athletes and after labour.

•• Suicide jumpers may have an isolated transverse sacral fracture.
•• Patients without neurological deficit present with pain in the low back,
buttock or perianal region, which increases on sitting or defecating.
•• Isolated urinary retention has been reported.
•• Neurological deficits may be unilateral or bilateral.
•• It is important to assess the S2−S5 roots by checking rectal sphincter tone
and action, saddle and perianal pinprick sensation and reflexes (anal and
bulbocavernosus).
•• Digital rectal examination (and vaginal examination) may reveal an open
fracture.
•• The sacral root injury can range from neurapraxia to neurotmesis.
Chapter 50 • Lumbar and Lumbosacral Injuries
395
DIAGNOSTIC TESTS
•• Nearly 60% of sacral fractures are missed in the initial plain film radiography.
•• Sacral fractures are difficult to visualise on an anteroposterior (AP)
radiograph because of the tilt of the sacrum.
•• The lateral views are obscured by soft tissue of the buttocks.
•• Tracing the arcuate lines in the sacrum may detect an inobvious fracture.
•• The outlet view of the pelvis provides a good AP view of the sacrum and
the inlet view displays the sacral spinal canal.
•• Lateral view of the sacrum can be supplemented by sagittal CT recon-
struction.
•• The transverse fractures are best made out in coronal or three-dimensional
CT reconstruction.
•• H- (or U) shaped fracture is often seen in patients with osteoporosis.
•• CT can also display anatomical variants due to sacral dysmorphism.
•• MRI is sensitive to the marrow oedema that accompanies a sacral insuf-
ficiency fracture.
•• Oblique coronal MRI of the sacrum can show the whole length of sacral
nerves and depicts root compression by fracture fragments.
•• A complete urodynamic evaluation with cystometrography and sphincter
electromyography is needed for proper bladder assessment and management.
•• Sphincter electromyography is useful for monitoring the sacral roots during
surgery.
MANAGEMENT
•• Most sacral fractures can be treated non-surgically.
•• These include stable, undisplaced sacral fractures without pelvic ring
disruption, fractures that spare the lumbosacral junction and fractures
without neurological injury.
•• Bed rest and analgesics suffice.
•• Transverse fractures with minimal displacement or angulation can also be
managed conservatively, if the patient has only minimal deficits.
•• Painful insufficiency fractures can be treated by percutaneous polymeth-
ylmethacrylate sacroplasty.
•• Sacral fractures that are a part of an unstable pelvic fracture require external
or internal pelvic fixation.
•• Surgery is recommended for those with neurological deficits and imaging
documented root compression.
•• Delayed pain is a common problem and often calls for surgical exploration.
•• The nerve roots must be exposed by sacral laminectomy/foraminotomy
and freed from compression by fracture fragment or entrapment within
the fracture.
•• After operative reduction, internal fixation of sacral fractures is done with
iliosacral screws, posterior sacral plating or posterior ilio sacro ilial bars.
•• Iliolumbar (lumbopelvic) fixation can be done to avoid hardware prominence
or skin ulceration associated with iliosacral screws.
•• Triangular osteosynthesis fixation entails placement of L4, L5 pedicle
screws, posterior ilial and iliosacral screws. This allows early full weight
bearing at 6 weeks while preventing loss of reduction in comminuted vertical
shear transforaminal sacral fractures.
396
•• Lumbosacral dislocation is managed with pedicle screw stabilisation. L4

often needs to be included.
•• Sacral alar or S2 screws may be used to augment the inferior part of the
construct.
•• In Aihara type 5 injuries, L5 pedicle screw cannot be placed. Hence,
additional anterior fusion is needed. Circumferential fusion is often needed
in type 4 and 5 injuries.
•• The improvement in sphincteric and sexual dysfunction is poor compared
to the recovery from pain after sacral fracture management.
•• Severe angulation, displacement of fracture and neurotmesis indicate a
poor prognosis.
51
CHAPTER Penetrating
Injuries of the Spine
Harjinder S Bhatoe
MISSILE INJURIES
INTRODUCTION
•• Missile injuries of the spine (MIS) are the third most common cause of
spinal cord injury after motor vehicle accidents and falls.
•• Management of MIS has evolved through the various wars; nevertheless,
the debate on the aim and scope of surgical management of these injuries
is far from settled.
LOCATION OF WOUND
•• Spinal injury at more than one site is highly unusual in civilian MIS, while
these may be seen more often in military practise.
•• Most of these injuries are located in the thoracic spine (54%), followed by
lumbosacral (33%) and cervical (13%) region.
MISSILES AND MECHANISM OF INJURY

The injury is produced by the following mechanisms:
•• Direct crush injury: The missile crushes the tissue in its path, producing
cord and nerve root laceration over more than one segment and an
external communicating wound. The cord may be damaged by bone or
disc fragments, even though the bullet does not come in contact with the
spinal cord.
•• Cavitation: Cavitation may stretch the neural tissue as the energy is
transferred to the wound track producing damage. The temporary cavity
collapses, leaving behind a smaller, permanent track.
•• Concussive wave: Myelopathy may be seen even if there has been no
damage to the discoligamentous or disco-corporeal components of the
spine in HVMIs. This occurs due to a concussive wave, which traverses
the cord as the missile passes close to it, producing cord concussion and
oedema. The severity of myelopathy is usually mild.
•• Intramedullary haematoma: Injury to brachial nerve rootlets may lead to
their avulsion at their origin from the cord and an intramedullary haematoma.
The patient will have features of brachial plexus injury, with myelopathy;
the latter is usually mild and resolves in due course.
398
APPROACH TO A PATIENT WITH MISSILE

INJURIES OF THE SPINE
•• MIS should never be approached in isolation; the initial principles are
resuscitation, securing airway and haemodynamic stabilisation, so as to
preserve perfusion to vital organs.
•• Hypotension may be due to neurogenic or hypovolaemic shock, and the
distinction may not immediately be apparent; nevertheless, accompanying
bradycardia is more often a feature of neurogenic shock.
•• A judicious combination of intravascular volume replacement, vagolytics
and vasopressors may be required for resuscitation.
•• Cervical spine injury may be accompanied by vascular, pharyngeal,
tracheo-oesophageal or pulmonary injury, while dorsal spine injury may be
accompanied by haemopneumothorax or cardiac tamponade.
•• Dorsolumbar injuries may be complicated by retroperitoneal or intraperito-
neal injuries, colonic injuries being of immediate concern for their potential
for contamination.
•• Wounds of entrance and exit are carefully examined for cerebrospinal fluid
(CSF) leakage and the extent of tissue damage is assessed.
•• Baseline neurological assessment is extremely important.
•• In an unconscious patient, the attitude of the limbs and presence of sponta-
neous movements is noted as is the response to pain, and the muscle tone.
Some idea of sensory level may be possible by noting response to pinprick.
•• In a conscious patient, motor-sensory evaluation is carried out, and an
appropriate neurological grade is assigned.
•• Frankel grade is easy to apply and useful to stratify the patients with MIS,
and can be used to prognosticate the outcome.
•• Benzel and Larson devised a more comprehensive scale which utilises
seven grades instead of five of Frankel grading (Table 1).
Imaging
Plain Radiography
•• Multiplanar spinal radiographs should be obtained to detect metallic
fragments, and their craniocaudal as well as anteroposterior distribution.
•• Fractures and dislocations are readily detected by plain radiographs.
•• Presence of metallic or bone fragments should be noted within the spinal
canal or in the neural foramina.
Table 1: Neurological grading system (Benzel & Larson, 1987)

Grade I: Complete functional neuronal transection. No motor or sensory function below the level
of injury.
Grade II: Motor complete. No voluntary motor function below the level of injury, with preservation
of some sensation.
Grade III: Motor incomplete—non-functional. Minimal non-functional voluntary motor function
below the level of injury.
Grade IV: Motor incomplete functional. Unable to walk; some functional motor control below
the level of injury.
Grade V: Motor incomplete—functional. Limited walking, lack of endurance or fear of falling.
Grade VI: Motor incomplete—functional. Unlimited walking, difficulties with micturition and
slightly discoordinated gait.
Grade VII: Normal.
Chapter 51 • Penetrating Injuries of the Spine
399
•• Plain radiographs will also detect subcutaneous emphysema, haemopneu-

mothorax or pneumoperitoneum in the presence of associated injuries.
Myelography
•• In the absence of computed tomography, myelography is a good substitute
to detect dural injury as evidenced by extravasation of intrathecal contrast.
•• A myelographic block may be an indication for surgery, and complications
like arachnoiditis are rarely seen with water soluble contrast media, like
iopamidol or iohexol.
•• However with the widespread availability of CT scanners, myelography
is to be avoided.
Computed Tomography
•• Computed tomography (CT) is the diagnostic modality of choice in the
evaluation of MIS.
•• Precise delineation of the fracture can be made, and intraspinal fragments
and soft tissue foreign bodies can be visualised.
•• CT myelography can be useful to detect the extravasation of contrast and
CSF fistula.
•• Magnetic Resonance Imaging (MRI) is the imaging modality of choice for
assessing the extent of spinal cord injury, yet its use in MIS is restricted
due to the possibility of movement of the ferromagnetic missile fragments.
•• MRI is especially useful in the diagnosis of spinal injury if the missile has
exited, provided there has been no associated injury to the disco-corporeal
components of the spine.
•• MRI is also useful in the follow-up of such patients to detect the possible
formation of post-traumatic syrinx, in the setting of delayed neurological
deterioration.
Treatment Philosophy
Surgical versus Conservative Management
•• Surgery for missile injury of the spine has been a matter for debate, with
most of the early military studies uniformly advocating surgical intervention,
while the civilian studies have adopted a more selective approach.
•• Proponents of surgical intervention cite prevention of infection, CSF
leakage, lead toxicity, pain and late deterioration as the goals, and the
possibility of neurological improvement following surgery.
•• Moreover, increased incidence of wound infection and CNS infections is
reported in patients who have undergone surgical exploration.
•• Differences in the regional anatomy of the spinal cord and the greater
potential for recovery in injuries involving the nerve roots account for the
differences in the effects of surgery in the thoracic, thoracolumbar and
lumbar regions.
•• A peripheral nerve or root injury leaves the cell bodies intact, and there
is relative abundance of myelin surrounding the axon. Disintegration of
a motor axon within a peripheral nerve due to local injury, progresses
proximally to the next node of Ranvier.
•• In the region of axonal degeneration, the Schwann cells proliferate and
form neurilemmal tubules.
400
•• Growth from the central end of the damaged axon can be guided across
the sites of trauma, allowing motor reinnervation over-time.
•• These factors contribute to the favourable outcome in cauda equina injury.
•• Based upon a review of various studies in the preceding decades, coupled
with their own wartime experience, Bhatoe and Singh formulated indications
for surgery in MIS as follows:
–– Incomplete neurological deficit
–– Cauda equina injuries
–– Cervical cord injuries
–– Presence of external CSF fistula
–– Worsening of existing neurological deficit.
Intraspinal Fragment
•• The main question to be answered is whether to remove the bullet or not.
•• The consensus of opinion at present seems to be to remove intraspinal
fragments located in the cauda equina and in the cervical spine.
•• Cauda equina injuries carry the potential for better recovery, and preven-
tion or treatment of radicular pain can be achieved, while the cervical spine
fragments are removed to obviate or treat radicular pain as well as with
the hope of effecting recovery even of a single root, which can influence
the rehabilitation process.
CURRENT MANAGEMENT
•• Broad spectrum antibiotics, preferably ones that cross into the CSF, are
administered on admission.
•• There is no reported benefit of administering methylprednisolone in patients
with MIS.
Wound Debridement
•• Debridement of wounds of entry and exit is carried out at the time of initial
admission.
•• Devitalised tissue, foreign bodies and debris are excised, and haemostasis
is achieved.
•• Extensive soft tissue injuries as those sustained with high-velocity missiles
(HVMs) or by multiple pellets sprayed over a wide surface area, may require
assistance from a reconstructive surgeon.
Post-Operative Management
•• Care of paraplegic and quadriplegic patients demand the highest level of
dedication and care from the nursing staff.
•• Kinetic therapy table provides ease of turning the patient to prevent pressure
ulceration.
•• Antibiotics are administered for a period of 14 days.
•• Rapid mobilisation is essential and a multidisciplinary rehabilitation
programme is commenced early.
SEQUELAE
•• Pain and delayed neurological deterioration constitute two broad groups
of sequelae of MIS.
Chapter 51 • Penetrating Injuries of the Spine
401
Pain
•• There are three distinct variants of pain syndrome following initial recovery
from MIS. These are:
1. Central pain of spinal deafferentation: This type of pain is dysaes-
thetic in nature. Carbamazepine and amitriptyline have been tried
with varying success. In thoracic cord injuries, dorsal root entry zone
lesioning and spinal cord stimulation have shown promising results.
2. Radicular pain: This type of pain is seen more often with cervical cord
and cauda injuries, and is characterised by burning sensation over the
extremities with a dermatomal localisation.
3. Vertebral pain: Pain arising from disco-corporeal elements is fairly
localised over the region of injury. There may be local tenderness.
Imaging may reveal infective sequelae, and treatment would consist
of debridement with the possibility of stabilisation.
Delayed Neurological Deterioration

•• Deterioration may occur due to infective sequelae, especially osteomyelitis.
•• Cord compression can also occur due to exaggerated granulomatous
response, especially in injury due to steel and glass.
•• Other causes of deterioration are formation of post-traumatic spinal
cysts (post-traumatic syringomyelia) and intraspinal migration of missile
fragments.
•• Post-traumatic cystic myelopathy follows tethering of the contused cord and
localised arachnoiditis with alteration in CSF flow; these lead to rostral and
caudal cystic degeneration and cord cavitation.
•• Migration of bullets in the subarachnoid space can lead to new deficits.
•• All patients with delayed neurological deterioration should be investigated
by CT myelography or by MRI, subsequent to which, further treatment
can be planned.
•• Extradural cord compression may require debridement with or without
instrumentation. Post-traumatic cystic myelopathy is improved by shunting
and excision of migrating bullets is curative.
Lead Toxicity
•• Retained bullets and shrapnel tend to get sealed off by fibrosis and lead is
not absorbed to cause lead toxicity.
•• However, symptoms of lead poisoning (abdominal pain, anaemia, head-
aches, memory loss, muscle weakness) may occur, if the lead object is in
communication with synovial fluid, such as a joint or pseudocyst.
•• Treatment consists of chelation therapy with ethylenediaminetetraacetic acid
(EDTA), d-penicillamine or dimercaprol or British anit-lewisite (BAL).
Section V: Peripheral Nerve
52
CHAPTER
Anatomy and
Physiology of the
Peripheral Nerve
Sharma M  Gupta A  Mehta VS
NEURON
Classification
On the Basis of Processes
•• Unipolar neurons: Only one process leaves the cell body. They are
sensory in function and located in the craniosacral ganglia.
•• Bipolar neurons: A single dendrite and a single axon leave the body. They
are purely sensory in function and located in the cochlear and vestibular
ganglia of the VIII nerve, in the olfactory nerve and in the retina.
•• Multipolar neurons: Most common type of cells. Have numerous branched
dendrites projecting from the cell body, and on the opposite side, there is
a single process called the axon. They are the largest population of nerve
cells and form motor neurons, interneurons, pyramidal cells, Purkinje cells
and neurons of the autonomic nervous system.
On the Basis of Function
•• Central cell body
–– Cortical neurons: Impulses from the cerebrum, cerebellum and optic
lobes to the affector organs.
–– Interneurons: Connector neurons.
–– Central effector neurons: They include motor neurons, autonomic
neurons and hypophyseal neurons.
•• Peripheral cell body
–– Peripheral effector neurons: From the autonomic and invertebrate
ganglia.
–– Bipolar neurons: Those of the optic, vestibulocochlear, olfactory and
cutaneous neurons.
Structure
Cell Body
•• It contains a large, central nucleus with a prominent nucleolus and it gives
rise to the axons and the dendrites (Fig. 1).
•• It is located at the dendritic zone-end of the axon, but it can be within the
axon or attached to the side of the axon.
•• It also contains Nissl substance which contains rosettes of polysomes and
rough endoplasmic reticulum, and hence, has a role in protein synthesis.
•• Nissls substance is also present in the dendrites, but is not present in the
axon hillock or the axon.
Chapter 52 • Anatomy and Physiology of the Peripheral Nerve
403
Fig. 1: Diagrammatic representation of a multipolar neuron
Dendrites
•• The cell body gives rise to 5–6 processes that extend outwards and branch
extensively. The small, knobby projections of the dendrites are called
dendritic spines. The dendrites conduct impulses towards the cell body.
Axons
•• An axon is a neuron process that originates from a thickened area of the
cell body called the axon hillock.
•• The first portion of the axon is called the initial segment.
•• The axon divides into terminal branches, each ending in a synaptic knob
also called terminal buttons or axon telodendria.
•• The cytoplasm present inside the axon is called axoplasm and the outer
membrane is called the neurilemma.
Schwann Cells
•• They extend along the axon from its origin to its termination.
•• They form the myelin sheath around the larger axons.
•• Smaller axons are surrounded only by the Schwann cell cytoplasm.
•• Along the length of the myelinated axon, are small gaps in the myelin sheath
between individual Schwann cells, called the node of Ranvier.
•• Such axons that do not have a myelin sheath are called unmyelinated.
NERVES
•• Nerves are part of the peripheral nervous system.
•• Afferent nerves convey sensory signals to the central nervous system, for
example, from skin or organs, while efferent nerves conduct stimulatory
signals from the central nervous system to the muscles and glands.
•• Afferent and efferent fibres are often arranged together, forming mixed
nerves.
•• Nerves carry action potentials which begin typically in the cell body of a
neuron and propagate rapidly down the axon to its tip or “terminus”.
•• The signals cross over from the terminus to the adjacent neurotransmitter
receptor through the synapse.
Section V • Peripheral Nerve
404
Histology of a Nerve Fibre

Endoneurium
•• It is a connective tissue layer surrounding each nerve fibre.
Perineurium
•• It is a connective tissue layer which surrounds each fascicle (a bundle of
nerve fibres).
Epineurium
•• It is the connective tissue layer surrounding each nerve (Fig. 2).
Basic Nerve Physiology

•• Tables 1 and 2 show nerve fibre types, function and the numerical
classification.
Excitation and Conduction

•• Two types of physio-chemical disturbances are produced:
1. Electrotonic potentials which are non-tonic propagated potentials.
2. Action potentials are the propagated disturbances.
•• Conduction is an active, self-propagating process and the impulse moves
along the nerve at a constant amplitude and velocity.
•• The electrical events in neurons are rapid, being measured in milliseconds
and the potential changes are small being measured in millivolts.
Resting Membrane Potential
•• It is the negative potential inside the cell membrane when the cell is at rest.
In neurons, it is –70 mV.
Latent Period
•• If the axon is stimulated and a conducted impulse occurs, a characteristic
series of potential changes known as the action potential is observed.
•• When a stimulus is applied, there is a brief, irregular deflection of the
baseline, called the stimulus artefact.
Fig. 2: Cross-sectional anatomy of the human tibial nerve

405
Table 1: Nerve fibre types and functions

Fibre type Function Fibre Conduction Spike Absolute
diameter velocity duration refractory
(micron) (m/s) period
A alpha Proprioception and 12–20 70–120
somatic motor
Beta Touch and pressure 5–12 30–70 0.4-0.5 0.4-1
gamma Motor to muscle 3–6 15–30
spindles
delta Pain, cold, touch 2–5 12–30
B pre-ganglionic <3 3–15 1.2 1.2
autonomic
C dorsal root Pain, temperature, 0.4–1.2 0.5–2 2 2
mechanoreception,
reflex response
sympathetic Post-ganglionic 0.3-1.3 0.7-2.3 2 2
sympathetic
A and B fibres are myelinated, C fibres are unmyelinated.
Table 2: Numerical classification

Number Origin Fibre type
Ia Muscle spindle, annulospiral ending A alpha
Ib Golgi tendon organs A alpha
II Muscle spindle, flower-spray endings, touch, pressure A beta
III Pain and cold receptors, some touch receptors A delta
IV Pain, temperature, and other receptor Dorsal root C
•• The stimulus artefact is followed by an isopotential interval called the latent

period that ends with the start of the action potential and corresponds to
the time it takes for the impulse to travel along the axon from the site of
stimulation to the recording electrodes.
Action Potential
•• The first manifestation of the approaching action potential is an initial
depolarisation of the membrane.
•• After an initial 15 mV of depolarisation, the rate of depolarisation increases.
•• The point at which this change occurs, is called firing level or threshold.
•• Thereafter, depolarisation reaches and overshoots the isopotential line to
approximately +35 mV.
•• It then reverses and falls rapidly to the resting level.
•• When repolarisation is about 70% completed, the rate of repolarisation
decreases and the tracing approaches the resting level more slowly.
•• The sharp rise and rapid fall are the spike potential of the axon, and the
slow fall is called the after depolarisation.
•• After reaching the previous resting level, the tracing overshoots slightly
in the hyperpolarising direction to form the small but prolonged, after
hyperpolarisation.
406
All or None Law

•• Threshold intensity: It is the minimal intensity of stimulating current that
acting for a given duration will just produce an action potential.
•• The threshold intensity varies with the duration—with weak stimuli, it is
long and with strong stimuli, it is short.
•• The relation between strength and duration of the stimulus is called the
strength-duration curve.
•• The action potential fails to occur if the stimulus is sub-threshold in
magnitude, and it occurs with a constant amplitude and form, regardless
of strength or form, if it is at or above threshold intensity.
•• The action potential is thus, all-or-none in character and is said to obey
the all-or-none law.
Ionic Basis of Excitation and Conduction
•• The cell membranes of nerves contain different types of ion channels,
some are passive, some are voltage-gated, while others are ligand-gated.
•• It is the behaviour of these channels, and particularly sodium and potassium
channels, that explains the electrical events in the nerves.
Ionic Basis of the Resting Membrane Potential
•• Due to the difference between the permeability of membranes to different
ions, there is a greater efflux of K compared to the influx of Na, which results
in a negative potential inside the cell membrane which is termed as the
resting membrane potential.
Ionic Fluxes During Action Potential
•• This is due to the changes in membrane conductance of sodium and
potassium.
Neuromuscular Junction
•• The neuromuscular junction is the connection between an efferent nerve
and muscle fibres controlled by this nerve.
•• Transmission is universally mediated by acetylcholine released from the
presynaptic terminal, by the arrival of an action potential.
•• The release of this neurotransmitter is mediated by fusion proteins on the
membrane and appears to be dependent on an influx of calcium ions.
•• Once the acetylcholine is released into the synaptic cleft, it rapidly diffuses
to the postsynaptic membrane, where it binds to acetylcholine receptors.
•• These, in turn, trigger a rapid influx of calcium into the muscle cells,
triggering muscle contraction.
•• The remaining acetylcholine in the synaptic cleft is rapidly degraded by
acetylcholinesterase to prevent desensitisation of the synapse.
•• If, after peripheral nerve injury or transection, the neuromuscular junction
does not undergo excitation at all, over a period of time, the density of
acetylcholine receptors gradually declines.
•• In fact, it has been shown that after 18–24 months of loss of nerve continuity,
the neuromuscular junction undergoes irreversible loss of excitability,
resulting in no clinical motor improvement, if surgery is delayed up to this
time.
407
Peripheral Nerve Transection

•• Once a peripheral nerve has been transected, Wallerian degeneration
of the distal axons begin and macrophages enter the area to remove the
myelin and axonal debris.
•• During this process, the basement membrane which surrounds the axon
and Schwann cell, remain intact.
•• Schwann cells line-up in the basement membrane tube and synthesise
growth factors, which attract axonal sprouts formed at the terminal of the
proximal segment of the severed axon.
•• The basement membrane tubes provide pathways for the regenerating
axons to follow to the muscles and skin.
•• The Schwann cells then remyelinate the newly formed axons; however, the
newly formed myelin is thinner than normal and the newly formed internodes
are shorter than normal.
Seddon’s Classification of Nerve Injury

•• This is the earliest and the most well-known classification system. He
described three grades of severity:
•• Neuropraxia:
–– An injury to the nerve covering (called the myelin sheath), but not the nerve,
by trauma or compression which causes blockage of the nerve signals.
–– Larger nerves covered by greater amounts of myelin are most
susceptible to this injury.
–– Reflexes, muscle function, vibratory and two-point discrimination
are typically lost, while pain, temperature and autonomic function
(sweating and circulatory regulation controlled by nerves) are typically
preserved.
–– Repair may take days to months, and healing is usually perfect as only
the sheath needs be repaired. This corresponds to Sunderland’s first
degree injury.
•• Axonotmesis:
–– Involves disruption of the nerve itself, but the surrounding and
supportive nerve myelin sheath is not affected.
–– Causes include long or severe periods of compression, pulling or loss
of blood flow to the nerve.
–– All nerve types may be affected.
–– Nerve fibre healing occurs at a rate of 1 mm per day from the point
of injury.
–– Recovery is usually good, although, the further from the spine the
injury occurs, the better the prognosis.
–– This corresponds to the 2nd or 3rd degree injury in Sunderland’s system.
•• Neurotmesis:
–– A disruption of both the nerve fibre and the supportive myelin sheath.
–– This injury may be seen with severe trauma such as lacerations,
gunshot wounds, open bone fractures, punctures, and exposure to
toxins.
–– Healing is usually poor without surgical repair.
–– This corresponds to the 4th or 5th degree injury in Sunderland’s
system.
408
Sunderland’s Classification of Nerve Injury

•• After Seddon’s description, Sunderland in 1978, proposed his own system
of grading nerve injuries into five increasing grades.
•• First degree: Injury with only local changes to the nerve sheath (myelin).
•• Second degree: Incomplete injury to the nerve axons (the functional unit
of the nerve). Nerve itself is still intact.
•• Third degree: Severe axonal injury with scar tissue. Nerve itself may be
injured, but is still intact.
•• Fourth degree: Complete disruption of axon. Nerve itself may be severely
injured, but is still intact.
•• Fifth degree: Complete transection of the nerve.
Neurotrophic Factors
•• Neurotrophins are a family of molecules that encourage survival of nervous
tissue.
•• Neurotrophic factors are secreted by cells in a neuron’s target field and
act by prohibiting the neuron from apoptosis. In this way, target neurons
are not removed.
•• The neurotrophin family includes the nerve growth factor (NGF), brain-
derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin
4 (NT-4).
•• There are two classes of receptors, p75 and the “Trk” family of tyrosine
kinases receptors.
•• p75 is a low affinity neurotrophin receptor, to which all neurotrophins bind.
•• The Trk family includes TrkA, TrkB and TrkC, and will only bind with
specific neurotrophins, but with a much higher affinity. The Trks mediate
the functional signals of the neurotrophins.
•• Nerve growth factor is the prototype for the neurotrophin family of
polypeptides which are essential for the development and survival of
certain sympathetic and sensory neurons, in both the central and peripheral
nervous systems.
•• The physiological relevance of these sources is not established.
•• NGF is critical for the survival and maintenance of sympathetic and sensory
neurons.
•• NGF is released from the target cells, binds to and activates its high affinity
receptor (TrkA), and is internalised into the responsive neuron.
•• The NGF/TrkA complex is subsequently trafficked back to the cell body.
•• This movement of NGF from axon tip to soma is thought to be involved in
the long-distance signalling of neurons.
•• There is recent interest in the role of these neurotrophic factors in assisting
and guiding the process of nerve and axonal regeneration, which is being
tried using synthetic tubes and scaffolds for neuronal and glial cells in nerve
injuries and root avulsions.
53
CHAPTER
General Principles of
Management of
Peripheral Nerve Injuries
David A Omahen  Hazem Eltahawy  Abhit Guha
ANATOMY
•• The neuronal axon and its surrounding Schwann cells can be viewed as
the functional unit of a peripheral nerve.
•• A collection of connective tissue, known as endoneurium, surrounds each
individual nerve fibre.
•• A nerve is composed of several fascicles, or group of axons, surrounded
by a sheath of compact connective tissue called the perineurium.
•• This thin layer is the anatomical substrate of the “blood-nerve barrier” akin
to the “blood-brain barrier”, to provide a proper external environment for
axonal conduction.
•• The tensile strength of a nerve is from the mesodermal derived epineurium,
which can be subdivided into the looser internal epineurium separating the
individual fascicles, and the stronger external epineurium which envelops
the entire nerve and provides the main tensile strength.
•• It is this external epineurium that is most often used to insert sutures during
nerve grafting (Fig. 1).
•• Interspersed between these layers of the nerve, there are numerous
longitudinally oriented blood vessels to provide a rich vascular plexus to
the nerve.
•• However, the microcirculation can be compromised to a significant extent
and lead to nerve dysfunction and pain by systemic diseases such as
diabetes and local therapies such as radiation.
Fig. 1: The internal microarchitecture of a peripheral nerve

410
PATHOPHYSIOLOGY OF NERVE INJURY

•• In cases of nerve entrapment or other forms of compressive nerve
injuries, early changes include endoneurial oedema secondary to impaired
venous flow, and breakdown of the blood-nerve barrier at the level of the
perineurium.
•• Morphological studies have revealed relative sparing of smaller and
unmyelinated fibres, with greater damage to large myelinated fibres.
•• This process leads to paranodal or segmental demyelination within a few
days, resulting in blockage of axonal conduction.
•• This form of injury, if the nerve is caught, leads to a neuropraxic injury,
not accompanied by axonal severance, and usually full recovery within a
few weeks is possible once the nerve microcirculation is stabilised with
restoration of the segmental foci of demyelination.
•• In cases of more severe nerve injury with interruption of the axon
(axonotmesis or neurotmesis), characteristic pathological changes occur.
•• Within 24 hours, distal Wallerian degeneration begins with associated
fragmentation of cellular components, breakdown of the axon and myelin
sheath, and phagocytosis by invading macrophages and Schwann cells.
•• Subsequent failure of conduction at the neuromuscular junction also occurs.
•• Proximal to the site of injury, the process of chromatolysis takes place with
swelling of the cell body and clumping of chromatin.
NERVE REGENERATION
•• Recovery from axonotmesis or neurotmesis involves axonal regeneration.
•• First, there is a reversal in the visible changes of chromatolysis with an
increase in neuronal metabolism leading the cell body to produce axoplasm,
which in turn forms the regenerating axon tips called “growth cones”.
•• Axonal outgrowth can commence as early as one day after injury and this
regenerative response can continue for 12−18 months.
•• The ability of the growth cones to reach their target organs depend upon
the distance they need to travel, the presence of residual endoneurial
tubes to guide them, and the degree of scarring present at the site of injury.
•• If an axon reaches the correct end target, which is estimated to be at a
rate of 1 mm/day or 1 inch/month, effective though often sub-maximal
reinnervation can occur up to 12−18 months post-injury.
•• During this time, physiotherapy and occupational therapy are of paramount
importance to maximise recovery and prevent secondary problems such
as contractures.
•• Exercise has the capacity to further improve function resulting from the
reinnervation, by promoting muscle-fibre hypertrophy and increased size
of the motor-units or number of muscle-fibres supplied by a nerve ending
by sprouting.
CLASSIFICATION SYSTEMS FOR PERIPHERAL

NERVE INJURY
•• There have been several attempts to classify peripheral nerve injury based
on anatomical and clinical criteria.
•• Broadly, nerve injuries may be classified as open or closed.
•• Open injuries can further be subdivided into sharp (knife, glass wound, etc)
or blunt (compound fractures, gunshot wounds, etc).
Chapter 53 • General Principles of Management of Peripheral Nerve Injuries
411
Figs 2A to C: The Seddon’s classification of peripheral nerve injury. (A) Neu-

rapraxia refers to temporary loss of conduction along a nerve without axonal
de generation. (B) Axonotmesis involves degeneration of the axon with
preservation of the surrounding supporting soft tissue sheath. Spontaneous
recovery can occur since sprouting growth cones are guided to their appropri-
ate targets along these sheaths. (C) Neurotmesis involves gross interruption
of nerve continuity, and requires operative repair to restore continuity
•• Closed injuries (brachial plexus stretch injury, etc) are often injuries in
continuity, with mechanical distortion, intraneural and extraneural scarring
and ischaemia, all playing a role in the pathophysiology.
•• At a pathological-clinical level, two systems of classification have gained
widespread use in clinical practise (Figs 2A to C).
•• The first is the Seddon’s system, which introduced the terms neurapraxia,
axonotmesis and neurotmesis.
–– In the setting of a closed injury, the only way to distinguish between
neurotmesis and axonotmesis is to surgically explore and inspect the
nerve.
–– Figure 2 illustrates the injury patterns described in the Seddon’s system.
PATHOGENESIS OF PERIPHERAL
NERVE INJURIES
Open Injuries
Laceration Injuries
•• Of all the mechanisms of peripheral nerve injury, this is the one most likely
to lead to transection.
•• Even with near or complete functional loss, approximately 20% of nerve
fibres are left in at least partial continuity.
•• Generally these injuries fall into two major categories: Sharp and blunt.
•• Sharp laceration, as caused by glass, knives or razors, is usually dealt with
via exploration and primary repair if a major nerve injury is accompanied
by severe loss of function.
•• Blunt injury, such as that inflicted by chainsaws or commercial machinery,
is usually dealt with in a delayed manner, as there is usually a variable
and unpredictable amount of non-viable tissue proximal and distal to the
site of injury.
•• The injured nerve stumps can be sutured to nearby soft tissue planes to avoid
retraction if they are identified during repair of the associated soft tissue injuries.
412
•• At a later time, non-viable tissue will become more clearly demarcated,

allowing trimming of the stumps back to viable tissue prior to repair.
Gunshot Wounds
•• With gunshot wounds, a variety of injuries can occur depending on the
nature and velocity of the missile, as well as the trajectory.
•• Progressive loss of function and pain, audible bruits or palpable thrills, or
evidence of distal ischaemia may indicate a major vascular injury.
•• Entities such as pseudoaneurysm formation, compressive haematoma, major
vessel transection or arteriovenous fistulae may necessitate acute exploration.
•• Otherwise, serial clinical and EMG examination to document the course of
any spontaneous recovery during the first 2−3 months is usually advised.
Iatrogenic Injuries
–– Direct injection injuries occur most commonly to the sciatic nerve at the
buttock and the radial nerve in the upper arm and may be associated
with development of chronic pain.
–– The lesion should be explored if no evidence of improvement occurs
during 3 months of serial evaluation.
–– Intra-operative nerve action potentials (NAPs) are invaluable in decid-
ing how to deal with such injuries.
Closed Injuries
Stretch Injuries
•• Stretch injuries occur when traction on a nerve exceeds the elastic limit
of the nerve.
•• They are often associated with spinal injury or joint dislocation.
•• This often results in formation of a neuroma-in-continuity with a high
likelihood of neurotmesis and obliteration of fascicular anatomy.
•• Widespread and varying injury occurs along the length of the nerve.
•• As with other lesions in continuity, they are best dealt with by careful
longitudinal evaluation and delayed surgical intervention, when indicated.
Crush Injuries
•• Crush injuries involve variable combinations of stretch, contusion,
ischaemia and blunt transaction.
•• They are usually dealt with in a delayed manner, as described for stretch
injuries.
Ischaemic/Compressive Injuries
•• With ischaemia, damage may occur not only to the nerves themselves, but
also to their supportive environment.
•• Painful paraesthesias followed by progressive loss of function, swelling
of an extremity, skin discolouration and signs of distal peripheral vascular
compromise may signal an evolving compartment syndrome, which requires
urgent treatment with fasciotomies.
Electrical/Thermal Injuries
•• Severe scar formation and potential extensive necrotic soft tissue loss,
often accompany these injuries.
•• Graft and/or flap reconstruction is often required.
•• The accompanying nerve injury is usually extensive, non-focal and difficult
to treat.
413
CLINICAL AND ELECTROPHYSIOLOGICAL

EVALUATION
•• Symptoms of peripheral nerve injury include pain, dysaesthesias and partial
or complete loss of motor and sensory function.
•• Evaluation involves a thorough history and physical examination, relevant
radiological studies and electrodiagnostic evaluation.
•• Tinel’s sign refers to paraesthesias elicited by regenerating axonal growth
cones when tapping along the course of a nerve, and is useful in the
localisation of a nerve injury. The course of regenerating sensory axons
can be mapped by progressive distal advancement of Tinel’s sign. Reflex
changes should also be evaluated.
•• Electrophysiological studies involve those undertaken serially pre-
operatively to determine if and what degree of spontaneous recovery is
occurring to augment the clinical examination.
•• In an effort to identify injuries that will not require surgical intervention, an early
study is performed 2 weeks post-injury followed by studies at 2−3 months.
•• Differentiation between axonotmesis and neurotmesis requires delayed
nerve conduction studies.
•• In the case of axonotmetic injury, regenerating axons will cross the site of
injury and grow distally.
•• Intra-operative electrophysiological examination, comprising direct nerve
stimulation, sensory evoked potentials (SEPs) and NAPs are important
adjuncts to the microscopic and macroscopic status of the nerve, enabling
the neurosurgeon to undertake optimal surgical decisions.
•• Post-operative serial electrophysiological examination which usually com-
mences 2−4 months after nerve surgery, are also utilised to complement
the clinical follow-up for determining the extent of neural reinnervation.
RADIOLOGICAL EVALUATION
•• Currently, radiological examination plays little role in the management
decisions for nerve injuries.
•• However, emerging improvements in MRI neurography techniques may
provide clues about peripheral nerve injuries.
•• Correlation with histological and clinical evidence of axonal degeneration
and regeneration has been good.
•• MRI may be useful in evaluating suspected spinal roots avulsion.
MANAGEMENT OF PERIPHERAL
NERVE INJURIES
•• Sharp open nerve transections should primarily be repaired with end-to-
end nerve suturing of the epineurium at the time of initial debridement of
the wound.
•• Blunt open nerve injuries in which the transected nerve ends are ragged
and contused is better repaired after a 3−4 week delay, allowing for a
reduction in tissue oedema, and more importantly scar formation at the
edges of the transected segment.
•• Scarring allows for discrimination between healthy proximal and distal nerve
ends and the fibrosed nerve segments. Fibrosed segments can then be
resected back to normal fascicular structure at both ends, and then a repair
with or without nerve grafts can be performed.
414
•• Closed injuries often require more complex management decisions.

•• The nerve remains in continuity in most such injuries.
•• Stretch or compression injury causes injury of varying severity. Given
enough time, spontaneous recovery occurs in 80% of closed nerve injuries.
•• The surgeon’s task is early identification of the cases in which there is lack
of clinical or electrophysiological recovery.
•• Most surgeons believe that, if no signs of regeneration are seen after
3−4 months, operative intervention is the best course of action.
•• The location of the injury is another important consideration.
•• In proximal lesions, such as in the supraclavicular brachial plexus, waiting
too long for recovery to manifest, may miss the window of opportunity for
useful outcome from nerve repair.
•• However, age is an important factor as the regenerative capacity of infants
or young adults is much more than older adults, hence, we tend to be more
aggressive in this age group, even after a prolonged delay.
•• In proximal brachial plexus injuries with documented nerve root avulsion,
consideration should be given to direct neurotisation.
•• This involves providing viable motor axons from a donor nerve, whose
function is redundant or less important, to a denervated distal muscle group.
•• Early operation is associated with the following advantages:
–– Less scarring which simplifies dissection of peripheral nerve elements
–– Direct evaluation of anatomic and electrophysiological continuity which
dictates the necessity of a surgical repair and
–– Earlier repair may result in better outcome with faster reinnervation of
denervated muscle.
PRINCIPLES OF SURGICAL NERVE REPAIR

•• Surgical intervention for peripheral nerve injuries has two goals.
•• The first is diagnostic, whereby one determines the site(s) of nerve injury
by macroscopic, microscopic and intra-operative electrophysiological
evaluation.
•• Most often this can be predicted by the pre-operative clinical and
electrophysiological evaluation, but confirmation with the exposed nerves
is required.
•• Multiple sites of injuries along the course of a nerve pathway are common,
especially in stretch injuries, hence exposure of the full length of the nerve
(i.e. supra-clavicular, retro-clavicular and infra-clavicular brachial plexus
exposure) is advised.
•• The second surgical goal is therapeutic intervention to optimise nerve
regeneration.
•• This depends not only on the extent of the injury, but also the pre-operative
goals, knowledge of what reinnervation is realistic given the patient
characteristics, etc.
•• Multiple types of interventions include a simple external neurolysis if
physical and electrical continuity is present, excision of the neuroma in
continuity and direct end-to-end repair if the gap is minimal, interpositional
nerve grafts from donor sites such as the sural nerve or direct or indirect
neurotisation procedures, if endogenous proximal nerve fibres cannot be
obtained.
•• Basic principles of surgery include the following:
415
–– Exposure of the Healthy Nerve, Proximal and Distal to the Site

of Injury:
¾¾ A generous skin incision is based on the surface anatomy of the
nerve and centred on the site of injury.
¾¾ Careful proximal and distal exposure of the suspected lesioned
area is performed.
–– Intra-operative Electrophysiological Evaluation:
¾¾ Intra-operative electrophysiological evaluation includes the record-
ing of SEPs, NAPs and electromyography (EMG).
–– Intra-operative Microscopic Examination by Quick (Frozen)
Section:
¾¾ After each slice, the fresh ends are re-examined under the
microscope and the cut slice is submitted for quick pathological ex-
amination by frozen section to look for a normal fascicular pattern.
–– Fascicular Microsuture Technique:
¾¾ The nerve ends are carefully inspected under the surgical mi-
croscope to determine the fascicular topography. Use 9-0 nylon
epineurial stitches to approximate the fascicles in a tension-free
manner.
Technical Pearls
1. Avoidence of tension.
2. Using a minimal number of sutures.
3. Maximising the number of motor fibres available for repair.
4. Matching the graft to recipient nerve fascicles.
POST-OPERATIVE MANAGEMENT
Immobilisation
•• The extremity is immobilised in the exact position, in which it was placed
during the operation.
•• After that, gradual mobilisation is encouraged.
•• An active physiotherapy program is crucial to maintain muscle bulk and
prevent frozen joints.
Follow-up Electrodiagnostic Studies

•• Serial electrophysiological studies can be very useful in detecting early
signs of muscle reinnervation several months before muscle contraction
is clinically evident.
•• The results of these studies, when positive, can provide hope to the patient
and can also be helpful in predicting clinical outcome.
54
CHAPTER
Surgical Anatomy and
Management of
Brachial Plexus Injuries
Venkataswami R  Purushothaman V
SURGICAL ANATOMY
•• The brachial plexus is constituted by the ventral rami of C5 to T1 nerve
roots.
•• They can have a contribution either from C4 wherein it is called prefixed,
or contribution from T2 when it is called post-fixed.
•• As the roots emerge from the intervertebral foramina, they lie on the
scalenus medius muscle behind the scalenus anterior.
•• The phrenic nerve travelling on the surface of the scalenus anterior must
be identified, dissected and neurolised, if necessary, and kept out of harm’s
way, while dividing the scarred muscles.
•• The phrenic nerve when traced upwards, leads to the C4 root, and
sometimes, this will be an important guide to locate the C5 and proceed
downwards.
•• The roots and trunks lie in the posterior triangle of the neck, the divisions
lying behind the clavicle, the cords behind the pectoralis major muscle and
the nerves below the pectoralis minor muscle.
•• The C8 and T1 lie on the first rib in close relation with the subclavian
vessels.
•• The suprascapular, axillary and musculocutaneous nerves are important
as they control shoulder and elbow function. Most of the nerve crossings
involve these branches.
•• The suprascapular nerve is the first branch from the upper trunk. The
axillary nerve is the smaller of the two main divisions of the posterior cord.
The other one is the large radial nerve. The musculocutaneous nerve is
the lateral branch from the lateral cord.
•• From the clinical examination and functional point of view, the C5 and C6
roots are for shoulder and elbow functions and C8 and T1 for hand and
forearm functions.
•• C7 contributes to shoulder, elbow and hand functions. In other words, C7
has considerable cross-innervations with C5, C6 and C8.
•• Because of this cross-innervation, no single muscle is innervated by C7
alone. Therefore, C7 transection will cause minimal muscle dysfunction
which is compensated very quickly.
CLASSIFICATIONS
•• It can be classified on functional and clinical basis under various head-
ings:
Chapter 54 • Surgical Anatomy and Management of Brachial Plexus Injuries
417
Anatomical
•• Upper plexus.
•• Lower plexus.
•• Total.
•• The injury can be either complete or incomplete.
•• Depending on the nature of violence, it can be compression, traction,
division, rupture or avulsion.
•• Division is usually seen in direct penetrating injury like stab or gunshot
injuries.
•• Based on the level of lesion in relation to the clavicle, they can be
supraclavicular or infraclavicular lesions.
•• Infraclavicular lesions can be associated with vessel injury and skeletal
injuries, including fractures of the humerus and scapula.
•• In relation to the sensory ganglion in the dorsal rami, it can be pre-ganglionic
or post-ganglionic.
•• The pathological classification of Sunderland helps in deciding on the type
of repair required in each instance (see Chapter 53).
CLINICAL EXAMINATION
•• One should be familiar with areas of absolute sensory loss and their
corresponding roots.
•• It is essential to differentiate a pre-ganglionic from a post-ganglionic lesion.
•• Horner’s syndrome is characteristic of root avulsion of C8 and T1.
•• Diaphragmatic paralysis is seen in a C4 lesion.
•• Tinel’s sign is absent in pre-ganglionic lesions.
•• The presence of Tinel’s sign is quite useful, as it indicates that some roots
are regenerating and it is a post-ganglionic lesion.
•• The paravertebral muscles are paralysed in pre-ganglionic lesions. A
classical example is winging of the scapula.
•• Paravertebral anaesthesia and sweating in the anaesthetic area are
pathognomonic of a pre-ganglionic lesion.
•• Sensory nerve action potential (SNAP) is positive in the anaesthetic areas
and there will be a positive axonal reflex. Somatosensory evoked potential
(SSEP) will be absent.
•• The roots can be damaged at five possible sites:
1. Immediately proximal to the trunks. In this case, the serratus anterior
and rhomboids may be intact.
2. Proximal to white rami communicans—C8. Horner’s syndrome will be
present.
3. Proximal to grey rami communicans. Sweating in anaesthetic areas
will be seen.
4. Proximal to dorsal root—Paravertebral muscles are paralysed.
5. Proximal to posterior root. Here axonal reflex will be present.
•• The presence of deep pressure pain is an indication of continuity of that
nerve and its roots. This is performed by applying full pinch pressure across
the patient’s finger tip at the base of the nail.
DIAGNOSTIC STUDIES
•• They can be broadly classified into imaging studies and neurophysiological
investigations.
418
Imaging Studies
•• Plain radiographs of the cervical region, upper chest and upper arm are
essential.
•• Fracture of the transverse process of the cervical spine strongly indicates
avulsion of the roots at C4, C5 and C6 levels from the spinal cord, as these
roots are intimately related to the transverse processes.
•• One should suspect damage to C8 and T1 roots, and the subclavian vessels
when there is an associated fracture of the first rib and clavicle.
•• Chest X-ray is essential. Elevation of the diaphragm indicates damage to
the phrenic nerve.
•• CT myelography is sensitive in identifying small meningocoeles at the site
of root avulsion from the spinal cord.
•• Normal rootlets are shown as thin linear filling defects that arise from the cord
and converge as they enter the nerve root sheath. The origin of the roots is
seen as fine streaks. They cause the filling defect in a normal myelogram.
•• MRI is helpful in identifying root avulsion.
•• A good MRI can show an intact root, a pseudomeningocoele, the continuity
of the plexus, the scarring in the scalene muscles, etc. Being non-invasive,
MRI has literally taken the place of CT myelogram.
•• The recent 3T MRI is even more valuable in assessing the integrity of the
brachial plexus.
Neurophysiological Examination
•• In recent years, neurophysiological examination has been used in locating
the level of the lesion in brachial plexus injuries, but it has its own limitations
and clearly defined areas.
Electromyography
•• Electromyography (EMG) is not useful in the first 10–14 days when axonal
degeneration changes do not appear, but the presence of voluntary motor
unit action potentials exclude complete transaction of a nerve root.
•• Absence of signs of denervation in a paralysed muscle after 2–3 weeks
indicate a neuropraxic lesion.
•• Paraspinal EMG can differentiate in between pre-ganglionic and post-
ganglionic lesions.
Sensory Nerve Action Potentials

•• The cell bodies of the sensory axons are located in the dorsal root ganglion.
•• When the lesion is proximal to the dorsal root ganglion, the peripheral
sensory axons retain continuity with their cell bodies and do not undergo
Wallerian degeneration.
•• Therefore, demonstration of SNAP in nerves whose cutaneous territories
are anaesthetic, is evidence of a pre-ganglionic lesion.
•• SNAP can be elicited in the superficial radial (C6), median and ulnar
nerves (C6, 7, 8).
•• C5 cannot be studied, as it has no significant representation in these
peripheral nerves. In this situation, histamine test of the axonal reflex may
be useful in examining the C5 root.
•• In a combined pre-ganglionic and post-ganglionic lesion, SNAP is not reliable.
419
Somatosensory Evoked Potentials

•• SSEP is essentially an intra-operative test to establish the continuity of
the root with the cord and to the brain in cases of post-ganglionic lesions
where the root stumps are seen in the region of the intervertebral foramen.
•• In essence, absent SSEP means root avulsion.
MANAGEMENT
•• When to intervene surgically, is the most debatable point. Whether we
operate or not from day one, the following have to be ensured:
–– Mobilise all the joints
–– Splint the shoulder in abduction
–– Electrical stimulation of the muscles to minimise muscle atrophy
–– Electrical stimulation is advised in all patients, even while they are at
home.
•• In the pre-operative period, all groups of muscles are targeted, whereas in
the post-operative period, only the repaired nerves and their target muscles
are stimulated.
•• Stimulation of the repaired nerves and target muscles is done with a
frequency of 2 Hz, pulse width of 200 microseconds and output current of
5–10 mA. This is done twice daily for 15 minutes per nerve muscle unit.
•• Majority of neurosurgeries all over the world, is in favour of early exploration
and nerve reconstruction.
•• In early exploration, some surgeons are in favour of operating on day one
or after 3–4 weeks; the period required for neuropraxia lesions to recover.
Others like to wait for 3–4 months.
•• Surgical intervention is necessary, if the lesions are pre-ganglionic.
•• Early exploration has many advantages. It is easy to dissect. Diagnosis of
various lesions is made early. Before the muscles start wasting, one must
pave the way for their re-innervation.
Surgical Exploration
•• The aim of exploration is to do a nerve reconstitution which may be by
decompression, neurolysis, direct repair, nerve grafting, nerve crossing
or direct neurotisation.
Direct Nerve Repair
•• It is not indicated commonly.
•• Only in sharp penetrating injuries it is possible, especially when the
exploration is immediately after injury.
•• It will be a rewarding experience as the recovery is good.
•• When the gap is not suitable for direct repair, interfascicular nerve grafting
is the procedure of choice.
Neurolysis
•• It is indicated in the presence of scarring involving the plexus. It is common
in compression and traction lesions.
•• This scarring is classified into three types:
–– Type A: Scarring outside the plexus
–– Type B: Interfascicular scarring
–– Type C: Scarring involving the perineurium and endoneurium.
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Nerve Grafting
•• In cases of post-ganglionic rupture and in 4th degree damage, it is essential
to resect the scarred areas and connect the cut ends with a nerve graft.
•• If the rupture is just outside the intervertebral foramina, one has to assess
the viability of the proximal roots.
•• Root cross-section should show the fascicles, and positive SSEP and
muscle contraction on stimulation of proximal motor branches confirm
the viability.
•• It is always better to spread the grafts, so that there is space between them.
This will facilitate vascularisation.
Nerve Crossing
•• In pre-ganglionic and in severe post-ganglionic root avulsions where the
proximal nerve is not available, the only option is to neurotise the distal
nerves.
•• The aim should be to restore shoulder, elbow and hand functions by
neurotising the suprascapular, axillary, musculocutaneous, nerve to triceps
and median nerve, utilising nearby healthy nerves.
•• One of the most important factors for success in nerve crossing is the
neuronal quantum. It must have adequate axons to achieve good functions.
•• The density of the axons of each nerve has been worked out and it is mandatory
that at least 30% of axonal density is recruited to achieve good results.
•• Nerve crossing is always better, if it is done more peripherally, because
the recovery can be quick.
•• Sensory motor mismatching can be avoided, co-contractions can be
avoided and double level lesions can be skipped which are common in the
suprascapular and axillary nerves.
•• Ideal recipient nerves are pure motor nerves like the suprascapular, nerve
to biceps, nerve to brachialis, nerves to triceps, anterior and posterior
interosseus nerves and the axillary nerve, where the sensory branch can
be isolated and left behind.
•• These nerves are dissected close to the hilum. They must supply a single
muscle, but if they supply multiple muscles, all of them must have a
synergistic function. Nerve crossing can be done for sensory nerves also.
•• Commonly performed nerve crossing procedures are:
–– Spinal accessory to suprascapular
–– Intact ulnar nerve as donor
–– Triceps nerve branches to axillary nerve
–– Intercostal nerves.
Direct Neurotisation
•• Re-innervation of the denervated muscle can be done by implanting into
it a new nerve or grafts connected with the proximal stump of the proper
nerve and divided into several artificial branches.
•• It is done with contralateral C7, vascularised ulnar graft.
FUNCTIONAL FREE MUSCLE TRANSFER

Doi Procedures
•• The original technique of double functional muscle transfer consisted of
five established reconstructive procedures done in two stages.
•• This technique yielded the most reliable prehensile function after irreparable
injuries according to Doi.
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First Stage
•• Surgical exploration of the brachial plexus, intra-operative diagnosis using
electrophysiologic testing and repair of the disrupted cervical roots, when
possible.
•• The first “first functional muscle transfer” (FFMT) supplied by the spinal
accessory nerve transfer to restore elbow flexion and finger extension.
Second Stage
•• The second FFMT supplied by the fifth and sixth intercostal nerves to
restore finger flexion.
•• Transfer of the third and fourth intercostal nerves to the motor branch of
the triceps brachii muscle (done concomitantly with the second FFMT) to
restore elbow extension.
•• Transfer of the supraclavicular sensory nerves or the intercostal sensory
rami to the median nerve or the ulnar nerve component of the medial cord
of the brachial plexus (done concomitantly with the second FFMT), to
restore hand sensibility.
55
CHAPTER
Management of
Injuries to Specific
Peripheral Nerve
Gupta A  Ahmad FU  Mehta VS
Evaluation of Nerve Injury

•• Clinical history should include the mode of injury, time since injury, extent
of functional impairment, associated injuries (vascular, bony, visceral, etc)
and evidence for recovery of functions.
•• Examination should include the degree and distribution of muscle wasting,
grade of power in different muscles, range of movements and extent of
sensory impairment.
•• Local examination for the presence of neuroma, Tinel’s sign, associated
bony or vascular injury, external wounds and deformities are important.
•• The presence of Tinel’s sign is useful to localise a nerve injury. Tinel’s sign
refers to paraesthesias elicited by tapping along the course of a nerve.
Progressive distal advancement of Tinel’s sign over time can be useful
clinically to follow the course of regenerating sensory axons.
•• Electrodiagnostic tests are useful adjuncts to clinical examination.
•• Serial electrodiagnostic studies can also detect a distally advancing nerve
conduction response representing the regenerating front of axons.
•• Two to three weeks after an axonotmetic or neurotmesis grade of injury,
the results of electromyography (EMG) become abnormal.
•• Spontaneous activity, including fibrillations, fasciculations and positive
sharp waves develop in the affected muscles.
•• Radiology is not of much use in surgical decision making, except for
demonstration of associated fractures and callus formation.
Philosophy of Management
•• Both neuropraxic and axonotmetic grades of traumatic injury do not require
•• Patients with such injuries should be followed-up with serial clinical and
electrodiagnostic examinations to document recovery and confirm the
diagnosis.
•• Complete nerve injuries may represent either an axonotmetic or
neurotmesis grade of injury.
•• It is important to distinguish between these two, as the latter requires
surgery for recovery to occur.
•• Traumatic peripheral nerve injuries can be classified into open and closed
injuries.
•• Decision making for open injuries is relatively straightforward.
•• Immediate repair of acute sharp lacerating injuries should be undertaken,
with the aim of performing a primary end-to-end suture repair.
Chapter 55 • Management of Injuries to Specific Peripheral Nerve
423
•• Contraindications to primary repair are extensive bruising, destruction of

tissues, contamination of the wound, ragged nerve ends or loss of length
of nerve.
•• Under these circumstances, the nerve ends should then be tagged together
to prevent further retraction and for identification later.
•• The surgery should then be performed 3–4 weeks later when the associated
wound has healed.
•• This delay will allow for demarcation of the healthy proximal and distal
nerve ends from the intervening scarred segment.
•• Lesions in continuity cannot be accurately assessed during the acute
period, when seen during tendon repairs or open reduction of a fracture.
Closed Injuries
•• In the majority of closed traumatic injuries, however, the nerves are not
actually transected.
•• Instead, a “lesion in continuity” representing the damaged segment of nerve
may be produced, which results in either a neurapraxic, axonotmetic or
neurotmesis grade of injury.
•• These injuries should be explored:
–– When nerve function is steadily deteriorating.
–– When recovery stops before reaching any useful degree.
–– When spontaneous recovery is overdue: If there is no clinical or
electrophysiological evidence of recovery, even after the time it was
expected to occur (3–4 months in brachial plexus injury, but different
in different nerve injuries), the nerve should be explored.
–– When there is a painful traumatic neuroma.
Treatment Options
•• The surgical techniques applicable to peripheral nerve surgery include both
external and internal neurolysis.
•• External neurolysis:
–– Involves freeing the nerve from its bed, by removing constrictive
adhesions attaching it to the surrounding tissues. Surgical resection of
the scar may promote recovery of nerve function.
–– While performing intra-operative recordings of the nerve action
potentials (NAP) on a lesion in continuity, stimulating and recording
electrodes should be placed on the nerve proximal to the lesion to
assess the NAP.
•• Internal neurolysis:
–– Indicated in cases in which an injury is more severe at one portion of
the nerve than another, in the presence of an NAP transmitted across
the lesion.
–– Split or partial graft repairs may be necessary, when individual
fascicles or bundles of fascicles do not transmit NAPs.
•• The nerve ends should carefully be looked at to determine the fascicular
topography before approximating them.
•• Another method is to utilise surface vessels for alignment.
•• A minimum number of sutures should be used to decrease scarring.
Sutureless Repair
•• Laser welding, cuff union or fibrin adhesives of axon conduits have been
used to approximate fascicles in the hope of reducing scar tissue formation.
424
•• Improved functional results using these techniques have not yet been
demonstrated definitively.
Nerve Grafts
•• Several types of nerve autografts have been described which include:
1. Cable nerve graft: Many parallel grafts of donor peripheral nerves are
used to match the thickness of the recipient nerve.
2. Group interfascicular nerve graft: The fascicles at the proximal and
distal ends are appropriately grouped and matched with cable grafts.
3. Free neurovascular nerve grafts: A nerve is transferred along with its
vascular pedicle.
4. Pedicle nerve graft: A full thickness nerve graft is transferred in a two-
stage procedure.
5. Tubal graft: Using a vein, artery or other mesothelial tubes.
Post-operative Management
•• It is extremely important that patients undergo regular physical therapy,
both supervised and on their own, to maintain range of movement and to
optimise the recovery of motor function as re-innervation of muscles occur.
•• Along with physiotherapy, occupational therapy, orthosis, limb
reconstruction, and wherever required, psychotherapy should be used in
the post-operative period.
56
CHAPTER
Entrapment Syndromes
Gupta A  Ahmad FU  Mehta VS
INTRODUCTION
•• Entrapment neuropathy is defined as a condition in which a nerve is
continuously irritated by compression created by encroachment or
impingement by a nearby anatomical structure.
•• The most common entrapment neuropathy is carpal tunnel syndrome
followed by ulnar nerve entrapment at the elbow.
TRAUMATIC AND ENTRAPMENT NEUROPATHIES

The common sites for entrapment neuropathies are:
•• Carpal tunnel syndrome.
•• Ulnar nerve at elbow or wrist.
•• Cervical or lumbosacral radiculopathies (includes thoracic outlet
syndromes).
•• Median nerve at elbow.
•• Anterior interosseous syndrome.
•• Radial nerve in upper arm.
•• Sciatic nerve.
•• Common peroneal nerve at knee.
•• Tibial nerve at knee.
•• Lateral cutaneous femoral nerve (meralgia paraesthetica).
•• Spinal accessory nerve in posterior cervical triangle.
•• Subscapular neuropathy.
PATHOPHYSIOLOGY
•• The clinical manifestations of neuropathy depend on the type and
distribution of the affected nerve modalities, the degree of nerve or myelin
damage, and the course of the disease.
•• Demyelinating neuropathies primarily affect the myelin sheaths whereas,
axonal neuropathies target the peripheral nerve axons.
•• When motor nerves are damaged, weakness and muscle atrophy occur.
•• Damage to sensory nerves can cause loss of sensation, paraesthesia and
dysaesthesia, pain and sensory ataxia.
•• Autonomic dysfunction can result in postural hypotension, impotence,
gastrointestinal and genitourinary dysfunction, abnormal sweating and
hair loss.
•• Involvement of small myelinated and unmyelinated sensory fibres typically
result in impaired pin prick and temperature sensation, numbness, and
painful burning, cold, stinging, or tingling paraesthesia.
426
•• Large diameter sensory fibre involvement manifests as loss of vibration and

position sensation, sensory ataxia and numbness or tingling paraesthesia.
•• Deep tendon reflexes are frequently diminished or absent, particularly in
the demyelinating neuropathies.
Carpal Tunnel Syndrome

•• Synonym: Median nerve entrapment at the wrist.
•• This is the commonest kind of entrapment seen in clinical practice.
•• This was a severe entrapment accompanied by pain, paresthesias, loss of
sensation and infrequently even ulceration in the fingers 1 to 3.
Aetiology
•• The aetiology of carpal tunnel syndrome is compression of the median
nerve in the carpal tunnel.
•• The carpal bones form the floor and walls of the carpal tunnel, and the roof
is created by the transverse carpal ligament.
•• Nine flexor tendons with their sheaths accompany the median nerve in
the carpal tunnel.
•• Just before entering the carpal tunnel, the median nerve gives off the palmar
cutaneous branch that carries sensory fibres from the thenar eminence.
•• After the median nerve exits from the carpal tunnel, it gives off the thenar
motor branch innervating the abductor pollicis brevis, the opponens pollicis
and the first and second lumbrical muscles.
•• Carpal tunnel syndrome occurs in conditions that either reduce the space
in the tunnel or cause increased susceptibility of the nerve.
•• Reduced space may be caused by tenosynovitis, rheumatoid arthritis,
ganglia, osteophytes, osteosis, anomalous muscles or tumours.
•• Fluid retention is thought to be responsible for it in pregnancy, during
lactation or during the use of oestrogens.
•• Conditions which increase the susceptibility of the nerve are diabetes,
hypothyroidism, hereditary neuropathy with pressure palsies, acromegaly,
focal amyloid deposition that can be idiopathic or secondary to a genetic
defect, systemic amyloidosis or dialysis.
•• Work-related carpal tunnel syndrome occurs with repetitive hand and wrist
movement and is seen with a variety of activities and occupations.
•• Increased pressure within the carpal tunnel due to certain positions of the
hand and wrist and oedema of the flexor tendons are thought to contribute
to occupational carpal tunnel syndrome.
•• Acute carpal tunnel syndrome is mostly seen in the setting of traumatic
injury to the hand or wrist, and occasionally, the forearm. It can be caused
by the common Colles’ fracture of the distal radius.
•• Furthermore, bleeding into the carpal canal due to coagulation disorders
seen in cases of leukaemia, haemophilia or anticoagulant therapy can
provoke acute carpal tunnel syndrome. Urgent surgical release is indicated
for acute severe carpal tunnel syndrome.
Associated Disorders
•• Amyloid neuropathy
•• Amyloidosis
•• Colles’ fracture
•• Diabetes mellitus
•• Dialysis
Chapter 56 • Entrapment Syndromes
427
•• Hereditary neuropathy with pressure palsies

•• Hypothyroidism
•• I-cell disease and pseudo-Hurler polydystrophy
•• Median neuropathy
•• Mucopolysaccharidoses
•• Repetitive strain injury
•• Rheumatoid arthritis.
•• The clinical manifestations of carpal tunnel syndrome consist of intermittent
pain, numbness and tingling in the fingers that is dependent on the position
of the hand and wrist and commonly associated with subjective weakness
of grip.
•• The symptoms occur initially at night only and may wake the patient from
sleep.
•• In more severe cases, the symptoms occur also during the day.
•• They are often provoked by hyperextension or hyperflexion of the wrist
during activities such as driving, or during work-related repeated hand
movements.
•• The pain can radiate up into the forearm or even up to the shoulder.
•• There frequently is subjective hand swelling and stiffness.
•• The patient will often shake the hand and fingers in an effort to obtain relief
from the discomfort (flick sign).
•• On clinical examination, there can be a discrete sensory disturbance in the
lateral three fingers and weakness or atrophy of the thenar muscles with
a positive Tinel’s sign over the carpal tunnel.
•• Phalen’s test, where the patient is asked to hyperflex the wrist for one
minute, may provoke the symptoms. Phalen’s test is more specific for
carpal tunnel syndrome than Tinel’s sign, but both can be present in
normal individuals.
•• It is, more often, the clinical history than the physical examination that is
highly suggestive of carpal tunnel syndrome.
•• Carpal tunnel syndrome should be differentiated from cervical radiculopathy,
polyneuropathy, other entrapment of the median nerve, ulnar neuropathy,
and brachial plexopathy.
•• Non-neurologic causes of wrist and hand pain include de Quervain’s
tenosynovitis of the abductor pollicis longus and extensor pollicis brevis
tendons, trigger finger, non-specific tenosynovitis, osteoarthritis of the basal
joints of the thumb, and Raynaud’s disease.
Diagnostic Workup
•• Electrophysiological testing has an important role in the diagnostic workup
for carpal tunnel syndrome.
•• Electrodiagnostic testing usually includes motor and sensory nerve
conduction studies of both median nerves and at least one ulnar nerve.
•• Needle examination of the abductor pollicis brevis muscles is routinely
performed to look for denervation.
•• Sensory nerve conduction studies are the most sensitive in confirming
the diagnosis.
•• The most common finding is an increase in distal latency due to focal
slowing of conduction across the carpal tunnel.
428
•• The next most sensitive feature is a decrease in amplitude of the sensory

response.
•• In severe carpal tunnel syndrome, there is acute or chronic denervation on
needle examination of the abductor pollicis brevis, suggesting axon loss of
median motor nerve axons.
•• The MRI of the wrist can document abnormalities in the median nerve that
are compatible with carpal tunnel syndrome.
•• The MRI may be helpful if tumours or other structural abnormalities are
suspected.
•• A routine wrist X-ray is not useful, unless it is to demonstrate a fracture
at the wrist.
Management
•• Carpal tunnel syndrome, unless accompanied by a severe clinical deficit,
is usually first treated conservatively with the use of a resting wrist splint
and adviced to reduce provoking activities.
•• This is successful in about 50% of patients and gives permanent relief only
in 50% of these patients.
•• Steroid injections into the carpal tunnel can provide immediate relief, but
this is usually not sustained and local complications may occur.
•• If conservative treatment is not effective, surgical carpal tunnel release
is performed.
•• This results in an improvement rate of 80−90%.
•• Patients can usually return to work in 2−3 weeks. It should be kept in mind
that this rate of success comes down significantly in patients who would
be seeking compensation.
•• Endoscopic carpal tunnel release supposedly produces less scarring than
open surgery, but precludes visualisation of the median nerve properly.
•• Controversy remains regarding which procedure is the best. However,
certain advantages of endoscopic treatment are earlier return to work, less
immediate post-operative pain and avoidance of post-operative splinting.
Prognosis and Complications
•• The prognosis for recovery is good with either conservative or surgical
treatment.
•• The complications include persistent weakness and sensory loss in the
distal median nerve distribution.
•• The most dramatic complication is complex regional pain syndrome, a
condition which is characterised by severe pain, hyperalgesia, dysaesthesia
and trophic disturbances.
Median Nerve Entrapment at Other Sites

•• Entrapment of the median nerve at other regions of the upper limb is much
less common.
•• After carpal tunnel syndrome, the most common median nerve entrapment
is the pronator teres syndrome.
•• Other less common entrapment sites include the ligament of Struthers,
lacertus fibrosus and the tendinous origin of the flexor digitorum superficialis.
•• Struthers’ ligament can compress the median nerve.
Ulnar Nerve Entrapment at the Elbow

•• Ulnar neuropathy is the second most common entrapment neuropathy.
429
•• In contrast to carpal tunnel syndrome, in which sensory impairment is

generally the most significant disability, motor loss is usually the most
important problem in ulnar nerve entrapment, most notably in the intrinsic
muscles of the hand.
Aetiology
•• There are at least four potential sites of compression of the ulnar nerve in
the region of the elbow:
–– At the medial intermuscular septum (arcade of Struthers) just above
the elbow.
–– In the retroepicondylar (ulnar) groove.
–– At the humeroulnar aponeurotic arcade (“cubital tunnel”).
–– At the point of exit of the nerve from the flexor carpi ulnaris.
•• In the majority of patients with ulnar neuropathy at the elbow, the initial
symptoms are intermittent ulnar distribution numbness and tingling, often
associated with elbow flexion.
•• Similar to carpal tunnel syndrome, these symptoms are most noticeable
at night.
•• Patients may not seek medical care until significant intrinsic hand muscle
atrophy develops.
•• The ulnar sensory distribution typically includes the palmar surface of the
little finger and the ulnar half of the ring finger.
•• Sensory loss is usually easiest to detect over the tip of the little finger, and
diminution of sensibility is usually more pronounced for light touch and
two-point discrimination as opposed to pinprick and temperature.
•• The ulnar nerve provides fine motor control, co-ordination, and dexterity
to the hand, in contrast to the median nerve that provides more in the way
of raw power.
•• The median nerve has been called the “workman’s nerve” and the ulnar
nerve the “musician’s nerve”.
•• A frequent early manifestation of ulnar neuropathy is a tendency of the
small finger to get “hung up”, as when placing the hand in a pocket, and an
abducted posture of the small finger on examination (Wartenberg’s sign).
•• Observing the patient’s ability to touch the index to the small finger is a
good test of interosseous function.
•• Another useful manoeuvre is to have the patient press their first dorsal
interosseous or abductor digiti minimis together to see if one side
overpowers the other.
•• Froment sign results from substituting the flexor pollicis longus to adduct
the thumb and provide a pincer function.
•• The ulnar griffe, or claw deformity, is due to weakness of the third and the
fourth lumbricals.
•• In ulnar lesions, unopposed extensor tone at the metacarpophalangeal
joints and unopposed flexor tone at the proximal interphalangeal joints
draw the ring and small fingers into a position with extension at the
metacarpophalangeal joints and flexion at the proximal interphalangeal
joints.
•• Clawing varies depending on the amount of muscle weakness, the laxity
of the metacarpophalangeal joints and the level of the lesion.
•• A “low” (distal) ulnar lesion with preserved function of the flexor digitorum
profundus induces more clawing than a “high” (proximal) ulnar lesion,
where the accompanying long finger flexor weakness creates less of the
430
unopposed flexor pull deforming the ring and small fingers. Conditions
other than ulnar neuropathy can produce a hand deformity mimicking
ulnar clawing.
•• Evaluation of a patient with suspected ulnar neuropathy at the elbow should
include examination of the elbow both for range of motion and for deformity.
•• Impaired range of motion, flexion contracture, valgus deformity, or other
bony or joint abnormality suggests an elbow level lesion.
•• Reproduction of symptoms with elbow flexion and ulnar groove pressure
can be informative. Worsening of the hypaesthesia or pain with sustained
elbow flexion, especially if combined with digital pressure over the nerve,
suggests ulnar nerve compression near the elbow (the “elbow flexion” test).
•• A nerve conduction study is also a useful diagnostic test, with conduction
delays of at least 10 m/s in the affected arm relative to the unaffected arm.
•• When significant atrophy is noted, differences of at least 15 m/s are
typically found.
Management
•• The treatment of ulnar neuropathy at the elbow is generally considered
surgical, but many patients, especially those with mild involvement, may
recover spontaneously or with conservative treatment.
•• Anterior transposition of the nerve is the most common for this condition
operation.
•• The two types of transposition methods now commonly employed are:
1. The subcutaneous, or superficial, and
2. The submuscular, or deep.
•• The main advantage of decompression and medial epicondylectomy over
transposition is preservation of the ulnar nerve blood supply, as extensive
dissection with the possibility of devascularisation of the ulnar nerve is
unnecessary.
Radial Nerve Entrapment

•• Radial neuropathy most commonly presents with sudden painless wrist
and finger drop.
•• There may be associated paraesthesias or numbness over the dorsum
of the hand.
•• Radial neuropathy is most commonly due to compression at or around
the spiral groove.
•• Due to its more proximal innervation, the triceps muscle is spared.
•• Elbow flexion may seem to be intact due to the biceps muscle compensating
for the weakened brachioradialis muscle.
•• Motor deficit involves wrist and finger extensor muscles.
•• Sensation is impaired over the dorsum of the hand, mainly in the region of
the first and the second metacarpals.
•• Lesions, a few centimetres distal to the elbow result in posterior
interosseous neuropathy.
•• Tenderness can occur 5 centimetres distal to the elbow.
•• Useful features are pain reproduction or exacerbation by pressure, resisted
supination with 90-degree elbow flexion or middle finger extension, and
relief by local anaesthetic injection.
•• There is typically no sensory loss.
•• A handcuff or watchband may additionally compress the median and ulnar
nerves.
431
•• Superficial radial neuritis, or Wartenberg’s syndrome, is associated with

pain at the radial styloid radiating to the hand and is exacerbated by ulnar
deviation of the wrist.
•• Tinel’s sign is usually positive over the junction of the middle-to-distal third
of the radius.
Aetiology
•• Compression, trauma and entrapment are the main mechanisms of radial
nerve injury.
•• Tumour, systemic disease and birth trauma constitute less common causes.
•• Radial nerve compression is most frequently at or within close vicinity of
the spiral groove.
•• The radial nerve, in “saturday night palsy”, may be compressed during
sedation, deep sleep, inebriation or by the head of a sleeping partner.
•• Triceps muscle fibrosis induced by chronic analgesic intramuscular injection
may cause severe progressive painless radial neuropathy.
•• Radial nerve compression may occur more proximal due to inappropriate
crutch pressure at the axilla, prolonged tourniquet application, frequent
automated blood pressure cuff inflation or poor arm position during
anaesthesia.
•• Radial nerve compression at the axilla or arm may be associated with ulnar
or median nerve dysfunction.
•• The differential diagnosis of radial neuropathy includes C7 radiculopathy,
posterior cord brachial plexopathy and extensor tendon rupture.
Management
•• With few exceptions, conservative management with clinical and
electrodiagnostic follow-up is the rule for radial neuropathies.
•• Most patients with radial palsies induced by compression recover fully
within 2−12 months.
•• Faster and more complete recovery is anticipated with neuropraxia.
•• All patients with radial neuropathy should wear a splint with passive
dorsiflexion at the wrist and fingers.
•• Indications for early exploration of post-traumatic radial neuropathy include
complex humeral fractures or weakness developing after closed reduction
of a simple fracture.
•• Exploration of a simple humeral fracture may be delayed for 2 months to
allow for spontaneous radial nerve recovery.
•• Successful nerve graft induces return of function in 12−18 months.
•• Delayed tendon transfers may restore wrist extension.
•• Conservative management of spontaneous superficial radial neuropathy
includes prevention of external compression at the wrist, avoidance of
repetitive wrist movements, nocturnal wrist splints and local anaesthetic
or steroid injection.
•• Otherwise, surgical decompression is effective as it is for traumatic radial
nerve laceration.
Sciatic Neuropathy
•• Sciatic neuropathy presents, usually acutely, with foot weakness, pain
and sensory loss.
432
•• Foot pain and dysaesthesia are common major symptoms in most patients.
•• The foot weakness is commonly manifested as a foot-drop, which results
in a diagnostic challenge as sciatic neuropathy may imitate a peroneal
neuropathy at the fibular head.
•• In severe sciatic neuropathy, weakness of hamstrings (knee flexion) and
gastrocnemius muscles (plantar flexion) is also present.
•• The ankle jerk is usually depressed or absent.
•• Sensory loss and dysaesthesia of the sole and dorsum of the foot and
lateral leg are common.
•• Sciatic neuropathy is caused by external compression of the nerve, or by
stretching around the hip during surgical procedures. Less common causes
include injection injuries, vasculitis and gunshot or knife injuries.
•• The treatment of patients with sciatic neuropathy is mostly directed towards
the management of pain with tricyclic antidepressants, anticonvulsants
and topical analgesia.
•• Initially, the foot-drop will require an ankle-foot orthosis.
•• Leg elevation and stockings are useful when swelling is prominent.
•• Surgical exploration and neurolysis or grafting is sometimes necessary
in patients who do not show signs of re-innervation, on conservative
management.
•• Common causes of foot drop are elaborated in Table 1.
Piriformis Syndrome
•• The sciatic nerve along with the inferior gluteal and pudendal nerves exits
the pelvis through the lower part of the great sciatic foramen deep to the
piriformis muscle.
Table 1: Clinical differential of common causes of foot drop

Peroneal L5 Lumbar Sciatic
neuropathy at radiculopathy plexopathy neuropathy
the fibular head (lumbosacral (mainly
trunk) peroneal)
Common Compression Disc herniation, Pelvic surgery, Hip surgery, injec-
causes (weight loss, spinal stenosis haematoma, pro- tion injury, coma
peri-operative), longed labour
trauma
Ankle Normal Weak Weak Normal or mildly
inversion weak
Toe flexion Normal Weak Weak Normal or mildly
weak
Plantar Normal Normal Normal Normal or mildly
flexion weak
Ankle jerk Normal Normal (unless Normal (unless Normal or
with S1) with S1) depressed
Sensory Peroneal only Poorly demarcat- Well demarcated Peroneal and
loss ed, predominantly to L5 dermatome lateral cutaneous
big toe of calf
Pain Rare, deep Common, Common, can be Can be severe
radicular radicular
433
•• The piriformis is attached to the inner face of the bony pelvis and the
greater trochanter.
•• The development of the syndrome depends on muscular activity and
hypertrophy.
•• The symptoms are pain, paraesthesiae and motor weakness.
•• Due to the involvement of the pudendal nerves, the patient along with
sciatica, may have pain radiating to the groin.
Management
•• The treatment of the piriformis syndrome is controversial and often difficult.
•• Conservative therapy includes stretching of the piriformis muscle by flexion,
adduction and internal rotation of the symptomatic hip.
•• Injection into the piriformis muscle with corticosteroids, preferably done
under imaging guidance, may also result in relief of buttock pain.
•• Botulinum toxin injection may reduce the pain in a significant number of
patients.
•• Surgical exploration of the sciatic nerve in the region of the piriformis muscle
is indicated only in cases resistant to conservative therapy.
•• Abnormal bands or vessels constricting the sciatic nerve in the buttock
should also be removed.
•• Section of the piriformis muscle is the most popular advocated procedure,
but its value is uncertain.
•• Sciatic nerve varices may respond to foam sclerotherapy, leading to
complete obliteration of the offending vein.
Thoracic Outlet Syndrome (TOS)

•• Before discussing the clinical manifestations, it is important to distinguish
the different forms of TOS.
•• True neurologic or neurogenic TOS:
–– The disorder itself is rare and is usually due to congenital anomalies,
but presents in middle-aged women and almost always unilaterally.
–– Symptoms include weakness and wasting of hand muscles, and numb-
ness in the hand.
•• Non-neurogenic TOS: This is the common form of TOS, and also the most
non-specific form. The most prominent symptom of this disorder is pain,
and neurologic/electrophysiological findings are limited.
•• Arterial TOS: Arterial TOS is rare and is also caused by a congenital
anomaly. It affects both males and females, and is often found in young
people. Symptoms may include hypersensitivity to cold in the hands and
fingers, numbness or pain in the fingers, and finger ulcers (sores) or severe
limb ischaemia (inadequate blood circulation) in unusual cases.
•• Venous TOS: This is also a rare disorder which affects both men and
women. The exact cause of this type of TOS is unknown, but it has been
reported as presenting suddenly following unusual, prolonged limb exertion.
•• Traumatic TOS: This syndrome may be due to either trauma, such as a
motor vehicle accident, repetitive activities, or with hyperextension injury.
The common presentation in this syndrome is pain and paraesthesias, and
uncommonly, weakness.
434
Aetiology
•• There are three major causes of TOS:
1. Anatomic: Anatomical variants at the scalene triangle, often due to
the anterior scalene muscle frontally, middle scalene muscle posteri-
orly, and the upper border of the first rib inferiorly, can account for at
least some cases of neurologic TOS.
2. Trauma or repetitive activities: Hyperextension injury during motor
vehicle accidents, with subsequent fibrosis and scarring may lead to
non-neurogenic forms of TOS. Musicians may be susceptible due to
positioning of their shoulder in abduction or extension for long periods
of time, although this is unlikely to lead to neurogenic TOS.
3. Neurovascular entrapment: Entrapment may occur in the costocla-
vicular space between the first rib and the head of the clavicle. This is
a more frequent cause of non-neurogenic TOS.
•• True neurologic TOS:
–– Usually presents with unilateral symptoms and signs, and often starts
with pain.
–– The typical patient has previously been described as a young, thin
female with a long neck and drooping shoulders.
–– It is the lower two nerve roots of the brachial plexus, C8 and T1, which
are most commonly (90%) involved, producing pain and paraesthesias
in the ulnar nerve distribution.
–– Pain may be accompanied by paraesthesias, which are often intermit-
tent and often can be nocturnal, leading to the patient waking up from
sleep.
–– Sensory loss may occur over the same anatomical distribution, with
a pattern clinically referable to the lower trunk of the brachial plexus.
–– Weakness and muscle atrophy will tend to affect distal muscles of the
arm, and classically affect the thenar muscles more than the hypoth-
enar muscles.
–– Tinel’s sign over the supraclavicular fossa has been described as a
potential diagnostic feature.
–– The elevated arm stress test (EAST) is possibly the most reliable
screening test, although it is non-specific and evaluates all three types
of TOS.
•• A number of diseases can mimic the presentation of TOS. In most clinical
situations, TOS is a diagnosis of exclusion.
•• Ulnar and median nerve entrapment.
•• Cervical disc herniation.
•• Cervical vertebral osteophyte formation.
•• Brachial plexitis.
•• Pancoast tumour.
•• Nerve sheath tumour.
•• Spinal cord tumour or other mass lesion.
•• Syringomyelia.
•• Multiple sclerosis.
•• Complex regional pain syndrome.
435
Diagnostic Workup
•• Nerve conduction studies and EMG can be helpful in the diagnostic
evaluation of patients with suspected TOS.
•• In severe cases of true neurogenic TOS, nerve conduction studies may
reveal the following characteristics:
–– Decreased amplitude of ulnar sensory nerve action potentials
–– Decreased amplitude of median compound motor action potentials
–– Normal or slightly decreased ulnar compound motor action potentials
–– Normal median nerve sensory nerve action potentials.
•• Cervical spine and chest X-rays can identify bony abnormalities, including
cervical ribs or prominent, often “peaked” C7 transverse processes.
•• Anomalous cervical ribs are found in approximately 10% of patients with
TOS (compared to 0.5% in the normal population).
•• The MRI and CT are most useful in the identification of conditions in the
differential diagnosis of neurogenic TOS.
Management
•• For most patients with true neurogenic TOS, conservative treatment is
reasonable to offer first.
•• Conservative management includes the modification of behaviour by
avoiding provocative activities and arm positions.
•• Improvement with purely conservative management of TOS ranges from
50 to 90%.
•• Surgical intervention is usually indicated in the true neurogenic form of TOS,
in which conservative management most often is unsuccessful.
•• The two most commonly used surgical approaches for the treatment of
neurogenic TOS are the anterior supraclavicular and the transaxillary
approach for resection of the first rib.
•• The anterior supraclavicular approach is preferred by most neurosurgeons,
as it provides for wide exposure of the supraclavicular plexus and middle
two-thirds of the first rib, where most of the congenital bands are located.
The first rib can be resected using this approach. Relief can be expected
in about 80% of cases.
•• The transaxillary approach with resection of the first rib is the technique
preferred by most thoracic surgeons and many vascular surgeons.The
advantage of this approach is easy access for resection of the entire first
rib without significant risk to neurovascular structures.
Meralgia Paraesthetica
•• This is a painful condition attributed to entrapment or injury to the lateral
femoral cutaneous nerve at the site where the nerve leaves the pelvis.
•• The patient with meralgia paraesthetica may complain of a dull ache,
itching, numbness, tingling or burning sensation over the lateral and
anterolateral thigh.
•• The pain associated with this condition may vary in intensity from mild to
very severe and frequently occurs following activity with relief following rest.
•• The lateral femoral cutaneous nerve originates from the posterior division
of the L2 and L3 nerve levels and is a pure sensory nerve. Following
emergence from the intervertebral foramina of L2 and L3, the nerve
traverses the abdomen, first making an appearance at the lateral border
of the psoas muscle, and then passing obliquely across the iliacus muscle
towards the anterior superior iliac spine.
436
•• The nerve then exits the pelvis just medial to the anterior superior iliac spine
(ASIS) by traversing the fibres of the inguinal ligament.
•• The nerve is surrounded by the tendinous fibres of the inguinal ligament
at this point and makes a right-handed bend to change direction from a
horizontal course in the pelvis to a more vertical course in the lateral and
anterolateral thigh.
•• Various hypotheses have been formulated for the cause of this condition
based on the anatomical relationship between the lateral femoral cutaneous
nerve and the structures associated with the inguinal region.
•• The nerve may be angulated or compressed against a sharp edge of
fascia as it pierces the iliac fascia prior to exiting the pelvis beneath the
inguinal ligament.
•• The nerve may be subjected to friction where it is wedged between the
attachment of the inguinal ligament and the ASIS.
•• The nerve may pass through the tendinous fibres of the inguinal ligament
and be pinched at this site.
•• In diagnosing meralgia paraesthetica, care should be taken to rule out
intraspinal, retroperitoneal, abdominal, or pelvic pathologies, diabetes
mellitus, and L3 disc prolapse.
•• Clinically, L3 disc prolapse may produce alteration of the patellar reflex. In
contrast, the reflex will not be altered in meralgia paraesthetica.
•• Most cases of meralgia paraesthetica will respond to conservative care.
•• Modalities that may prove helpful in the treatment of this condition may
include ultrasound, electrical stimulation, or transverse friction techniques
to break up possible adhesions affecting the lateral femoral cutaneous
nerve at the inguinal region.
•• Postural alterations and functional spinal problems should also be
addressed in the management of this condition.
•• Rarely, surgical release is required.
Section VI: Infections
57
CHAPTER
Brain Abscess
Dharkar SR  Sardana VR  Purohit D
INCIDENCE
•• The incidence of brain abscess is comparatively higher in developing
countries as compared to developed countries.
•• In India, it is approximately 8% of all intracranial space occupying lesions.
•• Brain abscesses are encountered about one-sixth as frequently
as bacterial meningitis and account for approximately 0.7% of all
neurosurgical operations.
•• Several authors have reported a male preponderance (as high as 3:1).
AETIOPATHOGENESIS
•• Brain abscess develops either:
–– In association with a contiguous suppurative focus e.g middle ear,
–– After cranial trauma,
–– Haematogenous spread from a distant focus,
–– Cryptogenic origin, or
–– Due to miscellaneous causes.
In Association with Contiguous Suppurative Focus

•• Brain abscesses occurring due to local extension from contiguous infective
foci, like traumatic, surgical, congenital, otic or paranasal infections, usually
manifest adjacent to the predisposing focus.
•• They occur as a result of either:
–– Direct extension through associated osteitis or osteomyelitis
–– Retrograde thrombophlebitic spread via diploic or emissary veins into
the intracranial cavity or
–– Via local lymphatics.
•• Bone infection of the walls of the paranasal sinuses or of the middle and
inner ears is the usual precursor of a brain abscess.
•• The bone is infected through a necrotic area of mucosa, or by spread
through lymphatics and veins penetrating the bone leading to osteomyelitis.
•• In long standing cases, caries of the bone leads to dehiscence, the common
sites being the posterior wall of the frontal sinus, the tegmen tympani and
the lateral part of the posterior surface of the petrous bone (Trautmann’s
triangle).
•• The dura mater may completely resist infection so that an extradural
abscess is formed. During the process granulation tissue covers the
outer surface of the dura mater.
Section VI • Infections
438
•• Penetration of the dura mater probably takes place along the course of
small vessels which traverse its thickness; they may thrombose and provide
convenient pathways.
•• In the majority of cases where a brain abscess is secondary to adjacent
bone disease, the brain is adherent to the patch of inflamed dura mater.
Otogenic Abscess
•• The commonest cause of brain abscess is spread of infection from the
middle ear and mastoid, which in India accounts for 40–63.3%.
•• Typically brain abscesses related to otogenic infection are solitary and they
most often develop in the inferior portion of the ipsilateral temporal lobe.
•• In contrast to otogenic infections, mastoid infection typically leads to an
abscess in the ipsilateral cerebellar hemisphere.
•• Chronic otitis media and/or mastoiditis leads to intracranial extensions 4–8
times more frequently than does the acute disease.
•• Cholesteatomas complicating chronic otitis or mastoiditis are additional
risk factors, increasing the incidence of intracranial extension of infection
from 23.2–74%.
Paranasal Sinus Infection
•• Local spread from infection of the paranasal sinuses leading to abscess
formation in the brain, accounts for approximately 15% patients. In many
Western series, it is reported to be more common than otogenic abscess.
•• Most abscesses complicating infection in the frontal, ethmoid or maxillary
sinuses occur in the frontal lobe.
•• Intracranial abscess resulting from sphenoid sinusitis tends to occur in
either the temporal lobe or the pituitary fossa.
Periodontal Infection
•• They are more likely to occur after infection of the molar teeth, since the
infection can spread between the muscles of mastication along the fascial
planes to the skull.
•• The site of the abscess is most commonly the frontal lobe, but temporal
lobe abscess can also occur by direct extension.
Bacterial Meningitis
•• Rarely, brain abscesses can result as a complication of meningitis.
•• They occur more frequently in neonates, particularly infants with gram
negative meningitis.
•• Cerebral abscesses have been associated with more than 70% of
Citrabacter diversus meningitis in infants.
Post-traumatic
These are usually a sequele of a compound skull injury.
•• These abscesses result from retained contaminated bone fragments,
foreign bodies, hair, etc.
•• Patients having skull base fractures with cerebrospinal fluid (CSF) fistula
or bleeding through the ear and/or nose are always at risk of developing
intracranial infection and rarely an abscess.
•• Post-traumatic abscesses may not develop immediately after the primary
injury and in fact many years may elapse before such abscesses appear.
Chapter 57 • Brain Abscess
439
Metastatic Abscess
•• Metastatic abscess results from haematogenous spread of micro-organisms
from other parts of the body, frequently from chest infection like lung
abscess, bronchiectasis, empyema and cystic fibrosis.
•• Other remote foci of infection include wound and skin infections,
osteomyelitis, pelvic infection, cholecystitis and other forms of intra-
abdominal sepsis.
•• About 5–18% of patients with cyanotic heart disease develop a brain
abscess.
•• Fallot’s tetralogy is the most common cause for brain abscess.
•• Intracardiac right to left shunt allowing direct entry of blood containing
bacteria to the cerebral circulation bypassing the pulmonary filter,
hypoxaemia, metabolic acidosis, increased blood viscosity from
compensatory polycythaemia resulting in low perfusion areas (microinfarcts)
in the brain provide the perfect milieu where micro-organisms settle down
and multiply to form an abscess.
•• Regardless of the source, haematogenous brain abscesses occur in the
distribution of the middle cerebral artery, mostly in the parietal and frontal
lobes with a predilection for the left side.
•• Metastatic abscess formation usually begins at the corticomedullary junction
(grey and white junction) where brain capillary flow is slowest.
•• They are more frequently multiple and are more likely to be multi-loculated.
•• They tend to be less well encapsulated than those which occur by spread
from a contiguous site.
Cryptogenic
•• In a number of cases in which no focus of primary infection can be found,
they are embolic in nature and originate from minute lesions giving rise
to bacteraemia.
•• Such bacteraemia may occur during surgical procedures on the tonsils
and teeth.
Miscellaneous Causes of Brain Abscess

•• Brain abscesses may result as a complication of other non-neurosurgical
procedures such as submucous dissection of the nasal septum, cranial
traction with Crutchfield skull tongs, use of a halo orthosis and secondary
to bacteraemia following dilatation of oesophageal stricture and sclerosis
of oesophageal varices.
Post-operative Abscess
•• Brain abscesses as a complication of intracranial procedures are rare as
compared to local wound infection, cranial bone flap osteomyelitis, epidural
abscess, subdural empyema or meningitis.
•• Deep wound infections, cranial bone flap infections and the presence of
CSF leak increase the risk of formation of a brain abscess.
MICROBIOLOGY OF BRAIN ABSCESS

•• The microbes responsible for the formation of an abscess depend on the
pathogenic mechanism involved.
440
•• In many instances, more than a single bacterial species can be isolated

from the brain abscess.
•• In non-traumatic brain abscess, Streptococci including aerobic, anaerobic
and Microaerophilic streptococci are isolated in 60–70% of cases.
•• These bacteria, particularly Streptococcus milleri, are part of the normal
bacterial flora of the oral cavity, appendix and female genital tract.
•• Bacteriosides and enteric bacteria are recovered in 20–40% of cases and
Staphylococcus in 10–15% of cases.
•• Staphylococcus infection is usually caused by penetrating head trauma
or bacteraemia secondary to endocarditis. Clostridia infections are most
often post-traumatic.
•• Listeria monocytogenes, a gram-positive bacillus with special tropism for
the central nervous system (CNS), accounts for 10% of CNS infections.
Brain abscess due to Listeria has a poor prognosis and is associated with
a high mortality.
•• Klebsiella pneumoniae is a very uncommon microbial agent to cause
multiple brain abscesses in neonates that respond poorly to antimicrobial
agents.
•• K. pneumoniae brain abscess may occur in the absence of meningitis and
even in the absence of any identifiable risk factors.
PATHOGENESIS OF DEVELOPMENT OF BRAIN

ABSCESS AND CAPSULE FORMATION
•• Abscess development and maturation depends on a number of factors
including local tissue oxygen tension, the underlying cause of infection,
virulence of the offending organism, the type of organism (e.g. bacterial,
fungal, etc.), and the host immune response.
•• Britt et al identified four stages in the encapsulation process namely:
1. Early cerebritis (1st to 3rd day)
2. Late cerebritis (4th to 9th day)
3. Early capsule formation (10th to 13th day)
4. Late capsule formation (day 14th and beyond).
•• The onset and duration of each of these stages is not absolute and may be
altered by antibiotic therapy, administration of corticosteroids and alterations
in the immune status of the host.
Early Cerebritis Stage (1st to 3rd Day)

•• It is characterised by the presence of a necrotic centre of purulent material
accompanied by local inflammatory response surrounding the adventitia
of blood vessels.
•• This response is maximal on day 3 and results in marked oedema formation.
•• The lesion is not demarcated from the surrounding brain at this stage.
•• Histopathologically, the early cerebritis stage is characterised by a core of
purulent material surrounded by a zone of granulation tissue of variable
thickness comprised of inflammatory cells, neovascularity and hyperplastic
fibroblasts.
•• Thrombosis of the local vasculature, perivascular cuffing and perilesional
oedema is seen extending into the surrounding white matter.
441
Late Cerebritis Stage (4th to 9th Day)

•• The necrotic centre enlarges due to pus formation during the late
cerebritis stage, which is surrounded by a zone of inflammatory cells and
macrophages.
•• Fibroblasts begin to lay down a reticular network, which is the precursor
of the collagen capsule.
•• Oedema is maximal during this stage and reactive astrocytes become evident.
Early Capsule Formation (10th to 13th Day)

•• The spread of infection and subsequent destruction of the parenchyma is
limited by the important event of capsule formation which begins by the
10th day after the initial response to bacterial invasion.
•• During this process, fibroblast activity infiltrates the brain surrounding the
zone of cerebritis, and collagen and reticulin fibres are deposited.
•• The developing capsule is surrounded by an active zone of vascular
hyperplasia and perivascular cuffing.
•• Inflammatory cells may be observed infiltrating the adjacent leptomeninges
if the abscess is near the brain surface.
•• On the medial and ventricular side of the abscess, capsule formation is
slow and incomplete.
•• This is believed to be related, at least in part, to the amount of cerebral
blood flow and tissue oxygen tension adjacent to the developing capsule,
which in turn may affect the ability of collagen to form triple helix strands.
•• This probably explains the propensity for abscesses to rupture into the
ventricular system rather than into the subarachnoid space and also may
account for the predilection of daughter abscesses to form on the thinner
side adjacent to the white matter.
Late Capsule Formation (14th Day and Beyond)

•• Late capsule formation is characterised by five distinct histologic zones:
–– Necrotic centre
–– Peripheral zone of inflammatory cells and fibroblasts
–– Dense collagen capsule
–– Layer of neovascularity just external to the capsule with residual cer-
ebritis
–– Zone of oedema and reactive gliosis external to the capsule.
CLINICAL FEATURES
•• Brain abscess mostly occurs during the first two decades of life with a
prediliction for males.
•• In infants, they usually occur following septicaemia or meningitis, and are
mostly multiple.
•• The presenting features depend on the size, location, multiplicity of the
lesion, the virulence of the organism, the host response, and the severity
of cerebral oedema.
•• The symptoms of brain abscess are indistinguishable from those of a tumour
or a space occupying lesion.
•• However, the symptoms of brain abscess are more rapidly progressive
than those associated with a neoplasm and are like rapidly expanding
intracranial mass lesions.
442
•• These include headache, seizures and focal neurological deficits.

•• The classical clinical triad of headache, fever and neurological deficit is
seen in 50% of cases.
•• The neurological deficit will depend upon the location of the abscess.
•• An abscess in the posterior frontal and parietal lobe causes hemiparesis,
whereas varying degrees of dysphasia and visual field defects are seen
in a temporal lobe abscess.
•• Cerebellar abscess manifests with ataxia and nystagmus.
•• Pre-operatively, seizures occur in 30–50% of cases.
•• Involvement of the III or VI cranial nerve may occur due to raised ICP.
•• Infants usually present with progressively enlarging head, bulging
fontanelle, separation of sutures, vomiting and seizures. Infants usually
have irritability and poor feeding.
•• Adults with normal host response frequently show a rapid onset and
progression of symptoms. In contrast, immunocompromised patients may
have an insidious onset of symptoms, in which case high index of suspicion
is necessary to make an early diagnosis.
LABORATORY INVESTIGATIONS
•• The total leucocyte count is frequently normal or is only mildly elevated
(less than 15,000 cells/cubic mm) in 60–70% of patients.
•• In cases of brain abscess with concomitant meningitis or acute systemic
infection, the WBC count may be elevated above 20,000 cells/cubic mm.
•• The erythrocyte sedimentation rate is elevated in about 90% of cases, but
it is a non-specific indicator of infection.
•• The CRP has been found to be a useful marker for differentiating brain
abscess from other slowly progressive intracranial mass lesions. CRP levels
return to normal after successful treatment and persistently elevated CRP
indicates incomplete treatment.
•• The blood cultures are usually negative. However, in patients with brain
abscess associated with septic embolisation from an intravascular
endothelial infection such as endocarditis or mycotic aneurysm, it may
grow the causative organisms.
•• The CSF analysis is non-specific. There may be mild pleocytosis with WBC
count lower than 100 cells/cubic mm, unless there is co-existing meningitis.
The CSF protein contents are mildly elevated (usually <100 mg/dL) and
CSF glucose levels are generally normal except in patients with frank
meningitis where CSF glucose is low. Cultures are usually sterile.
•• As a rule if a brain abscess is suspected lumbar puncture should not be
performed.
•• Molecular techniques can increase the number of identified microbial
agents in cerebral abscesses. The ability of detecting bacterial pathogens
directly from the clinical brain abscess specimens can be achieved by
polymerase chain reaction (PCR) amplification and sequencing of bacterial
16S ribosomal deoxyribonucleic acid (rDNA).
RADIOLOGICAL INVESTIGATIONS
X-ray Skull
•• The skull radiographs are often normal in patients with brain abscess, but in
some patients specially in young children and those with chronic abscess,
signs of raised ICP may be evident.
443
•• In post-traumatic abscess, air inside the cranial cavity may be visualised.

•• Evidence of paranasal sinusitis and mastoiditis can also be seen in the
plain skiagrams of the skull.
•• Plain X-ray chest and an appropriate investigation for any associated
pathology help to rule out pulmogenic and cardiogenic cause of an abscess.
Computed Tomography
•• CT is excellent for detecting sinusitis, mastoiditis and soft tissue infections
that may be predisposing factors for a brain abscess.
•• Apart from early detection and accurate localisation, it provides valuable
information regarding staging of an abscess, associated hydrocephalus,
raised ICP, oedema, associated infection, pathology like subdural
empyema, ventriculitis, meningitis, multiplicity of an abscess, loculations
and to some extent the nature of the pus.
•• The classic appearance on a contrast enhanced CT scan is a lesion having
a smooth, thin, regular wall with a decreased density both in the centre of
the lesion (representing pyogenic material) and in the surrounding white
matter (representing oedema).
•• On non-contrast scan, the wall may be isodense or denser than the brain.

•• MRI is more sensitive than CT scan and is capable of detecting a brain
abscess in the earliest stage of development.
•• Even the plain MRI is characteristic of brain abscess and is specific to
make an accurate diagnosis.
•• Additional advantages of MRI include better anatomic details, multiple
imaging planes, lack of bony artifacts, especially in the posterior fossa and
increased sensitivity for follow-up examination.
•• Characteristic T1-weighted images show a peripheral zone of mild
hypointensity relative to adjacent brain, representative of oedema formation,
surrounding a central region of more marked signal hypointensity,
indicative of the necrotic centre of the abscess. The capsule separates
these two regions and appears as a discreet rim that is isointense to mildly
hyperintense.
•• On T2-weighted sequences, the signal intensity of the zone of oedema
increases markedly compared with the adjacent brain, while the central core
is isointense to hyperintense compared with grey matter. The capsule now
appears as a well-defined hypointense rim at the margin of the abscess.

•• Magnetic resonance spectroscopy (MRS) has emerged as a powerful tool
to non-invasively differentiate a brain abscess from a tumour.
•• The presence of amino acids (AAs) on in vivo H-MR spectroscopy is a
sensitive marker of pyogenic abscess, but its absence does not rule out
a pyogenic aetiology.
•• The presence of acetate (Ac) with or without succinate (Suc) favours an
anaerobic bacterial origin of the abscess, which may also be seen in some
of the abscesses secondary to facultative anaerobes.
•• It might be also possible to differentiate tuberculous abscesses from
pyogenic abscesses by using magnetisation transfer MRI and in vivo MRS,
which could be of value in influencing the management of such cases.
444
Diffusion Weighted Imaging

•• Abscess has high signal intensity with low apparent diffusion coefficient.
•• In contrast, necrotic or cystic tumours show low signal intensity in diffusion
weighted imaging indicating a high apparent diffusion coefficient.
TREATMENT
Medical Treatment
•• In selected patients, especially those in whom the abscess is still in the
cerebritis stage and in those patients where the brain abscess is not
associated with signs of raised ICP (clinically as well as on CT scan) and
particularly those patients who have an abscess less than 3 cm in size, it
can be managed conservatively with antibiotics alone.
•• High-risk patients with bleeding diathesis caused by thrombocytopaenia
(platelet count less than 30,000 cells/cubic mm) or coagulopathy where
even minor surgery is contraindicated are best treated with medical
treatment.
•• Antibiotic therapy started early during the cerebritis stage or in small
abscesses may result in complete cure.
•• The choice and efficacy of antibiotic depends on a number of factors
including whether a particular antibiotic is bacteriocidal or bacteriostatic,
type of causative microbials, whether it can cross the blood-brain barrier
and blood-CSF barrier, route and duration of therapy, the host response
to infection, the concentration of the drug at the site of abscess and
predisposing factors.
•• A detailed investigation of aspirated pus, both routine microscope and
aerobic and anaerobic cultures is mandatory. A special effort is needed to
be made to look for a possible fungal or tubercular aetiology.
•• Antibiotics like chloramphenicol, metronidazole, sulphonamides, isoniazid,
rifampin and flucytosine, which penetrate well into normal brain and CSF,
have potential utility for the treatment of brain abscesses.
•• Evaluation of vancomycin in cases of Staphylococcal brain abscess has
shown that the penetration of vancomycin is excellent.
•• Pre-operative use of antibiotics would prevent the spread of infection during
aspiration or surgical removal of the abscess.
•• Earlier, penicillin and chloramphenicol were mainly used in treatment of
brain abscess, particularly before cultures were obtained. They are now
replaced with cefotaxime, vancomycin and metronidazole.
•• The indications for non-surgical treatment are:
–– Patients who have a small abscess (less than 3 cm in diameter)
–– Patients who have no signs of raised ICP
–– Patient who is alert
–– Clinically stable patient with no neurological signs
–– Patient with multiple lesions
–– Patients having high-risk for surgery and anaesthesia.
Surgical Treatment
•• Surgery is indicated to confirm the diagnosis, to obtain a sample for culture
for identification of specific pathogens and sensitivity to particular antibiotics,
and to remove as much purulent material as possible.
445
•• Surgery should also be performed when there is clinical deterioration,

significant mass effect, neurological deficit, multiple lesions in surgically
accessible locations, doubtful diagnosis, presumably resistant organisms
and multiple loculations.
•• Many surgical procedures (including drainage, aspiration, excision) have
been described for the treatment of a brain abscess, but these days
aspiration and surgical excision are the most commonly and widely used
procedures.
•• Aspiration is a rapid and safe procedure, especially when the patient has
markedly raised ICP and the abscess is located in an eloquent area.
•• Aspiration is usually performed under local anaesthesia, except in children.
•• It can be done with the use of stereotactic technique, real-time ultrasound,
particularly in infants with open fontanelle or under CT scan guidance.
•• Stereotactic aspiration of an abscess is useful in a deep-seated abscess e.g
abscess in the brainstem or thalamus, and even in a multi-loculated abscess.
•• If the abscess does not reduce in size and the quantity of pus does not
subsequently decrease (even after 3−4 aspirations), excision of an abscess
should be planned.
•• The advantage of secondary excision over primary is that the surrounding
oedema is significantly less after multiple aspirations.
•• Post-traumatic abscesses containing bone fragment or foreign body,
however, require primary excision.
•• Proper and thorough wound toilet and removal of hair, foreign body, etc.
are essential to prevent recurrence. Multi-loculated abscesses also mostly
require secondary excision.
Role of Corticosteroids
•• The use of corticosteroids in the treatment of brain abscess is controversial.
•• Corticosteroids significantly reduce cerebral oedema and mass effect that
accompany brain abscess.
•• Corticosteroids, however, inhibit the migration of leukocytes and diminish
the effectiveness of the host response when used in the early cerebritis
stage.
•• Administration of corticosteroids should, therefore, be avoided in the early
stages of brain abscess development.
COMPLICATIONS
Epilepsy
•• Epilepsy is a common sequel of brain abscess occurring in 30–50% of
patients.
•• The maximum frequency of seizures occurred during the 4th and 5th year
after diagnosis.
•• Due to the high incidence of seizures, all patients with supratentorial brain
abscess should be given prophylactic anticonvulsants for 1–2 years.
•• The anticonvulsant should be tapered if the electroencephalography shows
abscence of epileptogenic activity.
•• Patients having intractable seizures may sometime respond to temporal
lobe resection or resection of the seizure focus.
58
CHAPTER Scalp and
Skull Infections
SCALP LACERATIONS
•• Most scalp lacerations heal without complications, but mismanagement of
the same may end up in infections.
•• Prevention of scalp infection can be achieved by following the basic
principles of wound management like reducing tissue contamination,
meticulous wound toilet, debriding devitalised tissue, restoring perfusion in
poorly perfused wounds and establishing a well-approximated skin closure
without tension.
•• Care has to be taken to remove any contaminants or foreign bodies within
the wound.
POST-OPERATIVE SCALP INFECTION

•• Post-operative wound infections are divided into five categories as:
1. Dirty (brain abscess, ventriculitis, meningitis, etc.)
2. Contaminated (compound skull fractures, open lacerations, CSF
fistulae, etc.)
3. Clean contaminated (entry into paranasal sinuses, transphenoid/
transoral procedures, prolonged surgery),
4. Clean with foreign body (shunts, EVD, ICP monitors, DBS electrodes,
etc.)
5. Clean (ideal operating conditions).
CRANIOTOMY AND SCALP INFECTION

•• The predisposing factors for post-craniotomy infection include:
–– Emergency level of surgery
–– Long duration of surgery (>200 minutes)
–– Duration of stay in ICU (>72 hours)
–– Penetration of paranasal sinuses
–– CSF fistulae
–– Multiple surgeries via same incisions
–– Use of permanent implantable foreign materials (acrylic, metal wires,
ventricular catheters, etc.)
–– Tight haemostatic skin clips resulting in skin necrosis.
Chapter 58 • Scalp and Skull Infections
447
DEEP BRAIN STIMULATION AND

SCALP INFECTION
•• Placement of the hardware in cases treated by deep brain stimulation has
its potential complications of malfunction, lead migration, fracture, scalp
erosion or infection.
•• To tackle the above problem, a temporo-parieto-occipital flap based on
the superficial temporal artery with or without scalp expansion, and a scalp
fasciocutaneous flap with or without cranioplasty can be used.
PIN SITE SCALP INFECTION

•• Immobilisation using the halo vest and Gardner Well’s skull tongs requires
placement of skull pins. In such patients, pin site infection may be seen.
•• Staphylococcus aureus has been the most common pathogen in these
infections.
•• Superficially infected pins can be managed with local pin care and oral
antibiotics.
•• Persistent or severe infections require pin replacement to a nearby site,
parenteral antibiotic therapy, and incision and drainage of any abscess,
may be needed.
OTHERS
•• Patients having presurgical scalp infections like pediculosis capitis or
scabies, are prone to peri-operative scalp infections.
•• If the neurosurgical procedure is not an emergency, as is not the case
always, then it is advisable to operate after complete treatment of local
scalp infections.
Diagnosis
•• The infection may be superficial when the dermis and epidermis is involved
or deep when the galea and the underlying bone are involved.
•• Staphylococcus aureus is the predominant pathogen followed by hospital
acquired pathogens like Pseudomonas and Klebsiella.
•• Anaerobic pathogens and the gas forming Clostridium species infecting
the scalp have also been reported.
•• The patient may have evidence of local signs of infection like erythema,
swelling, inflammation, tenderness and warmth.
•• There may be a fluctuant collection or a discharging sinus with a
serosanguinous or purulent discharge. The discharge needs to be sent
for aerobic, anaerobic and fungal cultures.
•• If tuberculosis is suspected, then tubercular culture also needs to be done.
Management
•• General risk factors for infection like diabetes mellitus, obesity, malnutrition,
chronic renal failure, advanced age and use of steroids, should be noted
and appropriate measures taken to tackle them.
•• When the infection is superficial, oral antibiotics and anti-inflammatory
agents are sufficient.
448
•• If the infection is deep, it may require wound debridement along with

administration of intravenous antibiotics depending on the sensitivity of
the organism.
•• If the infection has spread to the bone, then often it necessitates removal
of the bone flap. A secondary cranioplasty will be required at a later date.
SKULL OSTEOMYELITIS
•• Although osteomyelitis can affect any bone in the body, involvement of the
skull bones is a rare entity.
•• One of the earliest reports of osteomyelitis of the skull was the one by
Sir Percival Pott, who described a subperiosteal abscess of the frontal
bone occurring as a complication of trauma causing a puffy swelling in the
forehead. It has since derived its name, Pott’s Puffy tumour.
Pathogenesis
•• Haematogenous spread of infection to the skull is a rare entity.
•• Skull osteomyelitis, in most of the instances, is a result of contiguous
spread of infection.
•• The probable sources of infection being:
–– Post-traumatic following compound fracture of the skull
–– Post-craniotomy
–– Secondary to sinusitis, mastoiditis
–– Intracranial infections
–– Scalp infections
–– Dental procedures
–– Dermatological procedures
–– Cryptic osteomyelitis.
Pathogens
•• The common pathogens are microaerophilic streptococci, including
alpha-haemolytic Streptococcus, Staphylococcus, Peptostreptococcus,
bacteroides species and other anaerobes such as Fusobacterium.
•• Other organisms that have been reported include gram-positive organisms,
Aspergillus, Mycobacterium and Candida.
•• In patients with immunocompromised state and prolonged steroid use,
organisms like Salmonella,Cryptococcus and Treponema pallidum have
been isolated.
•• There are a few reports of skull osteomyelitis due to fungi like mucormycosis,
madura mycosis and others.
Clinical Features
•• These patients present with generalised symptoms like fever, headache,
vomiting, fatigue/malaise along with scalp tenderness and swelling.
•• Pott’s puffy tumour is the term given to a subperiosteal abscess of the frontal
bone, usually presenting as a localised swelling of the soft tissues in the over-
lying region of the forehead, and is associated with localised osteomyelitis.
•• Patients with skull base osteomyelitis can present with headache and a
variety of cranial neuropathies, often a combination of VI and lower cranial
nerve (CN) neuropathies.
•• The source of infection in the form of ear infection or sinusitis needs to
be looked for.
Chapter 58 • Scalp and Skull Infections
449
•• In a typical case of skull base osteomyelitis, the temporal bone is involved,

whereas in atypical or central type of skull base osteomyelitis, the sphenoid
occiput or the clivus can also be involved.
Investigations
•• Blood investigations often show an increase in the acute phase reactants
like ESR, WBC count and CRP counts.
•• On plain radiographs, the skull lesions appear as lytic areas and these
changes take several months to be seen.
•• Initial CT scan may not show evidence of the disease, whereas in the later
part of the disease, evidence of lytic bony lesions is seen.
•• On MRI, the lesions appear hypointense in T1 and hyperintense in T2.
•• In skull base osteomyelitis, it is very difficult to differentiate this condition
from skull base malignancies and other non-neoplastic conditions which
may mimic this entity.
•• Various nuclear medicine imaging techniques like gallium-67 scintigraphy,
indium-111 white blood cell scans, technetium-99m methylene
diphosphonate (MDP) bone scans and single-photon emission computed
tomography (SPECT), have been used to investigate post-operative
osteomyelitis and also to follow-up patients on treatment.
•• Lee et al. classified the patients with skull base osteomyelitis using
technetium-99 SPECT into four grades:
1. Mild uptake
2. Focal mastoid/temporal bone uptake not reaching the midline
3. Petrous temporal bone uptake reaching the midline
4. Uptake crossing the midline, involving the contralateral temporal bone
•• Histopathological examination of the biopsy/debrided tissue is essential
along with pyogenic, fungal and tubercular cultures, as HPE may not be
diagnostic at times.
Management
•• Surgical resection of the diseased bone with adequate clearance of the
associated pathology e.g pus granulation tissue is required.
•• Post-operatively, the patient has to be on long-term antibiotics for complete
clearance of the infection.
•• Pseudomonas being the commonest pathogen, antipseudomonal antibiotics
have to be started empirically and once the culture and sensitivity report is
available, it may be changed if necessary.
•• In a few patients with troublesome chronic osteomyelitis, in spite of repeated
debridement, the infection might persist. In such instances, a combination
of extensive surgical debridement and a free flap transfer to cover the
defect is effective.
•• A latissimus dorsi muscle flap with a split skin graft has been preferred by
a few surgeons.
•• A multidisciplinary approach with an infection specialist and a plastic
surgeon might be necessary for such cases.
•• Complications of skull osteomyelitis include intracranial extension resulting
in epidural, subdural or brain abscess, sinus thrombosis, cranial nerve
palsies and death.
•• Mortality from complications is 20−40%.
•• With accurate diagnosis and prompt treatment, the complications can be
avoided to get a better outcome.
59
CHAPTER
Subdural Empyema
Mathuriya SN  Pathak A  Khandelwal N
INTRODUCTION
•• The term subdural empyema (SDE) is used for suppuration in the pre-
existing space between the dura and the arachnoid.
•• Various other synonyms of this condition are pachymeningitis interna,
purulent pachymeningitis, cortical abscess and subdural abscess.
•• It has been reported either intracranially or in the spinal canal, the latter
localisation being quite rare.
•• It is a rare, but serious illness with a declining mortality rate and rather
frequent neurological sequelae.
•• Morbidity and mortality in intracranial and spinal SDE directly relate to the
delay in diagnosis and therapy.
•• Although considered uncommon, subdural empyemas (SDEs) constitute
13% and 23% of all intracranial bacterial infections, usually presenting
with a fulminant clinical picture and rapidly progressive neurological deficit.
•• They occur more frequently in children than in adults.
•• Intracranial SDEs, the majority of which are supratentorial in location, are
common neurosurgical emergencies in developing countries, especially in
the paediatric age group.
•• Infratentorial SDE is a life-threatening rare complication of bacterial
meningitis.
•• Empyema should be considered in a patient with suspected or proven
bacterial meningitis and associated ear, nose or throat infection with
neurological signs.
•• The common sources of infection are paranasal sinus infection, otitis media,
trauma, upper respiratory tract infection, subdural effusion and meningitis.
•• The spread of infection into the subdural space can be due to direct
extension through the bone and dura, which is the common route in patients
with otitis media or mastoiditis.
•• However, in SDEs secondary to sinusitis, the mode of spread is usually
by retrograde thrombosis of the dural and intracranial veins from septic
thrombophletitis.
•• The location of a SDE varies according to the source of infection: Frontal
in case of sinusitis, occipital and temporal region in case of otitis media.
•• The pathological findings consist of an inflammatory process mostly in the
subdural space, with a small group having associated meningitis.
•• Subdural empyema in neonates and infants are, for all practical purposes
secondary to meningitis.
Chapter 59 • Subdural Empyema
451
•• However, the secondary changes, e.g. venous thrombosis, cerebral

oedema, haemorrhagic changes and superficial abscess formation are
responsible for the overall clinical presentation and prognosis.
•• The clinical presentation usually is dramatic.
•• The majority of patients have altered sensorium.
•• Features of raised intracranial pressure, headaches, nausea and vomiting
are also quite common.
•• Enlarging head and bulging fontanelle are seen in neonates and infants
with a subdural empyema.
•• Focal symptoms in the form of speech disturbances, hemiparesis and
seizures may also be seen.
•• The factors to be incriminated for rapid clinical deterioration in SDE are:
–– Products of bacterial metabolism including toxins which may have a
direct effect on neural and glial tissue
–– Venous obstruction and stasis leading to infarction secondary to
cerebral venous thrombosis.
IMAGING
•• The CT scan still remains the initial, common modality for diagnosis.
•• Minimal midline shift and swelling of the ipsilateral hemisphere may be
the only clue as distinction of SDE from the surrounding brain is difficult
in the acute phase prompting the need for serial CT scans with contrast
enhancement.
•• Magnetic resonance imaging (MRI) has a major role in diagnosing and
reducing mortality in subdural empyema as the actual empyema can
be demonstrated in the acute phase using coronal and sagittal images,
especially for collections near the base of skull, tentorium and over the
convexity.
•• SDEs have high signal intensity on diffusion weighted images (DWIs) and
low signal intensity on ADC maps, with an ADC value lower than that of
the normal cortical grey matter.
•• Diffusion MRI can be valuable in distinguishing SDE from effusion and in
the follow-up of subdural collections.
MICROBIOLOGY
•• The primary source of infection may have a relationship to the organism
isolated from SDE.
•• Aerobic, microaerophilic streptococci and anaerobic organisms are
commonly isolated from empyemas secondary to paranasal sinusitis.
•• In post-traumatic or post-surgical cases, Staphylococcus aureus is found.
•• In children with SDE secondary to meningitis, the organism commonly
encountered is Haemophilus influenzae or Streptococcus pneumoniae.
•• It is, however, not uncommon to isolate species of Salmonella, Escherichia
coli or other rare organisms.
MANAGEMENT
•• SDE is a neurosurgical emergency which requires prompt intervention.
•• The extent of subdural pus accumulation has a statistically significant
bearing on the chances of survival without severe disability, as extensive
SDE involves the adjacent cortex, especially through widespread
thrombophlebitis.
452
•• Surgery was the mainstay of treatment in the pre-antibiotic era.

Subsequently surgery along with antibiotics helped to lower the mortality
rates.
•• Proponents of surgical treatment of SDE claim an added advantage that
it decreases the toxic and inflammatory influence on the brain and its
blood supply which diminishes due to mass effect.
•• The advantage of surgery lies in achieving two main objectives, e.g.
penetration of antibiotics into loculated areas of suppuration and
identification of the offending organism.
•• The type of surgical procedure is variable. Craniotomy or craniectomy is
non-controversial for posterior fossa SDE.
•• Percutaneous aspiration through an open fontanelle in infants or twist drill
hole aspiration in children still remains a preferred method of treatment of
supratentorial empyemas.
•• Early surgery can salvage most patients and obviate the need for permanent
cerebrospinal fluid diversion procedures.
•• Surgery (evacuation of empyema and mastoidectomy), antibiotics and
management of hydrocephalus are the mainstays of treatment.
•• Paediatric supratentorial SDEs, although rapidly fatal if not identified
promptly, can be effectively managed with early surgical drainage.
•• Patients with altered sensorium, deteriorating neurological status, focal
deficit or failed conservative therapy demand surgical evacuation.
•• A localised area of pus in the supratentorial compartment needs
percutaneous needle aspiration and evacuation in infants or through burr
holes in children and adults.
•• Diffuse area of pus with midline shift, multiloculated or parafalcine SDE
should be evacuated through craniotomy. All posterior fossa SDEs should
have a craniotomy/craniectomy for evacuation.
•• Follow-up CT scan is mandatory for all patients, whether treated
conservatively or surgically.
60
CHAPTER Spinal Epidural and
Intramedullary Abscess
Ashish Suri  Shashwat Mishra  Ajay Garg
SPINAL EPIDURAL ABSCESS (SEA)

•• Spinal epidural space infections are being noted more frequently in recent
times as a result of increasing number of spinal surgeries, percutaneous
spinal procedures, emergence of the human immunodeficiency virus
epidemic and advances in spinal imaging modalities.
•• Due to their low incidence and confusing symptomatology, they continue
to pose a diagnostic challenge.
Relevant Anatomy and Pathophysiology

•• The spinal epidural space is a sleeve-like compartment between the dura
and the periosteum and is filled with fat, epidural arteries and venous
complexes.
•• This compartment is developed well posterior and lateral to the thecal sac,
but is only a potential space anteriorly where the dura and the periosteum
are closely approximated.
•• When suppuration of the epidural space occurs, it spreads over several
contiguous spinal segments and is typically located in the posterior space.
•• Epidural space collections anterior to the spinal cord generally result from
infectious spondylitis or neoplastic affection of the vertebral bodies.
•• Thus, in the Indian context, anteriorly located epidural abscesses are mostly
noted in association with tubercular spondylitis.
•• The SEAs most frequently occur in the thoracic and lumbosacral spine,
which are also the most commonly accessed spinal segments in surgery
and other procedures.
•• The mechanism of spinal cord injury due to epidural abscesses remains
unclear.
•• The pathological mechanisms suggested include mechanical cord
compression and septic thrombophlebitis with subsequent cord infarction.
Epidemiology
•• All age groups are susceptible. However, SEAs are more frequently
diagnosed in the 4th decade onwards.
•• Risk factors identified include predisposing medical conditions (diabetes
mellitus, alcoholism and immunosuppression), spinal abnormalities, surgical
intervention, spine trauma and presence of potential sources of infection
(skin and soft-tissue infections, osteomyelitis, urinary sepsis, indwelling
vascular access, intravenous drug use).
454
•• Staphylococcus aureus is the commonest micro-organism isolated from

these suppurations.
•• Common microbial patterns seen in different clinical scenarios are listed
in Table 1.
Clinical Features
•• Fever, back pain and neurological deficits constitute the classical clinical
triad of SEAs.
•• Back pain is the most common and earliest symptom reported by patients.
•• A staging system has been proposed describing the progression of
symptoms in SEAs (Table 2).
•• The duration of these symptoms and the time of progression from one
stage to another are highly variable between patients and may range from
hours to months.
•• It is apparent that clinical features of SEAs in the initial stages mimic
common pathological spinal conditions. Radicular pain in the cervical and
lumbar regions radiates to the extremities in classical patterns, but in the
thoracic region, pain may vaguely extend to the chest or the abdomen,
misguiding even the most discerning clinician.
•• The SEAs following invasive procedures (secondary SEAs) on the spine
differ in clinical presentation from the spontaneously occurring SEAs
(primary SEAs).
•• The secondary SEAs occur in otherwise healthy individuals without
significant comorbidities.
•• Typically the patient presents with worsening pain at the surgical/puncture
site along with tenderness and, occasionally, purulent discharge from the
wound.
Table 1: Risk factors and common micro-organisms causing spinal

epidural abscessess
Risk factors Common micro-organisms
Injected drug use Staphylococcus aureus, Pseudomonas aeruginosa
Diabetes mellitus Multiple
Recent invasive spinal procedures S. aureus, S. epidermidis
Morbid obesity Multiple
Skin infections or abscesses S. aureus, S. epidermidis
Penetrating spinal trauma S. aureus, S. epidermidis
Transient bacteraemia Multiple
Multiple medical illnesses Multiple
Immunosuppression Bacterial, mycobacterial, fungal
Table 2: Clinical staging of spinal epidural abscesses

Stages Clinical features
I Back pain
II Radiating pain
III Sensory deficits, motor deficits, and bladder and bowel dysfunction
IV Paralysis
Chapter 60 • Spinal Epidural and Intramedullary Abscess
455
•• Patients developing spontaneous or primary SEAs, following haematogenous

dissemination of infection to the vertebral bodies or disc spaces develop
discitis or osteomyelitis prior to the appearance of SEAs.
•• Due to the chronic inflammatory nature of the infection, the patients
generally have back pain, systemic complaints (e.g. fever, anorexia, night
sweats, weight loss, etc.) and neurological symptoms of prolonged duration.
•• Spinal cord compression by epidural granulation tissue and caseous pus
may be responsible for sudden neurological worsening in Pott’s spine and
may warrant urgent surgical decompression.
Diagnosis
•• Clinical findings, supporting laboratory data and suggestive imaging
features are collated to establish the diagnosis of SEAs.
•• However, it can be confirmed only by drainage of the abscess.
Laboratory Investigations
•• Routine laboratory studies reveal leukocytosis and elevated acute phase
reactants (C-reactive protein), which are non-specific markers of any
inflammatory process.
•• Cerebrospinal fluid (CSF) examination typically reflects parameningeal
inflammation with leukocytic pleocytosis and increased protein levels.
•• The CSF cultures are usually negative and lumbar puncture carries a high-
risk of dissemination of the infective organism into the CSF.
Imaging
•• A plain radiograph or CT of the spine may reveal narrowing of the disc
space and bone lysis to indicate the presence of discitis and osteomyelitis.
•• Both contrast-enhanced MRI and computed tomography (CT)-myelography
of the spine are highly sensitive (more than 90%) in diagnosing SEA.
•• Similarly, radionuclide scanning (with technetium, gallium or indium) may
show increased uptake, helping to identify the affected site.
•• MRI is the imaging method of choice because it is non-invasive, multi-planar
and without any radiation exposure.
•• It delineates both the longitudinal and the paraspinal extension of the SEA
and thereby helps in surgical planning.
•• In addition, it may help to differentiate infection from cancer on the basis
of the appearance and the signal intensity of the image.
•• The SEA is isointense to hypointense compared with the spinal cord on
unenhanced T1-weighted images, and increased in intensity on proton-
density and T2-weighted images.
•• After contrast administration, SEA may show homogeneous enhancement,
likely representing thickened, inflamed tissue with microabscesses or
peripheral enhancement surrounding a central focus of low signal intensity
representing a necrotic abscess or a combination of both patterns.
Treatment
•• Prompt surgical drainage of SEA followed by appropriate systemic antibiotic
therapy is almost always indicated to reduce the risk of sepsis and further
neural injury.
•• In addition to blood cultures, other potential sources of infection are sampled
prior to the initiation of systemic antibiotics.
456
•• Pre-operative neurological status is an important predictor of outcome;

hence early surgical intervention is appropriate.
•• If profound neurological deficit persists for greater than 24–36 hours,
recovery is unlikely following decompression.
•• Depending upon the location of the abscess and surgical feasibility,
the epidural space is explored by laminectomy, hemilaminectomy or
interlaminar fenestration.
•• The purulent material and granulation tissue are then removed and samples
collected for microbial culture.
•• Purely medical therapy may be considered in a few clinical scenarios. If the
patient is at poor surgical risk, declines surgery or has complete paralysis of
more than 3 days duration, antibiotic therapy is initiated following collection
of samples for microbial culture and the patient is closely monitored for
response.
•• Very small abscesses without significant neurological symptoms may
also be managed conservatively under close observation and frequent
neurological assessment.
•• Surgical drainage is indicated if the symptoms worsen or signs of sepsis
appear during systemic antibiotic therapy.
•• While awaiting culture results, empirical antibiotic therapy must be
directed against S. aureus (the most common pathogen), including
coverage for methicillin resistant organisms and gram-negative bacilli.
•• The ideal duration of therapy is not well-established and generally
systemic antibiotics are recommended for a period of 6 weeks, as vertebral
osteomyelitis frequently coexists with SEAs.
•• When SEA develops following spinal instrumentation or epidural electrode
implantation, removal of the foreign material is necessarily required for
elimination of infection.
•• The role of steroids is controversial and may be used for temporary
stabilisation while preparing for surgery.
•• For tubercular epidural abscesses in neurologically intact patients, standard
four-drug (HRZE) or five-drug (HRZES) antitubercular therapy is initiated.
•• At least 18 months of antitubercular therapy is recommended
[1 month HRZES + 3 months of HRZE and 15 months of HRE (H = Isoniazid,
R = Rifampicin, Z = Pyrazinamide, E = Ethambutol, S = Streptomycin)].
SPINAL INTRAMEDULLARY ABSCESSES

•• Intramedullary abscesses within the spinal cord are extremely rare, if one
excludes cases where the infection spreads to the spinal cord from the
contiguous vertebral body, disc space or a dermal sinus.
•• The precise incidence of spinal intramedullary abscesses (SIAs) remains
unclear.
Pathogenesis
•• Metastatic dissemination of infection from extraneous foci, contiguous
spread from an infected dermoid, dermal sinuses, disc or vertebral bodies
are commonly implicated in the causation of these abscesses.
•• Iatrogenic intramedullary abscesses, following surgical procedures on the
spinal cord, may also occasionally be encountered.
•• The cervical and upper dorsal cord are thought to be the commonest site
of cryptogenic abscesses.
Chapter 60 • Spinal Epidural and Intramedullary Abscess
457
•• Congenital midline neuroectodermal defects (spinal dysraphisms) were

identifiable in 44% of the cases.
•• The commonly noted stigmata of these dysraphic defects were pigmented
naevi, sinus tract openings, blind dimple and inflamed skin nodule.
Abscesses seen in this setting were common in the thoracolumbar region.
•• Intramedullary abscesses are common in the paediatric age group because
of the frequent predisposing developmental spinal cord anomalies.
•• The stages of evolution of spinal intramedullary abscesses are similar to
those seen in a pyogenic brain abscess.
•• Areas of necrosis surrounded by purulent myelitis are seen in the initial
stages.
•• Later, a well-vascularised thick capsule surrounds the core of purulent
material.
•• Subsequent CSF dissemination and leptomeningeal spread of infection
can complicate the clinical picture.
•• Septic phlebitis with cord infarction may also contribute to cord damage.
•• Abscesses resulting from septic emboli have a predilection for the lower
cervical and upper thoracic cord as these spinal segments have a relatively
richer blood supply.
Clinical Features
•• Pain, fever and rapidly progressive neurological deficits constitute the
commonest symptomatology of SIAs.
•• Evidently, transverse myelitis and SEAs closely mimic the presentation
of these abscesses and must be entertained in the differential diagnosis.
•• Deterioration in sensorium and clinical features of sepsis are ominous and
indicate leptomeningeal or systemic spread of infection.
•• Staphylococcal species are the most common organisms isolated from
these suppurations.
•• The observed microbial pattern in relation to the proposed mechanism of
infection is presented in Table 3.
Management
•• Similar to pyogenic brain abscesses, generally a combination of medical and
surgical therapy is considered appropriate for intramedullary abscesses.
•• Surgical intervention is absolutely necessary in cases of abscesses
associated with dermoids and epidermoids and dermal sinus tracts.
Table 3: Microbiology of intramedullary spinal abscesses

Mechanism of infection Microbiology Antimicrobial therapy
Contiguous spread from Staphylococcus epidermidis, Vancomycin + cefotaxime +
dermal sinus opening S. aureus and anaerobes metronidazole
Following spinal surgery S. aureus, S. epidermidis, Vancomycin + ceftazidime ±
Enterobacteriacea, Gram metronidazole
negative bacilli
Haematogenous spread Similar to primary source Culture based
Cryptogenic Listeria monocytogenes, Ampicillin + cefotaxime +
Viridians streptococci, metronidazole
Hemophilus species, anaerobes
458
•• A minimum of 4–6 weeks of parenteral antibiotic therapy is essential.

•• The standard surgical management entails laminectomy, midline myelotomy
and drainage of the pus and excision of an underlying lesion, if any.
SPINAL INTRAMEDULLARY TUBERCULOMAS

•• Intramedullary tuberculomas in the spinal cord are extremely rare even in
regions where tuberculosis is endemic.
•• Nevertheless, it remains an important differential diagnosis of intramedullary
lesions in the Indian population.
•• Intramedullary tuberculomas are encountered usually in the younger age
groups and have been most frequently reported in the thoracic spinal cord.
•• The patient may present with signs of subacute cord compression with
classical signs of myelopathy.
•• However, varied presentation, such as Brown-Sequard syndrome and acute
urinary retention have also been reported.
•• The MRI appearance of intramedullary tuberculomas can vary according
to the stage of evolution of the lesion.
•• In the early stages, tuberculomas may be indistinguishable from myelitis
with homogeneous enhancement of the cord.
•• Eventually, these lesions progress to the characteristic ring enhancing
“target appearance” with a central hypointense core and hyperintense
periphery on T2-weighted sequences along with evidence of expanded
cord substance.
•• The ideal treatment of intramedullary tuberculoma is controversial.
•• A balanced approach is adopted with the understanding that antitubercular
therapy (12–18 months duration, standard four drug regimen) is the
cornerstone of management.
•• Surgery is presently recommended for patients who worsen on
antitubercular regimen with increasing mass effect or in patients with
uncertain diagnosis.
•• Improvement is generally seen with antitubercular therapy, unless the
patient harbours a resistant form of the organism or the deficits are long-
standing and established.
61
CHAPTER Tuberculosis of the
Central Nervous System
PN Tandon  Anil Pande
INTRODUCTION
•• The tubercular manifestations of central nervous system (CNS) disease
may involve the meninges and parenchyma, or there may be focal
involvement of the spinal cord and its adjacent osseous structures.
•• Cranial tuberculosis may be parenchymal (tuberculoma, abscess,
encephalopathy), meningeal (meningitis, pachymeningitis) or calvarial
(osteomyelitis).
•• Spinal tuberculosis can be vertebral (caries or Pott’s spine), meningeal
(pachymeningitis, arachnoiditis) and parenchymal (spinal tuberculoma).
•• Children are commonly affected between 6 months and 4 years and adults
between 20 years and 50 years.
•• In addition to HIV-1 co-infection, other conditions associated with CNS
tubercular involvement include recent measles infection and malnourishment
in children; and alcoholism, malignancies, immunosuppressive medication
and non-HIV immunosuppressive conditions in adults.
PATHOGENESIS
•• The M. tuberculosis is member of the M. tuberculosis complex that includes
M. africanum, M. bovis and M. microti.
•• M. tuberculosis is an anaerobic, non-motile, non-spore forming bacillus
that is weakly gram-positive and the main cellular reservoir is tissue
macrophages though the organism exists extracellularly.
•• The bacteria resist decolourisation of carbol fuschin by acid alcohol in the
Ziehl-Neelsen process due to the high lipid content of the cell wall.
•• Intracellular parasitism is accomplished by a variety of mechanisms that
include altered trafficking of bacteria during endocytosis, interference with
host Ca2+ signalling pathways and induction of maturational arrest of the
phagosome.
•• Recent molecular biological studies have revealed that M. tuberculosis
contains diverse chemical substances, lipids, polysaccharides and
tuberculoproteins which are responsible for the various immune
phenomena, viz. resistance, sensitivity, virulence, granuloma formation
and chronicity of infection.
•• These immune responses are primarily cell mediated, involving a complex
interplay of T and B lymphocytes and macrophages, and mediated by
various lymphokines, and immunoglobulins.
460
CENTRAL NERVOUS SYSTEM TUBERCULOSIS

•• Central nervous system tuberculosis is usually secondary to a haemato-
genous spread from a primary infection elsewhere in the body.
•• Uncommonly, it could be the result of direct spread from a lesion in the
neighbourhood, e.g. otitis media or spinal caries.
•• There is enough clinical and experimental evidence to indicate that
meningitis is the result of a discharge of tubercle bacilli into the CSF from
a caseous focus (“Rich focus”) in the brain or the meninges, and not a
consequence of primary haematogenous spread.
•• In contrast, a parenchymatous tuberculoma is due to direct haematogenous
spread to the brain.
•• The inflammatory cells (lymphocytes, monocytes and plasma cells)
accumulate in the subendothelial region of the vessel and with further
cellular proliferation there is a displacement of the intact endothelium with or
without tuberculoma formation, and this proceeds to complete involvement
of the vessel with a contiguous inflammatory process.
•• TNF-alpha is an important proinflammatory cytokine, once the bacteria enter
the CSF, infected monocytes and macrophages show increased expression
of surface ICAM-1 and increased migratory activity across the endothelial
and epithelial bilayers, activating intracellular signalling pathways and
secretion of proinflammatory cytokines.
•• The majority of cases of CNS tuberculosis seen in India have been found to
be due to the human type of tubercle bacillus (M. tuberculosis var. hominis).
•• The Mycobacterium avium complex was found in 50% of AIDS patients.
•• The presence of HIV-1 induced immunodeficiency is a powerful cofactor for
the development of disseminated tuberculosis and, therefore, the proportion
of extrapulmonary cases has increased.
INTRACRANIAL TUBERCULOMAS
Pathology
•• Tuberculomas of the brain vary in size from less than a centimetre to 8−10
centimetres in diametre.
•• In its mature form it presents as a well-circumscribed, nodular, firm to hard,
greyish-yellow relatively avascular mass.
•• Some of these present on the surface of the brain, in which case they may
get adherent to the dura.
•• The lesion is surrounded by varying degrees of oedema and gliosis.
•• The so-called capsule of a tuberculoma is nothing more than compressed
gliosed brain tissue.
•• A true fibrocollagenous capsule does not exist, even though at surgery the
lesion appears to shell out from the surrounding brain.
•• The cut surface presents a creamish-white gritty caseating centre with
crenated margins, surrounded by a firm to hard greyish rim of varying colour,
composed of granulomatous tissue and compressed gliosed brain matter.
•• Microscopically, the lesion is a classical tuberculous granuloma,with central
coagulative necrosis surrounded by epithelioid cells, Langhans giant cells
and an admixture of lymphocytes and plasma cells.
•• There may be satellite granulomas at the periphery of the lesion and foci
of perivascular infiltration.
Chapter 61 • Tuberculosis of the Central Nervous System
461
•• Careful examination of the central region of the mass may reveal acid
fast bacilli in appropriately stained sections. As a rule, there is a paucity
of organisms.
•• The tuberculoprotein or some of the antigenic components released by
the destruction of the bacilli may, by complex immune reactions with a
number of polyclonal and monoclonal antibodies, lead to the formation of
the tuberculoma.
•• Besides the classical lesion described above, there are a variety of atypical
manifestations: Sinh et al. described several of these atypical lesions.
•• Tuberculoma En Plaque: The angiographic appearance of such lesions
may mimic a meningioma due to their increased vascularity. At surgery
also, these are found to be adherent to the dura and may grossly resemble
a meningioma en plaque.
•• Tuberculous Abscess:
–– It is important to differentiate a tuberculous abscess from a classical
tuberculoma with central caseation, softening and liquefaction.
–– A ‘tubercular abscess’ lacks granulomatous change, and histologically
resembles a chronic pyogenic abscess, except that acid fast bacilli are
seen in the pus.
•• Cystic Tuberculoma:
–– These tuberculomas are rare.
–– The cyst contained clear yellow fluid and the cyst wall has typical
tuberculous pathology.
–– Sridhar et al. have proposed a classification of cystic tuberculomas:
Type I—intralesional cyst within tuberculoma; Type II—intralesional
cyst at the periphery of the lesion; Type III—extralesional (the cyst is
subdural in location) and Type IV—extralesional (the cyst lies between
the lesion and the brain).
–– The types I and II require radical excision whereas types III and IV
require excision of the solid part alone.
•• Multiple Grape-like Tuberculomas: Another rare presentation is in the
form of a grape-like cluster of multiple immature tuberculomas. These may
resemble a cluster of cysticercus cysts.
•• Microtuberculomas:
–– With the advent of the CT scan, a large number of cases who
presented with a solitary small disc or ring, 5−7 mm in diameter,
surrounded by perifocal oedema were labelled as micro tuberculosis.
–– Such a lesion may represent the initial stages of evolution of a tuber-
culoma.
–– These have been observed at autopsy in cases of tubercular menin-
gitis.
•• Calcified Tuberculoma: Calcification is uncommon in a tuberculoma and
is reported in 2−6% of cases. However, occasionally, a tuberculoma may
present as a fully calcified mass. It is important to realise that such a lesion
is not inactive or healed.
•• Tuberculous Encephalopathy with an “Inconsequential” Tuberculoma:
–– The condition is characterised by obvious oedema with varying
degrees of perivascular myelin loss and, in some, even haemorrhagic
leucoencephalopathy.
–– They have been designated by Dastur et al. as ‘tuberculous
encephalopathy’ who attributed it to an allergic reaction to proteins
liberated from lysed tubercle bacilli.
462
Microscopy
•• In addition to describing the fine structure of these lesions, including
evolution of the epithelioid cells, they elaborated the ultrastructural basis
of vasculopathy in and around a tuberculoma.
•• EM examination of the reactive border zone revealed the varied pleomorphic
cellular, vascular and necrotic reactions characteristic of these lesions.
•• It was demonstrated that a variety of cells surrounding the central necrotic
area participate in phagocytosis. All these cells were large mononuclear
cells, the commonest being the epithelioid cell.
•• They demonstrated the evolution of the epithelioid cell from a mononuclear
cell and also showed that overt macrophages full of secondary lysosomes
and phagosomes contained ingested osmophilic debris.
•• There was marked proliferation of the basement membrane into concentric
layers in the vessels in the reactive border zone.
•• The proteinaceous material in the basement membrane may act as an
antigen and be responsible for the vasculitis and brain damage associated
with tuberculomas.
Clinical Features
•• Age and Sex: There is no age immune to CNS tuberculosis, but 60−70%
of patients with tuberculomas are below the age of 20 years.
•• Sites:
–– Tuberculomas may occur at any site within the brain; the cerebrum and
cerebellum, owing to their bulk, are the most common sites.
–– The cerebellum was found to be a more frequent location in children
and the cerebral hemispheres in adults.
–– Tuberculomas have been documented in the intrasellar region, brain-
stem, thalamus, basal ganglia, mesencephalon, cerebellopontine
angle, optic chiasma, the pineal region, in the ventricles and the
aqueduct.
•• Symptoms and Signs:
–– Tuberculomas generally, present as slow-growing intracranial space
occupying lesions.
–– The constitutional symptoms and signs of an inflammatory lesion are
uncommon.
–– A history of exposure to a person with open pulmonary tuberculosis,
especially a close relative, should arouse the suspicion of tuberculous
aetiology in a patient suspected to harbour a brain tumour
–– Focal seizures are frequently the first symptom.
–– Symptoms and signs of raised intracranial pressure are seen in large
tuberculomas.
–– Focal neurological deficit, appropriate to the site of the lesion, is
observed in approximately 50%.
Investigations
•• None of the currently available diagnostic procedures, either singly or in
combination, are able to provide an unequivocal diagnosis of an intracranial
tuberculoma.
•• Efforts are underway to develop specific and sensitive immunodiagnostic
tests, but so far these fall short of the desired accuracy.
463
•• The erythrocyte sedimentation rate is often raised, though it may be normal.

•• The Mantoux test is generally positive but a negative Mantoux test does
not rule out a tuberculoma, nor does a positive test establish the diagnosis.
•• A plain X-ray of the chest is mandatory as an active tubercular lesion
significantly increases the possibility of an intracranial mass being a
tuberculoma.
•• PCR is a useful diagnostic aid.
•• Plain X-rays of the skull may show signs of raised intracranial pressure
and, uncommonly, calcification.
•• The CT morphology depends on the stage of evolution and the maturity
of the lesion.
•• The important CT characteristics are summarised below: (Bhargava and
Tandon)
–– In a non-contrast enhanced scan tuberculomas are generally,
isodense with the surrounding brain. However, hypodense or slightly
hyperdense lesions are well-documented.
–– These enhance markedly on administration of contrast.
–– Perifocal oedema, usually quite out of proportion to the size of the
lesion, is common.
•• The lesions manifest in one of the following three forms:
–– Small discs and rings measuring less than a centimetre. They are
sharply outlined and homogeneously enhancing, surrounded by
perifocal low attenuation representing oedema.
–– A large ring, usually 1−2 cm in diameter, with a uniformly enhancing
periphery and central lucency, though not as marked as in a pyogenic
abscess.
–– Large nodular masses with an irregular outline.
•• Multiple lesions representing one or more of the above varieties, occurring
in the same patient, are seen in 15−20%.
•• Intracranial tuberculomas usually show complete hypointensity, isointensity
or central hyperintensity with a hypointense rim on T1-weighted images and
isointensity and/or hypointensity on T2-weighted images.
•• The intensity of a tuberculoma on T1-weighted images depends on the number
of macrophages, the degree of fibrosis, gliosis and lipid contents.
•• Lipids are the major contributor to the low-signal intensity on T1 images.
•• Solid caseation appeared hypointense and liquid appeared hyperintense on
T1-weighted images.
Magnetic Resonance Spectroscopy:
In vivo, proton MR spectroscopy of the hypointense lesions shows a
characteristic lipid peak on stimulated echo acquisition mode (STEAM) and
point resolved spectroscopy sequence (PRESS).
Stereotactic Biopsy
•• When the diagnosis of a lesion, suspected to be a tuberculoma, is in doubt,
one may start a trial of antituberculous treatment or do a stereotactic biopsy.
•• Stereotactic biopsy gives a definite diagnosis to enable the treatment to
be based on firm grounds.
464
Treatment
•• With the availability of CT, the diagnosis has become more reliable and the
effect of medical treatment can be evaluated non-invasively.
•• This has radically changed the indications for surgery.
•• It is now generally, agreed that surgery is indicated:
–– If vision or life is threatened due to a severe increase in intracranial
pressure
–– When the diagnosis is in doubt.
•• In all patients with a reasonable suspicion of a tuberculoma, with no
imminent threat to vision or life, a course of multi-drug antitubercular
chemotherapy is initiated.
•• Steroids may be added in case of CT or MR response to treatment is
closely monitored.
•• As a rule, clinical improvement is obvious within 2−3 weeks and significant
reduction in the size of the lesion can be documented by CT or MR within
4−6 weeks.
•• Complete resolution of the lesion depends on its size, and is seen as early
as 10−12 weeks for small lesions and even large lesions may resolve
completely in 6−8 months time.
•• Medical treatment may not resolve all tuberculomas. The lesion may
develop central liquefaction, may remain unchanged or even paradoxically
increase in size.
•• The reason for the lack of response and the paradoxical response is not
clear.
•• There are two controversial questions in respect of medical therapy:
1. The ideal combination of drugs
2. The duration of the treatment.
•• Among the antitubercular drugs, rifampicin, isoniazid, pyrazinamide and
streptomycin are bactericidal, and the former three penetrate the blood-
brain barrier both in the presence and in the absence of inflammation.
•• Hence, ideally, these constitute the important first line of drugs.
•• After the initial treatment with three drugs, any two of these three or only
INH and ethambutol are used for another 12−15 months.
•• Recently, streptomycin had to be reintroduced in some patients in whom
there was no adequate response to a three drug regimen.
•• It is important to realise that most antitubercular drugs have side/toxic
effects. These should be assiduously looked for and patients should be
warned to report immediately, if any untoward reactions are observed.
•• Liver toxicity is a real problem with the use of rifampicin. It may be better
to evaluate liver function periodically by appropriate tests.
•• There is a risk of optic neuritis when ethambutol is used.
•• It is desirable to use pyridoxine (10 mg) as prophylaxis against peripheral
neuritis encountered with the use of isoniazid and ethambutol.
•• The ototoxic complications of streptomycin are well known.
Multi-drug Resistant Tuberculosis

•• Multi-drug resistant tuberculosis is becoming a common problem and
results from inappropriate dosage, use of a single drug or inadequate
duration of therapy.
465
•• The resistance is influenced by bacterial genome changes.

•• The coexistence of HIV/AIDS infection increases the chances of developing
multi-drug resistance.
Surgical Treatment
•• The guiding principles for surgery are:
–– Total excision of easily accessible lesions in non-eloquent areas of the
brain should be done.
–– No attempt should be made to excise large tuberculomas en-masse.
Piecemeal removal or initial debulking does not increase the risk of
meningitis if the patient is covered with antitubercular drugs.
–– Subtotal or partial excision of lesions situated in or near eloquent along
with appropriate chemotherapy is generally curative areas.
–– No attempt should be made to excise aggressively tuberculomas at-
tached to vital structures like the brainstem or the major dural venous
sinuses.
–– Simple evacuation of the central liquefied caseous material from a
tuberculoma or pus from a tubercular abscess may be adequate for
treatment of deeply situated lesions, i.e. those in the thalamus, basal
ganglia and brainstem. This may preferably be carried out stereotacti-
cally.
–– Small, circumscribed lesions, the so-called microtuberculomas could
be excised stereotactically, if the diagnosis is in doubt.
–– Residual lesions, or in cases of multiple tuberculomas, the lesions that
have not been excised, respond well to chemotherapy.
–– A ventriculoperitoneal shunt may be required for patients with gross
hydrocephalus.
62
CHAPTER
Tuberculous Meningitis
PN Tandon  Anil Pande
INCIDENCE
•• The incidence of tuberculour meningitis (TBM), in patients with tuberculosis,
has been reported to vary from 7% to 12%.
•• TBM is a disease of childhood, with the maximum incidence around 3 years.
•• It is uncommon before 6 months of age and rare before the age of 3 months.
•• The incidence in adults is increasing and adults account for 50% of patients.
AETIOPATHOGENESIS
•• Much of the characteristic pathology of TBM is recreated with the subara-
chnoid injection of tubercular proteins alone.
•• The spectrum of CNS tuberculosis is varied, and both the host and bacterial
genotype influence the development of disseminated disease.
•• A cascade of proinflammatory cytokines (e.g. tumour necrosis factor, TNF
alpha, interferon, Gamma-cytokines) influence the cell mediated response.
•• TBM is correctly characterised as a meningo-vasculo-encephalitis as the
meninges, parenchyma and vasculature are all involved.
•• There is a thick subarachnoid tubercular exudate resulting in basal
arachnoiditis.
•• The small and medium sized arteries that traverse the exudates develop
an inflammatory tuberculous arteritis and the adventia and intima develop
typical tubercular granulomatous lesions.
•• The intima may be damaged by fibrinoid hyaline degeneration and this leads
to vascular occlusion by a reactive subendothelial cellular proliferation.
EARLY DIAGNOSIS
•• Constant awareness of the disease and clinical suspicion are prerequisites
for early diagnosis.
•• Usually the clinical features include fever, meningismus, nausea and
vomiting, and neurological deficits including cranial nerve involvement,
motor paresis and a bulging fontanelle in infants.
•• Modified criteria of Ahuja are useful to diagnose the disease and include
the following:
A. Clinical—Fever with or without change in the temperature over a
period of 2 weeks with or without any cause (mandatory), loss of
appetite, irritability, headache, vomiting, meningeal signs, convulsions
and focal neurological deficits; known contact with sputum positive
adult tuberculosis (optional).
Chapter 62 • Tuberculous Meningitis
467
B. Cerebrospinal fluid (CSF)—Pleocytosis with more than 20 cells/

mm3, lymphocytes more than 60%, protein more than 100 mg% and
sugar less than 60% of corresponding blood sugar.
C. Radiological—Computerised tomography (CT) studies of brain show-
ing two or more of the following:
1. Exudates in the basal cisterns and/or in the Sylvian fissures
2. Hydrocephalus
3. Infarcts
4. Gyral enhancement.
D. Extraneural tuberculosis—Active tuberculosis of lungs, gastrointes-
tinal tract, lymph nodes, skeletal system as evidenced by appropriate
radiological or microbiological evidence or by the presence of casea-
tion necrosis on histological examination.
Diagnosis of TB meningitis is classified into four groups based on the above
clinical and laboratory criteria.
1. Definitive TBM
a. Clinical criteria
b. Bacterial isolation from CSF or diagnosis at autopsy
2. Highly probable TBM
b. All three of B, C and D above
3. Probable TBM
b. Any two of B, C or D
4. Possible TBM
b. Any one of B, C or D.
•• CSF examination at the least suspicion is essential.
•• Apart from changes in cells and proteins, enzyme-linked immunosorbent
assay (ELISA) tests are most useful.
•• The polymerase chain reaction (PCR) is useful in the rapid diagnosis of
tubercular meningitis and has a sensitivity varying from 31% to 60%.
•• Microscopic observation drug susceptibility (MODS) assay format detects
the presence of 65 kD HSP antigen which is specific to M. tuberculosis
and is a reliable diagnostic marker of TBM.
•• IgG reactivity to lipoarabinomannon (LAM) in the CSF is very useful in the
early diagnosis of TB meningitis and is superior to PPD in the diagnosis
of TBM.
•• Culture of the bacteria takes 2−6 weeks.
•• Centrifugation and filtration methods are used to increase the yield of
positive cultures.
•• The isolation rates for the BACTEC 12B medium and LJ medium were
93% and 39%, respectively.
LATE DIAGNOSIS AND COMPLICATIONS

•• The most common complication of tubercular meningitis, where surgery
is helpful, is post-meningitic hydrocephalus resulting from a blockage of
the CSF pathways as a result of inflammation, the incidence of which may
range from 38% to 80%.
468
•• Tubercular meningitis may also present with raised intracranial pressure

(ICP), mimicking a brain tumour, cerebral abscess or tuberculoma.
•• A progressive hemiparesis due to vascular involvement in tubercular
meningitis may resemble an intracranial space occupying lesion.
•• Occasionally, a tuberculoma may follow or be associated with tubercular
meningitis.
•• Basal arachnoiditis due to tuberculosis may be localised and cause
neurological deficits or hydrocephalus.
•• Compression of the optic chiasma may result in impairment of vision.
•• Spinal arachnoiditis, often associated with meningitis, may result in spinal
cord compression.
Acute Stage of the Disease

Raised Intracranial Pressure Pathogenesis
•• Most of the cases of TBM are associated with raised ICP, which is caused
by brain oedema, increased proteins in the CSF, poor absorption of CSF
and obstruction to CSF flow.
•• In the early stages, there is a mild increase in ICP due to the general
inflammatory processes.
•• Later, cerebral oedema with associated tuberculous encephalopathy
occurs, possibly on the basis of an allergic reaction.
•• The large arteries at the base of the brain get occluded or compressed
with resulting ischaemic oedema and infarction in the affected territory.
•• Radioisotope studies have shown no significant obstruction to the flow of
CSF from the ventricular system to the subarachnoid space in the acute
stage.
•• However, in later stages the obstruction to CSF flow may be at a variety of
sites—aqueduct, fourth ventricle, tentorial opening or the arachnoidal villi.
It may even be at more than one of these sites.
Diagnosis and Treatment
•• A patient with TBM and associated acute intracranial hypertension may
present with an alarming picture of impaired level of consciousness and
decerebrate spasms.
•• These patients are usually young and the signs of meningitis may be
minimal.
•• The correct diagnosis can be arrived at only by an examination of the
lumbar CSF.
•• The risk of lumbar puncture in the presence of raised ICP is minimised by
anti-oedema measures like IV mannitol which helps to reduce cerebral
oedema.
•• CT studies may show acute oedema with compressed narrow ventricles
or hydrocephalus with a dilated ventricular system.
•• The addition of acetazolamide and furosemide, to antituberculosis
chemotherapy, is effective in controlling ICP.
•• If acute hydrocephalus still develops, repeated ventricular tapping or
external ventricular drainage with a closed system is essential to reduce
ICP. This may be done directly through suitably placed burr holes or after
inserting an Ommaya reservoir.
469
Subacute and Chronic Stage of the Disease

Tuberculous Endarteritis
•• Vascular involvement in TB meningitis is usually a tuberculous endarteritis
affecting the smaller blood vessels and resulting in multiple focal
neurological signs, due to localised areas of infarction.
•• In late cases, these areas get calcified and are visible in the plain X-rays
as irregular small areas of dense calcification.
•• Such calcification is more common than the one seen infrequently in
tuberculomas.
•• The resultant clinical picture will vary with the areas involved, e.g. hypo-
pituitarism or hypothalamic obesity in association with basal calcification.
Involvement of Large Arteries
•• The large arteries may be displaced, kinked or obstructed by the
tuberculous exudates at the base of the brain.
•• The siphon of the internal carotid artery, its bifurcation and the proximal
segments of the middle cerebral artery are most commonly involved.
Occasionally, the anterior cerebral artery may also be narrowed or occluded.
•• The affected artery shows changes of periarteritis and a massive subintimal
fibrosis, narrowing or occluding the lumen. These changes have been
demonstrated by arteriography and at autopsy.
Tuberculomas and Tuberculous Abscess
•• They manifest as a space occupying lesion, requiring appropriate investigations
and treatment.
•• CT or MRI scan helps to localise the lesion, which may be excised with
complete relief.
•• These are characterised by an encapsulated collection of pus containing
viable tubercular bacilli and 50% of the cases developed TB abscess while
on ATT for TB meningitis.
•• Only multilocular abscesses or those with thick capsules required excision,
the rest were managed with aspiration and ATT.
Basal Meningitis
•• Plaque simulating a neoplasm: As the disease becomes more chronic, the
meningeal exudates become firm, organised and adherent to the base of
the brain.
•• In some areas, the exudates becomes plaque-like, a few millimetres thick,
almost like a granuloma, whilst the rest of the exudates clear up.
•• At times, when the process has become more chronic and localised, woody
hard fibrosis of the leptomeninges may produce a bizarre clinical picture
without clinical evidence of meningitis.
•• Such cases may simulate posterior fossa tumours, foramen magnum
lesions or intracranial abscesses.
•• MR is helpful in differentiating these conditions.
•• In these cases, the disease, though localised, is still in an active form.
•• The patient may present with headache, vomiting and drowsiness, and
mild pyrexia is present.
•• The clinical picture often simulates a posterior fossa neoplasm if a definite
history of TBM is not available.
470
•• The CT shows a dilatation of the ventricular system with no enlargement

of the subarachnoid space.
•• The fourth ventricle may be displaced and distorted.
•• At surgery, a thick carpet of granulation tissue is seen obliterating the
cisterna magna and the exit foramina of the fourth ventricle.
•• A ventriculoperitoneal shunt is more effective.
Hydrocephalus
•• More often, the exudates get organised and there is a fibrous obliteration
of the subarachnoid space.
•• The disease dies down, but hydrocephalus develops and leads
to progressive mental deterioration and impairment of the level of
consciousness.
•• The hydrocephalus may be communicating or non-communicating.
•• The raised ICP in subacute and chronic TBM is essentially due to the
hydrocephalus produced by the obstruction of the CSF pathways.
•• Blockage of the arachnoid villi contributes to the production of hydrocephalus.
•• A common site of obstruction is in the basal cisterns like the cisterna pontis,
interpeduncularis and ambiens.
•• In the majority of cases, the hydrocephalus is of the communicating variety as
confirmed by isotope cisternography.
•• At times, the exudates block the foramen of Munro or the foramina of Luschka
and Magendie preventing the exit of CSF from the fourth ventricle.
•• Blockage of the aqueduct of Sylvius may be caused by the exudates or by
ependymitis with local oedema, or an associated small intrinsic tuberculoma.
Clinical Picture
•• This depends upon the stage of the disease when hydrocephalus sets in.
•• In the acute stage, when the symptoms and signs of meningitis dominate,
the development of hydrocephalus is heralded by increasing ICP, while
the systemic and meningitic signs appear to be responding to treatment.
•• Infants develop a bulging fontanelle, enlarging size of the head and
increasing drowsiness.
•• On the other hand, hydrocephalus may manifest months after the treatment
for meningitis has been completed. At this stage, there are no clinical
features of meningitis or systemic toxaemia. The patient presents with
symptoms and signs of raised ICP, only the history indicating the aetiology.
•• Amongst adults, one occasionally sees a patient presenting with raised
ICP, with or without any neurological deficit, and with no clinical evidence
of meningitic or infective pathology.
•• Investigations reveal a communicating hydrocephalus.
•• CSF examination or a contrast enhanced CT may reveal the inflammatory
nature of the lesion.
•• The possibility of tuberculosis being the cause of the condition is often
presumptive.
Investigations
•• In the acute stage, CSF examination reveals evidence of meningitis,
predominantly lymphocytic pleocytosis, raised proteins and diminished
sugar.
•• In the chronic stage, the CSF may be normal or may show mild pleocytosis
and increase in proteins.
471
•• Coexistent syndrome of inappropriate secretion of antidiuretic hormone

(SIADH) and cerebral salt wasting syndrome should be looked for and
treated.
•• Polyurea, hyponatraemia, volume depletion and increased sodium
excretion are pointers.
•• Computerised tomography:
–– It establishes the diagnosis of hydrocephalus and may suggest a pos-
sible tuberculous aetiology.
–– Basal exudates can be detected and their severity ascertained. Such
exudates, though characteristic of TBM, are not diagnostic and can be
seen in other bacterial, fungal and carcinomatous meningitides.
–– The most specific feature of TBM is hyperdensity in the basal cistern
area prior to IV contrast medium administration, and the most sensitive
feature is basal enhancement.
–– The severity of hydrocephalus can be quantified in the CT by plani-
metric measurement of the surface area of the brain and the ventricle.
–– The degree and significance of hydrocephalus is calculated by the
ventricular size index (VSI), which is a ratio of the bifrontal diameter
over the frontal horn diameter.
–– A VSI range of 30−38% signifies mild hydrocephalus, 39−45% moder-
ate hydrocephalus and severe hydrocephalus is indicated by VSI of
46% and above.
–– Periventricular lucency indicates transependymal CSF flow and is
caused by elevated ICP or spread of the inflammatory process.
–– CT also reveals the presence or absence of infarcts and tuberculomas
which have a direct relevance to therapy and prognosis.
–– Abnormal CT scan findings may persist even after 6 months and
despite good clinical improvement.
•• SPECT reveals more frequent abnormalities compared with EEG and CT
scan.
•• Cortical hypoperfusion with or without basal ganglia hypoperfusion is
associated with frontal rhythmic intermittent delta activity (FRIDA) and
diffuse slowing on EEG.
•• BAER and VEP may have a role in evaluating these patients and show
characteristic changes.
•• Magnetic resonance imaging:
–– Reactive diffuse meningeal enhancement occurs in the early period of
tubercular meningitis on contrast medium enhanced T1 weighted MR;
this later becomes limited to the basal regions.
–– The most specific feature of TBM is hyperdensity in the basal cisterns
prior to administration of contrast medium.
–– Magnetisation transfer MRI is an important modality to detect infectious
meningitis of different aetiology and the visibility of the meninges on
precontrast T1 weighted MTMRI images is highly suggestive of TBM.
Treatment
•• The scope of surgical management has increased due to availability of
shunt systems and the endoscope.
•• In those subacute and chronic patients of TBM, which have developed
hydrocephalus, a ventriculoperitoneal shunt is indicated.
•• Mild hydrocephalus (VSI 30−35%) is treated with acetazolamide (20 mg/
kg/day in three divided doses).
472
•• A large volume of evidence has accumulated to show that dissemination

of the disease is rare if the shunt is inserted under adequate cover of
chemotherapy, even whilst the disease is active.
•• After the insertion of the shunt, most of the patients show gradual recovery,
even though the CSF may continue to show some abnormality.
•• The level of consciousness improves and the neurological deficit regresses.
•• Endoscopic surgery:
–– Confirming that the hydrocephalus is non-communicating is very impor-
tant in the management of hydrocephalus secondary to TB meningitis.
–– The endoscope can also be used for third ventriculostomy and/or
fenestrate loculations and the septum, thereby reducing the number
of shunts.
•• Corticosteroids:
–– The use of steroids under ATT cover is advocated and improves
outcome.
–– The use of steroids decreases cerebral oedema, and the production
of cytokines and other chemicals in the immunopathogenesis of TBM.
–– Corticosteroids are given during the first month of treatment with IV
dexamethasone (0.6−1.2 mg/kg/day in three divided doses) for 1 week
followed by oral prednisolone (2 mg/kg/day in three divided doses).
•• Antituberculous drugs:
–– The first-line drugs used are isoniazid, rifampicin and pyrizinamide, all
of which are bactericidal.
–– Ethambutol, a bacteriostatic drug or streptomycin in children too young
to be monitored for visual acuity, are included in the initial treatment
regimen if there is a possibility of drug resistance.
–– Rifampicin is given orally (10 mg/kg). It is contraindicated in jaundice
and pregnancy and has adverse effects of liver toxicity, GI symptoms
and rarely shock and respiratory collapse.
–– Isoniazid is given orally or by the intramuscular route (3−10 mg/kg).
It is contraindicated in drug induced liver disease and has adverse
effects like peripheral neuropathy, psychosis, optic neuritis and,
occasionally, lupus syndrome.
–– Pyrazinamide is given orally (20−30 mg/kg) and is contraindicated in
liver damage and can cause hepatitis.
–– Ethambutol is given orally (15 mg/kg) and is contraindicated in pres-
ence of optic neuritis and can cause optic neuritis, colour blindness
and peripheral neuritis.
–– Streptomycin is given as intramuscular injections (1 g/day)
(20−25 mg/kg). It is contraindicated in pregnancy and old age and can
cause ototoxicity and renal damage.
–– The duration of ATT (short term/long term) is controversial and many
neurosurgeons prefer to give 18 months of antituberculous drugs.
•• Anticonvulsants: Anticonvulsants are necessary because of the high
incidence of seizures in patients with TBM. Patients with focal or generalised
seizures or tonic spasms that occur more than once, or associated with
abnormal scans or EEG findings are started on anticonvulsants.
SEQUELAE OF THE DISEASE

1. Optochiasmal arachnoiditis
2. Malnourishment
3. Endocrine abnormalities
473
Tuberculous Spinal Arachnoiditis

Incidence
•• Tuberculous spinal arachnoiditis is generally a complication of meningitis.
•• It has been reported in 10−30% of cases, either during the course of
treatment of TBM or several months or even years after the arrest of the
disease.
•• Isotope cisternography in patients undergoing treatment for TBM revealed
a much higher incidence of spinal involvement than clinically suspected.
•• In some cases, the disease may start primarily as spinal meningitis.
•• This is due to rupture into the subarachnoid space of a tuberculous focus
(tuberculoma) on the surface of the cord.
•• In some cases, the spinal lesion may spread to involve the cranial cavity
resulting in a full fledged picture of TBM.
Pathology
•• Tuberculous spinal arachnoiditis usually occurs concomitantly with TBM.
•• The spread of infection from the cranial cavity to the spinal canal is
responsible for those cases associated with a known case of TBM.
•• In these cases, besides the cranial basal exudates, there is often a thick
exudate in the spinal theca.
•• At times the cranial basal exudates may be slight, whereas the spinal
involvement may be quite marked.
•• The maximum involvement is in the dorsal or dorsolumbar region.
•• The leptomeninges are infiltrated with fibrinopurulent exudates in different
stages of organisation depending upon the stage and duration of the illness.
•• The longitudinal extent of the lesion is variable, involving only a few
segments or extending throughout the spinal canal.
•• Macroscopic nodular tubercles may be seen on the surface pointing to
the diagnosis.
•• The dura is adherent to the exudates overlying the spinal cord.
•• In chronic cases, the fibrocollagenous tissue may acquire a woody
hardness.
•• The cut surface of the cord is atrophic and soft due to oedema.
•• Microscopically, the characteristic tubercular lesions, fibrinous exudates,
caseation necrosis, granulomas with epithelioid cells, Langhans giant cells,
lymphocytes and plasma cells are obvious.
•• With the passage of time, the exudates get organised and tuberculous
granulation tissue is found to envelop the cord.
•• Occasionally, fibrosis sets in and thick fibrous tissue may either
constrict the spinal cord or the spinal nerve roots or both, producing a
myeloradiculopathy.
Clinical Features
•• The possibility of the coexistence of spinal arachnoiditis with TBM is
considered when such a patient develops root pains, weakness of the
lower limbs and sphincter disturbances.
•• This is confirmed by lumbar puncture, which reveals evidence of a partial
or complete block with increase in the protein content of the CSF with a
variable lymphocytic cellular response.
•• The glucose tends to be low.
•• When spinal arachnoiditis is not associated with the cranial manifestions,
it presents essentially as spinal cord compression.
474
•• In the acute stage, there may be systemic manifestations like malaise

and pyrexia.
•• Both in the subacute and chronic stages of the disease, root pains,
progressive paraparesis or quadriparesis with sphincter involvement are
the presenting features.
•• As the lesion is usually diffuse, one often finds a mixture of a level of sensory
loss and extensor plantar responses that suggest a high dorsal lesion, and
absent reflexes in the lower limbs.
•• Lumbar puncture reveals a partial or complete block with the CSF showing
increased proteins and a mild cellular lymphocytic response.
•• Lumbar myelogram may show an incomplete block, with the contrast
flowing very slowly in small fragmented globules or a complete block
with an irregular margin. The block is likely to be at a level lower than the
expected clinical level.
•• Cisternal myelogram shows the upper level of the block which often
confirms a very extensive lesion.
Magnetic Resonance Findings
•• TB leptomeningitis is characterised by loculation of the CSF, subarachnoid
nodular lesions, nerve root thickening and clumping seen in the lumbar
region, or complete obliteration of the subarachnoid space.
•• Gadolinium MR may show linear enhancement of the surface of the spinal
cord and nerve roots or plaque-like enhancement of the dura-arachnoid
complex.
•• Intramedullary lesions, like tuberculomas, cord oedema and cavitations,
are well seen.
•• Increase in CSF intensity on T1 weighted images leads to loss of cord CSF
interface or a shaggy outline.
Treatment
•• Having established a diagnosis of spinal arachnoiditis, the treatment is
essentially medical.
•• Antituberculous drugs, with a full course of steroids, may be of help in a
fair number of patients.
•• Intrathecal administration of hydrocortisone 25 mg or methyl prednisolone
twice a week may help in the further resolution of the exudates.
•• Surgery may be offered only if the diagnosis is in doubt, if the lesion is
fairly localised and not diffuse or if the imaging is suggestive of a cyst at
the expected clinical level.
63
CHAPTER
Tuberculosis of the Spine
Sridhar K
INCIDENCE
•• Of all the patients with tuberculosis, nearly 1−3% has involvement of the
skeletal system.
•• Vertebral tuberculosis is the commonest form of skeletal tuberculosis,
most series reporting an incidence of up to 50% of osteoarticular
tuberculosis.
•• Spinal tuberculosis can occur at any age and affects both sexes equally.
PATHOLOGY AND PATHOGENESIS

•• Tuberculosis is the prototype of a granulomatous disease in man.
•• The tubercle comprises of an organised microscopic aggregation of plump
rounded histiocytes (macrophages) that vaguely resemble epithelial cells
and are therefore called epithelioid cells.
•• At the margin of a cluster of epithelioid cells there may be some Langhan’s
multinucleate giant cells, formed by the fusion or internal nuclear divisions
of macrophages.
•• Around this is a collar of plump fibroblasts interspersed with mature
macrophages and lymphocytes.
•• The tubercles thus formed grow by expansion and coalescence.
•• The characteristic caseation occurs in the central region of the epithelioid cells.
•• The caseous material may soften and liquefy.
•• Marked exudative reaction is a common feature of spinal tuberculosis.
•• The incidence of exudative response is much higher amongst patients from
developing countries.
•• A “cold abscess” is composed of serum, leucocytes, caseous material, bone
debris and bacilli.
•• It can penetrate the ligaments and migrate along fascial planes, often
presenting far from the site of infection.
Route of Infection
•• The spinal disease is always secondary to a primary lesion, usually from a
visceral focus, and occurs due to haematogenous spread.
•• Involvement of different parts of the spine and the presence of associated
visceral lesions imply a bacillaemia causing the spread of infection from
the primary focus.
•• Infection may reach the spine due to a bacillaemia or through the Batson’s
plexus of veins.
476
•• The primary focus may be active or quiescent and may be in the lungs,
mediastinal lymph nodes, kidneys or other viscera.
•• Simultaneous involvement of the paradiscal part of two contiguous
vertebrae suggests spread of infection via the common blood supply to
the region.
Types of Lesions
•• Classically, four types of involvement of the spinal column have been
described in spinal tuberculosis:
1. A paradiscal lesion which arises from arterial spread of the infection
2. The central type of vertebral body involvement of one or more distant
or adjacent vertebrae (this is often associated with tuberculous menin-
gitis as the spread of the infection is via the Batson’s plexus of veins)
3. The anterior type with cortical bone destruction
4. Appendiceal type.
•• The paradiscal lesion begins in the vertebral metaphysis, erodes the cartilage
plate and destroys the disc. The cartilaginous end plate acts as a barrier, but
once invaded, destruction of the disc progresses rapidly due to its relative
avascularity, and the infection goes on to involve the adjacent vertebrae.
•• In the central type of lesion the infection begins in the midsection of the
body instead of the metaphysis. It extends centrifugally to involve the whole
body. Following the infection, marked hyperaemia and osteoporosis occur.
The body, which is thus softened, easily yields under gravity and muscle
action, leading to compression, collapse and bony deformation.
•• Anterior lesions lead to cortical bone destruction beneath the anterior
longitudinal ligament. Spread of the infection in the subperiosteal and
subligamentous planes, allows extension of the infection to adjacent
bodies without involvement of the intervening disc space. Stripping of the
periosteum results in loss of the periosteal blood supply to the body. This,
along with thrombo-embolic phenomena, periarteritis and endarteritis
can lead to ischaemic reactions of the bone contributing to the vertebral
collapse.
•• In the appendiceal type the pedicle, the lamina, the articular process or
the spinous process is affected primarily.
Neurological Involvement
•• Neurological involvement is the most serious of the complications of spinal
tuberculosis.
•• The overall incidence of neurological complications varies between 10%
and 40%.
•• The risk of paraplegia is highest in lesions of the cervico-dorsal region.
•• Involvement of the cauda equina in the lumbar and lumbosacral regions
is seen less frequently.
•• The spinal cord may be involved during any phase of the disease, in the
active phase within the first 2 years or in later years after the disease has
become quiescent.
•• The severity of the neurological deficit can be graded depending on the
degree of motor involvement.
•• The cause of paraplegia in most cases is compression of the spinal cord
due to one of the following mechanisms:
Chapter 63 • Tuberculosis of the Spine
477
1. In active disease:
a. Abscess (fluid or caseous)
b. Granulation tissue
c. Sequestrated bone and disc
d. Pathological subluxation or dislocation of vertebrae.
2. In healed disease:
a. Transverse ridge or bone anterior to the spinal cord;
b. Stretching or attrition of the cord due to spinal deformity
c. Fibrosis of the dura.
•• In a given case more than one factor may contribute to the pathogenesis.
Pathology
•• The extradural mass, caused by an abscess, sequestrae or granulation
tissue, fills the epidural space and spreads around the dural sac, thus
compressing the spinal cord.
•• It may get adherent to the dura, which becomes thickened by the formation
of new fibrous tissue on its outer surface.
•• The granulation tissue causes loss of function by not only direct
compression of the cord, but also by impeding venous drainage, thus
causing cord oedema.
•• As a rule the dura constitutes a very good barrier against the spread of
infection.
•• The usual pathological lesion in the cord, in the early stages, is a vacuolar
type of myelin degeneration seen in the lateral or anterolateral columns.
•• This is more diffuse than seen in ischaemic lesions and may be secondary
to venous obstruction.
•• Acute severe lesions of the cord may be produced where there is rapid
collapse of a vertebral body with the cord stretched over a relatively intact
intervertebral disc or when sequestrae are pushed backwards into the
spinal canal by a sudden angulation .
•• Infarction of the spinal cord may occur due to endarteritis, periarteritis or
thrombosis of the arterial supply of the cord.
•• An important radicular supply to the cord may be compromised occasionally
at the intervertebral foramen before it enters the dura.
•• Angulation of the spine on healing may lead to the formation of a bony ridge
or spur called ‘an internal gibbus’ on the anterior wall of the spinal canal,
resulting in a slow and progressive paraparesis.
•• The clinical picture has three components:
1. The systemic illness
2. The osseous lesion
3. Neurological complications.
•• As with tuberculosis elsewhere in the body, there may be malaise, pyrexia,
loss of appetite and weight, and night sweats.
•• Back pain is a predominant clinical feature.
•• The spine is stiff and painful on movement, with spasm of the paravertebral
muscles.
•• Angulation of the spine in the form of a kyphosis or gibbus is seen as the
disease advances.
478
Associated Lesions
•• The incidence of associated visceral lesions (of the lung, kidney or lymph
nodes) varies between 40% and 50% in different series.
Neurological Deficit
•• The degree and extent of the neurological deficit depends on the site of the
disease, the direction of spread and the pathological changes produced.
•• While usually the onset of symptoms is slow and progressive, in a small
percentage of cases the paraplegia may be of sudden onset and nearly
complete from the beginning.
•• Tandon and Pathak have divided the clinical picture of Pott’s disease into
four groups:
1. Paraplegia arising in a known case of spinal tuberculosis
2. Paraplegia as the presenting symptom of spinal tuberculosis
3. Spinal tumour syndrome
4. Paraplegia due to tuberculosis of the posterior neural arch.
IMAGING
Plain X-rays
•• The paradiscal lesion is the commonest lesion seen.
•• Narrowing of the disc space is the earliest radiological finding on plain
X-rays, and when associated with a loss of definition of the paradiscal
margins of the vertebra, the diagnosis of tuberculosis is obvious.
•• Lytic areas in the metaphyseal regions of the body may not be seen early,
as foci less than 1.5 cm in diameter are not demonstrable on a conventional
radiograph.
•• At least 30−40% of calcium should be lost before a radiolucent area is
visible on a plain X-ray.
•• Sclerosis may be seen in up to 50% of patients at presentation.
•• The central type of disease arises from the centre of the vertebral body,
which loses the normal bony trabeculae and may show as areas of
destruction.
•• In the anterior type of lesion, the infection begins beneath the anterior
longitudinal ligament. This results in erosion of the peripheral parts of the
vertebral body (in front and on the sides), which is seen well in the lateral
or oblique views as shallow excavations.
•• The tendency for erosion is greater when the aorta is in close proximity
to the paravertebral abscess as the transmitted pulsations compound the
pressure caused by the abscess.
•• Stripping off of the periosteum deprives the bone of its blood supply, making
the bone more liable to the destructive and scalloping effects of the lesion.
•• Lesions of the pedicle, transverse process and the spinous process appear
as erosion of the region involved and may be missed in the plain X-rays
unless specifically looked for.
•• Wedge collapse of adjacent vertebrae with paradiscal bone destruction
causes forward angulation of the spine and when this involves a large
number of adjacent vertebrae a severe kyphotic deformity results.
•• A paravertebral shadow is commonly seen on the plain X-rays due to the
presence either of an abscess or extension of tuberculous granulation
tissue.
479
•• An abscess produces typical radiological findings depending on its size and

location: an abscess in the cervical region causes a widening of the space
between the pharynx and the vertebral body and upper thoracic abscess
causes a squaring of the superior mediastinal shadow when small, or a
V-shaped shadow when large, shifting the apices of the lungs laterally
and downwards; abscesses below D4 take up a typical fusiform shape;
and those below the diaphragm produce a widening of the psoas shadow.
•• CT scan is useful in assessing the destructive lesions in the vertebral
column.
•• CT helps to diagnose spinal tuberculosis in the initial stages.
•• Inaccessible fixed areas of the spine, difficult to see in conventional
radiographs, are seen with ease on axial CT sections.
•• Calcification, representing retained bone fragments, seen with paraspinal
collections and in regions of bone destruction, is said to be pathognomic
of tuberculous infection.
•• It represents the lack of the necessary proteolytic enzymes in Mycobacterium
tuberculosis that are necessary to lyse the bone.

•• The advantages of MR include high resolution, direct multiplanar
imaging, detection of marrow infiltration and the early detection of
intradural infection.
•• The technique used should be modified, depending on the site and extent
of the infection, using spin echo and T1-weighted imaging for localisation
of the lesion.
•• Extradural extension of the disease is better visualised with either a
T2-weighted image or a short T1 inversion recovery technique (STIR).
•• The latter technique has a higher sensitivity, but is less specific than the
T2-weighted images.
•• Both are useful in showing vertebral and intradural disease, but epidural
spread may not be detected early, as the abnormal signal obtained may
be isointense with CSF. Sagittal T1-weighted images using contrast are
necessary to detect early epidural spread of the infection.
•• The involvement of the paraspinal soft tissues is best seen in coronal
sections.
•• MR is also helpful in revealing associated lesions like intraosseous
abscesses, paraspinal cold abscess, vertebral body and disc collapse,
spinal deformity, skip lesions, epidural and intraspinal extension,
involvement and compression of the cord or nerve roots and appendicular
lesion.
•• T1-weighted images may show a decreased signal from the affected
vertebral marrow, reduced disc height, involvement of the paraspinal tissues
and extradural extension.
•• The T2-weighted images show an indiscriminately increased signal from the
marrow, discs and soft tissues. The use of gadolinium enhanced imaging
is advantageous.
•• Response to therapy may be seen as an increase in the signal intensity
from the affected vertebra on T1-weighted images.
•• This has been found to correlate well with clinical signs and symptoms.
•• However, radiologically evidenced progression of bone destruction may be
seen up to 14 months after the initiation of anti-tubercular therapy.
480
•• Distinguishing spinal tuberculosis from other spinal diseases, especially

pyogenic and fungal spondylitis and also metastatic disease of the spine
is important.
•• Features that are indicative of a tuberculous infection are:
–– Calcification within a paravertebral abscess
–– Presence of a large paravertebral abscess
–– Involvement of more than two vertebral levels
–– Involvement of the posterior elements
–– Multicentric disease
–– Subligamentous spread
–– Heterogeneous MR signal.
TREATMENT
Evolution of Surgical Treatment
•• The surgical procedures performed in the preantibiotic era included the
drainage of abscess (Pott 1779), laminectomy (Chipault 1896), laminotomy
(Fraser), costotransversectomy (Menard 1894), posterior mediastinotomy
(Obalinski), lateral rachiotomy (Capener 1933) and anterolateral
decompression (Ito 1934, Dott and Alexander 1947).
Posterior Fusion
•• This provided internal stability to the diseased spine, and helped to avoid
recurrence of the disease and the development of paraplegia.
•• It also shortened the period of immobilisation.
•• However, kyphosis could develop in spite of the posterior fusion and
there was also an appreciable incidence of pseudoarthrosis following the
procedure.
Antibiotic Therapy
•• The introduction of anti-tubercular drug therapy dramatically improved the
results of non-operative therapy and of posterior spinal fusion.
•• The most spectacular effect of the drugs was the disappearance of sinuses,
ulcers and abscesses and the elimination of post-operative dissemination
of the infection.
•• Such a dramatic improvement in the prognosis encouraged surgeons to
adopt total excision of the lesion along with anti-tuberculous chemotherapy.
This was the standard treatment between 1950 and 1960.
Conservative Therapy
•• In the pre-antibiotic era the treatment primarily consisted of attention to
general health and nutrition, external immobilisation of the spine, and
prolonged bed-rest extending over months. Some daring surgeons used
the above mentioned surgery for associated spinal compression.
•• Conservative therapy had many advocates and has been successfully used
in many countries even if there was evidence of early spinal compression.
•• Patients with Pott’s disease are still being treated with reasonal success by
the administration of anti-tubercular drugs, bed rest and braces.
481
Bed Rest or Ambulation

•• The current regime generally advocated:
–– It is advisable to patients on chemotherapy to have bed rest without
immobilisation for 4−6 weeks till the pain and spasm disappear and the
general health improves.
–– They are then allowed to get up, but wear braces which can be dis-
carded after a period of 6−8 weeks.
–– The chemotherapy is continued for 18 months.
–– The family members and contacts are checked for the presence of
tuberculous infection at the beginning of the treatment.
Excisional Therapy and Grafting

•• Excisional therapy has given good results and is widely followed.
•• Where there is extensive destruction and sequestra, evacuation of
tuberculous pus and debris and removal of sequestra of disc and bone
result in the opening up of new vascular channels in the ischaemic areas
with reduction of general toxaemia and reduction in total healing time.
•• Indications for surgery include, progressive bone destruction, increase
in the size of the abscess, failure to respond to conservative therapy,
uncertainty in diagnosis, recrudescence of local disease and development
of neural complications or pain in the spine due to mechanical instability
during conservative treatment.
Bone Grafting
•• Bony fusion occurred earlier and in a higher proportion of patients in the
group with bone graft.
Instrumentation
•• Recently introduced spinal Instrumentation helps to produce rigid fixation
of the involved segments of the spine to allow uninterrupted healing, as
movement in and around the spinal cord is still possible after anterior strut
grafting.
•• The instrumentation procedures also prevent any increase in spinal
deformity that may occur in the course of healing.
•• The type of instrumentation used is of individual choice and is also
dependent on the age of the patient.
•• The fixation devices and techniques are variable. It is essential that all
internal implants are MR compatible, to permit future MR examinations
of the patient.
Factors Influencing Results

•• The decision on the type of surgical therapy depends on many factors
which include the general health of the patient, the presence of concomitant
infection elsewhere, the facilities available for surgery and the avoidance
of secondary infection.
•• Prolonged disease, undernutrition and the presence of disease elsewhere
influence the overall results and additional measures may have to be
adopted.
482
•• The unfavourable factors were extensive vertebral destruction necessitating

a graft spanning more than two disc spaces, the involvement of thoracic
vertebra or a marked pre-operative kyphotic deformity.
Surgery for Paraplegia

•• Surgery to decompress the spinal cord is indicated in patients:
–– Who fail to respond to conservative treatment
–– Develop paraplegia while on appropriate chemotherapy
–– Patients in an advanced stage of disease when delay in decompression
is risky
–– Patients with posterior neural arch disease
–– Those with “spinal tumour syndrome” and
–– If the diagnosis is in doubt.
•• Relief of pressure on the spinal cord by the most appropriate technique is
the aim of treatment when paraparesis starts to appear.
•• Bed rest and anti-tubercular therapy alone have been found sufficient in
mild paraparesis.
•• However, if there is no obvious improvement within two or three weeks,
surgical decompression becomes necessary.
•• Simple drainage of the cold abscess would be sufficient in those cases
where the tension inside the abscess is the cause of cord compression.
•• Laminectomy is an unsatisfactory procedure except in a few cases when
the compressing element is posterior, as in tuberculous disease of the
neural arch, or in spinal tumour syndrome.
•• The route of approach has to be tailored to the level of the lesion, the
amount of compression and the general health of the patient.
•• Delaying surgical decompression for too long in the presence of paraplegia
may lead to problems, like extradural fibrosis, which may be difficult to
eradicate.
RECENT TRENDS IN THE MANAGEMENT OF

SPINAL TUBERCULOSIS
•• The aims of treatment are to confirm diagnosis, achieve bacteriological
cure, prevent and/or treat deformity and neural compression.
•• With better chemotherapeutic drugs available that reach pus, granulation,
caseous material and bone, non-operative management has become more
effective, especially in cases diagnosed early.
•• Radical resection has been defined as excision of the disease focus to
uncover the dura mater as completely as possible until healthy bleeding
bone is reached.
•• Debridement, on the other hand, has been defined as removal of pus,
granulation tissue, caseous tissue and loose sequestrated bone from
lesions and also part of the viable bone needed to decompress the spinal
cord leaving a relatively stable spine.
•• It is now recommended that radical excision is not necessary for
infective spinal lesions, like tuberculosis, where effective anti-tubercular
chemotherapy is available.
•• When one considers spinal instability related to tuberculosis it is essential
to remember that the pathophysiology is different compared to trauma.
483
•• Pathological fractures, involvement of the anterior and posterior spinal

elements, translation or dislocation of the destroyed vertebrae, and long
segment disease with kyphosis should all be considered as signs of
instability.
•• In the cervical spine the anterior approach is presently established as the
approach of choice.
•• In the case of thoracic tuberculosis, a transthoracic transpleural approach
gives an excellent exposure of the diseased segments.
•• The lumbar and lumbosacral spine may be approached retroperitonially.
•• Video-assisted thoracoscopic surgery (VATS) has been used by a few
surgeons for short segment disease where there is no lung disease and
especially for biopsy or for decompression of a cold abscess.
Late Onset Paraplegia

•• Years after the primary disease of the spine, has ‘healed’ paraplegia
may develop due to recrudescence of active disease at the original site
or as a result of chronic compression and ischaemia of the cord due to
pronounced kyphosis.
•• Anterior decompression is helpful for these patients.
Correction of Kyphosis
•• In many cases, proper posturing and wearing of braces when indicated,
help to correct a tendency for kyphosis.
•• In patients with kyphosis, correction can be attempted successfully during
excisional surgery and bone grafting.
•• Occasionally, special measures may be required.
Indications of Surgical Therapy

•• Neurological signs not improving or worsening within 4 weeks of adequate
conservative and drug therapy.
•• Development of neurological signs with progression while on adequate
therapy.
•• Recurrence of neurological signs after improvement.
•• Rapid onset paraplegia.
•• Paraplegia with flexor or painful spasms.
•• Posterior spinal disease with spinal tumour syndrome.
•• Prevertebral cervical abscess with difficulty in deglutition.
•• Late onset paraplegia.
•• Correction of kyphosis.
•• When the diagnosis is in doubt.
64
CHAPTER
Surgery for Leprosy
Sridhar K
PATHOLOGY OF NERVE INVOLVEMENT

Common Sites
•• The nerve gets involved either during the normal course of the disease or
during a reactive phase.
•• The nerves which are usually involved are the ulnar, the median and the
radial nerves in that order in the upper limb, and the common peroneal and
the posterior tibial nerves in the lower limbs.
•• The facial and the trigeminal nerves are the only cranial nerves commonly
involved.
•• The superficial radial, the superficial peroneal, the greater auricular and
the sural nerves which are purely sensory, when involved, show thickening
which may help in establishing the diagnosis.
•• The reason why some nerves are involved at specific sites is not clear.
Some common anatomical features have been noted in these nerves at
these specific sites:
–– The affected nerves lie at a comparatively superficial plane where the
temperature is low.
–– The site of involvement is near a joint where there is frequent motion.
–– The involvement is near an area of constriction like an osseofibrous
tunnel, intermuscular septum or retinaculum.
–– The nerves lie over bony prominences.
•• The ulnar nerve is the commonest nerve to get involved; the common site
of involvement being proximal to its passage under the osseofibrous tunnel
behind the epicondyle.
•• Median nerve palsy is commonly at a lower level; the long flexors of the
fingers and thumb escape and only the intrinsic muscles of the hand are
paralysed.
•• The common peroneal nerve, like the ulnar nerve, is involved as it curves
round the neck of the fibula and produces a foot drop.
•• The posterior tibial, like the median nerve, gets involved before it enters
the flexor retinaculum near the ankle.
•• Branches of the VII cranial nerve, mainly the ones supplying the orbicularis
oculi and frontalis, are involved as they cross the zygomatic arch and are
near the temporomandibular joint.
Chapter 64 • Surgery for Leprosy
485
Entry of Bacilli into the Nerve and

Establishment of Neuritis
•• Various theories have been postulated regarding the mode of entry of the
bacilli into the nerves:
–– Phagocytosis by Schwann cells in the outer layers of the dermis and
once engulfed the bacilli travel by contiguity from Schwann cell to
Schwann cell or within the axons. There are many objections to this
theory.
–– Penetration of the perineurium: The perineurium is a formidable barrier
in leprosy and this explanation is also not satisfactory.
–– The most plausible hypothesis is that the bacilli enter via the endoneu-
rial blood vessels.
•• Bacteraemia is a normal finding in patients with untreated lepromatous
leprosy.
•• Once the bacilli enter the nerves, they multiply and produce an inflammatory
response and the antigens, which leak out, produce an immunological
response.
•• Both the inflammatory and the immunological responses promote nerve
damage.
•• Depending on the immune response of the body, the pathology of
destruction varies from the tuberculoid to the lepromatous spectrum of
disease.
•• In the tuberculoid variety, the host resistance is high and the immunological
reaction is primarily responsible for the destruction.
•• The opposite end of the spectrum is lepromatous leprosy, where the host
resistance is very poor and bacilli enter and multiply unchecked.
•• However, the multiplication is a slow process. Borderline leprosy produces
a mixed picture.
Nerve Damage in Reactions

Type I Reaction (Reversal or Upgrading Reaction)
•• This occurs most commonly in the borderline type of leprosy and tends to
develop in the early months of treatment. It may also occur in untreated cases.
•• The existing lesions flare up with erythema and oedema due to an increase
in the immune response.
•• In borderline leprosy, there are surviving Schwann cells enclosed in rigid
inflammatory tubes.
•• During the reaction, the pressure within the tubes increases rapidly causing
demyelination.
•• The damage is sometimes very rapid without even pain or tenderness.
Hence, decompression becomes urgent to preserve function.
Type II Reaction (Erythema Nodosum Leprosum)
•• Erythema nodosum leprosum (ENL) is an immune-mediated complication
of leprosy presenting with inflammatory skin nodules and involvement of
multiple organ systems including the peripheral nervous system, often
running a protracted course.
•• Immune complex production and deposition as well as complement
activation have long been regarded as the principal aetiology of ENL.
486
•• Here, crops of new lesions appear and the nerve damage is a slow process
with the formation of antigen-antibody immune complexes.
•• These are usually found in patients with lepromatous leprosy who are under
treatment for months or years.
•• Nerve decompression is not urgent as the disease process is slow and
conservative treatment can be tried for an adequate period.
•• The vasa nervorum may get involved in both the reactive phases and in
the natural process of the disease and contribute to the nerve damage.
Nerve Abscess
•• These are focal areas of necrosis involving one or more fascicles.
•• Early in the disease, the fascicles change from a greyish to a yellow colour
and undergo liquefaction.
•• Initially, the epineurium thickens around the area of inflammation and as
the pressure builds up, the epineurium may give way and the contents track
outside the nerve, forming a paraneural abscess which may reach the skin.
CLINICAL FEATURES OF NEURITIS

•• Local pain in the area of involvement of the nerve, sometimes, excruciating
and not relieved by analgesics is a common symptom.
•• Absence of pain does not rule out neuritis; sometimes neuritis may progress
rapidly, without any appreciable discomfort.
•• Pain, numbness or tingling in the distribution of the affected nerve is noticed
by many patients.
•• Thickening of the nerves, generally at specific sites (described above) is
common.
•• Thickening of the ulnar, lateral popliteal, greater auricular, radial cutaneous
and median nerves can be easily made out by palpation. This feature is an
important sign in suspecting the diagnosis.
•• Occasionally, when only one nerve is thickened, diagnosis may be difficult
and a biopsy may be needed.
•• Pain and restriction of movement may be present on stretching the nerves
by moving the adjoining joint.
•• Sensory loss along the distribution of the nerve is an important clinical
feature.
•• The loss is usually patchy.
•• Motor weakness occurs in the concerned muscles, with evidence of wasting.
•• Nerve conduction studies may support the diagnosis.
•• Those associated with spinal cord diseases like syringomyelia, amyotrophic
lateral sclerosis and motor neuron disease.
•• Those associated with peripheral nerve lesions:
–– Damage by pressure such as spinal root compression, carpal tunnel
syndrome and Bell’s palsy.
–– Polyneuritis:
¾¾ Hereditary—Hypertrophic interstitial neurop athy, peroneal
muscular atrophy.
¾¾ Metabolic—Diabetes, poryphyria, amyloidosis.
¾¾ D eficiency—Vitamin B 1 and B 12 , especially associated with
malnutrition and alcoholism.
Chapter 64 • Surgery for Leprosy
487
¾¾ Toxic—Lead, mercury and alcoholism

¾¾ Malignant—Carcinoma of bronchus.
•• Those associated with muscle disease: Myopathies.
•• Those associated with trophic changes: Diabetes, tabes dorsalis.
•• The salient features of nerve involvement in leprosy can be summarised as:
–– Localised irregular nerve thickening in an endemic area is almost
always due to leprosy.
–– Muscle weakness is always of the lower motor neuron type and never
involves the girdle or trunk muscles.
–– Sensory loss is patchy and mixed.
–– Position sense is always preserved.
–– The central nervous system (CNS) is never damaged and the tendon
reflexes are normal.
TREATMENT
Medical
•• As per the national leprosy eradication programme operational guideline
depending on the severity of illness, the patients are divided into two
categories, viz. “paucibacillary” in less severe cases and “multibacillary”
in more severe cases.
•• For the paucibacillary disease, a 6 month regimen with dapsone
100 mg daily and rifampicin 600 mg once a month is given as a supervised
treatment.
•• For the multibacillary cases, the treatment is for 2 years. Dapsone 100 mg
and clofazamine 50 mg are given daily.
•• Rifampicin 600 mg and clofazamine 300 mg are given once a month under
supervision.
Treatment of Acute Neuritis

•• Prednisolone given in high doses is useful as an anti-inflammatory drug
and as an immunosuppressant.
•• The initial dose of 50−60 mg/day is gradually stepped up under supervision.
•• Other anti-inflammatory drugs are also administered along with steroids.
•• Thalidomide and cyclosporine A have also been used.
Surgical Decompression
•• If there is progressive nerve involvement under medical treatment,
decompression is necessary.
•• In type I reaction, the progress may be rapid and if no response is detected
in 8−10 days, it is better to decompress.
•• Earlier the decompression is done, before permanent nerve damage sets
in, the better are the results.
•• In the ENL type of reaction, a conservative line of management may be
followed.
Indications for Decompression

•• If any of the following occur in spite of full medical treatment, decompression
is indicated:
–– Progressive nerve deficit.
–– Sudden increase in nerve deficit indicating an active increase in the
internal nerve pressure.
488
–– Increase in the intensity of pain and tenderness in the nerve.

–– Positive stretch sign.
–– For the ulnar nerve, a positive compression sign and pain elicited by
flexion and ulnar deviation of the wrist with the fingers closed.
–– Pain as the ulnar nerve slides forward on flexion of the elbow.
PARALYTIC DEFORMITIES
Hand
•• In an ulnar claw hand, as the intrinsic muscles are paralysed, the
metacarpophalangeal (MP) joints are kept hyperextended and the arch
gets reversed with the convexity on the palmar side. The interphalangeal
(IP) joints are kept flexed due to the paralysis of the interossei. The aim
is to restore MP joint flexion and IP joint extension to enable grasping.
•• In median nerve palsy, the abductor pollicis brevis and the opponens
pollicis are paralysed and the patient is not in a position to rotate the
thumb medially.
•• The primary aim in restoring pinch is to provide abduction and rotation of
the thumb, so that it can oppose the other fingers.
–– The procedures adopted to restore function in the hand are:
¾¾ Dynamic tendon transfer
¾¾ Static procedures.
–– The procedures to correct secondary deformities include release of
skin contracture, capsulotomy and arthrodesis.
Other Conditions to be Treated

•• Claw hand
•• Foot Drop
•• Facial Palsy
•• Tarsorrhaphy
•• Dynamic Transfer
Miscellaneous Surgical Conditions
•• Contractures
•• Trophic foot ulcer
•• Facial deformities
•• Gynaecomastia.
65
CHAPTER
Cysticercosis
BS Sharma  Sarat Chandra P
INTRODUCTION
•• Cysticercosis is a zoonotic parasitic disease caused by infection with the
larval stage of the pork tapeworm Taenia solium (T. solium).
•• In humans, the parasite commonly infests the central nervous system
(CNS), where it produces a pleomorphic clinical disorder called
neurocysticercosis (NCC).
•• Cysticercosis is currently considered the most common parasitic disease
of the CNS.
LIFE CYCLE AND PATHOGENESIS

Life Cycle
•• T. solium has a complex two-host life cycle.
•• Humans are the only definitive hosts and harbour the adult tapeworm,
whereas both humans and pigs may act as intermediate hosts (Fig. 1).
The Adult Worm
•• The adult T. solium is a hermaphrodite and inhabits the small intestine of
man, where it attaches to the bowel wall by its suckers and hooks.
•• It has a head (scolex) outfitted with four suckers and a double crown of
hooks, a narrow neck and a large body (strobila) that measures 2−4 metres
and is composed of several hundreds of units (proglottides).
Disposition of Gravids
•• Gravid proglottides are frequently detached from the distal end of the worm
and are excreted in the faeces.
•• Each proglottid contains as many as 50,000−60,000 fertile eggs, which can
remain viable for a long time in water, soil and vegetation.
•• In places with deficient disposal of human faeces, pigs may ingest stools
contaminated with T. solium eggs.
The Larval Stage (Intermediate Host-Pig)
•• Once ingested by the pig, the invasive oncospheres (embryos) in the eggs
are liberated by the action of gastric acid and intestinal fluids and actively
cross the bowel wall, enter the bloodstream, and are carried to the muscles
and other tissues where they develop into larval vesicles or cysticerci.
Ingestion of Larvae by Humans
•• Humans are accidental intermediate host
490
Fig. 1: Life cycle of T. solium (pig tapeworm) and T. saginata (cattle tapeworm).
Note: Humans normally behave as definitive hosts by lodging the adult worms.
However, either by regurgitation of eggs, ingestion of food contaminated with
cysticercal eggs or by orofecal contamination, they become accidental intermedi-
ate hosts and develop cysticercosis
•• Humans act as intermediate hosts for T. solium by accidental ingestion of

T. solium eggs, leading to development of cysticercosis.
•• When humans ingest undercooked pork meat infected with cysticerci, the
larva evaginates in the small intestine, its scolex attaches to the intestinal
mucosae and it begins forming proglottides.
•• The mechanism by which eggs cross the bowel wall and lodge in human
tissues is the same as that described in pigs.
Pathogenesis
•• The main sources from which humans acquire cysticercosis are ingestion
of food contaminated with T. solium eggs and fecal-oral contamination in
tapeworm carriers.
•• In addition, poor hygienic practises in food handling by T. solium carriers
represent a threat to their communities.
•• Improperly cooked vegetables or improperly washed salads represent an
important source of contamination.
•• The cysticerci are fluid-filled vesicles consisting of two main parts:
–– The vesicular wall:
¾¾ The vesicular wall is a membranous structure composed of three
layers: (1) an outer or cuticular layer; (2) a middle or cellular layer
with pseudoepithelial structure and (3) an inner or reticular layer.
–– The scolex: The invaginated scolex has a head or rostellum armed
with suckers and hooks and a rudimentary body or strobila that
includes the spiral canal.
•• Cysticerci in the brain parenchyma are usually small and tend to lodge in
the cerebral cortex or the basal ganglia.
Chapter 65 • Cysticercosis
491
•• These cysts rarely measure more than 10 mm because the pressure of

the brain parenchyma usually does not allow further growth of the cyst, but
giant cysticerci have been described.
•• The most common location of subarachnoid cysticerci are the sylvian fissure
and the basal cisterns.
•• Ventricular cysticerci may be small or large, are usually single, and may
or may not have a visible scolex. They may be attached to the choroid
plexus or may be freely floating in the ventricular cavities. The most
common location of these cysts is the fourth ventricle, although, they may
also be found in the third and lateral ventricles. Intraventricular cysts tend
to acquire large size.
•• Spinal cysticerci may be intramedullary or located in the subarachnoid
space, and their morphology is similar to those cysts located in the brain.
•• Cysticerci located in the basal CSF cisterns may undergo a disproportionate
growth of their membrane, with extension processes attached to each other,
which tend to gather in clusters resembling a bunch of grapes (racemose
cysticercosis).
•• It is a common practice to refer to cysts that have a scolex as Cysticercus
cellulosae, and those without a scolex as Cysticercus racemosus; however,
such terminology may create confusion because they are both forms of
the same parasite—T. solium—and commonly coexist in the same patient.
Stages of Involution of Cysticerci

•• After entering the CNS, cysticerci are in a vesicular stage in which the
parasites are viable and elicit little inflammatory changes in the surrounding
tissues.
•• Cysticerci may remain for a long time in this stage because the host
develops a state of immune tolerance to the parasites, caused by active
immune evasion mechanisms of the cysticerci.
•• After a variable and undetermined time cysticerci enter, as the result of
immunologic attack from the host, a process of degeneration that ends
with the death of the parasite.
•• This continuation of involution has been classified by Escobar into four
stages which these cysticerci pass through in this degenerative process,
namely: viable; colloidal; granular nodular and nodular calcified cyst.
Pathologic Changes in the Central Nervous System

•• NCC may lead to multiple of pathologic lesions in the CNS.
•• Apart from the diversity in number, location, size and shape of parasites,
the inflammatory reaction around cysticerci usually induces various changes
in the brain parenchyma, meninges, cerebral ventricles and spinal cord.
Parenchymatous
•• The inflammatory reaction surrounding parenchymal brain cysticerci is
mainly composed of lymphocytes, plasma cells and eosinophils, and is
usually associated with some degree of oedema and reactive gliosis, and
varies according to the stage of development of the cysticerci.
•• Massive cerebral infections may cause an encephalitic picture (cysticercotic
encephalitis) because of overwhelming inflammation around many parasitic
cysts, a syndrome that occurs more frequently at younger ages and in
women.
492
•• In contrast, some patients may tolerate hundreds of intraparenchymal

cysticerci with only minimal symptoms.
•• Single small enhancing lesion (SSEL) is the commonest form of NCC in
India.
•• It commonly presents with simple partial, partial complex, simple partial
with secondary generalisation or generalised seizures.
•• Tuberculous granuloma, microabscess, focal meningoencephalitis, postictal
enhancement, neoplasm and vascular lesion should be considered in the
differential diagnosis.
Meningeal
•• Meningeal cysticerci elicit an intense inflammatory reaction in the
subarachnoid space, with formation of a dense exudate composed of
collagen fibres, lymphocytes, multinucleated giant cells, eosinophils and
hyalinised parasitic membranes.
•• This causes abnormal thickening of the leptomeninges at the base of the
skull, from the optochiasmatic region (optochiasmatic arachnoditis) to the
foramen magnum.
•• The optic chiasm and cranial nerves arising from the ventral aspect of the
brainstem are usually entrapped in this dense exudate, leading to visual
field defects and other cranial nerve dysfunction.
•• Luschka and Magendie foramina of may be occluded by the thickened
leptomeninges, with the subsequent development of hydrocephalus.
•• Blood vessels, mainly those arising from the circle of Willis, may also be
affected by this inflammatory reaction.
•• The walls of small penetrating arteries are invaded by inflammatory cells,
leading to a proliferative endarteritis with occlusion of the lumen (cysticercal
vasculitis).
Intraventricular and Subarachnoid

•• This form of NCC is seen in 15−54% of cases (Table 1).
•• The oncosphere reaches the ventricular cavity by way of the choroid plexus.
•• It migrates through the ventricular system, occluding vital communication
corridors causing acute episodes of ventriculomegaly with sudden death
or mass effect with focal compression.
•• This form has a rapidly progressive clinical course demanding prompt
action.
•• The fourth ventricle is the commonest site (53%) followed by third ventricle
(27%), lateral ventricle (11%) and the aqueduct (9%).
•• Isolated cystic lesions within the lateral ventricle are mobile (migratory) and
transventricular is usually towards the fourth ventricle due to the effects
of gravitational forces.
•• This results in entrapment of cyst in the fourth ventricle due to the small
size of foraminae of Luschka and Magendie.
•• Ventricular entrapment may occur secondary to ependymitis causing a
double compartment syndrome.
Table 1: Causes of hydrocephalus

1. Direct obstruction by intraventricular cysts
2. Cysticercal meningitis
3. Ependymitis (obstructive by granular proliferations and communicative by reducing absorp-
tion)
493
Spinal
•• This form occurs in 1.6−13% of cases with NCC.
•• The clinical features depend upon site of lodgement of parasite. Two forms
of spinal NCC are recognised.
•• Leptomeningeal (Extramedullary) form: It is 6−8 times more common
than the intramedullary form. This occurs by downward migration of larva
from the cerebral to the spinal subarachnoid space.
•• Intramedullary form: This form is uncommon. It occurs through
haematogenous spread. The parasite commonly lodges in the thoracic
spinal cord according to the percentage distribution of blood flow to the
spinal cord.
CLINICAL MANIFESTATIONS
•• Clinical manifestations of NCC are varied and non-specific, and recognition
of a typical syndrome is not possible.
•• This pleomorphism is related to individual differences in the number, size
and topography of lesions and in the severity of the host’s immune response
to the parasites.
•• Epilepsy is the most common form of presentation of NCC and usually
represents the primary or sole manifestation of the disease.
•• Seizures occur in 50−80% of patients with parenchymal brain cysts or
calcification, but are less common in other forms of the disease.
•• Most of these patients have normal neurological examinations.
•• In general examination, it is important to look for any subcutaneous,
submucosal, subconjuctival, intraocular or intramuscular swellings .
•• The routine practice of neuroimaging and serological studies in every
patient with adult-onset epilepsy is mandatory to confirm or exclude the
diagnosis of NCC.
•• Pyramidal tract signs, sensory deficits, cerebellar ataxia, signs of brainstem
dysfunction and involuntary movements are among the most common focal
signs observed in patients with NCC.
•• A number of patients with NCC present with increased intracranial pressure
that may be associated with seizures, focal neurological signs or intellectual
impairment.
•• Hydrocephalus, related to cysticercotic arachnoiditis, granular ependymitis
or ventricular cysts, is the most common cause of this syndrome.
•• The various clinical manifestations of NCC are depicted in Table 2.
RADIOLOGICAL INVESTIGATIONS
•• Plain X-rays of muscles and skull may show cigar-shaped calcification.
•• In the CT scan, single or multiple, variable sized, low density rounded
cystic lesions with a small hyperdense eccentric mural nodule (spot)
representing the scolex giving a “starry night” effect in the parenchyma,
are suggestive of NCC.
•• Ring enhancement occurs either due to inflammatory reaction or granuloma
formation.
•• Perilesional oedema is seen around dying cysts.
•• The ventricles look small and throttled in patients with multiple diffuse
parenchymatous lesions. The encephalitic variety shows extensive oedema.
494
•• Degenerated cysts are seen as single or multiple pin head size calcified dots
without preferential localisation.
•• Additional extracranial cysts in the temporalis or nuchal muscles with a
honeycomb appearance may be seen.
•• In cases of hydrocephalus, contrast CT ventriculography is required for
localisation of CSF obstruction and to confirm the actual presence of the
parasite.
•• MR imaging is quite specific.
•• The number, clumps, multiplicity and additional cysts in other locations are
well delineated by this non-invasive diagnostic tool.
•• It differentiates the various stages of evolution, i.e. live, dying and calcified cyst.
•• Fluid in live cysts parallels CSF in its intensity.
•• The scolex appears as a mural nodule of high-signal intensity on T1 and low-
signal intensity on T2 weighted images like a hole with a dot or pea-in-a-pod.
•• In a degenerated cyst, the fluid becomes turbid (colloid vesicular stage)
appearing as high-signal intensity in the T1 image.
•• In the granulo-nodular stage on gadolinium injection, ring enhancement
(isointense on T1 and hypointense on T2 image) occurs and there is a variable
degree of perilesional oedema.
•• The racemose type cysts are seen as large lobulated cysts without a scolex,
whereas the cellulose type contains a scolex inside a vesicle.
•• MRI is useful on follow-up to see the disappearance or reduction in the number
and size of cysts in patients on treatment.
•• The degeneration occurs via a sequence of events, which may be
differentiated with MR imaging studies:
1. Vesicular stage (active, live or developing cyst form):
–– This presents as a fine, brittle, translucent membrane of uniform
thickness with a small denser area corresponding to the scolex and
containing colourless transparent fluid similar to CSF intensity on MRI.
–– The scolex appears as a mural nodule of high-signal intensity on T1
and low-signal intensity on T2 sequences like a hole or pea-in-a-pod.
–– There is no perilesional oedema.
–– This type of cysticercosis cellulosae is common in the brain paren-
chyma.
–– Cysticerci developing in the ventricle and subarachnoid spaces reach
a larger size without a scolex, with a membrane of irregular thickness
and usually clustered in multiple vesicles like raceme called cysticer-
cus racemosus.
2. Colloidal stage (degenerating cyst): The membrane becomes thick
and opaque and clear fluid is replaced by whitish gel appearing as
high-signal intensity on T1 weighted images.
3. Granular stage: The gel undergoes calcium deposition. Ring
enhancement occurs after gadolinium injection and there is variable
degree of perilesional oedema.
4. Calcified stage: This appears as hypointensities on both T1 and T2
sequences.
DIAGNOSIS
•• Diagnosis of NCC is made when there is history of exposure in an endemic
area, positive stool examination, peripheral blood or CSF eosinophilia,
CSF lymphocytosis, positive immunological tests in blood and CSF,
495
Table 2: Revised diagnostic criteria for neurocysticercosis

Categories of criteria Criteria
Absolute 1. Histological demonstration of the parasite from biopsy of a brain
or spinal cord lesion
2. Cystic lesions showing the scolex on CT or MRI
3. Direct visualisation of subretinal parasites by funduscopic
examination
Major 1. Lesions highly suggestive of neurocysticercosis on neuroimaging
studies*
2. Positive serum EITB† for the detection of anticysticercal
antibodies
3. Resolution of intracranial cystic lesions after therapy with
albendazole or praziquantel
4. Spontaneous resolution of small single enhancing lesions‡
Minor 1. Lesions compatible with neurocysticercosis on neuroimaging
studies§
2. Clinical manifestations suggestive of neurocysticercosis||
3. Positive CSF ELISA for detection of anticysticercal antibodies or
cysticercal antigens
4. Cysticercosis outside the CNS¶
Epidemiologic 1. Evidence of a household contact with T. solium infection
2. Individuals coming from or living in an area where cysticercosis
is endemic
3. History of frequent travel to disease-endemic areas
ELISA = Enzyme-linked immunosorbent assay
* CT or MRI showing cystic lesions without scolex, enhancing lesions or typical parenchymal brain calcifications.
† Enzyme-linked immunoelectrotransfer blot assay using purified extracts of T. solium antigens, as developed by the
Centres for Disease Control and Prevention (Atlanta, GA).
‡ Solitary ring-enhancing lesions measuring less than 20 mm in diameter in patients presenting with seizures, a
normal neurological examination, and no evidence of an active systemic disease.
§ CT or MRI showing hydrocephalus or abnormal enhancement of the leptomeninges, and myelograms showing
multiple filling defects in the column of contrast medium.
|| Seizures, focal neurologic signs, intracranial hypertension and dementia.
¶ Histologically confirmed subcutaneous or muscular cysticercosis, plain X-ray films showing “cigar-shaped”
soft-tissue calcifications, or direct visualisation of cysticerci in the anterior chamber of the eye
viz. complement fixation test (CFT), enzyme-linked immunosorbent assay

(ELISA) and enzyme linked immunoelectrotransfer blot assay (EITB).
•• The criteria are shown in Table 2.
•• Absolute criteria allow unequivocal diagnosis of NCC, major criteria strongly
suggest the diagnosis but cannot be used alone to confirm the disease,
minor criteria are frequent but non-specific manifestations of the disease
and epidemiologic criteria refer to circumstantial evidence that favour the
diagnosis of cysticercosis.
•• The revised criteria are simpler, containing only definitive and probable
diagnosis as the diagnostic guidelines (Table 3). A brief description of each
criterion is provided here.
TREATMENT
•• The mainstay of NCC is medical management.
•• However, some cases do require some form of surgical intervention either
to treat the pathology itself (e.g. cyst excision) or to treat the consequences
496
Table 3: Degrees of certainty for the diagnosis of neurocysticercosis

Diagnostic certainty Criteria
Definitive 1. Presence of one absolute criterion
2. Presence of two major plus one minor and one epidemiologic
criterion
Probable 1. Presence of one major plus two minor criteria
2. Presence of one major plus one minor and one epidemiologic
criterion
3. Presence of three minor plus one epidemiologic criterion
The presence of two different lesions highly suggestive of neurocysticercosis on neuroimaging
studies should be considered as two major diagnostic criteria. However, positive results in two
separate types of antibody detection tests should be interpreted only on the basis of the test
falling in the highest category of diagnostic criteria
of the pathology (e.g. hydrocephalus) or to establish the diagnosis in

clinically equivocal cases.
•• NCC has been classified depending upon the location of cysts, clinical
presentation, prognosis and viability of cysts.
•• Treatment of NCC principally consists of control of seizures, oedema and
intracranial pressure followed by definitive treatment.
Medical Treatment
•• Cysticidal drugs, namely albendazole and praziquantel, have been shown
to be effective in all forms of NCC.
•• Albendazole in a dose of 15 mg/kg/day for 8 days is reported to be more
effective than praziquantel in a dose of 50−100 mg/kg/day for 15 days.
•• The duration of treatment ranges 8−21 days and 1−30 days for
albendazole and praziquantel, respectively.
•• Recently, ultrashort single day therapy with praziquantel 75 mg/kg/
day divided in three 25 mg/kg/doses each, given at 2 hourly intervals
(7−9−11 AM) has been introduced.
•• Four hours later (3 PM), 10 mg dexamethasone intramuscular or 80 mg
oral prednisolone is given followed by the same doses of steroids for
the next three mornings.
•• Steroids prevent secondary inflammatory reactions triggered by acute
destruction of the parasite.
•• Cysticides induce destruction of 96% of the parasites located in the brain
parenchyma including giant or large clumps of cysts.
•• If cystic lesions remain unchanged on repeat MRI, 1−2 months after
praziquantel therapy, an additional course of praziquantel is given.
•• Currently, albendazole 15 mg/kg/day for 2 weeks is the treatment of choice
in patients with uncomplicated fourth ventricle NCC without hydrocephalus.
•• Repeat albendazole therapy or an additional course of praziquantel
100 mg/kg/day for 2 weeks may be required in non-responders.
•• In patients with hydrocephalus, a ventriculoperitoneal shunt should be
inserted and steroids in the form of dexamethasone 10 mg intramuscular
or prednisolone 80 mg orally should be started prior to cysticidal treatment
to reduce the risk of shunt block.
497
Symptomatic Medical Therapy

•• Since most patients with NCC have seizures, antiepileptic drugs are
frequently used.
•• In patients with calcifications, the administration of standard doses of a
single, first-line antiepileptic drug, e.g. phenytoin or carbamazepine, usually
results in adequate control of seizures.
•• Corticosteroids are also frequently used in patients with NCC. They are
usually administered at the time of antiparasitic therapy to decrease
neurological symptoms resulting from the death of the parasite.
•• Also, steroids represent the primary form of therapy for cysticercotic
encephalitis, where up to 32 mg/day of dexamethasone may be needed
to reduce the brain oedema accompanying this condition.
•• Absolute indications for corticosteroid administration during antiparasitic
drug therapy include the management of patients with giant subarachnoid
cysticerci, ventricular cysts, spinal cysts and multiple parenchymal brain
cysts.
•• In most of these cases, corticosteroids must be administered before, during
and even some days after the course of antiparasitic drugs to avoid the
risk of cerebral infarcts, acute hydrocephalus, spinal cord swelling and
massive brain oedema.
Surgery
•• In general, surgery is required when:
–– The diagnosis is uncertain.
–– Cysts exhibit tumour-like effect (oedema and/or mass effect) which are
refractory to medical treatment.
–– Hydrocephalus.
–– Intraventricular cysticerosis is diagnosed.
–– Presence of acute or sub-acute rise of ICP.
•• For parenchymatous type of cysticercosis, the following surgical approa-
ches are recommended:
–– Stereotactic excisional biopsy/open craniotomy and cyst removal is
recommended in cases of a single giant cortical cyst or large clumps
exhibiting tumour like behaviour, if the lesion is in a surgically ac-
cessible area, is producing progressive deficits or not responding to
cysticidal therapy.
–– Supratentorial decompressive craniectomy/craniotomy/ lobectomy is
undertaken when the pseudotumour type of oedema is refractory to
medical treatment, particularly in the disseminated variety of the dis-
ease frequently seen in India.
–– For Intraventricular and subarachnoid forms of NCC, the surgical
procedure usually used which includes a shunting procedure for
managing hydrocephalus, cyst removal or excision through a posterior
fossa craniotomy for fourth ventricle/subarachnoid cysts and supraten-
torial open or stereotactic craniotomy for subarachnoid third or lateral
ventricle cysts.
•• More recently, endoscopic excision has been advocated both for
supratentorial and infratentorial intraventricular cysts.
•• Endoscopic third ventricular cyst removal may be carried out very effectively
using a rigid rod lens endoscope through a frontal burr hole.
498
•• It is usually not possible to remove the cyst in toto, and the cyst usually
gets ruptured during removal. Some authors have hence advocated
intraventricular injection of steroids to prevent an anaphylactic reaction.
•• Combined endoscopic removal of the cysts with a third ventriculostomy
and/or a septal pellucidotomy gave excellent results.
•• Intramedullary and clumped leptomeningeal cysts producing symptoms
by mass effect and not responding to cysticidal drugs may be removed
via laminectomy or laminoplasty.
•• While selecting the surgical approach for intraventricular NCC, the surgeon
should consider:
–– Presence of associated ependymitis with its implications in accom-
plishing complete excision of cyst and the need for a shunt.
–– Presence of ventricular entrapment (double compartment syndrome).
–– Potential of cyst migration with posture and frank transition from one
ventricular cavity to the other.
–– Potential for increase in size of the cyst with local mass effect.
–– Potential for rapid clinical deterioration and/or sudden death.
–– Potential for presence of additional cysts at other sites.
–– Feasibility of stereotactic/endoscopic excision/aspiration in lateral and
third ventricular cysts.
–– Selection and institution of surgical approaches that establish alterna-
tive routes of CSF flow, e.g. fenestration of the septum pellucidum
•• Insertion of the ventriculoperitoneal shunt is indicated in the presence of
hydrocephalus.
•• Intermittent long-term prednisolone therapy after V.P. Shunt reduces shunt
malfunction and may improve the functional status of the patient.
PREVENTION AND CONTROL

•• Transmission of T. solium has largely been eliminated in developed
countries by improving public sanitation and meat inspection.
•• Another important source of human cysticercosis is through fecal-oral
contamination, and hygienic measures, such as adequate hand washing,
proper education, periodical deworming, that reduce the risk are highly
recommended.
•• Transmission through consumption of uncooked vegetables and fruits (e.g.
use of improperly washed salads) is yet another source of contamination.
Hence, eating salads or raw fruits from street side vendors should be
avoided.
66
CHAPTER
Hydatid Disease
Dharkar SR  Vikram M
PARASITOLOGY
•• Hydatid disease is caused by the parasite tapeworm (Taenia) Echinococcus
(Platyhelminth).
•• There are two main varieties of Echinococcus:
(i) Echinococcus granulosus, causing the classical hydatid disease,
prevalent in various parts of the world
(ii) Echinococcus multilocularis, uncommon and reported only from some
parts of Europe.
•• Echinococcus granulosus produces hydatid cysts in man and in other
animals and is endemic in sheep rearing areas.
•• Its larval form is called the hydatid cyst.
•• The definitive hosts of these parasites are the various carnivores, the
important one being the dog.
•• The mature tapeworms live in the small intestines of the dog.
•• The intermediate host includes all mammals, especially sheep.
•• Man gets infected occasionally by accidental contamination of the hand with
the faeces of infected dogs or by ingestion of food infected with the ova.
•• Human beings are infested by eating contaminated food, or from the fingers
as a result of fondling dogs whose skin may be contaminated by the ova
of the worm.
•• The dog, in its turn, is infected by eating the offal of infested sheep.
•• In man, the eggs, after reaching the stomach, lose their enveloping layer,
thereby releasing the hexacanth embryos.
•• The hexacanth embryo passes through the wall of the gut into the portal
system and then to the liver, where a hydatid cyst may develop.
•• The embryo can successfully pass through the capillary filters of the liver
and lungs and get entry into the systemic circulation and thus reach the
central nervous system, the cranium and the vertebrae.
•• The liver is affected in about 65% of cases, the lungs in about 15−20% and
the brain in about 2−5% of cases.
CEREBRAL ECHINOCOCCOSIS
Pathology
•• The hydatid cyst is unilocular, slow growing and may attain a large size in
the liver, lungs and spleen.
•• The cysts are somewhat smaller in the brain, although, a cyst measuring
up to 12.5 cm in diameter has been reported.
500
•• The cyst wall is made up of three layers:

–– The outer layer is thin
–– The intermediate layer is made up of laminated chitinous material
–– The inner one is the germinal layer.
•• To the inner layer are attached brood capsules, containing scolices, which
are the heads of the embryonic worm.
•• The fluid in the cyst is watery and colourless, but, occasionally, may be
whitish or yellow.
•• It contains scolices, brood capsules (referred to as hydatid sand) and,
occasionally, daughter cysts.
•• The cyst is well delineated from the surrounding brain.
•• Cerebral cysts are nearly always single, large and confined to the white
matter.
•• Multiple hydatid cysts represent a secondary form of the disease,
resulting from either rupture of a cyst in the left side of the heart, or
traumatic, spontaneous or surgical rupture of the primary cerebral
hydatid cyst.
•• Secondary cysts lack a brood capsule and are infertile. For unknown
reasons, the hydatid cyst has a predilection for the white matter.
•• Cerebral hydatid cysts are more common in children and young adults.
•• They are mostly supratentorial and tend to occur in the distribution of
the middle cerebral artery.
•• Infratentorial involvement is unusual.
•• As the hydatid cyst grows in size, it compresses and distorts the
surrounding brain tissue and displaces blood vessels.
•• There is no neural tissue reaction, unless the cyst is disturbed.
•• Daughter cysts are more frequent in the brain than elsewhere.
•• The cyst may cause raised ICP by its size and/or interference with
cerebrospinal fluid (CSF) pathways.
•• The cyst, as it grows, may produce asymmetry of the cranium, and localised
thinning, erosion and bulging of the calvarium overlying the cyst.
•• The average growth of a hydatid cyst has been estimated at about 1.5 cm/
year to 10 cm/year.
Clinical Features
•• Cerebral hydatid cysts are most commonly seen in children and in young
adults.
•• While in adults, focal neurological signs predominate, children primarily
present with features of raised intracranial pressure.
•• Cracked-pot resonance (McEwen’s sign) is common in children.
•• Macrocrania or swelling of the head over the area of the hydatid cyst is
seen quite commonly.
•• Papilloedema occurs not infrequently and may progress to secondary
optic atrophy.
•• The cyst is located most commonly in the posterior part of the cerebral
hemisphere and hemianopia is an important sign.
•• Contralateral hemiparesis may be present.
•• Mental changes are more frequent in adults and seizures more frequent
in children.
•• Minimal contralateral cerebellar signs may be present and may lead to
faulty localisation.
Chapter 66 • Hydatid Disease
501
Diagnosis
•• A raised eosinophil count in the blood, a positive Casoni’s intradermal skin
test and Weinberg’s complement fixation test may be of help in diagnosis.
•• When there is suspicion of hydatid disease, indirect haemagglutination,
immunoelectrophoresis and indirect immunofluorescence tests should be
carried out.
•• As a screening test, radial double diffusion and latex agglutination tests
should be performed.
•• Positive results may then be confirmed by immunoelectrophoresis and
indirect immunofluorescence and negative ones by electrophoresis and
electrosineresis.
•• Radiological examination of the skull may show evidence of raised
intracranial pressure.
•• The skull vault overlying the cyst may show localised thinning, erosion
and bulging.
•• Angiograms show marked displacement of the vessels which curve around
the periphery of a circular avascular area.
•• There are no abnormal vessels.
•• Rarely a blush may be noted if the surrounding tissue is inflamed but this
carries less significance than in tumours.
•• The CT scan reveals an intraparenchymal hypodense lesion with a
clearly defined margin.
•• The cyst fluid has the same density as that of the CSF, but hydatid sand,
if present, may increase the attenuation values.
•• Rarely, the margin may show enhancement. This occurs when the
cyst is infected.Peripheral enhancement has also been reported in an
extradural cyst.
•• Perilesional oedema and mural nodules are significantly absent, thus
differentiating the lesion from a brain abscess and other cystic tumours.
•• On the MR, the unilocular cysts are large and spherical with thin walls
which partially reach the brain surface.
•• In MRI scan, these lesions have high signal intensity on T2-weighted
images and low signal intensity on T1-weighted images, and are slightly
hyperintense with respect to CSF on balanced images
•• After contrast administration, the walls of these lesions may or may not
enhance mildly.
•• A secondary process involving the cyst, such as calcification, infection,
rupture of entodermic membrane or perifocal oedema, may also be
identified.
•• MR imaging is believed to be more sensitive and reliable than computed
tomography (CT) in depicting the pericyst layer, which appears as a
halo, or in showing perilesional oedema.
•• In formulating a differential diagnosis, the most difficult lesions to
distinguish from hydatid cyst are arachnoid cyst and epidermoid tumuor.
•• Epidermoids usually have a slightly hyperintense signal intensity on
proton density weighted MR images and they usually engulf nerves
and vessels, whereas arachnoid and hydatid cysts displace adjacent
structures.
•• Racemose cysticercosis in the subarachnoid space should also be
considered in the differential diagnosis.
502
Treatment
•• Treatment of a hydatid cyst is surgical.
•• The aim of surgery must be total removal of the cyst without rupturing it
so as to prevent contamination of the operative field with living scolices.
•• The craniotomy should be large and that the cyst wall be exposed by a
series of radiating cortical incisions, termed Dowling’s episiotomies.
•• A thin cyst wall, periventricular location and micro-adhesions to the
surrounding brain tissue were the main surgical problems resulting in
rupture in about 12% of cases resulting in distal deposit of secondary cysts
elsewhere on follow-up.
•• If accidental rupture of the cyst occurs, irrigation with hypertonic saline (3%)
is recommended in the hope of destroying the scolices in the operative field
through osmotic desiccation.
•• If the cyst is completely removed without spilling its contents, complete
cure can be expected.
•• Saline injection into the opposite lateral ventricle has also been performed
to facilitate the removal of cysts without spillage.
•• In deep-seated cysts located in eloquent and vital areas such as the
brainstem, management by internal decompression by aspiration followed
by extirpation of the cyst wall, protecting the surrounding cisterns and CSF
spaces may be done without anaphylaxis or dissemination.
•• The absence of anaphylaxis has been explained by evasion of the host
immune attack against the parasite by the suppression of T-lymphocyte
function and inhibition of macrophage-lymphocyte interaction.
•• Rapid decompression caused by evacuation of a large cyst may result in
disturbances in autoregulatory mechanisms, which need to be watched for
in the post-operative period.
•• Occasionally, when there is previous spillage or added infection, the cyst
becomes adherent to the surrounding brain and removal without rupture
becomes difficult.
•• Although protoscolicidal agents do not penetrate large hydatid cysts in
sufficient quantity, highly soluble albendazole can be used over a prolonged
period for the treatment of small multiple cysts in inaccessible sites.
•• A combination of praziquantel and albendazole is more effective than
either drug used alone.
67
CHAPTER Other Parasitic
Infestations of the Brain
Sridhar K  Vikram M
SCHISTOSOMIASIS (BILHARZIASIS)
Parasitology
•• The parasite belongs to the group of trematodes or flukes and three varieties
have been recognised: S. japonicum, S. haematobium and S. mansoni. S.
japonicum is found in China, Japan, Philippines and Burma.
•• Man is the definitive host, while the intermediate host is a freshwater snail.
•• Infection occurs in human beings as a result of bathing or wading in
infected water.
•• The adult worms live in the veins and travel to different parts of the body
via the nervous plexuses.
•• The eggs and the adult worm may travel through the veins to the brain
or the spinal cord. Involvement of the central nervous system (CNS) in
schistosomiasis is uncommon.
Route of Involvement
•• The most common route of infection of the CNS is through the venous
communications described by Batson.
•• The adult worm lies in the pelvic venous plexus and the ova are carried via
the anastomoses between the pelvic veins and the vertebral venous plexus.
•• This explains the more common involvement of the conus medullaris.
•• Since, the parasite inhabits the portocaval venous system, cerebral
schistosomiasis and myelopathy are forms of ectopic schistosomiasis.
•• Depending on the parasite species and localisation of the eggs within the
CNS, a variety of neurological syndromes may occur.
•• Infestation of the brain may result in acute encephalopathy, seizure
disorders, mass lesions and paresis.
CEREBRAL SCHISTOSOMIASIS
•• Though clinically apparent involvement of the CNS in schistosomiasis is
rare, cerebral involvement is almost always due to S. japonicum.
•• Clinically silent ova deposition in the brain occurs frequently in severe
hepatosplenic schistosomiasis.
Schistosoma Japonicum
•• The ova of S. japonicum have a strong tendency to localise in the brain,
especially in the cerebral cortex, basal ganglia and internal capsule.
504
•• The main neurological manifestations include: (i) diffuse meningitis and/or

encephalitis; (ii) varying degrees of motor deficit from cortical, subcortical
or capsular lesions and (iii) syndromes simulating brain tumours.
•• On CT scanning, a variety of abnormalities may be seen including focal
contrast-enhancing mass lesions and parenchymal lucencies with or
without oedema.
•• Multiple focal lesions may also be seen.
•• Magnetic resonance imaging (MRI) demonstrates one or more areas of
hypointense and hyperintense signals with contrast enhancement.
•• Histopathologically, the affected areas show inflammatory changes around
the ova, with oedema, parenchymal necrosis, cellular infiltration with giant
cells and granuloma formation and occasionally, vasculitis.
•• Often, a fibrocaseous mass is formed which closely resembles a
tuberculoma.
Treatment
•• Antischistosomal drugs, corticosteroids and surgery are the modalities of
therapy available for treating NS.
•• Praziquantel is the drug of choice for S. japonicum infestation.
68
CHAPTER
Spinal Hydatidosis
Harjinder S Bhatoe
•• Echinococcosis or hydatid disease is the larval stage of infection caused

by cestodes of the genus Echinococcus, whose life cycle involves two
mammalian hosts.
•• The definitive hosts are carnivores, in whom the adult worm is present in
the intestines.
•• Classic cystic echinococcosis is caused by the larva of Echinococcus
granulosus (E. granulosus), a species adapted to dogs and a wide variety of
domestic and sylvatic animal intermediate hosts (e.g. sheep, buffalo, etc.).
•• The large size, often attained, is responsible for neurological pathogenicity
and morbidity.
LIFE CYCLE AND SPINAL IMPLANTATION

•• After ingestion of protoscolices originating from fertile hydatid cysts, sexual
maturity of the adult tapeworm is reached within 4−7 weeks.
•• The fully mature adult E. granulosus is a small tapeworm approximately
3−7 mm in length.
•• It firmly attaches to the mucosal wall of the small intestine of the canine host.
•• Development from ovum to oncosphere takes place in utero in the adult
worm.
•• The oncosphere measures about 0.018 mm and is bilaterally symmetrical,
possessing three pairs of hooks, muscle fibres and glands that aid in
penetration and locomotion in the intermediate host.
•• The oncosphere and its surrounding membrane are called the cestode
eggs.
•• These eggs are shed with faeces into the external environment, and remain
viable on the furry coat of the canine.
•• These eggs reach the alimentary canal of the intermediate hosts by
ingestion (close contact with dogs, contamination of water, foodstuffs,
salads, etc.).
•• Their own lytic secretions facilitate the oncospheres to hatch, and their
passage through the gut mucosa. Entry into the circulatory system occurs
through the portal system, when the preferred site of implantation is the
liver, lymphatics.
•• Once the oncosphere passes through the liver, it enters into the pulmonary
circulation where it can evolve into a pulmonary hydatid.
•• Passage into the systemic circulation can lead to any of the organs
becoming the site for implantation.
506
•• Spinal implantation can occur via the systemic circulation, or through the
valveless epidural venous plexus that communicates with the pelvic and
retroperitoneal venous channels; the circulation in the epidural venous
plexus is transiently reversed during straining and Valsalva manoeuvre.
•• Once the oncosphere reaches its preferred site, cystic development begins
by degeneration of the oncospheral stage and emergence of the vesicular
metacestode stage.
•• The cyst expansively grows by concentric enlargement.
•• In general, hydatid cysts increase in diameter by 1−5 cm each year.
INCIDENCE
•• The human form of echinococcosis is more common in warmer climates,
especially in rural and farming communities where sheep rearing is an
important occupation.
•• While skeletal hydatid constitutes 2.8−3% of human echinococcosis, spinal
involvement occurs in one third to half of these cases.
PATHOGENESIS AND PATHOLOGY

•• Spinal hydatid is always primary, i.e. due to the implantation and
development of the larva in the affected organ.
•• The primary lesion in the bone is characterised by multiple infestations
through the arterial circulation or via the epidural venous plexus through
portovertebral channels whenever the flow in the latter is transiently
reversed (as during straining or Valsalva manoeuvre).
•• The embryos lodge preferentially in the vascularised region of the centre
of the vertebral body.
•• Growth occurs within the intratrabecular space, destroying the bone-like a
tumour and eliciting no inflammatory response.
•• The organism spreads beneath the periosteum and ligaments.
•• Formation of vesicles replaces the medullary tissue and bony architecture
and is destroyed by pressure, with widening of bony canals resulting in
formation of rounded areas of rarefaction; eventually, the pedicles, adjacent
ribs and laminae are eroded.
•• The unyielding nature of the osseous compartment restricts cyst expansion
resulting in fragmentation and conglomeration of daughter cysts.
•• Perforation of the cortex and periosteum results in extraosseous extension,
which may be extraspinal, paraspinal or intraspinal.
•• Spinal cord compression occurs once, when the bony centre has been
perforated.
•• Spinal cord compression may also result from transforaminal extension of
the cyst into the spinal canal, and there may be a dumb-bell extension of
the cyst into the spinal canal.
•• Adjacent vertebrae may be involved by extension beneath, the anterior
longitudinal ligament, and rarely across the intervertebral disc.
•• The fully developed metacestode (hydatid) of E. granulosus is typically
fluid-filled and unilocular, but multiple communicating chambers also occur.
•• Structurally, the cyst consists of an inner germinative layer of cells
supported externally by a characteristic acidophil staining, acellular,
membrane of variable thickness.
•• Cytoplasmic extensions of the germinative layer unite to form a syncitium,
which is differentiated into numerous microtriches.
Chapter 68 • Spinal Hydatidosis
507
•• The microtriches project peripherally into the laminar layer towards the host
tissues surrounding the cyst.
•• Surrounding the parasitic cyst is a host-produced granulomatous adventitial
reaction of extremely variable intensity.
•• Small secondary cysts, called brood capsules, bud internally from the
germinative layers and by polyembryony.
•• They then produce multiple protoscolices. A protoscolex is a scolex with
the rostellum and suckers deeply withdrawn into the post-sucker region.
•• In humans, the slowly growing hydatid cysts may attain a volume of many
litres and contain thousands of protoscolices.
•• Primary infection with Echinococcus larva elicits an early immune response
in the intermediate host as evidenced by specific antibody and cellular
responses.
•• The immune response is biphasic: an early response that is directed against
the recently hatched preimplantation stage of the larva, and the second
against the established metacestode at the site of formation of hydatid cyst.
•• Immune mechanisms in the first phase are more effective in destroying the
larva than those against the established metacestode.
•• In E. granulosus cysts, the protective mechanism is probably related to
sequestration of the parasite by the laminated and germinative membranes
and host capsule, which greatly limit the exchange of high molecular weight
substances between the host and the parasite.
CLINICAL FEATURES
•• Spinal hydatidosis is a slow growing lesion usually seen in the third or
fourth decades of life.
•• Clinical presentation is determined by the vertebral level of involvement
and the degree of spinal cord compression.
•• An expanding cyst in the vertebral body gives rise only to persistent
backache, which worsens with passage of time.
•• A diffuse paraspinal swelling may be visible externally, while craniovertebral
junction involvement may present with a visible mass in the oropharynx
and nasopharynx.
•• There are no specific features diagnostic of the lesion and the diagnosis
may be suspected in patents living in endemic areas, or in those people
who have stayed in endemic areas.
•• Almost all reported cases have myelopathy as their presenting feature.
•• The onset is insidious in the form of easy fatigability, stiffness of the limbs
with difficulty in brisk walking or doing fine skilful motor work with the hands.
•• However, if the cyst is intramedullary or intradural extramedullary,
myelopathy sets in early and is more severe as compared with
predominantly vertebral involvement.
•• A pathological fracture of the vertebra or vascular involvement may cause
acute paraplegia.
•• Spinal echinococcosis has been classified into five clinical subgroups:
1. Primary intramedullary hydatid cyst: Rarest form of spinal involve-
ment, myelopathic features are early and progressive.
2. Intradural extramedullary hydatid cyst.
3. Intraspinal extradural hydatid cyst.
4. Hydatid disease of the vertebra: This is the commonest form of spinal
involvement seen clinically, where a growing cyst encroaches upon
the spinal canal.
508
– Thoracic and lumbar spinal involvement occurs in about 75% of all

cases with vertebral echinococcosis.
– Association of vertebral lesion with costal involvement is considered
as a diagnostic of vertebral echinococcosis.
5. Paravertebral hydatid disease: The spinal canal may be invaded
secondarily by cysts located in the mediastinal, retroperitoneal and
paraspinal regions.
IMAGING
Plain Radiographs
•• Plain radiographs may reveal an osteolytic lesion of the vertebral body
(with destruction of the areolar pattern of the bone).
•• There may be erosion of transverse processes, adjacent ribs and pedicles.
•• Preservation of discs is a common finding.
•• The enlargement of the cyst results in punched out radiolucent areas initially
without sclerosis. Sclerosis around the radiolucent area may be seen later
in the course of the disease.
•• Vertebral collapse due to a pathological fracture along with a paravertebral
soft tissue shadow may be seen in advanced stages of the disease.
•• A paravertebral mass is often seen, which may be fusiform in appearance.
•• Many of these patients have already had treatment with antituberculous
therapy for variable periods.
•• Chest radiograph may show an associated pulmonary hydatid.

•• MRI is now the imaging modality of choice for diagnostic evaluation of
spinal echinococcosis.
•• MRI provides accurate details of the intradural and extradural compartments
together with multiplanar imaging, so that the exact relationship of the cyst
with the surrounding structures is known and the surgical approach can
be planned.
•• Typically, the cyst appears as a multiloculated hypointense mass on
T1-weighted images, which is brightly hyperintense on T2-weighted
imaging.
•• The intensity differences may reflect the viability of the cyst. Whereas a
viable cyst appears hypointense on T1-weighted images with isointense or
mildly hyperintense cyst wall, it is the T2-weighted sequence that indicates
whether the cyst is viable.
•• A decrease in hyperintensity and an increase in hypointensity from a
collapsed cyst indicate a non-viable cyst.
•• Proton density weighted images are also useful in determining cyst viability
and gadolinium enhancement correlates well with various stages of cyst
degeneration.
Computed Tomography
•• With increasing utilisation of MRI in the evaluation of myelopathy, the role
of CT has become more specific.
•• Detection of calcification in the cyst wall, delineation of bony erosion and
size of intraosseous cysts and assessment of adjacent bony architecture
prior to instrumentation are the principal uses of CT.
Chapter 68 • Spinal Hydatidosis
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SEROLOGICAL DIAGNOSIS
•• While imaging is the mainstay of pre-operative diagnosis in spinal hydatid
disease, serologic tests may be useful in confirming presumptive imaging
diagnosis.
•• Rupture of the cyst is followed by an abrupt rise in antibody titre.
•• Enzyme linked immunoabsorbent assay (ELISA) and indirect
haemagglutination or indirect immunofluorescence tests are highly sensitive
procedures for screening of serum for diagnosis of hydatid infestation.
•• Confirmation can be obtained with an immunoblot assay for specific antigen-
antibody bands or gel diffusion for echinococcosis arc protein.
•• In seronegative cases, a presumptive diagnosis may be confirmed by
demonstrating protoscolices or hydatid membranes in the liquid obtained
by percutaneous aspiration of the cyst contents.
•• Ziehl Neelsen stain is particularly useful for easy identification of the
elusive hooklets.
•• Closed aspiration under ultrasound or CT guidance combined with medical
treatment appears to be safe and is now a standard practice.
SURGICAL MANAGEMENT
•• Surgery is the mainstay in the definitive management of spinal
echinococcosis, especially in the presence of compressive myelopathy.
•• The aim of surgery is to preserve and improve neurological function and
provision of spinal stability with eradication of the parasite.
•• The exact location of the cyst determines the surgical approach to the
lesion.
•• Posterior exposure may be made by laminectomy, especially in the
presence of an intradural cyst.
•• Extensive involvement of vertebral bodies requires an anterolateral
transthoracic approach.
•• Vertebral body resection and stabilisation by instrumentation and fusion
can be carried out.
•• A combination of anterior and posterior approaches may be required.
•• Spinal fixation can be done as a first step, before excision of the cyst.
•• A reasonable suspicion of hydatid cyst can be made from pre-operative
imaging studies, and appropriate precautions should be taken to prevent
spillage of cyst contents.
•• Scolicidal-soaked gauze should be packed around the cyst wall.
•• A layer of isotonic saline-soaked gauze is first placed over the neural
tissues, and scolicidal-soaked gauze is then placed over the saline-soaked
gauze to avoid direct contact of neural tissue with scolicidal solution.
•• Inspite of attempts at extensive exposure for radical excision, the cyst may
be removed incompletely.
•• Spillage from a viable cyst should promptly be recognised and
antianaphylactic measures instituted.
•• All patients, irrespective of the extent of resection of the cyst, must receive
albendazole or mebendazole in the post-operative period.
MEDICAL MANAGEMENT
•• Both albendazole 10−15 mg/kg/day and mebendazole 40−50 mg/kg/day
have been effective.
510
•• Drug treatment may have to be administered continuously or punctuated

by treatment-free intervals for a period of three to six months.
•• These drugs can also be administered pre-operatively to inactivate the
scolices, altering the integrity of the membrane and thus safe surgical
manipulation of the cyst(s).
•• These drugs are teratogenic and are contraindicated during pregnancy.
•• All patients must undergo MRI after 12 months of treatment: Static size,
reduction in the cyst size or disappearance of the cyst indicates effective
therapy.
PERCUTANEOUS ASPIRATION, INJECTION,

REASPIRATION (PAIR)
•• According to the WHO advisory group, PAIR is indicated in inoperable
cases and those who refuse surgery.
•• The procedure involves percutanous puncture using sonographic guidance,
aspiration of substantial amounts of liquid contents and injection of scolicidal
agent (e.g. 95% ethanol and 0.5% cetrimide) for at least 15 minutes,
followed by reaspiration.
•• Concurrent treatment with albendazole/mebendazole improves the efficacy
and safeguards against spillage and secondary implantation.
PREVENTION OF ECHINOCOCCOSIS
•• Prevention of human echinococcosis involves the dual approach of regular
deworming of dogs and ensuring meat hygiene.
•• Infected animal carcasses have to be destroyed, so that these are not
consumed by dogs.
69
CHAPTER
Fungal Infections
Anil Pande
INTRODUCTION
•• Fungal infections of the nervous system constitute an important, though
not frequent, entity with their own etiopathogenesis, pathology and clinical
picture. Their incidence is increasing owing to the HIV-AIDS epidemic and
in patients on immunosuppression therapy.
GENERAL CONSIDERATIONS
•• The pathogenic fungi may be unicellular or multicellular.
•• Many are dimorphic, that is, they can take two different types of form; a
unicellular (yeast form) and a multicellular (mycelial form).
•• The mycelial forms can be septate or non-septate, that is branched or
unbranched.
•• They may be capsulated or non-capsulated.
•• The fungal cell wall is of great complexity and this polysaccharide capsule
is of great use in characterising these lesions, and in protecting them and
the fungal cell wall components.
•• Whenever the immune system wavers in its effectiveness in extremes of
age, disease and debilitation or, whenever immunosuppression occurs
due to AIDS, diabetes, drugs or blood dyscrasias, the fungi find a foothold.
•• The factors that have contributed to the increasing incidence of fungal
infections are:
–– Prolonged use of broad-spectrum antibiotics and the use of anti-
metabolites and steroids.
–– Social evils such as drug addiction and substance abuse.
–– Diseases like diabetes mellitus, renal failure, malnutrition, AIDS and
systemic lupus erythematosus.
–– Increase in international travel with the risk of environmental exposure.
–– Longer survival of patients with lymphoproliferative malignancies.
–– Larger ageing population.
–– Near drowning episodes.
•• Mycotic infections enter the differential diagnosis of many neurological
conditions, even in an apparently fit individual.
•• They produce a wide range of pathology depending on the host response
to the fungus: Inflammatory reactions, chronic round cell infilteration,
chronic suppuration, granulomatous inflammation, calcification, infarction,
hypersensitivity and/or antibody production.
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CLASSIFICATION
•• Fungi are classified as follows:
Pseudo Mycetes
•• Blastomycetes, Candida, Coccidiodes, Cryptococcus, Histoplasma,
Paracoccidiodes and Sporotrichum.
Septate Mycetes
•• Aspergillus, Cephalosporum, Cladosporum, Diplo-rhinotrichum,
Hormonodendrum, Paecilomyces, Penicillum.
Non-septate Mycetes
•• Absidia, Basidobolus, Cunninghamella, Mortierella, Mucor, Rhizopus.
Fungi-like Bacteria
PATHOGENESIS
•• The pathogenicity of fungi is attributed to their neurotropism, and to the
altered defence mechanisms in the host.
•• Fungi causing systemic and CNS infections possess thermotolerance and
resist phagocytosis by capsule formation, intramacrophage germination
and toxin production.
•• Fungi can grow either as yeast or moulds at different times of their life cycle.
•• This is known as dimorphism. The morphology and size of the fungus
determine the pathology of these lesions.
•• Small yeast forms (Blastomycosis, Coccidiodes, Cryptococcus and
Candida) reach the small arterioles and capillaries and produce meningitis
and subpial ischaemic lesions.
•• Intermediate size pseudohyphae (Candida) obstruct small blood vessels
leading to necrosis and abscess formation.
•• The larger hyphal forms (Aspergillus, Zygomyces, Cladosporium) block
larger vessels and give rise to large infarcts and granulomas.
•• Disorders of phagocytic function predispose patients to develop CNS
aspergillosis, mucormycosis and candidiasis.
•• Impairment of cell-mediated immunity predisposes to CNS Cryptococcal,
Histoplasma, Coccidioidal and Blastomycotic infections.
•• Impairment of granulocyte function predisposes to Candida, Aspergillus
and Zygomycetes.
•• Recently, in some fungi, cytoplasmic hormone receptors have been
demonstrated, which interact with human corticosteroid and sex hormones.
•• The receptors have been reported in Candida albicans, Coccidioides immitis
and Paracoccidioides brasiliensis
•• Basically, fungi affecting the CNS can be divided into two groups:
1. Pathogenic or endemic fungi: They affect healthy hosts. These are
endemic in various parts of the world.
2. Opportunistic fungi: These fungi usually cause infections in
immunologically compromised hosts and in the presence of
predisposing factors (diabetes, malignancies, renal failure, AIDS,
etc.).
Chapter 69 • Fungal Infections
513
Pathogenic Fungi
•• The site of primary infection is usually in the lung and rarely in the skin.
•• In addition, primary lesions may occur in the mucosa of the mouth and
pharynx as in paracoccidioidomycosis and in the gastrointestinal tract as
in histoplasmosis.
•• The organisms spread to the CNS by the bloodstream from the primary site.
•• Rarely, meningitis may ensue due to direct spread from osteomyelitis of
the skull or vertebra, e.g. Coccidioides immitis.
•• Direct spread can also occur from the paranasal sinuses and middle ear.
Opportunistic Fungi
•• The primary site of entry in aspergillosis and cryptococcosis is the lung,
with subsequent bloodstream spread to involve the CNS.
•• Some fungi (Aspergillus, Zygomyces) spread directly from the nose and
paranasal air sinuses and less often from the ears.
•• Occasionally, the brain is directly infected after a head injury or craniotomy.
•• In candidiasis, the normal commensal multiplies and enters the blood at
any site where there is a defect in normal surface defence mechanisms.
Meningitis
•• The prototype fungus that primarily causes meningitis is Coccidioides
immitis.
•• Involvement of the leptomeninges is typically widespread, the basal
meninges being maximally involved.
•• The basic pathologic lesion of coccidioidomycosis is a combination of
suppurative and granulomatous inflammation.
•• In the infected tissue, the endospores are surrounded by polymorphs and
in granulomas the spherules are surrounded by mononuclear cells and
giant cells.
•• The chronic inflammatory response results in thickening of the meninges,
hydrocephalus, arteritis, cranial nerve palsy and infarctions.
•• Other fungi (Blastomyces, Paracoccidioides and Histoplasma) may also
cause meningitis.
•• As in tuberculosis, there may be spinal meningitis in blastomycosis where
there is an extradural infection of the vertebrae and intervertebral discs.
Meningoencephalitis
•• Fungi, like Cryptococcus neoformans and the Candida species, are prone
to cause meningoencephalitis.
•• In cryptococcosis, cystic clusters of fungi are spread throughout the brain
with little or no surrounding inflammatory response and predominantly
involving the basal ganglia and the cortical grey matter.
•• The cystic lesion contains a gelatinous polysaccharide material.
•• This polysaccharide antigen is detectable in spinal fluid and serum, and
forms the basis of a commercially available latex agglutination test, which
is 90% sensitive and highly specific for diagnosis of cryptococcosis.
Brain Abscesses/Infarction/Haemorrhages
•• Aspergillus, Zygomycetes, Blastomyces, Paracoccidioides and Candidiasis
cause these lesions, as also Nocardia, Actinomyces, and Coccidio-
idomycoses.
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•• Some dermatiaceous fungi produce brain abscess, especially in the frontal

lobes, even in the absence of a disseminated lesion, e.g. Cladosporium
trichoides and Phialophora.
•• Disseminated candidiasis mainly produces microabscesses, though
macroabscesses, glial nodule formation, granulomas and fungal balls
may also be found.
•• Rarely, Candida may directly invade blood vessels causing haemorrhage,
necrosis and infarction.
•• Vasculitis is characteristic of invasive aspergillosis and mucormycosis.
•• Direct spread occurs from the paranasal sinus to the brain with subsequent
vasculitis, especially in diabetic patients.
CLINICAL FEATURES
•• There are no pathognomonic signs or symptoms of fungal infection of the
CNS.
•• However, a constellation of specifically affected organs and some
characteristic pathological features help the physician make a presumptive
diagnosis.
•• In non-endemic areas, a history of travel to a region of the world where the
organisms grow, may point towards the correct diagnosis.
•• A history of near drowning episode is inquired into. Occasionally, there
may be no neurological symptoms or signs.
•• The clinical features may be divided into the following groups:
Meningeal Syndromes
•• The common symptoms are headache, nausea, vomiting, neck stiffness
and fever.
•• In 40% of the cases of cryptococcosis, visual impairment, diplopia and
papilloedema occur.
•• Cranial nerve palsies may also be seen.
•• Alteration of the mental status may be caused by encephalitis or
hydrocephalus.
•• Seizures may occur.
•• Focal signs due to arteritis, granuloma or abscess may be present.
•• In patients with AIDS, cryptococcal infection may cause retrobulbar neuritis,
choreoretinitis, internuclear ophthalmoplegia and reverse ocular dipping.
•• The clinical picture of meningitis varies in the immunocompromised and
non-compromised hosts with a paucity of symptoms and signs in the former.
Space Occupying Lesions

•• Granulomas, abscesses or hydrocephalus cause symptoms and signs
relating to the affected area.
•• There may be features of increased intracranial pressure. Aspergillosis
typically presents in this way.
•• In blastomycosis, the patient has progressive paraplegia with sensory
manifestations and sphincter disturbances due to spinal cord involvement.
•• Blastomycosis may also involve the vertebrae and the intervertebral discs
producing a gibbus simulating caries spine.
•• Extradural or intradural cryptococcal granulomas have been reported in the
spinal cord, producing features of compressive myelopathy.
515
Rhinocerebral Syndrome
•• This syndrome presents with orbital pain preceded by a watery nasal
discharge, which becomes bloody and purulent.
•• There is facial oedema with proptosis and visual loss.
•• Involvement of the carotid artery produces hemiparesis.
•• This is classically found in zygomycosis, where blackish necrotic areas
called eschars are seen on the hard palate or the nasal turbinates.
•• Rhinocerebral mycosis has a high morbidity and mortality, despite institution
of aggressive management.
•• Allergic fungal sinusitis can lead to formation of a “fungocoele”, which
expands with time causing bony destruction and intraorbital and intracranial
extension, but characteristically is non-invasive and can be removed bluntly
leaving the mucosa intact.
•• Trans-sphenoidal, trans-ethmosphenoidal, endoscopic transnasal and,
rarely, transbasal bifrontal approaches may be utilised.
•• Prolonged antifungal treatment is not required, but steroids help.
Stroke Syndromes
•• Aspergillosis or zygomycosis may produce sudden onset of a focal deficit
due to invasion of blood vessels.
•• Unlike bacterial mycotic aneurysms, fungal mycotic aneurysms occur in
the larger arteries.
•• Candida infection may result in an embolic stroke.
Skull Base Syndromes

•• Orbital apex syndrome, cavernous sinus syndrome, proptosis with or
without ocular palsy, polyneuritis cranialis and orbitocranial syndrome
may occur.
Spinal Syndromes
•• Myelopathy and radiculopathy due to involvement of the vertebral column,
and extradural, intradural and intramedullary lesions may be seen.
DIAGNOSIS
•• Suspicion of CNS mycosis is the most important initial step in the diagnosis.
•• Laboratory tests should be directed to discover evidence of immunological
compromise and of fungal infection elsewhere in the host.
Evidence of Fungal Infection in the

Cerebrospinal Fluid Examination
•• CSF protein is elevated and glucose diminished. In aspergillosis with
deep-seated granulomas, the CSF is normal.
•• Cell count: A mononuclear pleocytosis is seen ranging between 20 cells/
mm3 and 500 cells/mm3, but, occasionally, in candidiasis and zygomycosis,
there may be a polymorphonuclear increase.
•• Cytological examination of the CSF may occasionally reveal the fungus.
For cryptococcal meningitis, India ink preparation is a simple and effective
test.
516
•• Positive cultures confirm the diagnosis of fungal meningitis, but may be

difficult to obtain or may take a long time. Cryptococcal meningitis shows
a positive culture in 75% of patients and Coccidioidomycosis meningitis
in 30−50% of patients.
•• Immunological tests: In cryptococcal meningitis, the latex agglutination
test for capsular polysaccharides in CSF is positive in 90%.
Imaging Techniques
•• CT or MRI scan may reveal features of meningitis, granulomas, hydro-
cephalus, infarction or spinal cord compression.
•• In rhino-orbital syndromes, CT or MRI is especially helpful.
•• CT scan usually underestimates the degree of involvement by the organism,
and shows paranasal sinusitis, small areas of bony destruction, and
absence of separation of periosteum from the medial orbital wall.
•• The granulomas appear as irregular hypodense lesions with irregular and
minimal contrast enhancement and disproportionate perilesional oedema.
•• The MRI is very useful to visualise ocular muscle or nerve involvement and
will show involvement of the paranasal sinuses or mastoid.
•• Granulomas have a low T2 intensity compared with surrounding
hyperintense cerebral oedema.
•• This characteristic low intensity in T2 is due to high levels of iron,
magnesium and manganese in the fungus.
•• Diffusion weighted imaging is useful in detecting early lesions and in
differentiating these from progressive multifocal leukoencephalopathy
and neoplasm.
•• MR spectroscopy in aspergilloma is non-specific with high choline, low
creatinine and lactate with no N-acetyl aspartate.
•• Cryptococcus pseudocysts which are formed due to the dilatation of the
Virchow Robin spaces with mucoid gelatinous material produced by the
capsule of the organism are seen in clusters in the basal ganglia and
thalamus and are pathognomic of cryptococcal infection.
•• Deep cerebral infarcts are seen as areas of hyperintensity on T2W1 images.
•• Ring enhancing T2 heterointense lesions with irregular walls and non-
enhancing intracavitary projections having a low ADC are indicative of a
fungal abscess.
•• Spinal involvement shows disc involvement or sparing, heterogeneous
marrow signal alteration and extensive extraosseous involvement and
variable bony deformity and destruction.
•• The following classification of Rhinocerebral fungal infections depending
on the extent of the lesion has been proposed.
Stage I: Purely rhino-sino-orbital.
Stage II: Involvement of the bone without dural breach in addition
to sinus involvement.
Stage IIIA: Spread of infection from the paranasal sinus to the skull
base, involvement of the bone and breach of the dura.
Stage IIIB: Infection involving the brain parenchyma.
Stage IV: Fulminant meningoencephalitis and large infarcts.
Biopsy
•• When a diagnosis cannot be made otherwise, biopsy of the lesion may
become necessary.
517
•• In every case where a granulomatous lesion is encountered, investigations

for fungi should be done in addition to histopathology and culture sent for
pyogenic organisms.
•• The specimen should be sent in normal saline and stained with periodic
acid Schiff stain or Grocott’s methanoamine silver stain, especially for
aspergillosis and zygomycoses.
•• In the case of Cladosporium and other dermatiaceous fungi, hematoxylin
and eosin stain is adequate.
•• A careful search for evidence of fungal Infections elsewhere in the host
•• Searching for the source of infection elsewhere in the body is essential,
e.g. lung, skin, bone and sinuses using X-rays and serological tests; and
identification of the organisms by smear, culture, histopathology from pus,
sputum, blood and skin.
•• Skin tests for Coccidioides, Histoplasma or Blastomyces may indicate
exposure to the particular fungus.
Evidence of Immunological Compromise

•• Complete blood count and blood chemistry are carried out to identify
predisposing conditions, such as leukaemia, lymphoma, diabetes mellitus,
renal failure and AIDS.
TREATMENT
Non-specific Measures
a. Control of predisposing factors which are mentioned earlier.
b. Treatment of intracranial hypertension, e.g. mannitol and furosemide.
Specific Measures
Antifungals can be classified as:
–– Polyenes: Amphotericin, nystatin
–– Azoles: Miconazole, Ketoconazole, osaconazole, ravuconazole,
voriconazole, eberconazole, itraconazole.
–– Antimetabolic: Flucytosine
–– Antiprotozoal: Atovaquone
–– Echinocandins: Caspofungin, misafungin, aniducafungin.
•• The antifungal agents commonly used are amphotericin B, flucytosine and
azole derivatives.
•• The duration of the treatment varies from 4 to 6 weeks.
•• Immunocompromised patients take longer to experience remission.
•• The treatment should continue till active systemic or CNS infection has
disappeared.
•• Long-term maintenance therapy is considered in immunocompromised
patients.
•• Other drugs under trial:
–– Amphotericin B encased in liposomes reduces drug toxicity to the host,
allowing administration of higher doses of the drug.
–– Voriconazole is considered the gold standard of systemic antifungal
treatment and is superior to conventional amphotericin and has im-
proved survival rates in patients with cerebral aspergillosis.
518
–– Rifampicin given along with amphotericin B potentiates the activity of

the polyene against multiple yeasts, including Candida, Histoplasma
and Cryptococcus.
Surgical Management
•• Surgery may entail stereotactic biopsy and, if possible, aspiration of an
abscess.
•• Stereotactic craniotomy can be useful to place an appropriate flap and
localise the lesion.
•• Besides diagnostic biopsy, surgery may be needed for CNS mycoses.
•• Brain abscesses, especially Blastomyces and Histoplasma abscesses, can
be surgically treated along with amphotericin.
•• Large cryptococcomas (greater than 3 cm) in accessible locations should
also be considered for surgery.
•• Drainage of the paranasal sinuses with excision of the granuloma is
indicated in the rhinocerebral syndrome.
•• Focal infection with Cladosporium requires surgical excision of the lesion.
•• Hydrocephalus may require shunt surgery.
•• Insertion of the Ommaya type reservoir helps in prolonged intraventricular
or cisternal chemotherapy. Spinal compression requires surgery to remove
granulomas or abscesses.
PROGNOSIS
•• In most fungal infections, the prognosis depends on the duration of the
disease before the diagnosis and on whether any underlying disease can
be controlled.
•• Specific prognosis factors have been identified in cryptococcal, candidal
and coccidioidal meningitis.
Poor Prognostic Factors

1. Cryptococcal meningitis:
i. Initial positive India ink test.
ii. High CSF opening pressure.
iii. Low lumbar CSF leucocytes (less than 20/mm3)
iv. Cryptococci isolated from extraneural tissue.
v. Absent anticryptococcal antibody.
vi. Initial CSF or serum cryptococcal antigen titre greater than 1:32.
vii. Corticosteroid therapy for lymphoreticular malignancy.
2. Candidal meningitis:
i. An interval from the onset to diagnosis of more than 2 weeks.
ii. CSF glucose level below 35 mg/dL.
iii. Development of intracranial hypertension or focal neurological deficit.
3. Coccidioidal meningitis:
i. Presence of hydrocephalus.
ii. Presence of an underlying disease.
iii. Non-Caucasian races.
•• Without treatment, fungal meningitis is a fatal disease.
•• In CNS coccidioidomycosis, virtually all the patients die within 2 years.
•• By administering amphotericin B directly into the CNS the mortality has
decreased to less than 50%.
519
CRYPTOCOCCOSIS
•• Cryptococcus neoformans has a worldwide distribution and is associated
with soil enriched by pigeon droppings.
•• The disease may be seen in patients with disorders of the reticuloendothelial
system and also in previously normal individuals.
•• The route of infection is through the respiratory system, which may result
in a subclinical infection or a cavitating lesion in the lung.
•• Involvement of the CNS is in the form of basal meningitis, meningoencephalitis
and mass lesions such as granulomas or cysts.
Cerebral Cryptococcosis
Pathology
•• Meningitis is localised mainly to the cerebral and cerebellar hemispheres,
and the meningeal exudate is made up of a minimal inflammatory response.
•• The leptomeninges become thickened and the infection spreads along the
distended Virchow-Robin spaces.
•• When present, it consists of lymphocytes, plasma cells, eosinophils and
multinucleate giant cells.
•• The nuclei of the giant cells are more centrally located than in the Langhans’
cell and may contain cryptococci.
•• There is a change in infection trend due to the marked improvement of the
quality of life produced by the highly active antiretroviral therapy.
ASPERGILLOSIS
•• Aspergillus species are among the commonest saprophytes and are found
abundantly in the soil and decaying vegetation.
•• Aspergillus fumigatus is the most common cause of granulomatous infection
in man and in a recent series it was identified in 63% of cases of fungal
infection.
•• Infection may be associated with an immunocompromised state and may
also occur among intravenous drug abusers, following open heart surgery,
trauma, etc.
•• Infection may also start in the paranasal sinuses and mastoids and spread
to the surrounding tissues and the basal dura.
•• The organism shows a high affinity for blood vessels.
•• The vessel walls are invaded, resulting in secondary thrombosis and
haemorrhage. Involvement of small vessels may lead to multiple small
haemorrhagic infarcts.
•• Larger vessels, like the carotid artery or the basilar artery, may also be
involved. Subarachnoid haemorrhage may occur from the rupture of
mycotic aneurysms.
•• The most striking histological picture here is the vascular invasion and
thrombosis.
•• Abscesses may form and may be single or multiple.
•• They are seen as pale areas with petechiae or as necrotic and haemorrhagic
areas with a central cavitation.
•• The degree of inflammation varies according to the stage of the infection
and the individual patient.
•• Granulomatous masses occur, either in association with a chronic infection
or as a solitary mass. These are hard, relatively avascular and cut like an
unripe pear.
520
•• Microscopically, these are made up of aggregates of lymphocytes, plasma

cells and epithelioid cells in necrotic tissue, with varying amounts of
collagen. Langhans’ type of giant cell may occasionally be seen.
•• Diagnosis of aspergillus is made following biopsy and culture of the fungus.
•• Patients with invasive aspergillosis may produce specific antibodies
which may be detectable by ELISA, double diffusion or counter immuno-
electrophoresis.
•• As the aspergillus is not a member of the normal microflora, the detection
of antibodies becomes significant.
•• As antifungal drugs are not very effective against aspergillus, excision of
the mass lesions is the treatment of choice.
•• Operative decompression may be required for patients with granulomatous
masses causing cord compression.
•• Complete excision may not be possible and may cause cord damage.
•• Amphotericin B preferably liposomised in combination with 5-fluorocytosine
are the drugs of choice.
•• Recently, good results have also been achieved with imidazole derivatives,
e.g. ketoconazole and miconazole. Itraconazole in high dose (16 mg/kg/
day) is given.
CANDIDIASIS
•• Candida albicans is a true yeast and a normal constituent of the human
flora.
•• Most of the Candida infections are due to infection from the oropharynx,
skin, intestine and vagina of healthy individuals.
•• In most clinical cases, infection is opportunistic and is found in association
with surgical or other trauma, immunosuppression, prolonged antibiotic
usage, drug abuse or AIDS.
•• Infection in a previously healthy individual is also known.
•• CNS infection is by haematogenous spread, though occasionally direct
spread does occur through the oral cavity, orbit or middle ear following
surgery or trauma.
•• CNS involvement occurs in 50% of patients with systemic candidiasis and
up to 80% of patients with Candida endocarditis.
•• CNS candidiasis may present as meningitis, a granuloma or as an abscess.
•• In the early stages, the lesions resemble haemorrhagic infarcts. These later
develop into abscesses and granulomas without a central focus of necrosis.
•• Candida granulomas are multiple and are most commonly located at the
junction of the grey and white matter.
•• Mycotic aneurysms and abscesses are the other presentations of cerebral
candidiasis.
•• Occasionally, a patient with candidial endocarditis may present with a stroke
due to embolic phenomena.
•• Candidiasis of the CNS cannot be identified by skin tests.
•• Meningitis can be diagnosed by lumbar puncture and analysis of the CSF.
•• When mass lesions are suspected, CT or MRI scan is the investigation
of choice.
•• CT scans in an immunocompromised patient may show areas of low density
without enhancement.
•• Treatment is by removal of the source of infection at the earliest with control
or stabilisation of the underlying debilitating disease.
521
•• Untreated meningitis has a morbidity of 80%, while cure rates in patients

treated for meningitis are about 90%.
•• Mass lesions require surgical excision for diagnosis and as definitive
treatment.
•• Itraconazole, ketoconazole and nystatin may be used as prophylaxis in
susceptible patients.
MUCORMYCOSIS
•• The clinical spectrum of mucormycosis is produced by several genera of
fungi including Rhizopus, Rhizomucor and Absidia.
•• Almost invariably, infection with this group of fungi is associated with some
other significant diseases like diabetes immunocompromised states or
with drug addiction.
•• The majority of patients have poorly controlled diabetes mellitus, the
predisposing factor in such cases being the acidosis rather than the
hyperglycaemia.
•• Renal transplant patients, patients with sepsis or severe dehydration and
patients with haematological malignancies are prone to this infection.
•• The organisms spread by direct extension along nerves, blood vessels
and cartilage.
•• Like aspergillus, these organisms show a strong tendency to involve blood
vessels.
•• Entry into the CNS is from adjacent structures such as the paranasal
sinuses or the orbit.
•• The rhinocerebral form is the commonest type of penetration and is seen
in 80−90% of cases.
•• Brain abscess may develop secondary to the pulmonary focus and is seen
in immunocompromised patients.
•• Mucormycosis should always be thought of while examining inflammatory
or necrotic tissue from the orbit or nasal region.
•• Microscopically, polymorphs are seen, clustered mainly around blood
vessels.
•• Non-septate hyphae with right angle branching are seen in large numbers
around and within the walls of the blood vessels of the brain and meninges.
•• The classical clinical picture of the rhinocerebral form is a poorly controlled
diabetic patient with facial or periorbital pain and nasal discharge.
•• Epistaxis may occur.
•• Examination of the nose may reveal gangrenous changes in the turbinates.
•• Black necrotic lesions may be seen on the hard palate. These are
not pathognomonic for mucormycosis, as they may also be seen in
Pseudomonas and Aspergillus infections.
•• External ophthalmoplegia and proptosis are common findings, and there
may be loss of vision secondary to central retinal artery occlusion. This
finding is important, as vision is usually not lost early in bacterial cavernous
sinus thrombosis.
•• The fungus advances along the base of the brain and may cause facial
nerve palsy.
•• Carotid artery involvement may cause cerebral infarction and focal deficit,
which is seen in one-third of the patients.
•• Upwards extension of the infection through the orbital roof may result in a
frontal lobe abscess.
70
CHAPTER
Viral Infections
Ravi Ramamurthi  Ramamurthi B  Ravindranath Kapu
•• Viral infections of the central nervous system (CNS) are of interest to

neurosurgeons, as they may have to treat the acute phase of some
infections, help in establishing diagnosis by brain biopsy, or deal with the
sequelae of viral infections like persistent pain or intractable epilepsy.
•• The possibility of virus aetiology of CNS tumours is also an area of interest.
•• Recently, interest in viral infections has been renewed due to many factors:
the emergence of HIV/AIDS; the increasing use of immunosuppression; the
possibility of an increase in viral diseases due to the prevention of bacterial
infections; rapid growth of the basic knowledge of virus biology and of CNS
structure and function; improved diagnostic techniques enabling better
study of viral infections and the development of effective antiviral agents.
•• Viruses are minute particles (virions) measuring 20−300 nm in diameter.
•• They consist of only one type of nucleic acid either DNA or RNA, which
is surrounded by a protein unit called capsomere, enveloped in a lipid
membrane.
•• Viruses may destroy a cell completely, live in it for many years to get
reactivated, stimulate the cell to unrestricted growth or disrupt cell function
without causing death of the cell.
•• The CNS seems especially susceptible to viral infections, due to its lack of
capacity for regeneration and its complicated metabolic pattern.
•• The presence of a blood-brain barrier, and a limited immune response,
also contribute to this susceptibility.
•• Certain viruses exhibit selective neurotropism e.g rabies, polio, Japanese
encephalitis virus etc.
•• Neurotrophism refers to the affinity of a virus for a particular neural cell, and
Neurovirulence is the ability of the virus to produce neurological disease.
•• Viruses enter the body through the skin, the gastrointestinal tract or the
respiratory system.
•• The spread of viruses in the body occurs through the bloodstream as in
enteroviruses and measles and mumps viruses, or through the nerves as
in polio, herpes and rabies.
•• Neural spread is via axoplasmic transport through axons to the sensory
ganglia.
•• Viral spread along neurons may also occur via the perineural lymphatics
or the Schwann cells surrounding the axons.
•• It is the presence of specific viral receptors on the neural cells that makes
the specific neurons susceptible.
Chapter 70 • Viral Infections
523
•• The other factors that determine susceptibility are the state of differentiation
and mitotic activity of the neural cells, the density of the neural and
supporting cells and the various CNS immune responses to viral infections.
•• Immune responses induced in the body to viral infections may be humoral
and directed against the virus particles, or cell mediated directed against
the infected cell during which virus specific cytotoxic lymphocytes are
generated.
•• A variety of cytokines and lymphokines, such as interferons that limit viral
replication, are also produced in response to the infection.
•• Depressed cell mediated immunity leads to the development of viral
diseases like subacute sclerosing panencephalitis (SSPE) due to measles
virus, progressive multifocal leucoencephalopathy (PML) due to JC virus
and encephalitis due to the herpes simplex virus (HSV) and the varicella
zoster virus (VZV).
•• Depressed cell immunity may also lead to persistent polio or echovirus
infections of the CNS.
•• Viral encephalitis may be produced by both conventional viruses and
unconventional viruses.
•• The characteristics of conventional viruses have been well dcomented.
•• The unconventional viruses, also called slow viruses or prions, contain
protease resistant proteins, but neither DNA nor RNA.
•• Our understanding of viral diseases has been advanced considerably by
recently developed technologies like improved methods of serological
diagnosis, molecular diagnostic methods and neuroimaging techniques
like MR and SPECT.
•• Nucleic acid amplification methods have improved the detection of common
(HSV, Enterovirus and VZV) and uncommon viral pathogens.
HERPES SIMPLEX ENCEPHALITIS

•• Herpes simplex encephalitis (HSE) virus is the most common cause of
viral encephalitis.
•• These viruses are of two types (HSV-1 and HSV-2) which, although
morphologically identical, are composed of two antigenetically different
viral agents.
•• Type I spreads through the oral route and Type II through genital
contamination.
•• Maximum involvement in case of HSV-1 infection is seen in the temporal
and inferior frontal lobes.
•• Oedema and haemorrhages are the prominent features.
•• Lymphocytic infiltration, perivascular cuffing, necrosis and intranuclear
inclusion bodies are also seen.
•• The progression of symptoms simulates a rapidly evolving ICSOL and
uncal herniation can occur.
•• CSF shows lymphocytosis and the EEG is pathognomonic with high voltage
periodic discharges confined to the temporal region.
•• The diagnostic gold standard is the detection of HSV DNA in the
cerebrospinal fluid by PCR.
•• The HSV PCR has been noted to have a high sensitivity, around 96−98%.
•• Computed tomography (CT) and MRI show oedema and haemorrhages in
the frontotemporal regions.
524
•• Brain biopsy from the temporal region with isolation of the virus was used
as a diagnostic measure for many years.
•• With immunofluorescence and electron microscopy, the diagnosis from the
biopsy material can be confirmed within a few hours in the majority of cases.
•• Presently acyclovir is the drug of choice.
•• Acyclovir is administered in a dose of 30 mg/kg body weight divided into
three daily doses mixed with 100 mL of IV fluids and given over a 1 hour
period.
•• When symptoms of raised intracranial pressure are present, hyperventilation
utilising artificial ventilation and diuretics are indicated.
•• If medical measures fail, temporal lobectomy should be done to relieve
raised ICP.
•• Neonatal HSE is caused by HSV II.
•• The infection is acquired by the infant during delivery.
HERPES ZOSTER (VARICELLA ZOSTER)

•• Varicella (chickenpox) virus may cause meningoencephalitis, transverse
myelitis, Guillain-Barré syndrome (GBS), Reye’s syndrome or acute
cerebellar ataxia.
•• Reye’s syndrome and GBS may occur in association with other viral
infections also.
•• This virus can also cause vasculopathies which can lead to ischaemic
infarction of the brain and spinal cord, as well as aneurysm formation,
subarachnoid and cerebral haemorrhage, carotid dissection and, rarely,
peripheral arterial disease.
•• Herpes zoster is a late manifestation of varicella infection, and is often a
reactivation of latent viral infection of the posterior root ganglion.
•• Other areas where this virus can become latent are the nerve cell bodies,
and also in the non-neuronal satellite cells of the cranial nerves or
autonomic ganglia.
•• It is more common in the elderly and may affect the trigeminal, the
geniculate or the dorsal root ganglion.
•• Motor complications, like facial palsy or localised wasting of muscles, may
occur in about 5% of cases.
•• Facial nerve involvement in cephalic herpes zoster occurs in about 12%
of patients, causing the Ramsay Hunt syndrome.
•• HSV can cause herpes zoster associated cerebral angiitis.
•• These can be seen as ovoid, round lesions at the grey-white matter junction
on imaging.
•• Acyclovir is effective in treating herpes zoster and is helpful in reducing pain.
•• This is given in a dosage of 10 mg/kg every 8 hours for 10−14 days.
•• Post-herpetic neuralgia may be a distressing phenomenon requiring
treatment.
•• Newer drugs, like valacyclovir and famciclovir, are considered to have
similar or even superior efficacy and good safety and tolerability.
RAMSAY HUNT SYNDROME

•• Also known as herpes zoster oticus, geniculate neuralgia or herpes zoster
auricularis, it involves the facial and auditory nerves which accounts for
12% of all cases of facial nerve palsy.
525
•• It is the second most common cause of atraumatic peripheral facial nerve

paralysis.
•• Vesicular eruptions may manifest on the pinna, tragus, in the auditory
canal and on the tympanic membrane, as well as anywhere in the facial
nerve distribution.
•• The presenting complaints are hearing impairment, nystagmus, vertigo,
facial nerve palsy (mimicking Bell’s palsy) and loss of taste sensation in
the anterior two-thirds of the tongue.
•• The site of the lesion causing vestibular symptoms in RHS could be in the
labyrinth, and/or in the superior and inferior vestibular nerve.
•• Compared with Bell’s palsy, patients with zoster oticus often have more
severe paralysis at onset and are less likely to recover completely.
•• Petrositis with multiple cranial nerve palsies is also seen in RHS.
•• Bilateral Ramsay Hunt syndrome has also been reported in diabetic patients
and these patients should be treated with appropriate metabolic control,
NSAIDs and intravenous acyclovir, which should be started at the earliest.
•• Varicella zoster virus DNA level in saliva helps in understanding the kinetics
of the viral reactivation in the facial nerve, as well as in the oropharyngeal
epithelium, in patients with Ramsay Hunt syndrome.
•• This virus can be diagnosed using real time PCR in cerebral spinal fluid
analysis.
REYE’S SYNDROME
•• This is of neurosurgical interest due to the cerebral oedema and high
intracranial pressure seen in the condition.
•• The administration of aspirin during a viral illness in children has been
identified as a probable cause of this syndrome.
•• Some children who are recovering from viral infections may become ill
with headache, vomiting, confusion and restlessness due to acute cerebral
oedema and hepatic failure due to fatty infiltration of the liver.
•• Serum ammonia levels are elevated and sugar levels are low.
•• Urgent treatment with hyperventilation, diuretics like mannitol or furosemide,
and control of hypoglycaemia is indicted.
•• The mortality rate is high.
CREUTZFELDT–JAKOB DISEASE
•• Creutzfeldt-Jakob disease (CJD) is caused by slow viruses or prions that
cause Kuru.
•• The neurosurgical interest is limited to brain biopsy to establish the
diagnosis.
•• Extreme care is needed during such a procedure to prevent transmission
of the disease to other patients and to the surgeon.
•• The other human disease caused by slow viruses is Gerstmann-Straussler
syndrome.
•• CJD presents as a subacute dementia, evolving over weeks to several
months and is accompanied by pyramidal, extrapyramidal and cerebellar
signs.
•• The iatrogenic route is the only route of transmission (contaminated surgical
instruments such as EEG electrodes, organ transplants such as cornea
transplants and growth hormone prepared from human pituitaries).
526
RABIES VIRUS
•• This belongs to the Lyassavirus group of the Rhabdoviridae.
•• It contains a single stranded RNA with a helical symmetry.
•• Six to seven nanometres spike projections are present on the envelope and
on electron microscopy it has a characteristic bullet-shaped appearance;
the virion measures 130−240 x 80 nm.
•• The commonest mode of transmission in man is by the bite of a rabid
animal usally a dog but bats, forrest fox and racoons or the contamination
of scratch wounds by virus infected saliva.
•• Other modes of transmission are mucous membranes of the mouth,
conjunctiva, anus and genitalia, aerosol transmission and infected corneas.
•• Following inoculation, the virus replicates in the striated or connective
tissue at the site of inoculation and enters the peripheral nerves through
the neuromuscular junction spreading to the CNS in the endoneurium of
the Schwann cells.
•• Finally, there is widespread CNS involvement with the neurons infected
with the virus showing structural abnormalities.
•• Within 2−3 weeks of the rabid dog bite the patient suffers with flu-like
symptoms.
•• Soon after, the symptoms expand to slight or partial paralysis, cerebral
dysfunction, anxiety, insomnia, confusion, agitation, abnormal behaviour,
paranoia, terror and hallucinations, progressing to delirium.
•• These symptoms progress to hydrophobia, brain damage and finally death.
•• The method for diagnosing rabies is by performing PCR or viral culture on
brain samples taken after death.
•• Inclusion bodies called Negri bodies are 100% diagnostic for rabies
infection, but are found in only about 80% of cases in the saliva and CSF.
•• One dose of human rabies immunoglobulin (HRIG) and four doses of rabies
vaccine over a 14-day period should be administered following a bite by a
suspected rabid animal as a prophylactic.
•• As much as possible of this dose should be infiltrated around the bites,
with the remainder being given by deep intramuscular injection at a site
distant from the vaccination site.
•• There is no known cure once the disease manifests itself.
H1N1 VIRUS
•• A new pandemic arose in the United States in April, 2009 which was swine-
origin influenza A (H1N1) virus.
•• The H1N1 virus usually causes febrile respiratory symptoms including
fever, cough, sore throat, etc.
•• These symptoms are usually self-limiting, but they can cause neurological
symptoms like seizures and altered sensorium with abnormal
electroencephalograms.
•• The MRI reveals brainstem encephalitis manifested pontine enlargement
and increased signal lesions in the pons.
•• MRI is superior to CT for detecting brainstem encephalitis.
•• Oseltamivir and rimantadine are useful in therapy.
EPSTEIN-BARR VIRUS
•• Epstein-Barr virus (EBV) causes aseptic meningitis, encephalo-myeloneuritis
and neuritis.
527
•• The EBV neuropathies present with ophthalmoplegia, lumbosacral

plexopathy, and sensory or autonomic neuropathy.
•• The association of the virus with neurological disease was suggested by
a positive serum heterophile antibody titre, and later by the presence of
EBV DNA, antibody or both in CSF.
•• CSF from patients with EBV infection of the nervous system contains mainly
EBV-specific CD8+ T cells, a few CD4+ T cells and no CD19+ B cells.
•• EBV infects B and T lymphocytes of more than 90% of the general
population before adulthood.
•• Primary infection results in transient viraemia, followed by a rapid immune
response.
•• EBV replicates in the oropharynx and is transmitted through oral secretions.
•• It is estimated that neurological complications occur in 1−5% of individuals
with infectious mononucleosis.
•• Virtually all CNS lymphomas in AIDS patients contain EBV DNA.
•• These also cause infectious mononucleosis, nasopharyngeal carcinoma,
Burkitt’s lymphoma, Hodgkin’s disease and lymphoproliferative disease in
immunocompromised individuals.
CYTOMEGALOVIRUS
•• Cytomegalovirus (CMV) produces neurological disease predominantly in
infants with congenital infection.
•• Neurological complications include microcephaly, seizures, hypotonia, acute
brachial plexopathy and spasticity.
•• In immunocompetent adults, the most common neurological complication of
CMV infection is Guillain-Barré syndrome.
•• CMV polyradiculopathy in patients with AIDS begins insidiously as a
cauda equina syndrome with paraesthesias and distal weakness (usually
asymmetric), incontinence, and sacral-distribution sensory loss.
•• CSF might show neutrophilic or mononuclear pleocytosis, or an elevated
protein and depressed glucose content.
•• Imaging studies (MRI) show enhancement in the ventricular ependymal and
focal disease has been attributed to CMV vasculitis or demyelination.
•• Characteristic owl-eyed cytomegalic inclusions and CMV-specific antigens
have been found in brain tissue and blood vessels of AIDS patients with
subacute encephalopathy.
JAPANESE ENCEPHALITIS
•• This is caused by a Flavi virus.
•• It is the most common vaccine-preventable cause of encephalitis in Asia.
•• Among the affected individuals 20−30% of patients die, and 30−50% of
survivors have neurological or psychiatric sequelae.
•• Symptoms develop after an incubation period of 5−15 days.
•• These include fever, headache and other non-specific symptoms.
•• The classical description of JE includes a Parkinsonian syndrome
with mask-like facies, tremors, cog wheel rigidity and choreoathetoid
movements.
•• Seizures are common, especially among children.
•• Status epilepticus, brain hypoxia, increased intracranial pressure, brainstem
herniation and aspiration pneumonia are the most common complications
associated with poor outcome and death.
528
•• Microglial activation following JEV infection has been found to influence

the outcome of viral pathogenesis.
•• Activated microglia secrete cytokines, such as interleukin-1 (IL-1) and
tumour necrosis factor alpha (TNF-a), which can cause toxic effects in
the brain.
•• Other soluble factors, such as neurotoxins, excitatory neurotransmitters,
prostaglandin, reactive oxygen and nitrogen species, are secreted by
activated microglia.
•• MRI of the brain is better than CT for detecting JEV associated
abnormalities such as changes in the thalamus, basal ganglia, midbrain,
pons and medulla.
•• Thalamic lesions are the most commonly described abnormality; although
these can be highly specific for JE in the appropriate clinical context, they
are not a very sensitive marker of JE.
•• JEV infections are confirmed most frequently by detection of virus-specific
antibody in CSF or serum.
•• A c u t e - p h a s e s p e c i m e n s s h o u l d b e t e s t e d f o r J E V - s p e c i f i c
immunogl obulin M (IgM) antibodies using a capture enzyme-linked
immunosorbent assay (MAC ELISA).
•• More recent studies have shown the utility of nucleic acid amplification
tests (NAAT) for diagnosing JE in some patients with encephalitis or
aseptic meningitis, but this method still lacks the sensitivity needed for
routine diagnosis.
•• No specific antiviral agent or other medication to mitigate the effects of
JEV infection is available.
•• In March 2009,the food and drug administration (FDA) approved a new
inactivated Vero cell culture-derived JE vaccine (JE-VC) for use in persons
aged greater than or equal to 17 years.
•• This is given in two doses of 0.5 mL each by the intramuscular route
administered 28 days apart.
71 Acquired Immunodeficiency
CHAPTER Syndrome and the
Neurosurgeon
Sarat Chandra P  Vivek Tandon
THE VIRUS
•• HIV is a type of RNA virus, known as lentivirus which is sub-grouped under
the Retroviruses, and attacks the immune system.
•• HIV virion is icosahedral in shape.
•• The envelope contains two major proteins (gp 120 and gp 41) which form
external spikes and it has nine genes.
•• Three genes (Gag, Pol and Env) are needed to make the structural proteins
for the new virus particles.
•• HIV virus has been found in the body fluids like semen, cervical secretions,
plasma, CSF, tears, saliva, urine and breast milk.
•• The concentration of virus in these fluids varies considerably and the most
infectious are semen, cervical secretions and blood.
•• The most common modes of transmission are by intimate sexual contact,
(anal, vaginal or oral),transfusion of infected blood products, use of
contaminated needles, and from mother to child in utero or at birth.
PATHOGENESIS
•• Once the virus has gained entry into the body of the host, it attaches to
a special glycoprotein called CD4 present on the helper/inducer T cells.
•• This allows the viral envelope to fuse with the cell membrane, and contents
of the HIV particle enter the cell.
•• Inside the cell the viral enzyme, reverse transcriptase, converts viral RNA
into DNA, which attaches to the human DNA by the HIV enzyme integrase.
•• This provirus may lie dormant for a long time but, on activation of the cell,
the HIV gene is converted into messenger RNA using the human enzymes
and it is transported outside the nucleus, where it is used as a blueprint for
producing new HIV enzymes and proteins.
•• These together form new viral particles which are released from the cells
and infect new cells, starting the cycle again.
•• CD4 helper T cells are important for a strong immunological response
against foreign antigens.
•• They secrete interleukin 2, interferon, and B cell growth and differentiating
factors.
•• They also help in activating CD8 T cells, B cells and macrophages.
•• The defects in immunity are not only explained by the quantitative
abnormalities of the lymphocytes, but also by the qualitative defects of the
CD4 responsiveness caused by HIV.
530
•• The defect in the B cells leads to generalised hypergammaglobulinaemia

and can depress B cell responsiveness to new antigens.
•• Therefore, the immunodeficiency of HIV is mixed where both humoral and
cellular immunity are affected.
•• The virus directly causes a variety of neurologic effects, mostly due to
release of cytokines and other neurotoxins by the infected macrophages
and microglia.
•• HIV mediated effects on neurons and oligodendrocytes are felt to involve
indirect pathways where viral proteins, like gp120 and Tat, trigger the
release of neurotoxins from the macrophages and also from the astrocytes.
•• Impairment of excitatory neurotransmitters and calcium flux are also
implicated for neurological deterioration.
CLINICAL FEATURES
•• The complications of HIV related infections and neoplasms affect virtually
every organ system.
•• This varied clinical spectrum of illness ranges from an acute seroconversion
illness to a chronic asymptomatic carrier to full blown AIDS.
•• The acute HIV syndrome is seen in 50−70% of individuals infected with
HIV, approximately 3−6 weeks after the primary infection.
•• The typical symptoms are fever, pharyngitis, lymphadenopathy, headache,
retro-orbital pain, arthralgias, myalgias, lethargy, malaise, anorexia and
nausea.
•• Neurological features may include meningitis, encephalitis, peripheral
neuropathy, myelopathy, dermatological rash and mucocutaneous
ulceration.
•• These symptoms occur with an initial burst of plasma viraemia.
•• The hallmark of progressive disease is declining number of CD4
lymphocytes and a low CD4/CD8 ratio.
•• Patients with positive HIV serology and who have ever had a CD4
lymphocyte count below 200 cells/mcL or a CD4 lymphocyte percentage
below 14% are considered to have AIDS, because the resulting state of
immunodeficiency with such low levels of CD4+ T cells count is severe
enough to predispose the individual to opportunistic infections and
neoplasms and hence for clinically apparent disease.
•• Physical examination may be entirely normal and abnormal findings range
from completely non-specific findings of generalised lymphadenopathy to
highly specific findings of hairy leukoplakia of the tongue, Kaposi’s sarcoma
and cutaneous bacillary angiomatosis.
•• Systemic complaints include fever, weight loss and night sweats.
•• Weight loss involves disproportionate loss of the muscle mass and is
attributed to multiple factors like anorexia, nausea, vomiting, malabsorption,
recurrent diarrhoea and increased metabolism due to fever.
•• Pulmonary diseases, like Pneumocystis pneumoniae, are one of the most
common opportunistic infections associated with AIDS; other infections
include bacterial, mycobacterial and viral pneumonias.
•• Apical infiltrates and disseminated disease associated with mycobacteria
are more common in AIDS patients when compared with immunocompetent
persons.
•• Other lung diseases associated with HIV are Kaposi’s sarcoma, non-
Hodgkin’s lymphoma and interstitial pneumonitis.
Chapter 71 • Acquired Immunodeficiency Syndrome and the Neurosurgeon
531
•• Gastrointestinal manifestations include oral candidiasis or hairy leukoplakia

which is caused by Epstein-Barr virus, angular cheilitis, recurrent
aphthous ulcers, candidial oesophagitis, hepatic disease due to infections
(mycobacteria, CMV, hepatitis B/C) and neoplasms like lymphomas,
acalculous cholecystitis, enterocolitis and malabsorption syndrome.
•• Endocrine dysfunctions are hypogonadism in men and thyroid function
abnormalities.
•• Skin manifestations include viral infections (herpes simplex, herpes zoster,
molluscum contagiosum from poxvirus), bacterial infections (Staphylococcal
boils, furuncles, impetigo; bacillary angiomatosis due to Bartonella hensalae
and Bartonella quintana) seborrhoeic dermatitis, xerosis, psoriasis and
skin malignancies.
•• HIV related malignancies include Kaposi’s sarcoma, non-Hodgkin’s
lymphoma, primary CNS lymphoma (PCNSL) and invasive cervical
carcinoma.
NEUROLOGICAL MANIFESTATIONS OF
ACQUIRED IMMUNODEFICIENCY SYNDROME
PRIMARY CENTRAL NERVOUS

SYSTEM LYMPHOMA
•• Primary CNS lymphoma is a primary intracranial tumour occurring
commonly in patients who are immune suppressed and typically in AIDS.
•• More than 90% are associated with Epstein-Barr virus infection and 20%
of all cases of lymphomas in AIDS are due to PCNSL; these are seen
to occur in 10% cases of AIDS.
•• Mean CD4+ count at the time of diagnosis is around 50/µL; thus due to
severe immune suppression the prognosis is poor.
•• In the immune competent population PCNSL occurs in the later age
group, i.e. 50−60 years, median age being 54 years (in immune
compromised patients median age at diagnosis is 34 years).
•• There is an increasing trend in incidence of PCNSL in the immune
competent population.
•• Most PCNSLs are diffuse large B cell non-Hodgkin lymphomas and they
occur more commonly in the frontal lobes, deep nuclei and periventricular
region in the supratentorial compartment, while in the infratentorial
compartment the commonest location is the cerebellum.
•• They present with seizures, headache, cranial nerve deficits, altered
sensorium and features of mass effect, associated with systemic features
of fever, night sweats or weight loss.
•• Imaging (MRI) shows multiple ring enhancing lesions (one to three), usually
in the deep white matter.
•• They usually present with multiple ring enhancing lesions with mild mass
effect and oedema on CT.
•• On MRI, unlike non-AIDS cases where homogeneous enhancement of
contrast is seen, these patients have target lesions on T2-weighted images
(hypointense centre with surrounding hyperintensity).
•• Higher incidence of multicentric lesions is seen in AIDS patients compared
to non-AIDS cases of PCNSL.
532
•• Differentiation with toxoplasmosis may be difficult needing confirmatory brain

biopsy in solitary lesions or when trial toxoplasmosis therapy has failed.
•• Surgical decompression does not alter the prognosis and the role of surgery
is usually limited to biopsy, for which stereotactic techniques are commonly
used as the lesions are often deep seated.
•• The treatment of choice, once the diagnosis is confirmed by biopsy, is
whole brain radiation therapy, a total of 40−50 Gy given in 1.8−3 Gy daily
fractions along with corticosteroids.
•• Median survival for patients with AIDS is less in comparison to the immune
competent patients, for whom is 10−18 months.
PROGRESSIVE MULTIFOCAL
LEUCOENCEPHALOPATHY
•• It is usually a fatal viral disease caused by a polyomavirus called “JC virus”.
•• The antibodies for JCV are present in 60−80% of adults, but usually remain
latent and cause PML specifically in patients who are immunocompromised,
e.g. AIDS, allograft recipients, patients receiving chemotherapy, drugs
(like natalizumab and infliximab), chronic steroid therapy and autoimmune
disorders (like SLE).
•• It is believed that PML occurs more commonly in HIV infection in comparison
to any other immune suppressive condition because HIV infection of the
brain makes JCV more active in the brain.
•• PML is characterised by progressive damage or inflammation of the white
matter of the brain at multiple locations.
•• Focal myelin loss occurs with sparing of the axon cylinders, causing
impairment in transmission of the nerve impulses.
•• These are surrounded by the hypertrophic astrocytes and abnormal
oligodendroglia with eosinophilic inclusion bodies.
•• Symptoms include cognitive impairment, blindness, cranial nerve or motor
weakness, sensory deficit and ultimately coma.
•• PML is like other demyelinating diseases but, since oligodendrocytes, which
are myelin producing cells are destroyed, it progresses more rapidly and
leads to death within a few months.
•• The median survival with PML in patients with AIDS is 6 months, but longer
survival is also seen.
•• Confirmatory diagnosis of PML is made by testing for JC virus in CSF or
in brain biopsy.
•• CT scan shows areas of diffuse low density and MRI shows high intensity
areas on T2-weighted images. The virus attacks the oligodendrocytes and
hence there is progressive involvement of the white matter.
•• Contrast enhancement is absent because there is absence of inflammatory
response. Extensive white matter high signal on T2 weighted/FLAIR (fluid
attenuated inversion recovery) is therefore the hallmark of this disease with
sparing of the cortical grey matter.
•• No enhancement on contrast, no mass effect, no oedema and more ill
defined borders help in distinguishing it from toxoplasmosis.
•• No treatment is effective, although some promise has been shown with the
use of antiretroviral therapy initially, as the immunity improves.
•• However, patients on highly active antiretroviral therapy (HAART) can
develop a rare fatal complication of immune reconstitution syndrome which
increases the damage caused by the infection.
533
TOXOPLASMOSIS
•• It is the most common cause of a space occupying lesion of the CNS in
patients with HIV.
•• Patients present with headache, focal neurological deficits, seizures and
cognitive deficits.
•• Imaging studies show typical peripheral contrast enhancing lesions which
have a predilection for the basal ganglia.
•• The major differential diagnosis may be lymphoma and distinction between
the two may be impossible in some cases.
•• Features that favour toxoplasmosis are basal ganglia involvement, variable
contrast enhancement, ring enhancement and micro haemorrhages.
•• AIDS related lymphoma, in contrast to classical lymphoma, can also be
cortical and tends to involve the grey and white matter, is associated with
leptomeningeal thickening and is occasionally subependymal or wholly
intraventricular.
•• For a single lesion on MRI, an empiric trial of toxoplasmosis therapy may
be instituted and MRI is repeated after 2 weeks.
•• If the lesion has not decreased in size, then biopsy of the lesion is indicated
to confirm the diagnosis.
•• Toxoplasmal infection can also cause meningoencephalitis and
encephalopathy. This usually occurs when CD4 count fall below 200/mcL.
MENINGITIS
Cryptococcal Meningitis
•• This has been reported to be the commonest opportunistic infection
in India.
•• Diagnosis in patients with AIDS, presenting with features of fever, headache
and meningismus is based on positive latex agglutination test (CRAG
positive = 70%) or positive spinal fluid examination for Cryptococcus.
•• Classical meningial signs may or may not be present.
•• Meningismus is present in less than 20%.
•• Treatment with Amphotericin B and flucytosine for 6−8 weeks is moderately
effective in eradicating the infection.
Carcinomatous Meningitis
•• This can occur in patients with lymphoma, presenting with features of
multiple cranial nerve involvement and meningeal signs.
•• CSF may not show any abnormality, but biopsy is diagnostic.
•• Radiotherapy to the skull base and intrathecal methotrexate are the
available treatment options, but the prognosis remains poor.
Aseptic Meningitis
•• It can occur in 1−2% cases of recently infected individuals.
•• A more indolent aseptic meningitis is seen in around 60% cases of HIV
carriers.
•• CSF examination is suggestive of meningitis, but serological and culture
tests are negative.
•• HIV has been isolated from the CSF, and is believed to be the pathogenic
organism.
534
TUBERCULAR INFECTION
•• It is one of the most common infections associated in HIV-AIDS in India.
AIDS ENCEPHALOPATHY AND AIDS

DEMENTIA COMPLEX
•• HIV encephalopathy is a part of acute HIV syndrome.
•• HIV associated progressive encephalopathy is a syndrome complex seen in
children while, in adults, the AIDS dementia complex (ADC) is also known
as HIV associated dementia complex.
•• These are characterised by cognitive, motor and behavioural features.
•• It is associated with advanced age and lower CD4+ counts.
•• With the use of HAART, a less severe dysfunction, minor cognitive disorder
(MCMD) has become more common than ADC.
•• Clinical features include impaired mentation, decreased work productivity,
inattentiveness, memory loss, decreased libido, apathy, depression, sleep
disturbances, psychosis and, rarely, seizures.
•• Motor abnormalities include weakness and imbalance of gait.
•• At a later stage global dementia with memory loss and impaired speech
may develop leading to a persistent vegetative state.
•• CSF studies show elevated protein (60%) and immunoglobulin IgG (80%).
•• The CSF is usually acellular but mononuclear infiltrates may be seen in 25%.
•• Presence of oligoclonal bands, HIV antibodies and testing of HIV in CSF
using PCR (best) may also yield positive results.
•• Neuroimaging studies may reveal diffuse cortical atrophy with periventricular
hyperintense signals in T2-weighted images in MRI.
•• EEG shows generalised slowing in the later stages.
•• Microgliosis is often perivascular and vacuolation may also be seen.
•• HAART is the treatment of choice and drugs with good CSF penetration
(lamivudine, stavudine, zidovudine, indinavir, nevirapine) should be used.
•• Tricyclic antidepressants or neuroleptics should be used for the depressed
and agitated patients, respectively.
•• Poorer prognosis is associated with lower CD4 counts, higher HIV RNA
levels, anaemia, low body mass index, higher constitutional symptoms and
lower educational levels.
HIV MYELOPATHY
•• Myelopathy is a late presentation of HIV disease and most patients will
have concomitant HIV encephalopathy.
•• Vacuolation of the white matter of the cord is seen.
•• The syndrome is similar to Vitamin B 12 deficiency and, therefore, a
nutritional cofactor is believed to be involved.
•• The diagnosis is of exclusion and patients presenting with spastic
paraparesis with paraesthesias leading to incontinence should be evaluated
by lumbar puncture to rule out CMV polyradiculopathy.
•• Lymphomatous deposits in the epidural space can cause cord compression
in HIV and hence an MRI or CT scan to exclude the above should be done.
•• Transverse myelitis due to herpes zoster or CMV can occur.
PERIPHERAL NERVOUS SYSTEM

•• HIV may cause inflammatory polyneuropathies, sensory neuropathies and
mononeuropathies.
535
•• Around 30% of patients with AIDS may develop peripheral neuropathy.

•• Presenting features are tingling, numbness and pain in the lower limbs.
•• Symptoms are out of proportion to objective findings on examination.
•• This is believed to be due to the direct effect of HIV on the nerves and is
improved with zidovudine.
•• However, drugs like stavudine and didanosine, can also cause peripheral
neuropathy.
•• Evaluation to rule out other causes, like alcoholism, thyroid disease, vitamin
B12 deficiency and syphilis, should be done.
•• Gabapentin has been seen to provide symptomatic relief and response to
amitryptyline is uncommon.
•• A Guillain-Barré syndrome like demyelinating neuropathy is seen in HIV
infected patients and it usually occurs before frank immunodeficiency
develops.
•• Improvement with plasmapheresis supports the immune mediated
causation.
OTHER UNCOMMON NEUROLOGICAL

PRESENTATIONS
1. Myopathy: Zidovudine can also cause myopathy. If creatinine kinase levels
are greater than 1000 units/L then the dose of zidovudine should either be
decreased or stopped.
2. Retinitis: CMV retinitis is the most common cause of visual diminution in
patients with AIDS and, therefore, visual complaints in HIV patients must be
evaluated urgently. Other rare retinal infections can be due to concomitant
herpes virus and Toxoplasma.
DIAGNOSIS OF HIV
•• The tests for HIV include antibody and antigen assays.
•• HIV antibody testing conventionally is done by ELISA which is a good
screening test.
•• To avoid false positive results in repeated tests, confirmation must be done
by Western Blot which, when combined with ELISA, yields specificity of
greater than 99.99%.
•• Indeterminate results may be seen in HIV II infection, autoimmune diseases,
pregnancy and early HIV infection.
•• HIV rapid antibody test produces results in 10−20 minutes and is utilised
as a screening procedure and the results need to be confirmed with the
standard tests as described above.
•• Complete blood count in HIV cases may show anaemia, neutropaenia and
thrombocytopaenia.
•• Absolute CD4 lymphocyte count (< 200 cell/mcL) is the most widely used
predictor for disease progression.
•• The percentage of CD4 lymphocytes may be more accurate (<14%).
•• HIV viral load tests can measure the actively replicating viruses and they
are better for diagnosis in acute HIV infection before seroconversion.
MANAGEMENT OF INTRACRANIAL LESIONS

•• HIV cases are on the rise and due to frequent involvement of the nervous
system neurosurgical consultations are being frequently sought for brain
536
biopsy, as the diagnostic dilemma often persists despite rapid progress in

the diagnostic and neuroimaging techniques.
•• PML is usually identifiable on neuroimaging, but it might be impossible
at times to differentiate toxoplasmosis from lymphoma and, therefore, it
is imperative to obtain baseline toxoplasmosis titres of all AIDS patients.
•• The chances of toxoplasmosis are higher with serum antibodies greater
than 1:16 (usually > 1:256).
•• Thus, patients in whom titres change over a period of time and neuroimaging
shows presence of multiple ring enhancing lesions, particularly in the basal
ganglia region, they have higher chances of having toxoplasmosis.
•• The treatment of choice for toxoplasmosis is pyrimethamine 200 mg
loading dose, followed by 75−100 mg/day with sulphadiazine 75 mg/kg
orally loading dose then 25 mg/kg every 6 hours. Folic acid tablets (10 mg)
should be given along with each dose of pyrimethamine.
•• In cases of sulpha drug allergy, sulphadiazine may be replaced with
clindamycin. Other alternative treatment options for complete intolerance
are spiramycin and atovaquone.
•• PCNSL is suspected in patients with single ring enhancing lesions with
neurological deterioration in AIDS.
•• A lumbar puncture should be done in such cases if imaging is not suggestive
of mass effect.
•• Around 10 mL of CSF is needed for cytology and is positive for PCNSL in
10−25% of the patients.
•• CSF analysis for PCR amplification of JC virus and Epstein Barr virus can
also be done.
•• Biopsy may be needed to confirm the diagnosis prior to starting
radiotherapy.
•• Early biopsy to prevent inadvertent delay in trial of antibiotic therapy, has
been recommended by some, while other centres have even recommended
empiric radiation therapy for highly suspicious cases of lymphoma.
BIOPSY IN AIDS
•• Biopsy is recommended in the following settings in AIDS cases:
–– Lesions are atypical for toxoplasmosis
–– Negative toxoplasmosis titres in the presence of intracranial space
occupying lesion(s)
–– Patients who fail to respond to empirical treatment for toxoplasmosis
–– Presence of extraneural neoplasm or infectious disease process
involving the CNS.
•• As most of these lesions are usually deep and the risk of open biopsy in
AIDS is higher, stereotactic biopsy must be preferred in appropriate cases.
•• Biopsy should be taken from the centre of the lesion which is most
accessible and located in the least eloquent area of the brain.
•• All biopsy specimens should be subjected to histopathological examination
and microscopic examination for TB and fungus.
•• Immunoperoxidase staining is done for Toxoplasma and cultures done for
TB, fungi and bacteria.
RISKS FOR HEALTH PROFESSIONALS

•• The most effective way of protection is by routine use of protective gloves,
impervious gowns, face mask and goggles.
537
•• The precautions recommended for staff during surgery are:

–– Have vaccination against hepatitis B
–– Cover all cuts and abrasions with waterproof dressings
–– Do not pass sharp instruments hand to hand
–– Do not use hand needles
–– Do not guide needles with fingers
–– Do not re-sheath needles
–– Dispose of all sharp instruments safely into approved containers
–– Put disposables and waste into yellow clinical waste bags for
incineration.
ADDITIONAL PRECAUTIONS WHEN

CARING FOR KNOWN HIV POSITIVE
AND HIGH-RISK PATIENTS
•• Consider non-operative management.
•• Remove unnecessary equipment from theatre.
•• Observe highest level of theatre discipline.
•• Have only experienced surgeons and health care workers in the operation
theatre.
•• Use double gloves, high efficiency masks, eye protection, boots, impervious
gowns, closed wound drainage.
•• Use disposable anaesthetic circuitry or appropriate method of deconta-
mination.
•• Disinfect theatre floor with hypochlorite.
Section VII: Vascular Disorders
72
CHAPTER Subarachnoid
Haemorrhage
Chandramouli BA  Arivazhagan A
INTRODUCTION
•• Subarachnoid haemorrhage (SAH) is a neurological emergency
characterised by haemorrhage into the subarachnoid space, which is
normally filled with cerebrospinal fluid.
•• It is one of the most important causes of sudden, acute severe headache,
and needs to be considered in its differential diagnosis.
AETIOLOGY
•• The most common cause of SAH is trauma.
•• However, among SAH due to non-traumatic causes, 85% are due to
ruptured cerebral aneurysms.
•• In a small proportion of cases, connective tissue disorders have
been implicated as the cause of SAH. These include Ehlers-Danlos
syndrome, pseudoxanthoma elasticum, polycystic kidney disease and
neurofibromatosis type I.
•• The other causes of SAH include arteriovenous malformation (AVM),
dural venous sinus thrombosis, intracranial arterial dissection, mycotic
aneurysms, bleeding diathesis and drug-induced SAH.
•• The various causes of SAH have been summarised in Table 1.
CLINICAL FEATURES
•• The most common and classical presentation of SAH is the sudden onset
of severe headache, often described as “the worst headache of one’s life”.
•• The headache is acute, peaks rapidly, wakes the patient if asleep and
persists for days not responding to conventional analgesics.
•• It is often holocranial, may sometimes be localised to one side or to the
occipital or retro-orbital region. It is frequently associated with pain and
stiffness of the neck.
•• Sometimes neck pain may predominate over cranial symptoms.
•• The sensorium is often altered in patients with SAH due to sudden rise in
•• Transient loss of consciousness can occur in 33% of patients and around
20% may be comatose at presentation.
•• Seizures occur in about 20% of patients with SAH.
•• Seizures occur more frequently with middle cerebral artery (MCA)
aneurysms, posterior communicating artery (PCom) aneurysms, associated
intracerebral haematoma and hypertension.
Chapter 72 • Subarachnoid Haemorrhage
539
Table 1: Causes of subarachnoid haemorrhage

• Trauma
Vascular
• Ruptured intracranial aneurysms
• Arteriovenous malformations
• Tumours with haemorrhage
• Pituitary apoplexy
Vasculopathy
• Collagen vascular disease
• Amyloid angiopathy
• Arterial dissection
Haematological
• Anticoagulant therapy
• Leukaemia
• Hepatic or renal disease-induced coagulopathy
Drugs
• Cocaine, amphetamine, ephedrine
•• The following points in history should carefully be evaluated to suspect

the diagnosis:
–– Onset of headache: Abrupt onset/during exertion
–– Severity
–– Quality: Distinct/unique
–– Associated symptoms: Nausea, vomiting, seizure, diplopia
–– Alternate causes for headache
–– Enquire about: Alcohol consumption, smoking, hypertension, cocaine
use
–– Family history or past history of SAH.
•• Many patients with SAH give history of mild headache with nausea or
vomiting suggesting a minor bleed prior to the ictus. This is referred to as
“warning leak or sentinel haemorrhage”.
•• Sentinel haemorrhage is reported to occur in 40−50% of patients with SAH
and is usually noted within 2−8 weeks prior to SAH.
•• CT scan of the brain is usually not very reliable in diagnosing or ruling out
sentinel haemorrhage.
•• The patient’s level of sensorium, presence of focal motor deficits and cranial
nerve palsies, if any, should be recorded on examination.
•• Meningismus or nuchal rigidity is noted in 50% of patients due to meningeal
irritation following SAH. It can manifest within 6−24 hours after SAH.
•• The patient also needs to be evaluated for systemic effects of SAH in detail
before surgical management.
•• Examination of the fundus may reveal papilloedema, subhyaloid, retinal
or preretinal haemorrhage. Subhyaloid haemorrhage results in bright red
blood near the optic disc obscuring the underlying retinal blood vessels.
Section VII • Vascular Disorders
540
•• Certain clinical features in a patient with SAH can suggest the specific
location of the aneurysm.
•• Visual symptoms can occur due to aneurysms in the region of the anterior
communication artery (ACom), ophthalmic and superior hypophyseal
segments of the internal carotid artery, giant aneurysms of PCom and
anterior choroidal artery.
•• Aneurysms of the posterior communicating artery cause third nerve palsy
with pupillary involvement.
•• Multiple cranial nerve palsies can occur in a cavernous carotid aneurysm.
They can present with acute retro-orbital pain, decrease in visual acuity,
proptosis and paresis of cranial nerves III, IV and VI.
•• A ruptured cavernous carotid aneurysm does not result in SAH but causes
carotid cavernous fistula. However, an intradural extension of the aneurysm
can result in SAH.
•• Hypothalamic dysfunction and diabetes insipidus are more common in
patients with anterior communicating artery aneurysms.
•• Basilar bifurcation aneurysms can present with third nerve palsy, chiasmal
compression or Weber’s syndrome. Intraventricular haemorrhage and
hydrocephalus can occur.
Grading of Clinical Status

•• Various clinical grading methods have been proposed for evaluating
patients with SAH. Hunt and Hess classification (Table 2) and World
Federation of Neurosurgical Societies (WFNS) grading (Table 3) are the
most commonly used systems for evaluation.
Table 2: Hunt and Hess classification of SAH

Grade Clinical features
0 Unruptured
1 Asymptomatic or mild headache, slight nuchal rigidity
2 Moderate-to-severe headache, nuchal rigidity, no neurological deficit other than cra-
nial nerve palsy
3 Mild focal deficit, lethargy, confusion
4 Stupor, hemiparesis
5 Coma, extensor rigidity
Table 3: World Federation of Neurosurgical Societies: Grading scale for SAH
Grade GCS Focal deficit
1 15 Nil
2 13−14 Nil
3 13−14 Present
4 7−12 Absent or present
5 3−6 Absent or present
541
MISDIAGNOSIS OF SUBARACHNOID
HAEMORRHAGE
•• The missed diagnosis is often attributed to:
–– Lack of awareness
–– Failure to do relevant investigations and
–– Failure to interpret the investigation results.
•• The common clinical misdiagnoses made were migraine/tension headache,
viral infection, hypertension/encephalopathy, sinusitis, meningitis, etc.
INVESTIGATIONS
Imaging of the Brain
•• CT brain is the most commonly performed investigation in a patient with
suspected SAH.
•• Subarachnoid blood appears in plain CT scan as a hyperdensity in the
subarachnoid space.
•• The hyperdensity of the blood is related to the concentration of globin in
the haemoglobin molecule.
•• The identification of subarachnoid blood in CT scan depends on the amount
of bleed, density of blood and the time interval between the ictus and imaging.
•• Blood with low haematocrit values does not appear hyperdense in CT scan.
•• If a CT scan is performed within 24 hours after ictus, subarachnoid bleed
will be evident in 95−98% of patients who have blood demonstrated on
lumbar puncture.
•• As time elapses, haemolysis and dispersion of blood in the CSF occurs,
reducing the sensitivity of CT in detecting SAH.
•• Structures that can mimic SAH include calcification of the basal arteries,
falx, partial volume artifacts and streak artifacts. They can be recognised
by their focal nature and can be differentiated from SAH.
•• MR imaging, especially the FLAIR sequences may be a better imaging
modality to detect subacute SAH.
•• The amount of bleed has been graded by Fischer et al. and this can predict
the outcome of patients with SAH (Table 4).
•• The amount of subarachnoid blood directly correlates with the risk of
vasospasm.
•• Patients with Fischer’s grade 3 SAH have the highest risk of developing
vasospasm.
•• The location of an aneurysm causing SAH can be predicted in the majority
of cases based on the cisterns involved.
•• Intracerebral haematoma in the temporal lobe can occur following rupture
of MCA or PCom aneurysm.
•• ACom aneurysm bleed can cause gyrus rectus bleed.
Table 4: Fischer’s grading of subarachnoid haemorrhage

Grade 1 No detectable blood on CT scan
Grade 2 Diffuse thin SAH Vertical layers <1 mm thickness
Grade 3 Localised clot and/or thick SAH vertical layer >1 mm thickness
Grade 4 Intraventricular or intracerebral clot with diffuse or no subarachnoid
haemorrhage
542
•• An internal carotid artery (ICA) bifurcation aneurysm can result in

intracerebral haemorrhage extending into the putamen and thalamus,
although slightly anterior and inferior to the usual location of hypertensive
intracerebral haemorrhage.
•• Subdural haematoma can occur due to bleed from MCA or PCom aneurysm.
Lumbar Puncture
•• Lumbar puncture is the gold standard against which other investigations
have been compared for their sensitivity in diagnosing SAH.
•• Since the sensitivity of CT brain for detecting SAH is very high and it being
non-invasive, is considered the first choice of investigation.
•• A lumbar puncture is performed when the clinical presentation of the patient
is highly suggestive of SAH and the CT scan is negative or equivocal.
•• A lumbar puncture is usually positive in these patients if it is done after
6 hours, preferably 12 hours after SAH which allows for the formation of
metabolites of haemoglobin.
•• If the lumbar puncture is performed a few days after the ictus, then the
supernatant fluid will reveal xanthochromia, and crenated RBCs will be
detected in the sediment. Xanthochromia is the most characteristic feature of
SAH and occurs due to lysis of RBCs in the CSF, which imparts yellow colour.
•• It appears as early as about 3 hours after the ictus and persists for about
3 weeks.
•• A traumatic lumbar puncture can mimic subarachnoid haemorrhage (SAH).
•• It can be differentiated from spontaneous SAH by the fact that the blood
in the CSF clears in serial collecting tubes.
Angiography
•• Four-vessel catheter angiography is the gold standard investigation for
detection of the aetiology of SAH.
•• Angiography is mandatory in all patients with a CT diagnosis of SAH and in
patients with acute onset third cranial nerve palsy with pupillary involvement.
•• It establishes the cause of SAH in 85% of patients.
•• The risks of angiography needs to be considered while subjecting the
patient for the procedure, which include contrast reactions, nephrotoxicity,
puncture site haematoma, transient neurological deficits (1%) and
permanent complications (0.1−0.5%).
•• The overall complication rate is around 7%, with the majority of them being
puncture site haematomas.
•• In 15−20% of patients with SAH, angiogram may be negative and this
can be due to interpretive errors, cerebral vasospasm, spontaneous
thrombosed aneurysms, vascular lesions of the spine or spinal neoplasms
as the cause of SAH.
•• These patients require a repeat angiogram after 2−6 weeks.
•• Angiogram is often negative in perimesencephalic SAH, where blood is
located in the interpeduncular and perimesencephalic cisterns.
•• In conditions like pregnancy-induced hypertension, sympathomimetic drug
abuse, bleeding dyscrasias, use of antiplatelet agents and anticoagulants,
can result in SAH and when detected, they have to be corrected.
•• Computed tomography angiography and magnetic resonance angio-
graphy have been performed for detection of aneurysms as an alternative
to catheter angiography.
543
•• The main advantage of these procedures is the non-invasiveness.

•• CT angiography can be performed rapidly even in patients not medically
fit to undergo angiography, and as an emergent procedure in patients with
acute deterioration.
•• It can also be used as a screening tool in the patient’s group with high-risk
for aneurysms like those with collagen vascular disease and polycystic
kidney disease.
•• The main disadvantages of the procedure include contrast-related reactions
and nephrotoxicity.
•• The presence of intracerebral haematoma, calcification or aneurysmal clips
can affect the interpretation of the images.
•• Small posterior communicating segment aneurysms may be missed by
CT angiography.
•• Catheter angiography is considered the gold standard, while all other
procedures are compared against it for assessing their sensitivity and
specificity.
•• The sensitivity of CT angiography varies between 77% and 100%, while the
specificity ranges from 79 to 100% as reported in the literature.
•• MR angiography has a sensitivity of 85−100% for aneurysms larger than
5 mm size, while the sensitivity falls to 56% for aneurysms smaller than
5 mm.
•• The specificity of MRA for aneurysms ranges from 92−100%.
•• The disadvantages of MRA include longer procedure time, difficulty to
perform in emergent settings and in critically ill patients.
•• MRA can be performed in pregnant patients, and as compared to CT
angiography, can avoid the risk related to iodinated contrast and radiation.
MANAGEMENT OF SUBARACHNOID
HAEMORRHAGE
•• Despite early diagnosis and management, the 30-day mortality of
aneurysmal SAH approaches 50%.
•• Most deaths occur in the first week after the ictus.
•• Around 10% die before reaching the hospital and 25% die within 24 hours
of hospital admission.
•• The natural history of SAH is grim, even among good grade patients.
•• The leading causes of death include large intraparenchymal haematoma,
acute hydrocephalus, raised intracranial pressure, myocardial ischaemia,
cardiac arrhythmias, pulmonary oedema, respiratory failure, rebleed and
ischaemia secondary to vasospasm.
•• The level of consciousness at the time of admission is the most predictive
clinical factor of SAH.
•• SAH results in a wide gamut of changes in the patient, affecting multiple
systems in varied ways.
Acute Management
•• The goals of medical management include:
–– General care, stabilisation of acutely ill patients
–– Obliteration of the ruptured aneurysm at the earliest
–– Prevention of complications and sequelae of SAH.
•• Most of these patients experience photophobia due to SAH and hence
bright lighting is avoided in the room.
544
•• A water mattress or pneumatic mattress can be used to prevent deep

venous thrombosis.
•• Analgesics are administered to alleviate headache.
•• Patients may be agitated due to brain injury, hydrocephalus, raised
intracranial pressure or a full urinary bladder, which need to be taken
care of.
•• Sedatives are administered to reduce agitation. Straining at stools should
be avoided and hence a good laxative is prescribed.
•• Intravascular volume depletion is common following SAH. Disturbances of
water and electrolytes occur in about one-third of patients with SAH. They
occur more commonly in critically ill patients.
•• Hyponatraemia and volume depletion correlate with poor prognosis.
•• In the past, hyponatraemia in patients with SAH was attributed to SIADH
and treated accordingly. It is now recognised that the more common cause
for hypovolaemia is cerebral salt wasting (CSW).
•• The mechanism of water and sodium depletion in CSW has been correlated
with disturbances in levels of atrial natriuretic peptide and C-type natriuretic
peptide, as well as direct neural effects on renal function.
•• Assessment of volume status by careful recording of input and output,
Na+ and Cl– balance, daily body weight recording, or laboratory tests such
as elevated haematocrit or BUN:creatine ratio help in planning therapy.
•• Hypovolaemia predisposes to high incidence of cerebral vasospasm.
Hence, patients with SAH should be hydrated well to maintain a central
venous pressure of about 12−14 mmHg. Crystalloids are infused at the rate
of 125 mL/hour to maintain the central venous pressure.
•• Arterial hypertension is common in SAH resulting from elevation of
catecholamines and rennin production due to hypothalamic disturbances.
•• The other reasons for hypertension include raised intracranial pressure,
agitation, seizure, pain or vomiting.
•• Rapid and steep reduction in blood pressure might be dangerous, resulting
in drop in cerebral perfusion in patients with vasospasm and raised
intracranial pressure leading to neurological complications.
•• Moderate hypertension in a patient with mean blood pressure less than
120 mmHg may be reactive and need not be corrected.
•• The initial approach should be to control pain and agitation which can
reduce blood pressure.
•• A mean pressure greater than 120 mmHg should be treated with the goal
of cautious reduction.
•• Randomised trials have not been performed evaluating the benefit-risk
relationship of antihypertensive therapy in the hyperacute phase of SAH
prior to surgical or endovascular therapy.
•• Anti-oedema therapy with 20% mannitol is instituted in the presence of
diffuse cerebral oedema following SAH.
•• An external ventricular drainage may be required in the presence of acute
symptomatic hydrocephalus, although there is a risk of rebleed following
sudden decompression of the ventricles.
•• The cornerstone in medical management of SAH includes triple H therapy
(hypertension, hypervolaemia and haemodilution) and calcium antagonists.
•• Triple H therapy has been shown to be effective in prevention and treatment
of cerebral vasospasm.
545
•• Nimodipine, a cerebroselective calcium channel blocker, has been found to

reduce the risk of poor outcome and secondary ischaemia after aneurysmal
SAH.
•• Routine practise presently is to prescribe prophylactic anticonvulsants to
patients with SAH.
•• Platelet aggregation has also been considered to play a causative role in
secondary brain ischaemia following SAH.
•• A Cochrane review of all randomised controlled trials of antiplatelet therapy
revealed a trend towards better outcome in patients treated with antiplatelet
agents, possibly due to a reduction in secondary ischaemia, although the
results were not statistically significant. However, antiplatelet agents could
also increase the risk of haemorrhagic complications.
•• Raised intracranial pressure following SAH presents with depression
in sensorium, and can occur due to various causes like intracerebral
haematoma, intraventricular haematoma, hydrocephalus, cerebral oedema
and mass effect secondary to cerebral ischaemia.
•• General treatment strategies for managing raised ICP include head-end
elevation, maintaing fluid balance, use of anti-oedema measures, correction
of hyponatraemia, prevention of hypoventilation and hypercarbia, treatment
of fever and agitation.
•• Specific measures include evacuation of intracerebral haematoma, external
ventricular drainage for intraventricular haematoma or hydrocepahlus.
•• Hydrocephalus following SAH can be classified according to its time of
appearance as:
–– Acute: <12 hours
–– Subacute: A few days after ictus and
–– Delayed: Weeks to years after SAH.
•• Acute hydrocephalus is an important cause of raised intracranial pressure
and coma.
•• Subacute hydrocephalus is a cause of gradual decline in sensorium, 7−10
days following SAH.
•• SAH disrupts brain integrity and function and results in multi-system
involvement including cardiovascular, respiratory, metabolic, haematological
and immunological dysfunction.
•• The various changes that can occur following SAH include:
–– Cardiovascular: Arterial hypertension, intravascular volume deple-
tion, congestive heart failure and decreased cardiac output and left
ventricular dysfunction. ECG reveals ST depression, T wave inversion
and QT prolongation, and arrhythmias. Creatine kinase-MB and tro-
ponin I levels are raised in serum.
–– Respiratory: Cardiogenic pulmonary oedema, acute lung injury, acute
respiratory distress syndrome (ARDS), neurogenic pulmonary oedema
(NPE), pneumonia and pulmonary embolism.
–– Metabolic: Hyponatraemia due to SIADH or cerebral salt wasting,
hypernatraemia and stress hyperglycaemia.
Prevention of Rebleed
•• Early treatment to obliterate the ruptured aneurysm either by surgical
clipping or endovascular coiling is the most important therapeutic strategy.
546
PERIMESENCEPHALIC SUBARACHNOID
HAEMORRHAGE
•• Perimesencephalic haemorrhage is defined as blood confined to the
cisterns around the midbrain, usually in the interpeduncular and prepontine
cisterns, sometimes in the quadrigeminal cisterns.
•• It is assumed to be due to rupture of veins; the basis being that, in these
patients, the perimesencephalic veins drain directly to the dural sinuses
instead of the vein of Galen.
•• Around 2.5−5% of these patients have aneurysms of the basilar or vertebral
artery.
•• Thus, perimesencephalic SAH needs to be investigated with digital sub or
high quality CT angiography.
•• Headache in these patients develops gradually in comparison to
aneurysmal SAH. Patients are usually conscious, occasionally confused.
•• Rebleeding is very rare, almost unknown in perimesencephalic SAH.
73
CHAPTER
General Principles of
Management of
Intracranial Aneurysms
Tewari Manoj Kumar  Mathuriya SN  Khandelwal N
INTRODUCTION
•• Intracranial aneurysms (IAs) affect 5–10% of the general population and
represent a major public health problem.
•• In the absence of trauma, intracranial aneurysm (IA) is the leading cause
of subarachnoid haemorrhage (SAH) and accounts for approximately 85%
of the cases.
•• Contributing to the disease are a number of well-established risk factors
such as sex, hypertension, smoking, alcohol, low body mass index and
drug use.
•• Recent studies suggest that, in addition to these, genetic factors also
contribute to the pathogenesis of IA.
•• Given the large number of familial cases and increased incidence with other
genetic diseases such as autosomal dominant polycystic kidney disease
(ADPKD), a genetic contribution to aneurysm formation and rupture has
long been speculated.
GENETICS
•• Recent advances in genetic disorders and vascular abnormalities have
revealed several alterations in genes and gene products involved in the
remodelling of the extracellular matrix (ECM).
•• Supporting this notion, the content and structure of collagen and elastin
(ELN), the predominant elements in the wall of the aneurysm, are signi-
ficantly altered.
•• The ECM-related proteins discussed below have been identified in genetic
disorders and could be related to IA formation.
•• These are ELN, elastase 2 (ELA), alpha-1-antitrypsin (AAT), collagen III
(COL3A1), endothelial nitric oxidase synthetase, polycystin (PKD1) and
fibrillin (FBNI).
•• Notable heritable connective tissue disorders which have been associated
with IAs include polycystic kidney disease, Ehlers-Danlos syndrome type IV,
Marfan’s syndrome, neurofibromatosis type I, pseudoxanthoma elasticum
(PXE) and AAT deficiency.
•• Several vascular disorders have been associated with AAT deficiency,
viz. arterial aneurysms, spontaneous arterial dissections and arterial
fibromuscular dysplasias.
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CLINICAL FEATURES OF RUPTURED

ANEURYSMS
•• The hallmark of SAH is sudden, usually severe headache in about 80% of
cases and 45% complain of brief loss of consciousness.
•• About 35% have nuchal rigidity.
•• Aneurysmal rupture can lead to sudden death in about 12–15% of cases.
•• A variety of other symptoms may develop before aneurysm rupture.
•• They depend on the site and size of the aneurysm and include hemiparesis,
dysphasia, extraocular muscle impairment, visual loss, visual field defect,
localised headache and seizures and, sometimes giant thrombosed
aneurysms may present as a mass lesion.
•• Prior to frank bleed, many patients experience warning symptoms, the
so-called “sentinel symptoms”. These are reported to occur in as high as
60–70%. These consist of headache, retrobulbar pain and nuchal pain.
•• Ruptured aneurysms at specific sites may produce distinct clinical features.
•• Anterior cerebral artery (ACA) aneurysm rupture may produce brief
weakness of the lower extremities bilaterally.
•• Middle cerebral artery (MCA) aneurysms may produce hemiparesis,
paraesthesias, hemianopsia and dysphasia.
•• Seizures occur more commonly with anterior circulation aneurysms and
more so with MCA aneurysms.
•• Third nerve palsy or unilateral retro-orbital pain suggests an aneurysm arising
at the internal carotid anterior-posterior communicating artery junction.
•• Third nerve involvement can also occur with aneurysms originating in the
superior cerebellar artery (SCA).
•• Carotico-ophthalmic aneurysms and superior hypophyseal aneurysms may
produce unilateral visual loss or even bilateral field defects.
•• Focal neurological deficits after SAH may be due to mass effect from giant
partially thrombosed aneurysms, vasospasm, seizures or haematomas in
an intracerebral or subdural location.
•• In about 25% of patients with SAH, there may be vitreous haemorrhage.
CLINICAL PRESENTATION OF
UNRUPTURED ANEURYSMS
•• Unruptured aneurysms may be discovered incidentally or present with
neurological symptoms.
•• Acute neurological symptoms include ischaemia (37%), headache (37%),
seizures (18%), and cranial neuropathies (12%).
•• Chronic neurological symptoms include headache (51%), visual deficits
(29%), weakness (11%) and facial pain (9%).
•• As expected, larger aneurysms tend to present with neurological symptoms
because the average aneurysm sizes for these three groups were 1.1 cm,
2.1 cm and 2.2 cm in maximum diameter, respectively.
•• In addition, symptomatic aneurysms tended to be located along the proximal
internal carotid artery (ICA) with diameters never smaller than 3 mm.
DIAGNOSIS
•• The diagnosis of SAH due to rupture of IA is made on the basis of clinical
suspicion corroborated with non-contrast computed tomography (CT)
scan findings.
Chapter 73 • General Principles of Management of Intracranial Aneurysms
549
•• At times, when the history is suggestive of SAH, but CT is inconclusive, a

lumbar puncture may be required.
•• But the mainstay of the diagnosis is CT angiography (CTA) which is
undertaken after plain CT points to a vessel from which the bleeding has
occurred.
•• Plain CT brain can most accurately predict the nature and location of the
underlying vascular lesion.
•• Clotted blood is characteristically seen as a high attenuation lesion in the
subarachnoid cisterns.
•• The length of time for which the high attenuation persists depends upon
the amount of blood in the subarachnoid space, with 90% positivity during
the first 5–7 days, 88% positivity within 5 days and 57% positivity up to
6–14 days after the bleed.
•• The location of SAH may give information about the probable aneurysm
site, such as:
–– Anterior interhemispheric fissure (IHF) blood suggests bleed from the
anterior communicating artery (ACom) aneurysm
–– Distal IHF suggests rupture of a distal ACA aneurysm
–– Unilateral Sylvian fissure blood suggests rupture of an MCA aneurysm
–– Blood in the suprasellar cisterns is indicative of an ICA aneurysm
–– Interpeduncular cistern bleed points to basilar top aneurysm
–– Prepontine + cerebellopontine angle cisterns blood suggests a basilar
trunk and vertebrobasilar aneurysm and isolated intra IV ventricular
bleed is suggestive of distal posterior inferior cerebellar artery (PICA)
aneurysm.
–– Frontal intracerebral haemorrhage (ICH) is seen in A1, A-Com, internal
carotid bifurcation and M1 aneurysms.
–– Temporal ICH is seen in MCA aneurysms.
–– Basilar top and postero-superiorly directed ACom aneurysm may
produce pure intraventricular haemorrhage (IVH) only.
Computed Tomography Angiography (CTA)

•• Spiral and multi-slice CT is used for three-dimensional (3D) pictures to
investigate the cause of SAH.
•• Multi-planar reformation is the method of choice at the beginning of the
evaluation to confirm the aneurysm and to create coronal, axial, sagittal,
or oblique sections, followed by maximum intensity projection (MIP), which
however has a limited utility in CTA due to the higher attenuation of the
skull compared with intracranial arteries.
•• Once the aneurysm is identified, the volume-rendered 3D images are used
for depiction of the position and spatial orientation of the aneurysm neck and
sac, characterisation of arterial branching patterns at the neck and depiction
of the relationship of the aneurysm to local and regional bone anatomy.
•• An accurate anatomical evaluation is useful for assessment of the suitability
of an endovascular approach for aneurysm treatment.
•• The average sensitivity of CTA for the detection of IAs is about 90%.
•• However, for aneurysms less than or equal to 3 mm diameter, sensitivity
is reduced to 61%, whereas the detection rate increases to 96% for
aneurysms with a larger size.
550
Four-dimensional Computed
Tomography Angiography
•• Four-dimensional computed tomography angiography (4D CTA) entails
multi-slice CTA with a retrospective electrocardiographic-gated (ECG-
gated) reconstruction algorithm by use of technology that was developed
initially to examine coronary arteries.
•• It is a novel technology that includes time dimension, which is repeated
within the cardiac cycle.
•• This is an important difference between 4D CTA and conventional cerebral
angiography.
•• The purpose of 4D CTA is to clarify the value of aneurysm wall pulsations
and actual haemodynamic behaviour on the diagnosis and treatment of
patients with aneurysm.
Magnetic Resonance Angiography (MRA)

•• MRA is often impractical in severely affected patients due to long
examination time, low spatial resolution compared to digital subtraction
angiography (DSA), high cost, sensitivity to motion artifacts and difficulty
in demonstrating vessels with low flow.
•• These limitations make intracranial MRA a preferred screening modality
only for specific groups at higher risk of harbouring an aneurysm than the
general population, e.g. diseases of connective tissue such as Ehlers-
Danlos type IV, ADPKD, fibro-muscular dysplasia, neurofibromatosis type
1 and AAT deficiency.
•• The MRA is also recommended in families with greater than or equal to 2
first-degree relatives with SAH.
•• Three basic MRA techniques are currently utilised:
1. Time-of-flight (TOF)
2. Phase-contrast (PC)
3. Gadolinium enhanced MRA.
Intra-arterial Digital Subtraction Angiography (IADSA)

•• Angiography is still required for pre-operative planning.
•• IADSA is the accepted diagnostic procedure of choice for the assessment
of IAs and for the pre-operative treatment planning of patients and after a
negative CTA or MRA examination in a patient with SAH.
•• A four-vessel IADSA is still the most sensitive tool to detect an IA and is
the gold standard.
•• This is ideally performed with selective injection of the ICAs and vertebral
arteries within 24 hours of the bleeding.
•• The DSA should include sufficient views including lateral, anteroposterior
or angled anteroposterior, oblique and basal, and an unsubtracted film
also is necessary.
•• Adequate demonstration of neck of the aneurysm is important for planning
aneurysm clipping, as well as in predicting the success of treatment with
the Guglielmi detachable coils, because total occlusion is more likely in
aneurysms whose neck is 4 mm or less.
•• The primary advantage of IADSA over other imaging modalities is the
high resolution.
551
•• The selective intra-arterial injection of iodinated contrast medium ensures

optimal enhancement of the intracranial arteries with superior resolution
compared with that of CTA or MRA.
•• Very small diameter vessels and perforators can be imaged only on IADSA.
LOCATION OF INTRACRANIAL ANEURYSMS

•• Aneurysms commonly arise at the bifurcations of major arteries and from
branching sites.
•• Most saccular aneurysms arise in the circle of Willis or the MCA bifurcation.
•• Approximately 86.5% of all IAs arise in the anterior (carotid) circulation and
about 10% of IAs arise in the vertebrobasilar circulation.
•• About 3.5% of IAs occur at miscellaneous locations like the SCA and the
anterior inferior cerebellar artery.
•• Common locations include the ACom (30%), the junction of the ICA and
the posterior communicating artery (PCom) (25%) and the MCA bifurcation
(20%).
•• The ICA bifurcation (7.5%) and the pericallosal/callosomarginal artery
junction account for the remainder (4%).
•• Around 7% arise from the basilar artery bifurcation, and the remaining
3% arise at the origin of the PICA where it comes off the vertebral artery.
•• Saccular aneurysms are uncommon in locations other than the sites
mentioned above.
•• Aneurysms that develop at distal sites in the intracranial circulation are
often caused by trauma or infection.
•• Non-traumatic distal aneurysms, particularly along the ACA, have a high
frequency of multiplicity and spontaneous haemorrhage.
AGE AND SEX DISTRIBUTION

•• Aneurysmal SAH commonly occurs in the age group of 40–60 years with
a peak incidence in the fifties.
•• This is two decades older when compared to SAH due to arteriovenous
malformations and one decade younger when compared with hypertensive
intracerebral haematoma.
•• It thus, occurs in the population at their most productive age.
•• The majority of epidemiological surveys have reported a higher incidence
of SAH in women than men. The reason for gender-related differences is
unclear.
MANAGEMENT OF ANEURYSMS
•• Patients with ruptured IAs should be treated as soon as possible after the
haemorrhage to prevent re-bleeding and to provide adequate medical
treatment of vasospasm.
•• Until recently, the standard method of treatment for IAs has been surgical
clipping, however during the last decade, the introduction of Guglielmi
detachable coils has completely revolutionised the management of patients
with IAs.
•• The endovascular treatment of cerebral aneurysms consists of filling the
aneurysm sac with soft platinum coils through a microcatheter which is
usually placed at the neck of the aneurysm.
552
•• The choice of treatment depends upon the anatomical characteristics of the

aneurysm, mainly the size, location, neck width and the clinical condition
of the patient.
•• The dome:neck ratio should also be measured, since it significantly affects
the ability to completely coil the aneurysm.
•• Patients with poor Hunt and Hess grades, namely 4 and 5, are generally
poor neurosurgical candidates and can benefit from endovascular
treatment.
•• Patients with a basilar top aneurysm are good candidates for endovascular
coiling, as surgery is limited by the small working space at a depth and the
presence of perforating arteries to the brainstem.
•• MCA aneurysms are less suitable for coiling, as the secondary branches
are close to the neck and the neck is usually wide.
•• Although the results of endovascular treatment of small aneurysms (< 10 mm)
and aneurysms with small necks are promising, the rate of success is less in
aneurysms with larger diameters and wider necks.
•• One of the major disadvantages of coiling is the chance of partial recanalisation
of the aneurysm even in the first few months after a successful procedure due
to coil compaction.
•• Different options for aneurysm treatment have been recently proposed,
among which combined treatment of large-neck aneurysms with intracranial
dedicated stents and coils, balloon-assisted coiling (the so-called
remodelling technique) and bioactive coils which promote complete neck
endothelisation.
•• The therapeutic management of SAH has considerably changed since the
publication of the International Subarachnoid Aneurysm Trial study, the
only randomised trial which compared endovascular coiling with surgical
clipping in ruptured aneurysms.
•• The study shows that endovascular intervention with detachable
platinum coils in patients with ruptured IAs can improve the chances of
independent survival compared with neurosurgical clipping of the neck
of the aneurysm.
•• The results indicate that embolisation with coils is a reasonably safe
procedure with a low complication rate, not only in patients with a ruptured
aneurysm, but also in patients with an unruptured aneurysm and in patients
with a basilar bifurcation aneurysm.
•• Introduction of flow diverters is a useful addition to existing endovascular
therapy.
•• Although the natural history of ruptured aneurysm has been well defined,
there is still controversy regarding the natural history of unruptured
aneurysms, particularly those aneurysms which are less than 10 mm in size.
Intracranial Aneurysms in Children

•• The commonest site of an aneurysm in paediatric patients is the ICA
bifurcation followed by the MCA bifurcation and the vertebrobasilar system.
•• Large and giant aneurysms are commoner in children as compared to
adults.
•• The reported incidence is 20–45%.
•• The incidence of multiple aneurysms is less in children as compared to
adults.
•• The aetiology and pathogenesis of paediatric aneurysms are not clear.
553
•• Aneurysms in children are a result of expression of various vessel

dysfunctions, which result in transient or permanent failure to repair a
partial insult. In addition to congenital conditions (Marfan’s syndrome, Ehler-
Danlos syndrome, polycystic kidney disease, PXE, sickle-cell anaemia,
tuberous sclerosis), infection (bacterial endocarditis) and trauma (closed
and penetrating head injury, irradiation) also contribute to the aetiology of
aneurysms in paediatric patients.
•• The presenting features of IAs in the paediatric population are different
from those in adults.
•• The incidence of SAH in previous reports has varied from 35 to 100%.
•• Besides SAH, the presentation in this group included focal neurological
symptoms from mass effect such as proptosis, diplopia, hemiparesis,
chronic or intermittent headache, dizziness and so on.
Treatment
•• Just as for aneurysms in adults, the treatment for paediatric IAs has
undergone significant evolution in recent years.
•• At present, multi-modal treatment strategies are widely used as a standard
approach and have, therefore, resulted in significant improvement in patient
outcomes.
•• The choice of treatment method for a given aneurysm is made by a multi-
disciplinary team of neurosurgeons and interventional neuroradiologists.
•• Surgical clipping or endovascular treatment can be decided according to
site and size of the aneurysm.
•• Children withstand surgery better than adults due to greater brain functional
capacity and better vascular status.
•• The endovascular approach is preferred whenever possible technically, and
is less dependent on the patient’s clinical situation because the majority
of aneurysms in the paediatric population are either large or giant and/or
in the posterior circulation.
ANEURYSMS IN THE EIGHTH AND

NINTH DECADE
•• Elderly patients with aneurysmal SAH account for up to 40% of all patients
treated conservatively and surgically.
•• The percentage of elderly patients undergoing surgical treatment varied
from 7 to 30% of all aneurysmal SAH patients.
•• Advanced age is one of the recognised risk factors for poor outcome in
aneurysmal SAH patients.
•• The important predictors of outcome of patients in the eighth decade of
life were age, clinical pre-operative grade and pre-operative CT findings.
•• By contrast, in the ninth decade, clinical pre-operative grade and pre-
operative CT findings, but not age, were significant factors in the prognosis.
•• There is controversy whether poor grade patients be treated conservatively
or surgically, but recent studies show that even poor pre-operative grade
patients made a good recovery indicating that results of conservative
management can be catastrophic.
•• The site and size of aneurysms do not have much bearing on the outcome
in the elderly.
•• Other important factors in addition to clinical grade are associated
comorbidities, Fisher grade, associated ICH/IVH, pupillary status and the
554
FUSIFORM ANEURYSM
•• Fusiform aneurysm (FA) is defined as a circumferential arterial dilatation
resulting from pathological involvement of the entire artery.
•• All aneurysms exhibit a spindle shape when viewed externally.
•• Conceptually there is still confusion as to the aetiological, clinical and
radiological features of FAs.
•• Many investigators have applied the term “atherosclerotic” as the cause
of FAs.
•• In fact, advanced atherosclerotic arteries have a slightly fusiform
appearance.
•• However, the classic dissecting aneurysm also has a fusiform appearance.
•• The age and sex distribution of patients with FAs differ from those with
saccular aneurysms.
•• The mean age of patients is 45.1 years and the male:female ratio is 1.4:1.
•• The clinical features of FAs are categorised morphologically.
•• They can progress from a small focal dilatation or vessel narrowing to
a relatively thick-walled, tortuous dilatation and elongation of the artery.
•• FAs can be incidental or asymptomatic, discovered during work up for
unrelated symptoms.
•• They can present as a non-specific headache without haemorrhage or
other neurological signs or symptoms, as ischaemia, transient ischaemic
attack or complete stroke, as mass effect with or without seizure, or as
haemorrhage, subarachnoid or intraparenchymal.
•• Patients with small, large and giant aneurysms with focal dilatations of
their lumen had SAH rates of 80%, 62% and 23%, respectively, whereas
ischaemic symptoms, such as transient ischaemic attack or complete
stroke, were the presenting feature in 31%.
•• Haemorrhage is the most common presentation in patients with small
lesions with focal dilatation, whereas ischaemic symptoms are the most
common presentation of patients with stenosis or occluded vessels.
•• FA of the vertebral artery can present with hemifacial spasm due to mass
effect.
•• About 75% of FAs are seen in the anterior circulation and the rest in the
posterior circulation.
•• The MCA is the most common site for spontaneous FAs (75%), followed
by ICA and ACA.
•• Of the MCA, FAs 69% originate proximal to the MCA genu (M1 segment),
21% at the insular (M2) segment and 10% at distal (M3 or M4) branches.
•• Various aetiological factors for FAs have been proposed, including
atherosclerosis, vessel dissection and association with other diseases
such as Von Recklinghausen's disease, fibromuscular dysplasia, systemic
lupus erythematosus and various collagen-associated vascular diseases.
Pathogenesis
•• The initial event in the formation of atherosclerotic FAs is thought to be
lipid deposition in and beneath the intima.
•• This disrupts the internal elastic membrane and infiltrates the muscular wall.
•• Intramural haemorrhage and rupture of the atheroma leads to transmural
extension of the thrombus and thickens the intima to create the fusiform
shape of the aneurysm.
555
•• Rupture of the vasa vasorum by shear forces or by stress on the luminal

wall then causes intimal tear and fracture of the internal elastic membrane.
•• This permits bleeding into the arterial wall to form a haematoma.
•• If the dissection occurs between the internal elastic lamina and the
media, the vessel lumen becomes narrow or occluded with an intramural
haematoma and the patients present with ischaemic symptoms.
•• If dissection occurs between the media and adventitia, the aneurysm can
rupture and the patient will present with SAH or ICH.
Treatment of Fusiform Aneurysms

•• It depends on the presence and type of symptoms, the lesion size and
location, and the risk of any accompanying intervention.
•• In general the recommendation of conservative treatment for non-
symptomatic dissecting aneurysms.
•• However, clipping using encircling clips for focally dilated dissecting
aneurysms if they are found during surgery for another symptomatic
aneurysm, and aggressive surgical treatment for FAs which are not caused
by dissection, due to the possibility that they will progress.
•• Conservative treatment for patients with stenotic or occlusive lesions and
acute ischaemic symptoms.
•• Direct “aneurysm only” clip application was associated with a high rate
of re-growth of the lesion or re-bleeding caused by preserving flow in
the normal half of the affected vessel, despite excellent intra-operative
aneurysm obliteration.
•• Therefore, many authors recommend proximal occlusion or trapping with
or without resection combined with end-to-end anastomosis or external
carotid-internal carotid (EC-IC) bypass, but there is no consensus on this
issue.
•• Many authors recommend occlusion of the aneurysm and parent vessel
by endovascular methods.
MANAGEMENT OF RUPTURED ANEURYSMS

•• There is no controversy that ruptured aneurysms need to be tackled
either surgically or by endovascular treatment or by combined treatment,
but the important consideration is the status of the patient at the time of
presentation.
•• Patients who are in good Hunt and Hess grade/World Federation of
Neurosurgeons Scale are treated at the earliest while poor grade patients
are initially managed conservatively and once they improve then they are
taken up for definitive treatment.
•• Once detected or suspected to harbour an aneurysmal bleed the patient is
put on bed rest, analgesics are administered and the patient is adequately
hydrated.
•• Routine haematological investigations including coagulation profile and
biochemical investigations are done to evaluate the patient for CTA and
surgery.
•• A CTA is asked for to see the location of the ruptured aneurysm, its
relationship with the parent and other vessels, and configuration.
•• In the majority of cases it suffices, but in some cases an IADSA needs to
be done in addition.
556
•• Transcranial Doppler (TCD) sonography is performed to evaluate the flow

velocities in the intracranial vessels, which not only serves as a baseline
value, but also gives an idea about vasospasm.
Surgical Principles
•• Almost all anterior circulation aneurysms, the majority of basilar top and
P1-P2 junction aneurysms can be operated upon by the standard pterional
craniotomy.
•• At times some modification to it may be necessary as is required in distal
MCA and A2 segment aneurysms.
•• A fronto-orbito-zygomatico-temporal craniotomy may be required for some
basilar top aneurysms.
TRAUMATIC INTRACRANIAL ANEURYSMS

•• TICAs are commonly seen in young adults in their twenties.
•• This group is more vulnerable to risk of blunt and penetrating trauma.
•• There is a male predominance.
•• In children TICA can occur with less severe trauma and shaken-baby
syndrome can lead to TICA.
•• TICAs can be classified in numerous ways either on the basis of aetiology
into blunt trauma or penetrating injuries, or iatrogenic injuries.
•• Penetrating injuries are further subclassified into secondary to missile
injuries or secondary to stab injuries.
•• Alternatively they can be classified on the basis of anatomy into
extracerebral (middle meningeal artery) or intracerebral groups.
•• The latter is again subdivided into two groups as proximal to the circle
of Willis which includes ICA supraclinoid and infraclinoid segments and
vertebrobasilar artery and distal to the circle of Willis which includes
subcortical and cortical branches.
Pathogenesis
•• The mechanism of TICA formation is different for different aetiologies.
•• While a shearing injury of the vessel or entrapment of a cortical branch
within a widened linear skull fracture or tearing process which occurs while
a freely mobile vessel is rubbed against a fairly hard edge explains TICA
formation in blunt trauma; a low speed bullet injuring the vessel wall explains
a TICA following a missile injury.
•• Pathologically TICAs can be classified into three groups:
1. True aneurysms (resulting from partial laceration of the vessel wall,
i.e. injury to the intima or adventitia or both)
2. Pseudo or false aneurysms
3. Mixed aneurysms.
•• In a pseudo-aneurysm there is complete disruption of the arterial wall and
subsequent haematoma formation which undergoes fibrous reorganisation
enclosing the lumen and forms the wall of the aneurysm.
•• A mixed aneurysm occurs when a true aneurysm ruptures forming a false
aneurysm attached to it.
•• TICAs are usually seen on the secondary branches, while saccular
aneurysms occur on the large blood vessels at the base of the brain or
major branches.
557
•• TICAs are located along the course of the artery often near the sharp
edges, while saccular aneurysms are at the bifurcation of major vessels.
•• A patient with TICA gives a history of trauma which could be blunt or
penetrating.
•• Blunt trauma is usually a major trauma in adults and is often a minor
trauma in children.
•• The patient may present either awake or may have any degree of altered
sensorium.
•• Penetrating injury through the thin orbital roof of a child is known to result
in TICA.
•• A person who is awake usually complains of headache.
•• Cranial CT shows haemorrhage which could be either intraparenchymal,
intraventricular, subarchnoid or subdural. Initial management focuses on
diagnosis and management of the presenting head injury.
•• A triad of unilateral blindness, cranial base fractures and recurrent epistaxis
should lead to suspicion of an ICA injury originating at the base of the brain.
•• In about 10–20% of the cases the aneurysm may be asymptomatic.
•• In infants a growing aneurysm can lead to a growing skull fracture.
•• TICAs can be diagnosed by delayed CTA or MRA.
•• Angiographic features suggestive of TICA include delayed filling and/or
excessive delay in emptying of the sac, lack of relationship with arterial
branching, irregular appearance and absence of a neck.
•• Endovascular procedures have their own associated morbidity.
•• A high neck:fundus ratio may make an endovascular procedure difficult.
•• Placement of a balloon or coil directly into a pseudo-aneurysm may lead
to massive haemorrhage.
•• In such situations endovascular trapping or occlusion of the parent artery
with detachable balloon or endovascular stent placement appears to be
a safe procedure.
POST-OPERATIVE MANAGEMENT OF
INTRACRANIAL ANEURYSMS
•• In the post-operative period, vasospasm and development of hydrocephalus
are the main causes of neurological worsening in addition to other causes
such as electrolyte imbalance.
•• Post-operatively patients are assessed neurologically, and with TCD and
CT scan.
•• Patients at risk of developing vasospasm are monitored closely in the
intensive care unit.
•• All patients are given nimodipine, starting within 4 days of SAH and
continued for 21 days regardless of admission grade. The usual dose for
an adult is 60 mg 4th hourly.
•• There is controversy regarding this and many surgeons do not give
nimodipine.
•• Neurological status is watched carefully and TCD studies are done to
detect vasospasm early.
•• Rising values of TCD velocities guide the timing of more aggressive therapy.
558
•• The mainstay of medical treatment is triple-H therapy where volume

expansion is achieved with packed blood cells, and colloids or hypertonic
saline solution.
•• A central venous pressure of greater than 8 mmHg or pulmonary wedge
pressure greater than 14 mmHg is usually enough to dilute the haematocrit
to less than 35%.
•• An adequate level of haemoglobin should also be maintained.
•• Endovascular therapies for vasospasm are used when either aggressive
medical therapy fails or when the TCD velocities rise, or when there are
several risk factors for vasospasm.
•• Transluminal balloon angioplasty is used to mechanically dilate the segment
of the large arteries such as ICA, MCA and ACA A1 segment.
•• The effect of angioplasty lasts for 7 days which corresponds to the duration
of vasospasm.
•• Smaller vessels, such as the A2 segment, are not amenable to angioplasty
and are instead treated with intra-arterial papaverine or verapamil.
•• Hydrocephalus is a common complication of SAH due to ACom aneurysms,
especially when there is a significant intraventricular bleed. More than
half of the patients may require either external ventricular drainage or a
permanent ventriculoperitoneal shunt.
•• Fenestration of the lamina terminalis at the time of surgery appears to
reduce the need for ventriculoperitoneal shunting later on.
•• Patients with ACom aneurysms are susceptible to electrolyte abnormalities
of which hyponatraemia is frequently seen (incidence 18%) lasting 1–5 days
after surgery.
•• This is treated with normal saline infusion, supplemental salt intake and if
need be with hypertonic saline infusion.
74
CHAPTER Vasospasm and
Its Management
Anil Pande  Ravi Ramamurthi
INTRODUCTION
•• The term “vasospasm” is used to denote an abnormal, inappropriate or
unnatural constriction of the vascular lumen.
•• Cerebral vasospasm results in a decrease in cerebral blood flow,
disturbance in autoregulation and delayed cerebral ischaemia (DCI).
•• It generally involves medium and large sized cerebral arteries and usually
occurs between the 4th day and 14th day after subarachnoid haemorrhage
(SAH).
•• It is maximal during day 6−8th and spontaneously resolves by the 12−14th
day and rarely may be sustained over 2 weeks.
•• Around 30−70% of aneurysmal SAH patients will develop cerebral
angiographic vasospasm with delayed neurological defects manifesting
in 30−50% of patients.
•• Vasospasm causes death and disability in 12−17% of SAH patients and is
the most important factor in the eventual outcome.
•• Vasospasm can also occur following traumatic brain injury with or without
SAH.
•• It has been seen following cranial surgery, lumbar puncture, brain tumour
bleed, hypothalamic injury and following cranial infections.
•• Arterial narrowing has been seen in migraine and in non-infectious vasculitis.
•• Vasospasm accounts for 3−7% of all strokes and carries a mortality rate
as high as 40% and is more serious than re-bleeding as a cause of death
and disability due to cerebral ischaemia and infarction.
•• Delayed cerebral vasospasm has traditionally been recognised as the most
treatable cause of morbidity and mortality from SAH.
•• The physiological and cellular events of acute brain injury, which occur
during the first 24−72 hours following aneurysm rupture are also contributing
factors along with delayed cerebral vasospasm to the final patient outcome.
INCIDENCE
•• The incidence of vasospasm following aneurysmal SAH varies from
20% to 40% in different large series.
•• The incidence and time course of symptomatic vasospasm parallels to that
of arterial vasospasm.
•• However, although 40−70% of patients have evidence of arterial narrowing
confirmed by angiography (Angiographic vasospasm) or Doppler
ultrasound, only 20−30% develop the clinical syndrome (Symptomatic or
clinical vasospasm).
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CHRONOLOGY
•• Angiographic spasm is usually seen on cerebral angiography 7 days after
the SAH (it may be seen as early as 3 days after the haemorrhage), but is
not seen angiographically before the 3rd day.
•• If seen earlier after SAH it is due to an earlier episode of bleed.
•• The vasospasm is maximal during 7−8 days (4−14 range) following bleed
and usually subsides in 2 or 3 weeks.
•• Brawley et al. demonstrated a biphasic response of cerebral vasospasm
in experimental SAH. The acute phase starts within minutes and lasts up
to 1 hour. The chronic phase begins 4−24 hours after the bleed.
•• Three phases in the evolution of chronic vasospasm were proposed by
Kapp et al. (1) an initial muscular contraction; (2) secondary injury to the
arterial wall due to injury to the internal elastic lamina and (3) the further
cascade of repair.
•• Suzuki recognised that early spasm is induced by mechanical stimulation
and serotonin, and the second phase by release of oxyhaemoglobin from
haemolysis of the clot.
•• Oxyhaemoglobin is maximally released on the 7th day and then it gets
converted to methaemoglobin which disintegrates into haeme and globulin
which get absorbed by the 15th day.
•• Thus, the onset of vasospasm and its resolution correspond to the time
taken for the lysis of erythrocytes and the final clearance of the breakdown
products from the subarachnoid CSF spaces.
Immediate or Acute Vasospasm

•• The role of this sudden spasm may be protective for arresting the bleed.
•• The oscillating pattern of regional cerebral blood flow (rCBF) in the
period of early recovery after SAH resembles the pattern of synchronised
vasomotion.
Early Spasm
•• It is the spasm seen after 25−30 minutes after SAH.
•• Early vasospasm, which is defined as arterial narrowing seen on diagnostic
angiography within the first 48 hours of aneurysmal rupture, is a rarely
reported and poorly defined phenomenon in patients with SAH.
•• This early spasm, seen in animal experiments, is not often seen perhaps
because imaging is rarely done immediately after the rupture of the
aneurysm in clinical setting.
Late Vasospasm
•• This is the spasm which appears on day 3−14 and occasionally lasts for
2−3 weeks.
•• Rarely vasospasm may be seen after 2 weeks of SAH.
RISK FACTORS FOR DEVELOPING

VASOSPASM
•• Several factors including a large volume of blood in the subarachnoid
space as seen on CT, an initial loss of consciousness, poor clinical grade
of SAH (poor neurological condition), pre-existing hypertension, basilar
artery aneurysms, an anatomically incomplete circle of Willis and history
Chapter 74 • Vasospasm and Its Management
561
of smoking. Other factors like age less than 50 years, hyperglycaemia, the
duration of unconsciousness after SAH, the plasma level of brain natriuretic
peptide (BNP), have been suggested as predictors for the development of
cerebral vasospasm after SAH.
SITE OF OCCURRENCE
•• Vasospasm occurs only in arteries and is not seen in smaller arterioles or
capillaries or veins because arteries have a well developed circumferential
layer of smooth muscle, the tunica media.
•• The perivascular sympathetic plexus is well developed and these
sympathetic nerves arise in the superior cervical sympathetic ganglion.
•• The middle cerebral artery is most frequently associated with vasospasm
and this has been attributed to haematomas in the Sylvian fissure being in
close proximity of the vessel.
•• Bilateral spasm occurs with anterior communicating aneurysms and other
aneurysms that are closer to the mid-sagittal line.
•• In multiple aneurysms the spasm may be used to localise the site of the
ruptured aneurysm.
•• Internal carotid aneurysms are associated with wide spread and diffuse
spasm which can extend to the opposite side.
CLASSIFICATION AND
GRADING OF VASOSPASM
•• Vessel narrowing due to atherosclerosis or an arteritic process has to be
differentiated from vasospasm.
•• Congenital hypoplasia of vessels must be borne in mind and usually is
easily differentiated from vasospasm.
•• With hypoplasia the curvature of the internal carotid artery (ICA) and the
contralateral A1 segment tends to be large.
•• Cerebral vasospasm can be classified variously according to location,
severity and symptomatology.
•• One classification divides vasospasm into three types, namely—
‘subangiographic’, ‘angiographic’ and ‘clinical’ vasospasm.
1. Subangiographic vasospasm is the type that affects small caliber ves-
sels and is not seen on standard cerebral angiography. Clinical findings,
cerebral blood flow studies and perfusion imaging pick up this subtype.
2. Angiographic vasospasm is vasospasm as seen on cerebral angiog-
raphy. Many patients with significant narrowing may be asymptomatic.
In vasospasm due to aneurysmal SAH the vasospastic arteries tend to
be close to the site of the aneurysm rupture. Distant arteries can also
be affected in a “diffuse” or “generalised” manner.
3. Clinical vasospasm is the type where the patient develops neurological
signs and symptoms and these may not correlate with the radiological
findings.
•• On conventional, angiography vasospasm can also be classified as ‘local’,
‘diffuse’ or ‘segmental’.
1. Local—when the spasm is limited to one vessel.
2. Segmental vasospasm affects only a part of the vessel.
3. Extensive or generalised type is when there is spasm of at least two
major vessels.
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•• Sano and Saito classified vasospasm into three types: Type 1—extensive
diffuse; Type 2—multi-segmental and Type 3—local. Type 1 was
prognostically the worst, Type 3 was good and Type 2 was located between
these two types.
Classification According to Size of Vessel

Small Vessel Spasm
•• There is impairment of vasodilatory capacity of small vessels distal to the
vasospastic basal arteries after SAH and this concept of small vessel spasm
is based on haemodynamic and histological evidence.
Large Vessel Spasm
•• Large vessels are the common site of spasm and may include the carotid,
vertebral, middle cerebral arteries (MCA), anterior cerebral arteries (ACA),
posterior cerebral arteries (PCA) and other cranial arteries.
Grading According to Severity

•• As the diameter of arteries is reduced, the velocity of blood going through
them increases.
•• A progressive increase in this velocity as observed by transcranial Doppler
indicates the severity of vasospasm.
•• Vasospasm has been graded as moderate when the velocity is 120−200
cm/sec and severe when the velocity exceeds 200 cm/sec.
•• Vasospasm according to its severity is usually classified into three grades:
Grade I: The vessel still has 50% of luminal flow.
Grade II: There is more than 50% of reduction of the lumen.
Grade III: The vessels are barely visible on angiography.
Fisher Grading System

•• Patients were grouped as low risk (Grades I and II) and high-risk (Grades
III and IV) for developing vasospasm.
•• Fisher grade correlated with symptomatic vasospasm in only half the
patients and they concluded that a new predictive CT grading scale for
vasospasm may be necessary.
AETIOPATHOGENESIS OF VASOSPASM
•• Pathophysiology of cerebral vasospasm is complex and poorly understood
and that the ischaemia and inflammation secondary to SAH affects smaller
vessels differently than larger ones.
•• Cerebral vasospasm and early brain injury (EBI) are among other causes
of subsequent morbidity and mortality.
•• The distribution of blood in the subarachnoid space, elevation of intracranial
pressure, reduced cerebral perfusion and cerebral blood flow trigger the
acute injury cascade leading to microvascular injury, plugging of vessels
and release of vasoactive substances by platelet aggregates, alterations
in the nitric oxide (NO) and nitric oxide synthase (NOS) pathways and
lipid peroxidation.
BIOLOGY OF CEREBRAL BLOOD VESSELS

•• The vasodilation is primarily mediated by NO and the vasoconstriction by
endothelin.
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•• Peroxidative membrane damage in the arterial smooth muscle cell leads

to prolonged arterial contraction that occurs during vasospasm (Fig. 1).
•• Genetic and molecular changes in the brain, the vascular endothelium
and the vascular smooth muscle cells play an important role in the
pathophysiology of vasospasm induced by SAH (Fig. 2).
•• The SAH induces activation of immediate early genes and expression of
stress proteins and heat shock proteins such as HSP70.
•• Haeme present after SAH is metabolised by Haeme oxygenase to biliverdin
and carbon monoxide.
•• The SAH induces haeme oxygenase-1 in the glia without affecting its
isoform—haeme oxygenase-2.
•• Haemolysate-induced haeme oxygenase-1 and HSP70 expression may
be used as markers for cell damage in the infarcted brain associated with
SAH and vasospasm.
•• The pathogenesis of delayed ischaemic neurological deficits (DINDs) after
SAH has been related to products of haemolysis of the subarachnoid blood.
•• Fractionated plasma and white blood cells do not cause vasospasm, but
even the washed erythrocytes can cause vasospasm.
Fig. 1: Physiology of vasospasm showing the changes seen in the vessel
wall following damage
Fig. 2: Pathogenesis of vasospasm

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•• The breakdown of the erythrocyte is an important key event and the rate
of dissolution determines the period or duration of vasospasm.
•• Vasospasm can be ameliorated by clot removal or reduction of its volume
within 48 hours by surgery or by intra-cisternal t-PA and drainage.
•• Oxyhaemoglobin is released from the 3rd day in incubated mixtures of
blood and CSF and reaches peak levels after 7 days.
•• This oxyhaemoglobin, derived from lysis of the red blood cells in the
subarachnoid space, has been implicated in several cascades causing
vasospasm.
SYMPATHETIC PLEXUS
•• The cerebral vessels, especially the pial vessels, are densely innervated
by noradrenergic sympathetic nerves that arise in the superior cervical
sympathetic ganglia and enter the intracranial cavity along the walls of
the carotid artery.
•• These cause constriction of the vessels and the interruption or temporary
blockage of these causes relaxation and dilatation.
•• The spinal arteries are also innervated by several systems that contribute
to the control of spinal cord blood flow.
•• The sensory fibres of the upper cervical nerves have a vasodilatory effect
on the anterior spinal arteries (ASA).
•• The SAH causes vasospasm by various neurochemical mechanisms.
•• Suzuki et al. were early proponents of sympathectomy for vasospasm;
many surgeons strip off the sympathetic plexus from the spastic vessels
during surgery.
•• Using minimally invasive techniques the superior cervical sympathetic
ganglion can be blocked to relieve spasm.
Role of Nitric Oxide in Vasospasm

•• Cerebrovascular tone is regulated by a dynamic balance of relaxing and
contracting factors.
•• The reduction in the level of NO is a known mechanism of delayed
vasospasm after SAH.
•• Evidence for a causative role for NO includes the disappearance of
NOS from the adventitia of vessels in spasm, the destruction of NO by
haemoglobin released from the clot into the subarachnoid space, and
reversal of vasospasm by intracarotid NO.
•• Loss of the endothelium-derived relaxing factor—NO in the presence
of oxyhaemoglobin and overproduction of endothelin-1 stimulated by
oxyhaemoglobin have been postulated as causes of delayed cerebral
vasospasm after SAH.
APOPTOSIS AND VASOSPASM

•• Apoptosis has been implicated in pathogenesis of aneurysmal SAH
vasospasm.
•• Following SAH causing vasospasm and resultant ischaemia, apoptosis
occurs in the hippocampus, BBB and the vasculature, along with necrosis.
•• Several apoptotic pathways are believed to be involved in SAH, including
the death receptor pathway, caspase-dependent and caspase-independent
pathways, and the mitochondrial pathway.
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EARLY BRAIN INJURY

•• Brain injury after SAH is a biphasic event with an acute ischaemic insult
at the time of the initial bleed and secondary events such as cerebral
vasospasm 3−7 days later.
•• The physiological and cellular events of EBI make significant contributions
to patient outcomes and may even be a more significant factor than delayed
cerebral vasospasm.
•• A number of pathways have been recognised as having a role in the
aetiology of EBI.
•• Cerebral vasospasm and EBI after SAH are due to a combination of
physiologic insults to the brain, resulting in global ischaemia, BBB
breakdown, brain oedema and cellular death signalling.
CLINICAL FEATURES OF VASOSPASM

•• Symptomatic vasospasm is the clinical syndrome of cerebral ischaemia
associated with angiographically documented narrowing of a major cerebral
territory.
•• Hemiparesis, hemihyperaesthesia, dysphasia, paraparesis, impaired
sensorium, headache, low-grade fever and meningismus are the clinical
features seen.
•• Progressive impairment in level of consciousness or increase in focal
neurologic deficit occurring after four days of an episode of SAH should prompt
investigation to rule out vasospasm and also other causes of neurological
deterioration like electrolyte disturbance (hyponatraemia), infection (meningitis
and sepsis), hydrocephalus and seizures (non-convulsive status).
•• Patients can be asymptomatic despite angiographic vasospasm.
•• Diffuse vasospasm may present with progressive deterioration in level of
consciousness. Meningismus is also seen.
•• The Hunt and Hess grade on admission correlates with risk of developing
vasospasm.
INVESTIGATIONS
•• A haemogram, serum electrolytes, chest X-ray, USG abdomen, renal
function, liver functions and a complete coagulation profile are done.
•• Angiography still remains the main modality of investigating and treating
vasospasm.
•• Investigations to measure cerebral perfusion include cerebral blood flow
studies, positron emission tomography (PET), single-photon emission
computed tomography (SPECT), xenon CT and TCD among others.
Cerebral Blood Flow Studies

•• A variety of cerebral blood flow studies are in clinical use. These use
radiolabelled H2O, CO and O2 with very short half-lives for measurement
of parameters like rCBF, cerebral metabolic rate of oxygen (CMRO2) and
oxygen extraction factor (OEF).
•• The extent and degree of ischaemia, penumbra, oligaemia, hyperperfusion
and normal haemodynamics are investigated.
•• In patients with vasospasm leading to ischaemic insult the regional oxygen
extraction factor (rOEF) is elevated and in patients with a completed stroke
the rOEF is normal.
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Electroencephalography
•• Currently electroencephalography (EEG) is not commonly used, but a
decline in the per cent of Alpha waves (6−14 Hz) predicts the onset of
vasospasm and this is more sensitive than both angiography and TCD.
•• A decline of EEG power or its amplitude was also a sensitive pointer to
vasospasm development.
Transcranial Doppler
•• Transcranial Doppler (TCD) uses the Doppler effect principle.
•• Ultrasound signals are reflected off moving objects (RBCs in case of blood)
and the frequency of the reflected signal changes in direct proportion to
the velocity of the moving object.
•• Low frequencies, 1−2 MHz, reduce the attenuation of the ultrasound wave
caused by bone.
•• It is now an established method for diagnosing haemodynamically
significant vasospasm in major intracranial arteries.
•• It is safe, inexpensive and readily available.
•• It is a cost effective, portable, non-invasive test that can be repeated as
often as necessary.
•• There are four acoustic windows: (1) transtemporal; (2) transorbital; (3)
suboccipital and (4) retromandibular.
Angiography
•• Angiography is still the main modality of investigation and offers the combined
advantage of providing an opportunity for therapy, if necessary, in the form of
mechanical (balloon angioplasty) and pharmacological angioplasty.
•• Conventional four-vessel angiography is usually performed using the
transfemoral route using Seldinger’s technique. Arterial spasm is seen as
concentric narrowing of vessels, and this must be differentiated from other
causes of arterial narrowing such as congenital arterial hypoplasia, pressure
effect of a haematoma, hypertensive arteriosclerosis and narrowing due to
increased intracranial pressure.
•• The risk of vasospasm due to angiography is 1% and there is a 0.5−1%
risk of an adverse vascular event.
•• Yamakami et al. classified angiographic findings into the following five
types: (1) diffuse, (2) peripheral, (3) proximal-severe, (4) proximal-mild
and (5) no spasm.
•• The computerised tomography (CT) scan is the preliminary investigation
after a thunderclap headache and can help in studying various causes of
vasospasm.
•• When delayed neurological effects due to vasospasm and resultant
infarction or haemorrhage appear, it is the primary investigation for guiding
treatment.
Computerised Tomography-Angiography
•• CT-angiography is a non-invasive and cost-effective investigation and is
replacing conventional angiography.
567
•• Rapid technological advances and latest generation scanners provide better

quality images and can be considered an adequate stand alone modality
of investigation for detection of vasospasm and its causative pathologies.
•• Multislice CTA can detect angiographic vasospasm after SAH with accuracy
similar to that of DSA. It is highly sensitive, specific and accurate in detecting
mild and moderate cerebral vasospasm.
•• It is less accurate for detecting abscence of vasospasm and marked
vasospasm. The limitation is its reduced reliability when more distal and
intermediate degrees of spasm are encountered.
Single-Photon Emission Computed Tomography

•• The single-photon emission computed tomography (SPECT) uses CT with
radioisotopes like inhaled intravenous xenon-133 or intravenous technetium
99-HM-PAO (Hexamethyl-propyleneamine oxime) to image topographically
the blood flow in the superficial and deep regions of the cerebrum.
•• The SPECT should be considered as the first test for the detection of
clinically suspected vasospasm and may obviate the need for invasive
studies before the onset of treatment.
•• The SPECT scan shows hypoperfusion in regions with angiographic
vasospasm.
•• The SPECT cannot differentiate between infarcted and ischaemic regions
and can miss a bilateral hypoperfusion state as it compares one hemisphere
with another to detect hypoperfusion.
•• The SPECT may also help to prognosticate patients with a poor outcome.
•• The SPECT brain perfusion studies can contribute to the diagnosis of
vasospasm complicating SAH.
Xenon-Computed Tomography Scan

•• Xenon-CT scan (Xe-CT) imaging technique uses the ready diffusion
capacity of inhaled xenon gas across vessel walls into brain parenchyma.
•• The amount of the xenon then attenuates the CT rays and behaves like
iodinated contrast material.
•• The amount of xenon in the parenchyma is thus proportional to the blood
flow. This rCBF data is then combined with a conventional anatomic scan
creating a functional image.
Perfusion Computed Tomography Scan

•• Perfusion CT studies involve sequential acquisition of cerebral CT sections
obtained in an axial mode during the IV administration of iodinated contrast
material.

•• Magnetic resonance imaging (MRI) is a very sensitive investigation and
diffusion and perfusion weighted imaging and other MRI protocols are
being used to pick up ischaemia due to vasospasm, which can lead to
infarction if left untreated.
•• MRI can also predict tissue histopathology and may be useful for assessing
pharmacological treatments designed to ameliorate SAH.
568
Magnetic Resonance-Angiography
•• MR-angiography (MRA) has been reported to have a sensitivity of only
46% and specificity of 70%, as there is the problem of motion artifact and
difficulty in visualising distal vessels and branches.
•• Technical hardware and software advances are rapidly increasing the role
of MRA in the investigation and management of vasospasm.
Positron Emission Tomography Scan

•• rCBF and regional cerebral metabolic rate of oxygen (rCMRO2) can be
measured with PET in patients with SAH and hemiparesis due to cerebral
vasospasm.
•• The impact of secondary insults such as acute hydrocephalus, brain
oedema, vasospasm, seizures, hypotension and hypoxaemia are likely
to be dependent on the degree of primary injury, which can be assessed
by PET.
TREATMENT
Initial Intensive Care Unit Management
•• Patients with vasospasm are admitted to neurosurgical service and are
managed within the neonatal intensive care unit (NICU).
•• If vasospasm is suspected clinically or by TCD standard triple-H therapy
is started after the offending aneurysm has been secured by clipping or
neurointerventional methods.
•• The patient is monitored by neurosurgeons preferably trained in both open
microneurosurgery and neurovascular interventional methods.
Triple-H Therapy
Induced Hypertension, Hypervolaemia, Haemodilution
•• Attempts to improve cerebral perfusion by volume expansion and induced
hypertension are commonly practiced.
•• This increases CBF and decreases the haematocrit.
•• It is a safe and effective modality of treatment to prevent ischaemic
neurological deterioration.
•• The duration of “triple-H therapy” varied from 2−7 days with an average of
4.6 days and complications included hypokalaemia, haemorrhagic infarct
and septicaemia which worsens brain oedema in the presence of acute
infarcts and hence is contraindicated in such patients.
PHARMACOLOGICAL PREVENTION
OF VASOSPASM
•• The agents that have been tried include papaverine, procaine, cyclandelate,
nitroglycerin, reserpine, kanamycin, platelet aggregation inhibitors,
prostaglandin antagonists and serotonin antagonists among others.
•• None of these have been found to be effective.
Calcium Channel Blockers

•• The intracellular calcium ion is a key player in the development of muscle
contraction of the vessel wall and calcium antagonists, like nimodipine,
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nicardipine and magnesium sulphate block, the slow channels of calcium

which inhibit the contraction of smooth and cardiac muscles.
•• The skeletal muscles are not affected and these agents are very useful to
prevent the onset of vasospasm and can help in its reversal.
•• These agents are hypothesised to prevent brain injury by other mechanisms
than blockage of slow calcium channels and also have a role in cerebral
protection.
Nimodipine
•• Nimodipine is a calcium antagonist that has a selective CNS action and
blocks the dihydropyridine sensitive (L-type) calcium channels.
•• Other similar drugs used less commonly are nicardipine, nifedipine and
diltiazem.
•• Oral nimodipine is given in dose of 60 mg four times a day and reduces
infarcts and bad outcomes.
•• Calcium channel blockers are thought to be more neuroprotective than
counteractive to vasospasm itself.
•• Their benefit may derive from their prevention of calcium entry into
ischaemic cells, their anti-platelet effect and ability to dilate leptomeningeal
arteries.
•• The calcium theory of neuronal damage has been recently adapted to SAH.
•• It is proposed that haemorrhagic insult to the brain causes free radical
mediated destructive reactions of membrane phospholipids, and the
consequent decrease of phospholipid dependent enzymatic activities,
such as Na+-K+ ATPase.
•• Patients should be monitored for renal failure, GI side effects, dependent
oedema and PO, which are potential side effects of calcium channel
blocker use.
Nicardipine
•• Nicardipine was found to induce the recovery of Na+-K+ ATPase activity,
in experimental SAH thus exerting a brain protective role.
•• High-dose intravenous nicardipine has been shown to reduce the incidence
of angiographic and symptomatic vasospasm in patients with aneurysmal
SAH, but treatment may be complicated by side effects, including
hypotension or azotaemia.
Free Radical Scavengers

•• Free radicals reaction initiated by the lysis of clot has been implicated in
the pathogenesis of vasospasm.
•• Oxyhaemoglobin has a direct effect on the vessel wall causing
vasoconstriction and also causes injury due to the release of superoxide
ion that injure the endothelial lining.
•• Free radical induced lipid peroxidation has been identified as a potentially
important contributor to both the arterial narrowing of vasospasm and the
final cascade of ischaemic cell death.
•• Tirilazad mesylate is a non-glucocorticoid 21-aminosteroid that exerts its
anti-lipid peroxidation action through co-operative mechanisms—a radical
scavenging action (i.e. chemical antioxidant effect) and a physicochemical
interaction with the cell membrane that serves to decrease membrane
fluidity (i.e. membrane stabilisation).
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•• It is a potent inhibitor of lipid peroxidation and also acts as a free radical

scavenger.
•• Other drugs with similar mechanism of action are nicarven and ebselen.
Endothelin
•• Endothelins are 21-amino acid vasoconstrictor peptides and are the most
potent naturally occurring vasoconstrictors.
•• They can be produced by the vascular endothelium and smooth muscle
cells.
•• Three endothelin genes have been identified and the proteins are called
endothelin-1 to 3.
•• Endothelin-1 is a powerful endogenous vasoconstrictor substance produced
by endothelial cells, and causes significant and sustained vasospasm.
•• Endothelin receptor antagonists (TAK-044) cause prevention or reversal
of vasospasm.
Vasoconstriction due to Deficiency of Endothelial Nitric Oxide
•• The NO donors like sodium nitroprusside and nitroglycerin are used.
•• The NO is an extremely potent vasodilator and accounts entirely for the
biological effect of endothelium-derived relaxing factor.
•• It acts through cyclic guanylic acid-dependent protein kinases and reduces
the protein-dependent inflammatory response in the vessel wall secondary
to vasospasm.
•• Intrathecal sodium nitroprusside was suggested as a treatment for cerebral
ischaemia in patients with severe, medically refractory vasospasm after
SAH (10−40 mg single dose and 2−8 mg/h as infusion, 4 mg/mL,1−2 mL
per dose up to three times daily for a week).
Recombinant Tissue Plasminogen Activator

•• It is well established, that the amount of blood in the basal cisterns has a
correlation with the development of vasospasm.
•• Hence, continuous cisternal irrigation post-operatively to reduce the
incidence of symptomatic vasospasm has been tried and an improved
clinical outcome reported.
•• A single bolus of 10 mg of thromboplastin activator (TPA) injected into
the basal cistern helps in clearing the subarachnoid clot post-operatively.
•• The other agents tried with varying results are streptokinase and urokinase.
Papaverine
•• Papaverine (phosphodiesterase inhibitor) is an alkaloid and a powerful
vasodilator.
•• It acts directly on the smooth muscle cells of the arterial wall by trans-
endothelial absorption.
•• It is given in the dose of 200−300 mg over 30 minutes.
•• Since the absorption is trans-endothelial, it is not surprising that the best
results have been obtained with an infusion close to the site of spasm.
•• An angiographic response is seen in 80−95% of cases.
•• A clinical response is seen in 25−50% of cases.
•• Another endovascular treatment strategy for vasospasm is intra-arterial
infusion of papaverine.
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Intra-arterial Papaverine
•• Intra-arterial infusion of papaverine is being used clinically as a vasodilator
for spastic arteries after SAH, since in vitro experiments demonstrated
that papaverine is one of the most potent vasodilators of human cerebral
arteries following SAH.
•• The potential adverse effects of papaverine which have been reported
include transient neurologic dysfunction, seizure, mydriasis, monocular
blindness, drug precipitation, increased intracranial pressure and even
aggravation of spasm.
•• Of these, by far the most common is elevation of the intracranial pressure.
Fortunately, this can usually be controlled (< 20 mm H2O) with a mannitol
infusion (25−50 gm).
•• Other complications which can occur with this form of treatment include
dissection and thromboembolism.
Statins
•• The use of simvastatin as prophylaxis against DCI after aneurysmal SAH
is a safe and well-tolerated intervention.
•• Its use attenuates serum markers associated with brain injury and
decreases the incidence of radiographic vasospasm and DID.
•• Currently pravastatin 40 mg daily orally or via NG tube for 21 days is
recommended to be initiated within 4 days of haemorrhage as it has been
shown to improve outcome of vasospasm.
SURGERY
•• The debate on the ideal method of tackling the problems of aneurysmal
bleed are unlikely to be resolved and probably clipping, coiling and
angioplasty will all have indications and advantages in specific situations.
•• Patients with unsecured aneurysms remote from an ischaemic middle
cerebral territory should probably be revascularised if cautious hypertension
fails to improve their condition.
•• Extracranial-intracranial bypass surgery offers another alternative to the
treatment of patients with vasospasm who have failed aggressive medical
management.
Interventional Neurosurgery
•• Endovascular intervention is contemplated when symptomatic cerebral
vasospasm is non-responsive to maximal medical management.
•• Balloon angioplasty is better than intra-arterial antispasmodics due to the
increased durability and long-lasting effects of the former and its lower
risk profile.
•• Structured neurointensive and endovascular treatment of imminent
vasospasm integrating papaverine administration and balloon angioplasty
are complimentary rather than alternative techniques.
•• Percutaneous transluminal balloon angioplasty is done with special balloon
tipped catheters to dilate the proximal major cerebral arteries and must be
done early when the other therapies fail to combat vasospasm.
•• Transluminal balloon angioplasty is effective in dilating larger proximal
vessels, but its access for dilation of smaller distal vessels is limited and
here intra-arterial vasodilating agents, including papaverine, nimodipine,
nicardipine, verapamil, milrinone, fasudil and colforsin are used.
572
•• Angioplasty is performed via a femoral artery approach; usually with a

6 or 7 French sheath using wire silicone balloon microcatheter systems.
Cerebrospinal Fluid Drainage

•• Enhanced cisternal drainage following early aneurysm surgery is indicated
for patients to effect continuous wash-out of subarachnoid blood clots and
reduce symptomatic vasospasm.
•• Enhanced post-operative cisternal drainage can reduce the incidence of
symptomatic vasospasm and is a beneficial outcome of early aneurysm
surgery.
•• Cisternal irrigation therapy with urokinase is safe and effective for the
prevention of symptomatic vasospasm after aneurysmal SAH.
Preventive Neurosurgery—The Future

•• The factors, like hyperglycaemia, hypertension, obesity and pre-existing
medical illness, increase the risk of developing vasospasm and these
create possibilities on how the problem of vasospasm can be dealt with
using principles of preventive neurosurgery.
•• The close causal relationship between cigarette smoking and aneurysms,
SAH and vasospasm has been proved conclusively and lifestyle changes
and health education can help to reduce the incidence of this devastating
condition.
•• Pretreatment with continuous wave ultraviolet (UV) light irradiation can lead
to significantly reduced degree of vasospasm and this prophylactic effect
of UV light on vasospasm was suggestive of involvement of apoptosis in
the mechanism of this effect.
75
CHAPTER
Cerebral Protection
Ravikant Palur  Ganesh K Murthy
PATHOPHYSIOLOGY OF INJURY TO THE

CENTRAL NERVOUS SYSTEM
•• Neuronal cell damage in a neurosurgical setting occurs commonly intra-
operatively with a varying degree of insult based on many factors.
•• However, the pathophysiological processes in intra-operative injury are
similar to those involved in other forms of injury to the central nervous
system (CNS) such as stroke and trauma.
•• Major advances in neurobiological research have outlined a cascade of
cellular events that occur in the injured tissue.
•• This cascade of events involves neuronal depolarisation, excessive
activation of excitatory amino acid receptors, energy depletion with
ionic refluxes, and activation of catabolic enzymes and subsequent lipid
peroxidation and free radical formation.
•• The main events leading to neuronal cell damage can be studied lucidly
under the following headings.
Intracellular Calcium Accumulation

•• There is considerable evidence that excessive intracellular calcium is a
fundamental mediator of cell death.
•• Removal of extracellular calcium prevents hypoxic neuronal death in cell
culture models.
•• Increases in intracellular neuronal calcium concentrations can occur from
many sources including multiple membrane channels as well as intracellular
storage sites.
•• Some of these sources are unique to neurons explaining the extreme
sensitivity of neurons to ischaemic and traumatic injury.
•• The role of intracellular calcium in neuronal injury is summarised in Figure 1.
Excessive Activation of Excitatory Amino Acid Receptors

•• Glutamate and aspartate are the major excitatory neurotransmitters in the
brain; ironically they are also potent neurotoxins.
•• Excitatory amino acids are present throughout the grey matter of the CNS.
•• These amino acids are packaged inside synaptic terminals and are released
into the extracellular environment for synaptic transmission.
•• Following their release into the synaptic cleft, they activate post-synaptic
receptors to facilitate excitatory neurotransmission.
574
Fig. 1: Role of intracellular calcium in neuronal injury
Fig. 2: Four mechanisms of increased extracellular glutamate during

trauma: (1) Increased pre-synaptic vesicular release; (2) Increased leakage
of neurotransmitter; (3) Decreased pre-synaptic neurotransmitter uptake;
(4) Decreased glial uptake (NMDA = N-methyl-D-aspartate)
•• They are then rapidly cleared from the extracellular space by energy
dependent cellular uptake mechanisms.
•• These uptake mechanisms fail when there is hypoxia-ischaemia, leading
to toxic accumulation of excitatory amino acids in the extracellular space.
•• This accumulation has been proven to destroy neurons in cell culture
(Fig. 2), and the injury thus caused appears to be mediated by excessive
activation of excitatory amino acid receptors that are linked to ion channels
with a high permeability to calcium.
•• Three major families of receptor subtypes have been identified:
–– N-methyl-D-aspartate (NMDA)
–– AMPA/Kainate (also referred to as “non-NMDA”)
–– Metabotropic receptors.
Voltage-Gated Calcium Channels

•• Voltage-gated calcium channels (VGCCs) are an additional avenue for
calcium to enter neurons.
•• These channels are involved in the release of glutamate into the synaptic cleft.
Chapter 75 • Cerebral Protection
575
•• Hence, inhibition of these VGCCs may provide neuroprotection indirectly

by decreasing excitatory aminoacid-mediated neurotoxicity.
Other Sources of Intracellular Calcium

•• There are numerous additional sources of intracellular calcium such as:
–– Energy depletion results in reverse operation of the sodium/calcium
exchanger, leading to further increases in intracellular calcium.
–– Release of calcium from intracellular storage sites during acute injury.
–– Non-specific leakage of toxic excitatory aminoacids into the extracellular
space leading to activation of receptors on neighbouring neurons and
culminating in propagation of the brain injury.
Lipid Peroxidation
•• Excessive levels of intracellular calcium mentioned above trigger an array
of neurochemical changes that eventually lead to neuronal injury.
•• Modulators, such as calpain and protein C and intracellular proteases, are
activated leading to damage of the cellular proteins.
•• Moreover, phospholipases trigger lipid peroxidation and the generation
of free radicals.
•• Lipid peroxidation is one of the most damaging consequences of elevated
intracellular calcium.
•• This progressive process can rapidly propagate through cell membranes
leading to membrane destruction.
•• Free radicals formed during the process of membrane destruction also
attack nearby glial cells and vasculature, which causes additional injury.
•• Brain tissue has very limited defences against these free radicals because
cerebral neurons have low levels of endogenous antioxidants.
•• This “neuronal injury” cascade following trauma, ischaemia or due to
hypoxia involving the CNS, ultimately leads to cell death.
Role of Oxygen-Free Radicals

•• Oxygen is both a life-sustaining and a life-threatening inhalant.
•• A free radical is defined as an atom of a molecule in a particular state with
an unpaired electron in its outer orbit.
•• It is now well recognised that oxygen-free radicals are formed during the
metabolism of all aerobic cells. There are several pathways in aerobic cells
that lead to the production of oxygen-free radicals.
•• The discovery of superoxide dismutase (SOD) by McCord and Fridovich
showed the way to research on oxygen-free radicals.
•• Evidence supporting the deleterious effects of oxygen-free radicals in many
pathological processes has grown considerably.
•• The current major candidates for a source of oxygen-free radicals are
(Fig. 3):
–– Accumulation of reduced metabolites
–– Xanthine oxidase
–– Mitochondria
–– Activated neutrophils
–– Arachidonic acid metabolism
–– Catecholamine oxidation.
576
Fig. 3: Sources of free-radical release and lipid peroxidation
•• The fact that oxygen-free radicals are one of the factors responsible for
cell damage is well documented in:
–– Traumatic brain injury
–– Cerebral ischaemia-reperfusion injury
–– Subarachnoid haemorrhage and vasospasm
–– Peritumoral brain oedema.
PROTECTIVE MECHANISM AGAINST

OXYGEN-FREE RADICALS
•• A variety of enzymatic mechanisms have evolved which provide protection
against oxygen-free radicals.
•• SOD scavanges the superoxide, which is formed during the process of
reduction of oxygen by aerobic cells.
•• Two other enzyme systems also help in the scavenging of hydrogen
peroxide; these are catalase and glutathione peroxidase.
•• Another endogenous defence exists in hydrophilic and hydrophobic regions.
•• In hydrophilic regions, ascorbic acid, cysteine, ceruloplasmin and transferrin
are the antioxidant compounds.
•• In hydrophobic regions, several fatty acids and vitamin E are the antioxidant
compounds.
MODALITIES OF CEREBRAL PROTECTION

•• The various modalities of cerebral protection available for therapeutic use
are shown in Table 1.
PHARMACOLOGICAL THERAPIES
Barbiturates
•• Barbiturates produce a dose related decrease in neuronal function that is
accompanied by a dose related decrease in cerebral metabolism.
•• Barbiturates interfere with synaptic transmission and multineuronal
networks, can exert a local anaesthetic effect on membranes, and can
enhance presynaptic inhibition by facilitating the binding of gamma-
aminobutyric acid.
•• The parallel decrease in cerebral oxygen consumption accompanying the
decrease in neuronal function reaches a plateau when neuronal function
is abolished as evidenced by isoelectricity on the EEG.
577
Table 1: Modalities of cerebral protection

A. Pharmacological therapies
1. Barbiturates
2. Isoflurane
3. Etomidate
4. Local anaesthetics
5. Calcium entry blockers
a. Flunarizine
b. Lidoflazine
c. Nimodipine
6. Diuretics
a. Mannitol
b. Furosemide
7. Corticosteroids
8. Diphenyl hydantoin
9. Perfluorochemical blood substitutes
10. Antioxidants/free radical scavengers
B. Non-pharmacological therapies
1. Hyperventilation
2. Hypervolaemia
3. Haemodilution
4. Induced hypothermia
5. Induced hypertension
6. Induced hypotension
•• The proposed mechanism of action of barbiturates can be outlined as

follows:
–– Decrease in cerebral metabolic requirements
–– Improvement in distribution of CBF
–– Suppression of seizures
–– Suppression of catecholamine induced hyperactivity
–– Anaesthesia, deafferentation, immobilisation
–– Loss of thermoregulation
–– Decrease in ICP
–– Decrease in cerebral oedema
–– Decrease in CSF secretion
–– Scavenging free radicals
–– Stabilisation of membranes
–– Blocking calcium channels
–– Alteration in fatty acid metabolism.
•• Barbiturates help in protecting against temporary focal ischaemia.
•• Prophylactic barbiturate treatment has been recommended for brain
protection during periods of focal ischaemia when temporary clamping of
a major cerebral vessel is necessary as during carotid endarterectomy,
aneurysm clipping or extracranial to intracranial bypass procedures.
•• Barbiturates have two major undesirable effects.
•• First they may decrease mean arterial blood pressure (MABP), especially
in patients who are hypertensive or hypovolaemic for any reason. They are
known to decrease cardiac output with either no change or an increase in
heart rate. At high doses, they decrease cardiac contractility, which may
lead to a need for vasopressors.
578
•• A second undesirable side effect of high dose barbiturate is delay in

awakening from anaesthesia and prolonged time to extubation.
•• The one clear contraindication to the use of barbiturates is the patient with
either acute intermittent porphyria or variegate porphyria.
•• In these patients, the increase in porphyrin synthesis that can be
provoked by barbiturates can precipitate an acute attack with widespread
demyelination leading to pain, weakness and possible paralysis.
Isoflurane
•• Isoflurane is unique among the volatile anaesthetics in that two MAC
isoflurane (2.4%) can induce a level of anaesthesia in man that is
characterised by an isoelectrical EEG and haemodynamic stability.
•• Isoflurane increases the tolerance of the brain to low blood flows.
•• It has the ability to lower cerebral metabolism significantly more than the
other volatile anaesthetics (halothane, enflurane, innovar) at the clinical
concentrations (0.5−1 MAC) used, thereby maintaining the oxygen supply-
demand ratio.
•• In addition, isoflurane provides protection by suppression of seizures,
reduction of catecholamine induced hypermetabolism and immobilisation,
deafferentation and anaesthesia.
Etomidate
•• Etomidate is another anaesthetic capable of producing a dose dependent
decrease in neuronal function with a parallel decrease in cerebral metabolism.
•• In addition, it is a direct cerebral vasoconstrictor with the ability to
significantly decrease CBF.
•• Other mechanisms that may contribute to protection against ischaemia
include redistribution of CBF, reduction in intracranial blood volume,
decrease in ICP, membrane stabilisation and attenuation of FFA liberation.
•• Etomidate has two advantages over the barbiturates if used as a protective
agent.
•• Even large doses of etomidate, sufficient to produce maximal suppression of
neuronal function and cerebral metabolism, do not produce cardiovascular
depression, hence eliminating the need for isotropic or vasopressor support.
•• Due to its shorter half-life, etomidate may allow a more rapid awakening
time than high doses of thiopental.
•• Etomidate has the disadvantage of suppressing the usual adrenocortical
response to stress.
Calcium Entry Blockers

•• Calcium entry blockers form a heterogeneous group of drugs; they block the
influx of calcium into the cell and can block the intracellular flux of calcium
into the mitochondria.
Classification of Calcium Entry Blockers
A. Myocardial, electrophysiologic and vascular effects:
–– Verapamil
–– Tiapanil
–– Diltiazem.
B. Predominantly vascular effects (Dehydropyridine derivatives):
–– Nifedipine
–– Nimodipine
579
–– Nisoldipine
–– Nitrendipine.
C. Only vascular effects:
–– Cinnarizine
–– Flunarizine.
D. Complex effects:
–– Lidoflazine
–– Perhexilene.
Primarily, four Ca+2 entry blockers have been studied for a possible role
in brain protection. They were chosen for study because they produced
vasodilatation in cerebral vessels in vitro.
Mechanism of Protection by Calcium Entry Blockers
A. Cerebral blood flow phenomena:
–– Improve ischaemic flow
–– Attenuate post-ischaemic hypoperfusion
–– Prevent vasospasm
–– Improve rheological properties.
B. Cellular changes phenomena:
–– Prevent enhanced proteolysis
–– Prevent formation of FFA and free radicals
–– Antioxidation.
Nimodipine
•• The calcium entry blocker most extensively studied for its protective effects
against cerebral ischaemia is nimodipine.
•• There are three prospective randomised double blind, placebo-controlled
studies on the use of nimodipine in patients with vasospasm after SAH.
•• All patients treated with nimodipine orally for 21 days after SAH had a
significantly lower incidence of delayed ischaemic deficits or death and had
significantly better neurological outcome than those patients given placebo.
•• Nimodipine acts through its effects on neurons by preventing Ca+2 entry
into the cells, Ca+2 sequestration by mitochondria and the alterations in FFA
metabolism and the arachidonic acid cascade or by free radical scavenging.
Flunarizine
•• Studies of flunarizine have focused on possible prevention of neurological
damage after complete global ischaemia.
•• However, inconsistent results are seen in ameliorating post-ischaemic
hypoperfusion or improving neurological outcome.
•• In addition, flunarizine precipitates in the lungs producing severe pulmonary
oedema. It is not likely to be useful clinically.
Diuretics
•• Diuretics have been used as adjunct therapy in brain protection primarily
for their role in decreasing cerebral oedema or in decreasing ICP.
•• The two common agents for neuroprotection are mannitol and furosemide.
Mannitol
•• The use of mannitol in neurosurgery has been studied for over 30 years.
•• Some of mannitol’s beneficial effects include osmotic diuresis, decreased
blood viscosity and free radical scavenging.
580
•• Mannitol has been shown to increase CBF in experimental and clinical

situations.
•• Maximum reduction in blood viscosity occurs during the first 30−60 min after
rapid infusion of mannitol; however, this is largely reversed within 4 hours.
•• The maximum white water content reduction in the control hemisphere was
at 60 min, whereas no reduction was seen in the lesioned, oedematous
hemisphere.
•• Mannitol also effects serum sodium and potassium acutely.
•• These changes may be of significance intra-operatively for patients with
severe cardiac or renal disease, particularly in any procedure in which
mannitol is given in high doses.
•• 20% w/v mannitol (0.5−2 g/kg) given over 30 min effects osmotic diuresis.
•• In case of aneurysmal surgery, a total dose of 2 g/kg is given when
temporary artery occlusion is planned.
•• Its action begins within 4−5 min and peaks in about 30−45 min.
•• The classic mechanism is believed to be movement of intracellular water
into the intravascular volume along the osmotic gradient (the osmolarity of
20% mannitol is 1098 osm/L).
•• Some evidence also exists that the rapid action of mannitol can be mediated
by decreased production of CSF.
Furosemide
•• Furosemide is the diuretic most commonly used intra-operatively in
neurosurgery.
•• It is a potent loop diuretic that decreases ICP by venodilatation and by
decreasing total intravascular blood volume, and causes the diffusion of
oedematous fluid into the vasculature.
•• Furosemide selectively dehydrates abnormal ischaemic or traumatised
cerebral tissue and, therefore, may act synergistically with mannitol.
•• Large doses of furosemide also decrease CSF production.
•• The recommended dose ranges 0.1−1 mg/kg followed by 0.3 mg/kg every
4 hours.
•• Given its relative safety and effectiveness, furosemide should be considered
intra-operatively whenever ICP reduction or fluid volume reduction is
indicated.
Steroids
•• Although, several mechanisms have been suggested for the neuroprotective
effects of corticosteroids, its major action is probably inhibition of lipid
peroxidation.
•• The efficacy of steroids in reducing vasogenic peritumoral oedema is well
documented, but whether corticosteroids have the same efficacy in intra-
operative ischaemic cerebral oedema is uncertain.
•• Other mechanisms by which steroids prove helpful is in scavenging of free
radicals, reduction of CSF production and increasing the seizure threshold.
•• The side effects of steroids have been frequently cited as a reason for
avoiding their usage.
•• Gastrointestinal bleeding and infections are two major complications with
steroids.
•• In conclusion, the use of steroids remains controversial for intra-operative
neuroprotection while they are effective in vasogenic peritumoral oedema.
Hence, judicious usage of steroids is warranted.
581
Phenytoin
•• Phenytoin has been shown to stabilise membranes and slow the release
of K+ from ischaemic neurons.
•• Increase in extracellular K+ concentration causes contraction of vascular
smooth muscle, thereby further reducing CBF and increasing glial water
content resulting in cytotoxic oedema.
•• Phenytoin has also been shown to attenuate FFA accumulation during
complete global ischaemia, thereby preventing the arachidonic acid
cascade leading to the production of endoperoxides, prostaglandins and
free radicals, and the potential detrimental effects these could have in
ischaemic cells.
Perfluorochemical Blood Substitutes

•• These are small biologically inert particle fluorocarbons (perfluorodecalin
and perfluorotripropylamine) emulsified and suspended in an iso-osmolar
mixture of intralipid, glycerol and fatty acids.
•• Suggested mechanisms of protection include increasing oxygen availability
to the tissues, decreasing blood viscosity, preventing narrowing of the
vascular lumen and increasing flow to the ischaemic areas via collateral
circulation because of the small particle size.
Sendai Cocktail
•• Suzuki advocated a combination of mannitol (500 mL of 20% solution or
100 gm), Vit. E (500 mg) and dexamethasone 50 mg, often referred to as
Sendai cocktail, for protection during temporary arterial occlusion.
•• Up to 60 or more minutes of temporary arterial occlusion were possible by
this regime without apparent post-operative neurological deficits.
Excitotoxic Antagonists
•• A major role for excitatory neurotransmitters, notably glutamate, in ischaemic
cerebral injury has been well documented.
•• The relationship between excitatory neurotransmitters and increased
intracellular calcium has been established.
•• Excitotoxic injury appears to be the result of activation of several receptors:
(a) N-methyl-D-aspartate (NMDA) receptor; (b) amino-3-hydroxy-5-methyl-4-
isoazole propionic acid receptor and (c) additional receptors.
•• The antagonists commonly in use are dextromethorphan, its primary
metabolite dextrorphan and CGS-19755.
•• The limiting factors for the clinical trials to date are significant side effects
and unproven efficacy.
Antioxidants/Free Radical Scavengers

•• Given that the three primary mechanisms of ischaemic brain injury are loss
of calcium homeostasis, acidosis and increased free radical production, it
is not surprising that antioxidants or free radical scavengers should be a
part of pharmacological neuroprotection.
•• An oxygen-free radical scavanger is a compound that removes free radical
species.
•• A list of known oxygen-free radical scavangers that have been demonstrated
to be useful in animal models is shown in Table 2.
582
Table 2: Oxygen-free radical scavengers

A. Enzymatic
a. Superoxide dismutase
b. Catalase
c. Allopurinol, oxypurinol (xanthine oxidase inhibitor)
B. Non-enzymatic
a. Dimethyl sulfoxide (DMSO)
b. Dimethylthiourea (DMTU)
c. Deforoxamine
d. Mannitol
C. Hydrophilic
a. Ascorbic acid (vitamin C)
b. Glutathione peroxide
c. L-methionine
D. Hydrophobic
a. Vitamin E
b. Barbiturates
•• Although multiple approaches to inhibit lipid peroxidation and free radical

formation have been attempted, substantial clinical benefits have not been
clearly documented in human trials with these agents.
•• Vitamins C and E have a very slow onset of action, while deferoxamine
does not cross the blood-brain barrier.
•• Only two agents are likely to be candidates for intra-operative use primarily
as antioxidants in the near future, SOD and tirilazad mesylate (TM).
•• SOD has been shown to be effective in treating the vascular changes and
increased ICP that occur in several types of brain injury, such as fluid-
percussion injury and cold injury.
•• Since SOD has a biological half-life of only 5 min, it has been conjugated
with polyethylene glycol (PEG-SOD) for human trials.
•• TM is an L1-aminosteroid that was developed specifically to maximise the
inhibition of lipid peroxidation by glucocorticoids, such as methylprednisolone,
but eliminates the unwanted glucocorticoid effects.
•• Two well-studied protective proteins, heat shock protein 72 (Hsp72) and
SOD2 were genetically targeted for expression in astrocytes using the
astrocyte-specific human glial fibrillary acidic protein (GFAP) promoter.
NON-PHARMACOLOGICAL THERAPIES
Hypothermia
•• Conditions of metabolic inhibition that reduce O2 and glucose consumption
may provide protection for the ischaemic brain owing to the diminished gap
between demand and supply.
•• Mechanism of Protection by Hypothermia
–– Reduction in cerebral metabolism: Activation metabolism (neuronal
function) and residual metabolism (cellular integrity)
–– Membrane stabilising effect: Sodium channels restriction and reduc-
tion in Na+ and K+ flux.
583
–– Reduction in cerebral oedema.

–– Reduction in ICP.
•• The therapeutic benefit of deep hypothermia against cerebral ischaemic
injury is largely as a result of reduced metabolic demand and decreased
cerebral metabolic rate of oxygen consumption.
•• Deep hypothermia of less than 27°C requires cardiopulmonary bypass, with
surgery, general anaesthesia and complex equipment to provide support
of the circulation since the heart commonly fibrillates at a temperature
below 26−28°C.
•• From clinical trials and animal studies, it is clear that hypothermia alone will
not provide complete protection or stimulate the repair that is necessary
for normal neurodevelopmental outcome.
•• Other agents such as xenon, N-acetylcysteine, erythropoietin, melatonin
and cannabinoids are discussed as future potential therapeutic agents that
might augment protection from hypothermia.
Recommended Limits of Total Circulatory Arrest
under Deep Hypothermia
Circulatory Core
arrest time temperature
Adult neurosurgical procedures 45−60 min 15−18°C
Paediatric cardiovascular operations 60−90 min 18−20°C
Systemic Effects of Deep Hypothermia
A. Clotting defects:
–– Heparinisation with inadequate reversal
–– Thrombocytopaenia
–– Abnormal platelet function
–– Inhibition and deficiencies of factor I, II, V, VII, X and XII.
B. Altered delivery, metabolism and effects of anaesthetic agents.
C. Decreased O2 availability.
D. Disturbed acid/base balance.
E. Decreased hepatic and renal function.
F. Decreased carbohydrate metabolism.
G. Reduced cerebral blood flow, increased cerebrovascular resistance.
H. Increased blood viscosity.
I. Cardiac arrhythmia.
J. Shivering
–– Deep hypothermia is therefore not practiced currently.
Hyperventilation
•• Controlled hyperventilation producing hypocapnia is an effective short-term
means of reducing ICP by decreasing CBF and cerebral blood volume
when PaCO2 decreases.
•• Cerebral vessels vasoconstrict until the limit of vasoconstriction is reached,
which occurs at a PaCO2 of approximately 20 mmHg.
•• If PaCO2 decreases below 18−20 mmHg, ischaemia may occur.
•• It is hypothesised that hyperventilation might exert a protective effect in focal
cerebral ischaemia by vasoconstricting normal cerebral vessels, thereby
shunting blood from the normal tissue to the ischaemic area (Robin Hood
Steal phenomenon).
584
Hypertension, Hypervolaemia and

Haemodilution (Triple-H Therapy)
Hypertension
•• Cerebral vasospasm occurring as a consequence of SAH is usually
accompanied by ischaemia and disturbed auto regulation.
•• Induced hypertension may be effective in reversing the effects of focal
ischaemia only if CPP is raised before the endothelial cells and the BBB
have been damaged by the ischaemia.
Hypervolaemia
•• Although there is little evidence to substantiate a direct relationship between
intravascular volume and CBF, expansion of intravascular volume by colloid
infusion has been commonly used to treat focal cerebral ischaemia.
Haemodilution
•• Blood viscosity varies inversely with the shear rate of the fluid and is,
therefore, greater at lower flow rates.
•• During and after cerebral ischaemia, blood viscosity increases as a result
of shift in electrolytes and water from plasma to tissue.
•• Haemodilution would decrease blood viscosity and improve cerebral
perfusion during and after ischaemia.
•• There are three major types of haemodilution depending on the amount
of volume expansion.
•• Hypovolaemic haemodilution is produced by phlebotomy and less fluid
replacement.
•• Isovolaemic haemodilution is produced by exchanging fluid for blood.
•• Hypervolaemic haemodilution is produced by infusion of fluid (colloid or
crystalloid) into the circulation.
Agents for Volume Expansion

Crystalloids Colloids
a. Normal saline a. Blood
b. Ringer’s lactate b. Albumin
c. Hypertonic saline c. Dextran
d. Hypertonic Ringer’s lactate d. Hetastarch
e. Dextrose solution. e. Perfluorocarbons.
Induced Hypotension
•• Induced hypotension is employed to reduce blood loss.
•• It is necessary to distinguish prolonged induced hypotension during
procedures in which blood loss is virtually continuous (extensive spinal
fusions or the resection of large vascular tumours), from temporary induced
hypotension to facilitate control of unexpected profuse bleeding (premature
rupture of aneurysm or AVM).
•• In the former situation, the induced hypotension is elective and is
undertaken with maintenance of adequate perfusion of neural tissue as an
essential goal. In the latter situation, the induced hypotension is emergent
and is undertaken at the risk of ischaemic injury to neural tissue.
585
Relative Contraindications to Induced Hypotension

•• Ischaemic cerebrovascular disease
•• Ischaemic coronary artery disease
•• Chronic hypertension
•• Hypovolaemia
•• High (> 45) or low (< 30) haematocrit
•• Extremes of age.
Complications of Induced Hypotension
•• Stroke
•• Cardiac arrest or myocardial infarctions
•• Hepatic failure
•• Renal failure or renal artery thrombosis
•• Retinal artery thrombosis.
Agents for Induced Hypotension
•• Inhalation anaesthetic (increased isoflurane)
•• Intravenous anaesthetic (propofol, thiopental, etomidate)
•• Vasodilator (sodium nitroprusside, nitroglycerine, hydralazine)
•• Sympathetic blocker (esmolol, labetalol)
•• Ganglionic blocker (trimethapan)
•• Narcotic (sufentanyl)
•• Adenosine (less commonly used at present).
76
CHAPTER
Paraclinoid Aneurysms
Vijendra Kumar Jain  Sanjay Behari  Bernard Lyngdoh
INTRODUCTION
•• Paraclinoid aneurysms arise from the internal carotid artery (ICA) distal to
the cavernous sinus but proximal to the posterior communicating artery.
NEUROANATOMY
Paraclinoid Internal Carotid Artery
•• The modification of Fischer’s classification proposed by Bouthillier and
colleagues classifies segments of the ICA in an anterograde sequence.
•• The cavernous segment of ICA is designated the C4 segment.
•• After exiting from the cavernous sinus, the ICA bends twice to form the
anterior loop and reverses its course by 180 degrees.
•• Here, it is surrounded by the anterior clinoid process laterally, the optic
strut anteriorly and the carotid sulcus medially.
•• The intracavernous ICA is separated from the intradural space by two layers
of the cavernous sinus dura, an inner membranous layer and the outer dura
propria. These layers split at the anterior clinoid process.
•• The clinoidal (C5) segment of the ICA is the part of the ICA from the proximal
to the distal dural ring.
•• This part of the ICA is regarded as extracavernous and extradural.
•• Aneurysms located proximal to the distal dural ring do not cause
subarachnoid haemorrhage (SAH) and, therefore, do not produce the same
morbidity as do aneurysms arising from the intradural part of the artery.
•• The veins of the cavernous sinus may extend through the incompetent
proximal dural ring up to the distal dural ring through the space between
the dural rings and the ICA.
•• The distal dural ring forms the boundary between the extradural and the
intradural spaces and marks the end of the clinoid (C5) segment and the
beginning of the ophthalmic (C6) segment of the ICA.
•• The clinoid space is the potential space between the outer and the inner
dural layers and is occupied by the anterior clinoid process. It is a potential
space, since it is only created after an anterior clinoidectomy.
•• The proximal ophthalmic (C6) segment of the ICA lies under the anterior
clinoid process beyond the distal dural ring.
•• The ophthalmic artery arises distal to the distal dural ring from the
rostromedial aspect of the C6 segment of the ICA.
•• It travels through the optic foramen lying inferior and lateral to the optic
nerve.
Chapter 76 • Paraclinoid Aneurysms
587
•• In 2−16% of cases, it may also arise proximal to the distal dural ring either
from the C5 or from the C4 segment.
•• The superior hypophyseal arteries arise from the posteromedial wall of
the proximal C6 segment, vary from 1−5 in number and cross over the
diaphragma sellae. Occasionally, they may originate near the distal dural
ring, within the carotid cave or may even be intracavernous.
•• The paraclinoid segment of the ICA, therefore, extends from the proximal
dural ring to the origin of the posterior communicating artery and
encompasses both the clinoid (C5) and the ophthalmic (C6) segments.
Classification of Paraclinoid Aneurysms

•• This is based upon the site of origin of the aneurysm on the C5 and C6
segments of the ICA and the direction of projection of these aneurysms,
as was primarily proposed by Barami et al.
•• Carotico-ophthalmic Aneurysms:
–– These aneurysms arise from the origin of the ophthalmic artery.
–– They usually arise from the dorsal surface of the C6 segment, project
superiorly into the subarachnoid space and displace the optic nerve
superiorly and medially.
–– Their neck as well as their dome is intradural.
–– Occasionally, the ophthalmic artery arises from the C5 segment of the
ICA proximal to the distal dural ring in which case the neck and the
dome of the aneurysms are extradural.
–– These lesions either present with SAH, or if they grow to a large size
cause optic nerve or chiasmal compression.
•• Ventral or Posterior Wall Aneurysms:
–– They originate between the ophthalmic and the posterior communicat-
ing arteries and project into the cavernous sinus.
–– The neck lies 180 degrees opposite to the origin of the ophthalmic artery.
–– They are not associated with an arterial branch.
–– Although, they look and behave like other saccular aneurysms, they
are often blister-like with a relatively thin wall and a broad base, and
are extremely fragile.
–– Therefore, during the post-subarachnoid haemorrhage period, their
surgical treatment carries a high morbidity rate.
–– The dome may project towards the roof of the cavernous sinus and
involve the IIIrd nerve.
–– Thus, large aneurysms of this type occupy both the intradural and
the extradural spaces.
•• Superior Hypophyseal Aneurysms:
–– They arise from the medial surface of the proximal C6 ICA closely
related to the origin of the superior hypophyseal artery distal to the
ophthalmic artery.
–– The neck as well as the dome are intradural and they project medially
above the diaphragma sellae.
–– A variant of this aneurysm arises from the carotid cave, with its neck
and fundus being intradural and projects inferomedially along the
medial aspect of the distal dural ring.
–– This may project below the diaphragma sellae and may be assumed to
be a sellar mass on CT imaging.
–– It arises at or below the dural ring around the ICA as it enters the
subarachnoid space.
588
•• Siphon or Transitional Aneurysms:

–– These giant aneurysms have a base extending from the distal cavern-
ous to the ophthalmic segments.
–– The dome may elevate the roof of the cavernous sinus, enlarge the
proximal and distal dural rings, and also extend intradurally.
•• These aneurysms may present as SAH with sudden severe headache,
decreased visual acuity, visual field deficits, changes in colour vision,
diplopia or retro-orbital pain.
•• Occasionally, transient ischaemic attack or stroke, dizziness, facial pain
or numbness, audible bruit, panhypopituitarism and epistaxis have been
described.
SPECIAL RADIOLOGICAL CONSIDERATIONS

•• On CT, in patients with SAH, the extent of haemorrhage is graded using
Fischer’s classification.
•• Thin section CT of the clinoidal region with bone windows determines the
position of the ICA, aneurysmal calcification and clinoidal erosion.
•• An aneurysmal calcification with clinoidal erosion may predispose to an
inadvertent tearing of the aneurysm during clinoid drilling to expose it.
•• On cerebral angiography, carotid-ophthalmic, ventral wall and transitional
aneurysms are better visualised on the lateral projection; superior
hypophyseal and carotid cave aneurysms are better seen on anteroposterior
and submentovertical projections.
•• Intra-operative angiography has been a useful adjunct during direct surgery
for paraclinoid segment aneurysms.
•• It may reveal either a residual portion of the aneurysm after clipping or
compromise of the patency of the ICA that was not easily apparent under
direct microscopic vision.
•• Thus, clip repositioning with intra-operative angiography has improved the
radiological efficacy of direct surgery.
•• On MR imaging, the precise dimensions of an aneurysm with a thrombus
may be determined.
•• The coronal images delineate superior hypophyseal and carotid cave
aneurysms.
•• The infradiaphragmatic location of the latter is also determined on MR
studies since these aneurysms can only be accessed by dividing the
diaphragma sellae.
•• Testing for collateral flow in patients with a large broad necked aneurysm
before either surgery or endovascular therapy where ICA occlusion is a
possibility.
•• For a large or giant aneurysm, the suitability of permanent ICA occlusion
is determined by the balloon test occlusion (BTO) accompanied by a
clinical examination that does not suggest any asymmetry of clinical signs;
angiographic criterion, in which symmetry of flow in both hemispheres or
in the anterior and posterior circulation throughout all phases of flow, is
determined; a single photon emission computed tomography (SPECT)
study, in which a decrease in perfusion during a hypotensive challenge with
a mean BP 20% below the baseline is determined; and xenon computed
tomography in which the symmetry of perfusion is determined.
Chapter 76 • Paraclinoid Aneurysms
589
•• In case the BTO with SPECT is well-tolerated, the ICA may be trapped.
•• In case it is not tolerated and perfusion defects are seen on SPECT,
a vascular bypass using superficial temporal to middle cerebral artery
anastomosis may be required.
THERAPEUTIC OPTIONS
Clip Alone
•• This is the ideal method of treatment since it provides a direct obliteration
of the aneurysm with preservation of the carotid and ophthalmic arteries
and a simultaneous decompression of the optic apparatus.
•• Even aneurysms with a broad neck may be dealt with using a clip.
Ligature and Clip

•• The purpose of the ligature is to narrow a broad neck sufficiently to allow an
easier application of the clip, but not to narrow the neck so much as to kink
the parent ICA.
Trapping of the ICA with or without

Extracranial-Intracranial Bypass
•• This takes care of aneurysms with a large neck, especially involving the
cavernous and clinoid carotid artery.
•• It is not the preferred method of treatment since cerebral ischaemia may
occur after trapping of the ICA, despite a successful pre-operative BTO.
Circumferential Wrapping
•• Occasionally, in blister like aneurysms with no neck and a fragile dome, a
circumferential clip graft may be applied.
•• Cardiopulmonary bypass with profound hypothermia and circulatory arrest
is a useful adjunct to both clipping and trapping as the aneurysm neck may
be identified and the fundus dissected with minimal bleeding.
Endovascular Treatment
•• Since paraclinoid aneurysms are more difficult to treat surgically and have
a higher surgical morbidity, endovascular treatment may have a more
prominent role in their obliteration.
•• This includes—coiling of the aneurysms with Guglielmi detachable coils
while preserving the parent artery; intravascular stenting; balloons to
remodel coils at the neck of the aneurysm and permanent balloon occlusion
of the ICA.
•• As an adjunct to surgery for the clipping of paraclinoid aneurysms, a
novel endovascular method utilised a balloon catheter with a coaxial
lumen inserted via the transfemoral route as a means of proximal control,
along with the provision for a simultaneous suction decompression of the
aneurysm and intra-operative angiography.
•• The main complications of endovascular coiling include coil compaction
leading to refilling of the aneurysm, blockage of parent vessel, progression
of aneurysm thrombosis to parent vessel or its subsequent embolisation
and aneurysm rupture during the procedure.
590
Surgical Considerations
•• The pterional craniotomy is the standard craniotomy for paraclinoid
aneurysms and the various steps taken are:
–– Proximal control of the parent vessel
–– Untethering of the optic nerve
–– Anterior clinoidectomy
–– Dural ring division
–– Dissection of the neck.
•• Clipping:
–– For clipping these aneurysms, the clip blades must assume a path
parallel to the parent vessel. Long straight, side angled or angled
fenestrated clips may be required to secure these aneurysms (with the
carotid artery placed within the clip fenestration).
–– The clip should be long enough to completely cover the neck but
not to impinge upon the ophthalmic, superior hypophyseal, posterior
communicating or anterior choroidal arteries.
–– For aneurysms with a large neck, clips may have to be applied in a
tandem fashion.
–– If the sac is large, the closing force of the clips may not be sufficient
to keep the neck of the aneurysm obliterated. This may require
fenestrated straight clips placed perpendicular to the tandem clips and
the long axis of the ICA.
–– In case of a long neck, neck shortening may be performed using
bipolar coagulation with constant irrigation.
–– When multiple tandem clips are being used, care should be taken that
the pulsations of the sac do not force the clips down against the parent
vessel, thus obliterating its lumen.
–– In heavily calcified or atherosclerotic aneurysms, the clip should be
placed slightly away from the neck and closer to the fundus in order to
prevent rupture of the vessel wall.
Precautions During Surgery

•• Prevention of optic nerve injurey
•• Avoidance of cerebrospinal fluid rhinorrhoea
•• Avoidance of arterial lumen compromise during aneurysm clipping.
Outcome
•• For successful management of paraclinoid aneurysms, the following are
essential requirements:
–– An understanding of the three dimensional anatomy of the paraclinoid
region and the radiological assessment of the ICA and the aneurysm
and the surrounding structures.
–– The acquisition of the surgical skills for high speed drilling close to the
aneurysm, drilling the anterior clinoid process, controlling the proximal
ICA, mobilisation of the optic nerve, dissection of the perforating
vessels, application of various complex clip configurations and the
utilisation of adjunctive measures like cerebral protection and proximal
ICA control.
–– The development of the capability for alternative therapeutic strategies,
like endovascular procedures, that can preserve the arterial lumen and
provide a lasting repair, using stents, coils or both.
77
CHAPTER Internal Carotid
Bifurcation Aneurysms
Mathuriya SN  Tewari Manoj Kumar  Mukharjee KK  Paramjeet Singh
INTRODUCTION
•• Internal carotid artery (ICA) aneurysms can be classified into seven groups
based on the site of origin, wall morphology, and clinical and surgical
behaviour: (a) ICA extracranial, (b) ICA petrous and ICA cavernous, (c)
ICA ophthalmic, (d) ICA wall, (e) ICA-PCoA (f) ICA-AChA and (g) ICA
bifurcation (ICBA).
•• Arterial bifurcations are sites of maximal haemodynamic stress, where
cerebral aneurysms commonly develop.
•• In ICBA, the neck may not necessarily exist exactly at the ICA bifurcation
and it often deviates slightly to the M1 or A1 side. It generally deviates to
the side of the anterior cerebral artery (ACA).
•• ICB aneurysms constitute 5% of all intracranial aneurysms.
•• There is a male predominance.
•• These are relatively uncommon and frequently rupture at a younger age
compared to other aneurysms.
•• Around half of these aneurysms rupture, of which 50% are smaller than
7 mm.
•• These have an embryogenetic factor responsible for their origin.
•• Mean age of presentation at the time of rupture is 41 years.
•• In the younger age group (less than 20 years of age) these constitute more
than 40% of all intracranial aneurysms.
•• The probable risk factor could be arterial wall developmental defects and
wider angle of the ICA bifurcation.
•• Around 7% of ICA bifurcation aneurysms are giant.
•• Multiple aneurysms are seen in 43% of patients and the most frequent site
of another aneurysm is on the MCA.
•• Bilateral ICA bifurcation aneurysms occur in 6%.
•• Rebleeding occurs in 30−33% before clipping. Angiographic vasospasm
is present in 33−63% of ICBA.
•• No clinical symptomatology is specific for ICBA.
•• SAH is seen in the anterior cisterns in 92% of patients on CT scan.
•• There may be an intracerebral haematoma (ICH) in the orbitofrontal gyrus
(9.5−20%).
•• Fluid attenuated inversion recovery (FLAIR) sequence of MRI has recently
been shown to be effective for detecting SAH in the subacute period when
CT sensitivity decreases.
•• Lumbar puncture (LP) detects blood in 98% of SAH patients.
592
•• Uncommonly, when the aneurysm grows to a large size, it can cause

pressure on the medial temporal lobe leading on to epileptic seizures.
•• Sometimes, if the aneurysm is totally medially directed, it can compress
the anterior third ventricle leading to hydrocephalus.
•• Digital subtraction angiography (DSA) confirms or excludes an aneurysm.
•• Around 2−5% of aneurysms which are missed on the initial study due to
vasospasm are detected on repeat DSA.
•• Magnetic resonance angiography (MRA) can effectively demonstrate large
aneurysms.
•• CT angiography (CTA) reveals most aneurysms larger than 2−3 mm.
This has a high diagnostic accuracy with false negative results in very
small aneurysms. Around 99% of ruptured aneurysms of 3−4 mm can be
recognised by CTA.
•• It delineates details of the fundus, neck and relations to the branches
and, sometimes, this proves a better investigation than DSA in large/giant
complex aneurysms (as far as visualisation of large branching vessels is
concerned, but not the perforators).
•• The CTA lacks visualisation of perforators and dynamicity of the circulation.
•• It is mandatory to preserve flow in all the perforators surrounding or
adherent to the aneurysm dome.
•• Conventional four vessel angiography, DSA or 3D DSA are the diagnostic
imaging methods. Many projections and angles, e.g. anteroposterior,
lateral, forward oblique, reverse oblique and basal views, are used.
•• These are to delineate the aneurysm sac, its direction, projection, neck
size, configuration and straddling on to initial M1/A1, perforators and their
relation to neck/sac, status of vasospasm, extent of cross circulation and
any other associated aneurysms.
•• The 3D DSA provides not only 3D visualisation of the endoluminal image,
but also provides most precise correlation between rotational images and
actual findings at surgery.
•• For intra-operative navigation, 3D CTA and/or DSA should be rotated to
illustrate:
–– The angioarchitecture of the ICA bifurcation and its relation to the skull
base
–– Projection of the ICBA dome and its relationship to the A1 and M1
segments
–– The probable site of rupture.
ANATOMY
•• The ICA, after emerging from the cavernous sinus, traverses in the carotid
cistern and gives off the ophthalmic (OphA), superior hypophyseal (SHAs.),
posterior communicating (PCom) and anterior choroidal (Ach) branches.
•• Preservation of the Ach during different steps of dissection for ICBA or
temporary clipping is of paramount importance.
•• Infrequently, up to 3 small perforators arise from the posterior wall of the
ICA and pass to: (a) the optic tract, (b) the premammillary part of the floor
of the third ventricle, (c) the optic chiasm and (d) the infundibulum.
•• Arteries related to the ICB area are ICA, ACA, MCA, perforators from A1,
M1 (medial and lateral striate), recurrent artery of Heubner (RAH), Ach,
diencephalic branches of PCom and temporal branches of MCA.
Chapter 77 • Internal Carotid Bifurcation Aneurysms
593
•• There are a large number of perforating branches with their course behind
the ICA bifurcation. These arise from: (a) the choroidal segment of the ICA,
(b) the Ach, (c) the RAH, (d) the medial lenticulostriate arteries (MLAs) and
(e) the lateral lenticulostriate arteries (LLAs).
•• These aneurysms are covered by arachnoid from the carotid, olfactory,
lamina terminalis and Sylvian cisterns. When the aneurysm grows, it occupies
the Sylvian cistern and cistern of the lamina terminalis and compresses the
M1, A1 and the perforators which are displaced around the aneurysm.
•• Disposition of arterial branches around the aneurysm depends on the
direction of the fundus and its projection.
PRE-OPERATIVE EVALUATION
•• Clinical evaluation, investigations and medical management are the same as
for all other patients with aneurysmal SAH in other locations.
•• CSF drainage, if necessary (through lumbar or ventricular route), is performed
to lower the intracranial pressure (ICP).
•• To achieve a safe exposure, dissection and clipping the following points
must be adhered to:
–– Specific microsurgical approach as dictated by the direction and
projection of the aneurysm and length of the supraclinoid ICA.
–– Wide exposure of the Sylvian fissure, parent artery, main arteries and
perforators.
–– Arachnoid is separated and cut.
•• After clip placement, inspection is made to confirm the preservation of
perforators and the patency of main vessels if necessary by microvascular
Doppler (IMD).
•• Intra-operative angiography or indocyanine green angiography (ICG, if
facility is available) is performed.
•• The distal end of the clip is visualised free from any vessels or a part of it.
•• After the clipping, the aneurysm dome is punctured and the collapsed sac
can be mobilised, coagulated, transected and removed.
•• Multiple clipping using two or more clips is occasionally required for wide-
neck aneurysms.
INTRA-OPERATIVE RUPTURE
•• Intra-operative rupture (IOR)1 can occur during craniotomy, after dural
opening, during dissection or while clipping.
•• Morbidity and mortality is around 30% in IOR.
•• Earlier in the surgery the rupture takes place the worse is the prognosis.
•• In case of rebleed during craniotomy (before bone flap removal) the
procedure is postponed.
•• If the IOR occurs just before/soon after dural opening then continuance of
operation with the aim to clip the aneurysm will add to the trauma caused
by the fresh insult. Hence, the dura is opened and a large pericranial or
fascial patch is sutured to reduce ICP.
•• The bone flap is placed in the abdominal wall.
•• In case a large ICH in the frontal lobe is detected on intra-operative
ultrasound, CT or MRI then one can go ahead with haematoma evacuation,
clipping of aneurysm, decompressive craniotomy, duroplasty and post-
operative artificial ventilation.
594
•• The two most common causes of intra-operative rupture soon after initiation
of the procedure are retraction of the frontal lobe and dislocation of the ICA
while the aneurysm dome is still adherent to the frontal lobe.
•• The risk is highest for anteriorly projecting aneurysms.
•• Short and sudden hypotension by cardiac arrest, induced by intravenous
adenosine can be used to facilitate quick dissection and application of a
pilot clip in case of uncontrolled bleeding.
•• If the rupture takes place before completing the dissection, temporary
clips must be applied to the parent vessel proximally and distally, and the
aneurysm is prepared for pilot clipping under local flow arrest.
•• In case the bleeding aperture is exposed/dissected, a tentative clip can be
applied on the aneurysm just proximal to the rent in the aneurysm.
•• Tentative clipping can either be a temporary clip or a permanent clip (mostly
permanent clip) depending on the force required/extent of dissection
completed at the tentative clip site.
GIANT ANEURYSMS
•• Giant ICBA comprise 7% of all ICBA.
•• The dome of a giant ICBA is usually at least partially covered by the frontal
lobe and extends also into the Sylvian fissure.
•• Perforating arteries frequently follow and/or arise from the base of these
aneurysms and it may be very difficult, even impossible, to dissect them
free. The perforators are often draped over the aneurysm neck and dome.
•• The large size, distorted anatomy, origins of the perforating arteries and
other arterial branches originating directly from the aneurysm, calcifications
at the base, and intraluminal thrombus, make microneurosurgical
management of giant ICBA an extremely difficult task.
•• Comprehensive pre-operative imaging by CTA, DSA and MRI is mandatory.
•• The 3D reconstructions of the CTA and rotational DSA help to show the
aneurysm orientation with relation to the bony landmarks and to identify
calcifications, thrombus, organised thrombus and their location in the
aneurysm.
•• DSA provides important information about the flow dynamics of the ICA
bifurcation complex.
•• Direct clip occlusion remains the most effective treatment for giant aneurysms
as well.
•• In addition to obtaining detailed radiological work up of giant ICBA the
points to be considered are:
–– A comparatively larger craniotomy flap
–– Obtaining lax brain prior to approaching the aneurysm
–– Wide roomy exposure of the Sylvian cistern
–– Satisfactory exposure of ICA, M1, A1 and PCom for temporary
occlusion, if required
–– Assessment of size of the neck and its contents
–– Relation of the neck to the origin of the M1 and A1 so as to exactly
assess the safe clippable portion of the aneurysm sac. Intraluminal
thrombus can be removed and a temporary clip is applied at the patent
portion of the aneurysm
–– Working out the location of organised clots/plaques in relation to the
aneurysm neck on MRI, CT/CTA+DSA
Chapter 77 • Internal Carotid Bifurcation Aneurysms
595
–– Disposition of vessels around are visualised at surgery and are

cautiously dissected
–– A stepwise dissection and clipping of the aneurysm dome/body using
a tentative clip and then proceeding towards the base to achieve the
desired complete occlusion.
COMPLICATIONS
•• Intra-operative non-progressive soft brain bulge in which a haematoma is
not likely needs to be managed by duraplasty, avoidance of muscle closure,
post-operative decongestant therapy and removal of bone flap (if required).
•• Immediate post-operative motor deficit could result from marked ischaemia
due to temporary clipping for a prolonged period in the absence of good
collateral flow.
•• All attempts must be made to enhance perfusion by Triple H therapy,
antivasospastic measures, vasodilators and others.
•• Dense deficit could result from perforator injury.
•• Delayed deficits can develop due to subdural/epidural/intracerebral
haematoma which could result from a little lapse in haemostasis/
coagulopathy.
•• The other causes of deterioration could be development of hydrocephalus
and vasospasm.
•• Deterioration can also take place due to meningitis, electrolyte disturbances
and seizures.
•• Medical problems like chest infection/myocardial ischaemia/pulmonary
ischaemia can lead to depressed respiration, hypoxia, hypercarbia and
perfusion insults.
•• Endovascular treatment is being increasingly utilised as a definite
therapeutic strategy. Hence a final decision regarding treatment of these
lessons should be taken in consultation with intervention at therapist.
•• Hydrocoils consisting of a carrier platinum coil coated with a layer of
hydrogel polymer have been shown to possess a potential to achieve higher
rates of volumetric occlusion as a result of expansion of the hydrogel after
contact with blood.
•• Aneurysms are packed as densely as possible until angiographically
complete occlusion is achieved and/or the last coil cannot be introduced
into the sac.
•• Volumetric occlusion has been found to be significantly greater with
hydrocoils than with bare platinum coils (about 70% vs 20–30%)
immediately after embolisation.
•• Basilar and ICA aneurysms are subject to constant arterial pulsations,
the so-called “water-hammer” effect, which may play an important role
in recanalisation of these aneurysms, especially following incomplete
occlusion.
•• Recanalisation and coil compaction remain major limitations of embolisation
therapy.
•• A higher tendency for aneurysmal recanalisation and regrowth occurs in
incompletely occluded aneurysms at initial treatment.
•• Those at the bifurcation or wide-necked aneurysms are at higher risk.
78
CHAPTER
Anterior
Communicating
Artery Aneurysms
Mathuriya SN
INTRODUCTION
•• The anterior communicating artery (ACoA) complex is the most frequent site
of intracranial aneurysms, and an anterior communicating artery aneurysm
(ACoAA) is the commonest aneurysm, a neurosurgeon tackles.
•• The anatomy of the ACoA is complex with frequent associated congenital
vascular anomalies.
•• These aneurysms are located posteriorly between the frontal lobes and their
close proximity to the hypothalamus, optic nerves, chiasm and their blood
supply makes surgery of these aneurysms difficult.
•• Saccular, fusiform, blister, multiple including kissing ACoA and giant types
have been described.
INCIDENCE
•• The ACoAAs form 30−37% of all aneurysms and comprise the largest
percentage of ruptured aneurysms.
•• They are found to be more common in men with a male:female ratio of 2.3:1.
•• These aneurysms are seen in the middle aged with a peak in the late forties.
•• The ACoAAs are very rare in children.
•• The inheritable connective tissue disorders like polycystic kidney disease,
Ehler-Danlos syndrome, Marfan’s syndrome, neurofibromatosis type 1 and
alpha 1 antitrypsin deficiency may be associated.
AETIOLOGY
•• Aneurysmal formation has multifactorial aetiopathogenesis with genetic,
molecular, structural and flow dynamics being among the many factors
involved.
•• The genesis and increase in size of ACoAAs is due to loss of normal balance
between vascular vectors, flow rheology and arterial wall characteristics.
•• The progressive thinning and weakening of the wall finally result in
aneurysmal rupture and SAH.
•• The direction of the aneurysm is determined by the direction of dominant
flow.
•• It has been found that aneurysms with small impaction zones, higher flow
rates into the aneurysm and elevated maximum wall shear stress were
more likely to rupture.
•• The angles of the arteries at bifurcations, as well as the blood flow cause
haemodynamic stress on the apical region, leading to aneurysm formation.
Chapter 78 • Anterior Communicating Artery Aneurysms
597
•• ACoAAs are associated with the smaller A1-A2 angle junction of the ACoA
complex, where higher haemodynamic stress occurs in patients with
normoplastic A1 segments.
MICROSURGICAL ANATOMY OF ANTERIOR

COMMUNICATING ARTERY COMPLEX
Anterior Cerebral Artery
•• This artery arises as one of the two terminal branches of the ICA at the
medial end of the Sylvian fissure.
•• It runs anteriorly and medially above the chiasm (70% of cases) or optic
nerve and enters the interhemispheric fissure.
•• Arteries from both sides are joined together by the ACoA at the beginning
of the interhemispheric fissure.
•• These two arteries then ascend in front of the lamina terminalis to pass
into the interhemispheric fissure.
•• The arteries make a smooth curve around the genu of the corpus callosum
and pass backwards in the pericallosal cistern.
•• The pericallosal artery continues backwards along the splenium to
anastomose with splenial branches of the posterior cerebral artery.
•• The recurrent artery of Heubner arises from the A2 segment in about 80%
of cases.
•• It then runs laterally and passes in close relationship to the superolateral
aspect of the proximal ACA or A1 segment.
•• It turns upwards and backwards to enter the anterior perforated substance.
•• The ACA is divided into three segments:
1. The segment from the bifurcation of the ICA to the point of origin of the
ACoA is known as A1 segment. This is also known as the horizontal
part of the ACA.
2. The segment distal to the ACoA up to the point of origin of the
callosomarginal artery is known as the A2 segment.
3. The part distal to the origin of the callosomarginal is termed
pericallosal artery.
•• Depending upon the site of origin the aneurysms are divided into the
following five groups:
1. Junction of the A1 segment and a perforating artery
2. A1 segment directly
3. Proximal end of A1 fenestration
4. A1 segment and cortical branch
5. Fusiform dilatation of A1 segment.
ANTERIOR COMMUNICATING
ARTERY COMPLEX
•• The ACoA overlies the optic chiasm at the level of lamina terminalis.
•• The average length of this artery is 4 mm (0.3−7 mm) and it consists of a
single or multiple channels.
•• Three to four branches arise from the posterior/inferior aspect of the ACoA
and supply the fornix and septal region.
•• Intrasellar aneurysms originating from the ACoA are located above the
chiasm or optic nerves.
598
A B
C D
Figs 1A to D: Patterns of circulation through the anterior part of the circle of Wil-
lis. (A) Type I circulation showing ipsilateral filling of the ACA on carotid injection.
(B) Type II circulation showing bilateral filling of ACA from either carotid injection.
(C) Type III circulation (dominant) with the opposite Alhypoplastic and with
poor collateral circulation. (D) Type IV circulation (dominant with foetal PCA)
with very poor circulation
•• The A1 courses above the optic chiasm or nerves to join the ACoA.
•• The junction of the ACoA with the right and the left A1 is usually above the
chiasm (70% of brains) rather than above the optic nerves (30%).
•• Sengupta et al. found the following four types of collateral circulation
(Figs 1A to D):
–– Type I: Ipsilateral (66%). In this type the aneurysm and the distal ACA
fill from one proximal ACA.
–– Type II: Bilateral (14%). The aneurysm and both the ACAs fill from
both carotid injections.
–– Type III: Dominant ACA (12%). The aneurysm arises from the axilla
of the two anterior cerebral arteries, both of which fill from one anterior
cerebral. The contralateral A1 segment is hypoplastic.
–– Type IV: Dominant ACA with foetal posterior cerebral artery (8%).
CLINICAL FEATURES
•• Most ACoAAs present with a bleed causing the classical “thunder clap”
headache described commonly by patients as the “worst headache of
their life”.
•• Not taking cognisance or failing to take this history can lead to the diagnosis
being missed with disastrous consequences.
•• These aneurysms can present with loss of consciousness, seizures,
anosmia, oculomotor nerve paresis, diabetes insipidus or hypothalamic
dysfunction.
•• The aneurysm can cause a large frontal haematoma or intraventricular bleed.
•• Acute and chronic hydrocephalus can be the cause of neurological
deterioration in these patients.
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The “ACoA Syndrome”

•• Patients with ACoAAs may present with memory disturbance, confabulation,
paraparesis and personality changes.
•• This has been characterised as the “ACoA syndrome”.
•• All these patients had evidence of frontal lobe dysfunction throughout their
post-operative course and deep venous thrombosis and pulmonary emboli
were common causes of morbidity and mortality.
•• The combination of vasospasm in the ACA distribution and lower extremity
weakness associated with cognitive and affective impairment that resolves
with time is common in patients with ACoAAs.
•• It is proposed that this constellation of clinical, radiographic and pathologic
findings be referred to as the “ACoAA paraparesis syndrome”.
•• Sensory disturbances are also seen. Occasionally Gait apraxia is defined
as the loss of ability to walk in the absence of weakness.
•• Extrapyramidal symptoms and incontinence result due to injury involving the
anterior cingulate gyrus, medial superior frontal gyrus or the superolateral
frontal gyrus.
•• Altered states of sensorium similar to akinetic mutism may be seen along
with abulia, a decrease in spontaneous speech with increased response
latency and decreased capacity to persist while doing an activity.
•• Vascular injury to the corpus callosum causes a type of disconnection
syndrome with ideomotor apraxia, agraphia and tactile anomia restricted
to the left hand.
•• Pathological grasp phenomena or alien hand syndrome can be an
associated finding.
•• Vascular injury to the frontal lobe or basal ganglia has been linked to the
pathological grasp reflex seen in these patients.
Neuropsychological Symptoms
•• These are common in patients with ruptured ACoAA.
•• Neuropsychological examination must be detailed and performed in all
patients with a suspected ACoAA both before and after surgery.
•• These include mini mental scale examination (MMSE), the micro cognitive
test, computerised assessment of cognitive function (CACF), Wisconsin
card sort, trail-making test, Rey’s complex figure test and recall and portions
of the Wechsler Memory Scale 3 among others.
•• The CT and clinical evidence suggested that infarction in the territory of the
ACoA was responsible for amnesia and personality change.
•• The medial septal nuclei, the paraventricular nucleus of the anterior
hypothalamus and the medial forebrain bundle were the probable regions
involved.
Visual Symptoms
•• The ACoAAs can cause visual symptoms by direct chiasmal and optic
nerve compression or due to indirect ischaemic aetiology.
•• It has been observed that as the aneurysm enlarges, the down-pointing
dome compresses the optic nerve from above and adheres to it.
•• When the aneurysm ruptures through the adherent dome, it bleeds directly
into the optic nerve, resulting in severe headache and monocular blindness.
•• Distortion or traction, and indirect pressure on the optic nerves at the
margins of the optic foramina also play an important role.
600
•• Interference with the blood supply of the optic nerve or chiasma either by
occlusion or distortion of the perforating arteries may be responsible for
these symptoms.
•• In large ACoAAs, the intra-aneurysmal thrombus may occlude the origins
of the branches supplying the optic nerves and chiasm, thus causing
ischaemia.
•• An adherent optic nerve to the fundus of the ACoAA may be damaged
from direct haemorrhage.
Endocrinological Symptoms
•• The syndrome of inappropriate secretion of antidiuretic hormone (SIADH),
cerebral salt wasting syndrome (CSW) and diabetes insipidus (DI) are
seen in these patients and they need to be differentiated as the treatment
modalities differ significantly.
Hydrocephalus
•• Hydrocephalus requiring shunt placement is a common complication after
aneurysmal subarachnoid haemorrhage (aSAH).
•• Cerebrospinal fluid (CSF) diversion procedures are often required in
patients with an ACoAA.
•• These aneurysms are close to the third ventricle and lamina terminalis
and often the aneurysmal bleed extends into the ventricle and can cause
acute hydrocephalus causing rapid clinical deterioration within 24−48
hours after SAH.
INVESTIGATIONS
Computerised Tomography (CT)/Magnetic Resonance
Imaging (MRI)
•• Computerised tomography (CT) of the brain is generally the first
investigation ordered after a thunderclap headache.
•• The CT shows characteristic anterior interhemispheric fissure SAH and
a frontal intracerebral haematoma should raise the suspicion of a bleed
due to an ACoAA.
•• Diffuse and extensive SAH is often seen and attention is then paid to look
for the usually globular hyperdense aneurysm in the ACoA region.
•• Flame shaped intraparenchymal haematomas in the gyrus rectus are
characteristic of ACoA aneurysmal bleed.
•• Calcified aneurysm and atherosclerotic walls may be seen in giant
aneurysms.
•• Hydrocephalus was seen in 25% of their cases.
•• Frontal lobe infarcts were seen in 20% of cases and bilateral anterior infarcts
were seen due to associated vasospasm.
•• A normal CT scan should be looked at with caution and if the history and
clinical features are pointing to an ACoA aneurysmal bleed a lumbar
puncture should be done to look for crenated RBCs and evidence of SAH.
3D Computerised Tomography Angiography
•• The 3D-4D CT angiography can be done in the emergency situation and
provides a very good information about these complex aneurysms and
adjacent structures and vessels.
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•• The CT angiography was reported to be superior to both DSA and MR

angiography in the evaluation of the arterial branching pattern at the
aneurysm neck, aneurysm neck geometry, arterial branch incorporation,
mural thrombus and mural calcification.
Magnetic Resonance Imaging and
Magnetic Resonance Angiography
•• The MRI shows these aneurysms and the regional neuroanatomy very well.
•• This is the best modality to visualise the associated infarcts and regions
of ischaemia.
•• Aneurysms missed on conventional angiography can be seen sometimes.
•• The morphology, configuration of aneurysm and fundus direction are well
observed.
•• The MRI is indispensible in the evaluation of giant ACoAAs as angiography
can underestimate the true size of the aneurysm due to a large thrombus.
Conventional Angiography
•• Multiple angiographic views (standard, oblique, submental vertex views)
are usually required to visualise these aneurysms.
•• Oblique views with the ACoA artery projected into the centre of the left and
the right orbits are essential pre-operative studies. A basal view is helpful.
•• Individual aneurysms are studied for their morphology, direction, flow
features and associated vasospasm.
•• Anterior communicating aneurysms rarely arise from the ACoA itself.
•• The aneurysm is usually to one side of the ACoA in relation to one of the
major vessels.
•• An understanding of this is important for successful occlusion of the neck
without compromise of other vessels.
CLIPPING AND COILING DEBATE IN

THE MANAGEMENT OF ANTERIOR
COMMUNICATING ARTERY ANEURYSMS
•• The ACoAAs are least amenable to interventional methods of treatment
due to multiple factors.
•• The endovascular techniques to treat aneurysms require that the intimal
proliferation occurs over the platinum coils and the thrombus forms to
obliterate the aneurysm.
•• In ACoAAs due to the aneurysm being in the direct line of flow this intimal
proliferation may be less optimal than in side wall aneurysms.
•• The ACoAAs are smaller and their sac may be too small for coil placement.
•• Other factors complicating this treatment were when the aneurysmal neck
was not clearly distinct from the adjacent or parent vessels or because the
aneurysm sac was too small and treatment may be difficult due to atheroma
of the cervical and intracranial vessels.
•• Giant ACoAAs are less amenable for treatment by coiling and tend to have
significant residual lumens and tendency to recanalise post-coiling and
these may require special types of stents.
•• The contention that microsurgical clip application should be the preferred
option in the treatment of ACoAAs with anteriorly directed fundi and that
endovascular packing is selected for those lesions with posteriorly directed
fundi, depending on morphological criteria is currently followed.
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SURGICAL TECHNIQUE
•• The majority of the aneurysms in this area point anteriorly and inferiorly,
and are safely clippable.
•• The posterior and superiorly pointing aneurysms are fraught with more
risks due to the proximity and involvement of ACoA perforators, recurrent
artery of Heubner and A2 segments.
•• Great skills and experience are required in the surgical management of the
ACoAAs due to the disproportionate fundus to neck ratio.
•• A broad based neck which incorporates the parent vessel and mass effect
that can totally alter regional anatomy may make clipping impossible at
times.
•• The ACoAAs present frequently with SAH when they are small.
•• Furthermore, unruptured ACoAAs may have increased risk of rupture
regardless of size; also they may be associated with other aneurysms.
•• The aim in microneurosurgical management of an ACoAA is total
occlusion of the aneurysm sac with preservation of flow in all branching
and perforating arteries.
•• The surgical trajectory should provide optimal visualisation of the ACoA
complex without unnecessary brain retraction.
•• Temporary clips, pilot clips and a wide selection of fenestrated and normal
clips along with a good surgical and radiological pre-planning are required
in complex giant aneurysms.
•• Cranial base approaches are routinely used and give more exposure with
minimal retraction of the brain.
•• The angles of approach and area of exposure to the ACoAAs associated
with pterional (PT), orbitopterional (OPT) and orbitozygomatic (OZ)
craniotomies before and after gyrus rectus resection differ.
•• The vertical and horizontal angles of approach to the ACoAA complex
are significantly larger for the OPT and OZ approaches compared with
the PT approach.
•• Use of the OZ approach may decrease the need for frontal lobe retraction
and resection of the gyrus rectus.
PRE-OPERATIVE MEASURES
•• All patients with a ruptured ACoAA should be immediately admitted in a
neurosurgical intensive care unit and standard guidelines for management
of SAH are useful to decide on patient management.
•• The patient is monitored closely to treat haemodynamic and neurological
deterioration.
•• Anticonvulsants, steroids and calcium channel blockers are used as
indicated.
•• Close watch is maintained to pick up vasospasm which may require
aggressive treatment.
APPROACHES TO ANTERIOR COMMUNICATING

ARTERY ANEURYSMS
•• The approaches to ACoAAs are: anterior, lateral and skull base approaches.
•• The anterior approaches include the anterior interhemispheric, basal
interhemispheric and the midline trephine approach.
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Side of Approach
•• These are usually approached from the right side to prevent injury to the
dominant hemisphere and because it is easier for a right-handed surgeon
to approach from the right side.
•• However, these aneurysms being in the midline are approached from
the left or right side depending upon the side of the dominant A1, and
associated frontal lobe haematoma, direction of the fundus, pre-existant
anterior cerebral territory infarct and radiographic characteristics seen on
angiogram and CT angiograms (Fig. 2).
•• The dominant A1 is used for achieving proximal control and also because
the dome of the aneurysm is generally pointing towards the direction of
main thrust of flow, i.e. away from the direction of the dominant A1.
•• If there is a large frontal haematoma then it is advisable to operate from
that side allowing for evacuation of haematoma and also preventing the
possibility of bifrontal injury.
•• Similarly, a large infarct on one side may warrant an approach from the
same side.
Approaches:
•• The subfrontal modified gyrus rectus approach
•• Pterional craniotomy
•• Anterior interhemispheric approach
•• The basal interhemispheric approach
•• Midline trephine approach
•• Other skull base approaches: In the orbitozygomatic approach and modified
orbitozygomatic approach removal of the orbital rim and the zygomatic
arch can be combined with a fronto-temporal craniotomy to gain additional
space, so as to decrease cerebral retraction.
•• Orbitopterional Approach: The orbitopterional (OPT) approach is an anterior
skull base extension of the PT approach that provides greater exposure to
the anterior cranial fossa, supra and parasellar regions and ACoA complex.
With use of the OPT approach, resection of the zygomatic arch is not
needed and extension of the temporal craniotomy is considerably less.
Fig. 2: Illustration showing the various directions of the ACoAA

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•• Orbitocranial approach
•• Supraorbital keyhole minicraniotomy
•• Endoscopic assisted microneurosurgery.
GIANT ANTERIOR COMMUNICATING

ARTERY ANEURYSMS
•• A giant intracranial aneurysm is defined as one larger than 2.5 cm in
diameter.
•• These represent about 5−8% of all intracranial aneurysms.
•• Patients with a giant aneurysm present with mass effect that causes visual
symptoms due to pressure on the optic nerves and chiasm, cranial nerve
dysfunction, hemiparesis, seizure or headache.
•• Hydrocephalus is due to pressure on the anterior third ventricle.
•• Dementia was usually caused by direct brain compression by the aneurysm
rather than by hydrocephalus. Optic apparatus compression occurred even
with smaller aneurysms (2.7–3.2 cm) when they pointed inferiorly.
•• Aneurysm neck clipping possible in half of the cases and special techniques,
including temporary clipping, evacuation of intraluminal thrombus, tandem
and/or fenestrated clipping, and clip reconstruction were often required.
•• Occlusion of or injury to the ACA is the main cause of poor outcome or death.
•• Proximal ACA occlusion, even of dominant A1 segments with small or no
contralateral A1 artery, was an effective treatment alternative and was
well tolerated as a result of excellent leptomeningeal collateral circulation.
•• Appropriate clip selection and proper sequencing of multiple clips are
important. Straight clips with short blades are preferred to avoid hindrance
of the surgeon’s operative field and interference between the clips.
•• Multiple and fenestrated clips may be required to reconstruct the vascular
anatomy.
•• These aneurysms can be trapped, opened and the thrombus removed using
a cavitron ultrasonic surgical aspirator (CUSA) and then the reconstruction
is done using various clips.
•• Vascular clamps may be required in some cases followed by definitive
clipping.
•• When direct surgical clipping or endovascular repair is contraindicated, the
high-flow EC-IC bypass is a viable surgical option.
FUSIFORM ANTERIOR COMMUNICATING

ARTERY ANEURYSMS
•• A thorough review of angiograms and 3D CT angiography reconstruction
is essential for planning the treatment images to identify the complex and
fusiform entity of ACoAA.
•• The importance of experience in operative techniques and thorough
knowledge of the ACoA anatomy in tackling these rare forms and maintain
flow in all vessels while surgically recreating an ACoA of normal calibre
can not be minimized.
BLISTER-LIKE ANTERIOR COMMUNICATING

ARTERY ANEURYSMS
•• Blister aneurysms are rare lesions characterised by a hemispherical shape
and fragile walls.
605
•• Blister-like aneurysms constitute technically challenging lesions that may

occur at the ACoA.
•• Usually, blister-like aneurysms have been reported to occur at non-
branching sites of the dorsomedial ICA.
•• The CT angiography is valuable in diagnosis.
•• Blister-like aneurysms should be suspected when DSA is negative for
subarachnoid haemorrhage.
•• These aneurysms arise from the horizontal portion of the ACoA without
any involvement of the branches of the ACA.
•• All such aneurysms are thin-walled and lacked a surgical neck.
•• These lesions are treated with straight fenestrated clips through the A1-
ACoA junction, thus remodelling the ACoA.
KISSING ANTERIOR COMMUNICATING

ARTERY ANEURYSMS
•• The term “kissing aneurysms” refers to two anatomically adjacent
aneurysms with different origins and partially adherent walls.
•• These require careful pre-operative planning and surgical techniques
like gyrus rectus resection, applying temporary clips on the A1 segment,
coagulation and shrinkage of one aneurysmal sac, appropriate clip selection
and sequencing.
•• Kissing ACoAAs can be successfully clipped.
COMPLICATIONS
•• Hydrocephalus, perforator and arterial occlusion, vasospasm, parenchymal
brain injury, neuropsychological sequelae and electrolyte disturbance are
common complications after aSAH from ACoAAs.
•• Intra-operative rupture
•• Injury to arterial branches and perforators
•• Brain retraction injury
•• Post-operative haematomas, optic nerve and chiasmal injuries and rarely
optic chiasm arachnoiditis due to wrapping of the aneurysm by material,
like muslin, are seen.
79
CHAPTER Distal Anterior Cerebral
Artery Aneurysm
Ravi Ramamurthi  Shivaram Bojja
INTRODUCTION
•• Distal anterior cerebral artery (DACA) aneurysms, located distal to the
anterior communicating (ACom) artery on the A2-A5 segment of the anterior
cerebral artery (ACA) are less common and account for 3.1–9.2% of all
intracranial aneurysms.
•• The characteristics of the aneurysm arising from distal accessory ACA are
considered similar to those of distal ACA aneurysms.
MICROSURGICAL ANATOMY
•• Most DACA aneurysms arise at the pericallosal-callosomarginal artery
(PerA-CMA) junction, which is usually located in the A3 segment of the
ACA around the genu of the corpus callosum.
•• The aneurysms can rarely arise at the origin of the frontopolar artery more
distally.
•• Aneurysms in the PerA-CMA junction are divided into two types according
to their location:
1. Supracallosal
2. Infracallosal.
•• Infracallosal distal ACA aneurysms are defined as those located in the
lower-half of the A3 segment, which makes it more difficult to gain proximal
control.
CLINICAL CHARACTERISTICS
•• The average age at presentation is 50 years with a slight female
preponderance.
•• Patients with ruptured DACA aneurysms present with symptoms and signs
typical of subarachnoid haemorrhage (SAH) with occasional monoparesis
of a lower extremity.
•• A hemispheric disconnection syndrome may occur if there has been a
significant intracallosal haemorrhage.
•• Intracerebral haemorrhage is a common (50%) complication of ruptured
DACA aneurysms.
•• DACA aneurysms are commonly associated with other intracranial
aneurysms and may be identified in patients investigated for SAH from
aneurysms at other sites.
Chapter 79 • Distal Anterior Cerebral Artery Aneurysm
607
INVESTIGATIONS
•• The computerised tomography (CT) findings are similar to those seen with
ACom aneurysms.
•• Hyperdense areas are seen in the interhemispheric fissure, cingulate
sulcus, pericallosal cistern and cistern of the lamina terminalis in ruptured
aneurysms.
•• A four-vessel digital subtraction angiography (DSA) is the investigation of
choice for evaluation of SAH from DACA aneurysms.
•• For determining the laterality of the aneurysm a unilateral injection of
contrast is done.
•• CT angiography is also useful to detect these aneurysms.
SURGICAL CONSIDERATIONS
•• As the two anterior cerebral arteries are side by side, in close proximity to
each other the effect of SAH, haematoma and surgical manipulation may
involve both the vessels. At surgery, if the callosomarginal artery is mistaken
for the pericallosal artery, the surgery will be difficult.
•• With the patient in the supine position, a craniotomy flap is raised, with
the medial limb over the sagittal sinus.
•• The callosomarginal and pericallosal arteries are closely related to
the neck and the fundus of the aneurysm and care should be taken to
preserve the continuity of the vessels while applying the clip.
•• Proximal control of the feeding artery is not easily possible in this
approach. Resection of a portion of the corpus callosum helps in
providing excellent exposure of the proximal A2 segment.
•• No untoward effects of small resection of the corpus callosum have
been noticed.
•• Occasionally, a transfalcine approach through the side opposite to the
lesion by cutting the falx, will help direct visualisation of the lesion and
clipping of the aneurysm.
•• Endovascular treatment by coiling, including parent vessel occlusion using
coils or coils combined with N-butyl-2-cyanoacrylate is safe and effective.
80
CHAPTER Middle Cerebral
Artery Aneurysms
Mathuriya SN  Pathak A  Gupta Vivek  Grover VK
•• They constitute around 20% of all cerebral aneurysms.

•• The commonest location is for both the ruptured and unruptured group
middle cerebral artery (MCA) bifurcation.
•• Mirror MCA bifurcation aneurysms are seen in 14% of patients.
•• The majority of MCA bifurcation aneurysms are located between two or
three M2 branches as a lateral extension of the M1 segment and they
project laterally.
•• Aneurysms in this location, more frequently than other locations, produce
ICH, but have a lesser incidence of hydrocephalous.
•• Aneurysms of the M1 segment arise at the origin of the temporopolar or
anterior temporal arteries (lateral wall) or in relation to the lenticulostriate
arteries [(medial wall) 10−15%].
ANATOMY
•• Middle Cerebral Artery: The MCA is classically divided into four segments.
These are: (1) the M1 or sphenoidal segment; (2) the M2 or insular segment;
(3) the M3 or opercular segment and (4) the M4 or cortical segment.
•• The MCA aneurysms can be classified location wise as: (1) M1 segment—
(a) at lenticulostriate arteries takeoff, (b) at temporal arteries take off,
(c) at frontal arteries take off; (2) MCA bifurcation or trifurcation and (3)
Distal sites on M2, M3 and M4 segments.
•• Most studies indicate that MCA bifurcation aneurysms are the commonest
(80−90%).
•• The MCA, after its origin from the inferier cerebral artery (ICA) lateral to
the optic chiasm, traverses underneath the anterior perforated substance
(APS) and 1 cm posterior to the lesser wing of the sphenoid.
•• In the Sylvian cistern, it makes a posterosuperior turn (genu) at the limen
to lie on the surface of the insula.
•• At the periphery of the insula, the branches of the MCA lie on the medial
surface of the frontal, temporal and parietal opercula.
CLINICAL FEATURES
•• Middle cerebral artery aneurysm rupture leads to a symptom complex which
is indistinguishable from subarachnoid haemorrhage (SAH) due to bleed
of an aneurysm in any other location.
•• Severe headache is the most prominent symptom of SAH which is usually
diffuse, but one-third of patients with MCA aneurysms have unilateral
headache.
Chapter 80 • Middle Cerebral Artery Aneurysms
609
•• More than half of the patients with a ruptured MCA aneurysm lose
consciousness, which is more than in aneurysms in other locations.
Intracerebral Haematoma
•• Around 30% of ruptured MCA aneurysms present with intracerebral
haematoma (ICH).
•• A haematoma extending into the frontal operculum and the temporal
operculum, bridging the sphenoid ridge, is virtually pathognomonic of a
ruptured MCA aneurysm.
•• Computed tomography (CT) is mandatory to diagnose SAH, IVH and ICH.
•• The location of the ICH, its size, extension and associated ischaemic
areas and infarcts in the temporal/frontal lobe or associated intra-Sylvian
haematoma (ISH) also help in diagnosing the site of aneurysm rupture.
•• Management of ISH needs appropriate and precise judgement as it involves
a large number of perforators in the Sylvian cistern with their variations and
adhesion to the haematoma.
•• Patients with temporal ICH are usually in poor grade or they may deteriorate
fast because of tentorial herniation.
INVESTIGATIONS
•• After CT has confirmed SAH, an angiogram/CTA is performed on an urgent
basis after confirming fitness for the same, mainly after assessing hydration
and renal parameters.
•• MCA bifurcation aneurysms have three main projections: (1) anterosuperior;
(2) posterior and (3) inferior.
•• These aneurysms are classified into five types:
(1) Intertruncal—These have a superiorly and posteriorly directed dome
and the base is usually towards the M2, and the M2 is commonly
involved in the base.
(2) Inferior MCA bifurcation aneurysms project inferiorly and anteriorly
towards the sphenoid ridge.
(3) Lateral aneurysms project in line with the long axis of M1.
(4) Insular MCA bifurcation aneurysms project towards the insula in the
coronal plane and medially in the axial plane. Types 2 and 4 are not
intertruncal and do not involve the M2.
(5) Complex MCA bifurcation aneurysms.
•• A detailed anatomical study, not only of the aneurysm complex (neck
size, fundus, lobes, rupture site) but also the vessel of origin, branching,
perforators close to the neck and fundus and their adherence, and any
branches originating from the fundus/just close to the neck, origin of other
vessels, type of circulation, displacement of vessels, vasospasm, any other
aneurysms and any associated lesions is essential for planning treatment.
•• Information about dynamic flow is important when DSA or 4D CTA is done.
•• All these details are useful for planning the type of treatment, type of
approach, exposure of vessels, temporary clipping and dissection around
the neck.
•• The 3D DSA provides most of the information required.
•• However, this being an endoluminal contrast study, it under represents all
intraluminal contents (plaques, calcification, etc.).
•• Distal MCA aneurysms arising from the second bifurcation are still in the
Sylvian fissure, but not those arising beyond the M3.
610
•• Almost all MCA aneurysms have a neck except fusiform, serpentine and
dissecting ones.
•• The CTA being a non-invasive, short procedure, not requiring much of the
patients’ co-operation can be used as a definitive diagnostic modality for
MCA aneurysm diagnosis.
•• Many MCA aneurysms are bulbous and broad necked.
•• The CTA can provide information to pre-operatively decide on the size and
shape of clips required, and also the need for multiple clips.
•• 4D Computed Tomography Angiography provides details of aneurysm wall
dynamics, e.g. dome pulsation, blebs and growth of aneurysm.
•• It entails CTA with a retrospective electrocardiography-gated reconstruction
algorithm by use of technology that was developed initially to examine
coronary arteries.
TREATMENT
•• Direct microsurgical repair is the most accepted, common, effective, and
safe modality to treat MCA aneurysms, specifically with a wide neck and
with major branches arising at the initial portion of the dome/base.
•• The peripheral location and comparatively well known anatomy and
characteristics are more suitable and acceptable for microsurgery.
•• Anatomical variations are seen, but usually are well known and described.
•• In spite of all these positive characteristics, these aneurysms do not have
that good an outcome in spite of a safe and non-complicated clipping
technique.
•• The responsible factors for poor outcome are: initial poor clinical grade;
hemiparesis/hemiplegia; dense SAH; ISH; large temporal/sometimes frontal
ICH and raised ICP.
•• Dense SAH and ISH cause vasospasm also.
•• Many a time a large temporal ICH demands an emergency evacuation and
clipping of aneurysm/EVT.
General Principles of Surgery

•• The general principles of surgery are an adequate exposure and no brain
retraction. These are the keys to successful aneurysm surgery. Excessive
retraction leads to unsatisfactory results. The critical elements of aneurysm
surgery are: (1) head positioning and fixation determined by the origin of
the aneurysm and direction of the fundus; (2) extent of bony exposure;
(3) relaxation of the brain via drainage of cerebrospinal fluid (CSF),
evacuation of haematoma or by other means like normoventilation and
cerebral decongestants in acceptable doses and (4) dissection should
routinely be limited within the subarachnoid space (SAS).
•• Three basic approaches have been described:
1. Proximal Trans-Sylvian—Splitting the Sylvian fissure medially and
following the MCA trunk distally.
2. Distal Trans-Sylvian—Following the major divisions proximally to the
aneurysm by opening the fissure peripherally/distally.
3. Superior Temporal Gyrus (STG) Approach—Making a small corticec-
tomy in the STG and subsequently entering the distal portion of the
Sylvian fissure and following the M2 branches to the aneurysm.
Chapter 80 • Middle Cerebral Artery Aneurysms
611
Intra-operative Microvascular Doppler

•• Intra-operative microvascular Doppler (IMD) is useful in preventing incorrect
placement of the clip more so in MCA bifurcation aneurysms due to the
need for confirming the patency of three and, sometimes, four vessels.
•• Mechanical arterial spasm is treated by topical sodium nitroprusside (SNP)
and its efficacy is verified by IMD.
•• This is a feasible, safe, and very reliable technique for aneurysm surgery.
•• Compared to other procedures such as intra-operative angiography, the
cost and efficiency of IMD is favourable.
•• In complex and large aneurysms, a suspected residual neck could be
detected by the typical turbulent flow.
•• A 20-MHz 1-mm vascular probe is an appropriate module for direct
insonation of the afferent and efferent vessels and the aneurysm sac before
and following surgical clipping.
Indocyanine Green Chorioangiography

•• It is an extremely useful non-invasive technique to help in dissection to obtain
a proper orientation, visualisation of perforators, wall thickness and plaques.
•• This is a great help in delineating the remaining aneurysm neck and any
vessel compromise due to the clip, the placement of which can be modified
accordingly.
Neuroprotection
•• In addition to the routinely used intravenous brain protectants (IVBP,
mannitol, antioxidants), the brain-protecting anaesthetic agents include
propofol, etomidate, pentobarbital and isoflurane.
•• These are administered individually or in combination.
•• Intermittent temporary clip application with periods of reperfusion had
significantly less chance of developing an infarction than those who
underwent one continuous episode of long occlusion.
•• Propofol and etomidate have been shown to decrease the cerebral
metabolic rate for oxygen (CMRO2) and have the ability to produce a
burst-suppression pattern on EEG with conclusive evidence of reduced
neuronal damage following experimental ischaemia.
Temporary Clipping
•• The safety and value of temporary clipping of the MCA are matters of
considerable controversy.
•• Temporary clipping helps in dissection of awkward necks, providing clarity of
vision, reducing tension in the sac, capacity to open the sac and evacuation
of clot. These render complete/near complete occlusion possible.
•• Pentothal is administered in a loading dose of 10 mg/kg body weight (BW) 5
minutes before temporary occlusion and a maintenance dose of 5−10 mg/kg
BW to produce burst suppression pattern on electrocorticography (ECOG).
•• Pentothal can also be introduced as 3−5 mg/kg BW intravenously (IV) which
is repeated every 15−20 minutes, if occlusion extends beyond that time.
100 gm mannitol, 20−30 minutes prior to temporary clipping, is protective.
1 gm methyl prednisolone, 50 ml/hr, low molecular weight dextran and IV
vitamin E or C have also been recommended for neuroprotection.
612
•• Hypertension is maintained at 150 mmHg systolic. Mild hypothermia of 33−34

degrees centigrade has also been found to be effective in a few isolated
studies.
•• The clip blades used should be of low force, the maximum being 70−80
gm (Sugita, Yasargil).
•• Higher force, longer duration and repeated application at the same
site may lead to partial endothelial damage to total desquamation and
fragmentation, thereby exposing the subendothelial layers, which is
followed by proliferation of smooth muscle cells, accumulation of connective
tissue and lipid deposition.
•• The changes in the smooth muscle cause changes in the adjacent nerve
fascicles impairing neurogenic innervation and autoregulatory function.
•• The vascular occlusion force is determined by four variables. These
are vessel diameter, blood pressure, clip blade contact area and vessel
elasticity.
•• A few moments after MCA occlusion, the blood flow falls to 10 mL/100 gm/
min in primates (normal 50 mL/100 gm/min), which is sufficient to induce
infarction within 6 hours.
•• This is sufficient to abolish electrical activity of the cortex, but reperfusion
within 15 minutes restores the activity.
•• Ischaemia induced in humans by temporary clipping depends on collateral
circulation, area containing deep perforators (with poor collateral flow) and
blood supply to major deep nuclei (6 minutes – 15 minutes).
•• Clinical/radiographic stroke takes place when occlusion lasts greater than
20 minutes. When hypertension and mild hypothermia are used, temporary
occlusion is tolerated better.
•• Temporary occlusion under somatosensory evoked potential (SEP) and
motor evoked potential (MEP) monitoring indicate that gradual attenuation
of SEPs/MEPs takes place after temporary vascular occlusion. This does
not cause ischaemic brain damage if recirculation is established within
about 10 minutes of the disappearance of the potentials. These have been
observed after ICA and MCA temporary occlusion.
•• Observations to be made after clipping are—ensure ample room for
adequate blood flow to all distal vessels from the bifurcation area and full
patency of distal branches from the bifurcation.
•• Distal tip of the clip is off any branches/perforators.
•• Sometimes, branches originate from the sac or even the dome.
•• Multiple clips to safeguard these branches are really mandatory.
Mini-craniotomy Approaches
•• With the aid of navigation, it is possible to easily locate MCA aneurysms and
perform minimally invasive surgeries such as mini-craniotomies, tailored
Sylvian dissection and successful clipping of unruptured MCA aneurysms.
•• Navigation systems incorporate almost real-time localisation, orientation
and guidance that facilitate minimally invasive techniques and enable
surgeons to achieve the desired results with accuracy and safety.
•• Minimally invasive techniques are contraindicated for giant aneurysms and
are not generally accepted for recently ruptured aneurysms.
81
CHAPTER Posterior Circulation
Aneurysms
Ashish Suri  Sachin A Borkar  Nalin K Mishra
MICROSURGICAL ANATOMY
The anatomy of the posterior circulation and its relationship to adjacent neural
structures can conveniently be divided into the following three neurovascular
complexes:
1. The basilar apex: Basilar artery (BA) bifurcation, posterior cerebral artery
(PCA), superior cerebellar artery (SCA), BA-SCA junction, upper basilar
artery.
2. The basilar trunk: Midbasilar artery, anterior inferior cerebellar artery
(AICA).
3. The vertebral trunk: Vertebral artery (VA), posterior inferior cerebellar
artery (PICA), VA-PICA junction, vertebrobasilar junction (VBJ).
Vertebral Artery (VA)

•• After its exit from the subclavian artery, the VA traverses through the
foramina transversaria of the lower six cervical vertebrae, arches over the
posterior arch of the atlas and penetrates the dura at the level of the foramen
magnum behind the occipital condyles to become intradural and intracranial.
•• The vertebral arteries are frequently asymmetrical in size, the left being
dominant in 90%.
•• The extradural branches are the muscular branches and the posterior
meningeal artery.
•• The intradural branches are the posterior spinal artery, the PICA, the
medullary perforating arteries and the anterior spinal artery.
•• The vertebral trunk is the intradural portion of the artery from its dural ring
to the VBJ.
Posterior Inferior Cerebellar Artery (PICA)

•• The PICA represents the largest and clinically most significant intracranial
branch of the vertebral artery.
•• It arises at the level of the olive (10 mm above the foramen magnum) in
around 92%.
•• The PICA can be considered as having four segments which are defined
by their relationship to adjacent cranial nerves.
•• The anterior medullary segment begins at the origin of the PICA, lies
anterior to the medulla and extends posteriorly past the hypoglossal rootlets
at the medial edge of the inferior olive.
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•• The second, the lateral medullary segment, extends from the olive along
the lateral surface of the medulla to the rootlets of the IX, X and XI cranial
nerves at the lateral edge of the olive.
•• The third, the tonsillomedullary segment, passes under or between the
rootlets of the CN IX, X, XI triad and around the cerebellar tonsil, then it
makes an inferomedial turn called the caudal (infratonsillar) loop.
•• The fourth segment of the PICA, the telovelotonsillar segment, passes along
the medial surface of the tonsil, ascends towards the roof of the IVth ventricle
and curves downwards again forming a cranial loop (supratonsillar loop).
•• The peak of the cranial loop is called the ‘choroidal point’ and is closely
related to the floor of the IVth ventricle.
Basilar Artery
•• This originates at the junction of the vertebral arteries at the level of the
pontomedullary sulcus, runs upwards anterior to the pons to terminate at
the level of the pontomesencephalic junction into two PCAs.
•• At the bifurcation point, it is closely related to both the oculomotor nerves.
•• The bifurcation is typically within 1 cm of the dorsum sellae in 90%.
•• This configuration means that the BA can bifurcate as far caudally as
10 mm below the pontomesencephalic junction or as far rostrally as the
mammillary bodies.
•• The location of the basilar bifurcation in relation to the dorsum sellae and
the posterior clinoid process is important in selecting the surgical approach
to clip an aneurysm.
•• The branches of the basilar artery include the pontomedullary artery, the
long lateral pontine artery, AICA, SCA, the posterolateral artery, PCA and
the caudal, middle and rostral perforators.
•• Perforating branches arise from the posterior and the lateral surfaces of
the basilar artery and not from its anterior surface.
Posterior Cerebral Artery (PCA)

•• This is the terminal branch of the basilar artery.
•• The basilar apex, along with its bifurcation into two PCAs, constitutes the
posterior portions of the circle of Willis.
•• The PCAs can be subdivided into three segments:
–– The P1 segment (basilar bifurcation to origin of posterior communicat-
ing artery) gives rise to the thalamoperforating arteries and long and
short circumflex arteries.
–– The P2 segment (starts at the PCA-PCom junction and extends to the
posterior aspect of the midbrain) courses through the crural and ambi-
ent cisterns giving origin to the anterior temporal, hippocampal, medial
posterior choroidal and posterior temporal arteries from the anterior
part; and middle, posterior and common temporal arteries and lateral
posterior choroidal arteries from the posterior part.
–– The P3 branch courses through the lateral part of the quadrigeminal
cistern towards the calcarine fissure and terminates into calcarine
and parieto-occipital arteries which supply the occipital and posterior
temporal lobes.
Superior Cerebellar Artery (SCA)

•• The SCA arises from the basilar trunk just before its bifurcation and
encircles the midbrain in the pontomesencephalic sulcus.
Chapter 81 • Posterior Circulation Aneurysms
615
•• Cranial nerve III separates the SCA and PCA.

•• The SCA passes between CN III and V into the cerebellomesencephalic
sulcus and gives off the superior vermian and lateral hemispheric branches.
Anterior Inferior Cerebellar Artery (AICA)

•• The AICA arises from the lower third of the basilar artery, courses around
the anterior and the lateral surface of the pons below and between
abducens fascicles and runs laterally towards the flocculus.
•• It has premeatal, meatal and postmeatal parts.
•• It gives origin to the internal auditory, subarcuate and recurrent perforating
arteries.
•• Along its course, it also sends branches to the upper anterolateral medulla,
CN VII and VIII, middle cerebellar peduncle and petrous surface of the
cerebellum.
Perforating Vessels
•• The basilar apex and PCAs give rise to a large number of essential
perforating arteries. These perforators can be divided into three categories:
1. The first group arises from the apex of the basilar artery itself, typi-
cally from the terminal 2−3 mm of the artery and supply the posterior
perforated substance, cerebral peduncles and lateral pons.
2. The second group of perforators arises from the posterior and the
superior aspects of the P1 segments of the PCA, along with long
and short circumflex arteries. Together, they supply the medial and
the lateral geniculate bodies (posterior thalamoperforating arteries),
interpeduncular fossa, mammillary bodies, cerebral peduncles and
posterior mesencephalon.
3. The third group arises from the superior and the lateral surfaces of the
PCom, supplies the hypothalamus and posterior optic chiasm anteri-
orly or perfuses the posterior perforated substance and the thalamus
posteriorly (posterior thalamoperfoarating arteries).
INCIDENCE
•• Aneurysms of the posterior circulation account for around 15% of all
intracranial aneurysms.
•• Morphologically, they can be saccular, fusiform or dissecting.
•• Saccular aneurysms of the posterior circulation most often occurs at the
basilar apex (45−55%), followed by the origin of SCA (15−24%), PICA
and PICA-VA junction (7−21%), PCA (10−14.5%), and lower third basilar
artery, VBJ and AICA (3−4%).
•• Saccular aneurysms of the AICA are the least common.
•• They most commonly present in the fifth and sixth decades of life, most
often in females.
•• Dissecting and fusiform aneurysms are more common in the posterior
circulation compared to the anterior circulation.
•• Giant aneurysms (>25 mm in diameter) occur in the posterior circulation
as frequently as in the anterior circulation and follow the same anatomic
distribution as the smaller aneurysms.
•• Anatomic variations and vascular abnormalities associated with posterior
circulation aneurysms include hypoplastic or foetal PCAs, persistent carotid-
to-basilar anastomosis and arteriovenous malformation in the occipital
lobes or cerebellum.
616
•• Connective tissue disorders (e.g. polycystic kidney disease, Marfan’s

syndrome, Ehlers-Danlos syndrome) can increase the likelihood of
aneurysms in the posterior circulation as they do in the anterior circulation.
•• The clinical presentation of posterior circulation aneurysms depends upon
whether the aneurysm has ruptured or not.
•• Almost 80% of posterior circulation saccular aneurysms present with signs
and symptoms of acute subarachnoid haemorrhage (SAH) almost always
without features localising the source of bleeding.
•• Headache, nuchal pain and rigidity, nausea, vomiting and altered sensorium
are the most common manifestations of rupture.
•• Intraparenchymal bleeding is rarely associated with rupture of posterior
circulation aneurysms due to the tough pial envelope of the brainstem.
•• Superiorly pointing basilar tip aneurysms, however, often rupture through
the floor of the IIIrd ventricle causing intraventricular haemorrhage and
obstructive hydrocephalus.
•• Likewise, a ruptured PICA aneurysm can present with IVth ventricular
bleed with hydrocephalous. Occasionally, a cranial nerve deficit points to
the origin of a particular aneurysm—oculomotor paresis (aneurysms of
basilar apex, upper basilar artery and superior cerebellar artery); abducens
dysfunction (aneurysms of VBJ and lower basilar trunk); VII and VIII cranial
nerve involvement (AICA); IX, X, XI (PICA); XII nerve involvement (PICA
and vertebral artery aneurysm).
•• Unruptured giant aneurysms of the vertebrobasilar system usually present
with mass effect on the adjacent cranial nerves and brainstem.
•• These signs can range from isolated cranial neuropathies to brainstem
compression syndromes that mimic posterior fossa tumours.
•• These include hydrocephalous (due to obstruction of CSF flow through
the cerebral aqueduct or IVth ventricle); contralateral hemiparesis with
ipsilateral IIIrd nerve palsy (due to compression of the cerebral peduncle
by a basilar tip or SCA aneurysm); dysphagia, dysarthria, cerebellar
symptoms (by compression of lower cranial nerves and cerebellum by a
giant vertebral artery aneurysm).
•• Dissecting aneurysms present with occipitocervical headache, SAH, non-
haemorrhagic infarction of the thalamus, brainstem, cerebellum or other
signs of cerebral thrombosis, oculomotor palsy, Horner’s syndrome or a
mass lesion.
DIAGNOSTIC STUDIES
•• The initial evaluation of a patient with suspected SAH invariably involves
computed tomography (CT), which clinches the diagnosis; allows
visualisation of any accompanying infarcts, cisternal clot, hydrocephalous
and a giant aneurysm.
•• The location of the SAH can sometimes provide a clue to the location of
the aneurysm, though it is not always a reliable indicator.
•• Basilar tip aneurysms can cause a large amount of clot in the interpeduncular
cistern.
•• PICA aneurysm rupture can cause IV ventricular bleed.
617
•• CT angiography may reveal a posterior circulation aneurysm with a three

dimensional external morphology and its relationship to the bony anatomy
of the skull base.
•• Magnetic resonance imaging (MRI) can be a helpful adjunct in the
evaluation of giant aneurysms of the posterior circulation and its relation
to the brainstem and cranial nerves.
•• MRI is not routinely used for the assessment of most saccular aneurysms.
Magnetic resonance angiography (MRA) has superseded MRI in that
respect.
•• High quality four-vessel digital subtraction angiography (DSA) in multiple
projections (anteroposterior, lateral, oblique, submentovertical) remains
the gold standard for diagnosis and surgical planning.
•• Pre-operative angiographic studies determine the following important
features:
–– Aneurysm’s vessel of origin.
–– Aneurysm’s shape, size and relationship to parent and adjacent arteries.
–– The presence and location of vasospasm.
–– The displacement of adjacent vessels, suggesting mass effect from
haematoma or partial thrombosis of an aneurysmal sac whose dimen-
sions are much larger than that seen on angiography.
–– The presence of associated multiple aneurysms or vascular abnor-
malities.
•• Four-vessel angiography also delineates features of the underlying
circulatory supply to the posterior fossa that may affect surgical strategy,
e.g. foetal PCA, dominant vertebral artery, etc. DSA is also essential to
assess the adequacy of filling of both vertebral arteries as well as possible
collateral circulation via the posterior communicating arteries (Alcock Test).
•• Dissecting aneurysms, more common in the vertebral circulation, can be
recognised as a double lumen (diagnostic hallmark), a narrow tapered
lumen (string sign) or an irregular post-stenotic dilated segment (pearl sign).
SURGICAL MANAGEMENT
•• Principles of surgery for posterior circulation aneurysms are essentially
similar to those followed for aneurysms of the anterior circulation—shortest
trajectory to the aneurysm, bone removal in lieu of brain retraction and
maximum dissection of the arachnoid from brain, vessels and nerves.
•• Several surgical approaches, viz. infratentorial, supratentorial, combined
supratentorial/infratentorial and transbasal have been used for successful
treatment of posterior circulation aneurysms.
•• The choice of surgical approach depends on the anatomical location, size
and projection of the aneurysm, relationship of the aneurysm to the foramen
magnum and midline, level of basilar bifurcation and the shortest possible
distance from the cranial surface to the aneurysm (Table 1).
•• The various approaches are:
–– Subtemporal approach
–– Pterional-trans-Sylvian approach
–– Orbitozygomatic and extended orbitozygomatic approach
–– Transpetrosal approach
–– Far lateral approach: Synonyms—lateral suboccipital approach, extreme
lateral approach, extreme lateral inferior transcondylar exposure (ELITE).
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Table 1: Surgical approaches for posterior circulation aneurysms

Aneurysms Trajectory Approach
Basilar top, Anterosuperior Subtemporal
PCA Pterional trans-sylvian (Yasargil)
SCA Trans-sylvian temporopolar (Sano)
Upper basilar artery Modified pterional transcavernous transsellar
(Dolenc)
Middle subtemporal transtentorial (Sugita)
Orbitozygomatic
Orbitozygomatic infratemporal
Extended orbitozygomatic approach
Midbasilar artery Lateral Transpetrosal (Kawase)
AICA Transtemporal (Sekhar)
Retrolabyrinthine transsigmoid (Gianotta and
Marceri)
Combined supratentorial and infratentorial
approaches (Kadson and Stein)
Transoral transclival approach (Saito)
Transoral transclival with Le Fort I maxillotomy
(Archer)
Extended middle fossa approach
VA Posteroinferior Midline suboccipital
PICA Paramedian suboccipital
VBJ Far-lateral approach (Heros)
Extended far-lateral approach
ALTERNATIVE SURGICAL STRATEGIES

•• Parent artery occlusion/proximal ligation/Hunterian ligation
–– The principle of this technique introduced by John Hunter about 200
years ago for giant aneurysms is to remove the forceful flow of blood
through the artery to the aneurysm and to depend upon collateral cir-
culation to nourish the part deprived of direct blood flow.
–– Proximal ligation is technically easy to perform; reduces the pressure
in the aneurysm and subsequently the incidence of rupture and en-
courages thrombus formation. However, unpredictable haemodynamic
complications ranging from ischaemia to thrombus formation and later,
migration from the stump can occur.
•• Wrapping
–– Muscle and various substances, such as methyl methacrylate, silicone,
polyvinyl and temporalis fascia, are used to wrap the aneurysms.
–– The purpose of wrapping is to induce fibrosis in the wall of the aneu-
rysm, thereby, decreasing the risk of rupture and re-bleeding.
–– However, the mass effect of the aneurysm is not removed by wrapping.
The aneurysm can continue to grow and erode even the coating of
methacrylate and rupture.
619
•• Trapping
–– Trapping the aneurysm involves isolating the aneurysm from the cir-
culation. Trapping of distal aneurysms is certainly possible, e.g. distal
PICA aneurysms.
–– Proximal trapping of PICA aneurysms may be possible, but should
be followed by some form of revascularisation if the vessel must be
trapped proximal to the choroidal point.
•• Revascularisation
–– If sufficient collateral flow is present, one can perform parent artery
ligation. However, if revascularisation is needed, aneurysm excision
with primary reanastomosis of the artery may be possible.
–– Alternatively, bypass from the extracranial circulation (superficial
temporal artery or occipital artery) to the posterior circulation (SCA or
PICA), or an interposition radial artery or saphenous vein bypass from
the external carotid artery (ECA) to SCA or PCA, may be useful.
•• Cardiac bypass with hypothermic circulatory arrest
–– Hypothermic circulatory arrest is a useful technique for giant and
complex posterior circulation aneurysms that cannot be treated by
conventional surgical and endovascular approaches.
–– With 24 degree celsius core cooling, the brain will be protected for 1
hour of complete circulatory arrest.
–– Draining the cerebral circulation allows the aneurysm to collapse and
permits the surgeon to dissect the perforators and branches away
from it.
–– However, it is associated with significant morbidity and mortality rates
related to systemic heparinisation, cardiopulmonary bypass, cardiac
arrest and prolonged ischaemia. Hence, it should be used with ex-
treme caution.
ENDOVASCULAR MANAGEMENT
–– The advent of endovascular techniques, particularly detachable coil
embolisation of aneurysms, has added a new treatment strategy for
the management of intracranial aneurysms.
–– Indications for endovascular treatment include aneurysms in surgically
difficult locations—basilar bifurcation, lower basilar trunk and VBJ; pre-
vious unsuccessful neurosurgical exploration and patients in whom the
surgical risk is unacceptably high, or in a medically unstable patient.
ENDOVASCULAR OBLITERATION
•• Intravascular obliteration of the aneurysm along with parent artery/flow
modification:
–– Detachable balloons:
¾¾ Silicone balloons filled with iso-osmolar contrast medium (Iohexol)
or solidification agent like HEMA (Hydroxymethyl methacrylate).
¾¾ Latex balloons filled with iohexol or silicone.
–– Flow modification techniques:
¾¾ Extracranial-intracranial bypass excluding the aneurysm.
¾¾ Parent artery obliteration proximal to the aneurysm with good collateral
flow.
•• Complications of balloon embolisation include intraprocedural aneurysm
rupture, incomplete occlusion of sac, distal propulsion of balloon and
migration of thrombus from the neck of the aneurysm.
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•• Intraluminal obliteration of the aneurysm—detachable coils:

A. Free pushable coils (Cook).
B. MDC—Mechanically Detachable Coils (Balt, France).
C. IDC—Interlocking Detachable Coils (Japan).
D. GDC—Guglielmi Electrically Detachable Coils (USA).
•• The most successful of all these and the one currently used by the majority
of interventional neuroradiologists is the Guglielmi Detachable Coils (GDC).
•• Factors that limit successful endovascular aneurysm occlusion include
dome-to-neck ratio less than 2, neck width greater than 4 mm, inadequate
endovascular access, unstable intraluminal thrombus and if any arterial
branch is incorporated in the neck of the aneurysm.
•• Those aneurysms with a dome-to-neck ratio that did not favour
endovascular therapy can be made more suitable for the procedure with
the use of a stent.
•• Complications of coiling of aneurysms include aneurysm perforation, parent
artery narrowing, parent artery occlusion, embolisation, coil migration and
post-embolisation aneurysmal haemorrhage.
MANAGEMENT OF GIANT POSTERIOR

CIRCULATION ANEURYSMS
•• A giant aneurysm is defined as one larger than 2.5 cm in diameter.
•• Treatment of giant aneurysms has traditionally been associated with the
higher morbidity and mortality than smaller lesions.
•• Giant aneurysms represent around 5−8% of all intracranial aneurysms.
•• Fifteen percent of these giant lesions occur at the top of the basilar artery,
and approximately 5% arise from the vertebral artery.
•• Several different strategies are currently available to manage giant
posterior circulation aneurysms.
•• Current treatment options for these lesions include direct surgical
techniques, endovascular techniques and combined approaches.
•• Regarding surgery, the aneurysm can be attacked directly with clipping
and resection of the mass lesion, or aneurysmorrhaphy with vessel wall
reconstruction.
•• Indirect surgical techniques include proximal occlusion and trapping
of the aneurysm using clips and ligatures above and below the lesion,
parent vessel occlusion or an extracranial to intracranial bypass
procedure.
•• Endovascular management includes occlusion of giant posterior
circulation aneurysm using GDC coils.
•• Other treatment options for giant posterior circulation aneurysms include
combined techniques.
•• In this approach, a surgical procedure, such as an intracranial to extracranial
bypass, can be performed prior to endovascular occlusion of the parent
vessel.
•• Alternatively, bypass techniques can be combined with endovascular
trapping of certain giant aneurysms or intra-aneurysmal endovascular
techniques.
82
CHAPTER
Giant Aneurysms
Sanjay Behari  Rabi Narayan Sahu  Rupant K Das  Vijendra Kumar Jain
INTRODUCTION
•• Giant aneurysms are aneurysms that are 2.5 cm or larger in size.
•• They represent approximately 5% of all intracranial aneurysms.
•• They most often present either in the 6th decade of life (in approximately
35% patients, i.e. one decade later than the smaller aneurysms) or in the
paediatric age group (5−10%).
•• Approximately 60% of giant aneurysms are seen in the anterior circulation,
especially on the internal carotid artery.
•• Giant posterior circulation aneurysms comprise 1−2% of aneurysms seen
in clinical practice and are often associated with much poorer outcomes
than anterior circulation aneurysms.
•• In the anterior circulation, the frequently encountered giant intracranial
aneurysms include intracavernous and petrous carotid aneurysms,
ophthalmic segment aneurysms, posterior communicating artery
aneurysms, carotid bifurcation aneurysms, anterior communicating artery
aneurysms and middle cerebral artery aneurysms.
•• Giant posterior circulation aneurysms have a predilection for the basilar
bifurcation, the vertebral artery at the origin of the anterior or the posterior
inferior cerebellar arteries and the vertebrobasilar junction.
PATHOLOGY
•• Giant aneurysms may be saccular or fusiform.
•• Saccular aneurysms may arise from gradual expansion of berry aneurysms.
•• Their fundus and neck grow both by growth of their wall as well as its
thinning and distension.
•• Due to the large volume within the aneurysm and resultant flow stasis,
intra-aneurysmal thrombosis and distal embolisation are frequent.
•• The turbulence of blood leading to endothelial damage within the aneurysm
may also lead to thromboembolic phenomena.
•• A thrombosed giant aneurysm may still bleed due to its thin walls.
•• Fusiform aneurysms result from weak vessel walls or from arterial
dissections.
•• Atherosclerosis and collagen vascular disease may be the predisposing
causes.
•• The atherosclerotic plaque extending from the parent vessel to the fundus
of the aneurysm may compromise the ostia of perforating vessels resulting
in ischaemia of the surrounding brain.
622
•• Fifty to sixty percent of giant intracranial aneurysms are either found
incidentally or for producing mass effect.
•• The commonly found aneurysms produce symptoms depending upon their
regional anatomy.
•• Cavernous internal carotid artery aneurysms present with retro-orbital
pain, diplopia, facial hypoaesthesia, ocular nerves palsies, hypopituitarism
or epistaxis.
•• Ophthalmic segment aneurysms present with retro-orbital or frontal
headache, decreased visual acuity or field defects.
•• Carotid bifurcation aneurysms present with homonymous hemianopia and
other visual field defects, seizures and hemiparesis.
•• Middle cerebral artery aneurysms may also present with hemiparesis,
speech disturbances, hemianopia and seizures.
•• Anterior communicating artery aneurysms may obstruct the foramen of
Monroe and cause hydrocephalous, cognitive disturbances due to bifrontal
mass effect, decreased visual acuity or field defects such as bitemporal
hemianopia.
•• Posterior communicating artery aneurysms may cause IIIrd nerve palsy
and trigeminal neuralgia.
•• Thirty to forty percent of giant aneurysms present with subarachnoid
haemorrhage; 3−5% present with cerebral ischaemia due to thromboembolic
phenomena, especially those in the middle cerebral artery and the internal
carotid artery.
•• Occlusion of the ostia of perforating vessels by thrombus or an
atherosclerotic plaque may contribute to ischaemia. Parent vessel occlusion
may also cause infarction.
•• Nearly 80% of patients with giant aneurysms presenting with subarachnoid
haemorrhage or mass effect die or develop severe morbidity within 5 years
if the aneurysm is left untreated.
•• Ophthalmoplegia or visual deficits may lead to visual impairment in the
involved eye.
•• Thirty to forty percent of posterior fossa giant aneurysms present with
•• The most common presentation of these lesions is mass effect compressing
the mesencephalon and diencephalon.
•• Basilar apex aneurysms may compromise the IIIrd and VIth cranial nerves;
midbasilar aneurysms may compromise Vth, VIth, VIIth and VIIIth cranial
nerves and vertebral aneurysms may compromise the lower cranial nerves.
•• Territory infarction and brainstem syndromes may occur if the perforators
get stretched and thrombosed by the pressure of giant aneurysms.
Skull Radiographs and Bone Windows of
Computed Tomographic (CT) Scans
•• A ring calcification, bony erosion of sella or skull base, erosion of anterior
or posterior clinoid process or sellar enlargement may be found, but these
are not characteristic of giant aneurysms and are more commonly seen in
other lesions specially tumours.
Chapter 82 • Giant Aneurysms
623
Computed Tomography
•• Non-thrombosed aneurysms are hyperdense and enhance uniformly after
contrast injection.
•• They are often round in configuration and are in close proximity to the
parent vessel.
•• Perianeurysmal oedema is rare.
•• In partially thrombosed aneurysms, a “target” sign may be seen. This may
present as a central or eccentric densely enhancing area representing the
flowing blood.
•• The peripheral thrombus may show a halo and heterogeneous or no
enhancement due to the presence of various stages of blood products.
•• The outermost rim of enhancement may be due to the vascularity of the
vasa vasorum.
•• A completely thrombosed aneurysm may be hypodense to hyperdense
depending upon the age of the clot. There may be a ring or intra-aneurysmal
calcification.
•• Three dimensional CT angiogram helps in defining the neck, perforators
and anatomy of the skull base and may be helpful in planning clipping
techniques.
Magnetic Resonance Imaging (MRI)

•• MRI may show a thrombosed giant aneurysm where only a small part of
the lumen was being filled up on angiography.
•• The laminated thrombus may give a heterogeneous intensity on T1- and
T2-weighted images.
•• The sagittal, coronal, axial and MR angiographic images help in completely
defining the aneurysm.
•• Gradient echo flow imaging may differentiate flow voids from bony
structures, calcification from thrombus and CSF pulsation induced artefacts
from pulsating vessels from actual aneurysms.
•• Thromboembolism may also be picked up on various MR sequences.
Digital Subtraction Angiography (DSA)

•• DSA is essential to visualise the shape and size of the giant aneurysm,
define the neck-fundus ratio and identify the taking up of the parent vessel
by the aneurysm.
•• Cross compression studies involve compression of the proximal portion
of the internal carotid artery harbouring the aneurysm while the opposite
carotid artery or the vertebral artery is injected with dye to assess the
collateral circulation to the brain on the side ipsilateral to the aneurysm.
•• The balloon test occlusion (BTO) helps in defining whether the patient
will tolerate proximal vessel control or ligation during aneurysm surgery.
•• The external carotid angiogram evaluates the status of the external carotid
system for a possible superficial temporal-middle cerebral artery or an
occipital artery-posterior inferior cerebellar artery bypass, if needed.
•• Superselective angiography helps in defining the neck of the aneurysm by
guiding the microcatheters to the aneurysm.
•• With a partially thrombosed giant aneurysm, the angiographic filling of the
lumen may not be a true estimate of the aneurysm size and may require CT
or MR reconstructed images to precisely define the size of the aneurysm.
624
•• Intra-operative angiography permits assessment of completeness of

aneurysm occlusion and patency of parent vessel following surgery.
•• It also serves as an adjunct to the surgical procedure since suction
decompression of the aneurysm or proximal control of the parent vessel
may be secured through the endovascular route; any residual neck of the
aneurysm may also be coiled under the same anaesthesia and permanent
proximal vessel coiling may be done after patency in the bypass graft has
been ensured.
•• To perform intra-operative angiography, the femoral sheaths are placed
pre-operatively and a radiolucent operating table and head frame are used.
SURGICAL TREATMENT
Aim of Surgical Treatment
•• To exclude the giant aneurysm from the circulation to prevent its rupture,
while maintaining the patency of the parent vessel.
•• To alleviate the mass effect caused by the aneurysm.
•• To prevent thromboembolic events.
Special Considerations for Giant Aneurysms

•• Assessment of cross flow:
–– In large or giant aneurysms, the suitability of a permanent ICA occlu-
sion is determined by the BTO accompanied by a clinical examination,
angiographic criterion in which symmetry of flow in both hemispheres
or in the anterior and the posterior circulation throughout all phases of
flow, as well as a good angiographic cross flow through the anterior
communicating artery (from the contralateral anterior circulation) and
through the posterior communicating artery (from the posterior circula-
tion) is maintained.
–– A single photon emission computed tomography (SPECT) study, in
which a decrease in perfusion during a hypotensive challenge with
a mean blood pressure 20% below the baseline is determined and
xenon computed tomography, in which the symmetry of perfusion is
determined.
–– In case the BTO with SPECT is well tolerated, the internal carotid
artery may be trapped, if required. In case the BTO is not tolerated
and perfusion defects are seen on SPECT, a vascular bypass using
the superficial temporal to middle cerebral artery anastomosis may be
required.
•• Reduction of ICP:
–– Corticosteroids and various dehydrants, such as furosemide and man-
nitol, may be administered to alleviate the raised ICP.
–– A ventricular drain or lumbar drain may decrease the brain swelling
and facilitate lobar retraction.
•• Neuro-protection during temporary clipping:
–– Barbiturate neuro-protection during temporary vessel occlusion in-
volves using thiopental sodium in a dose titrated to maintain burst
suppression on EEG.
–– Good hydration, oxygenation, mild hypertension, hypothermia (33−35
degrees), mannitol supplementation and calcium channel blockers have
all been used as neuroprotective agents during temporary clipping.
625
•• Proximal control: For proximal control of the internal carotid artery, there
are several strategies:
–– The common and internal carotid arteries may be exposed in the neck.
–– The portion of the ICA between the proximal and distal dural rings may
be exposed by dividing the distal dural ring circumferentially around the
ICA after the ophthalmic artery has been dissected free.
–– The petrous carotid artery may also be used for proximal control. This
is located extradurally deep to Glasscock’s triangle in the middle cra-
nial fossa. The boundaries of this triangle are the groove of the greater
superficial petrosal nerve coursing in an anteromedial direction in the
floor of the middle cranial fossa; the mandibular nerve exiting through
the foramen ovale and the line joining the foramen spinosum to the
arcuate eminence.
•• Intra-operative assessment of patency of parent vessel and comple
teness of aneurysm clipping:
–– Intra-operative angiography and Doppler studies give information
regarding patency of the parent vessel after successful clipping of the
aneurysm.
–– In case intra-operative trapping of the main artery is possible, the Dop-
pler helps in localising the superficial temporal artery for a possible
bypass with middle cerebral artery.
Surgical Technique
•• Exposure:
–– A giant aneurysm requires wide exposure often requiring skull base
approaches.
–– Wide Sylvian fissure dissection, opening of the basal cisterns to
release the cerebrospinal fluid and relax the brain, use of diuretics and
ventricular catheters all help in gaining a wide exposure without undue
brain retraction.
•• Considerations during clipping:
–– In clipping of a giant aneurysm, occasionally, the neck may be very
wide and not completely visualised.
–– Atherosclerosis may make the aneurysm wall extremely thin and prone
to rupture.
–– An aneurysm harbouring a thrombus at the neck may be difficult to
occlude unless proximal vessel temporary occludes and opening of the
aneurysm to strip the thrombus from the aneurysm wall is resorted to.
–– A number of different clip sizes and shapes may be required for ad-
equate clip placement.
–– The clip may slide down and cause parent vessel occlusion unless a
series of stacked clips are used for full deflation of the aneurysm prior
to clip placement.
–– Angled fenestrated clips with loops that go around the vessel wall and
right angled blades that clip the neck of the aneurysm and reconstruct
the vessel wall are often very useful.
–– Booster clips and extra long clips may also be required.
Adjuvant Techniques
•• Temporary clipping:
–– Proximal and distal clipping is useful during aneurysm dissection, in
case of aneurysm rupture during dissection, to deflate the fundus of
626
the giant aneurysm prior to clipping or arterial wall reconstruction and

to remove the thrombus from its neck to facilitate permanent clipping.
–– Neuroprotective agents, induced hypertension, mild hypothermia and
bypass grafts may help in increasing the ischaemia time.
–– Distal occlusion also decreases the risk of embolisation of the throm-
bus.
•• Wrapping:
–– This technique may be used for fusiform, thin walled aneurysms or
when a perforating vessel is originating from a part of the fundus of the
aneurysm that cannot be included in the clip.
–– This, however, is ineffective unless the entire aneurysm can be ex-
posed.
•• Suction aspiration:
–– After temporary clipping, the dome of the fundus may be aspirated to
shrink it prior to clipping of the neck.
–– Endovascular proximal vessel balloon occlusion followed by suction
aspiration of the aneurysm also facilitates its clipping.
•• Bypass:
–– The low flow superficial temporal artery-middle cerebral artery bypass
or the high flow saphenous vein interposition graft are placed.
–– The bypass may be done from the cervical internal or external carotid
artery to the M2 branch of the middle cerebral artery in the anterior
circulation and the occipital-PICA anastomosis or superficial temporal-
P2/3 bypass in the posterior circulation.
–– These techniques are especially helpful in case aneurysm trapping is
being planned or prolonged temporary occlusion of the parent artery is
anticipated considering its difficult location or large size.
•• Proximal vessel ligation:
–– This may be associated with nearly 30−50% incidence of ischaemic
complications without bypass.
–– Its effectiveness depends upon the adequacy of the collateral
circulation.
–– Intracavernous and petrous internal carotid artery aneurysms have a
90% occlusion rate; paraclinoid segment (with collaterals from oph-
thalmic artery) have a 75% occlusion rate and supraclinoid aneurysms
(with collaterals from anterior and posterior communicating and ante-
rior choroidal artery) have only a 50% occlusion rate.
•• Deep hypothermic circulatory arrest:
–– If the brain is cooled to 18 degrees centigrade even the brainstem can
tolerate ischaemia up to one hour.
–– At about 29 degrees centigrade, however, ventricular fibrillations are
precipitated necessitating the need to bypass the heart to perfuse the
brain and other vital organs while hypothermia is continuing.
–– Using circulatory arrest, the giant aneurysm may be decompressed by
draining a part of the blood volume into a storage reservoir to facilitate
clipping.
–– The disadvantages of this procedure are: Perforators may look like
arachnoidal bands and be inadvertently injured; ruptured perforators
may bleed when the pump is restarted; the aneurysm may fill up again
due to insufficient strength of the applied clips or heparinisation and
platelet depletion by the pump circuit may lead to persistent oozing.
627
•• Skull base approaches:

–– For giant paraclinoid/caroticoophthalmic aneurysms, a fronto-
temporal craniotomy and orbitozygomatic osteotomy and anterior
clinoidectomy provide access to the paraclinoid segment of the internal
carotid artery.
¾¾ Removal of the orbital rim also provides access to the anterior
cranial fossa base for a subfrontal clipping of giant anterior com-
municating artery aneurysms.
¾¾ Retraction of the temporal lobe posteriorly and drilling of the pos-
terior clinoid after this approach provides access to a high basilar
artery bifurcation.
–– The transcavernous approaches are extensions of the trans-Sylvian
or subtemporal approaches and provide access to the cavernous
sinus, the tentorial edge and the posterior fossa giving a good view of
the pons, midbrain, middle fossa and upper clivus.
¾¾ In Dolenc’s approach, after a frontotemporal craniotomy and ex-
tradural and intradural anterior and posterior clinoidectomy, the
cavernous sinus is entered into laterally along the IIIrd nerve.
¾¾ In the extradural temporopolar approach, an extradural resection
of the anterior clinoid during a frontotemporal craniotomy and orbit-
ozygomatic osteotomy is performed.
¾¾ With a trans-Sylvian exposure and retraction of the temporal lobe
posteriorly, the paraclinoid segment of the carotid artery is mobi-
lised laterally after dividing the dural ring.
¾¾ Kawase’s approach involves a subtemporal or frontotemporal
craniotomy, anterior petrosectomy from the middle fossa base and
opening the tentorium and lateral cavernous sinus wall to gain ac-
cess to the posterior fossa at the level of the lower midbrain and
pons.
–– The transpetrosal or presigmoid approaches involve removal of
the petros bone in addition to temporal or retrosigmoid bone removal.
¾¾ This provides access to the mid pons, upper medulla, lower basilar
trunk, vertebrobasilar junction and distal vertebral arteries.
–– The far or extreme lateral approaches involve drilling of the postero-
medial aspect of the occipital condyle after a standard retromastoid
suboccipital craniectomy to change a predominantly posterior ap-
proach to the brainstem to a more lateral one.
¾¾ They provide access to the lateral and ventral pons and medulla
and 7−12th cranial nerves. They also provide access to the verte-
bral artery from its intradural entry to the vertebrobasilar junction.
•• Endovascular techniques: Primary endovascular treatment for giant
intracranial aneurysms involves:
–– Stenting of the vessel with sheathed stents to exclude the aneurysms.
–– Endosaccular occlusion involves placement of thrombogenic metal
wires or coils, such as the Guglielmi detachable coils, to totally occlude
the aneurysm. Liquid material, such as N-butyl cyanoacrylate, that
becomes solid by precipitation or polymerisation, onyx whose solvent
dimethylsufoxide is washed away in blood leaving a precipitate within
the aneurysm, or neurocryl have been used.
–– Proximal vessel occlusion using coils, balloons or N-butyl cyanoacrylate
for aneurysms proximal to the circle of Willis which decreases the flow
within the aneurysm and induces thrombosis.
628
–– For proximal control of the parent vessel intra-operatively during an-

eurysm clipping, the site of occlusion may be chosen based on the
collateral flow distribution; a prior BTO also ensures the patient’s ability
to undergo proximal vessel occlusion.
–– Intra-operative endovascular suction decompression of the aneurysm
to make it smaller and more amenable to surgical clipping.
–– In poor grade patients after subarachnoid haemorrhage, with a broad-
based aneurysm in a location that requires a difficult exposure, partial
coiling reduces the immediate danger of rebleeding.
–– Flow reversal technique: In giant fusiform aneurysms of the proximal
basilar artery, proximal occlusion of both vertebral arteries reverses
flow through the basilar artery and decreases the intraluminal pressure
within the aneurysm leading to its thrombosis and shrinkage.
•• Endovascular embolisation is often not the primary choice of treatment in
giant aneurysms.
•• Giant aneurysms usually have a wide neck. Total occlusion requires dense
packing of the sac.
•• The wide neck predisposes to coil herniation and compromise of the
parent artery.
•• Intrasaccular thrombus increases the risk of recurrence due to migration
of coils into the thrombus.
•• The mass effect of the aneurysm is not alleviated and GDC does not protect
against thromboembolic events.
•• The coils may rotate, compact or remodel permitting re-entry of blood into
the aneurysm.
83
CHAPTER Incidental Intracranial
Aneurysms
Suresh Nair  A Mathew  G Menon
•• Although intracranial aneurysms are common affecting 5% of the

population,the incidence of subarachnoid haemorrhage is relatively
low (approximately 1 case per 10,000 persons per year), especially in
patients with small (<10 mm in diameter) aneurysms, suggesting that most
aneurysms do not rupture.
•• A great number of unruptured and often incidental intracranial aneurysms
are being diagnosed today because of the increasing age of the population
and improvement in imaging techniques.
•• Patients harbouring an unruptured intracranial aneurysm (UIA) are
potentially at high-risk of dying from subarachnoid haemorrhage (SAH).
•• Prevention of this rupture with surgical or endovascular treatment is
believed to be the most effective strategy to prevent mortality and morbidity.
•• The decision to treat or not to treat is important because treatment related
complications usually occur at or around the time of the procedure.
•• Therefore, the cumulative lifetime risk for rupture of an untreated
aneurysm needs to be evaluated to make a judgement of what is best
for the patient.
•• Also one should know the factors associated with risk of intracranial
aneurysm formation and subarachnoid haemorrhage and identify the subset
of people who can be screened for incidental aneurysms.
•• The majority of aneurysms are saccular in shape and result from a
combination of factors including degeneration and weakening of the
internal elastic lamina and collagen fibres of the arterial wall, as well as
the haemodynamic effects of fluid pulsations.
•• Factors associated with the risk of intracranial aneurysm formation and
subarachnoid haemorrhage can be classified as modifiable and non-
modifiable.
•• The major identified modifiable risk factors include active smoking,
hypertension, excessive alcohol consumption and possibly the use of
oestrogens.
•• The most important unchangeable risk factors are familial occurrence of
SAH and autosomal dominant polycystic kidney disease (ADPKD).
•• Aneurysms have also been associated with connective tissue diseases,
such as Ehlers-Danlos syndrome type IV, neurofibromatosis and Marfan
disease, but these disorders are rare, and therefore, the number of patients
with SAH related to them is small.
630
POPULATION AT RISK
•• A family history of subarachnoid haemorrhage is the strongest risk factor
and is defined as having at least one first-degree relative (parent, sibling
or child) with SAH.
•• Aneurysms are more commonly large and multiple in familial than in
sporadic SAH.
•• However, since only 10% of cases of SAH are associated with a family
history, large and multiple aneurysms are more commonly seen in sporadic
than in familial SAH.
•• Patients who have been successfully treated for an aneurysm are at risk
of developing new aneurysms.
ISUIA STUDY AND CONTROVERSIES

•• Asymptomatic unruptured aneurysms, which constitute between 17%
and 37% of all unruptured aneurysms, are less prone to bleeding than
symptomatic unruptured aneurysms.
•• Their annual bleeding rate has been the subject of much controversy.
•• Most of this controversy stems from the results of the International Study
of Unruptured Intracranial Aneurysms (ISUIA) which was first published
in 1998.
•• The ISUIA had two objectives. The first was to evaluate the natural history
of UIA, and the second was to establish the risk of treatment.
•• There is considerable evidence in literature that the majority of ruptured
aneurysms are smaller than 10 mm.
•• In the Co-operative Aneurysm Study angiographic studies revealed a
mean maximal diameter of 8.2+/–3.9 mm and a median diameter of 7 mm.
•• The available data suggests that increased aneurysm size is associated
with increased risk of rupture, small aneurysms certainly bleed and in
some patients, this risk of bleeding may be predicted by aneurysm growth.
SHOULD WE SCREEN FOR INCIDENTAL

ANEURYSMS
•• The benefits of screening for asymptomatic intracranial aneurysms have
never been quantified.
•• No clinical trials have been done on screening for aneurysms in patients
at increased risk and presumably such trials will not be done because the
follow-up needs to be 20 years or longer.
•• The goal of screening is not to detect or to treat an aneurysm, but to
increase the number of quality years of life.
•• Decisions therefore must be made from calculations and assumptions
about perceived quality of life.
•• Screening should be done in individuals with two or more affected first-
degree relatives, and in patients with ADPKD.
•• Screening should also be done in identical twins if SAH has occurred in
one of the twins.
•• Patients with Ehlers-Danlos syndrome type IV are advised against
screening because of the fragility of the vessel wall which substantially
increases risk of treatment.
Chapter 83 • Incidental Intracranial Aneurysms
631
MANAGEMENT ISSUES
•• We know that the rate of rupture of UIA is affected by factors such as
aneurysm size, aneurysm location, multiplicity of aneurysms, aneurysmal
growth, symptomatic aneurysms and patient factors such as age, gender
and history of hypertension and smoking.
•• The presence of severe progressive symptoms from an aneurysm within
the subarachnoid space is an indication for treatment regardless of the size
of the unruptured aneurysm.
•• Symptomatic unruptured aneurysms often require treatment because of
headaches, cranial nerve deficit, seizures, embolic stroke or hemiparesis.
•• The risk of bleeding is also greater in symptomatic unruptured than
asymptomatic unruptured aneurysms.
•• Symptomatic lesions represent about a third of all unruptured lesions,
but account for three quarters of the cases that bleed during observation.
•• Overall, the risk of complications from treatment is around 5% for death
or persisting impairment in activities of daily living, and 10% for persisting
cognitive deficits or reduced quality of life.
•• The risks are higher for neurosurgical clipping than for endovascular coiling,
especially in patients older than 50 years.
FACTORS ASSOCIATED WITH

SURGICAL OUTCOME
•• Increased aneurysm size is the most important factor associated with
surgical complications and poor outcome.
•• Aneurysms larger than 25 mm in diameter have a fourfold increased risk
compared with 5 mm aneurysms.
•• The association between increased aneurysm size and poor outcome
may be explained in part by the aneurysm’s intimate association with
small perforators, broad aneurysm neck, intraluminal thrombosis, or
atherosclerosis in the aneurysm neck or dome.
•• Even though advanced age is recognised as a poor prognostic indicator
for surgery, many surgeons have reported good surgical results in patients
older than 60 years.
•• Wide aneurysm neck reduces the success of endovascular procedures,
but generally play a less significant role in surgery.
•• Calcification in the aneurysm neck is associated with increased surgical
difficulty and is also associated with an increased incidence of cerebral
embolism and intra-operative bleeding from the aneurysm neck.
•• Patient related factors include advanced age, ischaemic cerebrovascular
disease, and medical conditions, such as diabetes mellitus, also increase
the risk of unruptured aneurysm surgery.
ENDOVASCULAR TREATMENT
•• In some patients endovascular coil occlusion is a valuable alternative to
surgery in the treatment of unruptured aneurysms, even though the long-
term effect on natural history remains uncertain.
•• Also there are difficulties in evaluating coil embolisation technology,
because the procedure is constantly being refined and additional
experience gained.
632
•• Procedural morbidity with this technique is between 6% and 19% in the

older series with overall favourable outcome in 82% and a mortality of 10%.
•• Endovascular procedures appear to be less successful than surgical
procedures in occluding unruptured aneurysms with only 50% achieving
complete occlusion.
•• A second limitation of an endovascular procedure is aneurysm recurrence,
which is between 16% and 32%.
MANAGEMENT GUIDELINES FOR

INCIDENTAL ANEURYSMS
•• Whether or not to treat a truly incidental (asymptomatic) aneurysm remains
controversial.
•• It is clear that size of the aneurysm is important; however, it is also clear
that there is no cut-off size below which rupture is not possible.
•• Small aneurysms have a risk of haemorrhage even though this risk may
be less than that of larger aneurysms.
•• In general, the risk that small aneurysms (<7 mm) will rupture is low,
particularly if they are on the anterior circulation.
•• Small aneurysms might therefore best be left untreated. However, this
approach is not appropriate for patients who have two or more relatives
who died from SAH.
•• In patients with small aneurysms (<7 mm), the decision on whether or not to
treat depends on the age of the patient, site of the aneurysm, accessibility
of the aneurysm for coiling in older patients, whether or not a previous SAH
has occurred and the ability of the patient to cope with the knowledge of
having an untreated aneurysm.
•• In patients with very small aneurysms (3 mm or less), follow-up assessment
to check whether or not the aneurysm is increasing over time seems to be
a reasonable approach.
•• Due to location and configuration, the decision making becomes more
problematic for truly incidental large and giant aneurysms, where risk of
treatment is very high.
•• In such cases, most surgeons consider age of the patient as an important
factor and tend to take a risk in a younger patient and to observe an older
patient with periodic imaging.
•• A more aggressive approach is pursued if significant growth of the
aneurysm is seen on follow-up imaging. One needs to address the issue
of treating an incidental aneurysm with open microsurgery or endovascular
occlusion.
•• With unruptured aneurysms one does not have the problem of swollen,
hyperaemic and friable brain that may be injured by retraction at surgery and
also there is no problem of vasospasm that may be exacerbated by surgery.
•• Therefore one tends to lean more towards open microsurgery under
identical circumstances with unruptured incidental aneurysms because
of the uncertainty about the long-term durability of coiling as opposed to
microsurgical clipping in experienced hands.
•• Open microsurgical clipping is therefore recommended for most aneurysms
of the anterior circulation and for vertebral artery including origin of PICA
or distal PICA or distal AICA aneurysms and aneurysms at the origin of
the superior cerebellar artery.
•• For most basilar aneurysms endovascular treatment is preferred.
Chapter 83 • Incidental Intracranial Aneurysms
633
•• It is very important to emphasise that the evaluation of “risk versus benefit”

is an ongoing process that continues until an aneurysm is secured by either
coiling or clipping.
THE AMERICAN HEART ASSOCIATION

GUIDELINES
•• Members of the Stroke Council recommended that incidental aneurysms
smaller than 10 mm in patients without a previous SAH should be observed
rather than treated unless the patient is young, there is a daughter aneurysm
or if there are unique haemodynamic features.
•• Patients with a family history of aneurysmal SAH also deserve special
consideration for treatment.
•• Aneurysms larger than 10 mm should be considered for treatment
depending on age, health and aneurysm risk factors.
ADVANCES
•• Recent advances in molecular genetics have made linkage studies possible
to map the chromosomal locus of a putative intracranial aneurysm gene
mutation.
•• One approach is to screen the human genome for intracranial aneurysm
genes by testing linkage of a large number of distinct highly polymorphic
genetic markers.
•• Another method for studying linkage is to analyse variations in the sharing
of marker alleles among affected sibling pairs only.
•• Polymorphisms of several genes have now been investigated in patients
with intracranial aneurysms.
•• Certain polymorphisms of the angiotensin I converting enzyme, matrix
metalloproteinases and endoglin genes may be associated with an
increased risk for aneurysm development.
84
CHAPTER Multiple Intracranial
Aneurysms
Mahmoud Rashidi  Anthony Sin  Anil Nanda
INCIDENCE
•• The overall incidence of this entity has been reported to vary from 7 to
30% among patients with intracranial aneurysms, although there is a study
reporting an incidence as high as 45% based on angiographic findings.
•• The incidence of multiple aneurysms is higher in women than men. The
cause of this higher incidence of multiple aneurysms in women is unknown.
The menopausal state and high prevalence of collagen diseases may play
a role in the formation of multiple aneurysms.
•• The correlation between increased age and multiple aneurysms is
controversial.
RISK FACTORS FOR MULTIPLE

INTRACRANIAL ANEURYSMS
•• Presence of chronic hypertension was a major risk factor for SAH.
•• Gender: A higher incidence of intracranial aneurysm formation has been
observed in the female population, especially among post-menopausal
women.
•• Arteriovenous Malformation:
–– The association of intracranial aneurysms and arteriovenous malfor-
mation (AVM) has been described for several decades.
–– The risk of haemorrhage is higher in patients with AVM and associated
aneurysms than for patients with AVM alone.
–– One hypothesis to explain association of aneurysms with AVM is
that haemodynamic stress on the feeding vessel leads to aneurysm
formation.
–– It has been shown that increased blood flow leads to degeneration of
arterial walls.
–– Because of the high-risk of intracranial haemorrhage in these patients,
aggressive treatment is necessary.
–– The treatment of these patients with complex vascular anomalies is
challenging and needs to be individualised.
–– Most authors agree that the aneurysms on the feeding arteries should
be treated before initiating definitive treatment of AVM.
•• Familial Aneurysms: Patients with familial aneurysms and multiple
aneurysms tend to be younger, and there is a higher incidence of middle
cerebral and internal carotid aneurysms.
Chapter 84 • Multiple Intracranial Aneurysms
635
•• Connective Tissue Disease and Congenital Disorders:

–– Rare cases of hereditary connective tissue diseases, such as poly-
cystic kidney disease, Ehlers-Danlos syndrome, pseudoxanthoma
elasticum and Marfan syndrome, have been known to be associated
with multiple intracranial aneurysms.
–– It has been proposed that an embryological endothelial defect in one
or two embryonic segments of the neural crest or mesoderm leading
to dysfunctional vessel wall remodelling in the presence of repeated or
long-lasting triggers is responsible for this.
–– Multiple aneurysms are also reported to be associated with moyamoya
disease, fibromuscular dysplasia, aortic coarctation and tuberous
sclerosis.
•• Sickle Cell Disease:
–– The endothelium is interrupted following repeated injury from adhesion
of the sickled erythrocytes to the endothelial cells.
–– This cascade may disrupt the supply of oxygen and other nutrients
throughout the entire vascular system and, in turn, the formation of an
aneurysm may be initiated at multiple locations.
•• Smoking:
–– A presumed molecular mechanism for negative risk factors of cigarette
smoking on aneurysm formation is based on a serum elastase/a1-
antitrypsin imbalance or increased elastase activity.
–– Repetitive transient increases of systemic blood pressure have been
observed for about three hours following cigarette smoking.
–– Thus, it is plausible that long-term smoking can weaken the cerebral
blood vessels by promoting degradation of elastin in the blood vessel
walls to initiate formation of aneurysm at anatomic sites of maximum
turbulence under the load produced by hypertension.
ANEURYSM DISTRIBUTION
•• The most common sites for multiple aneurysms are different from patients
with a single aneurysm.
•• In patients with multiple aneurysms, the most common sites are the internal
carotid artery (ICA) and the middle cerebral artery (MCA).
•• However, in patients with a single aneurysm, the anterior communicating
artery (ACoA) is the most common site.
PREDICTION OF RUPTURE SITE

•• The most common site of rupture in patients with multiple aneurysms as
compared to patients with a single aneurysm is ACoA.
•• In patients with SAH and multiple aneurysms, the ruptured aneurysm must
correctly be identified, especially in cases where clipping of all aneurysms
cannot be accomplished in a single operation.
•• False localisation of the ruptured site may result in disastrous post-operative
haemorrhage from the unprotected ruptured aneurysm.
•• With clinical signs, computed tomography (CT) and angiographic findings,
the site of ruptured aneurysm usually can be identified with a high degree
of certainty.
•• Other methods for predicting the rupture site are magnetic resonance
imaging (MRI) and electroencephalography (EEG).
636
•• In the majority of patients with multiple aneurysms, clinical signs are not
helpful for localisation of the ruptured aneurysm.
•• In some patients with cranial nerve palsy, the neurological examination will
help in identifying the site of rupture.
•• However, some other findings, such as hemiparesis, can be misleading.
•• CT plays a significant role in localising the ruptured site.
•• The haemorrhage site in CT can provide very important information, such as
focal blood collection in the specific cistern (suprasellar, perimesencephalic
clot in posterior communicating artery aneurysms), interhemispheric fissure
haematoma (in ACoA), intracerebral haematoma (in the temporal or frontal
lobes in MCA aneurysms), and the area of intraventricular haemorrhage
(isolated fourth ventricular haemorrhage in PICA aneurysm).
•• The angiographic signs that can help in localising the ruptured aneurysm
are as follows:
–– Aneurysm bleb
–– Irregular aneurysm contour
–– Focal vasospasm
–– Size of aneurysm
–– Focal mass effect from blood clot
–– Extravasation of contrast (rare cases)
–– Changing aneurysm shape in serial angiograms
•• In patients who have MRI, focal oedema or increased signal adjacent to
one aneurysm may indicate a recent haemorrhage.
•• In some cases, EEG findings may help in identifying a ruptured aneurysm.
•• To determine the site of ruptured aneurysm, one should use all the possible
information from clinical presentation, CT, angiography and, in some
patients, MRI and EEG.
TREATMENT
•• The treatment criteria for incidental multiple intracranial aneurysms are
similar to incidental aneurysms in general (See Chapter 83).
•• Studies have shown that the morbidity and mortality of patients with multiple
aneurysms with SAH was from the ruptured aneurysm.
•• Most authors suggest treatment of multiple aneurysms using a one stage
operation in early post-SAH period.
•• This can be accomplished with a standard or modified approach.
•• In some series, early surgery and one stage operations have been
associated with less surgical morbidity and mortality.
•• The favourable results with one stage operations compared to multi-stage
operations may be related to easier access to aneurysms.
•• In SAH patients with multiple aneurysms, the symptomatic aneurysm should
be treated first. The remaining aneurysms should be clipped from deep to
more superficial ones.
•• In these cases, clipping the symptomatic aneurysm may obscure the view
of deeper aneurysms or interfere with the clipping of the deeper aneurysms.
•• There are three options for a successful completion: (1) clip the deeper
aneurysm first with care not to disturb the ruptured aneurysm; (2) clip and
aspirate the symptomatic aneurysm to allow clipping deeper aneurysms,
and (3) treat the symptomatic aneurysm first and treat the deeper aneurysm
through a different approach.
Chapter 84 • Multiple Intracranial Aneurysms
637
•• The advantage of a one stage operation is to eliminate the need for a

second surgery, to be sure that the ruptured aneurysm has been clipped,
and to aggressively treat vasospasm with induced hypertension and
hypervolaemia without the risk of any aneurysmal rupture.
•• On the other hand, in the two stage operation, the exposure and clipping
is technically easier when the subarachnoid blood has been cleared and
the brain is less swollen.
•• The other therapeutic option in patients with multiple aneurysms is an
endovascular approach. In some cases, a combination of an endovascular
approach and open surgery is a valuable option.
OUTCOME
•• The prognosis of SAH patients with multiple aneurysms is less favourable
than for SAH patients with a single aneurysm, especially in elderly
individuals.
•• The factors that affect the outcome in patients with multiple intracranial
aneurysms include: (1) misdiagnosing the site of the ruptured aneurysm; (2)
failing to treat multiple aneurysms with multiple surgical approaches and (3)
associated complications of surgical treatment of unruptured aneurysms.
•• As the number of aneurysms increases, the surgical results become more
unsatisfactory.
•• Delayed neurological deficit has a major influence on the outcome of
patients with multiple aneurysms. Furthermore, patients with vertebrobasilar
aneurysms have a poorer outcome.
CONCLUSION
•• Multiple aneurysms occur in about one-third of patients with aneurysms.
•• They are more common in women and also in patients with familial
aneurysms.
•• Other conditions associated with multiple aneurysms include connective
tissue diseases and congenital disorders.
•• The site of rupture can be determined with high accuracy using clinical
signs, CT and angiographic findings.
•• If it is feasible, the symptomatic and asymptomatic aneurysms should be
treated in a one stage operation (with a standard or modified approach).
•• In some cases, the treatment of asymptomatic aneurysms could be done
in a second surgery a few weeks later.
•• Recently, one stage operations have become more frequent.
85
CHAPTER Intracranial Aneurysms of
Infective Origin
Sanjay Behari  Vivek Vaid  Awadhesh K Jaiswal  Vijendra Kumar Jain
•• Aneurysms of infective origin, often called mycotic aneurysms form about

0.5−6.2% of all intracranial aneurysms, occur more frequently in the anterior
circulation and may be multiple.
•• They clinically manifest in 2% of cases of bacterial endocarditis and 5−15%
of these are detected at autopsy.
AETIOPATHOGENESIS
•• In intracranial arteries, contrary to the systemic blood vessels, the internal
elastic membrane provides strength to the vascular wall.
•• The external elastic lamina is absent, the muscularis layer is thin and there
is no external support in the subarachnoid space.
•• Infection affects the internal elastic membrane leading to its damage.
•• Hydrostatic pulsations against a weakened wall lead to aneurysmal dilatation.
•• Haematogenous spread occurs via large calibre blood vessels to the tiny
nutrient vessels, the vasa vasora supplying the intracranial vessels.
•• Due to the small size of these vessels, the septic emboli cannot travel any
further and, therefore, block it establishing a local infection of the outer
adventitial layer of the blood vessel of the brain.
•• This leads to ischaemic necrosis and the local infection also spreads to the
subarachnoid spaces via the Virchow-Robin spaces.
•• The blood vessel progressively weakens due to establishment of infection
in a centripetal fashion in the vessel wall.
•• The hydrostatic pulsations of blood in the blood vessels cause progressive
dilatation of the vessel wall.
•• Occasionally, turbulence, atherosclerosis or trauma to the vessels may
lead to stasis of flow or endothelial damage causing direct implantation of
the septic emboli through the damaged endothelial surface.
•• Direct blood vessel invasion occurs due to the presence of endogenous
central nervous system infection.
•• A paranasal sinus infection may produce a contiguous spread to the
cavernous sinus or meningitis may involve the basal cisterns.
•• The blood vessels within the basal cisterns are surrounded by the infective
process leading to local invasion of the adventitia. This, especially, is the
pathogenetic mechanism in immunocompromised patients and patients
undergoing immunosuppressive therapy following organ transplants.
•• Patients with HIV infections, diabetes mellitus and immunocompromise
are more likely to have fungal infections, while patients having a septic
focus are more likely to be harbouring a multiple or distal aneurysms of
bacterial origin.
Chapter 85 • Intracranial Aneurysms of Infective Origin
639
CLINICAL FEATURES
•• If unruptured septic intracranial aneurysms are present, then the patients
may have a clinical symptomatology of sepsis without any signs pertaining
to the central nervous system.
•• In cases of spontaneous thrombosis or intracerebral haemorrhage, there
may be focal signs based on the site of infarction.
•• Subarachnoid haemorrhage may lead to sudden severe headache, neck
stiffness or even obtunded sensorium.
•• Early sentinel signs may often lead to an early identification of these lesions
provided a high index of suspicion is maintained.
•• Approximately 5% of patients with subacute bacterial endocarditis will
develop an intracranial lesion, so any neurological changes warrant
cerebrospinal fluid studies and CT/MRI.
•• These investigations may help in detecting a central nervous system
infection, but are relatively insensitive for detecting infective aneurysms.
•• Any abnormality in these studies in patients with neurological symptoms
thus warrants angiography.
RADIOLOGICAL FEATURES
•• On digital subtraction angiography, the infective aneurysms may be single
or multiple.
•• The anterior circulation is involved more often than the posterior circulation.
•• These aneurysms are typically fusiform and irregular, without the neck that
characterises saccular aneurysms.
•• The diagnosis of an infective aneurysm is fairly straightforward in patients
with endocarditis associated with distal aneurysms.
•• When evaluating proximal aneurysms, a combination of radiological findings
may help in diagnosing such aneurysms.
•• These include arterial stenosis or occlusion close to the aneurysm, the
presence of multiple aneurysms and rapid morphological changes within
the aneurysm.
•• CT angiography may be a less invasive and quicker technique to serially
follow-up these aneurysm.
MANAGEMENT ALGORITHM
•• The clinical decision making is based upon whether the aneurysm has
ruptured; whether there is a haematoma producing mass effect or increased
intracranial pressure and whether the parent artery is supplying eloquent
brain tissue.
•• Serial angiograms are necessary in patients being treated medically for the
concerned infection after aneurysm detection, since the characteristics of
infected aneurysms may change leading to six scenarios:
1. Spontaneous resolution with preservation of the parent artery
2. Spontaneous resolution with thrombosis of the parent artery
3. Increase in size
4. Decrease in size
5. Unchanged size with the same morphological features (stable)
6. Unchanged size with different morphological features (unstable).
•• Thus, if there are neurological symptoms with bacterial endocarditis or
sepsis (especially with the background of immunocompromise) then a
contrast enhanced MR or CT scan with CSF studies is required.
640
•• If it shows a positive intracranial finding, four-vessel angiography is

performed to detect an intracranial aneurysm.
•• If the angiogram is negative, then medical treatment may be continued.
•• If the angiography is positive for an infective aneurysm, but the patient
has an unstable medical condition, such as severe sepsis or congestive
cardiac failure rendering him unfit for surgery; or, there is no evidence
of intracranial haemorrhage or neurological worsening, then he may be
treated with antibiotics.
•• In both the above scenarios, angiography should be repeated after 2−4 weeks.
•• A patient harbouring an infective aneurysm should be placed on appropriate
antibiotics that achieve therapeutic levels in the central nervous system.
•• The correction of the cardiac disorder is also important in patients with
infective endocarditis.
•• The resolution of the aneurysm may occur on appropriate antibiotics
often with preservation of the parent artery. Therefore, if an aneurysm
is unruptured, or is in a difficult area to approach surgically or there
are multiple aneurysms, then a trial of antibiotic therapy alone may be
appropriate.
•• Medically treated patients with enlarging or dynamic unruptured aneurysms;
ruptured aneurysms in stable patients in surgically accessible areas,
especially in the presence of haemorrhage and mass effect causing
neurological worsening are eligible candidates for surgical intervention or
endovascular treatment.
•• Patients with ruptured aneurysms that are not associated with haematomas
and that do not involve eloquent vascular territory are treated endovascularly.
•• In patients, who also require continuous heparinisation for their prosthetic
cardiac valves, and those patients with compromised haemodynamic status,
especially with acute endocarditis, endovascular intervention, is desirable.
•• Therefore, endovascular therapy is the first choice for patients in stable
condition with ruptured aneurysms; surgical therapy is the first option
for patients in unstable condition with ruptured aneurysms and the
second option for patients in stable condition who experience failure of
endovascular therapy.
•• Medically treated patients with enlarging or morphologically changing
unruptured aneurysms also require direct surgical or endovascular
intervention.
•• The aims of surgery are to eliminate the infectious aneurysms from the
circulation, prevent ischaemic complications from arterial sacrifice and
evacuate any associated haematoma.
•• The surgical options available include trapping and resection of the
aneurysm, trapping and bypass to the distal parent artery, direct clipping
and wrapping of the aneurysm.
•• In contrast to primary aneurysms, surgery for these aneurysms is more
difficult as these aneurysms are situated more often on peripheral blood
vessel branches, the surrounding brain may be inflamed and oedematous
(both due to the presence of infection and the haemorrhage) and the blood
vessel wall is often friable.
•• The aneurysm is often sessile and may be arising directly from the blood
vessel wall without a neck.
•• Attempted clipping of an acute, friable infected aneurysm can lead to clip
erosion of the vascular wall as well as catastrophic peri-operative rupture.
Chapter 85 • Intracranial Aneurysms of Infective Origin
641
•• Occasionally, the only option left with the neurosurgeon for aneurysm
exclusion from the parent vessel may be trapping or excision of the parent
blood vessel.
•• A bypass procedure may be mandatory in case the parent vessel is
supplying an eloquent area of the brain.
•• Endovascular management may also involve parent vessel occlusion
after a test occlusion has negated the possibility of neurological deficits
developing after the procedure.
•• There has been a steady progress in the endovascular treatment and parent
vessel occlusion is not always necessary.
•• Improved microwires, microcatheters, stents and balloons have facilitated
access to the distal circulation.
•• Thus, balloon or stent assisted coil embolisation procedures may be used
to maintain parent vessel integrity, although with some risk of rupture, given
the fragility of the diseased parent vessels.
•• The timing of intervention in infected aneurysms is vital. The patients
harbouring these aneurysms may be systemically ill and anaesthesia
may pose an increased risk; antibiotic treatment helps to reduce systemic
infection as well as local inflammation in the arterial wall and facilitates
clipping or coiling of the aneurysm.
86
CHAPTER Intracavernous
Aneurysms
BS Sharma  VS Mehta
INTRODUCTION
•• Intracavernous aneurysms constitute about 5% of all intracranial
aneurysms.
•• Middle aged females are affected five times more commonly than males.
•• These aneurysms may be true or false.
•• The true aneurysms may be purely within the cavernous sinus or
transitional, i.e extending outside the sinus. In true intracavernous
aneurysms, the neck and dome of the aneurysm are contained within the
cavernous sinus. Rupture of true intracavernous aneurysms may cause
spontaneous carotico-cavernous fistula (CCF).
•• False aneurysms are secondary to head injury or following internal carotid
artery (ICA) injury during trans-sphenoidal or cavernous sinus surgery.
•• In the transitional variety, the aneurysm extends into the subarachnoid
space.
•• Intracavernous aneurysms may be saccular or fistulous.
•• Fistulous aneurysms may be spontaneous or traumatic.
•• About 15–20% of these are bilateral and 15–20% have associated
aneurysms.
•• Intracavernous aneurysms enlarge insidiously and are frequently of giant
size.
•• Management of these aneurysms is difficult and pose a major challenge
due to their intracavernous location, giant size, presence of atherosclerosis/
thrombosis/calcification, broad neck and incorporation or origin of a major
branch or perforators from the neck of the aneurysm.
CLINICAL FEATURES
Cranial Neuropathy
•• Cranial nerve deficit from II to VI alone or in combination occurs due to mass
effect causing progressive visual loss, decreased visual acuity, field defects,
diplopia, blepharoptosis and/or ophthalmoplegia. Proptosis, chemosis and
bruit occur in spontaneous CCF.
•• Parasellar syndromes which consist of pain in V1 and V2 and paresis of one
or two extraocular muscles are also due to mass effect of the aneurysm.
•• Rarely, they may present with bilateral VI cranial nerve paresis, and as
Tolosa-Hunt syndrome, with recurrent intolerable retro-orbital pain, ptosis
and diplopia due to oculomotor nerve and abducent nerve involvement.
Chapter 86 • Intracavernous Aneurysms
643
Pain
•• Causes of the pain associated with intracavernous aneurysms are:
–– Headache is caused by local irritation of the dura
–– Retro-orbital pain is caused by trigeminal nerve compression by an-
eurysm mass
–– Facial pain is caused by episodes of distension or enlargement of the
aneurysm and involvement of the trigeminal nerve. It may be severe,
intractable and episodic.
Subarachnoid Haemorrhage
•• Subarachnoid haemorrhage (SAH) occurs in transitional variety of the
cavernous aneurysm.
Epistaxis
•• In false aneurysms secondary to trauma, massive, delayed and life-
threatening epistaxis is a leading symptom.
•• In the presence of blindness or blurring of vision, recurrent epistaxis and
fracture of the skull base following trauma, early angiography should be
performed.
Transient Ischaemic Attacks

•• These are caused by thromboembolism.
INVESTIGATIONS
•• In addition to conventional angiography, three-dimensional (3D)
computed tomography angiography (CTA), slow injection angiography,
aneurysmography and balloon test occlusion (BTO) are useful in
determining the method of treatment.
•• At angiography size of the aneurysm, width of the neck, origin of a branch
or perforator from the neck, presence of thrombus and other aneurysms,
presence of waist deformation and collateral circulation should be studied.
•• Waisting seen in the angiogram indicates extension of the aneurysm into
the subarachnoid space, either through the dural ring or eroded dural roof
of the cavernous sinus.
•• The waist indicates that rupture would be life-threatening.
•• Deformation of the aneurysm may be due to compression against the optic
nerve or anterior clinoid process (ACP) with an intact dura.
•• Computerised tomography (CT) scan is useful in detecting bony erosion,
SAH and calcification.
•• Magnetic resonance (MR) detects the presence of thrombus.
TREATMENT
•• The indications for treatment are:
–– Impairment of vision
–– Severe intractable facial pain
–– Progressive ophthalmoplegia
–– Evidence of enlargement of aneurysm
–– Transient ischaemic attacks
644
–– Presence of waist in the angiogram

–– Risk or presence of SAH
–– Risk or presence of epistaxis.
•• Asymptomatic or minimal symptoms of compression can be observed,
especially in elderly patients.
METHODS OF TREATMENT
•• The aim of treatment is exclusion of the aneurysm from the circulation and
preservation of efferent flow.
•• This can be achieved by endovascular techniques or surgery.
Endovascular Technique
•• Selective endovascular occlusion with detachable balloon or Guglielmi
detachable coils via the arterial route or electrothrombosis by detachment
of platinum coils via the transvenous approach can achieve the objective.
•• Proximal segment cavernous ICA aneurysms (C3 position) with a definable
and narrow neck are better suited for endovascular treatment.
•• Endovascular treatment of giant and large aneurysms by using a
combination of stent placement and liquid polymer injection has been
successful. Angiographic controls showed complete thrombosis of the
aneurysmal sac with dramatic improvement of symptoms.
•• Follow-up magnetic resonance imaging (MRI) and digital subtraction
angiography 3 months after the procedure, confirmed total occlusion of
the aneurysm with normal circulation in the parent vessel.
Surgical Treatment
•• Surgical treatment of aneurysms can be done in two ways:
1. Direct surgical methods
2. Indirect surgical methods.
Direct Surgical Methods
•• These include clipping or resection followed by ICA wall reconstruction.
•• Direct clipping is recommended in aneurysms with a definable neck arising
from the anterior genu segment and in the transitional variety.
•• The cavernous sinus can be approached intradurally or extradurally (ED).
•• The ED approach provides complete exposure and good proximal control
of the ICA.
•• Pre-operatively, good cross-circulation through the anterior communicating
artery and retrograde filling of the ICA through the posterior communicating
artery is desirable, so that temporary occlusion of the ICA can be tolerated.
•• The cavernous sinus is approached directly using a combination of three
different techniques:
1. Pterional exposure of the ICA
2. Subtemporal exposure of the ICA
3. Extradural petrosal exposure of the ICA.
Indirect Surgical Methods
•• Proximal parent vessel occlusion or trapping is indicated in aneurysms with
a poorly definable neck, origin from the proximal cavernous segment of
the ICA, traumatic aetiology, fusiform aneurysms and when direct surgery
is not feasible or carries a high-risk.
Chapter 86 • Intracavernous Aneurysms
645
•• Before the ICA can be sacrificed, it is necessary to assess collateral flow

by angiographic BTO of the ICA.
•• This may be supplemented with electroencephalography (EEG),
transcranial Doppler (TCD), cerebral blood flow (CBF) studies using direct
intracarotid injection of Xenon, distal ICA pressure measurements and
single photon emission computerised tomography (SPECT) studies.
•• The BTO is deemed successful when there is good clinical tolerance
and there is adequate angiographic collateral circulation in the arterial,
parenchymal and venous phases with symmetric filling of both hemispheres.
•• Carotid ligation is also contraindicated in patients with recent SAH, poor
Hunt and Hess SAH grade, hypovolaemia, cerebral vasospasm and/or
intracerebral haematoma. Relative contraindications include presence of
atherosclerosis or aneurysms in the contralateral ICA.
•• Proximal Internal Carotid Artery Occlusion
•• Trapping: Immediate symptomatic relief is obtained by loss of aneurysm
pulsations and pressure. Aneurysm thrombosis occurs in the first post-
operative week, but retraction is maximal after several months and can be
monitored by MR angiography.
•• External Carotid-Internal Carotid (EC-IC) Bypass
Indications
–– In patients treated by ligation or trapping of ICA who have inadequate
collateral circulation, i.e. failed BTO
–– In patients with unclippable aneurysms, who have long-life expec-
tancy or are young, hypertensive, and/or have bilateral or associated
aneurysms. The EC-IC bypass preserves ipsilateral cerebral vascular
reserve
–– Failure of endovascular or clipping treatment
–– Interposition high flow saphenous vein graft (SVG) from the proximal
ICA or external carotid artery (ECA) in the neck to the middle cerebral
artery (MCA) bifurcation is the preferred procedure.
•• Superficial temporal artery to middle cerebral artery anastomosis
•• Internal Carotid Artery or External Carotid Artery- Middle Cerebral
Artery Bypass Using a Graft:
–– Saphenous vein graft harvesting
–– Radial artery graft harvesting.
COMPLICATIONS
•• Epidural, subdural or intracerebral haematoma may occur due to the use
of intraoperative heparin.
•• Infarcts may be deep-perforator related from temporary occlusion or
hemispheric due to hypoperfusion, embolism, graft occlusion, vasospasm
or meningitis in patients with poor collateral, inadequate protection during
surgery or protracted vascular occlusion.
•• Poor outcome or ischaemic complications are highest in the posterior
circulation.
GRAFT PROBLEMS
•• Shortest possible length of the graft and end-to-end anastomosis at both
ends are preferred to reduce the turbulent flow.
•• Annual occlusion rate is 1–1.5%.
•• The RAGs have better long-term patency rates.
646
Graft Failure
•• Early graft occlusion
•• Subacute Graft Occlusion
–– A vein graft undergoes structural changes in response to arterial
haemodynamics and the trauma of harvesting.
–– Subintimal fibrosis (arterilisation) occurs by the end of the 1st month
and so vein graft occlusions are common during this time.
–– Steroids protect venous endothelisation.
–– Subacute changes that threaten patency of the graft are
¾¾ Internal hyperplasia and medial fibrosis are due to ischaemia of the
media caused by interruption of the vasa vasorum.
¾¾ Valve fibrosis: Most valves lie flat posing no threat to patency, but
fibrotic change makes them impinge on the vascular lumen gen-
erating turbulence. This is why some people advocate valvotomy.
¾¾ Aneurysmal dilatation of the graft at the anastomotic site.
¾¾ Clamp stenosis may occur. Delicate clamps have to be used to
prevent this.
¾¾ Suture stenosis.
•• Delayed or Late Graft Occlusion: This occurs due to atherosclerotic
changes.
Treatment of Graft Occlusion

•• General: A hypercoagulable state is corrected by hydration. Slow flow is
corrected by occlusion, narrowing or artificial stenosis to obtain adequate
graft flow, e.g. ICA, proximal VA. Spasm is treated with 3% papaverine
local application.
•• Proximal anastomosis end problems affect flow into the graft. An
anastomotic kink can be corrected by pexy.
•• Tunnel compression is caused by narrowing of the tunnel which requires
surgical opening and dilatation.
•• Distal end problems occur due to a stitch applied through both walls and
it requires revision.
87
CHAPTER
Contemporary
of Intracranial Aneurysms
Uday Limaye  Anand S
In recent years endovascular treatment of Intracranial aneurysms has gained

increasing acceptance as the primary treatment of aneurysm at many sites
with a very high success rate. It is quite costly and required well trained
interventionists.
INDICATIONS FOR ANEURYSM COILING

•• Posterior circulation aneurysms
•• Multiple aneurysms
•• Paraclinoid aneurysms
•• Aneurysms with severe vasospasm
•• Patients in extremes of age
•• Giant/serpentine, fusiform, dissecting, mycotic and pseudoaneurysms
•• Blood-blister like aneurysms (Ogawa aneurysms)
•• Aneurysms with brain AVM
•• ISAT supports offering coiling when there is high likelihood of success.
LIMITATIONS OF ENDOVASCULAR TREATMENT

•• Tortuosity of neck vessels (Stability of arterial access is the primary step
for endovascular treatment)
• Broad neck of the aneurysms
•• Renal failure
•• Non-availability of modern DSA facility
•• High cost of material
•• Aneurysms with large parenchymal clot may require surgical evacuation
and clipping done in the same sitting.
STEPS OF ENDOVASCULAR COILING

•• All procedures are done under general anaesthesia
•• Transfemoral access is secured and adequate dose of heparin is given
•• The guiding catheter is placed in the appropriate artery [Cervical internal
carotid artery (ICA) or vertebral artery]
•• Microcatheter over microwire is navigated into the aneurysm carefully
under road map guidance
•• Aneurysm coiling is carried out with detachable platinum coils of suitable
sizes
•• Depending on an individual case balloon or stent assisted coiling is done.
648
POST-PROCEDURE MANAGEMENT
•• All patients post-coiling are admitted in the ICU
•• Continuous monitoring of vital signs and neurological examination at regular
intervals are done
•• Triple-H therapy and calcium channel blockers are used for treatment of
vasospasm
•• Patients with post-SAH hydrocephalus and intraventricular haemorrhage
may require external-ventricular drainage
•• Antiplatelet agents and low molecular weight heparin are used when
indicated.
FOLLOW-UP
•• Patients are clinically followed up at regular intervals
•• Angiographic follow-up is done at 3−6 months, 18 months, 3 years and
5 years interval with DSA, CT angiography or MR angiography.
EQUIPMENT AND DISPOSABLE MATERIAL

•• A fully equipped DSA catheter lab adds invaluable support for the
endovascular technique.
•• Biplane imaging, rotational angiograms, 3D-reconstruction techniques, flat
panel and digital zooming and CT like cross-sectional images can now be
obtained on high end DSA systems.
•• Good quality fluoroscopy with magnification and road map facilities are
basic necessities for endovascular treatment.
•• Guiding catheters—5F to 8F lumen:
–– Envoy (J & J Cordis)
–– Guider (Boston Scientific).
•• Microcatheters:
–– Eschelon (EV3)
–– Excelsior (Boston Scientific).
•• Microwires:
–– Transend 14 (Boston Scientific).
•• Detachable platinum coils:
–– 2D, 3D, 360, complex coils (Compass-Microvention, 360-Boston Sci-
entific, Orbit-Cordis and Morpheus-EV3)
–– Ultrasoft and hypersoft coils
–– Bioactive coils (Matrix, Boston Scientific)
–– Coated coils (Hydrocoils-Microvention).
•• Balloon remodelling catheters:
–– Hyperform (EV3)
–– Hyperglide (EV3).
•• Self expanding intracranial stents:
–– Neuroform (Boston Scientific)
–– Enterprise (J & J Cordis).
•• Stentgrafts:
–– Graft master (Jomed)
•• Liquid embolic agent:
–– Oynx (EV3)
–– NBCA glue (Histoacryl, B Braun).
Chapter 87 • Contemporary Endovascular Treatment of Intracranial Aneurysms
649
DRUGS USED DURING THE PROCEDURE

•• Heparin
•• Protamine sulphate for reversal of heparin effect if required
•• Contrast media (Nonionic ultravist, German remedies).
DRUGS USED IN ADVERSE EVENTS

•• Mannitol
•• Anticonvulsants
•• Abciximab
•• Right-PA.
TREATMENT OF VASOSPASM
•• Chemical angioplasty: Intra-arterial nimodipine therapy (3−4 mg/arterial
territory)
•• Balloon angioplasty: Focal spasm may be treated with balloons angioplasty.
SPECIAL CONSIDERATIONS IN ENDOVASCULAR

ANEURYSM TREATMENT
Dissecting Aneurysms
•• Dissecting aneurysms are commonly seen in the vertebrobasilar circulation.
•• All dissecting aneurysms are treated with endovascular technique.
•• Embolising the aneurysm with coils with parent vessel sacrifice is important
to prevent recurrence.
•• If this is not feasible, stents will have to be used.
Giant Aneurysms
•• The commonest location of these is the cavernous ICA followed by the
vertebro-basilar circulation.
•• Cavernous ICA aneurysms are treated with proximal parent vessel occlusion;
which is done after a successful balloon test occlusion of the artery.
•• Basilar giant aneurysms may be treated by flow reversal techniques with
occlusion of one or both vertebral arteries.
•• This requires the presence of prominent posterior communicating arteries.
Mycotic (Infective) Aneurysms

•• Mycotic (Infective) aneurysms are seen more commonly in patients with
infective endocarditis.
•• They are treated with antibiotics.
•• Ruptured mycotic aneurysms are treated with coils or glue with embolisation
of the parent branch vessel.
BALLOON REMODELLING CATHETERS

•• The balloon remodelling catheters are commonly used to protect the neck
of the aneurysm while coiling large wide neck aneurysms.
•• They are also used to seal the neck of the aneurysm during embolisation
of aneurysm with Oynx.
•• These balloons, on temporary inflation, occlude the neck keeping the coils
inside the aneurysm.
650
•• The balloon catheters available are: (a) hyperform and (b) hyperglide (EV3),
which can be used depending on the type and location of the aneurysm .
COATED/BIOACTIVE COILS
Matrix
•• Matrix detachable coils are platinum coils covered with a bioabsorbable
polymer (90% polyglycolide, 10% polylactide) and attached to a stainless
steel delivery wire.
•• The coil consists of 70% polymer and 30% platinum.
Hydrocoils
•• This device consists of a carrier platinum coil coupled to an expandable
hydrogel material, which undergoes a ninefold increase in volume when
placed into a physiological environment.
•• There is no concrete evidence in favour of these coils that they improve
long-term occlusion or significantly prevent recanalisation.
NEWER ADVANCES
Stent Grafts
•• Coronary stent grafts have been used infrequently in endovascular
treatment of giant or pseudoaneurysms.
•• They constitute a promising alternative for endovascular treatment.
•• They have mainly been used for the carotid circulation aneurysms.
•• The stent graft seals the neck of the aneurysm.
•• Long-term patency of the graft is an issue.
Oynx
•• Oynx (Micro Therapeutics, Inc. Irvine, CA) has been used to treat selected
cases of aneurysms.
•• It is an ethylene vinyl alcohol copolymer dissolved in the organic solvent
dimethyl sulfoxide (DMSO).
•• Oynx HD 500 has been used in selected cases of giant or large wide neck
aneurysms that are not suitable for coil treatment or in whom previous
treatment has failed to occlude the aneurysm.
COMPLICATIONS
•• Perforation
•• Thromboembolism.
Perforation
•• During coiling the microwire/microcatheter/coil may inadvertently perforate
the wall of the aneurysm.
•• This leads to SAH, which may increase the mortality/morbidity if not rapidly
controlled.
•• Heparin is reversed and the aneurysm is rapidly packed with coils.
•• Use of a remodelling balloon catheter for urgent tamponade is life saving.
•• Aneurysmal rupture is depicted by the issue of the tip of the coil or the
microcatheter outside the limit of the aneurysmal sac and/or extravasation
of contrast media during angiography.
Chapter 87 • Contemporary Endovascular Treatment of Intracranial Aneurysms
651
•• Aneurysm rupture may also lead to large parenchymal haematomas which

require surgical evacuation.
•• Rupture of the aneurysm into the ventricle may require an external
ventricular drainage to treat hydrocephalus.
Thromboembolism
•• It is a feared complication during the procedure leading to cerebral
infarction.
•• Medical treatment is modified during the procedure with an increase of
the systemic heparinisation, IIb/IIIa antagonist or intra-arterial fibrinolysis
with rt-PA.
DEVICE RELATED ISSUES

•• Malfunctioning of devices, may occur rarely.
•• Stretching of coil, non-detachment of coil, coil or stent migration, and
microcatheter/balloon rupture may rarely complicate a procedure.
RECANALISATION/RECURRENCE
•• The long-term stability of aneurysmal occlusion obtained with coils remains
the most significant limitation.
•• Recanalisation is commonly seen with large wide neck aneurysms or giant
aneurysms.
•• It depends on the initial packing or coil density at the time of first treatment.
•• Recanalisation occurs due to coil compaction, incomplete packing or neck
residue.
88
CHAPTER Vascular Malformations
of the Brain
CLASSIFICATION
•• The term “arteriovenous malformation” is commonly used to describe all
types of vascular malformations of the brain.
•• Though numerous classifications have been proposed by various authors,
the widely accepted classification is that propounded by McCormick in 1966
and is based on the morphology of the component vessels, the existence
of intervening neural elements and the biological behaviour of the lesion.
•• This classification, subsequently modified by him in 1978, is as follows:
–– Arteriovenous malformation (AVM)
–– Cavernous angiomas
–– Venous angiomas
–– Capillary telangiectasia
–– Transitional forms.
•• AVMs are the commonest of these lesions in surgical series, whereas,
venous angioma is the most common type of anomaly in large autopsy
series.
ARTERIOVENOUS MALFORMATIONS
Aetiopathogenesis
•• Although the definite aetiopathogenesis of these developmental vascular
malformations is still unknown, a genetic factor has been considered.
•• Familial or hereditary cases with various neurocutaneous syndromes are
often associated with such lesions.
•• Early development of the cerebral circulation has been divided into five
chronological stages.
•• AVMs of the brain are congenital lesions which develop during the late
somite stage, between the 4th week and the 8th week of embryonic life.
•• Cells (angioblasts) differentiate from the mesoderm during the 3rd week
of embryonic life forming small syncytial islands.
•• These syncytial cells develop tiny sprouts which interconnect them and
form a syncytial plexus.
•• Intercellular clefts now appear in this syncytial plexus and they later fuse
to form the primitive vascular lumen.
•• The syncytial cells enveloping these clefts become the endothelium of
the vessels and these later proliferate linking the vascular lumina into an
irregular endothelial vascular meshwork over the surface of the developing
brain.
Chapter 88 • Vascular Malformations of the Brain
653
•• The more superficial portion of this primordial vascular plexus forms the
arteries and veins, and the deeper portion resolves into the capillary
component.
•• The exact pathogenesis of AVMs is unknown.
•• Capillary agenesis during the second stage of development was postulated
as the predominant feature of congenital AVM by Olivecrona and Ladenheim.
•• However, Tonnis and Lange-Cosak, thought that the developmental arrest
took place during the fifth stage.
•• Kaplan et al. felt that, originally, many plexiform anastomoses exist between
arteries and veins which later get reabsorbed and disappear. Arrest of
development at this phase will lead to persistence of abnormal arteriovenous
(AV) communications.
•• The fact that AVMs of congenital origin are substantiated by the absence of a
history of trauma, stress and other potential causes of a vascular fistula, their
development and increase in size by displacement of the maturing brain at its
margin with preservation of neurological function.
Incidence
•• The incidence of AVMs in the co-operative study was one-seventh of that
of intracranial aneurysms.
•• The majority of patients present in the third decade.
•• Mean age of presentation is 33 ± 18 years with no sex predisposition.
•• There is another peak in the paediatric age group.
Location
•• Most of the medium and large AVMs extend over two or more anatomical
vascular territories.
•• Hemispheric AVMs situated in the watershed areas are usually supplied
by more than one arterial pedicle.
•• The parietal lobe is the commonest region involved in supratentorial lesions.
•• There is no significant hemispheric preference.
•• The majority of deep AVMs were located in the medial paratrigonal region
Pathology
•• Hemispheric AVMs are located in the middle cerebral, posterior cerebral
and anterior cerebral territories in declining frequencies.
•• An AVM is a cluster of congenital AV communications without an intervening
capillary bed.
•• Both the feeding arteries and the draining veins are tortuous and dilated.
•• These may derive arterial supply either from one or a combination of
epicerebral (perforators arising from pial vessels), transcerebral (major
parenchymal arteries and their branches) or subependymal vessels
(choroidal arteries).
•• The malformations supplied by the epicerebral vessels are confined to the
cortex and are drained by cortical veins.
•• The AVMs fed predominantly by the transcerebral vessels usually assume
the shape of a wedge, based on the surface with its apex often reaching
the ventricular wall.
•• These drain into both the superficial and deep venous systems.
•• The centrally located AVMs mostly receive feeders from the anterior as
well as the posterior circulation.
654
•• Malformations located in the watershed areas are always fed by more than
one major artery.
•• Depending upon the size, the malformation may involve one or several
adjacent lobes, the entire cerebral hemisphere or, rarely, the whole brain.
•• As the draining veins are arterialised, they are disproportionately enlarged
and often look like arterial feeders at operation.
•• The growth of the malformation proceeds apace with the growth of the brain.
•• In the absence of an interposed capillary bed with diminished resistance of
blood flow and deficient vasomotor control in the shunt, an increased amount
of blood passes through the malformation unutilised.
•• The malformation becomes a “parasite on the cerebral circulation”, depriving
the adjacent brain of normal perfusion.
•• Increasing “shunt flow” may even embarrass the cardiac output in neonates.
•• In the presence of large cortical draining veins, the arterial feeders are
often submerged within the brain parenchyma.
•• Large AVMs with associated varices do behave as space occupying lesions
producing neurological deficits either due to mass effect or because of
intracerebral steal.
•• The leptomeninges covering the malformation are often thickened and
opacified giving it a milky white appearance.
•• Most AVMs demonstrate a gliotic core associated with the nidus and a
gliotic wall around the malformation forming a “pseudo-capsule” which
helps in surgical dissection for total extirpation.
•• Hyaline degeneration causes collagenous replacement of the normal
smooth muscle component of the media in the main arterial feeders
adjacent to the malformation.
•• Smooth muscle and intimal nodules often project into the lumen of large
arterialised draining veins and their walls may reveal amyloid like material.
•• In between the component vessels, gliotic parenchyma and foci of
haemosiderin laden macrophages are often encountered.
•• Moyamoya disease, sickle cell disease, Marfan’s syndrome, Turcot
syndrome, hereditary haemorrhagic telangiectasia (HHT), Beckwith-
Wiedemann syndrome, high grade glioma, angioma, other vascular
formations, persistent trigeminal artery and metaplasia have been
associated with AVM.
•• Immediate perinidal brain tissue may show dilated capillaries with severe
congestion. These vessels are sometimes called “giant bed capillaries”
and are associated with significant ischaemia in the surrounding brain matter.
Molecular Basis
•• Expression of modulation of various molecules, receptors and mediators
has been implicated in the pathogenesis of AVM.
•• The IL-6 genotype is associated with increased expression of IL-6 in AVM
with increased angiogenesis and increased incidence of intracerebral
haemorrhage.
•• RASA 1 defects and phosphorylated extra-cellular signal regulated
kinase promote abnormal vascular remodelling, thus promoting AVM
pathogenesis.
•• Similarly, VERF–VEGF receptors and integrin alphabeta I have been
implicated in promoting growth of AVM.
•• Smoothelin expression is reduced in large AVMs resulting in associated
loss of contractile property associated with the homodynamic stress.
•• Tie-2 expression has also been implicated in a similar manner.
655
•• Smooth muscle cell specific protein marker SM2 is absent in normal

vascular structures and is expressed strongly in AVM.
•• The SAH induced vasospasm is mediated by endothelin 1 whose levels
are elevated in endothelial cells from ruptured AVM.
Natural History
•• There are several long-term studies reported in the literature, addressing
the issues of the natural history of AVMs.
•• Only 18–20% of cerebral AVM are diagnosed during infancy and childhood.
•• The onset of symptoms is maximal in the second and third decades,
although these lesions are present since birth.
•• This latency in the onset of symptoms is probably due to progressive
maturation and growth of the lesion and gradual changes in the adjacent
neural parenchyma.
•• Haemodynamic factors eventually lead, either to a weakening of the vessel
wall resulting in haemorrhage, or to irritation and gliosis of the surrounding
neural tissue causing seizures.
•• Growth of AVMs occurs in about 20% due to repeated haemorrhages,
gradual dilatation of the vessels, expansion of feeders, and recruitment
of new supply.
•• AVMs in the elderly may at times diminish in size, especially small AVMs
with a single feeder.
•• Occasionally, an AVM may disappear spontaneously as demonstrated
angiographically. Spontaneous occlusion of AVM and de novo occurrence
and growth of AVM, though rare, have been reported.
•• ICH is a presenting feature in 75–80% of cases and is associated with
higher morbidity and mortality.
•• The natural history of untreated cerebral AVM is worse in children with
longer life expectancy than in adults, higher annual risk of AVM bleed [3.2%
vs 2.2%] and a higher incidence of posterior fossa and basal ganglia AVM,
most of which present with massive haemorrhage.
•• Haemorrhage either at original presentation or during follow-up of an
untreated AVM appears to carry a lower morbidity than ICH from other
causes.
•• Risk of haemorrhage of grade IV and grade V AVM appears to be lower
than grade I through grade III.
•• Deep seated large AVM are more prone to haemorrhage.
•• Intracerebral haemorrhage in the paediatric age group differs from the adult
and is mainly due to vein related causes.
Clinical Features
•• An AVM may present with ICH, seizures, headaches, focal neurological
deficits, dementia, raised intracranial pressure, congestive heart failure
(especially in neonates) or unusual symptoms like trigeminal neuralgia or
hemifacial spasm.
•• Symptoms occur due to cortical venous hypertension, venous stasis and
ischaemia.
Haemorrhage
•• ICH was the most common mode of presentation of AVMs, with the majority
having bled before the age of 40 years.
656
•• It is the initial presenting symptom in 65–79% of cases.

•• The peak incidence of haemorrhage is between 11 years and 35 years
of age.
•• There is no gender preference for the propensity to bleed.
•• Although, it is conventionally believed that AVMs tend to rupture more
frequently during pregnancy, there is no convincing evidence to substantiate
such a belief.
•• Haemorrhage may be intraparenchymal, intraventricular, subarachnoid
or subdural.
•• Unlike saccular aneurysms bleed from an AVM is unrelated to stress,
activity, trauma or hypertension.
•• Predictors for a high-risk of AVM rupture are:
–– Age: There is a higher propensity for AVM to rupture in children.
–– Size: Small AVMs have an increased likelihood of bleeding because
of the higher pressures in the feeding artery. Small AVMs commonly
present with a massive intraparenchymal bleed.
–– Location: AVMs located in the posterior fossa have a higher risk of
rupture and also have a poorer outcome.
–– Past history of bleed: Incidence of an earlier bleed is followed by a
higher risk of second bleed in the 1st year.
–– Intranidal aneurysm: Demonstration of an associated intranidal
aneurysm suggests a high possibility of bleed.
–– Venous drainage: The deep drainage pattern may be associated
with stenosis of the vein of Galen which increases their propensity to
bleed; or else, the arterial pedicles of the deep seated central AVMs
being smaller, result in high flow and pressure within the nidus, thus
predisposing to their rupture.
–– Pathogenesis of haemorrhage: Venous obstruction resulting from
either a mechanical cause like venous stenosis or a relative haemo-
dynamic venous obstruction due to increased venous outflow results
in rupture of the thin-walled venous end, more so at the nidus-venous
junction.
¾¾ Haemorrhage may also result from rupture of an associated intra-
nidal aneurysm.
¾¾ The intranidal aneurysm occurs as a consequence of mechanical
or haemodynamic venous outflow obstruction.
Seizures
•• The second most common manifestation of AVMs is seizures, its incidence
being 10–50% in different series.
•• Seizures are more common with large, superficial, high flow malformations.
•• In the elderly, epilepsy is less frequent with an increased incidence of
infratentorial lesions.
•• Pathogenesis of seizures:
–– Although an AVM is a congenital lesion, the irritation and gliosis pro-
duced in the surrounding brain tissue with maturation of the lesion,
may result in a seizure disorder.
–– An epileptogenic focus may also be caused by associated cerebral
ischaemia due to steal in a high flow AVM.
–– Haemosiderin deposits and areas of intervening gliosis result from the
pressure of dilated vessels and/or decreased tissue perfusion due to
venous hypertension.
657
–– Mass effect, due to venous ectasia or pouches and retrograde dural

sinus hypertension resulting in hydrocephalus or raised intracranial
pressure, may also cause seizures.
Focal Neurological Deficits
•• Neurological deficits and mental changes are the result of arterial steal,
venous hypertension causing hypoperfusion of the surrounding brain
parenchyma, mass effect of the AVM or hydrocephalus.
Other Features
•• Large AVMs produce changes in the scalp and the skull.
•• The scalp veins may enlarge and also increase in number.
•• In some a thrill may be palpable over the neck vessels, associated with a
bruit. Bruit is more common when the malformation has connections with
the external carotid system.
•• Papilloedema and fundus changes, when seen, are mostly secondary to
SAH or a haematoma.
•• Mental changes are also common in posterior fossa malformation, when
all the blood vessels take part in the supply to the malformation.
Cardiovascular Effects
•• In very large AVMs with enlargement of the feeding vessels, and increased
blood flow, there is an associated change in the pulse pressure giving rise
to a water hammer pulse.
•• In the late stages, high output cardiac failure may result.
Haematological Effects
•• Some AVMs have a tendency to trap platelets which adhere to the poorly
formed endothelium of the malformation.
•• This may result in thrombocytopaenia and a bleeding diathesis.
HAEMODYNAMICS OF ARTERIOVENOUS
MALFORMATION
•• An AVM is typically an abnormality comprising of direct AV shunts,
characterised by the absence of the intervening capillary bed.
•• The absence of these resistance vessels, therefore, causes a low perfusion
shunt flow which adversely affects the brain parenchyma, either by altering
the blood flow pattern in the neighbouring areas causing “intracerebral
steal”, or, by affecting the metabolism in the adjacent normal tissue which
shows evidence of decreased glucose utilisation.
•• Feeding artery pressures in the AVM are an important determinant of the
haemodynamic events related to the lesion.
•• The pressure in the feeding arterial pedicle is determined by:
–– Size of the AVM: The smaller the size of the AVM, the higher will be
the feeding artery pressure
–– Length of the feeding artery: The smaller the feeding arterial seg-
ment, the higher will be the pressure within that vessel
–– Number of nutrient arteries to the adjacent parenchyma: The more
the number of nutrient branches, the less will be the pressure head
feeding the AVM
•• Shunt flow velocity within the AVM nidus is an important determinant of
the clinical manifestations and can be measured non-invasively by using
transcranial Doppler ultrasound.
658
INVESTIGATIONS
•• Plain X-ray skull may occasionally show evidence of calcification and/
or abnormal vascular markings on the skull, but this is not an important
investigative tool in the diagnostic armamentarium available today.
•• The CT scan is valuable in diagnosis. In the hyperacute and acute stages,
CT visualises the intracerebral haematoma and brain oedema better than
MR.
•• A plain CT scan may show an area of hypodensity within the haematoma.
•• This is a useful guide to the location of the nidus of the AVM as the “nidus
sparing sign”.
•• The presence of associated calcification is easily seen.
•• There may be evidence of “steal” phenomenon and hypoperfusion of the
surrounding brain in the form of perilesional hypodensity, grey matter
changes, disturbances of grey-white interface or cortical atrophy. Intrinsic
hypodense areas within the AVM may be visualised in a high resolution
scan, corresponding to the areas of gliosis or old haemorrhage.
•• Magnetic resonance imaging (MRI) will show areas of serpiginous flow void
on T1-weighted and T2-weighted images.
•• The signal intensity of the AVM may be paradoxically increased if there is
slow flow, stagnation or thrombosis within the vessels.
•• Areas of associated haemorrhage are revealed and old subclinical
haemorrhages, which are difficult to diagnose on a CT scan, can be easily
visualised.
•• The exact location of the AVM nidus, feeders and draining veins is easily
established in relation to the eloquent areas of the brain because of the
ease of multiplanar imaging.
•• Areas of cortical atrophy are also easily visualised. Serial MR imaging is
useful in diagnosis and management of occult AVM.
•• Functional MRI (fMRI) is useful in identifying language activation patterns
and the relative location of an AVM.
•• Brain plasticity in relation to structural abnormalities like AVM can be
demonstrated by fMRI.
•• MR tractography is useful in assessing the relationship between the AVM,
sensory motor fibres and tracts.
•• Magnetoencephalogram is useful in estimating an interictal paroxysmal
activity source in patients with AVM.
•• MR angiography (MRA) gives an excellent outline of the AVM with detailed
information on the arterial pedicles and venous drainage pattern.
•• The features to be noted in the feeding arterial pedicles are:
–– Whether it is a direct or an indirect feeder
–– Presence of stenotic segments in the arteries
–– Presence of any dural supply
–– Associated angiographic variations of the arteries
–– Presence of associated aneurysms which may be either dysplastic or
flow related
–– Presence of angiographic spasm (which is uncommon in this
condition).
•• A study of the nidus should be undertaken to evaluate:
–– The type of nidus, whether it is compact or diffuse. A compact nidus
should be further categorised as to whether it is single, multifocal or
multicompartmental
659
–– The size of the nidus

–– The presence of AV communications and flow characteristics: whether
a high flow or a low flow AVM
–– A high flow AVM is characterised by the presence of a large nidus,
usually larger than 4 cm, a few large feeders, high shunt flow within
the nidus, decreased circulation or dilated arteries in the adjacent brain
parenchyma and evidence of steal from adjacent vascular territories
–– Venous pouches
–– Intranidal aneurysms.
•• Careful observation of the venous drainage pattern is mandatory to note:
–– Drainage: Whether central, cortical or mixed
–– Variations in venous anatomy
–– Stenosis, thrombosis or kinking of the veins
–– Ectatic dilatations of the draining veins.
•• Studies necessary for pre-surgical planning include:
–– A good subtracted and magnified angiogram showing the above
mentioned features
–– The relevant frames to delineate the nidus of the AVM in relation to
bony landmarks like the coronal suture, external occipital protuberance
and external auditory meatus
–– Delineation of the cortical draining veins of both the hemispheres,
when an interhemispheric approach to the AVM is planned.
CAUSES FOR ANGIOGRAPHICALLY OCCULT

ARTERIOVENOUS MALFORMATIONS
•• AVMs that are not visualised on angiography, are termed angiographically
occult vascular malformations.
•• These may be either truly occult or may not be visualised due to the various
factors enumerated below:
–– Truly occult AVMs such as cavernoma, telangiectasia, thrombosed
AVM
–– Transiently occult AVMs due to destruction or compression by haema-
toma and/or oedema
–– Micro AVM
–– Intraluminal thrombosis because of stagnation or turbulent flow
–– Changes in blood vessels, e.g. fibrosis, spasm, placation or dysplastic
changes
–– Variable filling of the AVM during angiography.
•• CT angiography with spiral/helical CT and maximum intensity projection can
be used to display vascular images in a 3D format with excellent delineation
of the anatomical features.
•• Transcranial Doppler is useful in the study of intracranial vascular
malformations in neonates and children to evaluate the malformation as
well as the ICH.
•• Colour Doppler imaging can be used in pre-natal diagnosis of foetal brain
malformations.
•• Single-photon emission computerised tomography (SPECT) and functional
positron emission tomography (PET) scanning are useful for assessment
of the extent of hypoperfusion.
•• PET activation studies are also useful in precise location of cortical functions
of patients with an AVM to guide management as cortical functions may
undergo translocation when a huge AVM involves eloquent areas.
660
GRADING OF ARTERIOVENOUS
MALFORMATIONS
•• Total surgical resection of an AVM is determined by many factors:
–– Age and neurological status of the patient
–– Size (small, medium, large, giant)
–– Location, especially with respect to eloquent areas of the brain
–– Configuration of the nidus (compact or diffuse)
–– Number, size, type and source of arterial feeders
–– Nature of venous drainage (superficial, deep or mixed) and number
of draining veins
–– Haemodynamics of the AVM (shunt flow, degree of steal from the
surrounding parenchyma, feeding artery pressure and participation of
perforators)
•• An ideal system for grading should be simple, uniformly applicable, able
to predict operative difficulty as well as outcome, and should enable
comparison and evaluation of all treatment modalities.
•• The Spetzler and Martin grading system takes into consideration the size,
the venous drainage and the eloquence of the adjacent brain.
–– Points are assigned for each factor as follows:
1. Size of AVM
Small ( < 3 cm) 1 point
Medium (3–6 cm) 2 point
Large ( > 6 cm) 3 point
2. Eloquence of adjacent brain
Non-eloquent 0 point
Eloquent 1 point
3. Pattern of venous drainage
Superficial only 0 point
Deep 1 point
•• The grades are I to V and this is arrived at by adding the scores.
•• Grade I, i.e. a small AVM in a non-eloquent area with a superficial drainage
has the best prognosis; and grade V, i.e. a large AVM in an eloquent area
with deep venous drainage has the worst prognosis.
•• Inoperable lesions are in Grade VI and diffusely involve the brainstem or
hypothalamus.
89
CHAPTER Surgical Management of
Cerebral AVMs
Ravi Ramamurthi  Ravindranath Kapu
•• The management of an AVM can be a simple matter or a most challenging

neurosurgical exercise.
•• The following varieties of procedures that have been used for dealing with
this condition are:
–– Excisional surgery
–– Endovascular treatment
–– Radiosurgery
–– Combination of the above.
•• The criterion for cure of an AVM is the complete obliteration and non-
visualisation of the AVM on follow-up angiography.
CONSIDERATIONS IN
THE TREATMENT OF AVM
•• Important considerations for the treatment of an AVM are:
–– Factors related to the patient—age, general condition, neurological
state, occupation and psychological attitude.
–– Factors related to the AVM—natural history of the AVM, its mode of
presentation, and anatomic and haemodynamic characteristics of the
AVM.
–– Experience of the neurosurgical team and the available facilities.
Factors Related to the Patient

•• Age is an important determinant of surgical therapy.
•• Young patients have a high-risk of bleeding from an AVM and the
cumulative morbidity due to haemorrhage or seizures is very high.
•• While confronted with an older patient, the risk:benefit ratio for the individual
patient should be considered, keeping in mind the life span of the patient
and also the fact that the risk of bleeding may actually decrease after the
middle age.
•• A patient with a poor performance on the Karnofsky scale is unlikely to
have a good outcome.
•• Occupation of the patient and the psychological motivation are important
considerations, especially in relation to the post-operative morbidity.
Factors Related to the AVM

1. The natural history of cerebral AVMs leaves no doubt that the long-term
prognosis for patients with untreated malformations is grim.
662
2. Mode of presentation:
–– There is no argument as far as the treatment of AVMs presenting with
haemorrhage is concerned. They undoubtedly merit definitive treat-
ment.
–– With increasing understanding of their natural history, it is becoming
evident that AVMs presenting with non-haemorrhagic manifestations
also deserve aggressive management.
–– Patients with intractable headache alone, progressive neurological
deficits or hemifacial spasm, all need to be considered for definitive
treatment based on the individual merits of the case.
–– A fixed neurological deficit from a past haemorrhage does not improve
following surgical excision, but such patients, if young, are offered
definitive treatment in order to prevent recurrent bleeds and further
increase in morbidity.
–– An asymptomatic AVM in a young patient definitely deserves aggres-
sive management, whereas, in an elderly patient it may be left alone.
3. Anatomic and haemodynamic factors:
–– These are important determinants of the mode of therapy to be chosen
for a specific case.
–– While the majority of the AVMs can be surgically excised, it may be
difficult to operate on certain small AVMs in deep, inaccessible or
eloquent areas.
–– The same applies to very large, diffuse AVMs occupying almost an
entire hemisphere.
–– The relative merits of radiosurgery, embolisation or any of the combi-
nations of the available modalities need careful consideration.
SURGERY
•• Total surgical excision remains the gold standard for the treatment of an
AVM.
•• The aims of surgical excision are to interrupt the natural history of the
disease, and prevent future haemorrhage, decrease cerebral steal, improve
neurological deficits and to achieve seizure control.
Principles of Surgical Treatment

•• Unlike an aneurysm, the risk of immediate rebleed from an AVM is much
less.
•• Generally, the arterial feeders should be attacked first, followed by excision
of the nidus and finally resection of the draining veins.
•• Care should be taken to preserve the veins until the very end of the
operation.
•• When an intracranial AVM is resected, the goal should be complete
obliteration.
•• The timing of angiography and elective excisional surgery is delayed 2−3
weeks for the brain to recover from the initial insult, unless a large and
life-threatening haematoma warrants early evacuation.
•• Early angiography often fails to delineate the exact morphology of a
malformation in the presence of a sizeable haematoma.
•• In the presence of a haematoma with attendant cerebral oedema and raised
intracranial pressure, attempts at early surgical excision may often preclude
the chances of total extirpation of the malformation.
Chapter 89 • Surgical Management of Cerebral AVMs
663
•• While awaiting angiographic evaluation and definitive surgery, patients are

administered anticonvulsants and antioedema therapy if indicated.
•• Small AVMs located in the polar regions or on non-eloquent cortical
surfaces, with or without a bleed, pose little difficulty for total excision.
•• However, large high-flow AVMs or those with deep arterial feeders are often
a challenge for one stage surgical excision. In such lesions, pre-operative
embolisation, particularly of the deeper feeders, reduces shunt flow,
minimises intra-operative bleeding and avoids post-operative autoregulation
breakthrough syndrome.
•• For extensive malformations, certain surgeons employ planned staged
surgical resection without pre-operative embolisation, depending upon
sectorisation of the lesion.
•• Advances, like stereoscopic angiography, bipolar diathermy with automatic
irrigation, improved neuroanaesthetic management, application of Nd-YAG
laser photocoagulation, evoked potential monitoring for brainstem lesions,
intra-operative DSA facilities, intra-operative cerebral blood flow studies and
fluorescein angiography, as well as cortical mapping of the eloquent areas,
have profoundly expanded the limits of successful total excision of AVMs.
AVMs Associated with Aneurysms

•• The AVMs are associated with aneurysms in 3% of the cases.
•• Aneurysms in such a setting may be either flow related, developing as a
result of high flow through the AVM; or non-flow related, and located at the
common sites for aneurysms in the circle of Willis.
•• Flow unrelated aneurysms located outside the angioarchitecture of the AVM
are unlikely to regress after surgery for the AVM and may in fact enlarge and
rupture once the “sump” effect is eliminated following extirpation of the AVM.
•• These aneurysms should be operated upon before treating the AVM.
•• Regression has been noted in the size of a flow-related or dysplastic
aneurysm, or a distal aneurysm or aneurysmal dilatations located on the
trunk of the main feeding arteries after restoration of normal flow following
excision of AVM.
Haemodynamic Changes after Removal of an AVM

•• The immediate change that occurs following removal of an AVM is the
interruption of the nonperfusion flow and the conversion of shunt flow into
perfusion flow pattern.
•• There is an increase in the arterial end pressure, and the pressure at
the venous end decreases which results in an increase in the cerebral
perfusion pressure.
•• This increase in the perfusion pressure could be due to elevated plasma
renin and norepinephrine levels.
Post-operative Complications
•• Complications that may be encountered in the early post-operative period
are:
•• Brain swelling which can be caused by a venous infarct, retraction oedema,
haemorrhage from residual AVM, perfusion pressure breakthrough
syndrome or occlusive hyperaemia.
•• In AVMs with large-sized and long feeder vessels, when there is evidence of
stagnation of blood in the post-operative angiogram retrograde thrombosis
of the feeding artery may occur, especially in elderly patients.
664
•• Post-operative hyperthermia is another serious complication which can be

exacerbated by mild, intra-operative-induced hypothermia.
Normal Perfusion Pressure Breakthrough Syndrome

•• Two hypotheses for the cause of brain oedema and haemorrhage during
or after surgery for AVM have been proposed—normal perfusion pressure
breakthrough syndrome (NPPB) and occlusive hyperaemia.
•• The NPPB syndrome was described by Spetzler et al. in 1978 and is thought
to be related to dysautoregulation of circulation in the brain parenchyma
adjacent to an AVM.
•• It is, however, a rare occurrence when there is a large high-flow AVM, the
surrounding brain tissue is in a state of chronic ischaemia due to vascular
steal by the same parent vessel which feeds the AVM.
•• The vessels in this ischaemic, hypoperfused area will be in a state of chronic
vasodilatation in response to the persistent ischaemia and they lose their
inherent capacity for rapid autoregulation.
•• The rapid interruption in the flow to the AVM and restoration of perfusion
flow may result in an increased flow in these maximally dilated vessels
which are unable to contract in response to the increased flow.
•• This results in seepage of blood from these vessels into the adjacent brain
parenchyma.
•• This phenomenon is termed the Perfusion Pressure Breakthrough Syndrome.
•• The key factor in prevention of this malignant post-operative haemorrhage
and oedema is staged reduction of blood supply to the malformation.
•• This can be accomplished by staged surgical ligation of the feeders
•• The factors that help in predicting the risk of developing NPPB are:
–– Clinical evidence of cerebral ischaemia, e.g. focal neurological deficits,
headaches, seizures.
–– CT or MR evidence of cerebral atrophy resulting from hypoperfusion.
–– Angiographic evidence of large, high-flow AVM, numerous large
calibre feeding arteries, steal from other vessels, border zone location,
flow shift towards the AVM.
•• Pre-operative evidence of ischaemic rim around the nidus identified by
cerebral blood flow studies, low feeding artery pressure before removal
of AVM, immediate normalisation of arterial and venous pressures after
removal of the AVM, increased regional cerebral blood flow after removal
of the AVM.
Occlusive Hyperaemia
•• This hypothesis postulates that the malignant post-operative haemorrhage
and oedema can be caused by either arterial stagnation and obstruction
or venous outflow obstructions, which are in turn related to resection of
the AVM.
Post-operative Seizures
•• The incidence of post-operative seizures after removal of an AVM ranges
6.5−50%.
Results of Surgery
•• Immediate mortality due to surgery can be expected in the range of 1−6% .
•• Delayed mortality has been reported in 1−2%.
Chapter 89 • Surgical Management of Cerebral AVMs
665
•• Morbidity in the immediate post-operative period is seen in 20−44%, of

cases whereas over a period of time, the morbidity decreases to 2−6%.
•• The dramatic improvement in the neurological deficits in the majority
of patients is because of resolution of the pre-operative intra-cerebral
haematoma and restitution of normal cerebral perfusion.
•• Development of immediate transient neurological deficits may be because
of retraction oedema or due to the phenomenon of surrounding cortical
suppression described by Yasargil as “Temporary blocked syndrome”.
•• Patients in poor pre-operative clinical grade may be expected to have a
poor outcome.
EMBOLISATION
•• Interventional neuroradiologists can embolise the AVM nidus or the feeders
as definitive treatment, or as a part of the multimodality approach to the
management of large high flow AVMs.
•• Embolisation is also useful in occluding inaccessible feeders.
•• Current indications for embolisation can be divided into:
–– Pre-surgical embolisation for large or giant cortical AVMs, and
–– Embolisation before radiosurgical intervention to reduce the nidus size.
•• Embolic materials can be divided into solid or liquid agents.
•• Solid agents consist of fibres, microcoils and microballoons and liquid
agents include cyanoacrylate monomers such as I-butyl cyanoacrylate
(IBCA) and N-butyl cyanoacrylate (NBCA), ethylene vinyl alcohol (EVAl)
copolymer, absolute ethanol, with or without the use of contrast agents for
visualisation under digital subtraction fluoroscopy.
•• Usually the transfemoral route is employed.
Pre-radiosurgical Embolisation
•• Endovascular therapy for radiosurgical interevention for AVMs has three
potential goals:
1. To decrease target size to less than 3 cm in diameter, because smaller
volumes have a higher cure rate with less morbidity.
2. To eradicate angiographic predictors of haemorrhage, such as intra-
nidal aneurysms or venous aneurysms.
3. To attempt to reduce symptoms related to venous hypertension.
•• There is no ideal embolic material identified for pre-radiosurgical use.
Palliative Embolisation
•• This may be recommended for patients who have large, inoperable cortical
and subcortical AVMs and in those patients presenting with uncontrollable
seizures or with progressive neurological deficit due to secondary venous
hypertension and/or arterial steal phenomenon.
•• Cyanoacrylates and polyvinyl alcohol (PVA) cause acute inflammation and
angionecrosis in the early stage, followed by a late chronic inflammatory
response and foreign body giant cell reaction.
•• Complications encountered with embolisation may be due to the
haemodynamic alterations or due to the material used.
•• Haemodynamic alterations may cause increased risk of haemorrhage
because of pressure changes in the feeding artery and by recruitment of
collaterals, in cases of partial embolisation of the nidus.
666
•• Materials, like IBCA, may cause difficulty in dissection and retraction of the
AVM during subsequent surgery, because of its hard consistency and failure
of the vessels containing the IBCA cast to contract during coagulation.
•• Rarely, the IBCA cast may dissolve, resulting in recanalisation of the AVM.
•• Other complications that may be encountered include neurological
deficits due to occlusion of normal arteries, hyperaemia and swelling of
the surrounding parenchyma, catastrophic haemorrhage due to rupture
of arterial feeders or rarely, glueing of the catheter in situ due to rapid
polymerisation of IBCA.
RADIATION THERAPY
•• Conventional radiotherapy has no role in the treatment of AVMs.
•• However, stereotactic radiosurgery using charged particle beams (He,
proton or neutron), Gamma knife (Co-60) or linear accelerator have all
been found to be effective in the treatment of AVMs.
•• Radiosurgery is indicated:
–– In small (<2−3 cm), deeply located, surgically inaccessible AVMs in
eloquent areas of the brain with multiple small feeders.
–– In combination with surgery or embolisation for large AVMs,
inaccessible or unresectable residual AVMs.
–– In patients who are either not willing for surgery or poor surgical
candidates because of concomitant medical illness.
•• Ideal candidates for radiosurgery are the patients with small AVMs in
eloquent areas, preferably with an isolated pedicle (See next chapter for
details).
ELECTROTHROMBOSIS AND CRYOSURGERY

•• To overcome troublesome bleeding and facilitate total excision of deep
seated and large AVMs, Handa et al. employed electrothrombosis using
copper electrodes and direct current.
•• If a check angiogram does not reveal disappearance of the nidus, the AVM
is then excised easily.
•• However, this procedure has not gained wide popularity and is of historical
importance.
90
CHAPTER
Embolisation of
Intracranial Vascular
Malformation
Anil Karapurkar  Nishant Aditya
•• Arteriovenous malformations (AVMs) are the second most common

intracranial vascular malformations.
•• They are believed to be congenital or developmental in origin.
•• AVMs consist of a bunch of vessels, called nidus, which is made up of
vessels of variable diameter and vessel wall thickness.
•• The nidus may be compact or diffuse.
•• The AVM may be fed by one or more branches from cortical and deep
branches of the major arteries such as the ACA, MCA and PCA.
•• If the AVM is of the high flow variety, feeding arteries are dysplastic and
these dysplastic arteries may be associated with flow related aneurysms.
•• The draining veins have thick walls as they are arterialised.
•• In high flow AVMs, with or without arteriovenous fistula (AVF), the draining
veins may have large aneurysms or varices along their course.
•• There may be stenosis of the draining veins.
•• Haemorrhage may occur when there are venous anomalies or there are
sudden changes in venous pressure.
•• The brain surrounding the AVM may show areas of gliosis due to ischaemia
secondary to steal.
•• There may be calcification and cyst formation due to previous haemorrhage.
Some parts of the AVM may be thrombosed.
•• To standardise the management of AVMs, many classifications have been
proposed. The one commonly accepted is that of Spetzler-Martin.
•• The criteria which should be included in the classification are:
A. Weak spots—such as associated
¾¾ Juxta-nidal aneurysm
¾¾ Intra-nidal arterial aneurysm
¾¾ Aneurysm on the circle of Willis
¾¾ Subependymal venous aneurysm
¾¾ Stenosis along venous channels, especially when there is a single
draining vein,
¾¾ Congenital absence of the deep venous system which carries a
higher risk of haemorrhage;
B. Associated intra-nidal A-V fistula with very high flow across the nidus
which increases the risk of surgical extirpation and failure of stereotac-
tic radiosurgery (SRS).
•• In true intra-nidal A-V fistula, the microcatheter passes from the feeding
artery to the draining vein without the intervening nidus.
668
•• If there are “weak spots” even Grade IV or V AVMs according to Spetzler-

Martin classification should undergo targeted embolisation to reduce the
risk of haemorrhage.
•• The common presentations of brain AVM are: (1) haemorrhage (2) epilepsy
(3) progressive neurological deficit and (4) migraine and intractable
headache.
•• Clinical signs depend on the location of the malformation and the venous
drainage.
INVESTIGATIONS
•• CT scan after double dose contrast and CT angiogram on spiral or multi
slice CT scanning machines show the AVM nidus very well.
•• However, feeders, draining veins, associated aneurysms and haemo-
dynamics cannot be assessed.
•• It is also impossible to often delineate the precise nidus because of the
huge dilated early filling veins.
•• It is difficult to distinguish arteries from arterialised draining veins.
•• MRI sometimes is useful to show the true nidus.
•• However, it is difficult to get a true picture of the AVM on the MRI or MRA
even with the latest machines. At best, static images can be obtained. No
concept of the haemodynamics can be obtained.
•• Digital subtraction angiography (DSA) remains the gold standard in the
diagnosis of AVM.
•• Magnification, rapid subtracted filming at 6 or 12 frames per second and
multiple projections and rotational angiography provide all the desired
information.
•• For posterior fossa AVMs bilateral vertebral angiograms (VA) in addition
to bilateral internal and external carotid (ICA and ECA) angiograms are
mandatory.
•• For supratentorial AVMs, bilateral ICA, ECA and at least one VA angiogram
must be done.
•• The angiogram must be analysed carefully to include:
–– The precise site and size of the AVM
–– The arterial supply of the AVM
–– The venous outflow, whether superficial or deep, or both
–– Associated arterial aneurysm
–– Associated venous anomaly such as stenosis, absence of deep ve-
nous system, aneurysm or varix
–– Competition between the venous outflow of the brain and that of the
AVM
–– Functional antegrade flow in the superior sagittal sinus, as raised
venous pressure can cause a rise in ICP and papilloedema
–– Any evidence of mass effect due to associated clot as seen by
stretching and separation of arteries and veins
–– Any supply from external carotid branches.
INDICATIONS FOR TREATMENT

•• AVMs presenting with haemorrhage must be treated.
•• The mode of treatment—Surgery/Endovascular/Radiosurgery—would
depend on the site, size and “weak spots” of the AVM.
Chapter 90 • Embolisation of Intracranial Vascular Malformation
669
•• The management of incidental (those presenting with epilepsy) and Grade

IV and V AVM remains controversial.
•• Small AVMs are thought to bleed more frequently than large AVMs. They
must be treated.
•• AVMs, such as those in the basal ganglia and corpus callosum, which are
prone to re-bleed should be treated.
•• Spetzler-Martin Grade IV and V should be treated if there are weak spots,
such as intra-nidal or large flow related aneurysms, subependymal venous
aneurysms or significant flow limiting venous stenosis, which are likely to
bleed.
•• AVMs presenting with intractable epilepsy, severe headache which is
usually due to extracranial dural arterial supply and incidental AVMs with
“weakness” must be treated.
CONTRAINDICATIONS
•• Spetzler Grade V
•• Large diffuse AVM
•• Incidental large eloquent area AVM
•• Epilepsy as presenting feature in large AVM.
•• The results of treatment should be better than the natural history of the
disease.
•• Morbidity and mortality should be less than 4%.
•• The actual results, whether surgical or endovascular, are far worse.
•• In the best of hands, the complication rates are around 10−15%.
•• Embolisation must be planned for a patient.
•• It can be:
1. Definitive
2. Pre-SRS
3. Pre-surgery
4. For remnant following microsurgery
5. Remnant following SRS
6. Targeted for intra-nidal aneurysm
7. Intra-operative embolisation followed by excision
8. Targeted for other aneurysm (Guglielmi detachable coils) and
9. Targeted for headache.
•• Accessible small AVMs in non-eloquent brain with a single or multiple region
of the cortical venous drainage, such as small right frontal or temporal
AVMs, should be surgically excised unless there is a reasonable chance
of cure with embolisation alone.
•• A large AVM may be reduced in size by embolisation to make surgery
easier.
•• Intra-operative angiography and magnetoencephalography are useful
adjuncts.
•• Large AVMs, which are at a higher risk, should be subjected to targeted
embolisation of “weak spots”.
•• A larger or deeper AVM, which is at a high risk of haemorrhage, may be
treated by embolisation followed by SRS.
•• The chance of cure with SRS is about 90% if the AVM is smaller than 3
cm in diameter.
•• A large AVM may be reduced in size by embolisation so that it is amenable
to treatment by SRS.
670
EMBOLISATION
•• The ideal and curative treatment of AVM is to deposit liquid material like
Histoacryl or Onyx inside the nidus.
•• EEG and CSF pressure have also been monitored during embolisation.
•• Wada’s test for eloquent brain is done by injecting amobarbital. Around
30 mg of amobarbital is injected through a microcatheter. If there is loss of
function, embolisation is not done. Since there are false negative results,
Wada’s test has been abandoned.
•• Glue is injected only if the microcatheter is within the nidus.
•• For curative treatment, the entire AVM nidus including the proximal part of
the draining veins must be filled with glue.
•• Absolute alcohol has also been used for complete obliteration of the AVM.
•• Pre-operative embolisation can be with liquid embolic materials like Onyx
or Histoacryl or with particulate materials such as polyvinyl alcohol (PVA),
“cocktail” of PVA, absolute alcohol and Avitene, hydrogel particles or small
pieces of surgical silk.
•• The arterial supply to the nidus may be of two types: (a) End supply—The
artery ends in the glomus of the AVM and (b) “En-passage”. The artery
goes on to supply the normal brain and gives off feeders at right angles to
the long axis of the artery.
•• End type of supply is ideal for embolisation. Glue can be injected safely.
•• For en-passage type, if glue is injected, there is a high risk of occlusion of
a normal artery. For such lesions liquid coils are injected into the arteries
beyond the AVM.
•• Once the arteries are occluded glue can be safely injected. Occluding
arteries using coils proximally is safe because the pial network takes over
immediately.
•• Onyx is the other liquid embolic agent used in the treatment of brain AVM.
•• Onyx is ethyl-vinyl-alcohol-copolymer which is dissolved in a solvent called
dimethyl sulphoxide (DMSO).
Selecting Sections Judiciously for Pre-SRS Embolisation

•• Pre-surgical embolisation can be done with glue, Onyx or particulate matter.
•• Ideally, the less accessible deeper feeders from perforators should be
targeted. However, these are difficult to catheterise because they are
small and tortuous.
•• Cocktail, surgical silk or PVA particles are injected slowly with intermittent
contrast injections to monitor the progress.
COMPLICATIONS
Technical Complications
•• Technical complications are: (1) Failure to reach nidus; (2) Perforation
of artery by catheter or guide wire; (3) Spasm; (4) Occlusion of normal
branch by thrombus; (5) Glue injection into normal artery; (6) Passage of
glue into a normal cortical or deep vein, a dural venous sinus or the lung;
(7) Catheter getting glued and breaking off; (8) Catheter getting stuck in a
small artery due to vasospasm; (9) Perforation of microcatheter because of
forceful injection; (10) Rupture of missed small aneurysm; (11) Occlusion of
feeder without glue reaching the nidus, and (12) Occlusion of the draining
vein without obliteration of the nidus.
•• Haemorrhage and ischaemia are the two major complications.
Chapter 90 • Embolisation of Intracranial Vascular Malformation
671
CONCLUSIONS
•• Large Grade VI AVMs should be left alone except for targeted embolisation.
•• Grade IV and V AVMs should be treated if they are at risk of haemorrhage.
•• Targeted embolisation should be done for Grade IV and V.
•• Grade I should be surgically excised.
•• Grade II and III AVMs should be treated on merit, be it embolisation,
embolisation combined with surgery or SRS.
•• Grade IV and V can be treated by combining embolisation with SRS.
•• Small remnants after surgery can be treated by embolisation or SRS.
•• Small remnants after embolisation or SRS can be excised.
•• Small remnants after SRS can be retreated by SRS, if safe, excised or
embolised.
•• Embolisation with Histoacryl and Onyx is permanent.
•• Particulate matter, like PVA, silk or cocktail, is not recommended, except
as a pre-surgical procedure, as they can get reabsorbed.
91
CHAPTER
Stereotactic
Radiosurgery for
Cerebral AVMs
Ganapathy K
INTRODUCTION TO STEREOTACTIC
RADIOSURGERY
•• Stereotactic radiosurgery refers to the method of delivering a single high
dose ultra precise radiation (8−15 times that of a single conventional dose),
that is about 12−25 Gray (1,200−2,500 Rads), to a well-defined lesion,
using fixed stereotactic reference points.
•• Biological effects produced by radiosurgery range from blood vessel
thrombosis to reproductive cell death and frank necrosis within the treatment
volume.
•• Recently, it has been shown that the endothelium of AVMs has different
molecular properties and that these inflammatory molecules may be
biologically relevant in the response of vascular malformations to
radiosurgery and embolisation.
•• The source of radiation can be X-rays from a linear accelerator or cyberknife,
gamma rays from a cobalt unit (gamma knife) or charged particles.
•• The source of radiation (cobalt or X-rays) does not appear to make a
significant difference.
Advantages of Radiosurgery in the Management of

Cerebral Arteriovenous Malformations
•• Safe, post-treatment complications far less than in open surgery.
•• Complications are usually transient, mild and reversible.
•• No procedure related mortality.
•• Minimal or no hospitalisation is required.
•• No post-treatment convalescence.
•• Pre-treatment activities can be resumed immediately.
•• No procedure related risk of infection or bleeding.
Disadvantages of Radiosurgery in the Management of

Cerebral Arteriovenous Malformations
•• Not suitable for all cases.
•• Total obliteration only in 60−80% of cases.
•• 15−36 months waiting period.
•• Risk of haemorrhage till obliteration occurs.
•• Limitations and difficulty in post-treatment assessment.
•• Not freely available.
•• Considerable expertise and infrastructure required.
Chapter 91 • Stereotactic Radiosurgery for Cerebral AVMs
673
•• Extremely rare cases of delayed complications like cyst formation,

haemorrhage even after angiographically demonstrated total obliteration
and radionecrosis have been documented.
RADIOBIOLOGICAL EFFECTS OF STEREOTACTIC

RADIOSURGERY ON ARTERIOVENOUS
MALFORMATIONS
•• The underlying goal of treatment of AVMs by using high dose focused
radiation is to induce an inflammatory response in the vessel walls that
will result in a permanent thickening of pathological vascular channels,
leading to thrombosis.
•• AVMs are hamartomatous lesions of the brain resulting from embryogenic
maldevelopment.
•• They are histologically composed of a parenchyma with abnormal vessels
embedded in a connective tissue stroma.
•• The ionising radiation delivered by radiosurgery probably induces
proliferation of spindle shaped cells in both the subendothelial region of
the vessel wall and connective tissue stroma.
•• According to the immunohistochemical and ultrastructural characteristics,
these proliferating spindle cells are probably myofibroblasts.
•• The contractile capacity of myofibroblasts might explain the shrinkage of
AVMs after irradiation.
•• The most characteristic pathological feature of the necrotising radiation is
the occlusion of most of the small vessels within the targeted zone, leading
to a coagulative necrosis of all tissue elements.
•• The vessels of the AVM are thickened and fibrosed and the majority are
occluded by connective tissue over several months.
•• Thickening of the walls of the abnormal vessels was shown by histological
analysis.
STEREOTACTIC RADIOSURGERY FOR CEREBRAL

ARTERIOVENOUS MALFORMATIONS:
THE PROCEDURE
•• Stereotactic radiosurgery (SRS) should be carried out only in a tertiary
care referral centre.
•• Well-equipped departments of imaging sciences and radiotherapy with
medical physicists familiar with 3D treatment planning are a prerequisite
(the latter if a Linac based system is used).
•• Step 1—Fixing the frame
•• Step 2—Computerised tomography or magnetic resonance imaging data
acquisition
•• Step 3—Angiographic data acquisition
–– The patient is positioned on the angiographic table so that the frame is
in the centre of the table.
–– The angiographic localiser ring is placed on the stereotactic base ring.
–– A preliminary screening is done and fine adjustments made with the
image intensifier and tube so that eight fiducial markers are seen on
the PA projection and eight on the lateral projection.
–– A four-vessel angiogram is done to ensure that different arterial systems
contributing to the nidus are identified.
674
–– The images are transferred to the treatment-planning computer. Re-

cently, with increasing availability of 64 slice CT and with the possibility
of even a 256 slice CT, the use of DSA in treatment planning could
progressively decline.
•• Step 4—Treatment planning
–– Treatment planning differs depending on whether a gamma knife sys-
tem is used or a Linac based system. It also depends on the specific
equipment being used.
–– In the earlier days, one or more collimators of appropriate size were
chosen.
–– Now the micromultileaf collimator system for ultra-conformal radiation
is used.
–– A set of radiation beams is devised so that all of them converge on
the AVM.
–– Their passage through critical structures (from entrance to exit) is
avoided.
–– The plans are studied and modified till the proper dose distribution
within the target volume is obtained—sparing critical structures and
ensuring that the radiation dose outside the target volume is within
800 Cgy.
•• Step 5—Treatment
–– The actual treatment takes 30−60 minutes depending on the
complexity of the AVM.
–– After the radiation is completed, the frame is removed.
–– The patient is kept under observation overnight and can resume nor-
mal activities the next day.
Procedure Related Complications

•• In the appropriately chosen patient and with meticulous attention to minute
details, complications should be negligible.
•• Seizures occurred more often in the post-treatment period in AVMs than
in other lesions.
•• Hence, optimising anticonvulsant doses is essential, particularly in
supratentorial AVMs.
Embolisation Prior to Stereotactic Radiosurgery

for Arteriovenous Malformations
•• Embolisation can be used as a preliminary procedure to reduce the size
of the nidus and make it suitable for SRS.
•• Embolisation is effective only if the arterial feeders contribute to the
periphery of the nidus.
•• Often, following embolisation, the blood supply is cut-off in different portions
of the nidus making definition of the target volume difficult.
•• If SRS is done immediately after embolisation, the target volume will not
include portions of the nidus, which may form later following recanalisation.
•• Presence of intranidal glue also makes outlining the target volume difficult
in the CT and the MRI.
•• The ideal time interval between embolisation and SRS is yet to be
determined.
•• Usually a 4−12 weeks’ interval is preferred.
Chapter 91 • Stereotactic Radiosurgery for Cerebral AVMs
675
•• Endovascular treatment of cerebral AVMs following radiosurgery has also

been advocated.
•• The availability of Onyx has changed the concept of embolisation.
Location
•• SRS is particularly suitable for AVMs located in eloquent areas.
•• These include the post-geniculate visual pathway (to enhance the possibility
of preserving visual function) and the brain stem.
•• AVMs in the pineal region and the motor area are particularly suitable for
SRS.
Causes of Treatment Failure

•• Recanalisation after embolisation, re-expansion after haematoma
reabsorption and the presence of an intranidal fistula have been implicated
as causes for treatment failure.
•• Inaccurate target definition could be due to substandard imaging equipment
or operator error.
•• Lower radiation doses used for AVMs in critical regions or when the AVM
was unusually large may also contribute to treatment failure.
•• Statistically significant factors predictive of radiosurgical failure included
higher Spetzler-Martin grade, increasing AVM volume, lower peripheral
doses and a previous history of haemorrhage.
•• The maximum diameter, angiographic shape of the AVM nidus and
number of draining veins are also significant.
•• Smaller, compact AVMs with fewer draining veins respond well (Table 1).
Complications
•• Delayed cyst formation
•• A new paranidal aneurysm
Table 1: Factors related to complete AVM occlusion

Unfavourable group Favourable group
Large diameter nidus Small diameter nidus
Multiple veins Single vein
Higher Spetzler-Martin grade Lower Spetzler-Martin grade
Complex shape of nidus Compact shape of nidus
Low marginal dose High marginal dose
High-flow pattern Low-flow pattern
Prior embolisation No previous embolisation
Critical location of nidus Nidus located in non-eloquent area
Previous haemorrhage Absence of prior haemorrhage
Presence of associated aneurysm
Presence of associated AV shunting
Presence of calcification
Presence of intranidal fistula
676
•• Asymptomatic middle cerebral artery stenosis.

•• Chronic encapsulated expanding haematoma.
•• Asymptomatic dural arteriovenous fistula (DAVF) in association with nidus
obliteration after re-irradiation.
•• Haemorrhagic stroke, related to a previously irradiated, obliterated AVM.
•• Radiation necrosis occurring at the site of radiosurgically treated AVMs.
•• Radiation-induced oedema detected on MRI following SRS is not
uncommon.
92
CHAPTER Vein of Galen
Malformations
Anil Nanda
•• Vein of Galen malformations are rare vascular malformations.

•• They constitute approximately 1% of all intracranial vascular lesions and
nearly one-third of them are in the paediatric age group.
•• These malformations are usually situated in the midline, producing dilation
of the vein of Galen and are sometimes referred to as “aneurysms” of the
vein of Galen.
•• The high blood flow through this fistula or shunt is responsible for the
majority of symptomatology associated with these malformations.
ANATOMICAL CONSIDERATIONS AND

CLASSIFICATION
•• The vein of Galen is a centrally located short venous structure formed by the
confluence of the internal cerebral veins and the basal vein of Rosenthal.
•• It passes posteriorly, emptying into the straight sinus at its junction with
the inferior sagittal sinus.
•• The anatomic landmark of a vein of Galen aneurysmal malformation
(VGAM) is the presence of multiple arteriovenous shunts draining into a
dilated median prosencephalic vein, an embryonic vessel normally absent
in adults.
•• The structures drained by the vein of Galen include the thalamus, the medial
temporal lobes, the occipital lobes and the superior cerebellar vermis.
•• The vein of Galen lies in the quadrigeminal cistern and receives veins from
the ambient cistern, the pericallosal and occipital veins from the corpus
callosum cistern, and the precentral cerebellar vein from the superior
cerebellar cistern, as well as the internal cerebral veins from the velum
interpositum cistern.
•• Yasargil classified vein of Galen malformations morphologically based on
the arterial supply pattern of the malformation into four types:
–– Type I: Direct anastomosis between the vein of Galen and the perical-
losal arteries and the P3 segments of the posterior cerebral arteries.
–– Type II: Direct fistula between the thalamoperforating arteries (P1 seg-
ment) and the vein of Galen.
–– Type III: Combinations of Types I and II.
–– Type IV: It is simply a pial arteriovenous malformation that drains into
the vein of Galen.
•• In 1992, Lasjaunias proposed an angiographic classification that
differentiated “true” vein of Galen malformations (Yasargil Type I−III) from
the secondary malformations or dilatations (Yasargil Type IV).
678
CLINICAL FEATURES
•• Patients with vein of Galen malformations have clinical presentations that
can vary with age of onset.
•• The clinical classification for the malformation involves the correlation
of three features: (1) age at presentation; (2) clinical syndrome and
(3) pathophysiology.
•• Three characteristic groups have been identified: (1) the neonate presenting
with severe congestive heart failure; (2) the infant presenting with
hydrocephalus and/or seizures and (3) the older child or adult presenting
with headaches or subarachnoid haemorrhage.
•• The basis for most clinical symptoms is not the mass effect, but rather
the shunting of blood through the fistula that produces either cerebral or
coronary artery “steal”.
•• There is evidence that an autosomal dominant factor caused by mutations
in the RASA 1 gene may be involved in the pathogenesis of vein of Galen
malformations.
Neonates
•• About 40% of patients with vein of Galen malformation are diagnosed
during the neonatal period.
•• The malformation typically produces congestive heart failure (hypoxia, low
cardiac output, tachycardia and pulmonary oedema).
•• Cyanosis is very common and is typically refractory to medical therapy.
•• In addition, the cerebral artery “steal” can be associated with venous
hypertension, cerebral ischaemia and infarction.
Infants
•• Infants have a smaller shunt as compared to newborns.
•• Hydrocephalus and seizures are the most common presentations.
•• Head enlargement in infants can be caused by ventricular dilatation in the
presence of a distensible skull.
•• The fontanelle is full but seldom tense.
•• Overt signs of raised pressure (nausea, vomiting, lethargy, etc.) are rarely
present.
•• It is likely that the ventriculomegaly is a result of increased pressure in the
sagittal sinus or venous system that affects CSF absorption.
Older Children and Adults

•• They typically have a low-flow fistula or may have a Yasargil Type IV
malformation.
•• They present with subarachnoid haemorrhage, intracranial bleeds, headaches
or cognitive dysfunction.
•• They, occasionally, may present with hydrocephalus, but congestive heart
failure is very rare.
DIAGNOSTIC INVESTIGATIONS
•• Investigations of a patient with a suspected vein of Galen malformation fall
into three categories: (1) imaging of the brain; (2) imaging of the cerebral
vasculature and (3) various other investigations to assess the systemic
effects associated with the malformation.
Chapter 92 • Vein of Galen Malformations
679
Brain Imaging
•• Computed tomography and magnetic resonance imaging (MRI) are the
two definitive diagnostic modalities for this condition.
•• On a CT scan, the characteristic features are calcification, low-density
cystic spaces and post-contrast enhancement.
•• An MRI scan is more sensitive than a CT scan since it provides better
information concerning the malformation and its effects on the surrounding
brain.
•• Additionally, it provides greater details about the ischaemic changes
occurring in the affected brain and also depicts the patency and size of the
large arteries, veins and venous sinuses.
Cerebral Angiography
•• The final diagnosis of the malformation is provided by cerebral angiography.
•• This also provides information about the vascular anatomy that is essential
for treatment planning.
•• The vein of Galen forms an arc under the splenium of the corpus callosum,
curving posterosuperiorly towards the tentorial apex.
•• It is clearly seen on the lateral view, but is often obscured by the overlying
superior sagittal sinus on AP projections.
•• The two most widely referenced angiographic classifications are those of
Lasjaunias and colleagues and Yaşargil.
Other Investigations
•• These are designed to assess systemic abnormalities associated with the
condition such as hypertension, congestive heart failure and renal failure.
•• These include studies of arterial blood gases, chest radiology,
electrocardiography, echocardiography, serum electrolytes, serum
creatinine and urinary electrolytes.
•• Monitoring serial plasma BNP provides valuable information regarding the
need for additional evaluation or treatment of newborns with CHF and is
also helpful as a prognostic indicator.
•• Prenatal ultrasonography shows the characteristic midline tubular anaechoic
structure superior to the thalamus, which is contiguous with the dilated
sagittal sinus (comet tail or keyhole sign) and also reveals extracardiac
left-to-right shunt, featuring as a high-output heart failure in a neonate and
hypoxic-ischaemic brain lesions due to the ‘steal’ phenomenon.
•• More precise anatomy and location of foetal pathology, and additional
aetiologic information are the substantial advantages in doing fast MRI as
an adjuvant to ultrasonography.
•• Doppler evaluation is important in differentiating this lesion from other cystic
lesions of the brain because this is the only lesion that clearly displays
blood flow within it.
TREATMENT
•• Many series have been published that show patients with untreated vein
of Galen malformation typically die from a combination of cerebral and
cardiac events.
•• Most often, neonates succumb to their cardiac insufficiency, and older
children and adults succumb to the cerebral injury.
680
•• More important, despite modern treatment, the mortality rates for this
condition still approaches 79% for neonates and 39% for the remaining
population.
•• Patient selection and timing remain the keys in the management of this
condition.
•• It is more important to restore normal growth conditions than a normal
morphological appearance, with the primary therapeutic objective being
normal development in a child without neurological deficit.
Medical Treatment
•• In the newborn, initial treatment is usually aggressive medical stabilisation.
•• Congestive heart failure should be aggressively treated to stabilise the
accompanying pulmonary hypertension and cardiomegaly.
•• Ideally, intervention should be delayed until the infant is 6 months old;
however, if there are clinical signs of an acute deterioration, urgent definitive
treatment may be indicated.
Interventional Strategies
•• The selection of treatment is influenced by the age of the patient at
presentation and by the complexity of the malformation.
•• These modalities may include embolisation, surgery, shunting for
hydrocephalus or a combination therapy.
Treatment of Hydrocephalus
•• The results of most shunting procedures for ventriculomegaly in infants
and neonates are disappointing because intraventricular pressure is
invariably low.
•• It is, therefore, best to avoid ventricular shunting and aim the therapy at
correcting the basic pathology. This strategy has shown to normalise the
head circumference.
•• Sophisticated, high-resolution angiography and endovascular techniques
have been applied to the management of vein of Galen malformations.
•• This approach can be transarterial or transvenous through the torcula.
•• The transarterial approach is considered to be most suitable for Yasargil
Type I, II, or III malformations.
•• Lasjaunias and associates recommend that the transvenous approach be
limited to malformations where the arterial approach has failed.
•• Both approaches have been used with varying degrees of success for
Yasargil Type IV malformations. Each technique can be used alone or in
combination with surgery.
Surgical Treatment
•• Surgery should be delayed until both the medical condition and the
nutritional status of the patient are optimised.
•• Many infants and children may require definitive management of the
hydrocephalus before or after definitive surgery.
•• In addition, pre-operative embolisation of the accessible feeders has been
recommended to simplify the resection.
Chapter 92 • Vein of Galen Malformations
681
•• The galenic region can surgically be approached by the subtemporal,

transcallosal or transtentorial approaches.
•• However, the posterior interhemispheric approach is most commonly
used to adequately access a vein of Galen malformation and expose the
feeding arteries.
Radiosurgery
•• Stereotactic radiosurgery using gamma knife has recently been tested as
a treatment option for this formidable disease.
•• These results, although small in number, definitely point to another
potentially safe treatment modality in the future for vein of Galen
malformations.
93
CHAPTER
Cavernomas of the Brain
CE Deopujari
•• Developmental malformations affecting the blood vessels supplying the

brain most likely develop during the late somite stages of the 4th week of
embryonic life.
•• The traditionally used classification, described by McCormick, divides
these lesions on the basis of histopathological features into four categories:
–– Venous malformations;
–– Arteriovenous malformations;
–– Cavernous malformations, and
–– Telangiectases.
•• Cavernous malformations constitute 5−10% of all cerebrovascular
malformations and are the second most common intracranial vascular
malformations responsible for haemorrhage.
•• Cavernous malformations are variously known as cryptic angioma,
cavernous angioma, cavernous haemangioma, cavernoma and
“angiographically occult vascular malformation” (AOVM).
•• These vascular malformations are characterised by the presence of
sinusoid like capillary vessels.
•• These capillaries are adjacent to one another, with little or no intervening
neural parenchyma, while feeding arteries and draining veins are most
often normal in size.
•• The association of cavernous malformations with venous angiomas is
reported to be around 20−30% in the literature.
•• They are known to occur anywhere in the neuraxis including on cranial and
spinal nerves but are most commonly found in subcortical white matter,
external capsule and pons.
INCIDENCE
•• The exact incidence and prevalence of cavernous malformations are
unknown, as many of these lesions remain asymptomatic.
•• Before the introduction of modern imaging technology, cavernous
malformations were considered rare lesions.
•• These lesions are more common than are generally suspected. Based
on clinical series, the prevalence of cavernous malformation is estimated
at 0.5%.
AETIOPATHOGENESIS
•• The exact aetiology of cavernous malformations is not known.
Chapter 93 • Cavernomas of the Brain
683
•• Although cavernous malformations are known to be congenital in origin,

cases of de novo formation with previously documented normal MRI have
also been reported.
•• The lesions have also been known to appear following radiation therapy
and along the path of stereotactic biopsy.
•• Cavernous malformations are known to occur in both sporadic and familial
forms.
•• Almost 30% of the patients affected have the familial form of the disease and
it seems to be more common amongst the Hispanic American population.
•• The genetic basis behind the development of cavernous malformations
has been elucidated.
•• The gene for familial cavernous malformations, designated CCM1, to
chromosome 7q.
PATHOLOGY
•• Cavernous malformations are well circumscribed, discrete and multilobulated
lesions of various sizes.
•• The average size of the lesion tends to be 1−2 cm.
•• The gross appearance is likened to a mulberry owing to its dark red purple
colour.
•• Pathologically, they are composed of sinusoidal, dilated vascular channels
(caverns-lakes) lined by a single layer of endothelium devoid of elastin or
smooth muscle.
•• These vascular lakes are separated by a collagenous stroma.
•• On cut section, they appear like a honeycomb of thin walled vascular
spaces.
•• The lack of intervening brain parenchyma is a characteristic pathologic
marker.
•• Various degenerative changes, like hyalinisation, calcification, cyst
formation and thrombosis with varying degree of organisation, are common.
•• The surrounding parenchyma exhibits evidence of microhaemorrhages of
varying ages with haemosiderin-laden macrophages.
•• A gliotic reaction of the surrounding parenchyma may form a pseudocapsule
around the lesion.
•• Cavernous malformations occur throughout life but are diagnosed more
often in adults.
•• The symptoms generally start in the 20s and 30s. The lesions tend to occur
equally in men and women.
Seizures
•• Seizures are the most common presenting symptom, seen in 40−70% of
patients with cavernous malformations.
•• All types of seizures have been described in these patients including simple
partial, complex partial, focal, generalised tonic clonic or in any combination.
•• The exact mechanism by which cavernous malformations produce seizures
is unknown.
•• Local gliotic reaction, extensive haemosiderin deposition, recurrent
microhaemorrhages, calcification and frontal and temporal location are
frequently associated with the clinical presentation of epilepsy.
684
Haemorrhage
•• Though evidence of previous haemorrhage is present in almost every
lesion regardless of clinical history, overt haemorrhage is less frequent.
•• Overt haemorrhage has been defined as “symptomatic presence of
extralesional blood outside the confines of the haemosiderin ring on MRI
or at surgery”.
•• The risk of overt haemorrhage is definitely less than classic AVM, and has
been estimated to be around 0.25−13% per patient per year.
•• As the cavernous malformations are low flow and low pressure lesions,
haemorrhage usually displaces and compresses adjacent neural tissue
rather than destroying it.
Focal Neurological Deficit

•• This may occur in 20−40% of patients due to compression of the critical
areas of brain function.
•• The deficit may be acute and maximal at the onset, especially in cases
with lesions within the brainstem.
•• In the brainstem, where crucial tracts and nuclei are compactly arranged,
even small focal haemorrhage may be tolerated poorly.
•• Focal deficits secondary to mass effect may be subacute and progressive
if the lesion is located in the basal ganglia or thalamus.
Incidental
•• Between 15% and 20% of lesions are discovered incidentally during an
evaluation for headache or other unrelated neurological problems.
•• In familial patients with multiple cavernous malformations, few lesions are
symptomatic.
•• Other rare clinical presentations reported include cranial neuropathies
(trigeminal neuralgia), hypothalamic symptoms and hydrocephalus.
IMAGING
•• CT scan is 70−100% sensitive but less than 50% specific in detecting
cavernous malformations.
•• The lesion typically appears to be well circumscribed popcorn-like and
slightly hyperdense with faint enhancement on contrast.
•• Calcification and haemorrhage may also be seen.

•• It is the most sensitive and specific imaging modality available for detection
of cavernous malformations.
•• The lesion appears as a well-defined lobulated mass with a central core of
mixed signal intensities surrounded by a rim of hypointensity.
•• The mixed signal reflects acute and subacute haemorrhage in different
stages and the hypointense rim is due to perilesional haemosiderin
deposition.
•• The peripheral hypointensity blooms on T2 WI.
•• Gradient-echo (GRE) images are much more sensitive than conventional
sequences for detecting small cavernous malformations.
685
•• Based on the MRI appearance of cavernous malformations, Zabramski

classified these lesions into four types. Type I lesions are associated with
subacute haemorrhage and have a hyperintense central region on T1 WI.
Type II lesions contain loculated areas of thrombosis and haemorrhage
of variable age. Type III lesions show the imaging correlate of chronic
haemorrhage. Type IV lesions are difficult to detect on conventional
imaging.
•• Typically these lesions are small and hypointense on GRE sequences.
Angiography
•• Angiography is almost always normal and for this reason these lesions are
also known as angiographically occult vascular malformations. Occasional
abnormalities seen in association with cavernous malformation include
avascular mass lesion, capillary blush or evidence of neovascularity. Other
vascular malformations, like AVM or venous malformations, can be ruled
out using angiography.
•• The MRI appearance of cavernous malformations is characteristic but
not specific.
•• Other lesions to be considered in the differential diagnosis include neoplasm
with haemorrhage, especially haemorrhagic metastasis, calcified tumours
like oligodendroglioma or pleomorphic xanthoastrocytoma.
•• Thrombosed AVMs which are angiographically occult may also be confused
with cavernous malformations.
MANAGEMENT
•• Treatment options available for patients with cavernous malformations
include surgical excision, observation or occasionally, stereotactic
radiosurgery.
•• The choice of option depends on many factors like age, sex and general
medical condition of the patient, number and location of the lesions and
clinical presentation.
SURGERY
•• Well-accepted indications for surgical excision of cavernous malformations
are recurrent haemorrhage, progressive neurological deterioration, increase
in the size of the lesion, intractable seizures and a large lesion surfacing
near a pial or ependymal surface.
•• Surgical resection of accessible lesions is associated with low rates of
morbidity and mortality.
•• Surgical intervention in deep seated lesions, especially in the brainstem.
•• Intracranial cavernomas can be divided into two groups: (1) supratentorial
and (2) infratentorial.
Supratentorial Cavernous Malformations

•• Supratentorial cavernous malformations constitute about 75% of all
intracranial cavernous malformations.
•• They can be located superficially in either cortical or subcortical white matter
or may be deep near the internal capsule or thalamus.
686
•• Surgical strategies are modified based on the location of the lesion.

•• Pre-operative mapping of the critical brain areas using functional MRI allows
better planning of the craniotomy.
•• Frame-based or frameless stereotactic devices are frequently used to
minimise the size and invasiveness of the craniotomy.
•• Surfacing lesions can be identified easily by their characteristic purple-blue
mulberry-like appearance or by haemosiderin staining of the cortex.
•• If the lesion is located deeply, intra-operative ultrasound or neuronavigation
techniques can be used.
•• Intra-operative mapping using electrocorticography or awake craniotomy
should be considered while operating on lesions in eloquent areas.
•• Surgical resection of capsular or thalamic cavernous malformation
is associated with greater morbidity rates than for more superficial
hemispheric lesions.
Surgical Strategies for Epilepsy
•• If the seizures can be controlled easily with medications, the indications for
surgery in these patients are similar to those for patients with asymptomatic
cavernous malformations.
•• However, different surgical strategies need to be considered for patients
presenting with intractable seizures.
•• These patients should undergo a standard workup done for patients with
intractable epilepsy including an ictal and/or interictal EEG, video EEG if
required, neuropsychological testing, functional MRI to delineate speech
and motor areas and WADA testing.
•• Surgical options for these patients include lesionectomy alone, lesionectomy
plus resection of adjacent gliotic tissue and lesionectomy plus resection of
adjacent and even remote cortex that has been identified by electrophysiologic
testing as foci of epileptogenicity.
•• Removal of the lesion and the adjacent gliotic yellow-stained tissue has
shown to reduce the long-term frequency and severity of seizures.
•• Intra-operative aids, like image guidance or neuronavigation, intra-operative
USG, electrocorticography or awake craniotomy for brain mapping, are
helpful adjuncts.
Infratentorial Cavernous Malformations

•• Infratentorial cavernous malformations include those involving the
brainstem and cerebellum.
•• The lesions in the brainstem are of distinct importance owing to the critical
structures in the proximity.
•• To determine the best surgical approach for brainstem lesions, Spetzler
has described a “two point method” where one point is placed in the centre
of the lesion and a second point is placed where the lesion most closely
reaches the pial surface. Both the points are connected and the resultant
straight line through the least eloquent tissue dictates the most appropriate
surgical approach.
•• The brainstem can be approached through various routes depending on
the location of the lesion and pre-operative planning:
–– Midline suboccipital craniotomy with approach through the fourth ven-
tricular foramen for lesions bulging into the floor of the fourth ventricle.
–– Retrosigmoid suboccipital approach for lesions near the posterolateral
surface of the pons, cerebellopontine angle or superior lateral medulla.
687
–– Subtemporal approach for lesions in the anterolateral midbrain or

pontomesencephalic region.
–– Supracerebellar infratentorial approach for cavernous malformations
of tectal plate.
–– Far lateral or transcondylar approach to achieve an anterolateral tra-
jectory to the brainstem.
–– Orbitozygomatic approach to access the anterolateral midbrain and
interpeduncular fossa.
•• Surface lesions are readily apparent by their characteristic mulberry
appearance or by the haemosiderin staining of the overlying parenchyma.
•• Intra-operative monitoring of SSEP and BAER are useful adjuncts to help
minimise complications during brainstem surgery.
OBSERVATIONS
•• For incidentally detected cavernous malformations, the rate of clinical or
overt haemorrhage is very low and a first haemorrhage from a cavernous
malformation rarely is life-threatening.
•• Therefore, before intervention is considered solely to prevent haemorrhage,
other host-related factors need to be considered.
•• Such patients can be managed expectantly, with follow-up imaging at
regular intervals in order to detect lesion expansion or haemorrhage.
•• Conservative therapy is also indicated in patients who have had a single
haemorrhagic episode from a lesion that does not reach the pial surface.
RADIOSURGERY
•• The role of stereotactic radiosurgery in the management of cavernous
malformations is controversial.
•• As the complication rates are high and the reduced haemorrhage rate is
not comparable to the zero re-bleed rates after complete surgical excision,
radiosurgical treatment should be reserved for lesions that are truly
surgically inaccessible.
94
CHAPTER Other Vascular
Malformations of the Brain
Ravi Ramamurthi  Harinivas
VENOUS ANGIOMA
•• Venous angiomas are generally silent lesions because of their dynamic
features and are low-flow and low-pressure vascular structures draining
normal brain tissue.
•• Venous angiomas form the alternative venous drainage of the surrounding
nervous tissue because of the non-development of the normal venous
system.
•• They are made up of veins with abnormal structure with thick walls, dilated
lumen and of irregular calibre that converge radially towards a wide draining
vein (caput medusae).
Pathology
•• The causes of developmental venous anomalies are incompletely
understood.
•• It is believed that they are formed in the late stages of foetal maturation.
•• The lesion is composed entirely of veins, which are commonly thickened
and hyalinised, having minimal smooth muscle and elastic tissue.
•• The interspersed neural parenchyma is entirely normal.
•• Venous angiomas may be subclassified according to their pattern of venous
drainage into superficial (cortical) and deep (subependymal) types.
•• Two variants of the typical venous angioma have been described. These
are:
1. Venous angioma with arterial feeders also termed as medullary ve-
nous malformations with an arterial component or venous angiomas
with early filling vessels.
2. Varix or phlebectasia.
•• There is a radially arranged pattern of medullary veins converging centrally
on a single draining vein which is known as star cluster.
•• Histological examination shows that the capsule consists of an outer
collagenous layer and an inner granulated layer with deposits of
haemosiderin.
Natural History and Clinical Features

•• The natural history depends on the topography and location whether
hemispheric, deep-seated, brainstem, cerebellar or intramedullary regions.
•• These are the commonest of the vascular malformations in large prospective
autopsy studies, but the least common form encountered in clinical practice.
Chapter 94 • Other Vascular Malformations of the Brain
689
•• Their incidence may be still higher than is generally believed, since most of
these remain largely asymptomatic. Patients may present with headache,
nausea and vomiting, seizures, progressive neurological deficit and
haemorrhage (0.2% per year).
•• Changes due to old age, in an angioma, may increase its propensity to
cause symptoms.
•• The presence of an associated arteriovenous malformation (AVM) or a
cavernoma is not unusual in a patient with a venous angioma.
•• Coexistence of a cavernoma with a venous angioma occurs in about 8%
of cases, and in such a case it is usually the cavernoma which becomes
symptomatic and needs to be treated, rather than the venous angioma.
Investigations
•• The gold standard for diagnosing developmental venous anomalies is
conventional cerebral angiography.
•• Findings include normal circulation time, normal capillary and arterial
phases of study with the venous anomaly seen during the late venous
phase.
•• Computerised tomography (CT) scan without contrast administration may
show a hyperdense dot, caused by the pooling of venous blood.
•• Contrast enhancement reveals a stellate tangle of veins coursing into a
sharply defined linear interstitial vein draining towards the cortical or the
central system.
•• These are commonly seen in the frontal region near the angle of the
ventricles or in the cerebellum.
•• Conventional or digital subtraction angiography may reveal a faint capillary
blush passing into the venous phase or the classical “caput medusae” or
“hydra” appearance which is pathognomonic of a venous angioma.
•• The angiomas, showing a persistent blush, are believed to have an
increased tendency to bleed.
•• Yasargil has described the following criteria for diagnosis of venous
angioma on angiography:
–– Absence of arterial feeders
–– Appearance of the lesion in the venous phase of the angiogram
–– Presence of dilated medullary veins draining through a dilated
transcerebral or subependymal vein.
•• Magnetic resonance (MR) is superior to CT in the identification of a venous
angioma.
•• It delineates a curvilinear streak of signal void, best appreciated on T2W1
MR imaging (MRI) scan.
•• Hypointense areas may be visible in the body of the angioma, representing
the blood pool within.
•• These enhance brightly with contrast and the draining vein is seen well on
T2-weighted imaging. There may be a paradoxical high-signal intensity as
the flow in the draining vein is very slow. Some of these lesions may be
diagnosed on “Time of Flight” MR angiography.
Management
•• It is to be noted that these lesions have a very benign natural history and
only rarely do they cause haemorrhage.
690
•• The propensity of these lesions to cause seizures or focal neurological

deficit is difficult to ascertain.
•• These veins are anatomically aberrant, but physiologically essential and,
therefore, should not be interrupted.
•• Surgery is only indicated in the presence of a large haemorrhage causing
mass effect or a clearly documented seizures or focal neurological deficit
attributable to the angioma.
•• Radiosurgery has also been advocated for these lesions, but the results
are variable.
CAPILLARY TELANGIECTASIAS
•• Capillary telangiectasia (CTS) is a vascular malformation characterised by
multiple thin-walled vascular channels interposed between normal brain
parenchyma.
•• It has been hypothesised that CTS is an acquired lesion caused by other
underlying venous anomalies, but this theory is still debated.
•• This type of vascular malformation is also called capillary malformation.
•• It is usually asymptomatic and also remains angiographically occult, making
it difficult to ascertain its incidence.
•• However, rarely, intracerebral haemorrhage has been reported.
•• These are commonly located in the infratentorial compartment, the pons
being a favoured site.
•• Familial as well as multiple lesions have been reported.
•• This malformation results from vascular dilatation rather than vascular
proliferation and comprises of thin-walled capillaries which are devoid of
smooth muscle tissue or elastic fibres and usually drain into an abnormally
large central vein.
•• The intervening neural parenchyma is normal.
•• They are mostly asymptomatic.
•• If symptomatic, haemorrhage, seizures, cranial nerve paresis, extrapyramidal
disorders and focal hemispheric syndromes have been described.
Investigations
•• Radiological diagnosis of these lesions is very difficult, unless associated
with haemorrhage or calcification .
•• The CT scan is not sensitive enough to detect these minute lesions and in
most instances, these are not visible on angiography, although rarely an
angiogram may reveal an abnormal vascular blush or an early draining vein.
•• The MR may show an area of hypointense signal in T2W1 MRI scan.
•• Diffusion weighted imaging seems to be a useful adjunct for the diagnosis
of capillary telangiectasias which can be differentiated from tumours,
inflammatory and ischaemic lesions.
•• In some cases, imaging diagnosis will be difficult with conventional, MRI
because the lesion will not show characteristic signal loss on conventional
gradient-echo images.
•• In those cases susceptibility weighted imaging will be useful for diagnosis
as it will demonstrate marked signal loss of the lesion.
Chapter 94 • Other Vascular Malformations of the Brain
691
Management
•• Capillary telangiectasis may, at times, coexist with a cavernoma, and
according to Russell’s original hypothesis, these two represent different
stages in the development of the same disease entity.
•• As a rule, when coexisting with a cavernoma, it is the cavernoma that
becomes symptomatic, necessitating treatment.
•• No therapeutic intervention is indicated in an asymptomatic telangiectasia.
•• If presenting with haemorrhage, surgery may be indicated to evacuate the
haematoma.
•• It is usually on histopathological examination of the evacuated blood clot
and its periphery that the diagnosis of telangiectasia becomes evident.
HEREDITARY HAEMORRHAGIC TELANGIECTASIA

(OSLER-WEBER-RENDU DISEASE)
•• Hereditary haemorrhagic telangiectasia (HHT) is a form of capillary
telangiectasia characterised by the presence of multiple AVMs that lack
intervening capillaries and result in direct connections between arteries
and veins.
•• Although HHT is a developmental disorder and infants are occasionally
severely affected, in most patients, the features are age-dependent with
the diagnosis not suspected until adolescence or later.
•• The most common clinical manifestation is spontaneous and recurrent
epistaxis seen usually at a younger age.
•• Approximately 25% of individuals with HHT have gastrointestinal (GI)
bleeding, which most commonly presents after the age of 50 years.
Genetics
•• The HHT is caused by mutations in a number of genes involved in the
TGF-b/BMP signalling cascade:
–– ENG, the gene encoding the cell surface co-receptor endoglin.
–– ACVRL1 (ALK1), also a gene encoding a cell surface receptor.
–– SMAD4, a gene encoding an intracellular signalling molecule.
–– There may be some unidentified genes also involved.
•• Molecular genetic testing of ENG, ALK1 and SMAD4 detects mutations in
approximately 80–85% of individuals who satisfy an unequivocal clinical
diagnosis of HHT and is available on a clinical basis.
Diagnosis
•• The diagnosis of HHT is based on the presence of epistaxis, cutaneous or
mucosal telangiectases, visceral AVMs and family history.
Treatment
•• Epistaxis is treated with humidification, nasal lubricants, topical or systemic
hormones or anti-fibrinolytic agents, laser ablation, septal dermoplasty and
nasal closure.
•• The GI bleeding is treated with iron replacement therapy and, if needed,
endoscopic ablation, surgical resection of bleeding sites, and/or hormonal
or anti-fibrinolytic therapy.
•• Cerebral AVMs are treated, when indicated by location or symptoms, by
surgery, embolotherapy and/or stereotactic radiosurgery.
692
Genetic Counselling
•• The HHT is inherited in an autosomal dominant manner with considerable
intrafamilial variability.
•• Most individuals have an affected parent.
•• Prenatal testing is possible for pregnancies at increased risk if the disease-
causing mutation in the family is known.
CRYPTIC ARTERIOVENOUS
MALFORMATIONS
•• The term “cryptic” was proposed by Russell to denote a group of vascular
“hamartomas”, predominantly small AVMs, which often remained clinically
silent during the patients’ life time.
•• The terms “cryptic” and “angiographically occult vascular malformation”
(AOVM) were adapted to clinical use to describe vascular malformations
that are not demonstrable on angiography.
•• Cryptic AVM can cause highly variable neurological defects.
•• These lesions may present with a catastrophic and often fatal haemorrhage.
•• The mechanisms for failure of angiographic detection of an AVM are
manifold.
•• It is to be noted that the terms “cryptic” and “AOVM” are not synonymous.
•• While the cryptic AVMs are a histopathological entity, AOVMs may be
diagnosed by CT or MRI.
•• Angiographically occult AOVMs can now be readily diagnosed and
managed.
•• The AOVMs constitute a heterogeneous group of entities.
•• With increased understanding of the clinical significance of cavernomas
and venous angiomas, a more rational approach to their management has
become possible.
•• Rapid advances in the field of radiosurgery have made it easier to tackle
the small, deeply-located AVMs.
•• Surgery remains the mainstay of treatment in most instances.
•• Injection of 142Pr microspheres into arteries feeding an AVM in order to
simulate radioembolism has been proposed as a novel treatment method.
95
CHAPTER
Carotid Cavernous Fistula
INTRODUCTION
•• The carotid artery in a part of its intracranial course traverses the cavernous
sinus.
•• Carotid-cavernous sinus fistula (CCSF) develops when there is an abnormal
communication between the carotid artery (internal or external) or its
branches, and the cavernous sinus.
•• The cavernous sinus is not a dural sac carrying venous blood, as was
thought earlier, but is a plexus of veins enclosed between two layers of
the dura.
ANATOMY OF THE CAVERNOUS SINUS

•• The cavernous sinus is a plexus of veins encased in a double layer of dura
and located on either side of the body of the sphenoid sinus (Fig. 1).
•• The internal carotid artery (ICA), along with its surrounding sympathetic
plexus and the VI nerve, courses through the sinus.
•• The III, IV, V1 and V2 cranial nerves run forwards in the lateral wall of the
sinus enclosed in the double layer of dura.
Arteries
•• The carotid artery gives off three branches in the cavernous sinus.
•• The meningohypophyseal trunk, a constant branch, is the most proximal
and arises at the level of the dorsum sellae. This trunk gives off three
branches:
1. The tentorial artery also called the artery of Bernasconi-Cassinari
which supplies the tentorium.
2. The inferior hypophyseal artery which supplies the posterior pituitary.
3. The dorsal meningeal artery which supplies the clival area and the
VI nerve.
Fig. 1: Coronal section through cavernous sinus

694
•• The artery of the inferior cavernous sinus arises from the horizontal portion
of the intracavernous carotid. It supplies the inferior wall of the cavernous
sinus and the area of the foramen ovale and spinosum. This artery
corresponds to the carotid remnant of the embryonic dorsal ophthalmic
artery.
•• McConnell’s capsular arteries are seen in about 30–50%. They arise on
the medial side of the carotid artery about 0.5 cm beyond the artery of the
inferior cavernous sinus.
•• The ophthalmic artery may arise in about 8% from the intracavernous
carotid artery.
•• The branches of the ICA arising in the cavernous sinus anastomose with
the various branches of the external carotid artery (ECA).
•• The neuromeningeal trunk of the ascending pharyngeal artery, the recurrent
and anterior meningeal branches of the internal maxillary artery and the
cavernous branch of the middle meningeal artery are the arteries that
commonly anastomose with the cavernous branches of the internal carotid.
These arteries are important in Type C and D fistulas.
Veins
•• The tributaries of the cavernous sinus are many.
–– The superior and inferior ophthalmic veins and through them, the facial
veins.
–– The middle and inferior cerebral veins draining the cerebral substance.
–– The central retinal vein, the middle meningeal veins, the superior and
inferior petrosal sinuses and the emissary veins.
•• The two cavernous sinuses on either side are connected by intercavernous
communications.
•• These are:
1. The anterior intercavernous sinus: This measures 0.57–5.43 mm. It
may involve the whole of the anterior dura of the sella, may have a
curvilinear shape or may run at the level of the pre-chiasmatic groove.
2. The posterior intercavernous sinus: This varies in diameter from
0.71–4.14 mm.
•• The inferior cavernous sinus is not always seen. It may be plexus like, a
venous lake or of a mixed type and runs in the dura of the floor of the sella.
•• The basilar plexus is the largest intercavernous communication in the
majority. It is located at the level of the dorsum sellae.
CLASSIFICATION
•• Carotid-cavernous sinus fistula has been classified in many ways which
are as follows:
–– Spontaneous or traumatic
–– High or low-flow
–– Direct or indirect (dural) fistulae according to their arterial supply
determined angiographically.
•• The first two do not take into consideration the factors that are required in
the proper planning of the treatment of CCSF.
•• Barrow et al. classified them angiographically into four types (Figs 2A to D).
•• Type A:
–– This is due to a direct shunt from the ICA to the cavernous sinus.
–– They are high-flow and are usually caused by trauma and base of skull
fractures.
Chapter 95 • Carotid Cavernous Fistula
695
Figs 2A to D: Angiographically classification by Barrow et al. (A) Direct shunt

from the internal carotid artery to the cavernous sinus. (B) Shunt from dural
branches of the internal carotid artery to the cavernous sinus. (C) Shunt
from dural branches of the external carotid artery to the cavernous sinus.
(D) Shunt from dural branches of both internal and external carotid arteries
to the cavernous sinus
–– They may also be due to rupture of an intracavernous carotid

aneurysm.
–– Young men are commonly affected and the majority require treatment
as they do not close spontaneously.
•• Types B, C and D are dural or indirect fistulae.
•• In Type B there is a communication between the dural branches of the ICA
and the cavernous sinus. These are extremely rare.
•• Type C arises as a result of communication between the dural branches
of the ECA and the sinus.
•• Dural branches of the ICA and ECA take part in Type D fistulae which are
the commonest indirect fistulae.
•• They occur in middle-aged women, are low-flow and in 16–60% they
resolve spontaneously.
SYMPTOMS AND SIGNS

•• The symptoms and signs depend upon the type of fistula, the direction of
the venous outflow, either anterior or posterior, the anatomical location in
the cavernous sinus and the size of the fistula.
•• Rarely, there may be bilateral involvement.
•• Type A fistulae are direct, high-flow and mostly traumatic.
•• They occur most frequently after a closed head injury, though they may
occur as a result of direct penetrating injury or rupture of an intracavernous
carotid aneurysm.
•• A high index of suspicion is paramount in cases of polytrauma, where a
CCSF can be easily missed in the acute stage of injury.
•• A relatively high incidence of traumatic CCSF occurs in patients with middle
fossa fractures, especially those with transverse or oblique fractures.
•• Spontaneous non-traumatic direct CCSFs are extremely rare and an
underlying predisposing factor like systemic connective tissue disorders
such as Ehlers-Danlos syndrome may be seen.
696
•• It is probable that advancing age, menopause, hypertension and childbirth

may affect some pre-existing subclinical lesions in the arteriolar system like
aneurysms, leads to the development of spontaneous CCSF.
•• Low-flow fistulae occurring after trauma are usually due to avulsion of a
dural arterial branch.
•• Ocular signs and symptoms are produced when the major venous outflow
is through the superior or inferior ophthalmic veins.
•• The signs may be unilateral, bilateral or may occur only in the eye
opposite to the side of the fistula due to predominant drainage through the
intracavernous venous communications.
•• The ocular manifestations are pulsating exophthalmos, chemosis, ocular
nerve palsies causing diplopia, visual loss and exposure keratitis.
•• There may be venous and arterial stasis resulting in decreased ocular and
retinal perfusion.
•• Retinal and choroidal changes may include venous dilatation, retinal
haemorrhage, central retinal vein occlusion, central retinal artery occlusion,
cotton wool patches and serous retinal detachment.
•• Facial pain may occur due to involvement of cranial nerves V1 and V2.
•• A subjective and audible bruit will be present.
•• Headache may occur due to dural distension, raised intracranial pressure
(ICP) or subarachnoid haemorrhage (SAH).
•• Flow through the cortical veins can produce raised ICP.
•• Symptoms due to raised ICP, cerebral steal and SAH are uncommon.
•• When the major outflow is posteriorly into the basilar plexus, there may
only be a bruit.
•• Rarely, lower cranial nerve dysfunction affecting the VIII, XI and XII nerves
may occur.
•• In an occasional patient there may be only pulse-synchronous tinnitus.
•• Other rare presentations include brainstem compression and epistaxis.
•• In the low-flow Types B, C and D fistulae the clinical manifestations are
insidious in onset and include mild proptosis, chemosis, ocular pain and
glaucoma.
•• Sometimes they may lead to progressive visual loss.
•• The various theories and views regarding the pathogenesis of spontaneous
low-flow CCSF have been described by Barrow.
•• Differential diagnoses for CCSF include vascular lesions such as
arteriovenous malformation and cavernous sinus thrombosis, cavernous
sinus tumours, orbital tumours, skull base tumours and mucocoele.
•• Thyroid eye disease, orbital pseudotumour, and orbital vasculitis resulting
from Wegener's granulomatosis, polyarteritis nodosa, intracranial
sarcoidosis and Tolosa-Hunt syndrome may present like CCSF.
INVESTIGATIONS
•• Angiography is the best investigation for diagnosing and classifying CCSF.
•• Selective external carotid catheterisation will help in Type C and D.
•• The CT scan will be useful when there is evidence of steal or an
•• The imaging findings of carotid-cavernous fistula include dilatation of the
superior ophthalmic vein, enlargement of the cavernous sinus, proptosis
and thickening of the extraocular muscles.
•• Dilation of the superior ophthalmic vein is a specific imaging sign of carotid-
cavernous fistula.
697
•• An engorged superior ophthalmic vein presents with a characteristic

"hockey stick sign" on orbital B-ultrasound, CT and magnetic resonance
imaging.
•• Colour Doppler imaging has been found to be useful and correlates well
with the angiographic findings. Doppler also provides information about
the direction and velocity of flow and is useful in post-treatment follow-up.
•• Transcranial Doppler is also useful in assessment, as well as during balloon
occlusion. It is also useful in assessing tolerance to carotid occlusion
during treatment.
•• Brain single photon emission computed tomography scanning has been
used to assess the pre and post-embolisation blood flow to the brain,
especially in patients with steal phenomenon.
TREATMENT
•• Knowledge of the natural history of the disease is important in deciding
whether treatment is necessary or not.
•• Type A fistulae almost never close spontaneously, though this has been
reported. These require treatment.
•• Type B, C and D are low-flow and have been reported to close
spontaneously in 16–60% of cases.
•• The indications for immediate treatment are progressive visual loss, a
distressing bruit, diplopia and severe proptosis with corneal exposure.
•• Others can be kept under observation for 6 months after investigations
and angiography.
•• Angiography itself has been reported to have promoted closure of the
fistula,though the exact mechanism is not known.
•• Carotid compression therapy has also been successful in closure of 17%
of direct and 30% of dural CCSFs.
•• Treatment is offered when the fistula does not close or there are progressive
symptoms.
•• The purpose of treatment is to occlude the fistula without occluding the
carotid artery, as far as possible.
•• The methods available include endovascular techniques, surgery and
radiosurgery.
Endovascular Therapy
•• There have been tremendous technical advances in the field of
interventional neuroradiology which have simplified the treatment and also
given various endovascular treatment options while dealing with CCSF.
•• The majority of Type A fistulae can be treated by embolisation using
balloons, coils or embolic agents.
•• The balloons that are most favoured are silicone balloons filled with
2-hydroxyethylmethacrylate and radiopaque contrast material.
•• Coils made of platinum are used when balloon occlusion fails or cannot be
used due to the fistula being very small, when bony spicules may puncture
the balloon or when after balloon occlusion there is a small venous space
into which a balloon cannot be introduced.
•• Stent-assisted or balloon-assisted coil placement can be done.
•• Liquid embolic agents like onyx are also used to complement balloons or
coils, and rarely used as the sole strategy of management.
•• The route of access to the cavernous sinus for embolisation can be intra-
arterial through the carotid artery or intravenous through the superior
698
ophthalmic vein or the superior or inferior petrosal sinus through surgical

exposure.
•• The transvenous route through the inferior petrosal sinus is the best
endovascular approach to achieve cure.
•• Preliminary transarterial embolisation may be necessary if there are
extensive ECA feeders.
•• When endovascular techniques fail direct surgery is necessary to occlude
the fistula.
•• Type B fistula is very rare. As it cannot be occluded with a balloon, a direct
surgical approach should be considered.
•• Type C fistula is also rare and can be treated by embolisation of the external
carotid branches. The embolic materials that can be used are silastic beads,
Ivalon, gelfoam and isobutyl-cyanoacrylate. Ivalon is preferred.
•• Type D fistula is treated initially with embolisation of the ECA feeders. This
often leads to thrombosis of the fistula.
•• Covered stents have recently become available for various vascular
conditions including carotid-cavernous fistulas. The CCSF can be treated
while preserving the parent artery by reconstructing the arterial wall.
•• Embolisation of CCSF may carry a risk of inherent complication either from
the procedure or due to reopening of the fistula like transient aggravation of
symptoms, including increased proptosis, elevation of intraocular pressure,
choroidal detachment that required suprachoroidal drainage and venous
stasis retinopathy.
•• Other potential complications include uncontrolled bleeding, ophthalmoplegia
and cavernous sinus thrombosis.
Surgical Approaches
•• Surgery is indicated when embolisation fails or when it is contraindicated,
or when previous procedures have occluded the ICA and the fistula is still
patent.
•• The first surgical procedure to be used was carotid ligation in the neck.
•• Parkinson was the first to open the cavernous sinus and directly treat the
CCSF.
•• The cavernous sinus is opened between the III and IV nerves and this area
is known as Parkinson’s triangle.
•• Mullan, in 1979, exposed the cavernous sinus, opened it and introduced
agents like gelfoam and surgicel to occlude the fistula and retain the
patency of the ICA.
•• Dolenc, in 1983, described exposure of the entire cavernous sinus and
the petrous ICA. By removing the anterior clinoid process and de-roofing
the optic canal, the entire intracavernous carotid artery can be visualised.
•• Various methods have been used to occlude the fistula. These are
direct clipping, packing with muscle or other material, or microsurgical
reconstruction of the artery.
Radiosurgery
•• With the improved results of cerebral AVM treated successfully with
stereotactic radiosurgery, CCSF is also being treated using the same
principle.
•• Stereotactic radiosurgery forms an integral part of the multidisciplinary and
multimodality approach in treating carotid-cavernous fistulas.
699
•• Though radiosurgery has been used in many instances for treating CCSF,
its indications are still unclear.
•• Elderly patients with medical comorbidities, failed repeated endovascular
therapy and low-flow dural CCSF are among the few mentioned indications.
PROGNOSIS AND COMPLICATIONS

•• The mortality associated with CCSF is 1–2%.
•• Any treatment option that is offered to the patient should not exceed this
figure.
•• CCSF being an uncommon condition, the complication and mortality rates
depend on the experience of the interventional radiologist and the surgeon.
•• The complications that may occur are stroke due to ICA occlusion or
balloon migration.
•• The balloons that are used may rupture or shrink.
•• Venous rupture may occur when the transvenous route is used for
emolisation.
•• False aneurysms can form due to balloon shrinkage.
•• Cranial nerve deficits can occur due to pressure on the lateral wall of the
cavernous sinus and these usually recover spontaneously.
96
CHAPTER Dural Arteriovenous
Malformations
INTRODUCTION
•• These are defined as arteriovenous (AV) shunts from a dural arterial supply
to a dural venous drainage channel and constitute 10–15% of intracranial
arteriovenous malformations (AVMs).
•• These occur more frequently in women.
EMBRYOLOGY AND PATHOPHYSIOLOGY

•• Embryologically, the circulation of the brain and its coverings including dura,
skull and scalp are developed from a common origin.
•• Therefore, it can be anticipated that a vascular malformation developing
in one of these layers may have vascular participation from any or all of
the adjacent layers.
•• The dura mater has an extrinsic vascular supply.
•• Branches of the external carotid artery (i.e. middle meningeal, accessory
meningeal, posterior auricular, occipital and ascending pharyngeal arteries)
supply the lateral aspects and convexity of the dura.
•• Branches of the internal carotid artery supply the floor of the anterior cranial
fossa (anterior and posterior ethmoidal branches of the ophthalmic artery)
and the tentorium (dorsal meningeal branch and tentorial branch of the
meningohypophyseal trunk).
•• The dura of the posterior cranial fossa is supplied by branches from the
vertebral system.
•• Minute AV shunts exist between the meningeal arteries and the walls of the
major dural sinuses, which may have an important role in the pathogenesis
of dural arteriovenous malformations (D-AVMs).
•• The AVMs of the brain may receive blood supply from the dura mater in
some cases, whereas the dura alone is the seat of malformation in 10–15%.
•• The presence of the nidus within the leaflets of the duramater or tentorium
differentiates D-AVMs from the more commonly occurring parenchymal
or pial AVMs.
•• The nidus is usually in a well-defined region of the dural leaflet, often located
near a dural sinus and is the point of convergence of all arterial feeders,
which mainly arise from the dural arteries or from the pachymeningeal
branches of the cerebral arteries.
•• The venous drainage can be through either dural or pial channels, with
60–75% draining exclusively into the dural sinus.
Chapter 96 • Dural Arteriovenous Malformations
701
•• It is probable that increased pressure within the dural venous drainage

system results in retrograde leptomeningeal venous drainage and these
channels may often be noted to become tortuous or variceal.
•• The fact that the sigmoid sinus is often blocked in these patients was
observed by Sundt and Piepgras,who postulated that this obstruction may
be a sequel to an inflammatory process.
•• An inflammatory hypervascularity then develops into an arteriovenous
fistula (AVF).
•• Most AVMs associated with the meningeal artery in the anterior cranial
fossa are the pure dural type, where mixed pial-dural AVMs are rare.
•• There are two types of mixed pial-dural AVM in the anterior cranial fossa
based on the shunting point:
1. One with the nidus in the brain parenchyma of the frontal lobe.
2. Other with the shunting point in the dura mater.
AETIOLOGY
•• D-AVMs are acquired lesions and may result from traumatic or non-
traumatic causes.
•• Traumatic D-AVMs are often asymptomatic and are on many occasions
diagnosed as incidental findings on angiography. These are often located
at sites remote from the region of trauma.
•• Non-traumatic D-AVMs are postulated to occur secondary to venous
obstruction, usually thrombosis of one of the dural sinuses.
•• Venous obstruction may result in the formation of D-AVM, either by
enlargement of the normally present micro AV shunts within the dura or
by recruitment due to “sump” effect of arterial supply from the scalp, the
meninges and the cortex through AV shunting in the wall of the sinus.
•• This leads to secondary venous hypertension and results in retrograde
drainage in the leptomeningeal veins, predisposing to their tortuosity and
dilatation.
NATURAL HISTORY
•• D-AVMs have a highly variable natural history.
•• Patients may remain asymptomatic for many years.
•• Symptoms usually become manifested in the sixth and seventh decades
of life.
•• Clinical symptoms may either remain benign throughout or may rarely
follow an aggressive course, which is seen (in about 27%) more commonly
with lesions located at the tentorial incisura and the anterior cranial fossa.
•• An aggressive course in relation to D-AVMs is defined as haemorrhage or
progressive neurological deficit other than ophthalmoplegia.
•• The D-AVMs characterised by leptomeningeal venous drainage, variceal
or aneurysmal venous dilatation and Galenic drainage are especially more
prone to haemorrhage.
•• Haemorrhage may be the initial presenting feature in 17–24% of patients.
•• The risk of haemorrhage is more common with AVMs located at a distance
from a sinus, than in the lesions adjacent to a dural sinus.
•• The D-AVMs with haemorrhage as the initial presenting feature are
associated with a mortality of 30% and the incidence of recurrent lethal
intracranial haemorrhage (ICH) remains high.
702
•• Extensive D-AVMs may cause symptoms because of venous

hypertension and the resulting malabsorption of cerebrospinal fluid.
•• Spontaneous occlusion is seen more commonly with lesions adjacent
to the cavernous sinus.
•• In patients with polycythemia and D-AVFs that have a relatively low
risk of haemorrhage, polycythaemia should be treated first before
any interventional treatment, because venesections may lead to
spontaneous closure of the D-AVF.
CLASSIFICATION
•• The D-AVMs may be classified depending on the following factors:
–– Involved sinus (sagittal, cavernous, straight, sphenoparietal, trans-
verse or sigmoid)
–– Region of the dura involved (anterior, middle or posterior cranial fossa,
tentorium)
–– Venous drainage pattern (dural sinus, Galenic, pial, cortical)
•• The above mentioned systems may be combined and a reasonable working
diagnosis can be arrived at by including the anatomic location and the
venous drainage.
•• There are many classification schemes for D-AVFs.
•• The most useful and recent ones are the revised Djindjian and Merland
classification proposed by Cognard et al. and the classification proposed
by Borden et al. both of which are based on the initial classification.
•• Cognard et al. defined five types of D-AVFs based exclusively upon the
pattern of venous outflow:
1. Type I, located in the main sinus, with antegrade flow
2. Type II, in the main sinus, with reflux into the sinus (IIa), cortical veins
(IIb), or both (IIa+b)
3. Type III, with direct cortical venous drainage (CVR) without venous
ectasia
4. Type IV, with direct CVR with venous ectasia
5. Type V, with spinal venous drainage. They all focus on the patterns of
venous drainage.
CLINICAL FEATURES
•• The pathophysiological consequences and clinical manifestations are
related to specific stages of the evolution of D-AVMs.
•• Symptoms fall into one of the following six patterns:
1. Bruit
2. Headache, papilloedema and visual failure due to raised intracranial
pressure
3. Subarachnoid haemorrhage (SAH)
4. Ischaemic neurological deficit
5. Hydrocephalus and bruit in infants
6. Combination of more than one of these.
•• Clinical behaviour, inclusive of initial presentation and progression of
symptoms, is dependent on multiple, inter-related factors including location,
arterial feeders and venous drainage.
•• A catastrophic neurological course is primarily determined by the venous
drainage pattern.
Chapter 96 • Dural Arteriovenous Malformations
703
•• The first stage of evolution of D-AVMs, local increased venous pressure will
result in venous congestion, which may cause seizures and non-haemorrhagic
focal neurological deficits. Intracranial hypertension and papilloedema may
result, due to a generalised increase in venous pressure.
•• In the second stage of evolution, with recruitment of arterial feeders,
symptoms related to increased flow in the individual neural structures are
encountered. These are termed “neighbourhood symptoms” and include
headache, pulsatile tinnitus, cavernous sinus syndrome, trigeminal neuralgia
and hemifacial spasm.
•• The final stage in the evolution is characterised by retrograde leptomeningeal
venous drainage and variceal dilatations, which are responsible for ICH.
•• Bleeding occurs from these engorged and brittle leptomeningeal venous
connections and not from the nidus.
INVESTIGATIONS
•• Although computerised tomography and magnetic resonance (MR)
may suggest a vascular abnormality, detailed cerebral panangiography,
especially using digital subtraction techniques, remains the mainstay in
the diagnosis of D-AVMs.
•• Selective studies of bilateral internal and external carotid systems, along
with vertebral studies are essential.
•• Arterial branches within the dura are normally not visualised on
angiography, but in the presence of D-AVMs, the concerned vessels are
dilated and clearly visible.
•• Certain meningeal vessels, like the meningeal branch of the posterior
cerebral artery also called the “artery of Davidoff and Schechter”, is
angiographically demonstrable only in the presence of a D-AVM.
•• The nidus is usually limited to a well-defined focus within the dural leaflet
and is best visualised on ultra early arterial views, or on injection of either
contralateral or more distant feeding vessels.
•• Late arterial views, venous views and superselective injection of major
feeder vessels, demonstrate engorged vascular channels which may
occupy diffuse areas of the dura.
•• The shunt flow rate can also be estimated based on the evidence of steal
from a more distant artery.
•• The pathognomonic diagnostic feature of D-AVM on angiography is the
premature appearance of venous structures within or adjacent to the dura
mater during the arterial phase.
•• Dural venous sinus thrombosis will be seen on the venous phase and
may reflect:
–– Thrombus preceding the genesis of the AVM.
–– Accompaniment of spontaneous or induced thrombosis of an adjacent
D-AVM.
–– Angiographic artefact due to “steal” through other channels.
–– MR angiography is helpful in the non-invasive diagnosis of D-AVMs.
MANAGEMENT
•• Considering the wide variability of the natural history of D-AVMs, it is
mandatory to define the treatment strategy based on an individualised
risk-benefit ratio.
704
•• This depends on the clinical features, neurological status and the nature of
D-AVM as regards its location, extent and angiographic patterns.
•• A conservative approach and observation is advisable for lesions causing
only benign symptomatology.
•• Active intervention is indicated for D-AVMs associated with features
predisposing to progressive neurological deficit or haemorrhage or for
lesions with benign but distressing symptoms.
•• This definitive treatment may be in the form of arterial embolisation,
transvenous occlusion, surgical excision and radiation therapy.
•• Arterial embolisation using balloons, particulate matter or polymerising
chemical agents is a good adjunct in presurgical planning and is most
useful for isolated AV communications.
•• It has only a limited application in AVMs supplied by small, multiple feeders
from the internal carotid artery, e.g. D-AVMs of the tentorial incisura.
•• Transvenous occlusion using metal coils, gelfoam or balloons may be done
but is associated with significant morbidity.
•• Transarterial Onyx® embolisation of dural arteriovenous fistulas (D-AVFs)
with direct CVR is to be considered as a treatment option.
•• Surgical methods employed are:
–– Ligation of feeder vessel(s) which at best gives only transient relief of
symptoms
–– Excision of the entire anomaly with or without pre-operative embolisation.
•• The object of surgery is to resect the dural leaflets containing the nidus
and the adjacent sinus along with disconnection of leptomeningeal draining
pathways—the harbingers of fatal ICH.
•• Careful pre-operative angiographic analysis, judicious use of adjuncts like
pre-operative embolisation and meticulous haemostasis during surgery
help to improve surgical outcome.
•• Microscope-based intra-operative near-infrared indocyanine green (ICG)
videoangiography is useful as an adjunct to intra-operative or post-operative
digital subtraction angiography in aneurysm surgery.
•• Microscope-integrated repetitive ICG videoangiography during AVM
and D-AVF surgery is fast, easy to perform, simple, safe and is a useful
additional tool that can potentially lower the surgical risk in complex AVMs
and help avoid missed residuals.
97
CHAPTER Embolisation of Spinal
Vascular Malformations
Anil Karapurkar  Nishant Aditya
CLASSIFICATION OF SPINAL
VASCULAR MALFORMATIONS
•• Spinal cord malformations are complex.
•• Many classifications have been proposed over the years. The commonly
accepted ones are given in Tables 1A to C.
•• They are usually made up of single or multiple arteriovenous fistulas (AVF).
•• Niduses similar to those in brain AVMs are uncommon.
•• Since there is hypertrophy of the feeding artery, aneurysms along their
course are not infrequent.
•• The dilated arterialised veins may also show aneurysms along their course.
VASCULAR SUPPLY OF THE SPINAL CORD

•• Three longitudinal axes supply blood to the spinal cord; the single central
anterior spinal axis (ASA) and the paired posterolateral posterior spinal
axes (PSA).
•• They arise from the vertebral arteries just proximal to their junction.
•• The anterior and posterior axes receive tributaries at multiple levels
as they descend down the spinal cord. These tributaries are known as
radiculomedullary and radiculopial arteries.
•• The radiculomedullary arteries supply the anterior spinal axis and the
radiculopial arteries supply the posterior spinal axes.
•• In the cervical region, radiculomedullary arteries arise from both vertebral
arteries, ascending and deep cervical arteries, and in the dorsal and lumbar
region from the dorsospinal branches of the intercostal and lumbar arteries.
•• The most important contribution to the ASA is from the artery of
Adamkiewicz, which may arise anywhere from T8 to L1, more often on
the left side.
Table 1A: Spinal vascular malformations

Type I Spinal dural arteriovenous fistula
Type II Spinal AVM—Intramedullary
Type III Spinal AVM—Juvenile
Type IV Spinal AVM—Perimedullary AVF
706
Table 1B: Casasco classification

A. Simple:
A1. Spinal canal vascular malformation:
a. Intramedullary vascular lesions:
i. AVM
ii. AVF
iii. Cavernoma
iv. Telangectasia
b. Perimedullary AV fistula:
i. Type 1—small AVF, ASA or PSA and vein
ii. Type 2—ASA/PSA and vein dilated
iii. Type 3—giant AVF, multiple feeders
c. Spinal dural AVF with perimedullary venous drainage
d. Intracranial dural AVF with perimedullary venous drainage
e. Epidural AVF and AVM:
i. Single shunt
ii. Multiple shunts
A2. Perivertebral malformations:
a. Paraspinal
b. Costovertebral angle
c. Nerve root foramina
A3. Vertebral angiomas:
a. Non-progressive vertebral angiomas
b. Progressive vertebral angiomas
B. Complex:
a. AVM in spinal arteriovenous metameric syndrome (SAMS) at each spinal level—
involvement of all layers of integument, ectodermal and mesodermal, from skin,
subcutaneous tissue, muscle, bone, dura, subdural tissue, spinal cord
b. Disseminated angiomatosis (Osler-Rendu-Weber disease)
Table 1C: Classification (Spetzler)

Neoplasm
Aneurysm
Arteriovenous lesion:
A. AVF
a. Extradural
b. Intradural
i. Dorsal
ii. Ventral
B. AVM
a. Extradural
b. Intradural
i. Intramedullary
ii. Intramedullary-extramedullary
iii. Conus medullaris
Chapter 97 • Embolisation of Spinal Vascular Malformations
707
•• Another prominent radiculomedullary artery arises at the cervical level and

is called the artery of the cervical widening.
•• The anterior two-thirds of the spinal cord is supplied by the ASA and the
posterior one-third by the paired PSA.
•• The axis lies in the anterior commissure of the spinal cord and gives
rise to perforators throughout its length. These perforators are known as
sulco-commissural perforators. These perforators are usually not visible on
angiography unless they are hypertrophied in the presence of pathology
like spinal cord AVM.
•• For embolisation, these may have to be selectively cannulated to maintain
the continuity of the anterior spinal axis.
•• The clinical presentations of spinal cord AVM or AVF are different from
that of dural AVF (Table 2).
•• The clinical signs are due to:
–– SAH
–– Haematomyelia
–– Steal into AVF/AVM
–– Venous hypertension
–– Thrombosis of draining vein
–– Pressure of aneurysm, venous or arterial, true or false
–– Arachnoiditis
–– Syringomyelia and
–– Foix-Alajouanine syndrome, a result of chronic venous ischaemia of
the spinal cord.
•• SAH is usually due to rupture of an aneurysm or AVM nidus.
•• Thrombosis of the draining vein results in Foix-Alajouanine syndrome.
•• The clinical course is often characterised by exacerbations and remissions.
•• These are due to repeated haemorrhages from aneurysms or veins.
•• Rise in venous pressure results in clinical deterioration, e.g. after
constipation, coughing, sneezing, forward bending, pregnancy and
menstrual period.
•• Claudication pain is a common presentation in dural AVF.
•• Claudication pain and neurological deficit may be worsened by a heavy
meal. Spinal SAH may be confused with intracranial SAH. However, the
pain starts at the site of the spinal AVM and spreads upwards.
•• The neurological deficit usually starts in the lateral columns then spreads
to the corticospinal tracts and posterior columns.
Table 2: Clinical presentation

Dural AVF Intradural AVM/AVF
Gender Predominantly Male Male or Female
Mean age 40 years 25 years
Onset Gradual Sudden
First symptom Paresis or pain SAH
Exacerbation by activity 80% 25%
Upper limbs affected Never Sometimes
708
Table 3: Summary of clinical characteristics in AVMs (Spetzler 2002)

Characteristics Extradural-Intradural Intramedullary Conus Medullaris
Pathophysiology Compression, vascular Haemorrhage, Venous
steal, haemorrhage compression, hypertension,
vascular steal compression,
haemorrhage
Presentation Pain, progressive Acute myelopathy, Progressive
myelopathy pain, progressive myelopathy
myelopathy
Diagnostic MR imaging, MR imaging, MR imaging,
modality Angiography Angiography Angiography
High-flow, multiple
feeders
Previous Juvenile AVM, Classic AVM, None
nomenclature metameric AVM glomus type
•• Sphincter involvement is early, if the conus is involved.

•• Diagnosis, especially of dural arteriovenous fistula, is difficult and delayed
for several months before it is made (Table 3).
INVESTIGATIONS
•• Plain X-rays may show scalloping of the posterior surface of the vertebral
body, if there is a large venous varix.
•• Usually plain X-rays are non-contributory.
Myelography
•• Myelography with non-ionic contrast in the prone and supine positions may
show the coiled vessels on the dorsal surface of the spinal cord.
•• Arachnoiditis may also be recognised.

•• Computerised tomography scan with intrathecal contrast may show the
large serpiginous vessels.
•• CTA on the newer machines, if done carefully, often provides good
information.
•• The feeding arteries, nidus (if any), draining veins and aneurysms along
the feeders and draining veins may be seen.

•• Magnetic resonance imaging usually shows the lesion within the cord
very well.
•• In dural AVF, fusiform oedema of the conus is pathognomonic. It may
extend upwards into the dorsal cord for a variable distance.
•• The vessels may be seen on MRI myelography or T2-weighted images.
•• Associated lesions of the cord, cysts, arachnoiditis and syrinx are well seen.
•• Old haemorrhage may be seen as haemosiderin deposits.
Chapter 97 • Embolisation of Spinal Vascular Malformations
709
Magnetic Resonance Angiography

•• Magnetic resonance angiography (MRA), especially after contrast, shows
the vessels very well.
•• One may be able to identify the site of the AVF, the feeding artery and
draining vein.
•• The coiled vessels on the anterior and posterior surface of the cord are
well-seen.
Digital Subtraction Angiography

•• Digital subtraction angiography (DSA) is the gold standard for diagnosis.
•• For cervical lesions, bilateral vertebral (VA), bilateral subclavian, bilateral
external carotid and at least eight upper dorsal intercostal arteries must
be catheterised on both sides.
•• For lumbar lesions, bilateral intercostals, all lumbar and internal iliac
angiograms must be done.
•• For slow flow dural AVF, delayed filming up to 20 seconds is mandatory.
•• AP views are made of all vessels. Lateral and oblique views of the feeders
to the spinal cord and the malformation are made to get a complete picture
of the malformation.
•• AVM may be occult. Sometimes it may be necessary to repeat the
angiogram.
•• The DSA must be analysed carefully. When analysing the DSA, one must
find the feeders, draining veins and the nidus.
•• As has already been stated there may be no nidus at all. There may be
single or multiple AVF.
•• Sometimes, the transition from artery to vein in Type 1 AVF is subtle and
may be easily missed.
•• It is mandatory to demonstrate the normal supply of the cord and identify
the ASA and the PSA.
•• The same intercostal or lumbar artery may be supplying the cord as well
as the AVM. One must identify the shortest and easiest route to the feeder.
TREATMENT
•• Patients presenting with subarachnoid haemorrhage, spinal cord
haemorrhage, progressive neurological deficit or severe root pains need
to be treated.
•• AVMs located in the cervical and upper dorsal region are clinically more
aggressive, present with recurrent bleeds which cause severe neurological
deficits and need urgent treatment.
•• The aim of treatment is to find “weak spots” and obliterate them.
•• Complete cure is rarely achieved as the morbidity is much higher due to
erratic embolisation when attempting to obtain obliteration of the AVM.
•• Ligation of proximal feeders, without tackling the nidus, should be
condemned as collateral circulation from adjacent arteries immediately
takes over the supply.
•• The collateral feeders are usually small and tortuous rendering further
surgical or endovascular treatment impossible.
710
Table 4: Materials required

Access sheath
Spinal angio. Or Sim 1 cath
Non-ionic contrast
Microcatheter—Marathon, Magic 1.2 FM, Ultraflow
Microguide wire—Mirage 0.008”
Embolic material: Histoacryl with lipiodol, Onyx 18 or Onyx 34
Dural AVF
•• Dural AVF can be treated by surgery or by the endovascular route.
•• The aim of treatment is to find and obliterate the single draining vein as it
enters the spinal canal.
•• This is accomplished by depositing dilute histoacryl or onyx 1860 in the
draining vein and the dural malformation (Table 4).
•• During surgery, a limited laminectomy is done on the appropriate side; the
dura is exposed close to the intervertebral foramen where the bunch of
vessles on the dura is recognisable.
•• The dura is opened; the vein is identified as it enters the spinal canal.
•• The vein is coagulated and divided. The dura containing the malformation
may be coagulated and excised.
Complications
•• Rarely a patient may deteriorate after the diagnostic angiogram, especially,
if ionic contrast is used.
•• Occlusion of the draining vein without obliteration of the AVF or AVM
may result in haemorrhage. Haemorrhage may occur due to rupture of an
associated aneurysm.
•• The neurological deficit is due to ischaemia of the cord or haematomyelia
and may vary from complete motor and sensory paraplegia with sphincter
involvement to minor problems like backache.
•• The deficit usually recovers overtime with physiotherapy, but it may be
permanent.
•• Recovery of the sensory system, especially posterior columns, usually
occurs rapidly.
•• Motor recovery is slower.
98
CHAPTER Spontaneous
Intracerebral Haemorrhage
Ajaya Nand Jha  Vipul Gupta
INTRODUCTION
•• Intracranial haemorrhage (ICH) accounts for 10−30% of all stroke
admissions to hospital, and leads to catastrophic disability, morbidity and
a 6 month mortality of 30−50%.
•• ICH is classified as primary or secondary.
•• Primary ICH is when the haemorrhage originates from spontaneous rupture
of small arteries or arterioles damaged by chronic hypertension or amyloid
angiopathy.
•• Secondary ICH is when haemorrhage results from trauma, rupture of an
aneurysm/vascular malformation, coagulopathy or other causes (Table 1).
RISK FACTORS
•• Chronic hypertension causes degeneration, fragmentation and fibrinoid
necrosis of small penetrating arteries in the brain, which can eventually
result in spontaneous rupture.
•• Some people have discrete arteriolar microaneurysms (Charcot-Bouchard
aneurysms) at the site of vessel rupture.
•• Hypertensive ICH typically occurs in the basal ganglia (putamen, thalamus
or caudate nucleus), pons, cerebellum or deep hemispheric white matter.
•• Non-compliance with antihypertensive treatment increases the risk of ICH.
Table 1: Secondary causes of ICH

Trauma
Arteriovenous malformation
Intracranial aneurysm
Coagulopathy
Haemorrhagic conversion of cerebral infarct
Dural sinus thrombosis
Intracranial neoplasm
Cavernous angioma
Dural arteriovenous fistula
Venous angioma
Cocaine or sympathomimetic drug exposure
CNS vasculitis
Anticoagulant therapy
712
•• The second most common cause of primary ICH is cerebral amyloid

angiopathy.
•• The disorder is characterised by the deposition of amyloid-b peptide in
small to medium sized blood vessels of the brain and leptomeninges, which
results in vascular fragility.
•• After hypertensive ICH, repeat bleed occurs in as low as 2% of patients
per year if the blood pressure is well-controlled.
EMERGENCY DIAGNOSIS AND

ASSESSMENT OF INTRACEREBRAL
HAEMORRHAGE AND ITS CAUSES
•• The classic clinical presentation includes the onset of a sudden focal neu-
rological deficit while the patient is active, which progresses over minutes
to hours.
•• The smooth symptomatic progression of a focal deficit over a few hours is
uncommon in ischaemic stroke and rare in subarachnoid haemorrhage.
•• Headache is more common with ICH than with ischaemic stroke, although
less common than in subarachnoid haemorrhage.
•• Vomiting is more common with ICH than with either ischaemic stroke or
•• Increased systemic blood pressure (SBP) and impaired level of consciousness
are common.
Diagnosis
•• ICH is confirmed by computed tomography (CT) scan.
•• The volume of the haemorrhage can rapidly be estimated at the bedside
from the CT with the ABC/2 method, which involves multiplying the diameter
of the haematoma in three dimensions and dividing by two.
•• MRI is as sensitive as CT for the detection of ICH in the acute stage,
but is most commonly done as a follow-up study to detect vascular flow
voids, which are indicative of an arteriovenous malformation, chronic lobar
microbleeds on gradient echoimaging suggestive of amyloid angiopathy,
or a contrast-enhancing neoplasm.
•• Catheter angiography is the diagnostic test for vascular causes of
secondary ICH, such as an aneurysm, arteriovenous malformation, dural
arteriovenous fistula or cortical-vein thrombosis.
•• Indications for catheter angiography include subarachnoid haemorrhage,
abnormal calcifications, obvious vascular abnormalities and blood in
unusual locations such as the Sylvian fissure.
PATHOPHYSIOLOGY
•• The two most important new concepts are that many haemorrhages
continue to grow and expand over several hours after onset of symptoms—a
process known as early haematoma growth—and that most of the brain
injury and swelling that happens in the days after ICH is the result of
inflammation caused by thrombin and other coagulation end-products.
Early Haematoma Growth

•• Early haematoma growth is common and associated with neurological
deterioration and poor clinical outcome.
Chapter 98 • Spontaneous Intracerebral Haemorrhage
713
•• Even in the absence of known coagulopathy, about 38% of patients had

an increase in haematoma volume of more than 33% shown by CT within
3 hours of onset.
Perihaematomal Brain Injury

•• Brain-tissue injury and swelling, which can result in increased intracranial
pressure (ICP) or herniation related to compartmentalised mass effect, are
the primary causes of neurological deterioration after the first day.
•• The possible creation of an ischaemic penumbra in the brain tissue
immediately adjacent to an ICH, resulting in secondary neuronal injury and
cytotoxic oedema, was a major concern for many years.
•• PET and MRI studies, done as early as 6 hours after onset of symptoms,
have not shown tissue ischaemia in perihaematomal brain regions.
•• By contrast, an overwhelming haematoma-induced inflammatory response
has been identified which causes less brain swelling and tissue injury.
•• Plasma, that is rich in thrombin and other coagulation end-products,
released by the clotted haematoma seeps into the surrounding brain tissue,
and is the primary trigger of the inflammatory process.
PROGNOSIS
•• Mortality after ICH approaches 50% at 1 year.
•• Independent predictors for 30 days and 1 year mortality include large ICH
volume, coma, older age, intraventricular haemorrhage and infratentorial
location.
•• A useful clinical grading scale (the ICH score) that incorporates these five
elements allows rapid estimation of 30 day mortality on admission (Table 2).
MANAGEMENT
•• The patient’s neurological status should be assessed frequently with the use
of standard stroke scales such as the National Institutes of Health Stroke
Scale (NIHSS) and coma scales such as the Glasgow Coma Scale (GCS).
•• Blood pressure should be monitored adequately.
•• Airway and oxygenation can be assessed per respiratory status and pulse
oximetry.
•• Cardiopulmonary instability in association with increased ICP is to
be avoided to minimise deleterious effects in patients with limited
autoregulatory capacity.
•• Fluids given in the form of 0.45% saline or 5% dextrose in water can
exacerbate cerebral oedema and increase ICP because it flows down its
osmotic gradient into injured brain tissue.
Blood Pressure
•• The American Stroke Association (ASA) has recommended the following
guidelines for treating elevated blood pressure in patients with spontaneous
ICH:
–– If Systolic blood pressure (SBP) is more than 200 mmHg or mean arterial
pressure (MAP) is greater than 150 mmHg, then consider aggressive
reduction of blood pressure with continuous intravenous infusion, with
frequent blood pressure monitoring every 5 minutes.
714
Table 2: The ICH score

Component Points
Glasgow coma scale score
3−4 2
5−12 1
13−15 0
ICH volume (mL)
>30 1
<30 0
Intraventricular haemorrhage
Yes 1
No 0
Age (years)
>80 1
<80 0
Infratentorial origin
Yes 1
No 0
30 day mortality attotal points
5+ 100%
4 97%
3 72%
2 26%
1 13%
0 0%
–– If SBP is greater than 180 mmHg or MAP more than 130 mmHg and
there is evidence of or suspicion of elevated ICP, then consider
monitoring ICP and reducing blood pressure using intermittent or
continuous intravenous medications to keep cerebral perfusion
pressure greater than 60−80 mmHg.
–– If SBP is greater than 180 mmHg or MAP more than 130 mmHg and
there is no evidence of or suspicion of elevated ICP, then consider a
modest reduction of blood pressure (e.g. MAP of 110 mmHg or target
blood pressure of 160/90 mmHg) using intermittent or continuous
intravenous medications to control blood pressure, and clinically re-
examine the patient every 15 minutes.
[SBP: systolic blood pressure; MAP: mean arterial pressure].
•• Intravenous medications that may be considered for control of elevated
blood pressure in patients with ICH include labetalol, nicardipine, esmolol,
enalapril, hydralazine, nipride and nitroglycerin.
Management of ICP
•• An ICP monitor or external ventricular drain should generally be placed in
all patients with ICH in coma (Glasgow Coma Scale score of 8 or less),
with the goal of maintaining ICP below 20 mmHg and a minimum cerebral
perfusion pressure greater than 60 mmHg.
715
•• Emergency measures of ICP control are appropriate for stuporous or

comatose patients, or those who present acutely with clinical signs of
brainstem herniation.
•• The head is elevated to 30 degrees, 1.0−1.5 g/kg of 20% mannitol is given
by a rapid infusion, and the ventilation is controlled to maintain the pCO2
at 30−35 mmHg.
•• These measures are designed to lower ICP as quickly and effectively
as possible to buy time before a definitive neurosurgical procedure
(craniotomy, ventriculostomy, or replacement of an ICP monitor) can be
done.
•• Corticosteroids, such as dexamethasone, are not indicated.
Haemostatic Therapy
•• Eptacog alfa [recombinant activated factor VII (rFVIIa), Novoseven®, Novo
Nordisk A/S] is a powerful initiator of haemostasis currently approved for
treatment of bleeding in patients with haemophilia who are resistant to
factor VIII replacement therapy.
Reversal of Anticoagulation
•• Patients with warfarin-associated ICH should be treated with intravenous
vitamin K to reverse the effects of warfarin and with treatment to replace
clotting factors.
•• Prothrombin complex concentrate, factor IX complex concentrate and rFVIIa
normalise the laboratory elevation of the INR very rapidly and with lower
volumes of fluid than FFP, but with greater potential of thromboembolism.
•• FFP is another potential choice, but is associated with greater volumes
and much longer infusion times.
•• rFVIIa in doses ranging 10−90 µg/kg has been used to reverse the effects
of warfarin in acute ICH—primarily to expedite neurosurgical intervention—
with good clinical results.
•• Unfractionated or low-molecular-weight heparin should be reversed with
protamine sulphate and patients with thrombocytopaenia or platelet
dysfunction can be treated with a single dose of desmopressin (DDAVP),
platelet transfusions, or both.
Anticonvulsant Therapy
•• Acute seizures should be treated with intravenous lorazepam
(0.45−0.10 mg/kg) followed by an intravenous loading dose of phenytoin
or fosphenytoin (15−20 mg/kg), valproic acid (15−45 mg/kg) or
phenobarbital (15−20 mg/kg).
Fever Control
•• The incidence of fever after basal ganglionic and lobar ICH is high,
especially in patients with ventricular haemorrhage.
•• Paracetamol should be given and the body should be cooled externally in
all patients with sustained fever in excess of 38.3°C (101.0°F).
Management of Glucose
•• Evidence indicates that persistent hyperglycaemia (>140 mg/dL) during the
first 24 hours after stroke is associated with poor outcomes.
716
•• Insulin should be administered when the blood sugar level is >185 mg/dL
and sometimes when it is >140 mg/dL.
Nutrition
•• Enteral feeding should be started within 48 hours to reduce the risk of
malnutrition.
Deep Venous Thrombosis Prophylaxis

•• ICH patients are at high-risk for deep vein thrombosis and pulmonary
embolism.
•• Dynamic compression stockings should be placed on admission.
•• After documentation of cessation of bleeding, low-dose subcutaneous low-
molecular-weight heparin or unfractionated heparin may be considered in
patients with hemiplegia 3−4 days after the ictus.
Anticoagulation after ICH

•• The issue of reinstitution of anticoagulation after warfarin-related ICH
applies primarily to those patients who were taking warfarin for the
prevention of cardiogenic embolism associated with either prosthetic heart
valves or chronic atrial fibrillation.
Recommendations for the Management of ICH

Related to Anti-coagulation and Fibrinolysis Therapy
•• The decision to restart antithrombotic therapy after ICH depends on the risk
of subsequent arterial or venous thromboembolism, the risk of recurrent
ICH and the overall state of the patient.
•• For patients with a comparatively lower-risk of cerebral infarction (e.g.
atrial fibrillation without prior ischaemic stroke) and a higher risk of amyloid
angiopathy (e.g. elderly patients with lobar ICH) or with very poor overall
neurological function, an antiplatelet agent may be an overall better choice
for prevention of ischaemic stroke than warfarin.
•• In patients with a very high-risk of thromboembolism in whom restarting
warfarin is concerned, warfarin therapy may be restarted at 7−10 days after
onset of the original ICH.
SURGICAL MANAGEMENT
•• To achieve the goals of surgical treatment, the specific aims may include
decompression to reduce or prevent elevated intracranial pressure and
removal of the acute haematoma to reduce mass effect and to minimise
toxicity from blood breakdown products to the surrounding brain.
•• Several surgical options exist that vary in the degree of invasiveness and
associated morbidity.
•• These options include ventriculostomy, stereotactic aspiration of
haematoma with or without alteplase (rt-PA), endoscopic haematoma
evacuation, craniotomy for evacuation of haematoma and hemicraniectomy
for decompression with or without evacuation of haematoma.
Minimally Invasive Surgery

•• The purported advantages of minimally invasive clot evacuation over
conventional craniotomy include:
717
–– Reduced operative time

–– The possibility of surgery under local anaesthesia and
–– Teduced tissue trauma, especially for deep lesions.
•• Together, these advantages may also facilitate earlier evacuation of ICH
than is possible or practical with conventional craniotomy.
•• On the other hand, the reduced surgical exposure, the inability to treat
associated structural lesions (arteriovenous malformation or aneurysm), the
potential for re-bleeding related to the use of fibrinolytics, and the possibility
of an increased risk of infection related to prolonged indwelling catheters
are limitations of this approach.
Thrombolytic Therapy and Aspiration of Clots

•• Although stereotactic infusion of thrombolytic drugs into the clot cavity
apparently reduces clot burden and risk of death, re-bleeding is more
common and functional outcome is not improved; therefore, its usefulness
is unknown.
Decompressive Craniotomy
•• This technique has been reported to be beneficial in a number of
conditions, including hemispheric ischaemia stroke and ICH associated
with aneurysmal subarachnoid haemorrhage.
•• To date, no prospective randomised controlled trials show a convincing
beneficial effect on outcome for spontaneous ICH.
Timing of Surgery
•• No clear evidence at present indicates that ultra-early craniotomy improves
functional outcome or mortality rate.
•• Operative removal within 12 hours, particularly when performed by less-
invasive methods, has the most supportive evidence, but the number of
subjects treated within this window is very small.
•• Very early craniotomy (within 4 hours) may be associated with an increased
risk of recurrent bleeding.
CONCLUSION
•• Management of primary intracerebral haematoma, particulary the role of
surgery remains a controversial subject in spite of a number of collaborative
multicentric studies.
99
CHAPTER
Surgery for Stroke
Vincent Thamburaj A
•• Stroke is the second commonest cause of death in India.

•• Arterial thrombosis and atherosclerosis with occlusion of the cerebral
arteries is considered as the single most common cause of stroke in more
than 50% of patients.
•• Around 30−50% of the cases have had previous transient ischaemic
attacks (TIAs).
•• TIAs may be caused by embolism arising from an atheromatous carotid
lesion or from reduction in cerebral blood flow due to atheromatous
occlusion.
•• Coronary artery disease and rheumatic heart disease are responsible for
most of the cardioembolic strokes.
•• Other rarer causes include trauma to the carotid/vertebral arteries, collagen
diseases, moyamoya disease, fibromuscular dysplasia, vasospastic
conditions [subarachnoid haemorrhage (SAH), migraine, etc.], and the
conditions which alter the rheological properties of the blood such as,
polycythaemia, leukaemia, etc.
•• Epidemiological studies involving twins, siblings or families have found
evidence of a genetic influence in patients stroke.
•• There are risk factors such as hypertension, hypercholesterolaemia,
atherosclerosis, cardiac abnormalities, diabetes mellitus, obesity and lack
of physical activity.
•• Major risk factors identified in India are hypertension (>95 mmHg
diastolic), hyperglycaemia, tobacco use (smoking/chewing) and low normal
haemoglobin levels (less than 10 g).
CLINICAL FEATURES
Clinical presentations of cerebral ischaemia are commonly classified into:
•• TIA is traditionally defined as an episode of focal neurological dysfunction
as a result of ischaemia which resolves completely within 24 hours.
–– Most of these last for about 10 minutes.
–– The proposed new definition of TIA is a “brief episode of neurological
dysfunction caused by a focal disturbance of brain or retinal ischaemia,
with clinical symptoms typically lasting less than 1 hour, and without
evidence of infarction”.
–– TIAs are an important determinant of stroke, with 90-day risks of stroke
reported as high as 10.5% and the greatest stroke risk apparent in the
first week after the episode of TIA.
Chapter 99 • Surgery for Stroke
719
•• ‘Crescendo’ TIAs describe a cluster of attacks occurring at increasing

frequency or duration over a few hours or days. The patients are at risk of
imminent brain infarction.
•• Prolonged reversible ischaemic defect is one where the signs and
symptoms last longer than 24 hours, followed by complete recovery within
3 weeks.
–– They have a stuttering or gradual onset unlike a TIA, which has an
abrupt onset; they are most likely to be due to cardiogenic embolism.
•• Progressing stroke/stroke in evolution is one where the deficit continues
to progress in a stepwise fashion despite adequate medical therapy. It
appears to be more common in the vertebrobasilar territory, and 50% of
the patients will die if untreated.
•• Completed stroke is a stable, focal ischaemic neurological deficit:
–– There may be sudden unheralded progressive neurological deficit
(embolic stroke) or the deficit, more commonly, becomes complete in
a few hours (thrombotic stroke).
–– It is usually associated with altered sensorium in a few hours (throm-
botic stroke).
•• The earliest sign of the cardiovascular accident (CVA) is TIA.
•• Monocular blindness, dysphasia, localised sensory loss and hemiparesis
are some of the symptoms that strongly suggest a focal ischaemic episode,
and the location of the symptoms defines the vascular distribution of the
ischaemia.
•• Other symptoms, such as diplopia alone, syncope, etc. are far less specific
symptoms.
Carotid Territory
•• The classic history for TIA in the carotid system is one of abrupt onset of
contralateral weakness or numbness of the arm and/or leg.
•• Dysphasia occurs if the dominant hemisphere is involved.
•• Impaired vision of the eye on the side of diminished carotid flow takes place.
•• There are five clinical findings which would make one suspect involvement
of the carotid arteries:
–– Blindness in one eye during the TIA attack
–– Emboli in the retinal vessels
–– Bruit over the carotid artery
–– Significant lowering of the retinal arterial pressure on the affected side
–– Any sign of retinal artery ischaemia. Associated carotidynia (pain over
the carotids) suggests a carotid pathology.
Vertebro-basilar Territory
•• Damage to this system is also characterised by a very swift onset of
symptoms with neurological phenomena such as ataxia, monoparesis,
hemiparesis, quadriplegia, numbness (frequently shifting from one side to
the other), vertigo, defects in either visual field, diplopia, dysarthria, aphasia
and, occasionally, clouding of consciousness.
•• Vertigo is perhaps the most common symptom of TIA in this distribution.
Investigations
•• Evaluation of TIAs depends on the clinical symptoms, physical examination
and laboratory investigations.
720
•• Attention should also be given to clinical evidence of generalised

atherosclerotic disease, as death due to the complications of ischaemic
heart disease is the commonest outcome in patients with TIA.
•• Early attention should focus on risk factor modification, with emphasis on
the treatment of hypertension and smoking cessation.
•• TIAs should be regarded as an emergency.
•• The initial evaluation include laboratory tests, electrocardiography and
imaging studies.
•• It is recommended that CT or MRI of the head be part of the evaluation of
all these patients.
•• Doppler ultrasonography or other noninvasive investigations of the carotid
arteries should be performed rapidly, ideally within 24 hours.
•• CT will demarcate the area of ischaemia and exclude haemorrhage and also
show previous infarcts, if any. Small lacunar infarcts suggest an arteriolar
pathology (of the penetrating branches of major cerebral arteries). Wedge-
shaped infarcts suggest thromboembolism. Ill-defined border zone infarcts
suggest haemodynamic ischaemia.
•• CT angiography of cervical vessels reveals enough vascular details to
be useful as a diagnostic screening method in patients with presumed
atherosclerosis of the carotid bifurcation and accurately excludes and
detects aneurysms and AVMs.
•• MRI is more sensitive, in particular for previous vascular episodes. MR
angiography, a noninvasive test, can yield information regarding collateral
blood flow and is nearly as effective as conventional angiography in
estimating disease at the carotid bifurcation. It is suitable for replacing the
invasive conventional angiography method in most cases.
•• Ultrasonography, being cost effective, should be used as a screening
tool to exclude patients with no carotid artery disease from further
testing. Ultrasound evaluation of carotid artery morphology and flow
has been widely accepted as a noninvasive measure and has replaced
ophthalmodynamometry and oculoplethysmography that offer an indirect
indication of ipsilateral carotid occlusion.
•• B-mode ultrasound imaging provides images of various levels, or
planes, enabling the creation of a 3D image of the carotid artery wall and
surrounding structures.
•• Doppler testing measures the speed of arterial blood flow.
•• Duplex ultrasound (DUS) combines B-mode imaging and Doppler to
provide more details about the condition of the arteries than either test
alone can provide.
•• Transcranial Doppler (TCD) assesses intracranial arterial flow in the distal
internal carotid artery (ICA), the middle, anterior and posterior cerebral
artery stems, and the ophthalmic artery.
•• Conventional four vessel arteriography should include cerebral, carotid and
aortic arch studies and also cross carotid compression views.
•• Doppler C02/Acetazolamide (diamox) test: Cerebral blood flow (CBF),
measured early after acetazolamide administration, could be useful to
confirm the clinical diagnosis of TIA. No increase in CBF during hypercapnia
or following acetazolamide suggests that the cerebral arterioles are
maximally dilated and the procedures to improve the blood flow, such as
EC-IC bypass, will not help.
•• Single-photon emission computed tomography (SPECT) studies combine
nuclear medicine with computed tomography. Used in the early hours after
721
ischaemia, cerebral SPECT is able to reveal a deficit in local blood flow

before changes appear on CT or MRI.
•• Positron emission tomography (PET) can be used to measure CBF,
cerebral blood volume (CBV) and metabolism (CMR). Patients with low
CBF and high oxygen extraction fraction (OEF) have compromised cerebral
circulation and are expected to benefit from revascularisation.
SURGERY FOR STROKE PREVENTION

•• Carotid occlusive disease is the primary pathophysiological source of
10−20% of all strokes.
•• Carotid occlusive disease may be caused by a variety of disorders; but
the great majority of strokes of carotid origin are related to atheromatous
narrowing of these arteries.
•• Fibromuscular dysplasia is a non-inflammatory vasculopathy and is the
second most common cause of extracranial carotid stenosis usually at the
level of C2−C3, with sparing of the proximal ICA at the bifurcation.
•• Dissection of the cervical carotid artery has been categorised as traumatic
or spontaneous.
•• Spontaneous dissections can be associated with atherosclerosis or
fibromuscular dysplasia.
•• Traumatic dissections typically involve the distal extracranial ICA and
are thought to originate from impingement of the artery against the C2
transverse process during rotation with extension of the neck.
Direct Revascularisation Procedures

Carotid Territory
•• Carotid endarterectomy (CEA):
–– Removal of the stenotic, atheromatous lesion eliminates potential
sites of thrombi, thereby eliminating a potential source of emboli and
improves cerebral blood flow.
–– Indications: Carotid occlusive disease can be clinically divided into
two types: (i) Symptomatic and (ii) asymptomatic.
–– Symptomatic carotid stenosis usually refers to ischaemia in the distri-
bution of the ipsilateral stenotic ICA resulting in TIAs, amaurosis fugax
or completed stroke.
•• A diagnosis of asymptomatic disease is made in patients with any of the following:
–– Incidentally found carotid bruit.
–– Cerebrovascular symptoms referable to one carotid artery territory,
and demonstration of an asymptomatic contralateral carotid artery
stenosis or ulceration.
–– Patients, scheduled to undergo general or cardiac surgery with auscul-
tatory or radiographical evidence of carotid artery disease.
•• Prospective co-operative studies confirm that surgery has a role in the
treatment of this disease.
•• A review of these trials is imperative, if these data are to be applied to an
individual patient.
–– The North American Symptomatic Carotid-Endarterectomy Trial (NAS-
CET) and the European Carotid Surgery Trial (ECST)
–– A reanalysis of the final results of the ECST and NASCET suggested
that CEA is highly beneficial for 70−99% stenosis and moderately
beneficial for 50−69% stenosis.
722
•• Indications for asymtomatic carotid stenosis are still controversial.

•• In 1995, the asymptomatic carotid atherosclerosis study (ACAS) looked
at the benefits of surgery in patients with narrowing in the carotid artery in
the range of 60−99% stenosis.
•• There was no evidence of any more or less benefit as the narrowing
approached 99%.
•• ACST confirms there is overall benefit from carotid surgery in patients with
asymptomatic carotid narrowing of 60−99% in patients under the age of
75 years.
•• The most recent extensive analysis recommends the following for stroke
prevention:
–– Patients with recent TIA or ischaemic stroke within 6 months and ipsi-
lateral severe (70−99%) carotid artery stenosis should receive CEA by
an experienced surgeon with a morbidity and mortality of less than 6%.
–– Patients with recent TIA or stroke with moderate carotid stenosis
(50−69%) may have CEA depending on comorbid factors, whereas
CEA is not recommended for those with less than 50% stenosis.
–– When CEA is recommended, surgery should be performed within
2 weeks.
–– In those with symptomatic severe stenosis greater than 70% in whom
the stenosis is difficult to assess, carotid angioplasty is not inferior to
CEA, and may be considered.
–– Among patients with symptomatic carotid occlusion, extracranial-
intracranial bypass is not routinely recommended.
–– Endovascular treatment of patients with symptomatic extracranial ver-
tebral stenosis may be considered when patients are having symptoms
despite medical treatment.
–– For those with haemodynamically significant intracranial stenosis who
have symptoms despite medical therapy, the usefulness of endovas-
cular therapy is uncertain.
Surgical Risk Factors

•• The risk of stroke and death from carotid endarterectomy is related to
clinical and angiographic characteristics.
•• The patients may be classified into the following four groups to assess
the risk factor:
Group 1: Neurologically stable without medical or angiographic risk.
Group 2: Neurologically stable without medical, but with angiographic risk.
Group 3: Neurologically stable with medical and with or without angiographic
risk.
Group 4: Neurologically unstable with or without medical/angiographic risks.
•• As in any form of major surgery, patients with hypertension, chronic
obstructive airway disease, obesity and congestive cardiac failure are at
greater risk.
Surgical Technique
•• Pre-operative counselling is important as preparation of the patient mentally
helps a great deal in overcoming the fear and anxiety.
•• If the patient is on antiplatelets already, ASA may be continued through
the procedure, but Clopidogrel is stopped two days pre-operatively in our
practice.
723
•• In the operating room, the patient is sedated with 1 mg midazolam

intravenously after securing venous access and arterial pressure monitoring
catheter.
•• Arterial pressure is monitored continuously as fluctuations during the
procedure can affect the cerebral circulation.
•• Positioning of the patient is extremely important as hyperextension of the
neck may kink the vertebrals, which will be the likely source of blood supply
during cross clamping of the ICA.
Intra-operative Monitoring
•• Electroencephalography
•• Somatosensory evoked potentials (SSEP)
•• Measurement of ICA stump backpressure helps in deciding on the need
for a shunt.
•• Transcranial Doppler (TCD) detects high blood flow velocities.
Complications
•• Peri-operative complications of carotid endarterectomy are uncommon but
potentially devastating.
•• Appropriate patient selection, including careful assessment of techniques
aimed at prevention and monitoring of intra-operative complications and
post-operative care are mandatory.
•• Intracerebral haemorrhage is an unusual complication. The incidence of
intracerebral haemorrhage is increased in patients with critical carotid
stenosis; this is probably related to chronic impairment of cerebral
autoregulation.
•• Restenosis occurs in about 20%.
•• Aside from technical inadequacies, the continuation of cigarette smoking
post-CEA proved to be a significant risk factor; however, hypertension,
diabetes mellitus, family history, lipid studies, aspirin use and coronary
disease were not found to be significant risk factors.
•• Injuries to the cervical cranial nerves are a common consequence of carotid
endarterectomy.
Extracranial to Intracranial (EC-IC) Bypass

•• Superficial temporal to middle cerebral artery bypass (STA-MCA) is the
most widely used.
•• The first STA-MCA bypass was performed by Yasargil in 1969.
•• It involves anastomosis of the superficial temporal artery to one of the
cortical branches of the middle cerebral artery.
Vertebro-basilar Territory
•• Cerebellar infarctions carry a poor prognosis with an acute mortality rate
of 20−30%.
•• They are mostly due to diffuse atherosclerosis of the vessels with poor flow
due to stenosis and poor collaterals.
•• Medical therapy is the first line of management.
•• Several procedures have been tried in those with persisting symptoms.
•• The simplest procedure, perhaps, is carotid endarterectomy if a significant
stenosis is found while investigating a vertebrobasilar TIA and the stenosed
carotid may be asymptomatic.
724
•• It is most readily accepted if the angiogram shows filling of the posterior

cerebral artery via the stenotic ICA, or filling of the posterior circulation
from the ICA because of vertebral occlusion or a persistent hypoglossal
or trigeminal artery.
•• Anson and Spetzler reported good outcome with vertebral endarterectomy
which is similar to carotid endarterectomy.
•• Ausman and colleagues have described anastomosis of occipital artery to
the PICA for occlusion proximal to the PICA and a superior cerebellar artery
or P1 segment of the posterior cerebral artery anastomosis for lesions at
the mid or distal basilar and also recommend vertebral endarterectomy in
symptomatic patients with a functioning collateral or bypass.
•• Extracranially, the left subclavian artery, next to the carotids and the vertebrals,
is the most commonly involved in atherosclerosis.
•• Subclavian steal syndrome is most commonly treated by carotid-subclavian
bypass.
Indirect Revascularisation Procedures

•• Intracranial occlusive diseases form a heterogeneous group with diverse
pathogenesis.
•• Moyamoya, the commonest, is a progressive occlusive cerebrovascular
disorder characterised by bilateral stenosis and occlusions of the intracranial
arteries with extensive neovascularisation at the base of the brain.
•• It was first described in Japan and is now reported from all over the world.
•• The term moyamoya (Japanese for “puff of smoke”) was coined by Suzuki
and Takaku in 1969 in reference to the angiographic appearance of these
fine basal collaterals, and has since become the accepted term to define
the disease throughout the world.
•• The incidence of persistent primitive arteries is significantly higher in
patients with moyamoya disease, suggesting that congenital factors may
be important in the pathogenesis of this disease.
•• In paediatric-onset moyamoya disease, asymmetrical involvement of
bilateral ICAs and PCAs is common, and the ipsilateral ICA and PCA tend
to be predominantly involved.
•• The term quasi-moyamoya disease or moyamoya syndrome is typically
used to refer to patients who display intracerebral steno-occlusive lesions
and associated collaterals in other areas of the brain.
•• Treatment of all patients with intracranial small vessel occlusive diseases
is similar to that of moyamoya patients.
•• Patients present with stroke or intracranial haemorrhage due to bleeding
from the friable vessels with major morbidity and mortality.
•• Children usually present with cerebral ischaemia, while intracranial
haemorrhage is common in adults.
•• CT, MR imaging and MR angiography help in diagnosis.
•• CT may show multiple low density areas, and general atrophy, and contrast
enhancing curvilinear vessels in the basal ganglia and cortical surface.
•• Conventional four vessel angiography is rarely required.
•• 3D CT angiography is becoming an alternative. Without treatment,
there is progressive deterioration of neurological function and recurrent
haemorrhages.
•• Medical therapy with vasodilators, steroids and antibiotics is only minimally
effective.
725
•• STA-MCA bypass with or without a graft is re-emerging as a popular

procedure in adults.
•• Direct superficial temporal artery to middle cerebral artery bypass is
considered the treatment of choice, although its efficacy, particularly for
haemorrhagic disease, remains uncertain.
•• All these procedures share the common goal of providing a mechanism to
promote collateral blood vessels to reduce haemodynamic stress across
fragile moyamoya collaterals, and ischaemia. They provide no immediate
revascularisation. They rely on the subsequent formation of collateral
vessels to enhance blood delivery.
•• Encephalo-duro-arterio-synangiosis (EDAS):
–– In 1979, Matsushima and colleagues developed EDAS with the
assumption that the operation would cause the formation of spontaneous
anastomoses between the arteries of the cerebral cortex, dura mater
and scalp to treat moyamoya disease.
–– The STA is mobilised and placed directly on the cortex.
–– The free artery with a cuff of surrounding soft tissue is simply sutured
to the dura.
•• Encephlomyosynangiosis (EMS): It involves direct placement of the
temporalis muscle on the cerebral cortex
•• Encephalo-omental-synangiosis (EOS) may provide an alternative.
–– The omentum is mobilised from the abdomen in a subcutaneous tunnel
and placed over the cerebral cortex as a pedicle graft or, as a free graft
with microsurgical anastomosis of the gastroepiploic artery and vein to
the STA and the superficial temporal vein.
–– Placement of multiple burr holes to improve the vascular supply has
been reported with good outcome.
–– The placement of burr holes was described as a treatment after it was
noticed that neovascularisation was occurring at the site of previous
ventriculostomies.
–– Combined procedures, direct and indirect procedures or a combination
of indirect procedures give the best results.
SURGERY FOR ACUTE STROKE

•• Stroke is a generic term for a clinical syndrome that includes infarction,
haemorrhage and SAH.
•• Acute strokes may be classified into two general types: ischaemic and
haemorrhagic.
•• Approximately 80% of strokes are ischaemic.
•• Bland infarction is characterised by bland widespread leukocyte infiltration
and macrophage invasion, with only scattered red cells being found.
•• Twenty percent of strokes are haemorrhagic stroke which is due to
“spontaneous” intraparenchymal haematoma in 10% of cases; in 10% it is
haemorrhagic transformation of an ischaemic infarct.
Pathophysiology
•• Some degree of mass effect due to brain swelling is associated with acute
stroke.
•• It ranges from very insignificant, as in lacunar infarcts, to a massive swelling
due to multilobular infarcts with increase in intracranial pressure (ICP), brain
shift and uncal or cingulate herniation.
726
•• In early ischaemia, there is intracellular swelling due to derangement of

Na+/K+ pump in the glial membrane and cell metabolism resulting in Na+
and H2O accumulation resulting in cytotoxic oedema.
•• Cytotoxic oedema precedes the onset of vasogenic oedema.
•• The blood-brain barrier (BBB) is not disturbed initially. The cerebrospinal
fluid (CSF) formation is not increased.
•• Both the white and the grey matter are involved.
•• Within a few hours, the BBB is disrupted, and there is increased cell
permeability.
•• The extracellular space is enlarged; there is abnormal diffusion of nutrients
with consequent acidosis, hypoxia, and inflammatory changes.
•• Polymorphs intensively accumulate in the region of cerebral infarction; this
accumulation correlates with the severity of brain tissue damage and poor
neurological outcome.
•• Endogenous substances, such as histamine, bradykinin, excitatory
aminoacids, arachidonic acid, superoxide, hydrogen and hydroxyl radicals,
are released and vasogenic oedema is superimposed.
•• Superoxide dismutase is one of the major free-radical scavenging systems
that might play a role in both degenerative and acute diseases of the central
nervous system
•• Lactic acidosis due to lactic acid accumulation, and increased pCO2 can
denature the proteins and alter the activities of pH dependent enzymes.
Lactate enhances brain oedema.
•• This oedema aggravates the mass effect which in turn aggravates the
ischaemia.
Management
•• Principles for the treatment of acute stroke aim to minimise secondary
tissue damage caused by impaired microcirculation.
•• One way to achieve this is to treat the brain swelling and control the rise in
ICP, which improves leptomeningeal reperfusion of the affected territory.
Cerebral Infarct
Medical Therapy
•• Recent studies have shown a very high mortality rate of patients with
cerebral infarct despite aggressive medical treatment strategies to lower
ICP, which have included osmotherapy, hyperventilation, barbiturate
administration, hypothermia and anticoagulation therapy guided by ICP
monitoring.
•• None of these medical treatment options have improved outcome in
randomised clinical trials.
•• The long-term effects of osmotherapy with mannitol or hypertonic solutions
have not been ascertained yet.
•• There is not enough evidence supporting a prophylactic utility of standard
therapy with hypertonic solutions.
•• Vigorous prolonged hyperventilation has been discouraged because it may
reduce the brain’s ability to tolerate ischaemia and may, therefore, be more
harmful than beneficial.
•• Barbiturate therapy has failed to be of any benefit in the treatment of
oedema after severe brain ischaemia. The side effects include a reduction
in cerebral perfusion pressure, suppressed brainstem reflexes and
727
EEG abnormalities, in addition to respiratory complications, myocardial

depression with reduction in heart volume per minute, increased infection
rate, disturbances in electrolyte balance, impairment of liver function and
leukocyte depression.
•• Mortality rates are highest when lesions involve the trunk of one or more
of the main cerebral vessels.
•• In fact, occlusion of either the distal ICA or proximal MCA trunk has been
characterised as a “malignant” stroke.
•• It is characterised by rapid clinical deterioration due to brain swelling and
downward transtentorial herniation, and is associated with a mortality of 80%.
•• None of the available medical therapies provide substantial relief from the
oedema and raised ICP, or at best, they are temporising in most cases,
and surgery has a distinct role.
Surgical Therapy
•• Craniectomy and Decompression:
–– Decompression of the brain by turning the closed cavity of the skull into
an open one is an old neurosurgical technique and it has been applied
to treat conditions of uncontrollably elevated ICP.
–– A decompressive procedure in selected stroke patients is the most
practiced surgical intervention for acute strokes.
–– Any surgery should be effective, rational and safe.
–– An ipsilateral decompressive surgery fulfils all three criteria.
–– The procedure is, certainly, simple and safe.
–– The available results support the effectiveness of decompressive
surgery as a salvage procedure.
–– It is, perhaps, more appropriate in acute stroke where the mass effect
is restricted to one side only, unlike in head injury.
–– The idea is to give room for the swollen brain, reduce the pressure
gradient between the intracranial compartments, and tide over the crisis.
–– The technique is simple. Associated illnesses and the attitude of
the family members to accept a residual severe neurological deficit,
especially in developing countries where there are no adequate
rehabilitation centres, must also be considered.
–– As in any surgery, patient selection and meticulous post-operative
management play a major role in the outcome.
–– There are several different types of decompressive craniectomy:
¾¾ The lateral temporal or frontotemporal approach
¾¾ The bifrontal approach
¾¾ The suboccipital approach.
–– Traditionally, craniectomy is planned according to the area of infarct.
–– A wide craniectomy with a duraplasty is, routinely, recommended.
–– Bifrontal craniectomy is more commonly employed in traumatic brain
injury, especially in children.
–– Duraplasty is performed with either silastic lyodura or pericranial grafts.
–– This achieves smooth bulging rather than fungus like herniation of the
brain into the craniectomy, avoiding shearing injuries, impairment of
venous drainage, and enhancement of cerebral oedema.
–– Complications: The complication rate after decompressive
craniectomy is low and has no influence on the patient’s prognosis.
Few complications have been reported in the literature; subdural
haemorrhage as well as hygroma has occurred. Puncture was found
728
to be sufficient for the treatment of the hygroma. Next frequent is,

hydrocephalus; which may require ventriculo or lumboperitoneal shunt.
There is no report of death or permanent deficits related to the surgical
decompression itself.
–– Outcome: Decompressive craniectomy appears most promising as a
method of avoiding death from brain compression.
Revascularisation Procedures
•• The role of revascularisation procedures in acute stroke is still in the
experimental stage.
•• Emergency carotid endarterectomy is a controversial indication, becoming
less and less controversial of late. However there is no randomised trial.
•• Patients must have an angiographically demonstrated lesion and no
infarction on a CT.
•• Recent reports suggest moderate success of emergency carotid
endarterectomy in patients: (a) With cresendo TIAs; (b) with severe stenosis
in angiography; and (c) with disappearance of a previously auscultated
bruit, presumably indicating acute occlusion.
•• The presence of good collateral flow is a favourable prognostic sign.
•• Other procedures such as posterior circulation bypass, vertebral
endarterctomy, arterial anastomses and correction of subclavian steal have
not been tested sufficiently.
•• A number of experimental studies on embolectomy of intracranial vessels
have also been done.
•• Tissue plasminogen and interventional endovascular procedures are more
often preferred.
Haemorrhagic Stroke
•• As mentioned earlier, about 20% of strokes are haemorrhagic, which is due
to “spontaneous” intraparenchymal haematoma (SICH) in 10% of cases,
and haemorrhagic transformation (HT) of ischaemic stroke in 10% of cases.
•• HT may vary from patchy petechial bleeding to more confluent
haemorrhages, representing multifocal extravasation of blood from
capillaries or venules.
•• Approximately 20% of patients with cardioembolic stroke have haemorrhagic
transformation in the infarcted zone, usually occurring within 48 hours.
•• The pathogenesis of HT appears to relate to reperfusion and bleeding
from recanalised but ischaemically injured vessels by the natural, dynamic
dissolution of thrombi.
•• Reperfusion into the ischaemically injured vessels can therefore result in
varying degrees of blood extravasation through the damaged blood-brain
barrier.
•• It is suggested that hyperglycaemia, hypertension and restoration of blood
flow to ischaemic territories were strong risk factors for a haemorrhagic
infarct to develop.
•• On CT, HT appears as a discontinuous heterogeneous mixture of high and
low densities occurring within the vascular territory of the infarct in contrast
to SICH which appears as a discrete, homogeneous collection of blood
that often exerts mass effect and may extend beyond the original infarct
boundaries or even into the ventricles.
729
•• Traditionally, non-traumatic intracerebral haemorrhage is defined as

‘spontaneous’ intra-cerebral haemorrhage (SICH); it may, further be
classified as primary or secondary depending on the underlying cause.
•• Primary ICH accounts for approximately 70−80% of cases and is due to
spontaneous rupture of small vessels damaged by hypertension or amyloid
angiopathy.
•• Secondary ICH is associated with a number of congenital and acquired
conditions such as vascular anomalies, coagulopathies, tumours and
various drug therapies.
•• The common sites in order of occurrence are the basal ganglia, thalamus,
subcortical white matter of the cerebral lobes, cerebellum and brainstem.
•• Men are more likely to suffer an SICH than women and the likelihood
increases with age.
•• Cerebrovascular damage to small arteries and arterioles due to chronic
hypertension is recognised as the most significant cause of primary SICH.
•• Cerebral amyloid angiopathy (CAA) is the other major cause of primary
SICH and an important cause of lobar SICH in elderly populations.
•• In CAA, amyloid protein is deposited in the media and adventitia of cortical
and leptomeningeal blood vessels.
•• Histological examination of brain tissue obtained during surgery or at
autopsy is necessary for the definitive diagnosis of CAA.
•• Vascular anomalies are the second most common cause of SICH overall.
•• Venous malformations are the most frequently occurring vascular lesion
demonstrated in autopsy and radiological series.
•• Haemorrhage is not an uncommon presentation in cases of previously
unsuspected brain tumour; melanoma, choriocarcinoma, renal cell
carcinoma and bronchogenic carcinoma are the most frequent tumours
responsible for producing ICH.
•• Hypertension continues to be the single greatest modifiable risk factor
for SICH.
•• Diabetes mellitus is more commonly associated with SICH than with SAH.
•• Other risk factors include anticoagulants, especially in elderly patients
and hepatitis C virus infection as a result of subclinical clotting disorder or
vessel wall friability.
•• Pregnancy and puerperium can be associated with SICH due to dural
venous sinus thrombosis and eclampsia.
•• The clinical presentation is of a sudden onset of focal neurological deficit
progressing over hours with accompanying headache, nausea, vomiting,
altered consciousness and elevated blood pressure.
•• Supratentorial haemorrhage is commonly accompanied by vomiting and
altered consciousness, which is rare in ischaemic stroke.
•• Elevation in blood pressure occurs in as many as 90% of patients with SICH.
•• Seizures occur in approximately 10% of patients.
•• The type of focal neurological deficit, of course, depends on the location
of haematoma.
•• Blood may rupture into the ventricles and cause hydrocephalus.
•• Rarely, blood finds its way into the subarachnoid space.
•• Depending on clot size and location, this can result in brain herniation,
compression of the brainstem and death.
730
Investigations
•• Haematomas, even just a few millimetres in diametre, are rapidly and
accurately identified on CT scans.
•• In addition to the size and location of the SICH, CT can also suggest
potential causes, such as tumour, vascular malformation or aneurysm, and
SICH related complications, such as hydrocephalus, oedema, herniation
and intraventricular extension, are easily identified.
•• Haematoma expansion and oedema formation are believed to be the major
factors involved in secondary deterioration in level of consciousness, which
occurs within the first 24 hours after onset.
•• Haematoma expansion, reportedly occurs in 14−38% within the first
24 hours of admission.
•• Five factors were found to be associated with enlargement of the clot:
(1) admission shortly after onset of symptoms; (2) heavy alcohol
consumption; (3) irregular shaped haematoma; (4) reduced level of
consciousness and (5) low level of fibrinogen.
•• Haematoma volume calculation by CT helps in deciding on surgery.
•• Calculation of haematoma volume is directly possible with special software.
•• If direct volume measurements are not possible, a rapid, simplified method
of determining haematoma volume has been described and validated.
•• The formula used (A x B x C)/2 is an approximation for the volume of an
ellipsoid where A is the greatest haemorrhage diameter on axial CT scans,
B is the largest diameter 90° to A and C is the number of CT slices with
haemorrhage multiplied by the slice thickness.
•• In clinical practice, these measurements are usually performed informally.
•• MRI is more sensitive in detecting cavernous malformations than CT
scanning or angiography.
•• The MR imaging appearance of SICH is complex and depends on
haemoglobin breakdown products over time.
•• Four-vessel angiography may be needed for a definitive diagnosis of the
aetiology.
Pathophysiology
•• Haemorrhage most commonly results from rupture of the small penetrating
arteries damaged by the degenerative effects of chronic hypertension.
•• In 1868, Charcot and Bouchard described the rupture of “microaneurysms”
as the cause of SICH.
•• Recent investigators have questioned the existence of such microaneurysms,
suggesting that many of these structures are complex vascular coils,
subadventitial haemorrhages, or extravascular clots resulting from
endothelial damage by the haematoma.
•• The vasculopathy of chronic hypertension affects the perforating arteries
resulting in lipohyalinosis or focal necrosis.
•• This helps explain the distribution of hypertensive haemorrhages in
territories supplied by the lenticulostriate arteries (basal ganglia), the
thalamoperforating arteries (thalamus), the perforating branches of the
basilar artery (pons), and the superior and anterior inferior cerebellar
arteries (cerebellum).
•• Lobar haemorrhages in the elderly are often considered to be a result
of amyloid angiopathy, which preferentially involves the cortical and
leptomeningeal blood vessels.
731
•• Primary tissue damage and distortion occur at the time of haematoma

formation when the blood spreads between planes of white matter cleavage.
•• Both necrotic and apoptotic neuronal death appear to play a role.
•• Blood and plasma products, and thrombin formation mediate many
secondary processes initiated after SICH.
•• Inflammatory mediators from the blood can induce an inflammatory reaction
in and around the haematoma. Neutrophils, macrophages, leucocytes and
activated microglia are found associated with lesion.
•• The release of cytotoxic enzymes, free oxygen radicals, nitric oxide and
products of the phospholipid cascade are thought to contribute to secondary
neural injury and cell death.
•• Breakdown of the haematoma consists of invasion by macrophages,
progression of surrounding oedema, development of microvessels at the
clot margin and, eventually, gliosis.
•• The end result is a haemosiderin-stained scar or a cavity containing old
blood surrounded by fibrous tissue.
Management
•• The management of intraparenchymal haemorrhage is essentially the
same and as controversial as in ischaemic infarcts; the clot is the additional
problem.
•• In general, there has been a pessimistic attitude among many medical
professionals, including neurosurgeons, regarding treatment of SICH.
•• Some surgeons prefer a non-surgical approach.
•• Their claim is the damage occurs at the time of bleeding as the blood rips
through the brain and that attempts to remove the clot will only add to the
trauma.
•• Some others advocate early surgery in spite of the additional risk of
damaging the intact brain tissue.
•• They claim that the neurological deterioration does not always respond to
medical therapy alone, and, therefore, removal of haematoma should be
accomplished as soon as possible to decompress the clot and decrease
ICP to prevent secondary deterioration, and to improve perifocal vasogenic
oedema and local cerebral blood flow by preventing compartmental
pressure changes and consecutive reduction of the blood flow perfusion
pressure or by removing the changes caused by toxic breakdown of blood
byproducts.
•• Patients with relatively normal consciousness (GCS Scores 13−15) rarely
require surgery, whereas deeply comatose patients (GCS Scores 3−5)
rarely benefit from surgery.
•• There is good theoretical rationale for early surgery.
•• Haematoma evacuation may decrease the toxic effects of blood and plasma
break down products, diminish surrounding oedema and ischaemia, and
prevent haematoma expansion.
•• A reduction in haematoma volume in experimental studies decreases mass
effect, lessens ICP and limits the potential stimulus for oedema formation
and cell death.
•• Raised ICP is also treated, when appropriate, by aggressive medical
measures.
•• The ideal goal of surgical treatment of ICH is to remove as much blood clot
as possible, as quickly as possible, with the least amount of brain trauma
from the surgery itself.
732
•• If possible, surgery should also remove the underlying cause of ICH, such
as an arteriovenous malformation, and prevent complications of ICH such
as hydrocephalus and mass effect of the blood clot.
•• Neurosurgeons and neurologists invariably advocate that large cerebellar
haemorrhages with compression of the brainstem or obstruction of
the fourth ventricle should be surgically removed as soon as possible.
Associated hydrocephalus may require a drainage procedure.
•• Craniotomy and evacuation of the clot has been the standard approach for
removal of intraparenchymal haemorrhage and remains the most common.
•• In addition, a decompressive craniectomy with a duraplasty is performed
if necessary to combat brain swelling.
•• Its major advantage is adequate exposure to remove the clot. It is not
difficult or time-consuming.
•• The major disadvantage of a more extensive surgical approach is that it
may lead to further brain damage, particularly in patients with deep-seated
haemorrhages.
•• In addition, the effectiveness of clot removal by craniotomy is far from ideal.
Newer Techniques
•• The grim results of conventional craniotomy have stimulated a search for
more tolerable, less traumatic and safer methods of clot removal.
•• Technical advances in removal of ICH include improved localisation of the
haemorrhage by stereotactic devices or use of intra-operative ultrasound
and better surgical techniques.
•• Stereotactically controlled endoscopic evacuation is gaining popularity.
•• Innovations in devices to break up and remove the blood clot include,
modifications of an Archimedes screw inside a cannula, a specially
designed ultrasonic aspirator, a modified nucleotome, a double track
aspiration and intra-operative CT monitoring.
•• Clot evacuation may be combined with pharmacological therapy targeting
the inflammatory response, shown to develop around the haematoma and
leading to delayed cellular death as observed in experimental animal models.
•• Fibrinolysis aids rapid dissolution of the remaining blood.
•• The aim is to achieve a mass reduction as well as to reduce the extension
of perifocal oedema and minimise the amount of tissue damage.
•• Instillation of thrombolytics has also been used successfully for
haemorrhage within the ventricular system as well.
•• The most commonly used thrombolytic protocol has been administration
of 6,000 U of urokinase once or twice daily via a catheter into the bed of
the haematoma with subsequent drainage and aspiration.
•• A urokinase wash out can be performed for up to 7 days after the bleeding.
This procedure is often repeated over several days until the majority of the
haematoma has been aspirated.
•• Haematoma puncture and catheter placement for fibrinolytic therapy could
be achieved with high accuracy and safety using frameless stereotaxy.
Outcome
•• The natural course of spontaneous ICH leads to a 30-day mortality rate of
approximately 45% or more.
•• Spontaneous ICH is associated with a higher mortality rate than either
ischaemic stroke or SAH.
733
•• The patient’s initial level of consciousness, haematoma size, and

intraventricular extension of blood have proven to be accurate predictors
of outcome.
•• Less commonly, age, sex, hypertension and mass effect may indicate
harmful effects on outcome in patients with ICH.
•• Recently, three randomised control trails evaluating new strategies for the
treatment of the ICH have been completed.
•• The International STICH trial (early surgery versus initial conservative
treatment in patients with spontaneous supratentorial ICH) concluded that
there is no evidence of an overall benefit of early surgery when compared
to initial conservative treatment. One finding in a predefined subgroup,
that patients with superficial haematomas might benefit from surgery
(craniotomy), needs further exploration.
•• Stereotactic aspiration combined with instillation of fibryinolytic agent (the
SICHPA trial): The trial was prematurely stopped due to low recruitment.
A cautious conclusion could be made that stereotactic aspiration of
supratentorial haematoma after instillation of a plasminogen activator can
be performed safely. It may reduce the haematoma volume significantly.
•• Ultra-early haemostatic therapy by using the recombinant activated factor
VIIa (the Novo-7 trial): Treatment with activated factor VII within 4 hours
reduced haematoma expansion, decreased mortality, and improved clinical
outcome significantly, despite slight increase in the risk of thromboembolic
events.
•• The patients with smaller haematomas who are alert, stable or improving
should be treated medically and the patients with larger haematomas who
show progressive neurological deficit, prolonged functional impairment and
intracranial hypertension should be treated surgically.
•• Patients with a GCS score less than 5 should also be treated medically
because they generally die or have extremely poor functional outcome that
cannot be improved by surgery.
•• Easily accessible supratentorial haematomas with mass effect, especially in
the young and in those with a GCS score greater than 5, must be evacuated.
•• Patients with cerebellar haemorrhages greater than 3 cm or in whom
brainstem compression and hydrocephalus are present, should undergo
evacuation of the clot.
Pontine and Midbrain Haematomas
•• Pontine haemorrhages are devastating events. This haemorrhage is most
commonly at the junction of the tegmentum and the basis pontis.
•• The classical findings are those of quadriplegia, pin point pupils, paresis of
horizontal eye movements and rapid progression to coma.
•• Initially, the weakness may be asymmetrical but in the later stages, as the
neurological deficits advance, quadriplegia predominates.
•• The pupils are classically pin-point because of interruption of bilateral
sympathetic fibres.
•• Hyperpyrexia can occur but its abscense does not preclude the diagnosis.
•• These are unique brainstem lesions.
•• The presentation is acute in about two thirds of the cases, and subacute
and chronic cases do occur.
•• Presentation is with neuro-ophthalmological abnormalities, loss of
consciousness and headache.
•• This may be accompanied by hemiparesis, hemisensory loss or ataxia.
734
•• Vascular malformations are suspected in about a third of cases and in a

similar number no underlying cause is found.
•• Most patients improve with supportive care, although in rare instances,
surgery may be required if there is an underlying vascular malformation
like cavernous angioma.
SURGERY FOR STROKE REHABILITATION

•• There are no pharmacological measures available to enhance central
nervous system restorative processes after acute stroke, and implantation
of stem cells provides one promising approach, not only for cell replacement
but also for the provision of therapeutic molecules.
•• Stem cell therapy is still at the beginning of the road.
•• Cell transplantation is an experimental approach to restore brain function
in neurodegenerative disorders such as Parkinson’s and Huntington’s
disease.
•• Various cell types are under investigation in experimental stroke studies.
•• Human neuronal cells can be produced in culture, delivered frozen to a
hospital, thawed and processed, and implanted stereotactically into the
brain of patients with stroke.
•• Stem cell research presents many ethical and scientific questions as well
as future challenges.
•• Validation of neural transplantation and any other treatment for stroke
should critically be assessed in laboratory experiments and limited clinical
trials.
Section VIII: Tumours of the Spine and Spinal Cord
100
CHAPTER Clinical Features and
Diagnosis
Ravi Ramamurthi  Santhosh Mohan Rao K
TUMOURS OF THE SPINAL CORD

•• According to their anatomical location, spinal tumours are conveniently
classified as extradural and intradural, although some tumours could be
both inside and outside the dura.
•• Intradural tumours could be intramedullary or extramedullary.
•• Benign and malignant neoplasms may arise from intraspinal structures like
the meninges, spinal cord, nerve roots, blood vessels and other tissues.
Primary Extradural Tumours

•• Neurinomas, meningiomas and lipomas occur in that order of frequency.
•• Extradural cysts, congenital or acquired, may cause cord compression as
also a traumatic or spontaneous spinal extradural haematoma.
•• The other causes of extradural compression are non-specific granulomas,
tuberculomas and hydatid cysts.
Intradural Extramedullary
•• These tumours are the most common intraspinal tumours, neurinomas and
meningiomas being the most frequent.
•• Due to the presence of the filum terminale, intradural extramedullary
ependymomas can occur in the cauda equina region.
•• Huge tumours growing in the region of the cauda equina have been termed
giant tumours of the cauda equina and include neurinomas, meningiomas
and ependymomas.
Intramedullary Tumours
•• Most of the intramedullary tumours are malignant and belong to the glioma
group.
•• Both astrocytomas and ependymomas are more benign in the spinal cord
than in the brain. Glioblastomas are rare in the cord.
•• Intramedullary tumours may become partly extramedullary when they break
through the confines of the cord.
•• Most of the developmental tumours, epidermoids, dermoids and lipomas
are intramedullary lesions.
•• Angiomas, AV malformations and haemangioblastomas also belong
to the same group, though the bulk of these lesions may be truly
extramedullary.
Section VIII • Tumours of the Spine and Spinal Cord
736
TUMOURS OF THE VERTEBRAL COLUMN

•• Benign tumours of the vertebral column are rare, and include haemangioma,
chondroma, giant cell tumour, osteoma and fibroma.
•• Aneurysmal bone cyst usually affects the posterior neural arch, i.e. the
spinous process, the lamina and the transverse process, producing a cystic
enlargement of these structures.
•• Other benign lesions are chondromas, chondromyxoid fibroma and giant
cell tumour secondary to primary hyperparathyroidism.
•• Non-neoplastic benign lesions of the vertebral column that cause cord
compression are multiple hereditary exostoses, Paget’s disease, fibrous
dysplasia, achondroplasia, severe kyphoscoliosis and fluorosis.
•• Secondary malignant deposits are the commonest tumours of the vertebral
column. Breast, lung, thyroid and prostate are the common sites of the
primary lesion.
•• Reticuloendothelial tumours, like lymphomas and multiple myelomas, may
cause multiple deposits in the bone.
Intraspinal Extension of Paravertebral Tumours

•• Malignant lesions, like neuroblastomas, Ewing’s tumour, reticulum cell
sarcoma, lymphosarcoma and Hodgkin’s disease, frequently invade the
extradural space through the intervertebral foramen or by destroying the
bone.
•• Benign paravertebral lesions may also cause cord compression or cord
ischaemia.
•• Tumours in the neck, mediastinum or the abdomen may rarely extend into
the canal through the intervertebral foramina, for example, neurofibromas,
ganglioglioma, sympathicoblastoma, dermoids and benign cysts.
PATHOPHYSIOLOGY OF
CORD COMPRESSION
•• Rapidly growing lesions cause severe loss of function as there is no time
for the spinal cord to adjust itself.
•• On the contrary, a slow growing tumour may attain a large size and the
cord may still be viable although displaced and thinned out.
•• The lesion may compress and occlude vascular structures on the surface
of the cord or in the intervertebral foramina.
•• As the lesion grows, the veins are compressed resulting in congestion
and oedema.
•• Arterial compression occurs at a later stage and may sometimes lead to
distant effects as happens when the vertebral artery is compressed by a
foramen magnum lesion.
•• Pressure at the level of the 4th and 5th dorsal segments may cause a
greater deficit because of the watershed area in the vascular supply of
the cord at this level.
•• Extradural metastatic tumours often cause symptoms by interfering with
the vascular supply of the cord.
•• Vascular tumours may produce a steal syndrome by taking away the blood
from the affected region of the spinal cord.
•• In addition to the vascular effects, direct pressure on the cord and nerve
roots leads to interference with conduction, the long tracts being affected
early.
Chapter 100 • Clinical Features and Diagnosis
737
•• The presence of a tumour interferes with the normal movements of the

cord which occur during movements of the spinal column. Such impairment
contributes to cord damage.
•• In long-standing tumours, there may be gliosis in the spinal cord due to
ischaemia and the recovery may be incomplete, despite complete removal
of the tumour.
SYMPTOMS AND SIGNS OF

SPINAL COMPRESSION
•• The symptoms and signs include those produced by the involvement of
the nerve roots (posterior and anterior), the cord segments and the long
tracts, viz. the motor, sensory, autonomic and other tracts.
Involvement of the Posterior Root

•• Root pain, a symptom of posterior nerve root involvement, is the result of
pressure or, more commonly, of stretching of the nerve root by the tumour.
•• It occurs as an early symptom of an extramedullary tumour, and is usually
unilateral in benign tumours and bilateral in malignant tumours.
•• The pain radiates from the proximal to the distal region, although,
occasionally, a root irritation may manifest itself as a spread of pain from
the periphery to the centre.
•• The pain is often of a burning, hyperaesthetic type in the early stages.
•• When the thoracic roots are involved, the constricting pain is referred to as
girdle pain, especially when bilateral.
•• Root pain is increased by coughing, sneezing and movements of the spine,
or by any manoeuvre which increases intraspinal pressure like compression
of the jugular veins.
•• Though root pain is most commonly seen in extramedullary tumours, it may
appear in about 20% of intramedullary tumours also.
•• D4 root pain on the left side may simulate heart disease.
•• D8–D10 root pain may simulate diseases of abdominal organs, like the
gallbladder, appendix and kidney, while cauda equina pain may simulate
disease of the pelvic viscera.
•• Irritation of the posterior root may result in pruritis in the dermatomal
distribution and a rash.
•• With posterior root involvement, objective sensory loss occurs when at
least two adjacent roots are involved.
Involvement of the Anterior Nerve Root and

Anterior Horns
•• As the symptoms and signs of involvement of the anterior nerve root and
the anterior horn are the same, it is clinically impossible to differentiate
one from the other.
•• While the anterior nerve roots are involved only in extramedullary tumours,
the anterior horns can be involved in both intramedullary and extramedullary
tumours.
•• Involvement of either the anterior nerve root or the anterior horn is indicated
by progressive lower motor neuron paralysis, wasting and fasciculations of
the involved muscles with loss of reflexes.
•• The symptoms are more conspicuous when the cervical or the lumbosacral
segments of the spinal cord or the nerve roots are compressed.
738
•• In case the dorsal segments are involved, the wasting and weakness of
the paravertebral muscles results in scoliosis only if it involves a large
number of roots.
•• As the muscles have multisegmental innervation, involvement of a single
anterior nerve root or anterior horn cells of one spinal cord segment may
not produce recognisable weakness or wasting of the muscles.
•• Lower motor weakness with wasting or loss of a tendon or a cutaneous
reflex has an early localising value.
•• Fasciculations of the muscles are more common when the anterior horn
cells are involved and, thus, are more frequently seen in intramedullary
tumours. With a careful and detailed search, it is possible to detect
fasciculations in the wasted muscle more frequently.
•• Chronic irritation of the anterior horn cells by tumour or their isolation from
other neuronal influences may occasionally lead to a very high rate of firing
by these neurons, resulting in continuous activity or spasm of the muscles
of the concerned segment or in a localised myoclonus.
Segmental Involvement
•• Although segmental involvement of the cord may occur in extramedullary
lesions, it is common in trauma, haematomyelia and intramedullary lesions.
•• The clinically significant areas affected are the anterior horns and the
crossing of the spinothalamic tracts, in addition to the long tracts affected
at that level.
•• Anterior horn cells will be involved early when the tumour is situated either
anterior or anterolateral to the spinal cord, and late if the tumour is situated
posterior to the spinal cord.
Involvement of the Long Sensory Tracts

•• Subjective numbness, tingling, burning, sensation of cold and ‘pins and
needles’ are produced by irritation of the sensory pathways in the spinal cord.
•• Subjective sensory disturbances are more common in intramedullary
lesions.
•• In cervical lesions, irritation of the posterior column leads to Lhermitte’s
sign. The patient feels a sudden electrical shock-like sensation all over the
body when the neck is flexed.
•• The Lhermitte’s sign is seen in 38% of patients with multiple sclerosis (MS).
It is not specific to MS. This is seen in patients of MS with plaques at DREZ,
subacute combined degeneration of the cord, cervical extramedullary
tumour and radiation myelopathy.
•• Reversed Lhermitte’s sign is the same symptom seen in neck extension and
is due to the buckling of the ligamentum flavum into the already compressed
cervical cord as seen in cervical spondylosis.
•• An increase in pyramidal tract deficit caused by neck flexion and a
corresponding improvement of the symptom with neck extension is
suggestive of a compressive pathology in the cervical cord. This is called
Bristow’s symptom.
Sensory Disturbances
•• The objective disturbances vary according to the site of origin of the lesion
and direction of its spread and, thus, many varieties of involvement may
be seen.
739
•• A few definite patterns are identifiable with regard to the levels of sensory
loss, their direction of spread and the modalities involved. From these it is
possible to differentiate between extramedullary and intramedullary lesions.
•• There is a lamination or grouping of fibres in the lateral spinothalamic tract,
the fibres originating from the most distal parts of the body being situated
peripherally and those from the proximal parts of the body situated centrally.
•• In extramedullary tumours the sensory disturbance is maximal in the distal
parts of the body, being minimal near the level of the lesion. In other words,
the sensory disturbance is of the ascending type, the sensory loss starting
in the distal parts of the body and slowly progressing proximally.
•• In contrast, in intramedullary growths the maximum sensory disturbance is
at and below the segmental level of the lesion. The degree of sensory loss
diminishes in a descending direction and hence a suspended anaesthesia
or ‘anal sparing’ or sparing of sacral dermatomes is a characteristic feature
of an intramedullary growth.
•• In intramedullary growths, there may be dissociation between the degrees
of sensory loss for the various types of sensory modalities. This dissociation
of anaesthesia is not as commonly seen in intramedullary tumours as in
syringomyelia.
•• It must also be remembered that in both extramedullary and intramedullary
tumours, the intensity of loss of tactile sensation is less than that of pain
and temperature because of the presence of dual pathways for touch.
MRC Classification of Sensory Nerve Dysfunction
Grades:
S0—No sensation.
S1—Deep pain sensation.
S2—Skin touch, pain and thermal sensation, i.e. protective sensations present.
S3—S2 along with accurate localisation but deficient stereognosis. Cold
sensitivity and hypersensitivity are often present.
S3+—Object and texture recognition but not normal sensation. Good but not
normal two point discrimination.
S4—Normal sensation.
Motor Disturbance
•• Involvement of the pyramidal tract in the spinal cord results in loss of
voluntary power, spasticity, exaggerated tendon reflexes and positive
Babinski’s sign on the same side.
•• The ipsilateral limbs are affected first, followed by the opposite limbs, unless
the tumour is in the midline, when both sides are affected simultaneously.
•• Asymmetry in weakness, in spasticity and in reflex disturbances between
the two sides is characteristic of a tumour, in contrast to degenerative
disorders like primary lateral sclerosis or amyotrophic lateral sclerosis.
•• By the time the compression is far advanced, the asymmetry gives place to
a symmetric total paralysis on both sides resembling the picture of transverse
myelitis.
•• An extramedullary tumour in the cervical region affects the ipsilateral upper
limb first, followed by the ipsilateral lower limb, the opposite lower limb and
finally the opposite upper limb.
•• Pressure on the spinocerebellar tracts produces ataxia and tremor in the
limbs of the same side.
740
•• Hypotonia may occur early and may be so prominent as to suppress

exaggeration of reflexes even when Babinski’s sign has become positive.
Sphincter Disturbances
•• Disturbances of micturition appear when there is a loss of function in both
the pyramidal tracts, in the sacral spinal cord centres or in the corresponding
nerve roots in the cauda equina.
•• Intramedullary tumours affect bladder function early, as the upper motor
neuron fibres to the bladder lie deeper in the lateral column and occupy
an area nearer the centre of the spinal cord.
•• The autonomic fibres subserving micturition travel on the dorsal aspect of
the lateral columns.
•• If the tumour is situated above the level of the sacral centres of micturition
and the compression is partial, uninhibited neurogenic bladder results,
manifesting as urgency and precipitancy.
•• Advanced compression results in a reflex or an automatic bladder.
•• Pressure on or destruction of the sacral centres or the corresponding roots
of the cauda equina causes an autonomous bladder.
Bowel Function
•• Tumours above the level of the sacral centres impair voluntary control
of the sphincter and the sensation of rectal urgency is lost, resulting in
constipation.
•• Involvement of the sacral centres or the corresponding roots of the cauda
equina leads to paralysis of the sphincter and faecal incontinence.
Disturbances of Autonomic Functions

•• Interference with the sympathetic pathways in the spinal cord leads to a
characteristic dryness of the skin below the lesion.
•• By running one’s hand across the body the level of the tumour could be
localised by noting the level at which the dryness of the skin starts.
•• The skin of the involved areas is not only dry but often warm (occasionally
cold) and flushed also.
•• Segmental hyperhidrosis is an uncommon finding which is usually associated
with irritation or infiltration of preganglionic sympathetic fibres or the
sympathetic chain.
•• Trophic disturbances of the skin may also be seen.
•• Autonomic, sensory and motor deficits also interfere with the complex sexual
function.
•• Rarely, priapism may be seen in thoracic cord lesions, with retention of the
ejaculatory mechanisms.
•• At lower levels sexual function is lost.
Skeletal Symptoms and Signs

•• Obliteration of cervical or lumbar lordosis with limitation of movements may
be seen in extramedullary tumours of the spinal canal and is the result of
muscle spasm due to root irritation.
•• Intramedullary tumours, when slow growing, may cause scoliosis due to
weakness of the muscles supplied by the involved segments.
•• In primary and secondary malignant tumours of the vertebral column, the
spinous process of the affected vertebra often becomes tender.
741
•• A tumour situated at the level of the D4 vertebra will cause tenderness of

the D6 spine, as the concerned spinal cord segment is D6.
•• In tumours of the cauda equina several spines of the lumbar vertebra may
be tender, as several roots are stretched.
•• Head compression can elicit radicular symptoms. This is known as
Spurling’s neck compression test.
•• There are three methods of eliciting spinal tenderness, each with its own
significance.
•• The first is direct tenderness which is elicited by pressure over the spinous
process. A pathology involving the process or an advanced stage of the
pathology of the vertebral body will cause tenderness.
•• The second is twist tenderness elicited by attempting to twist the spinous
process between the thumb and the hand. Early vertebral pathology and
posterior element pathology produce tenderness.
•• The third method is deep thrust tenderness which is elicited by a guarded
thrust with the proximal part of the ulnar side of the fist. This must be done
very carefully.
CLINICAL FEATURES OF TUMOURS AT

DIFFERENT LEVELS
Cervical Region
•• Intracranial symptoms may appear early or later and include papilloedema
and hypoglossal weakness or paralysis in tumours at the foramen magnum
and upper cervical region.
•• Sleep apnoea can be a presenting symptom.
•• Suboccipital headache is an early and constant feature of lesions in this
region, present long before the signs of cord pressure become evident.
This headache is due to spasm of the suboccipital muscles as well as to
irritation of the C2 sensory nerve root.
•• Pain in the C2 dermatome becomes clinically significant if numbness and
paraesthesia develop in the same dermatome.
•• Torticollis may occur due to unilateral muscle spasm.
•• Signs and symptoms, referable to a clinical level far below the tumour, may
occur and confuse the clinical picture, e.g. wasting of the small muscles of
the hand and of the muscles of the neck may be seen in foramen magnum
tumours and is due to compression of one or both vertebral arteries or
the anterior spinal artery, whose branches supply the cord down to the
D4 segment.
•• Compression of the vertebral arteries may occur on turning the neck
resulting in vertigo, dizziness, unsteadiness or syncope.
•• Lesions above C4 are said to be in the blind zone of the cervical cord.
•• They can be elicited by the Shimizu reflex which was first described by
Shimizu in 1993.
•• The patient is seated with the elbow flexed to 90 degrees and the forearm
supinated. The examiner taps the tip of the spine of the scapula in a caudal
direction with the reflex hammer. The reflex involves movement of the
scapula from an abrupt stretching of the upper part of the trapezius. The
reflex is said to be positive if there is scapular elevation with or without
abduction of the humerus and is suggestive of cord compression between
C2 and C4.
742
•• Lesions at the 5th cervical segment cause wasting and weakness of the
deltoid.
•• Inversion of the radial reflex with loss of the biceps jerk, and an exaggerated
triceps reflex point to a lesion at the C5 level.
•• When the biceps is intact but the triceps is involved, the lesion must be as
high as the C6 nerve root.
•• The triceps is spared in C7 lesions.
•• Examination of the hand muscles will differentiate between C7, C8 and
T1 lesions.
•• C5 sensory involvement causes hyperaesthesia or pain over the shoulder
and the lateral aspect of the arm, in C6 root involvement there is pain or
diminished sensation along the outer aspect of the forearm, the thumb
and the index finger.
•• Pain radiating to the middle finger indicates C7 involvement, whereas
irritation of C8 and T1 causes pain along the ring and little fingers and the
medial aspect of the upper limb.
•• Horner’s syndrome may be elicited in T1 level lesions due to involvement
of the sympathetic system.
•• Clinical assessment of the diaphragm is important in all cases of cervical
spine lesions.
•• Sniffing is an important sign which is impaired in diaphragmatic lesions.
•• Hoover’s sign wherein there is epigastric angle widening with intercostal
contraction; this is counterbalanced by the diaphragm and is absent in
paresis of the diaphragm.
•• Tidal percussion done in the lower border of the 5th rib in the midclavicular
line gives an idea of diaphragmatic excursion. The normal diaphragm moves
up to the 6th intercostal space during inspiration.
Dorsal Lesions
•• The level of the lesion in the dorsal region can be assessed accurately
from the root pain or sensory loss.
•• In the upper part of the trunk, the C3–C4 roots supply the infraclavicular
region and the D3 root the area just below on the trunk; the D4 level is at
the level of nipple, D6 over the epigastrium, D10 at the umbilicus and D12
over the hypogastrium.
•• When the lesion is at D10 level, the upper abdominal muscles are normal
while the lower muscles are paralysed. This results in upward movement
of the umbilicus when the patient attempts to sit up from a supine position
(Beevor’s sign).
•• Extensive involvement of the dorsal cord may result in wasting of the
paraspinal muscles leading to kyphosis or scoliosis and is more common
in intramedullary lesions.
Upper Lumbar Segments

•• Following compression of the first and second lumbar segments the
abdominal reflexes are preserved, the cremasteric reflex is lost and the
knee jerks are exaggerated.
•• If the tumour involves the second, third and fourth lumbar segments, the
cremasteric reflexes are intact, the knee jerks are diminished or lost and
the ankle jerks are exaggerated.
•• There is wasting of the quadriceps with weakness or loss of extension of
the knee.
743
Epiconus Syndrome
•• This results from involvement of the L4-L5-S1 and S2 spinal cord segments.
•• It is characterised by weakness of abduction, external rotation and
extension of the thigh, and impaired flexion of the knee, and dorsi and
plantar flexion of the ankle.
•• Sensory disturbances occur in the L4 to S2 dermatomes.
•• The knee jerk is preserved and the ankle jerk is lost.
•• The bladder and rectum empty reflexly.
Conus Syndrome
•• The lower three sacral and the coccygeal segments comprise the conus
medullaris.
•• The clinical picture due to involvement of the conus is characterised by:
1. Retention of urine with overflow
2. Faecal incontinence
3. Impotence and
4. Perianogenital or saddle anaesthesia.
•• Sensory disturances occur in the S3, S4 and S5 dermatomes.
•• There are no motor disturbances in the lower limb.
•• The plantar reflex is flexor and the knee and ankle jerks are normal.
Cauda Equina Syndrome

•• The cauda equina consists of the five lumbar, five sacral and two
coccygeal nerve roots in the spinal canal (a total of about 48 nerve
roots) and extends over several vertebral levels.
•• Thus the clinical picture in tumours of the cauda equina varies according
to the level and the number of nerve roots affected.
•• If the tumour is small, only a few nerve roots will be affected with
corresponding lower motor neuron signs, whereas a large tumour will
implicate all the nerve roots at that level.
•• Pain is a common symptom and occurs in 95% of cases.
•• At the L2 vertebral level all the nerve roots can be implicated excepting
L1 which exits between the L1 and the L2 vertebrae.
•• All the muscles of the lower limb manifest lower motor neuron weakness.
•• Anaesthesia is present anteriorly below the level of the groin including
the genitalia and, posteriorly below the upper part of the buttocks.
•• There is retention with overflow of urine and incontinence of faeces.
•• All the reflexes in the lower limbs are lost.
•• At the L4 vertebral level, the L1, L2 and L3 nerve roots escape. Hence,
sensations are normal over the front of the thigh, and the function of
the quadriceps and the knee jerks are normal.
•• When the lesion is below S2 level, there is no paralysis of the muscles of
the lower limb.
•• A characteristic saddle shaped area of anaesthesia is seen over the
buttocks, perineum, scrotum and penis, and over a small strip running from
the perineum down the posteromedial aspect of the thigh.
•• The anal reflex is lost and the reflexes of the lower limbs are normal.
•• Retention of urine with overflow and rectal incontinence will be present.
•• This is similar to or even identical with the conus syndrome and, therefore,
neurologically it is not possible to differentiate between them.
•• A pure conus medullaris lesion is not seen in practice.
744
•• An extramedullary tumour at the level of the conus compresses both the

cauda equina and the conus. Hence, the clinical picture is mixed in the
early stages, whereas, in the later stages, a pure cauda equina type of
picture is seen.
•• An intramedullary tumour of the conus will initially produce a conus
syndrome, but in advanced cases the enlarged spinal cord compresses the
roots of the cauda equina and produces either a mixed or a cauda equina
type of clinical syndrome.
Differentiation between Extramedullary

(Intradural) and Intramedullary Tumours
•• The clinical differences between an extramedullary and an intramedullary
tumour are summarised in Table 1.
Table 1: Clinical differences between an extramedullary and

an intra-medullary tumour
S. No Feature Extramedullary Intramedullary
1. Root pain Common and early Late and uncommon
2. Sensory loss at the level of Nil or slight Wide
the tumour
3. Dysaesthesiae and paraes- Seldom, if at all Common at all stages
thesiae (due to irritation of
long sensory tracts)
4. Subjective sensation of Characteristic of high Not seen
intense cold cervical tumour
5. Distant sensory loss (due Ascending sensory Descending sensory
to involvement of long disturbance and no dis- disturbance with
sensory tracts) sociation dissociation
6. Muscle spasms (due to Fairly common Infrequent
irritation of anterior nerve
roots)
7. Lower motor neuron Absent except when Wide
paralysis with muscle nerve roots with exten-
atrophy sive motor supply, like
C8 and T1, are involved
8. Upper motor neuron Late Early
paralysis
9. Sphincter disturbances Late unless it is in the Early
region of sacral cord
10. Brown-Sequard type of Late unless it is in the Early
clinical picture region of sacral cord
11. Trophic disturbances Absent Fairly uncommon
of skin
12. CSF protein Marked increase Moderate increase
13. X-ray spine Bone changes common Bone changes only in a
few cases
14. Tenderness of spine Common Uncommon
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•• No single symptom or sign is pathognomonic.

•• The total clinical picture should be critically assessed without giving undue
importance to any one symptom or sign.
ALIGNMENT OF CORD SEGMENTS AND

VERTEBRAE
•• In the adult, the spinal cord ends at the lower border of the L1 vertebral
body.
•• There is a progressive increase in the difference between the cord
segments and the vertebral bodies, from above downwards.
•• The eight cervical cord segments extend from the foramen magnum to the
upper half of the C7 vertebral body.
•• The twelve dorsal cord segments lie opposite the lower half of the C7
vertebral body up to the lower border of the D9 vertebral body.
•• The D12, D8 and D4 cord segments are opposite the D9, D6 and D3
vertebral bodies, respectively.
•• The lumbar cord segments are opposite the D10, D11 and D12 vertebral
bodies.
•• The sacral and coccygeal cord segments, therefore, lie opposite the L1
body.
FUNCTIONAL SCORES IN SPINAL

CORD DISEASE
McCormick Classification
•• McCormick classification of clinical function in patients with intramedullary
spinal cord tumours:
–– Class I: Neurologically normal. Mild focal neurological deficit not sig-
nificantly affecting the function of the involved limb. Mild spasticity or
reflex abnormality. Normal gait present.
–– Class II: Presence of sensorimotor deficit in the involved limb, mild
to moderate gait difficulty, severe pain or dysaesthesia significantly
impairing the quality of life, although the patient can still function and
walk independently.
–– Class III: More severe focal neurological deficit with the patient
requiring a cane or a brace to walk or with significant bilateral UL
involvement, the patient may or may not be able to function indepen-
dently.
–– Class IV: Severe deficit with the patient requiring a wheelchair/cane/
brace with bilateral UL impairment. Patient not walking.
Nurick’s Grading for Cervical Myelopathy

G0: Signs and symptoms of root involvement present, no signs of cord
involvement.
G1: Signs of spinal cord involvement, normal gait present.
G2: Slight difficulty in walking, full time employment is not prevented.
G3: Difficulty in walking present which prevents full time employment. The
patient is ambulant without support.
G4: The patient is not usefully employed and is able to walk only with help/
support.
G5: The patient is chair bound/bed ridden.
746
Frankel’s Grading
A: Absent motor and sensory function.
B: Sensations present, motor function absent.
C: Sensations present, motor present but not useful (corresponds to MRC
grade 2 to 3).
D: Sensations present, near normal motor function.
E: Normal motor and sensory function.
101
CHAPTER
Vertebral Tumours
Deepu Banerji  Pallav Garg  Manoj Jain  Sanjay Behari
BENIGN TUMOURS OF THE SPINE

•• Eight per cent of primary benign bone tumours occur in the spine.
•• Amongst primary tumours of the spine, benign tumours account for
25−35%.
•• Osteoid osteoma, osteoblastoma and aneurysmal bone cyst tend to involve
the posterior elements, whereas the anterior elements are affected by giant
cell tumour, haemangioma and eosinophilic granuloma.
•• Similarly, different tumours tend to occur at different segments of the spine
with giant cell tumours usually seen in the sacrum.
•• Haemangiomas are more commonly seen in the thoracic and lumbar spine.
•• Osteoid osteomas are more commonly seen in the lumbar region, whereas
osteoblastomas equally occur in the thoracic and lumbar spine.
•• Pain is the most common presenting complaint.
•• In adults, this may be confused with the clinical manifestations of a
herniated disc.
•• In children, pain is less often a presenting complaint.
•• Osteoid osteoma and osteoblastoma are characterised by night pain which
is relieved by non-steroidal anti-inflammatory drugs (NSAIDs).
•• The symptoms of myelopathy occur with progressive increase in the size
of the tumour resulting in epidural compression.
•• This occurs more commonly with thoracic tumours due to the narrow canal
diameter at that level.
•• Tumours at the cranial or the caudal end of the spinal axis may occasionally,
present as large mass lesions due to the more capacious spinal canal at
these locations, that results in a relatively delayed neurological involvement.
•• Lesions of the lower end of the spinal canal may present with sphincteric
disturbances.
•• Sometimes, the patient may present with spinal deformity in the form of
scoliosis.
Investigations
•• Plain radiographs show varying features according to the type of the tumour.
•• Sclerotic changes are evident in osteoblastoma and osteoid osteoma.
•• Expansile-lytic lesions are seen in giant cell tumours and aneurysmal
bone cysts.
748
•• Vertebra plana is characteristically seen in eosinophilic granulomas

whereas haemangiomas are identified by their vertical trabeculae.
•• Scoliosis can be seen on the antero-posterior films.
•• MRI is the investigation of choice and reveals the extent of soft tissue
involvement along with the bony component.
•• In osteoid osteoma and osteoblastoma, the surrounding inflammatory
response may be picked up by the MRI giving an impression of a highly
aggressive tumour.
•• A bone scan, although non-specific, is frequently used as a screening tool.
•• In patients with sclerotic tumours, a high tracer uptake is seen.
Treatment
•• Surgical intervention is based upon the presentation and the type of the
tumour.
•• Enneking’s Type 1 (latent) tumours refer to incidentally discovered tumours
which require no treatment. This category includes incidentally discovered
haemangiomas and osteochondromas that are not endangering the thecal
sac.
•• Type 2 (active) lesions refer to symptomatic tumours. These need local
resection with curettage and include osteoid osteoma, haemangioma,
aneurysmal bone cyst and eosinophilic granuloma.
•• Type 3 (aggressive) tumours include giant cell tumour and osteoblastoma
which require wide excision. Adjuvant therapy is determined according to
the surgical decompression performed.
•• Radiation therapy is used in cases of neurological deterioration where
surgery is contraindicated or in cases of highly radiosensitive tumours.
•• Tumours responding well to radiotherapy include haemangiomas and
aneurysmal bone cyst.
•• Radiation therapy carries risk to the underlying neural tissue which needs
to be addressed.
Osteoid Osteoma
•• The lumbar spine is the most commonly affected area.
•• Male patients are affected more than the female ones (2:1).
•• There is no familial or racial predilection with the peak incidence being in
the second decade of life.
•• Pain is usually the presenting symptom with persistent night pain seen in
more than 50% of patients.
•• Radicular involvement is seen in less than 25% of the cases.
•• Scoliosis is seen in up to 70% of the cases.
•• Radiographic changes are seen in the lamina or the pedicle and tend to
involve a single vertebral level.
•• The tumour is seen as an isolated radiolucent area surrounded by a zone
of reactive sclerosis.
•• Sclerotic changes are seen on the radiographs and are due to reactive
bone formation. Hence, bone scan is positive in all the cases.
•• CT is the investigation of choice to delineate this bony lesion and
characteristically shows a well-defined oval area of lucency surrounded
by hyperdense reactive bone.
•• The area of lucency, also known as the “nidus”, may show contrast
enhancement due to the high vascularity of the lesion.
Chapter 101 • Vertebral Tumours
749
•• The treatment is complete surgical excision with curettage.

•• The osteoid osteoma appears as a soft, dark red or yellowish white nodule
surrounded by dense reactive bone.
•• Remission of pain is the indicator of complete excision.
•• Radiotherapy has no role in the treatment of this lesion.
•• At microscopy, irregular and haphazardly arranged woven bone trabeculae
are embedded in a fibrovascular stroma. The amount of woven and
unwoven (osteoid) bone varies among lesions.
Osteoblastoma
•• The thoracic and the lumbar segments are commonly affected.
•• Multiple vertebral levels are more frequently affected.
•• Male patients are affected more than the female ones.
•• These lesions share a common presentation of painful scoliosis with osteoid
osteoma, yet are larger as compared to the latter with a more aggressive
potential.
•• Patients usually present within 6−12 months of symptoms with pain that
persists during the night and is relieved by NSAIDs.
•• Radicular symptoms may occur in 50% of the cases with some cases
showing signs of myelopathy.
•• Another interesting feature is the higher incidence of epidural extension as
compared to paraspinal soft tissue involvement.
•• Radiographs usually reveal expansile-lytic lesions. Sclerotic changes are
evident in 10−15% of the cases.
•• The lesion appears as a “hot spot” on the bone scan and, therefore, this
investigative modality can be used for follow-up of patients.
•• CT scan is the investigation of choice and is very effective in deciding the
surgical plan for the patient. It shows an expansile-lytic lesion with internal
bone formation within the areas of lucency and surrounding sclerosis.
•• At the time of surgery, the tumour gives a variable picture of a homogeneous,
red to purple hypervascular friable granular mass.
•• Histologically, rich fibrovascular stroma with abundant osteoblasts is seen.
Cartilage is absent. The latter feature differentiates it from an osteosarcoma.
•• Epithelioid osteoblastoma is an aggressive malignant variant with atypical
osteoblasts.
•• The treatment is complete surgical resection with radical curettage of
surrounding normal vertebra.
•• Radiotherapy has a role in debilitated patients who cannot undergo surgical
resection.
Osteochondroma
•• All parts of the vertebra are equally affected.
•• A solitary lesion is a cartilage-capped broad based growth on a broad base
or stalk related to the epiphyseal growth plate.
•• Although most of these patients are asymptomatic, they may present with
mass effect in the form of myelopathy.
•• Another characteristic feature is that these tumours tend to stop growing
at skeletal maturity.
•• In cases of persistent growth, malignant transformation to chondrosarcoma
should be suspected.
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•• Both CT and MRI are highly effective as diagnostic modalities with MRI
being preferred since, the soft tissue margin surrounding the tumour can
be better identified.
•• Surgery is indicated only for symptomatic lesions or for lesions which show
persistent growth.
•• Histology shows a hyaline cartilage cap covered by a fibrous membrane,
the perichondrium and an underlying pedunculated bony stalk connected
to the underlying bone without any intervening cortex between the two.
Giant Cell Tumour

•• They are rarely seen before 20 years of age since they occur after skeletal
maturation.
•• They tend to occur more commonly in females.
•• The ends of the spinal column are the favoured sites with the sacrum being
most commonly affected.
•• In fact, they are the most common benign tumours of the sacrum. Sometimes
they are seen in patients with Paget’s disease.
•• Pain at the tumour site is the chief presenting complaint.
•• Due to their predilection for the ends of the spinal column, the duration from
the initiation of symptoms to their detection is much longer, sometimes as
long as 8 months.
•• Thirty to seventy-five per cent of patients present with neurological deficits
in the form of paraparesis with bladder and bowel involvement.
•• On plain radiology, they appear as expansile, septated, lytic lesions with
cortical breach and a small soft tissue component.
•• The vertebral body is more commonly involved.
•• They require complete en bloc resection with wide margins.
•• Grossly, the tumour appears light brown to bloody with focal necrotic areas
with a rubbery feel. The main histological features of giant cell tumours are
sheets of mononuclear round cells, scattered multinucleated osteoclast type
giant cells, with identical nuclei found in mononuclear and multinuclear cells.
•• Due to the vascular nature of the tumours that may result in large amounts
of intra-operative blood loss, pre-operative embolisation is recommended.
Eosinophilic Granuloma
•• This entity is the most benign form of histiocytosis X and manifests as a
solitary benign lesion.
•• This is usually seen in patients less than 20 years of age, with the thoracic
spine being the most commonly affected.
•• The clinical presentation is like that of any other bony tumour.
•• Sometimes, systemic symptoms of fever with weight loss may be seen.
•• On plain radiology, these characteristically show vertebra plana with disc
sparing.
•• On bone scan, they reveal cold spots.
•• MRI may give the false impression of these tumours being aggressive due
to a ‘Flare up’ response that may often occur.
•• Focal lytic areas with sclerosis may also be seen.
•• At histology, histiocytic cells with characteristic cytoplasmic granules (seen
by electron microscopy), known as Birbeck granules, may be seen.
•• The tumour is characterised by spontaneous regression often with an
excellent prognosis.
751
•• Since these tumours tend to spontaneously regress with reconstitution of

the vertebral body, surgical intervention is not always required.
•• Hence, the role of percutaneous biopsy is important, which can provide
tissue diagnosis thereby obviating the need for major surgery.
•• Surgery is indicated in patients with spinal instability and neurological deficit.
There is no role for radiotherapy. Recurrence is rarely seen.
Aneurysmal Bone Cyst

•• These tumours tend to affect patients less than 20 years of age.
•• There is no predilection for either sex.
•• Characteristically, these lesions tend to involve the posterior elements
much more as compared to the vertebral body. In fact, multiple levels of
involvement are commonly seen.
•• Pain is the most common presenting complaint along with spinal deformity
in the form of scoliosis and spinal rigidity.
•• MRI with contrast is the investigation of choice.
•• The lesions are lytic and expansile with a thin reactive bony rim. They
consist of large blood filled spaces and a network of fibrous tissue containing
immature bone, giant cells and macrophages.
•• Multiple septations may be seen within the lesion.
•• Surgical resection with curettage is the treatment of choice. These tumours
are vascular and tend to bleed a lot. Hence, pre-operative embolisation, if
possible, is recommended.
•• Sometimes, embolisation alone is found to be sufficient for controlling
these tumours.
•• Radiation therapy has no role as adjuvant therapy since even partial
resection is sufficient for tumour control. Sometimes, low dose radiation
is pre-operatively utilised to decrease the vascularity of the tumour which
may even be curative.
Haemangioma
•• Haemangiomas are true benign neoplasms of the bone and may
occasionally be hamartomatous in nature.
•• They tend to occur in the third decade of life with a slight predilection for
the female sex.
•• Sometimes, they are seen in patients with systemic conditions such as
Klippel-Trenaunay-Weber syndrome.
•• These tumours characteristically enlarge during the third trimester of
pregnancy, resolve following the delivery, but recur during subsequent
pregnancies.
•• They usually present with pain.
•• Radiographs demonstrate a characteristic vertical striated appearance of
the vertebral bodies due to ossification around areas of haemangioma. This
is termed as ‘honeycomb’ or ‘coudroy cloth’ appearance.
•• On CT, these lesions give the appearance of polka dots. The vertebral body
is more commonly involved than the posterior elements.
•• Many studies have reported contiguous multiple level involvement. The
thoracic spine is more commonly affected.
•• Grossly, the lesion arises from the periosteum or the marrow spaces
producing a honeycomb bloody mass.
752
•• Microscopically, numerous capillary channels with large feeding vessels

are seen.
•• These tumours are usually supplied by the intercostal arteries. Cavernous
vascular channels may also be seen. Angiographically, these lesions
demonstrate extensive tumour blush.
•• Embolisation of the vessels supplying the tumour should be performed
preoperatively, if surgery is being contemplated.
•• Radiotherapy has also been found to be useful. The recommended dose
is 30−40 cGy in a single course over 6−8 weeks.
PRIMARY MALIGNANT TUMOURS OF

THE SPINE
Chordomas
•• These are rare, slow growing tumours with a peak incidence in the 5th−7th
decade of life.
•• These are considered to arise from the remnants of the embryonic
notochord.
•• Male patients are affected more than females.
•• Though chordomas may occur at any level in the spine, the sacrococcygeal
region is the most commonly affected region followed by the clivus.
•• Pain is the most common presenting symptom.
•• It is initially local becoming radicular later on with nerve root compression.
•• A tumour in the lumbar region, may give rise to neurogenic claudication.
•• Bladder and bowel involvement occur late in the course of the disease.
•• Clival tumours present with headache, multiple cranial nerve palsies and
visual disturbances.
•• Myelopathy is seen with cervicothoracic lesions that are compressing the
thecal sac.
•• On MRI and intrathecal contrast sagittal reconstructed CT scans, they
present as destructive lesions usually spanning more than one level, with
disc sparing. Tumour calcification may also be seen.
•• CT helps to define the bony destruction, whereas the soft tissue extent is
shown best by the MRI.
•• Grossly, the tumours appear lobulated, grey, cystic or solid, firm to soft in
consistency. They tend to be well-circumscribed.
•• Microscopically, physaliphorous (soap bubble) cells are seen with a
vacuolated cytoplasm.
•• These tumours are locally aggressive with late metastasis.
•• Sometimes, radical resections result in spinal instability which requires
bone grafting with instrumentation.
Osteosarcoma
•• This is the most common primary malignancy of the skeletal system other
than a myeloma.
•• The spine is relatively less affected as compared to the rest of the skeletal
system.
•• Usually these tumours show a peak in the second decade of life with spinal
tumours appearing later as compared to osteosarcomas of long bones.
•• There is no sex predilection.
•• Pain is the most common presenting complaint which is initially localised.
753
•• Neurological deficits are commonly seen indicating epidural extension of

the lesion.
•• The classical findings in patients with limb osteosarcoma are periosteal
elevation and presence of Codman’s triangle.
•• In the spine, a mixed picture of osteolytic and osteoblastic lesions is seen.
•• Lesions usually involve the body, and posterior element involvement is
much less frequent.
•• Pathological fractures may also be seen.
•• CT scan helps to show the bony anatomy, whereas the MRI is helpful in
assessing cord compression along with the whole extent of the tumour.
•• Bone scans are helpful in identifying multiple lesions, which may be in the
form of ‘skip’ lesions.
•• Biopsy of the lesion should be undertaken before surgical resection is
performed.
•• Osteosarcomas are large vascular tumours with areas of grittiness.
•• Microscopically, it is characterised by the presence of woven bone formed
by osteoblasts, which may or may not be mineralised.
•• There are disorganised spicules or masses, or woven bone enmeshed in
a vascular bed. The bony spicules are surrounded by anaplastic spindle
or polygonal cells with mitosis and atypia.
•• The standard treatment protocol is neoadjuvant chemotherapy followed
by complete resection.
•• Treatment is started with two or three cycles of chemotherapy.
•• Surgery is planned after 10−16 weeks, allowing the tumour to regress,
following which radical excision of the tumour is done.
Chondrosarcoma
•• It is a malignant tumour forming hyaline cartilage (without bone) composed
of malignant chondrocytes.
•• It is more common in males with a peak age of incidence in the fifth decade
of life.
•• Although it usually arises primarily in the spine, it may occasionally occur
following malignant transformation of enchondromas or osteochondromas.
•• A hereditary association is seen in some cases with Ollier’s disease and
familial osteochondromatosis.
•• Patients usually present with pain in the involved segment with an
occasional radicular component depending upon the extent of the tumour.
•• The pain is exacerbated in the supine position.
•• Imaging characteristics depend upon the grade of the tumour.
•• Low grade tumours result in scalloping of the bone with cortical expansion.
•• With higher grade lesions, the lytic component increases.
•• Calcification may also be seen, which decreases with higher grade of
tumours.
•• There are often foci of spotty calcification. There may be calcified shadows
with radiating spicules arranged at right angles to the cortex.
•• CT and MRI are done for further delineation of the tumour and its
characteristics.
•• CT of the lung should also be done due to the tendency of this tumour to
metastasise to the lung.
•• Biopsy should be performed keeping in mind the surgical plan. Needle
biopsies yield little tissue, hence incisional biopsy is preferable.
754
•• Chondrosarcomas have been graded according to their histological

appearance:
–– Grade 1 tumours have mild cellular atypia with abundant hyaline matrix.
–– Grade 2 have significant atypia with abundant cartilaginous matrix.
–– Grade 3 have marked atypia with little cartilage matrix, mitotic figures,
necrotic foci and multiple giant tumour cells.
•• Complete surgical excision is the treatment of choice.
•• Instrumentation may be required for resultant spinal instability.
•• However, it is often technically not possible to completely remove these
tumours. In these cases, radiotherapy should be given to prevent the high
rates of recurrence that follow incomplete resection.
•• Cryosurgery has also been used when tumour-free margins are not
achieved during surgery.
•• Long-term survival is dependent upon the histological grade of the tumour.
Ewing’s Sarcoma
•• The overall incidence of Ewing’s tumour of the bone is around 6%.
•• This is a highly malignant tumour with male predominance and peak
incidence in the second decade of life.
•• The sacrum is commonly involved with the lumbar region being the next
in frequency.
•• The presenting symptom is pain with a variable severity of neurological
deficits in the form of sensorimotor and bladder/bowel involvement.
•• The patients may also present with cauda equina syndrome.
•• Radiographs show lytic lesions with a thin rim of sclerotic bone around
the margins.
•• Due to the tendency of these tumours to metastasise, particularly to the
lungs, CT chest should also be done.
•• Grossly, the tumour is grey-white to blue with semi-solid to gelatinous
consistency, and is extremely friable and highly vascular.
•• Microscopically, small round cells larger than lymphocytes with scant
cytoplasm are seen. Sometimes, a pseudorosette pattern may also be seen.
•• Tumours are disposed in sheets with a uniform population of tumour cells
displaying round nuclei, fine granular chromatin and a thin rim of cytoplasm.
•• Due to the difficulty in achieving complete excision of the tumour, which
is the aim of treatment, a multimodality approach is taken combining
chemotherapy, radiotherapy and surgical excision.
•• Incomplete resection results in higher recurrence rates. Hence, post-
operative radiotherapy is given in all such cases, the total dose being
4,000−6,000 cGy.
•• The 5-year survival rate is approximately 20% after using multimodality
treatment.
Plasmacytoma
•• These tumours are composed of malignant plasma cells and form a
subgroup of plasma cell dyscrasias.
•• These present as single bone lesions or may occur at extramedullary sites.
•• In the skeletal system, the spine is most commonly affected with the thoracic
spine being the favoured site.
•• Males are more commonly affected with the peak incidence occurring in
patients older than 50 years of age.
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•• Fifty per cent of these tumours may convert into multiple myeloma, if allowed
to persist for a sufficient time without treatment.
•• Pain is the most common presenting complaint.
•• However, bone destruction with collapse can result in cord compression
leading to myelopathy and even paraplegia in some cases.
•• On plain radiology, in the long bones, a characteristic “soap bubble”
appearance has been described.
•• Further tumour details are obtained with the help of CT and MRI.
•• These patients may produce paraproteins. These may be secretory or
non-secretory with occasional light chain urinary excretion.
•• Histologically, the entire spectra of plasma cell maturation may be seen
with basophilic cytoplasm and an eccentric nucleus.
•• Lesions can vary from being poorly differentiated to well-differentiated.
•• These tumours are highly radiosensitive.
•• Hence, radiation therapy is the first line of treatment with the radiation dose
being up to 3,500 cGy.
•• Surgical intervention is required for spinal instability and in cases of cord
compression.
•• Patients generally require stabilisation procedures.
•• Poor prognosis is indicated by the extent of soft tissue extension, old age
and persistent paraprotein production following treatment.
Multiple Myeloma
•• This is the most common primary malignancy of the bone.
•• It is a systemic plasma cell disorder where the bone marrow is first affected
resulting in its replacement by plasma cells followed by involvement of the
cortical surface with local extension.
•• Destruction of the bone marrow may result in normochromic anaemia,
thrombocytopaenia and neutropaenia.
•• Male and female patients are equally involved with 62 years being the
peak age of incidence.
•• The whole skeletal system is equally vulnerable.
•• Pain is usually the presenting feature with radicular and myelopathic
features depending upon the growth of the tumour.
•• Patients often present with pathological fractures.
•• Patients may also develop constitutional symptoms, like fever and fatigue,
due to chronic anaemia.
•• On plain radiographs, multiple destructive lesions are seen, which may
result in vertebral pathological fractures with cord compression.
•• Urinary examination is carried out for Bence-Jones protein.
•• Serum electrophoresis is also carried out to investigate for other
paraproteins.
•• Bone marrow smears reveal increased number of plasma cells which show
atypical features.
•• The beta-2 microglobulin level is measured and followed as a prognostic
factor.
•• Hypercalcaemia is reported with normal or slightly increased alkaline
phosphatase.
•• Renal function tests are also required, since this disease may result in
acute tubular damage causing renal failure.
•• Definitive diagnosis requires CT-guided bone biopsy which shows
fibrocollagenous tissue infiltrated by a monotonous population of mature
756
and immature plasma cells displaying predominantly eccentrically placed

nuclei with coarse chromatin, and moderate amount of cytoplasm.
•• Combined radiotherapy and chemotherapy form the first line of treatment.
•• Surgical therapy is indicated only in cases of spinal fractures resulting
in spinal instability or cord compression. In such cases, decompression
followed by instrumentation is required.
•• Since complete resection is not usually possible, radiotherapy should be
instituted following surgery.
•• A large number of chemotherapeutic agents are available with
cyclophosphamide and melphalan being equally effective.
•• Radiation therapy in conjunction with chemotherapy is especially helpful in
relieving pain and may also result in relief of neural compression.
Lymphoma
•• The spine is usually affected in cases of Non-Hodgkin’s lymphoma.
•• Usually multiple level involvement occurs although, occasionally, solitary
lesion is seen.
•• The peak age of incidence is after 40 years.
•• Lymphoma tends to involve the anterior column, the posterior columns
tend to be relatively spared.
•• Lymphomas are highly radiosensitive and chemosensitive.
•• Surgical therapy is reserved for cases with neurological deficits. In such
cases, instrumentation may be required to restore spinal stability.
Metastatic Tumours of the Spine

•• It has been widely accepted that lung and liver are the most common sites
for the seeding of metastatic foci.
•• The skeletal system is the third most common site for metastatic disease
with the spine harbouring the majority of these lesions.
•• The four common primary lesions that result in spinal metastasis are breast,
lung, prostate and kidney cancers.
•• In the paediatric population, neuroblastoma is the most common tumour
responsible for neurological dysfunction.
•• The thoracolumbar and the lumbar spine are the commonest sites of spinal
metastasis perhaps due to increasing amounts of bone marrow from the
cervical to the lumbar region.
•• However, the propensity for the disease to present with neurological
dysfunction is highest in the thoracic spine as the canal diameter is the
narrowest in this region.
•• Dommisse had suggested that the thoracic spine has the most critical
vascular area of the spine, particularly at the levels from T4 to T9. However,
this fact has been refuted and the thoracic region too has a well-developed
segmental blood supply.
PATHOGENESIS
•• Four pathways for spread of metastases to the spine have been determined.
•• The most common pathway is the venous system.
•• Batson had demonstrated the presence of valveless veins in the spinal
canal.
•• The blood from the vertebral body is drained by the basivertebral veins
which connect to the epidural venous plexus.
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•• The whole pathway is devoid of valves resulting in retrograde flow of

blood to the vertebral body whenever, there is a rise in the intra-abdominal
pressure.
•• This provides a pathway for the tumour cells to travel from the primary
site to the spine.
•• The vertebral venous plexus is in communication with the upper and lower
extremity, the head, the neck and the trunk allowing the spread of a variety
of tumours.
•• Arterial spread of the tumour occurs by means of the nutrient arteries.
•• Tumours of the lung and the prostate have been known to utilise this
pathway for their spread.
•• Some tumours have shown to have perineural and lymphatic spread.
•• Local extension of the tumour cells to the spine is also well-known with
lung carcinoma, tumours of the retroperitoneum and the mediastinum.
•• In order for the tumour cells to establish themselves at the target site, two
conditions need to be met.
•• Firstly, the tumour cells should be in adequate number, which in the spine
is facilitated by the valveless system of veins.
•• The second is the availability of an environment which allows the tumour
cells to proliferate.
•• Paget proposed his “seed and soil” hypothesis but could not provide
conclusive evidence in its favour.
•• It is now, believed that multiple factors are responsible for the spinal
seedling.
•• The cancellous bone within the vertebral body has been shown to be the
favoured site for tumour deposits.
•• Indirect mechanisms responsible for tumour destruction have been the
production of parathyroid hormone, PG E2, ACTH and calcitonin.
•• The intervertebral disc tends to be involved late in metastatic disease with
the cartilaginous endplates providing the barrier to the spread.
•• Involvement of the spinal canal occurs due to direct extension of the
metastasis from the vertebral body.
•• This results in compression of the vertebral venous plexus initially, which
results in the development of vasogenic cord oedema due to plasma
exudation and production of mediators such as prostaglandins.
•• Indomethacin which inhibits prostaglandin formation has been shown to
decrease cord oedema.
•• It is the rate of development of the vascular compromise that results in slow
or rapid neurological deterioration.
CLINICAL PRESENTATIONS
•• Although the clinical syndrome varies depending upon the site of
involvement in the spine, pain is the presenting feature in up to 90% of
these patients.
•• The pain initially is localised, being mild at the onset with progressively
increasing severity.
•• The duration of pain varies from 2 weeks to a year.
•• The character of the pain changes to a boring or burning nature with
progression of the disease.
•• The pain tends to persist at night.
•• Localised pain occurs due to periosteal or dural involvement.
758
•• The pain may later acquire a radicular nature due to the involvement of
the nerve roots.
•• The radicular pain may be unilateral or bilateral and is aggravated by
movements of the trunk.
•• Recurrence of pain in patients who have previously been treated signifies
tumour recurrence.
•• Motor deterioration tends to precede sensory or urological involvement.
•• Anterior horn cell involvement leads to lower motor neuron weakness at
that level with spastic weakness below.
•• Similarly, asymmetrical compression of the cord by the tumour results in
asymmetrical weakness with the ipsilateral side being affected earlier in
comparison to the contralateral side.
•• Lesions of the conus present with lower motor neuron weakness of the
lower limbs with absent plantars and hypotonia.
•• Saddle anaesthesia, for instance, is commonly seen in lesions of the conus.
•• The sensory level is usually localised to one or two dermatomal levels
below the vertebral levels.
•• The posterior columns may be involved early in dorsally located tumours.
•• Posterior column involvement may be manifested in the form of paresthesias
or numbness below the level of involvement.
•• Lhermitte’s sign may occasionally be positive in patients with cervical spine
involvement, especially occurring on flexion of the neck.
•• Bladder and bowel disturbances often occur late in the course of the
disease.
•• Their early involvement occurs in intramedullary metastasis.
•• In lesions above the level of the conus, patients present with spastic bladder
and constipation.
•• However, patients with conus lesions have a neurogenic lower motor neuron
type of bladder involvement with faecal incontinence.
•• Conus involvement may also result in impotence in males, whereas
priapism is seen with lesions above the conus.
•• Frenkel’s system is often used for assessing the neurological involvement.
Frenkel’s Classification
•• Grade A: Complete motor and sensory loss
•• Grade B: Complete motor and incomplete sensory loss
•• Grade C: Some motor function, incomplete sensory loss
•• Grade D: Useful motor function, incomplete sensory loss
•• Grade E: Normal motor and sensory function
•• Plain radiographs are often the first investigation performed. For radiological
changes to be seen, 40−65% lytic activity should have occurred.
•• The pedicles usually show the first evidence of metastatic disease.
•• “Winking Owl sign” refers to the absence of the pedicle on AP views.
•• Other findings are changes in the vertebral body morphology leading to
vertebral collapse, osteolytic lesions or focal/diffuse osteopaenia.
•• Sclerotic changes are suggestive of osteoblastic metastasis seen with
prostate and breast secondaries.
•• Bone scans form an integral part of the work up of metastatic disease. This
is usually performed with technetium-99m polyphosphate isotopes. Tracer
uptake is due to reactive bone formation.
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•• However, this is useful in determining the extent of bony involvement and

to identify the ‘hot’ spots where the biopsy is most likely to yield positive
results in cases with multiple levels of involvement.
•• MRI with contrast has been accepted as the investigation of choice and is
considered superior to CT myelography.
•• Metastatic lesions tend to enhance with gadolinium and the extent of
enhancement following treatment may be utilised to evaluate the response.
•• In the thoracic spine, however, due to motion artefacts produced by heart
and lung movements, MRI becomes less accurate.
•• Similarly, MRI cannot be undertaken in patients with steel implants,
aneurysmal clips and pace makers.
•• CT myelography is useful in recurrent cases with steel implants in situ.
CT delineates the bony margins better than the MRI, yet the soft tissue
delineation is not of the desired order.
•• Tumour markers are increasingly being measured to evaluate for metastatic
disease.
•• Prostate specific antigen (PSA) and carcinoembryonic antigen are routinely
estimated and their levels are believed to correlate with treatment efficacy.
•• Among other blood investigations serum electrophoresis, albumin to
globulin ratio and gammaglobulin levels are performed for detection of
myeloma.
•• Alkaline phosphatase is usually raised in metastatic disease except in
patients with multiple myeloma.
•• Percutaneous biopsy is useful in confirming the histological diagnosis of
metastatic disease.
MANAGEMENT
•• The options are steroid therapy, hormonal manipulation and chemotherapy.
•• However, hypercalcaemia is a known complication of metastatic disease
which is targeted by diphosphonates.
•• Chemosensitive tumours such as osteosarcoma and germinoma form a
subgroup where chemotherapy plays an important role in the management.
•• Hormonal manipulation has been found useful in metastases originating
from prostate tumours.
•• Steroids have been shown to partially reverse the neurological deficit
caused by metastatic disease and are believed to prevent oedema and
also have oncolytic activity.
•• Due to its high potency and salt retaining properties, dexamethasone is
the drug of choice.
•• Radiotherapy has been shown to have a definitive role in the treatment of
compressive metastatic disease.
•• Approximately, 3,000−5,000 cGy given in daily fractions of 200 cGy over
a 5-week period is recommended.
•• In cases with multiple-level metastasis, the whole spine needs to be
irradiated.
Surgical Management
•• Indications for surgical intervention are:
–– Acute neurological deterioration.
–– Progressive neurological deterioration while on conservative management.
–– Persistent unbearable pain despite all measures.
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–– Extensive destructive lesions causing spinal instabiltity.

–– Radioresistant tumour.
•• The aim of surgical intervention should not only be debulking the tumour,
but also to realign the spinal elements with restoration of spinal stability.
•• For surgical decompression, laminectomy has been found to be ineffective.
•• The posterolateral approach is often favoured as it allows tumour resection
around the circumference of the dural sac and nerve roots bilaterally.
•• Anterior approaches are particularly helpful for the cervical spine.
•• In the thoracic and abdominal regions, the anterior approaches give good
exposure, but anterolateral access is available on one side only.
Anterior Approaches
C1-C2 : Transoral/transmandibular
C3-C7 : Transcervical
C7-D1 : Trans-sternal/transthoracic
T3-T10 : Transthoracic/posterolateral thoracotomy
T11-L1 : Transthoracic, extrapleural, thoracoabdominal
L2-L4 : Retroperitoneal
L5-S1 : Transabdominal
•• Spinal stability needs to be maintained after the decompression. For this,
bone grafting with instrumentation is the procedure of choice.
•• Grafts can be autologous from the iliac crest, fibula or ribs.
•• They can be artificial grafts made of hydroxyapatite, methylmethacrylate
or ceramics.
•• Instumentation procedures have undergone rapid development and rods,
pedicle screws and cages are widely used.
102
CHAPTER Spinal Schwannomas
and Meningiomas
Trimurti D Nadkarni
INTRODUCTION
•• Spinal cord tumours account for about 15% of central nervous system
(CNS) tumours.
•• Primary spinal cord tumours may be benign or malignant.
•• Five to ten percent of primary spinal cord tumours originate from cells within
the spinal cord parenchyma.
•• The other 90−95% of primary spinal cord tumours arise from cells adjacent
to the spinal cord, such as those of the spinal nerve roots or meningeal
coverings.
•• Meningiomas and neurofibromas are the most common benign intradural
extramedullary spinal cord tumours.
CLASSIFICATION AND TERMINOLOGY

•• Spinal tumours are broadly classified as extradural or intradural based on
their relation to the dura.
•• Intradural spinal cord tumours can further be classified as intramedullary
and extramedullary according to their relationship to spinal cord.
•• A small number of spinal neoplasms can have both intramedullary and
extramedullary components communicating through the nerve root entry
zone.
•• Similarly, some intradural tumours may extend into the extradural
compartment through the nerve root sleeve.
•• Nerve sheath tumours are the most common type of intradural
extramedullary (IDEM) spinal cord tumours accounting for 25−30% of all
primary spinal cord tumours.
•• Meningiomas account for 20−25% of spinal cord tumours.
EPIDEMIOLOGY
Incidence
•• Nerve sheath tumours: Nerve sheath tumours are uncommon tumours in
the general population with an annual incidence of 0.3−0.4 per 100,000
persons.
•• Nerve sheath tumours account for 40% of all intradural spinal cord tumours
in adults.
•• In the spine, there is a male preponderance and the male to female ratio
is 1.25 to 1.5:1, in contrast to intracranial and peripheral sites where there
is a female predominance (1.5:1).
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•• The peak incidence of these tumours is in the fourth to sixth decade.

•• With nerve sheath tumours, two tumour populations need to be distinguished
which are schwannoma and neurofibroma.
•• Schwannomas are more common and are the largest category of nerve
sheath tumours.
•• Whereas schwannomas are encountered in patients with neurofibromatosis
(NF)-2 and in patients without NF, neurofibromas are found in patients with
NF-1.
•• Most nerve sheath tumours arise from a dorsal nerve root.
•• Neurofibromas represent a higher proportion of ventral root tumours and often
exhibit a dumb-bell configuration.
•• Meningiomas:
–– Spinal meningiomas account for 25% of all primary spinal cord tu-
mours and 12% of all meningiomas of the CNS.
–– They occur predominantly in the fourth to seventh decade; with a fe-
male to male ratio of 3.5 to 4:1.
–– Females usually between the fourth and fifth decades account for ap-
proximately 80% of spinal meningiomas.
–– Spinal meningiomas occur predominantly in the thoracic region (82%),
followed by cervical (15%) and rarely lumbar areas (2%).
•• Spinal meningiomas are mostly intradural and extramedullary in location.
•• Extradural meningiomas account for 5% of spinal meningiomas and are
more common in the younger age group.
HISTOPATHOLOGY
•• Nerve sheath tumours: Nerve sheath tumours usually arise from the dorsal
roots at various segmental levels of the spinal cord. They are avascular
and globoid, and without calcification.
•• The gross appearance of a neurofibroma is of a fusiform enlargement of
the involved nerve, without any identifiable nerve.
•• Microscopically neurofibromas consist of an abundance of fibrous tissue
and the nerve fibres are within the tumour substance.
•• Schwannomas appear as grossly smooth, globoid, eccentric masses with
identifiable attachment to the nerve root from which they arise.
•• Microscopically, schwannomas consist of elongated bipolar cells with
fusiform, darkly staining nuclei arranged in compact interlacing fascicles
with a tendency towards palisade formation (Antoni-A). A loosely arranged
pattern of stellate shaped cells (Antoni-B) is less common.
•• Meningiomas usually arise from arachnoid cap cells located at exit zones of
nerve roots or the entry zones of arteries into the spinal canal, accounting
for their predominant lateral location.
•• Macroscopically they vary from smooth lobulated to a fibrous sheath like
en plaque variety.
•• Consistency can vary from soft friable, fleshy rubbery to stony calcified.
•• The dural attachment is broader than expected.
•• Unlike intracranial meningioma, spinal meningiomas never penetrate the
pia. This simplifies surgical resection.
GENETIC ASPECTS
•• The chromosomal region involved has been localised to the centre of the
long arm of chromosome 22 in the bands 22q12.3-qter.
Chapter 102 • Spinal Schwannomas and Meningiomas
763
•• This is the same area that harbours the neurofibromatosis Type 2 (NF2)
tumour suppressor gene.
•• Other chromosomal abnormalities noted in meningiomas with clinical
progression to malignancy include loss of heterozygosity (LOH) for foci
on chromosome arm 1p, 9q, 10q and 14q.
•• As with meningiomas, monosomy 22 is the most frequent cytogenetic
abnormality in schwannomas.
•• The NF2 gene codes for a protein called merlin (i.e. meosin-ezrin-radxin-
like protein). Loss of expression of this protein was demonstrated in the
pathogenesis of schwannomas and meningiomas.
CLINICAL SYMPTOMS AND SIGNS

•• Spinal schwannomas and meningiomas are slow growing benign
extramedullary tumours of the spine and typically present with slowly
progressive signs of spinal cord compression.
•• Pain is a common initial symptom in extramedullary lesions.
•• Pain can have localising value in case of schwannomas as it arises from
the dorsal sensory root producing radicular pain.
•• Segmental involvement of the dorsal root entry zone or anterior horn cell
and roots result in specific sensory or lower motor deficit.
•• Distant clinical features result from long tract involvement like corticospinal,
spinothalamic and posterior columns.
•• In general these tumours tend to arise eccentrically, lying on one side of
the spinal cord either dorsally or ventrally.
•• This eccentric tumour position results in asymmetric cord compression with
higher incidence of Brown Sequard syndrome, i.e. ipsilateral involvement
of corticospinal and dorsal columns with contralateral involvement of the
spinothalmic tract.
•• Lesions of the upper cervical spine present with a unique syndrome which
produces disproportional loss of dorsal column sensation in the upper limbs
compared to the lower limbs, atrophy of intrinsic muscles of the hand, apart
from variable involvement of long tracts below the level of lesion.
•• Rarely, foramen magnum tumours can cause nystagmus due to pressure
on sulcomarginal fibres.
•• Involvement of the mid and lower cervical segments can lead to Horner’s
syndrome apart from long tract involvement.
•• Involvement of the upper thoracic segments can cause girdle type pain,
which is sometimes mistaken for pain of cardiac origin.
•• Thoracic lesions produce sensory loss well below the actual level of the
tumour.
•• Tumours of the lumbosacral and conus medullaris region of the spinal
cord can affect parasympathetic innervations of the bladder, bowel and
sexual organs.
•• Tumours of the cauda equina may selectively involve a single dorsal root
causing persistent discrete dermatomal pain for many months and may be
mistaken for disc prolapse.
•• Worsening of pain on recumbency is an important clinical feature of
extramedullary tumours and is most commonly associated with large cauda
equina tumours.
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DIAGNOSTIC IMAGING
•• Intradural extramedullary masses, like meningiomas and schwannomas,
compress and displace the spinal cord and cause widening of the adjacent
cerebrospinal fluid (CSF) spaces.
•• Gadolinium enhanced imaging increases the sensitivity of MRI in detecting
small tumours. Almost all spinal cord tumours exhibit some degree of
contrast enhancement.
•• Spinal nerve sheath tumours, like schwannomas and neurofibromas, are
difficult to distinguish on neuroimaging.
•• Both are isointense on T1-weighted images, have high signal on T2-
weighted images and enhance with gadolinium.
•• Schwannomas can have cystic regions or fatty degeneration, whereas
neurofibromas usually are homogeneous.
•• Nerve root tumours may have extradural extension through neural foramina
giving them a dumb-bell shape.
•• Imaging characteristics of spinal meningiomas are similar to their cranial
counterparts with iso- to hypo-intense signal on T1-weighted images, hyper-
intense on T2-weighted imaging and contrast enhancement.
•• Meningiomas typically demonstrate intense uniform enhancement.
•• Enhancement of adjacent dura strongly supports the diagnosis of meningioma.
•• Peritumoral hypointensity is commonly seen around a meningioma which is
due to CSF spaces.
•• Myelography and CT myelography are rarely used presently with
advancement in MR imaging.
TREATMENT
•• Surgical principles employed elsewhere for removal of benign tumours
also hold true for these benign extramedullary intradural spinal tumours
like nerve sheath tumours and meningiomas.
•• This includes patient positioning, optimum exposure, microscopic
assistance, tumour debulking, preservation of normal neural elements and
meticulous haemostasis.
Pre-operative Preparation
•• Intra-operative electrophysiological monitoring of both motor and sensory
tracts should be made available for the surgeon planning to resect an
intradural extramedullary tumour.
•• A Foley catheter and sequential compression device are routinely used.
•• Pre-operative antibiotic to cover Gram-positive bacteria and, steroids are
routinely given.
Operative Procedure
•• A typical intradural extramedullary tumour is approached posteriorly through
a posterior midline incision and multilevel laminectomy.
•• For tumours above the D2 level, the sitting position may be used as per
the surgeon’s preference.
•• A standard laminectomy extending approximately one level rostral and one
level caudal to the lesion usually provides sufficient exposure.
•• Occasionally, a facetectomy or partial pedicle resection may be necessary
to establish a ventrolateral corridor.
Chapter 102 • Spinal Schwannomas and Meningiomas
765
•• In a ventral or ventrolateral tumour, division of the dentate ligament would

be necessary.
•• Nerve sheath tumours:
–– Tumour removal requires identification of the proximal and distal end
of the nerve root to which the tumour is attached.
–– The nerve root of origin usually must be sacrificed to remove the
tumour.
–– Fortunately, most cervical tumours can be removed completely and
safely by an extended posterior exposure.
–– Complete unilateral facetectomy allows paraspinal access up to 3 cm.
–– An anterior transpleural or extrapleural thoracotomy provides excellent
visualisation of the paraspinal region.
–– The lateral extracavitary approach is useful as a single stage operation
in cases that require concomitant exposure of intraspinal and paraspi-
nal compartments.
–– This exposure is achieved through a hockey stick incision and allows
the surgeon to work on either side of the paraspinal muscles.
–– Lumbar dumb-bell tumours can also be exposed well through a lateral
extracavitary approach.
–– Dumb-bell sacral tumours usually require both anterior and posterior
exposures, which can be staged or performed simultaneously with the
patient in the lateral position.
•• Meningiomas:
–– Posterior laminectomy provides adequate exposure in most cases.
–– A unilateral laminectomy or facetectomy can be used for eccentrically
located or ventral tumours.
–– Most of the meningiomas displace the cord laterally and can be satis-
factorily removed by the posterior route.
–– Management of the dural base is the most controversial aspect of
treating spinal meningiomas.
–– The options include excision of the involved dura and reconstruction
with graft, or extensive in situ coagulation.
103
CHAPTER
Intramedullary Tumours
Bhawani S Sharma  Manish S Sharma
INTRODUCTION
•• Intramedullary spinal cord tumours account for 15−20% of all intradural tu-
mours and only 2−4% of all intrinsic tumours of the central nervous system.
•• The most common initial symptom is generalised back pain, which is very
difficult to distinguish clinically from back pain due to musculoskeletal
conditions.
•• Patients are often diagnosed only after the development of neurological
signs and symptoms that occur later in the course of the disease.
AETIOPATHOLOGY
•• Intramedullary spinal cord tumours mostly have a glial origin as they are
histologically and immuno-histochemically similar to normal ependymal
cells and astrocytes.
•• The exact aetiology remains unclear but is perhaps linked to genetic
mutations.
•• This is especially so in patients with neurofibromatosis; patients with the
NF1 gene may develop spinal astrocytomas, whereas patients with the
NF2 gene are predisposed to spinal ependymomas.
•• Spinal haemangioblastomas too may occur as a consequence of mutations
in the VHL gene in patients with von Hippel-Lindau disease and also in
those patients without the syndrome.
•• Histological subtypes: Astrocytomas and ependymomas are the most
common histological types of intramedullary tumours.
Astrocytomas
•• Astrocytomas comprise 90% of paediatric (<10 years) and 60% of
adolescent intramedullary tumours.
•• These have a predilection for the cervical and cervicodorsal cord (60%)
and are rare in the filum terminale.
•• This category covers all subtypes of tumours from Grades 1 through 4.
•• These include but are not limited to low grade fibrillary and pilocytic
astrocytomas, malignant astrocytomas, glioblastoma multiforme,
gangliogliomas and rarely oligodendrogliomas.
•• Most of these are Grades 1 and 2 fibrillary astrocytomas though 25% of
astrocytomas in adults may be malignant.
•• Most astrocytomas are infiltrative. This makes tumour excision very difficult
and associated with high morbidly.
Chapter 103 • Intramedullary Tumours
767
•• A radical removal should always be the primary goal because a simple

biopsy does not guarantee a fair neurological outcome.
Ependymomas
•• It appears that, as age increases, the incidence of ependymomas increases,
whereas that of astrocytomas decreases.
•• Histological subtypes include epithelial, tanycytic (fibrillar), subependymoma
and myxopapillary variants.
•• Unlike astrocytomas, these tumours are associated with neurofibromatosis
2 and are usually well circumscribed.
Haemangioblastomas
•• These benign tumours of vascular origin are commonly located in a dorsal
or dorsolateral position under the pia mater.
•• They account for about 3−8% of all intramedullary tumours and may be
associated with von Hippel-Lindau syndrome in 15−25% of all cases.
Lipomas
•• Lipomas in an intramedullary location comprise about 1% of all
intramedullary tumours.
•• These are commonly located subpially and become symptomatic in
adulthood.
Metastases
•• These account for fewer than 5% of all intramedullary tumours and are
relatively rare as both the spinal cord blood supply and the volume of the
cord are low.
•• Commonest primaries are malignancies arising in the lung and breast.
Miscellaneous Lesions
•• Intramedullary location of dermoid, epidermoid and neurenteric cysts is
well documented. These are often associated with occult or open spinal
dysraphism.
•• Melanocytomas, melanomas, fibrosarcomas, primitive neuroectodermal
tumours and cavernous malformations all can occur in an intramedullary
location within the spinal cord although these are exceedingly rare.
•• Another important differential diagnosis of a mass lesion within the cord
substance, especially in our country, is intramedullary tuberculoma and
cysticercus cyst.
CLINICAL FEATURES—SYMPTOMS
Pain
•• Pain and motor weakness are the most common presentations in adults
and children.
•• Intramedullary tumours produce an ill-defined pain which is seldom radicular
(except in cauda-conus lesions) but localises at the level of the lesion.
•• It is said to be more prominent at night in the supine position.
•• A sudden onset of pain indicates either an osseous collapse or an
intratumoural haemorrhage.
768
•• In fact, the absence of pain in a patient with radiographic and clinical

features of an intramedullary pathology may indicate a diagnosis of myelitis.
Motor Function
•• Intramedullary lesions classically produce a long segment lower motor
neuron type of weakness at the level of the lesion with atrophy, hypotonia,
areflexia and fasciculations, along with features of upper motor neuron
weakness below the lesion.
•• Weakness is maximal at the level of the lesion.
Sensory Abnormalities
•• Patients often complain of numbness which begins distally and then extends
proximally. This often takes the form of “glove and stocking”, “cape distribution”
or “dissociated anaesthesia”.
•• Anaesthesia may predispose to trophic ulcerations, especially in the upper
limbs in cervical lesions.
Autonomic Dysfunction
•• Urinary incontinence, especially in a toilet-trained child, is a significant
symptom which merits a detailed clinical and radiographic examination.
•• Myelopathic patients who develop a Horner’s syndrome or early onset
urinary or faecal incontinence should be suspected to harbour an
intramedullary pathology.
Spinal Deformity
•• Scoliosis may be the earliest sign of an intramedullary tumour in a young
child.
•• Local lumps, spinal point tenderness and the presence of stigmata of spinal
dysraphism are all indicators of underlying pathology.
CLINICAL EXAMINATION
•• Care should be taken to evaluate the ocular fundus and cranial nerves too
as intramedullary tumours may seed down from an intracranial pathology.
Fundus examination will also reveal stigma of Von Hippel Lindau’s disease.
•• High cervical lesions may also affect the lower cranial nerves and the spinal
nucleus and tract of the trigeminal nerve.
•• Rarely hydrocephalus may occur even in the absence of an intracranial
pathology due to an elevated protein concentration in the CSF, arachnoidal
fibrosis and subarachnoid metastases. This is more common in malignant
spinal cord tumours.
INVESTIGATIONS
Imaging
•• Contrast enhanced MRI remains the investigation of choice for patients
with a suspected spinal tumour.
•• Most intramedullary tumours expand the spinal cord, are hypointense on T1-
and hyperintense on T2-weighted sequences and enhance with contrast.
•• Ependymomas are more symmetrical, enhance with contrast uniformly and
are more frequently associated with polar cysts.
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•• Up to 65% of ependymomas may be associated with a syrinx.

•• Astrocytomas tend to be poorly marginated, enhance heterogeneously with
contrast and may be associated with intratumoural cysts and necrosis. Up
to 20% of astrocytomas may be associated with a syrinx.
•• Haemangioblastomas are intensely enhancing lesions located dorsally or
dorsolaterally within the spinal parenchyma and may be associated with flow
voids and large cysts or a syrinx out of proportion to the size of the tumour.
The entire neuraxis should be screened, if this pathology is suspected.
•• Metastases and lymphomas may be associated with leptomeningeal
enhancement. This sign also indicates tubercular, bacterial or fungal
myelitis.
•• Lipomas are unmistakable because of their MRI signal characteristics, they
do not enhance with contrast.
•• Non-tumourous conditions to be differentiated from syringomyelia, acute
multiple sclerosis and tuberculomas.
•• A pure syrinx does not enhance with contrast and is often associated with
a Chiari malformation.
•• Acute multiple sclerosis usually does not produce cord expansion.
•• Tuberculomas may appear hypointense on T2-weighted sequences.
Angiography
•• This investigation is seldom used for the investigation of intramedullary
spinal cord tumours except to rule out an arteriovenous malformation.
•• This may also be used to embolise a haemangioblastoma pre-operatively.
MANAGEMENT
Rationale of Treatment
•• A surgeon’s primary objective should be total tumour excision but this
has to be tempered by the need to maintain motor, sensory and sphincter
functions, especially when most patients will develop significant, possibly
transient, neurological deficits after intramedullary tumour resection.
•• The ideal surgical candidate is a patient with a progressive neurological
deficit who is still ambulant.
•• Taking the natural history of the disease into account, the risks of surgery
seem acceptable.
Surgical Management
•• The goals of surgery are total tumour removal with preservation of
neurological function.
•• Patients need realistic guidance, especially those who are functionally
intact, continent and have minimal neurological deficits.
•• Radical surgery for malignant spinal cord astrocytomas (WHO Grades 3
and 4) does not appear to be beneficial.
Pre-operative Management
•• Patients are usually administered intravenous steroids (dexamethasone
4 mg IV Q 6H) for 48 hours prior to surgery.
•• Patients with high cervical lesions are instructed in incentive spirometry.
•• Use of intravenous methylprednisolone succinate in loading doses of
30 mg/kg at the time of induction of anaesthesia followed by a maintenance
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dose of 5.3 mg/kg for the next 24−48 hours depending on the patient’s
post-operative neurological recovery.
SPECIAL INSTRUMENTS/TECHNOLOGY
Evoked Potential Recordings
•• Some surgeons routinely monitor somatosensory evoked potentials (SSEP)
during surgery by stimulating the median/ulnar nerves in the upper, and
the posterior tibial or peroneal nerves in the lower limb with low-voltage
electrical current and the evoked responses in the sensory cortex are
recorded through scalp electrodes.
•• Multiple responses recorded via scalp electrodes from the sensory cortex
are averaged on a computer to generate a standard reproducible waveform.
•• This waveform may be affected by the stimulus frequency, amplitude,
patient temperature and the concentration and type of anaesthetic agent.
•• Motor Evoked Potentials (MEPs) may be recorded via EMG electrodes in
the musculature of the upper and lower limbs after motor cortex stimulation
by scalp electrodes.
•• Direct epidural recording of spinal cord motor and sensory pathways may
be used for a more comprehensive assessment of intra-operative spinal
cord function.
Ultrasonic Aspirator
•• One of the absolute indications for the use of the ultrasonic aspirator is
intramedullary surgery.
•• The advantages of this equipment are several.
•• High-frequency ultrasonic waves are used to fragment the tumour, which
is subsequently aspirated.
•• This obviates the need to dissect the tumour sharply off the cord interface
and lessens traction on normal tissue. This minimises cord manipulation
and has helped to vastly improve outcome after surgery.
•• Newer models now include a pen type attachment that will only fragment
tissue without aspiration.
•• At low intensity, this device can be used as a dissecting tool, to gently peel
off the tumour from its interface with the cord. Unfortunately, hard calcific
tumours cannot be decompressed even with this device.
Laser
•• The CO2 laser has been used with varying degrees of success in the excision
of intramedullary tumours.
•• The advantage of laser is that it is haemostatic for capillaries and can help
resect hard tumours impervious to ultrasonic aspiration.
•• Its disadvantages lie in that it can indiscriminately vapourise normal tissue and
often slices through larger venules and arterioles producing haemorrhage.
Tissue Vapouriser
•• This implement assists cold cautery and is used with a needle attachment
to incise the pia over the dorsal midline of the cord substance.
•• The advantage of this tool is that the incision is precise and the cut is made
without charring.
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Intra-operative Ultrasound (iUSG)

•• Ultrasound is a valuable tool which can be used intra-operatively prior to
durotomy to determine whether the laminectomy/laminoplasty is adequate
or else needs to be expanded.
•• This saves time and ensures that the intradural part of the surgery is not
interrupted by the need to increase the bony exposure.
•• Likewise, after durotomy, iUSG can confirm the position, length and
adequacy of the myelotomy.
SURGICAL STEPS
Bone Removal
•• Great care is taken to ensure that the marking of the spinous processes is
correct as per the location and extent of the tumour.
•• Intra-operative C-arm to accurately map out the area of interest after the
patient is positioned supine.
•• Most surgeons prefer to perform an extensive laminectomy to ensure
that the origins of the dorsal nerve rootlets are clearly visible on both
sides and also that the lateral margins of the tumour can be adequately
decompressed.
•• Smaller tumours may be approached by a trap door laminoplasty.
•• A pneumatic drill is used to drill away the laminae till the ligamentum flavum
and epidural fat is clearly visualised.
•• The laminectomy should encompass the rostral and caudal ends of the
enhancing parts of the tumour as visualised on the mid-sagittal MR images.
•• Polar non-enhancing cysts do not need to be excised but need to be
encompassed by the laminectomy so that a clear plane of cleavage can
be established at the outset itself.
•• After bone removal, iUSG is used to confirm the adequacy of bone
exposure.
Durotomy
•• Incise the dura under microscopic vision beginning from cranial end and
proceeding caudally beyond the extent of the tumours.
•• As far as possible, the arachnoid mater is kept intact till the dura is hitched
up with 4-0 silk sutures to the drapes.
•• This prevents rapid dural decompression and the consequent epidural
haemorrhage from obliterating the operative field.
Myelotomy
•• Identify the midline not by the presence of the midline septum or a vein
but by a line equidistant from the origins of the dorsal nerve rootlets on
either side.
•• This is so because the tumour might have rotated the cord and the true
midline in any position is the landmark described above.
•• This myelotomy is then deepened till the tumour is reached.
•• The tumour is entered and biopsied using fine grasping or curette type
forceps.
•• The report of the frozen section is an additional guide for the surgeon
regarding the aggressiveness of the contemplated surgical resection.
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Ependymomas
•• Ependymomas push the normal spinal parenchyma aside, are distinct from
the surrounding spinal cord, usually with a well-defined plane of cleavage
and may be dissected from it.
•• They are firm and reddish-grey or yellow.
•• Cysts may frequently be found at either end of the tumour.
•• Smaller lesions often can be removed in one piece, but larger tumours
should be debulked so that the blood supply which is located ventrally may
be cauterised and cut before the tumour is finally removed.
Astrocytomas
•• Spinal cord astrocytomas do not have a clear interface with the normal
cord as they are infiltrating lesions.
•• Unfortunately, recurrence after incomplete removal is common, and
transformation to histologically malignant tumours has been noted to occur.
•• Malignant tumours (WHO Grades 3 and 4) are not amenable to complete
resection.
•• Extent of resection has not been associated with improved survival.
•• Rapid recurrence and disabling subarachnoid spread is the norm with
universal fatality before the first post-operative year.
Haemangioblastomas
•• Haemangioblastomas may occur sporadically or in association with the
VHL gene.
•• These highly vascular lesions appear yellow-orange to bright red and are
generally located subpially on the dorsal surface of the spinal cord as
isolated lesions or in association with the VHL gene.
•• These lesions have a clear demarcation from the rest of the cord and are
amenable to total resection.
•• Microsurgical resection is performed along the same lines as that for AVM
surgery.
•• The arterial supply, which is usually evident, must first be interrupted before
the tumour is debulked and excised.
Lipomas
•• Intramedullary lipomas are most commonly seen in the conus medullaris
in association with a dysraphic spine.
•• Isolated lipomas are very rare and are located on the dorsal surface of the
thoracic or cervical spinal cord.
•• They lack a clear demarcation from the cord. Maximal debulking serves
the purpose.
Intramedullary Metastases
•• These represent less than 8% of all intramedullary spinal cord tumours.
•• The most common primaries are lung and breast carcinomas.
•• In one third of all cases, the intramedullary metastasis may be the initial or
only manifestation of the primary tumour.
•• Progression is rapid and more than 80% of the patients die within 3 months
of first seeking medical attention.
•• Operative management is similar to that for haemangioblastomas.
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•• Methylprednisolone succinate is continued into the post-operative period
for 48 hours at the rate of 5.3 mg/kg/hour.
•• Patients with cervical intramedullary tumours are electively ventilated for
24 hours at the very least.
•• Extensive physiotherapy (active and passive range of motion) is instituted
from the first post-operative day. Preoperative training for this purpose is
helpful.
•• Air mattresses, two hourly change of posture, graduated compression
elastic stockings, laxatives and care of indwelling Foley’s catheter are
routine aspects of post-operative care.
POST-OPERATIVE COMPLICATIONS
Neurological Deficit
•• Around 50−70% of patients undergoing intramedullary tumour surgery are
likely to worsen neurologically post-operatively.
•• At least 20% of patients are expected to remain severely disabled.
•• Patients with better neurological function are better than those with poor
function at presentation.
•• The commonest neurological deficit that a patient is expected to experience
is loss of joint and position sense as a consequence of the injury to the
dorsal columns from the myelotomy.
•• The spinothalamic tracts may be injured during lateral dissection while
the corticospinal tracts are vulnerable during the ventral separation of the
tumour from normal cord.
Wound Dehiscence
•• This dreaded complication occurs more frequently in patients who have
either been previously operated upon or irradiated.
•• An associated CSF leak may result in meningitis and a possible fatality.
•• Management includes CSF diversion, debridement and primary resuturing
or plastic reconstruction using rotational flaps of the trapezius or latissimus
dorsi muscles.
Spinal Deformities
•• This delayed complication is seen more often in children and may result
in thoracic or lumbar spine kyphoscoliosis or swan-neck deformity of the
cervical spine.
•• Causes include denervation of paraspinal muscles by the tumour or during
surgery with a resulting unopposed flexion, especially in the cervical spine.
•• Following a laminectomy, the paraspinal muscles also no longer have an
osseous attachment.
•• Severe flexion deformity may result in spinal cord kinking and dysfunction
resulting in a delayed progressive neurological deficit which can mimic
tumour recurrence.
•• Re-exploration, instrumentation and fusion are indicated in this clinical
situation.
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ADJUNCTIVE TREATMENT
•• No study has demonstrated a beneficial effect of radiation therapy on
neurological function or survival in patients with glial spinal cord tumours.
•• However, most experts irradiate all adult patients with spinal cord
astrocytomas, regardless of the completeness of removal or the histological
grade of the tumour using 4,500 Gy given in divided doses.
•• Patients with ependymomas should not be irradiated after documented
complete excision.
•• Recurrences should be dealt with by redo-surgery and radiation if a residual
tumour burden exists.
•• The effectiveness of chemotherapeutic regimens using Carmustine and
BCNU similar to intracranial astrocytoma management is not clear.
•• Regardless of tumour histology or grade of resection, all patients require
lifelong surveillance with a contrast MRI of the craniospinal axis.
104
CHAPTER Congenital
Tumours of the Spine
CE Deopujari  AB Kakani
•• Tumours or tumour-like conditions that may affect the spinal cord

congenitally are dermoid and epidermoid cysts, teratomatous tumour,
lipoma, neurenteric cyst, arachnoid cyst, hamartomas, cavernomas and
angiolipomas.
•• Occasionally, astrocytomas may occur congenitally.
EPIDERMOID AND DERMOID CYSTS

•• Epidermoid and dermoid cysts account for less than 2% of all central
nervous system (CNS) lesions, the cranial to spinal ratio being 6:1.
•• However, these lesions make up to 17% of all spinal cord tumours in
children.
•• The pathogenesis of spinal epidermoid and dermoid cysts, as mentioned
by Dias and Walker, is mainly congenital, the origin being epithelial tissue
displaced during closure of the neural tube between the 3rd and 5th week
of gestation.
•• Repeated lumbar puncture, especially multiple lumbar punctures done
in the same patient, such as in the treatment of tubercular meningitis or
lumbar puncture done without a stylet in the needle, is an acquired cause for
occurrence of similar tumours which are then called implantation dermoids.
•• Such cysts are also reported to develop after surgery or trauma.
•• Unlike true neoplasms, which grow by progressive cell division, epidermoid
and dermoid cysts enlarge by desquamation of normal cells and secretions
of dermal elements into the cystic cavity.
•• The cysts contain keratinous material arranged in a lamellar fashion.
•• The outermost layer which is homogeneous gives this tumour its beautiful
pearly sheen.
•• Diagnosis of epidermoid and dermoid cysts is usually based on the
characteristic nature of their contents revealed by histological examination.
•• Both the cysts are lined by stratified squamous epithelium supported by
an outer layer of collagenous tissue.
•• The differentiation between the two is made by the fact that the lining of
the dermoid cyst also contains dermal appendages such as hair follicles,
hair, sebaceous glands and occasional sweat glands.
•• The connective tissue capsules that are located within the spinal cord are
surrounded by a zone of reactive gliosis.
•• The location of spinal epidermoid and dermoid cysts is variable, more
common sites being the lumbosacral (involving the conus medullaris and
cauda equina) and thoracic area.
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•• These may be either extradural, intradural extramedullary or intramedullary

in location.
•• These tumours are soft with a pliable capsule and grow very slowly.
•• As the cyst increases in volume, it conforms in shape to any available
cerebrospinal fluid (CSF) space and thus it attains a large size without
producing any symptoms from compression of neural elements.
•• These tumours thus become apparent usually in the second decade of life.
•• Around 50% of spinal epidermoid and dermoid cysts are associated with
other congenital anomalies of the spinal cord, vertebrae, overlying soft
tissue or skin.
•• This may be in the form of posterior spina bifida occulta, hypertrichosis and
similar other dermal abnormalities, especially posterior dermal sinuses.
•• The latter anomaly may predispose to recurrent pyogenic meningitis, and
should actively be sought while operating upon a patient with an epidermoid
or dermoid cyst.
•• The presence of these cutaneous markers aids in early diagnosis of these
tumours.
•• The occurrence of these anomalies in association with these tumours further
strengthens the theory of these lesions being of developmental origin.
•• The clinical presentation includes backache, progressive weakness in the
lower limbs, bladder or bowel symptoms and sensory dysfunction. Leakage
of the cyst contents in the CSF space is associated with recurrent episodes
of aseptic meningitis.
•• Constant irritation caused by this keratinous material is also responsible
for spinal arachnoiditis.
•• MRI has become the investigation of choice for early detection of these
tumours.
•• These cysts are typically isointense to slightly hyperintense compared to
CSF on all sequences.
•• Occasionally, the capsule may show enhancement on administration of
contrast.
•• The disparity in signal intensity most likely reflects variable lipid and protein
composition in these lesions.
•• Ideal treatment of these lesions consists of complete surgical excision
including excision of the capsule.
•• Many epidermoid and dermoid cysts have a clear plane of cleavage
between their lining membrane and the arachnoid membrane, enabling
the surgeon to excise them totally.
•• However, in some cases, due to the granulomatous reaction, the cyst
lining becomes nodular and becomes densely adherent to the surrounding
structures.
•• Any attempt at complete excision in such cases increases the risk of
neurological impairment. In such circumstances, it is wiser to excise
the easily separable portions of the capsule, leaving behind the densely
adherent portion.
•• Use of the operating microscope, good knowledge of surgical anatomy,
gentle handling of the tissues, intra-operative monitoring of evoked
potentials, use of CUSA and Laser allow many tumours to be excised totally.
•• Spilling of the contents into the subarachnoid space should be avoided as
the cholesterin and desquamated keratin act as irritants and cause aseptic
chemical meningitis and arachnoiditis.
•• Peri-operative use of steroids and intra-operative use of steroid containing
irrigation fluid is believed to help in alleviating the chemical irritation.
Chapter 104 • Congenital Tumours of the Spine
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SACROCOCCYGEAL TERATOMA
•• Sacrococcygeal teratoma, the most common congenital tumour, is a very
rare tumour occurring congenitally with an incidence of approximately one
in 40,000 births.
•• Almost 75−85% of these tumours occur in females.
•• The exact aetiology for the occurrence of sacrococcygeal teratoma is not
clear but it is thought that this tumour arises from totipotent cells of the
primitive knot.
•• Another theory suggests that the teratoma is an abortive attempt at twinning.
•• Well-defined body parts attached to these tumours suggest an incomplete
conjoined twin.
•• Sacrococcygeal teratomas are now increasingly being recognised
antenatally with the use of foetal sonography which may reveal foetal
hydrops, placentomegaly or polyhydramnios.
•• The foetal hydrops, as postulated by Langer et al. results from high output
cardiac failure caused by arteriovenous shunting within the tumour.
•• They even demonstrated reversal of foetal hydrops by foetal surgical
excision of the mass at 24 weeks’ gestation.
•• Other reported manifestations during the perinatal period include renal
failure and respiratory distress, trauma during delivery resulting in rupture
or severe haemorrhage, spontaneous rupture resulting in severe foetal
anaemia, consumption coagulopathy and steal syndrome.
•• Clinically sacrococcygeal teratomas may entirely be asymptomatic or may
present at birth as huge masses extending out from the sacrum and coccyx.
•• However, a few cases may entirely be intrapelvic or presacral and can only
be identified on rectal examination.
•• Altman et al. have classified sacrococcygeal teratomas into four types:
–– Type I—primarily external with a minimal presacral component (47%).
–– Type II—presenting externally, but with a significant presacral com-
ponent (35%).
–– Type III—tumour apparent externally, but the predominant mass being
pelvic with abdominal extension (9%).
–– Type IV—presacral without an external component (10%).
•• The presacral component may sometimes be large enough to cause
compression of the urinary or gastrointestinal tract resulting in obstructive
uropathy and chronic constipation.
•• Pathologically a teratoma contains elements from all three primitive germ
cell layers.
•• The sacrococcygeal region is the most common site of occurrence of these
tumours, the second most common being the gonads.
•• They may be solid or cystic, but mostly are made up of both components.
•• These tumours present in three distinct forms: (1) entirely mature adult type
tissue, which is clearly benign; (2) a mixture of mature and embryonic tissue,
the latter often having malignant potential and; (3) tumours containing
frankly malignant tissue.
•• The longer the tumour remains after infancy, the higher are the chances
of developing malignancy so that by one year of age well over 50% are
frankly malignant.
•• Clinical diagnosis of sacrococcygeal teratoma may not be difficult; however
the externally presenting tumour must be distinguished from lipoma and a
low myelomeningocoele.
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•• Sacrococcygeal teratoma in the presacral region is unfortunately seldom

discovered during early infancy and it needs to be differentiated from anterior
meningocoele, rectal duplication or other tumours like neuroblastoma.
•• The only curative treatment for sacrococcygeal teratomas is complete
surgical excision.
•• The role of chemotherapy and radiotherapy in these cases is not well
defined.
•• With careful technique and a team approach including the urosurgeon,
colorectal surgeon and oncosurgeon, it is usually possible to remove most
of these tumours without rupture or excessive blood loss, but the obviously
invasive malignant tumours cannot be removed so easily.
LIPOMA
•• Spinal lipomas are usually associated with dysraphism, in which the
intraspinal component communicates with a subcutaneous lipoma through
a defect in the posterior elements of the spine.
•• Nondysraphic true intradural spinal lipomas must be differentiated from
cauda equina lipomas or lipomas associated with dysraphism.
•• The former tumours, also known as subpial lipomas, are unique in that they
may occur anywhere in the spinal canal, unlike lipomas associated with
spinal dysraphism which occur predominantly in the lumbosacral region.
•• The dural layer is intact in true intradural lipomas and there is no tethering
of the cord.
•• The origin of these tumours is poorly understood but is thought to have an
embryological basis.
•• One of the earliest theories put forwards by Virchow was based on the
observation that adipocytes were present in the normal meninges and that
spinal lipomas resulted from the hyperplastic overgrowth of these cells.
•• It is postulated that lipomas develop when there is premature dysjunction
of the cutaneous ectoderm from the developing neural tube.
•• The surrounding mesenchyme migrates into the developing neural tube
and differentiates into fat.
•• True intradural lipomas are rare, accounting for less than 1% of all spinal
tumours.
•• In patients with nondysraphic spinal lipoma, the cutaneous anomalies are
generally absent and the clinical presentation is usually with symptoms
secondary to mass effect owing to the size of these lesions and not due
to tethering of the cord.
•• These tumours present with symptoms of progressive myelopathy including
gait difficulties, motor weakness, dysaesthetic sensory symptoms and
sphincter incontinence.
•• Infants and children on the other hand often develop tetraplegia or are
diagnosed as floppy infant syndrome.
•• Clinical presentation simulating muscular dystrophy and development of
scoliosis is also reported.
•• MRI is the investigation of choice to diagnose these lesions pre-operatively.
•• Hyperintensity seen on T1-weighted images is very characteristic of fat, and
further confirmation can be obtained by fat suppression studies.
•• The lesions are usually located in the dorsal aspect of the cord in the
cervical or thoracic region.
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•• The treatment of these lesions, like any other intramedullary lesion, is

challenging.
•• These tumours are not truly intramedullary but only subpial.
•• Complete surgical excision carries the risk of neurological impairment and
hence partial decompressive resection is recommended.
•• Improvement in neurological status of the patient following surgery is
exceptional; however, the pain disappears due to relief of pressure on the
dorsal columns.
•• Intra-operative ultrasonography may be useful to delineate the extent of
the lesion as lipomas are anechoic.
•• Laser vaporises the fatty tissue without physical manipulation of the neural
tissue and is an important adjunct in the surgery.
NEURENTERIC CYST
•• Neurenteric cyst also called enterogenous cyst, enteric cyst, gastrocytoma,
dorsal enteric fistula, split notochord syndrome and teratoid cyst, is
an infrequently reported congenital anomaly believed to be derived
from an abnormal connection between the primitive endoderm and the
neuroectoderm during the third week of gestation.
•• These cysts may be found within the brain, in the cerebellopontine angle,
mediastinum, abdomen and pelvis or even in a subcutaneous location, but
are more frequently located in the spinal canal.
•• Intraspinal neurenteric cysts account for less than 0.5% of all spinal
tumours.
•• A number of theories have been proposed to explain the occurrence of
endodermal tissue in the CNS.
•• In the trilaminar germ disc formed during the third week of development,
the outer layer, the ectoderm, faces the amniotic cavity and the inner layer,
the endoderm, faces the yolk sac in the opposite direction.
•• Between these two layers lies the mesoderm which gives rise to the
notochord.
•• The neurenteric canal is a temporary direct connection between the yolk
sac and the amniotic cavity through the primitive pit, thus connecting the
anlagen of the spine and gastrointestinal tract.
•• Therefore, malformation at this stage of development results in combined
anomalies of the vertebrae, spinal cord and the gut.
•• The common location of these cysts is the cervical or thoracic region
however, these cysts may occur at any location in the spinal canal from
the craniovertebral junction to the lumbosacral region.
•• Most of the cysts are located anterior or anterolateral to the cord, the dorsal
location being less frequent.
•• These may appear as intradural extramedullary masses or rarely as
intramedullary lesions.
•• Pathologically these cysts vary in complexity and composition.
•• Wilkins and Odum have classified these lesions on the basis of the
histological features of the cyst wall and its contents.
•• The walls of Type A cysts mimic gastrointestinal or respiratory epithelium
with a basement membrane supporting single or pseudostratified cuboidal
or columnar cells, which may be ciliated.
•• Type B cysts also contain glandular organisation, usually producing mucin
or serous fluid.
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•• Type C cysts are the most complex containing ependymal or glial tissue
within the cyst.
•• The World Health Organization has classified these cysts under the heading
of “other malformative tumours and tumour-like lesions” and has described
them as cysts “lined by mucin secreting epithelium resembling that of the
gastrointestinal tract”.
•• Neurenteric cysts are associated with multiple anomalies at single or
multiple levels including scoliosis, fused vertebrae, hemivertebrae, Klippel
Feil anomaly or spina bifida.
•• Cutaneous stigmata, as with other forms of occult spinal dysraphism, also
occur in association with these cysts. Other reported associations include
intradural lipoma, a meningomyelocele and syringomyelia.
ARACHNOID CYST
•• Intradural spinal arachnoid cysts are amongst the rarest causes of spinal
cord compression.
•• They have been described by various names including arachnoid
diverticula, subdural arachnoid cysts, leptomeningeal cysts, meningeal
hydrops and arachnitis cystica.
•• These are congenital collections of CSF contained within the arachnoidal
membrane and subarachnoid space.
•• The origin of arachnoid cysts is still a matter of debate, but most of the
cysts are thought to arise as developmental anomalies.
•• Very few are associated with other causes like neoplasm, arachnoiditis,
trauma and surgery.
•• There are many theories in the literature to explain the development and
expansion of these cysts.
•• Basaldella et al. have summarised these theories:
–– A ball valve mechanism, i.e. a possible anatomical communication
between the cyst and the subarachnoid space that can act as a one
way valve mechanism responsible for cyst enlargement.
–– An osmotic gradient between the intracystic and the extracystic
medium responsible for a gradient driven fluid transport (this theory
lacks support because of the compositional similarity between the CSF
and contents of the cyst).
–– A primary malformation of the arachnoid membrane.
–– Hypersecretive fluid production by cells lining the luminal cyst’s wall.
•• Ultrastructural examination of the cyst wall has revealed that it is formed
from splitting of the arachnoid membrane, with an inner and outer leaflet
surrounding the cavity.
•• As the cyst expands it causes progressive compression of the spinal cord.
•• The usual age of presentation is adolescence and young adulthood, males
being more frequently affected than females.
•• These cysts occur most commonly in the middle to lower thoracic spine but
are also known to occur in the lumbosacral and, rarely, cervical regions.
•• These lesions usually arise posterior to the spinal cord and can also
protrude into the neural foramen.
•• The most common clinical presentation is with motor weakness in the form
of spastic quadri or paraparesis.
•• Other symptoms include back pain, radiculopathy, sensory impairment and
sphincter disturbances.
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•• Symptoms can be intermittent or fluctuating and may be exaggerated by

Valsalva manoeuvres or positional gravitational forces.
•• MRI is the most effective modality for the diagnosis of arachnoid cysts.
•• The imaging characteristics of the arachnoid cysts are similar to CSF in
all sequences.
•• The anatomical relationship to the surrounding structures can be well defined.
•• Scalloping of the vertebral body and expansion of the spinal canal from
osseous remodelling suggests long standing mass effect from the lesion.
•• Treatment is usually conservative for patients with asymptomatic cysts,
with clinical and radiological follow-up.
•• The mainstay of treatment in patients with symptomatic neurological
deterioration is laminectomy with complete excision of the cyst.
•• If a portion of the cyst wall appears to be fused with the pia mater, attempts
at complete excision are not recommended.
•• Delayed deterioration of neurological function after initial improvement may
occur, and is attributed to either spinal cord ischaemia or spinal instability.
•• Cystoperitoneal shunt is recommended if the cyst extends over multiple
spinal segments or recurs after surgical excision.
•• Histological examination of the cyst wall should always be performed to
establish the diagnosis because it is difficult to distinguish an arachnoid
cyst from a neuroepithelial cyst on gross inspection.
MISCELLANEOUS LESIONS
Cavernous Malformation
•• Cavernous malformations are a subset of vascular malformations and are
variably referred to in the literature as cavernomas, cavernous angiomas
or haemangiomas.
•• These malformations are typically discrete, well circumscribed, reddish,
lobulated masses creating an overall appearance that has been likened
to “a cluster of mulberries”.
•• Microscopic examination of these lesions reveals blood containing
sinusoidal chambers lined by simple endothelium and lacking mature
vessel wall components.
•• There is no intervening neural parenchyma and they are surrounded by
a gliotic margin.
•• The exact cause of cavernous malformations remains obscure but these
lesions do have a familial predisposition.
•• MRI is the only confirmatory imaging technique showing salt and
pepper appearance due to haemosiderin deposition caused by multiple
haemorrhages.
•• Clinically these patients may present with either an acute onset of
neurological compromise or a slowly progressive neurological decline.
•• The surgical principles used in the resection of cavernous malformations
are the same as for other intrinsic cord lesions.
Angiolipoma
•• These are very rare congenital lesions affecting the spinal cord, and consist
of abnormally differentiated vascular and mature adipose tissue, usually
located in the epidural space.
•• The diagnosis of this lesion is usually suggested by the presence of a richly
vascularised component and its lipomatous contents.
105
CHAPTER Paediatric
Spinal Tumours
Venkatramana NK
EPIDEMIOLOGY
•• Spinal tumours are rare in children with an approximate annual incidence
of one per million.
•• Spinal cord tumours account for 4−10% of central nervous system tumours
in children of which 25−35% occur within the parenchyma of the cord.
•• Longitudinal “holocord” tumours are very rare and comprises 1% of these
lesions.
•• Common adult intradural extramedullary lesions, such as meningiomas,
neurofibromas and schwannomas, are rarely found in children.
•• In children, 40% of spinal tumours are intramedullary, 20% are intradural
extramedullary and 40% are extradural.
•• Epidural deposits are the commonest non-traumatic cause of paraparesis
in children.
•• The cervical spine is the region most frequently affected, followed by the
thoracic and thoracolumbar spine.
•• Spinal tumours are evenly distributed between males and females, but
a slight male preponderance is noted if congenital tumours are included.
•• Thirty to thirty-five per cent of histologically verified tumours are malignant.
•• Tumours of the posterior fossa in children may metastasise to the spinal
subarachnoid space and may rarely present with a spinal syndrome.
PATHOLOGY
•• The most common paediatric spinal tumours are astrocytoma (16%),
sarcoma (10%), neuroblastoma (9%), ependymoma (8%), dermoids (7%)
and teratomas (7%). Medulloblastoma, neurofibroma, metastatic carcinoma
and lipoma account for another 5%.
•• Spinal haemangioblastomas are very rare in children.
•• Ninety percent of intramedullary tumours in children are astrocytomas,
whereas 60% of adult intramedullary lesions are ependymomas.
•• The most common intradural metastatic lesion is medulloblastoma and
seeding may occur in 10−44% of cranial lesions.
•• Neuroblastomas are the most common cause of extradural cord
compression in children.
CLASSIFICATION
l. Congenital tumours: Teratomas, teratoid tumours, epidermoid, dermoid
cysts and lipomas.
2. Intramedullary gliomas: Astrocytomas, ependymomas, medulloblastomas,
glioblastomas and gangliogliomas.
Chapter 105 • Paediatric Spinal Tumours
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3. Tumours of the meninges and nerve roots—meningiomas and neurofibro-

mas.
4. Extradural extension of paraspinal tumours—neuroblastomas, reticulum
cell sarcoma and lymphosarcoma.
5. Vascular lesions such as cavernomas and haemangiomas.
6. CSF leptomeningeal secondaries—medulloblastomas, ependymomas, glial
secondaries and germ cell tumours.
7. Rare entities, PNET, ependymal cyst.
–– Most classification systems of childhood spinal tumours are based on
the anatomic location of the tumour.
–– They may be intramedullary, intradural extramedullary or extradural.
–– The most common intradural extramedullary masses are dermoid,
neurofibroma, schwannoma, epidermoid, PNET and meningioma.
–– Of these, neurofibroma, schwannoma and meningioma are usually
associated with NF type 1.
–– Extradural masses include sarcoma, neuroblastoma, teratoma, gangli-
oneuroma and lymphoma.
–– Extradural lesions account for about 25% of childhood spinal tumours.
–– Primary metastatic lesions are usually sarcoma and neuroblastoma.
–– Extramedullary tumours are quite evenly distributed throughout the
spine.
–– Sacral involvement is less common, except for developmental tumours.
–– Of these four categories, intrinsic gliomas of the spinal cord and
congenital tumours are more common in children than tumours of the
meninges and nerve root.
–– Congenital astrocytomas have been reported, the pathology being
similar to astrocytomas in older children.
–– Gangliogliomas compromise 30% of tumours in children under 3
years of age. Intramedullary cavernomas are rare and there is a male
preponderance (2:1) and they occur commonly in the cervical region.
•• It is difficult to get a proper history from children.
•• It is equally difficult to get an adequate history from the parents, as they
do not carefully observe the progress of the disease.
•• In addition, there are few reliable physical signs due to the difficulty in
examining the child.
•• The diagnosis is usually long delayed and it is not unusual even to miss
the diagnosis.
•• The median duration of symptoms is 9.2 months (range 1.6−27 months).
•• Malignant tumours have a shorter prodrome (median 4.5 months).
•• A period of close observation after hospitalisation is necessary to bring to
light signs and symptoms which were not recognised earlier.
•• Weakness of one of the extremities, usually a lower limb, and axial pain in
the spine are the most frequent symptoms in children.
•• Signs and symptoms depend on the location of the tumour, plane, extent
of spinal cord compression and bony involvement.
•• In most situations, the progression is indolent and may be associated with
exacerbations and remissions.
•• This axial pain, which is the commonest symptom, increases during
the night due to venous congestion and dural tube distension during
recumbency.
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•• Radicular pain is rare and is caused by nerve root pressure, distension

of the root or infiltration of dorsal root entry zone, and in extra medullary
tumours.
•• The pain can be atypical, simulating abdominal disease or disease
elsewhere in the body.
•• Tenderness and paraspinal muscle spasm may be present on examination.
•• An early and common symptom is diffuse rigidity of the spine, often out of
proportion to the objective neurological signs.
•• In the developing countries, this sign would most commonly suggest
tuberculosis of the spine.
•• Many spinal tumours in children used to be mistaken for anterior
poliomyelitis.
•• An intramedullary cervical cord tumour may be diagnosed as brachial
plexus palsy.
•• A few cases masquerade under the diagnostic label of general prostration,
malnutrition, behaviour problem and polyneuritis.
•• Hydrocephalus can be a manifestation of spinal tumour.
•• Gait disturbance, torticollis and kyphoscoliosis have been reported.
•• Prior history of surgery, especially for spinal dysraphism, should be asked
for as an intramedullary dermoid or lipoma (second tumour) may manifest
after many years.
•• Neurological deterioration years after closure of a meningocoele may be
due to an intramedullary dermoid.
•• Dermoids, epidermoids and lipomas may be associated with a dermal
sinus and present with bouts of recurrent bacterial meningitis or rarely
chemical meningitis which may be confirmed by microscopic observation
of keratin in CSF.
•• There may be either lower limb deformity, weakness or atrophic skin
ulcerations.
•• Rarely, there could be rapid progression, leading to acute paraplegia.
•• The other symptoms include motor disturbances, sensory disturbances
like paraesthesias, dysaesthesias, torticollis and sphincter dysfunction.
•• The only signs or symptoms may be inadequate motor milestones, irritability
and frequent urinary tract infections.
•• Children with slow growing extradural tumours may suffer from frequent
urinary infections and, also loss of bladder control in toilet-trained children
should raise the suspicion of a spinal lesion.
•• Motor deficits vary depending on the level of the lesion and the severity
of the compression.
•• Mild spasticity, increased reflexes and extensor plantar response with or
without clonus occur relatively early in tumours in the thoracic and cervical
regions.
•• Sensory changes are infrequent and quite often difficult to assess
accurately.
•• A complete haemogram, routine urine analysis and a X-ray chest provide
useful information indicating a possible etiology and the general health
status required for preoperative assessment.
•• Serum and urine levels of catecholamines: VMA and homovanillic acid
levels are elevated in patients with neuroblastomas.
785
•• Ewing’s sarcoma may manifest with leucocytosis, increased ESR and

elevated levels of LDH.
Imaging
•• Plain X-rays of the spine are abnormal in 70−80% of children with a spinal
tumour, as the immature spine of children is more vulnerable to increased
intraspinal pressure.
•• The high incidence of congenital tumours in children is also one of the
reasons for the higher incidence of vertebral changes.
•• A tomogram may disclose a diffusely widened spinal canal with relatively
localised erosion or flattening of pedicles.
•• Scalloping and scoliosis may also be present in long standing lesions.
•• Oblique X-rays may show an enlarged foramen as many childhood spine
tumours arise as a transforaminal extension of a paraspinal lesion. Loss
of a pedicle due to bony destruction is characteristically seen as “winking
owl sign” on AP views.
•• CT delineates the bony anatomy and reveals osseous destruction and
tumour calcification.
•• MRI with or without contrast is the imaging modality of choice.
•• It provides excellent images of extramedullary and intramedullary
neoplasms.
•• The T1-weighted image reveals the presence of rostral, caudal and
intramedullary cysts, as well as the solid component of the tumour.
•• T2-weighted images give a myelographic appearance to CSF and cysts.
•• Gadolinium enhancement is mandatory in suspected cases of spinal
tumours, which usually enhances the solid component and helps to
delineate the tumour from surrounding oedema.
•• In most circumstances, malignant tumours appear hypodense on T1 and
hyperdense on T2 with a non-uniform enhancement.
•• Ependymomas enhance brightly and homogeneously. They have polar
cysts with haemosiderin caps at their poles.
•• On axial view, they are usually located in the centre of the cord
•• Astrocytomas and gangliogliomas do not enhance as brightly and their
enhancement is not homogeneous and these are commonly eccentric
causing asymmetric enlargement of the spinal cord.
•• Cavernomas appear with a target sign, with an outside rim of haemosiderin
which is hypodense on T1 and T2 images.
•• Haemangioblastomas will show the brilliantly enhancing tumour nodule
and adjoining cysts.
•• Neuroblastomas are usually isointense or hypointense with areas of
necrosis.
•• Tumours, like dermoids, epidermoids and lipomas which contain fat or
cholesterol, have characteristic high signal intensity on plain MRI.
•• Positron emission tomography may help to categorise the lesions by
abnormal uptake of 18F and 11C-methionine.
THERAPEUTIC CONSIDERATIONS
•• The principles of management involve ascertaining the histological
diagnosis, preservation of neurological function, tumour debulking or gross
total resection, pain relief and spinal stabilisation.
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•• The majority of paediatric spinal neoplasms are benign, low-grade

astrocytomas or gangliogliomas with a slow indolent course and, whenever
feasible, gross total resection should be done without a neurological
compromise.
•• Weinstein described a system of surgical staging of spinal column tumours
and this is currently called Weinstein, Boriani, Biagini Surgical Staging system.
•• Boriani et al. have emphasised the importance of applying the Enneking
system of musculoskeletal tumours to these spine tumours.
•• This divides benign tumours into three stages: S1−S3, and malignant
tumours into four stages: Ia, Ib, IIa and IIb.
•• Two additional stages include metastatic high-grade intra- and extra-
compartmental tumours IIIa and IIIb.
•• Surgery can be tailored to be vertebrectomy, sagittal resection or posterior
arch resection with stabilisation as necessary.
•• Conservative expectant management may be an option in multiple small
lesions seen in a child with neurofibromatosis and von Hippel-Lindau
disease.
•• Spinal CSF leptomeningeal seeding and disseminated disease do not
warrant aggressive surgery.
Surgery
•• It is always advisable to perform a laminotomy in this age group to prevent
future spinal deformity.
•• Complications of laminectomy in children are extensive.
•• Laminectomy in children may be followed by a deformity of the spine, which
is usually not observed in adults.
•• In the lumbar region, an increase in lordosis, in the dorsal region, a
kyphoscoliosis and in the cervical region, an exaggerated lordosis may
ensue.
•• Therefore, as a preventive measure, an ambulatory plaster jacket or a brace
should be employed for at least 6−12 months when the laminectomy has
been extensive in a young child, with emphasis on regular spinal exercise.
•• The technique of osteoplastic laminotomy helps to preserve the posterior
elements, especially when a large area of the cord has to be exposed.
•• For intramedullary lesions, CO2 laser is helpful in doing the myelotomy.
Extradural Tumours
Primary Bone Tumours
•• Extradural tumours in children may be benign and include osteoid osteoma,
osteochondroma, osteogenic sarcoma, osteoblastoma, aneurysmal bone
cyst and eosinophilic granuloma.
•• These are usually amenable to resection and even partial tumour removal
provides excellent results in some of these cases.
Osteoid Osteoma and Osteoblastoma
•• These involve the lamina and pedicles of the cervical and lumbar spine
and result from a benign osteoplastic process comprising of numerous
osteoblasts which produce osteoid and woven bone.
•• Osteoid osteoma when small may be kept under observation and
spontaneous remission may occur.
•• If symptomatic, total excision should be achieved.
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Osteochondroma and Osteogenic Sarcoma

•• These originate from hyaline cartilage during adolescence, usually in the
posterior elements of the dorsal and lumbar vertebrae.
•• Surgical excision should be radical and gives good results.
Aneurysmal Bone Cysts
•• Aneurysmal bone cysts are benign and highly vascular lesions and can be
cured with surgery and bone curettage.
•• The aetiology of these lesions is yet unknown.
•• These lesions usually present in the second decade of life with local pain,
swelling and rarely, spinal cord compression.
•• They are expansile with blood-filled spaces in trabecular osteoid tissue
with multiple haemosiderin containing macrophages, multinucleated giant
cells and fibrous tissue.
•• Treatment includes pre-operative angiography, and when possible
embolisation, followed by complete excision.
Eosinophilic Granuloma
•• These are benign lytic lesions that affect the anterior portions of the cervical
vertebral bodies.
•• They may be isolated or part of syndromes, like histiocytosis X, Hand-
Schuller-Christian disease and Letterer-Siwe disease.
•• These often produces ‘concertina’ collapse or ‘vertebra plana’.
•• A small lesion may undergo spontaneous regression.
•• Low dose radiation or decompressive surgery with reconstruction is
recommended for expansile lesions causing neurological deficits.
Malignant Tumours
•• The role of surgery is palliative with most malignant extradural tumours.
•• Metastatic epidural spinal cord compression occurs in 3% of all children
with malignant solid tumours.
•• Neuroblastomas and ganglioneuroblastomas are operated upon for
establishing the diagnosis or in case of a rapidly deteriorating neurological
deficit.
•• These tumours are sensitive to radiation and chemotherapy.
•• Sarcomas may require surgery in order to decompress the neural elements.
•• Surgical decompression of neural elements significantly facilitates the
neuronal recovery and outcome, especially in children.
•• A combination of steroids, radiotherapy and chemotherapy may be suitably
adopted to improve the outcome.
Neuroblastomas
•• In children, the most common tumours to metastatise to the extradural
space are neuroblastoma and the less aggressive ganglioneuroblastoma.
•• This is the most common malignant paediatric spinal tumour and is derived
from embryonic sympathetic neuroblasts and primordial neural crest cells.
•• The tumours originate from the sympathetic chain and enter the spinal
canal via the neural foramina acquiring a dumbbell shape.
•• Surgical resection with multi-agent chemotherapy and radiation are
advocated.
Ewing’s Sarcoma
•• These highly mitotic tumours arise from postganglionic parasympathetic
neural crest cells.
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•• These occur mostly in the sacrum followed by the dorsal and lumbar spine.
•• These tumours are managed by initial biopsy.
•• If the lesion is low grade, radical excision is followed by radiotherapy and
chemotherapy.
•• If high grade then initial radiotherapy and chemotherapy are followed by
surgery.
•• Lymphomas, chordomas and rhabdomyosarcoma are the other malignant
tumours affecting the spine which may require surgery along with chemo-
and/or radiotherapy.
Intradural Extramedullary Tumours
•• The management of these tumours is less controversial than that of
intramedullary tumours.
•• The majority of them are benign and gross total removal is the cure.
•• Care should be taken to avoid cord manipulation.
•• Radiation therapy is reserved only for malignant lesions.
Intermedullary Tumours
•• They constitute 35−40% of all intraspinal tumours in children.
•• With the advent of modern neurosurgical appliances and imaging
advances, i.e. operating microscope and intra-operative monitoring, laser
and ultrasonic aspirator, radical surgery has become the order of the day.
•• The majority of intramedullary tumours are histologically benign and so a
radical approach has to be adopted.
•• Laminotomy is performed and the dura is opened over the entire length
of the tumour.
•• Intra-operative ultrasound gives a two dimensional image and echogenic
patterns are often helpful in identifying the cyst and the solid components.
•• The myelotomy is performed in the midline or through the dorsal root
entry zone.
•• Astrocytomas or gangliogliomas have a greyish yellow appearance with
occasional calcification but without a plane between the tumour and the
spinal cord. Hence, no effort should be made to develop an interface. Total
excision is seldom possible.
•• Ependymomas are typically red grey in colour and well demarcated from
the surrounding spinal cord and hence can be excised.
•• Lipomas are characterised by exceedingly poor demarcation between the
normal cord and the tumour. Internal debulking with ultrasonic aspirator
and then gradual removal of the tumour is practiced.
•• A transient post-operative neurological deterioration may be observed in
the majority, but the deficit will improve in a few weeks.
•• The incidence of post-operative deterioration is related to pre-operative
motor status.
EVOKED POTENTIAL MONITORING

•• The information provided by SSEP is sufficient to assess functional integrity.
•• However, during intramedullary tumour surgery, motor tracts may be
damaged independent of the sensory system and, in addition, sensory
potentials are often lost soon after myelotomy.
•• Therefore, motor evoked potentials (MEPs), which allow direct monitoring
of corticospinal tracts is preferable.
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•• A single electrical impulse results in the direct activation of fast conducting

axons leading to a potential D-Wave.
•• This can be recorded by an epidural electrode placed just distal to the
intramedullary tumour.
•• D-Wave amplitude signifies the measure of the number of functioning fast
conducting corticospinal fibres.
•• These motor potentials follow an on-off pattern and their presence indicates
intact motor control.
•• Improved electrical conductivity after tumour removal is invariably
associated with a benign post-operative course.
Post-operative Spinal Deformity

•• Scoliosis and kyphosis may evolve after surgery.
•• It is reported that 24−100% of patients experience instability after
laminectomy for resection of a spinal tumour.
•• Therefore, the surgeon must limit the laminectomy to as few segments
as possible and care must be taken to preserve the integrity of the facet
complex.
•• The need for spinal fusion is greatest in the thoracic and thoracolumbar
region.
•• The need to remove a greater number of laminae and pre-operative kyphotic
deformity are linked to spinal sagittal malalignment in children.
•• Age less than 3 years, pre-operative scoliotic deformity (Cobb angle >10
degree), thoracolumbar region and tumours associated with a syrinx in-
crease the odds of post-operative progression of deformity requiring fusion.
•• Osteoplastic laminectomy or bilateral laminotomy is preferred.
ADJUVANT THERAPY
•• Overall, there is no evidence that radiation improves the outcome in
low-grade astrocytomas or ependymomas.
•• Hence, radiation should be reserved only for malignant tumours.
•• However, In a review of the recent literature, several papers advocate RT
for low-grade astrocytomas with a 5-year-survival rate of 50−91%.
•• Survival rates of 55% at 5 years, 39% at 10 years and 79% overall
5-year-survival rate have been reported with conservative surgery and
radiotherapy.
•• Chemotherapy has rarely been used for intramedullary tumours and there
are no large studies documenting its efficacy.
•• Neurologic outcome is decided by the extent of safe microsurgical resection
possible and location of the tumour.
•• Cystic tumours are associated with a much better outcome.
•• Early surgery before significant deterioration is absolutely necessary and
prophylactic surgery has a role in spinal lipoma.
•• Patients should be operated upon early and those patients in McCormick
grades 1 and 2 do much better than grades 3 and 4.
Section IX: Disc Disease and Other Spinal Pathologies
106
CHAPTER Pathophysiology of
Disc Degeneration
ANATOMY OF INTERVERTEBRAL DISC

•• The 6 cervical, 12 thoracic and 5 lumbar discs (23 in all) are basically similar
in structure but they differ in size and shape according to the vertebrae in
between which they are interposed.
•• The end plates (EP) form the interface between the disc and the vertebral
body (VB) above and below it.
•• In each disc, the centrally located nucleus pulposus (NP) is contained by
the outer fibrous shell of the annulus fibrosus (AF).
•• The NP accounts for 50% of the volume of the healthy adult lumbar disc
but only for 33% of the volume of the thoracic disc.
Nucleus Pulposus
•• The nucleus pulposus is a hydrated gel made up of proteoglycans
interspersed by a random and loose network of fine fibrils of type II collagen
and elastin.
•• The major proteoglycan is aggrecan.
•• This substance is composed of anionic glycosaminoglycan (chondroitin
sulphate and keratan sulphate) and it contributes to the osmotic pressure
in the disc needed to resist compressive loads.
•• The NP is derived from the notochordal cells, which stop proliferating after
infancy.
•• In infants the water content of the disc is 90% and this comes down to
about 70−80% in young adults.
•• As age advances, there is progressive desiccation of the NP.
•• The water content of the NP is reflected by the T2 signal intensity on
magnetic resonance imaging.
Annulus Fibrosus
•• The annulus fibrosus is organised into about 12−25 lamellae.
•• Each lamella is composed of spirally running collagen fibrils with randomly
dispersed elastic fibres.
•• There are also other types of collagen (notably, type IX collagen forming
cross links and maintaining the network integrity) and other proteoglycans
such as lumican, biglycan, decorin and fibromodulin.
•• The direction of collagen fibrils in each lamella is tilted to the spinal vertical
axis by about 60° and alternates between one lamella and the next by 120°,
thus producing a woven basket appearance.
Chapter 106 • Pathophysiology of Disc Degeneration
791
•• The lamellar arrangement is better developed in the anterior part of the disc.
•• Elastin fibres lie between the lamellae, passing radially from one lamella
to the next.
•• The lamellae in the outer zone of the annulus attach directly to the VB
above and below (Sharpey’s fibres).
•• These outer lamellae contain type I collagen, which has high tensile strength
and they serve to stabilise the spine during torsional or bending movements.
•• The lamellae of the inner zone attach to the EPs and are composed of
the smoother and weaker type II collagen. The inner annulus acts as a
container for the NP and absorbs the force exerted by the nucleus on
compression loading.
•• The water content of the AF (about 70% of its weight) does not decrease
much with age, unlike the NP. However, the annular fibromodulin undergoes
age related changes.
•• The cells in the annulus are elongated fibroblasts.
•• The AF develops from the dark zone of the densely packed mesenchymal
cells in each sclerotome.
End Plates
•• The vertebral EPs are entirely composed of cartilage in infancy.
•• A rim of ossification appears in the periphery of the cartilaginous EP and
this annular epiphysis fuses with the VB.
•• By 20 years of age, only a small central disc of cartilage remains.
•• The EPs merge with the lamellae of the inner AF, completing the
encasement of the NP.
•• The vertebral EPs are derived from the light zone of the densely packed
mesenchymal cells in each sclerotome.
•• Blood vessels penetrate the EPs during foetal life but as the disc cells
involute, so do the blood vessels.
•• The empty channels left behind by the involuting vessels are possible
origins for Schmorl nodes.
Blood Supply
•• The intervertebral disc is the largest avascular structure in the body.
•• There are no blood vessels inside the NP at any age and in most of the
annulus during adult life.
•• The disc derives its nutrition from the capillary bed in the VB adjacent to
the EP.
•• The arterial supply to this vascular bed is derived from:
–– The centrum branches in the VB supplying the central region of the EP
–– From the ascending and descending branches of arteries on the ante-
rolateral surface of the VB and
–– From the anterior intraspinal arcade on the posterior surface of the
body.
•• Blood flow in the paradiscal capillaries is under humoral control, effected
by acetylcholine through muscarinic receptors. This is one mechanism by
which nicotine might adversely affect the disc nutrition.
Nerve Supply
•• There is no nerve supply to the NP or inner annulus.
Section IX • Disc Disease and Other Spinal Pathologies
792
•• Unmyelinated nerve fibres, unencapsulated and capsulated nerve endings

are found in the outer annulus.
•• The nerve endings in the lateral and anterior annulus serve a proprioceptive
function while those in the posterior annulus are also nociceptive.
•• In the lumbar region, the nerve endings on the posterior annulus are derived
from the sinuvertebral nerve (recurrent nerve of Luschka).
•• The sinuvertebral nerve arises from the dorsal division of the spinal nerve
root, re-entering the intervertebral foramen, dividing into a superior and
inferior branch to supply the disc above and below, as well as the posterior
longitudinal ligament, ventral dura, facet capsule and VB.
•• Pain originating from the structures supplied by the sinuvertebral nerve in
the lumbar region is referred to the buttock but not to the thigh or further
distally (unlike spinal nerve root pain) and is known as dorsal ramus
syndrome.
•• The nerve endings on the lateral and anterior annulus are derived from the
grey rami communicans.
•• In the cervical region the fibres from the grey rami communicans join the
sinuvertebral nerve.
•• The C1 and C2 sinuvertebral nerves also supply the atlantoaxial joints and
the dura of the posterior fossa.
Ligaments
•• The anterior longitudinal ligament (ALL) with a stronger attachment to the
VB and the posterior longitudinal ligament (PLL) with a stronger attachment
to the posterior annulus strengthen the disc, though they are not integral
parts of the disc.
•• The ALL and PLL act as multisegmental tension bands resisting extension
and flexion forces, respectively.
•• Each disc forms a motion segment unit with the zygoapophyseal (facet)
joints at that level.
•• The facet capsules, ligamentum flavum, interspinous, supraspinous and
intertransverse ligaments are important in maintaining the stability of the
motion segment, while at the same time allowing motion to occur.
PHYSIOLOGY OF INTERVERTEBRAL DISC

Nutrition and Metabolism
•• Smaller molecules diffuse in and out of the disc through the EP, while the
larger molecules are transported by bulk fluid flow.
•• Oxygen tension is low in the central region leading to anaerobic metabolism
and build up of lactate.
•• Endplate permeability and, therefore, disc metabolite transport normally
decreases during growth and ageing, but increases in the presence of disc
degeneration and following endplate damage.
•• The relative lack of blood supply causes limited cellular replication and this
accounts for the poor repair capacity in the injured adult disc.
•• In spite of the low blood supply, the matrix and disc cells are metabolically
active.
•• There are matrix metalloproteinases (MMP), a disintegrin and metallo-
protease (ADAM) and aggrecanases that break down the matrix proteins,
which are rebuilt by the disc cells.
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•• A healthy balance between breakdown and accumulation, which is

regulated by genetic and non-genetic factors, is essential for maintaining
the disc integrity.
Biomechanics
•• The water content of the nucleus is vital for its biomechanical properties.
•• When the load limits are exceeded, the EPs fail first before the AF.
•• This happens with compression loads of about 14000N in lumbar disc and
3000N in the cervical disc.
•• Water loss in the disc associated with ageing, reduces the viscoelastic
adaptability of the disc making it prone to fail.
•• A recent telemetric discometry study shows that the original studies had
overestimated the intradiscal pressure on sitting.
•• The pressure increased from 0.1 megapascal (MPa) on lying flat, to 0.46 on
sitting, 0.5 on walking, 0.92 on performing Valsalva manoeuvre, 1.1 while
standing up from a chair, 1.9 while holding a 20 kg weight well in front of
the chest and to 2.3 on bending forwards to lift a 20 kg weight (note that 1
MPa = 10 bar = 106 newton/sq.m).
Ageing Changes
•• Disc dehydration is caused by a decrease in the proteoglycan content of
the matrix in the NP.
•• There is decrease in the collagen content with replacement of type II
collagen by type I collagen in the inner annulus.
•• The type I collagen fibres become coarser and become more cross-linked,
thus increasing their stiffness.
•• The histological changes of ageing are believed to be the result of reduced
vascularity and they affect the EP first, then the NP, and, finally, the AF.
•• The loss of vertebral body bone mass in osteoporosis leads to bulging of
the EPs into the body and reduces the intradiscal pressure.
•• As the NP becomes desiccated, the AF has to bear more of the compression
load. The AF becomes stiffer but structurally weakened.
DEGENERATIVE DISC DISEASE (DDD)

Structural Changes
•• The structural failure manifests as three types of tears in the AF:
–– Circumferential tears occur between the laminae and are postulated
to be due to interlaminar shear stresses. The circumferential defects
are equally distributed in the anterior and the posterior AF.
–– Radial fissures progress outwards from the nucleus, usually posteri-
orly or posterolaterally. Biomechanical studies on cadaveric discs show
that cyclic loading in bending and compression causes radial fissures.
–– Peripheral rim tears are more often found in the anterior AF.
•• The NP tends to herniate along annular defects resulting in a disc prolapse.
•• The result may be a focal protrusion, extrusion or sequestration.
•• The biomechanical load that produces a posterior protrusion is a
combination of flexion and compression.
•• The load bearing shifts to the AF, causing the inner layers of AF to buckle
in towards the low-pressure area of NP. This stage is spoken of as ‘internal
disc disruption’.
794
•• The NP can then be driven up towards the VB, forming a Schmorl node.
•• The structurally weakened outer AF bulges out radially, seen in MRI as a
diffuse disc bulge.
•• Disc height loss also causes the ligaments to buckle into the canal adding to
the soft tissue component of canal stenosis.
•• Excessive annular loading also causes osteophyte formation or bony
enlargement and the end result of these changes is degenerative canal
stenosis.
•• It is now possible to study the abnormal segmental motion with kinematic
MRI.
Biochemical Changes
•• Loss of proteoglycan is the fundamental abnormality in DDD.
•• Undersulphation of chondroitin occurs more in the posterior part of the inner
AF and this might explains the occurrence of radial fissures in this region.
•• Loss of aggrecan allows penetration of molecules, such as interleukin-1
into the disc, which accelerate the progression of degeneration.
Vascular Changes
•• The vascular supply can be reduced by calcific atherosclerosis of the aorta
and lumbar artery stenosis and these are associated with DDD.
•• Even if the blood supply remains normal, nutrients may not reach the disc
cells if the EPs calcify, as is known to occur in scoliosis.
•• A fall in nutrient supply will ultimately lead to degeneration of the disc.
Inflammatory Changes
•• The lack of blood supply suggests that inflammation is not an important
issue in the causation of DDD.
•• However, inflammatory cells, mainly macrophages, have been found in
surgical disc specimens.
•• Both the acute and chronic herniations show activated T and B lymphocytes.
•• Surgical disc specimen analysis shows inflammatory cytokines, such as
interleukin-1 alpha, which in turn increases prostaglandin E2 (PGE-2)
production.
•• Positive straight leg raising test has been correlated with higher PGE-2
content in the disc.
Cause of Pain
•• It is simplistic to assume that pain in DDD is solely due to compression
on the nerve roots.
•• There are patients who present with back and/or leg pain without any
demonstrable dural tube or root compression.
•• Substance-P nerve endings have been demonstrated deep in the AF of
painful discs but only superficially in non-painful discs.
•• Experimentally acute exposure of a nerve root to NP material results in
axonopathy and nerve mechanosensitisation.
•• Chronic exposure results in mechanical desensitisation.
•• MR based study shows that even discs that reach the end stage of
degeneration (‘burnt out’) do not become painless.
795
AETIOLOGY OF DEGENERATIVE DISC DISEASE

•• Degenerative disc disease is multifactorial in aetiology.
•• Ageing and mechanical stress have been implicated for long but only
recently the genetic factors have gained ground as an important cause
for DDD.
Mechanical Load Injury

•• Trauma seems to act by creating microscopic damage to EPs, which allows
the NP pressure to get deflated, setting in motion the chain of events of DDD.
•• Nitric oxide may be the pathway mediating the suppression of proteoglycan
synthesis in response to abnormal loads.
•• In sportsmen, who subject their backs to inordinate loads, MR abnormalities
were found even at young age.
•• The L4-5 disc is more prone to degenerate in persons with L5 sacralisation,
obviously due to abnormal load distribution.
DISC REGENERATION
•• The possible approaches for preventing breakdown of disc matrix and
augmenting growth are:
–– Pharmacotherapy: Anti-catabolic therapy (e.g. inhibitors of MMP),
mitogens (e.g. growth factors), morphogens (e.g. bone morphogenic
protein) and intracellular regulators (e.g. Sox 9) are possible classes of
molecular drug therapies for the future.
–– Cell based therapy: Some substances required for molecular therapy
are large proteins and it is ideal to have them locally synthesised by
means of cell transplants or gene therapy, rather than administering
these exogenously.
–– Gene therapy: This involves the transfer of genes so that the recipient
cells express these genes and synthesise the RNA and the protein
they encode.
–– Other methods: Another possible approach is to improve the diffusion
into the disc. The diffusion enhancing effect of oral nimodipine has
been shown by an Indian clinical study and is yet to be exploited
therapeutically.
IMAGING CORRELATIONS
•• MRI is uniquely sensitive to the changes in the biochemistry of the
degenerating disc.
•• The loss of T2 signal from the NP on desiccation has been mentioned.
•• There is now evidence that the T1-rho relaxation time has a strong
correlation to the glycosaminoglycan content and the intradiscal pressure,
thus providing a means for imaging a biomechanical property.
•• By using dGEMRIC (delayed gadolinium-enhanced magnetic resonance
imaging contrast), the percentage of decrease in T1 was found to correlate
with the grade of DDD.
•• Scanning at 3 Tesla with sodium based imaging helps quantify the
proteoglycan content.
•• High intensity zones (HIZ) in the posterior annulus indicate painful
peripheral rim tear.
796
•• T2 and apparent diffusion coefficient (ADC) mapping has shown

characteristic diurnal differences in the NP, inner AF and outer AF from
morning to evening, again reflecting a physiological event.
•• The paradiscal vertebral marrow changes described by Modic have
extensively been investigated.
•• Type I change (T1 hypointense and T2 hyperintense) is associated with
fissured EPs and oedematous, vascularised fibrous tissue in the marrow.
It is significantly associated with segmental instability and low back pain.
•• Type II change (T1 hyperintense and T2 isointense or slightly hyperintense)
is due to replacement by yellow marrow. It is less clearly correlated with
back pain.
•• The type III change (T1 and T2 hypointense) is thought to be due to bony
sclerosis.
•• CT discography is another technique that reflects the pathology in the NP
and AF even before the disc herniates out.
107
CHAPTER
Cervical Disc Disease and
Spondylosis: Clinical
Features and Diagnosis
CE Deopujari  Rajiv Kumar
INTRODUCTION
•• The term “cervical spondylosis” is used broadly to describe the morphologic
manifestations of progressive degeneration of the spine.
•• It is considered the most common progressive disorder in the ageing
cervical spine and results from the process of degeneration of the
intervertebral discs and facet joints of the cervical spine.
•• Several predisposing factors, such as occupations requiring repetitive
motion of the cervical spine, previous injury with fracture or disc prolapse
and segmentation defects like hemivertebrae or fused vertebrae, may cause
acceleration of these changes.
•• Most people with degenerative changes of the cervical spine remain
asymptomatic.
•• Symptomatic patients are usually older than 40 years of age.
•• There are three main clinical presentations related to cervical spondylosis:
(1) neck pain and brachialgia; (2) radiculopathy; and (3) myelopathy.
•• Neck pain is the most common presentation and is frequently encountered
without a precipitating incident.
•• It may be acute or chronic and occurs more often from degenerative disc
than from degenerative facet changes.
•• Cervical radiculopathy refers to symptoms and signs of nerve root
compression and can be acute, subacute or chronic.
•• Radiculopathy due to soft herniated disc commonly produces weakness and
atrophy while a hard herniated disc produces sensory symptoms consisting
of paraesthesias, hyperaesthesias or hyperalgesias.
•• Motor and reflex changes occur less frequently and are often associated
with a chronic condition.
•• The most common roots affected are C5 and C6. This can be explained
by Sunderland’s observation that C4, C5 and C6 roots have a strong
attachment to the vertebral column while the others are relatively free.
•• Primary compression of the nerve root without impingement of the spinal
cord can result in a radicular pain pattern, loss of strength and/or sensation,
or diminished to absent reflexes.
•• Distribution of signs and symptoms in nerve root lesions are summarised
in Table 1.
•• Lesions affecting the C3 root cause sensory disturbances on the lower
occiput, the angle of the jaw and the upper neck.
798
Table 1: Distribution of signs and symptoms in nerve root lesions

Root Distribution of Distribution of Weak muscles Reflex change
involved pain paraesthesia
C5 Neck, shoulder, Lateral arm Deltoid, Diminished
and lateral arm supraspinatus, biceps,
infraspinatus brachioradialis
C6 Lateral arm and Lateral arm and Biceps, Diminished
forearm, thumb forearm, thumb brachioradialis, Biceps,
and index finger wrist extensors brachioradialis
C7 Dorsal arm and Middle and index Triceps and wrist Diminished
forearm, inter- finger extensors triceps
scapular area
C8 Medial forearm Medial forearm Intrinsic muscles Impaired
and hand, fifth and hand, fifth of hand Finger flexor
digit digit
•• A C3-4 disc resulting in C4 root compression does not produce motor deficit
or reflex changes but will produce pain and sensory changes in the neck,
scapular region and anterior chest wall.
•• A C4-5 disc produces C5 radiculopathy with pain in the shoulder and
anterior arm, weakness of the deltoid and biceps and loss of the biceps jerk.
•• A C6 radiculopathy affects the thumb and the index finger with loss of
biceps jerk.
•• A C7 radiculopathy causes pain and sensory changes in the medial aspect
of the forearm, weakness of the middle and index fingers and loss of
triceps jerk, whereas C8 root affection will affect the ring and little fingers
and weakness of the small muscles of the hand without reflex changes.
•• The abduction relief sign and Spurling’s sign are two examination
manoeuvres that implicate compression of a nerve root at the level of the
foramen.
•• Myelopathy may be precipitated by a large central disc herniation, but
is more commonly the result of spondylotic changes superimposed on a
congenitally narrow canal.
•• The clinical manifestation of myelopathy is characterised by the presence
of long tract signs which include hyporeflexia of the deep tendon reflexes
at the level of affection and hyperreflexia at the levels below the affection
in the upper limbs as well as in lower extremities, increased muscle tone
or clonus, and the presence of pathological reflexes, including Babinski’s
sign or Hoffman’s sign.
•• Inability to grip and rapidly release the fingers is an additional sign of a
myelopathic hand.
•• Early phase of cervical spondylotic myelopathy is also characterised by
clumsiness and unsteadiness of gait.
•• Severe muscle atrophy caudal to the level of stenosis is uncommon with
a spondylotic myelopathy, except in the later stages.
•• Frequently, a combination of radicular and cord symptoms is found
(radiculomyelopathy).
•• Acute exacerbation of radiculomyelopathy can occur in spondylotic patients
after minor trauma and occasionally after unrelated surgery.
Chapter 107 • Cervical Disc Disease and Spondylosis
799
Table 2: Differential diagnosis

Cervical radiculopathy Cervical myelopathy
Brachial neuralgia/neuropathy Amyotrophic lateral sclerosis
Carpal tunnel syndrome Primary lateral sclerosis
Vascular compression syndromes Multiple sclerosis
Vasospastic disorders Demyelinating conditions
Shoulder pathology Syringomyelia
Autonomic disorder Extramedullary tumours
Cardiac diseases Myelitis
Gallbladder disease Spinal AVM and Dural AVF
•• The majority of patients who present with myelopathic features have

concurrent axial neck pain.
•• The most frequent clinical finding or myelopathic sign found in these patients
is spasticity, followed by weakness.
•• Various autonomic symptoms can be produced by cervical disc disease,
e.g. vertigo, flushing, tinnitus and visual blurring.
•• These may be mediated by the sympathetic contribution to the sinuvertebral
nerves from the stellate ganglion.
•• Spondylotic changes at the uncovertebral joints may cause direct kinking
of the vertebral artery and produce similar changes, especially if the wall
of the vessel is atheromatous.
•• Autonomic pathways may also be responsible for the cervical angina
syndrome. Anterior chest wall pain is described with C6-7 disc prolapse.
•• Occasionally, anterior osteophytes may cause swallowing difficulty.
•• The differential diagnoses of cervical radiculopathy (Table 2) are brachial
neuralgia, carpal tunnel syndrome, vascular compression syndrome,
vasospastic disorders and shoulder pathology.
•• The pain and weakness of C5 radiculopathy is very similar to brachial
plexitis which presents with early deltoid weakness.
•• The pain and paraesthesiae of C6 radiculopathy may mimic carpal tunnel
syndrome.
•• Carpal tunnel syndrome is characterised by nocturnal dysaesthesia,
weakness and occasionally thenar atrophy in the distribution of the median
nerve.
•• The pain of lower cervical radiculopathy can mimic thoracic inlet syndrome.
•• Conditions that can mimic spondylotic myelopathy (Table 2) are amyotrophic
lateral sclerosis, myelitis, multiple sclerosis and demyelinating conditions.
IMAGING EVALUATION
•• Cervical X-rays may demonstrate loss of disc space height, spondylotic
bars, foraminal osteophyte, kyphosis, subluxations, posterior compression
from facet arthropathy or late autofusion of adjacent cervical segments.
•• Flexion-extension lateral films may be useful to assess significant instability.
•• Oblique views can also demonstrate foraminal osteophytes.
•• MRI is useful for evaluating the spinal canal diameter, spinal cord and various
components responsible for stenosis and compression, viz. intervertebral
discs, ligamentum flavum hypertrophy and vertebral ligaments.
800
•• Signal intensity changes on T2-weighted MRI scans at the level of spinal

compression are often increased in patients with cervical spondylotic
myelopathy.
•• These represent oedema, inflammation, ischaemia, myelomalacia or gliosis.
•• Occasionally, CT may be required for better delineation of bone anatomy
such as in OPLL.
•• CT is also useful for evaluating the transverse foramina, size and shape
of the spinal canal, facet and uncovertebral joints. Dynamic CT scans are
most useful for evaluation of instability.
•• CT myelography provides excellent visualisation of radicular or cord
compression in patients in whom MRI cannot be performed for any reasons.
Neurophysiologic Studies
•• Electromyography (EMG), nerve conduction velocity (NCV) and
somatosensory evoked potentials (SSEP) may be used to evaluate patients
with radiculopathy or myelopathy.
•• Brachial plexitis, carpal tunnel syndrome and thoracic inlet syndromes can
accurately be diagnosed with the help of these neurophysiological studies.
•• In nerve conduction studies amplitude, distal latency and conduction
velocity are measured. While amplitude corresponds to the number of
intact axons, distal latency and conduction velocity reflect the degree of
demyelination.
•• EMG helps to establish the degree of muscular impairment and the number
and the level of roots involved, and duration of the syndrome.
•• Motor neuron disease can accurately be diagnosed with proper EMG
examination.
•• Segmental dysfunction of the cervical cord can also be confirmed by an
abnormality of the spinal N 13 potential on SSEP.
108
CHAPTER Cervical Disc Disease and
Spondylosis Management
CE Deopujari  Rajiv Kumar  Rajan Shah
MEDICAL MANAGEMENT OF
CERVICAL SPONDYLOSIS
•• Medical management of cervical spondylosis includes pharmacological and
rehabilitation components and mainly targets at pain relief.
•• Acute neck pain can be managed with either non-steroidal anti-inflammatory
drugs or acetaminophen, supplemented with muscle relaxants in the first
2 weeks of symptoms.
•• Medical therapy in patients with radiculopathy and unremitting severe
pain despite a full trial of non-steroidal anti-inflammatory drugs may be
managed with a short course of steroids and paraesthesia may respond
to antineuralgic drugs, viz. gabapentin, pregabaline, etc.
•• Development of radicular deficit and/or progressive myelopathy should
be considered for termination of conservative management and surgical
intervention is recommended.
•• Active modalities are isometric exercises of the neck, postural re-education
and strengthening exercises for the neck, shoulder and back muscles.
•• Passive modalities are heat and cold application, ultrasound, cervical
collar, traction, massage, trigger point treatment and low power cold laser.
•• Traction or manipulation should be avoided.
SURGICAL MANAGEMENT OF CERVICAL

DISC DISEASE AND SPONDYLOSIS
•• Surgical intervention is indicated for patients with spondylosis who have
disabling pain refractory to conservative measures, acute cord compression,
signs of progressive cord dysfunction and progressive muscular weakness
or sensory impairment.
•• Precise correlation between clinical and imaging studies is necessary
before surgical intervention.
•• The goal of the surgical management of patients with radiculopathy or
myelopathy is decompression of the nerve root and spinal cord, elimination
of the anteroposterior flattening and distortion of the cervical cord.
•• Secondary surgical considerations include realignment of the cervical
spine, correction of cervical spinal instability and rectification of cervical
spinal deformity.
•• Two surgical approaches are available: the anterior approach and the
posterior approach with various degrees of laminectomy and laminoplasty.
802
ANTERIOR APPROACH
•• Patients with spondylosis with osteophytes, herniated disc or in those with
evidence of spinal cord compression or mechanically produced neck pain
can be approached via the anterior route.
•• The anterior approach to the cervical spine is easy and safe from levels
C3 through C7.
•• The anterior intervertebral route exposes the vertebral bodies, the discs
and the osteophytes that form in the ventral aspects of the root foramina
and spinal canal which can directly be removed.
•• The anterior approach has two distinct advantages: (1) osteophytes can
be removed safely and (2) fusion of the affected disc space provides
permanent immobility of that joint.
•• The disadvantage is that it does not afford access to posterior elements
that may be compressing the neural structures.
•• For cervical spondylotic myelopathy, the anterior cervical approach is
preferred if the compressive pathology is primarily ventral, localised to the
interspace or is associated with cervical instability, spondylolisthesis or
kyphotic deformity.
Anterior Cervical Discectomy

•• Anterior cervical discectomy (ACD) for cervical disc protrusions started with the
techniques described by Smith and Robinson in 1955, and Cloward in 1958.
•• In 1960, Hirsch showed that good stability and fusion could be achieved
without grafting.
•• In 1965, Robertson used the operating microscope for removing cervical
disc protrusions.
•• Hankinson and Wilson (1975) removed only the central portion of the disc
using a high-speed drill, leaving columns of disc intact laterally.
•• Removal of the posterior longitudinal ligament when it is involved in the
spondylotic compression appears necessary and essential. However,
routine removal of the stronger ligament in young patients when it is not a
component of the compression seems unnecessary.
•• The rationale for removing the posterior longitudinal ligament is that
following discectomy narrowing of the space could cause the ligament to
buckle and produce anterior spinal cord compression.
•• Removal of the foraminal osteophytes is an essential part of the procedure,
whether carrying out ACD or ACDF.
•• Complications of Anterior Cervical Discectomy: Anterior cervical
surgery may have complications, viz. hoarseness, tongue paralysis,
swallowing difficulty, Horner’s syndrome, oesophageal perforation and
fistula, spinal cord/root injury and vertebral artery injury.
Anterior Cervical Discectomy with Fusion

•• The clinical benefits of combining anterior cervical discectomy with bone
grafting (ACDF) versus performing anterior cervical discectomy alone for
cervical spondylosis remains controversial.
•• Discectomy alone requires less surgical time, is associated with fewer
complications and lower cost. Discectomy with fusion results in a more
rapid resolution of neck and arm pain while preventing post-operative
deformity of the spine by stabilising the abnormal motion segment, arresting
spur formation and preventing buckling of the ligamentum flavum and the
posterior longitudinal ligament.
Chapter 108 • Cervical Disc Disease and Spondylosis Management
803
Fusion of the Cervical Spine

•• The term fusion has become synonymous with insertion of the bone graft.
•• Bony fusion, if it occurs, does so after at least a few months, and in a
proportion of patients, never occurs.
•• The goals of the spinal internal fixation procedures are to achieve anatomi-
cal alignment, protect the neural elements and mechanically stabilise the
spine while attempting to preserve the motion of normal spinal segments.
•• These goals can only be attained by a satisfactory arthrodesis.
•• The success of a fusion ultimately depends on satisfactory bone healing as
instrumentation provides immediate but only temporary spinal fixation and
is susceptible to failure due to fatigue, loosening or breakage.
•• When a fusion is undertaken, graft-related complications may be such as
infection, collapse, extrusion, donor site complications like pain and infection
followed by failure of fusion.
•• In addition, fusion is said to predispose to accelerated adjacent level
degeneration.
Techniques of Anterior Spinal Fusion
•• The Smith-Robinson technique involves a thorough discectomy followed
by the insertion of a tricorticate iliac crest bone graft (Fig. 1).The disc space
is usually 1.6−2 cm deep and usually a 1.5 cm long graft is necessary.
•• A tricorticate graft is obtained from the anterior part of the iliac crest so
that its cancellous surfaces will lie against the subchondral bone above
and below the space, while its cortical part forms the support between the
vertebrae.
•• The Cloward technique accomplishes fusion with the use of a bone
dowel (Fig. 1). An autologous iliac crest graft is removed as a dowel or the
allogenic bone graft may be obtained from the bone bank. The bone graft is
obtained from the anterior superior iliac spine by applying the dowel-cutter
transversely on the ilium and a full thickness graft is obtained, leaving the
crest intact.
•• The Bailey-Badgley technique involves cutting a trough with a drill in the
anterior aspect of the vertebral bodies, which should approximately be
1.2 cm wide and 4.7 cm deep near the top of the upper vertebra (Fig. 1).
Cancellous chips from the iliac bone are packed into the disc space and then
an appropriate sized graft is inserted into the trough after applying traction.
Fig. 1: Techniques of anterior cervical fusion

804
•• Bloom and Raney recommend reversing the orientation of the graft so

that the round cortical edge of the iliac crest is placed posteriorly and the
cancellous edge anteriorly so that the protruding portion of the graft can be
trimmed without sacrificing the cortex and decreasing the strength of the graft.
•• White and Hirsch have found the Smith-Robinson configuration of graft
to be the strongest in compressive loading. The strong configuration of
Smith-Robinson arthrodesis is the result of leaving the cortical shell of the
vertebral body intact as 40−75% of the strength of the vertebra comes from
the cortical bone, and the emphasis given to preservation of the end plate.
•• Simmons et al. use a key stone graft for fusion . A rectangular graft is obtained
from the iliac crest and shaped to fit the trough by bevelling the ends upwards
and downwards to approximately 14−18 degrees. After distraction, the graft is
placed into the defect and it gets locked firmly on removal of the distraction.
Bone Grafts and Other Materials Used for Fusion
•• Autogenous bone grafts are mostly obtained from the iliac crest. The
advantages of autografts are that they are live, sterile and non-reactive
being genetically identical to the host.
•• Autogenous cancellous bone is currently the best material for its osteogenic,
osteoconductive as well as osteoinductive properties.
•• Cortical bone adds to the mechanical strength of the graft, but it is slowly
vascularised and is minimally osteoconductive.
•• A bicorticate or tricorticate iliac bone graft as used in most cervical fusion
procedures has the advantages of both.
•• Autogenous vascularised bone grafts can be obtained from the fibula, rib
or iliac crest for spinal fusion as they have superior healing capabilities.
These grafts hypertrophy when subjected to mechanical stress while non-
vascularised grafts resorb early and weaken.
•• Vascularised bone grafts are particularly helpful when the recipient bed is
devascularised, irradiated or scarred.
•• Allografts are transplanted from genetically known identical members of
a species and heal in a similar fashion when used for spinal fusion as the
autografts, although the vascular ingrowths are slower, lesser and new
bone formation is, therefore, delayed.
•• Allografts elicit an immunological reaction and may, occasionally, be
rejected.
•• Cages are now available into which a bone graft can be incorporated.
•• Cages are hollow implants that restore physiological disc height, prevent
disc space collapse and stimulate bony fusion by allowing new bone growth
within and around them.
•• Cages have fusion rates similar to those associated with bone grafts.
•• Complications related to the implantation of the cages are subsidence
into the adjacent vertebral bodies, cage dislocation, non-union and painful
pseudoarthrosis.
•• Methyl methacrylate usually acts as a spacer, which resists compression
and around which cancellous bone may be inserted to promote bony fusion.
This is usually reserved for patients with malignant tumours or when good
bone stock is not available, as it does not promote bone healing.
Instrumented Fusion
•• Casper’s trapezial osteosynthetic plate technique was originally described for
the treatment of cervical spine injuries but has successfully been employed
Chapter 108 • Cervical Disc Disease and Spondylosis Management
805
for treatment of spondylotic myelopathy, post-laminectomy kyphosis,

infections and tumours.
•• It permits neural decompression and immediate stability, is useful for
reducing spinal deformity, prevents bone graft migration and improves
fusion rates.
•• The posterior cortex should be engaged to provide immediate stability and
avoid pull out observed in the Casper and the AO plate systems.
•• The second generation systems (e.g. CSLP from Synthes, Orion from
Sofamer-Danek, Codman plate) allow screws to lock up with the plate and
engaging the posterior cortex may not be necessary.
•• Titanium plates, like in the Orion system, are much lighter, easy to use and
avoid difficulties in post-operative imaging.
•• The latest, third generation systems are the dynamic semi-constrained
plates to prevent stress shielding and allow subsidence.
Dynamic Fusion
•• Dynamic fusion or cervical total disc replacement has emerged as an
alternative for the management of cervical disc herniation.
•• The goals of cervical total disc replacement are to remove the offending
disc while maintaining disc height and segment motion.
•• Preservation of motion at the affected disc level restores normal
biomechanics and offers several advantages such as avoidance of adjacent
segment degeneration, donor site morbidity and early post-operative
mobilisation.
•• Inclusion criteria for cervical disc replacement include symptomatic disc
disease at a single level, and young patients (less than 60 years), while
exclusion criteria include prior fusion at an adjacent level, instability, and
severe facet arthrosis at the affected level.
•• Total disc replacement involves anterior decompression of the disc space,
similar to ACDF. The cervical disc prosthesis is then inserted into the
evacuated disc space in place of bone graft.
•• The cervical total disc replacement implants with the most extensive clinical
experience are the ProDisc-C (Synthes, Oberdorf, Switzerland), the Bryan
cervical disc (Medtronic Sofamor Danek, Memphis, Tennessee) and the
Bristol disc (Medtronic Sofamor Danek, Memphis, Tennessee).
Partial Median Corpectomy and Grafting

•• Anterior discectomy, osteophytectomy and interbody fusion by these various
methods have yielded results superior to decompressive laminectomy, if
the disease process is confined to one or two levels.
•• Surgery for more than three levels is not commonly performed because
of morbidity, prolonged operating time and concern regarding kyphotic or
swan neck deformity.
•• Partial median corpectomy and grafting has been recommended for such
cases.
•• The central two-thirds of the body is resected to ensure decompression of
the spinal canal, but not far enough laterally to disrupt the pedicles.
•• An iliac crest, tibial or fibular bone strut is then inserted into the slots in the
vertebral end plates at the rostral and caudal extremes of the resection sites.
•• The graft is locked in the slotted place with two-thirds of the graft coming
to lie posterior to the anterior aspect of the vertebral column.
806
•• Rengachary and Redford have modified this approach where a trough is

created in the superior and inferior end plates and the whole graft fitted in
the slots beneath the anterior cortex, to allow good contact and compression
of the graft.
POSTERIOR APPROACH
•• Dorsal compression is best treated by a posterior approach.
•• Posterior approach affords easy access to the posterior elements of the
vertebrae, dorsal and dorsolateral aspects of the spinal canal and its
contents from C1 to D1.
•• Cervical canal stenosis, either congenital or degenerative with hard disc
protrusions or hypertrophied ligamentum flavum compressing the cord is
readily relieved by laminectomy.
•• Also, decompression of the cervical roots posteriorly is easily accomplished
with foraminotomy.
•• A variety of posterior surgical procedures exist, including laminectomy,
laminoplasty, foraminotomy and posterior spinal instrumentation with or
without laminectomy.
•• Posterior surgical approaches have several advantages.
•• They generally require less surgical time and they frequently do not require
stabilisation, fusion or instrumentation.
•• The nerve roots are decompressed under direct visualisation, and there is
little risk to major vessels and structures.
•• Disadvantages include post-operative neck pain, spinal instability
stimulating further bone spur formation and an inability to access ventral
canal osteophytes.
Cervical Laminectomy
•• A good decompression can be achieved by a wide and extensive
laminectomy from C3-7 in cases of cervical canal stenosis, either congenital
or degenerative.
•• The laminectomy must be wide enough to demonstrate the posterior and
posterolateral aspects of the dural sac.
•• If the clinical features and pre-operative investigations indicate
radiculopathy without myelopathy, segmental hemilaminectomy and
foraminotomy provide excellent decompression.
•• The complications of extensive laminectomy are late development of spinal
deformity and peridural fibrosis.
•• These can possibly be avoided by expansive laminoplasty. Hirabayashi first
described the procedure in 1977. The expansive open door laminoplasty
is performed by completely incising the laminae on one side and partially
on the opposite side. Elevation with tilting of the laminae upwards on the
incised side allows enlargement of the canal.
Foraminotomy
•• Root compression in the absence of cord compression is best managed
by simple foraminal enlargement at the involved level.
•• Foraminotomy is also useful for radiculopathy caused by osteophytes or
by an extreme lateral soft disc herniation.
•• Posterior laminoforaminotomy is also an effective option in patients with
persistent radicular symptoms following an anterior procedure.
109
CHAPTER
Cervical Ossification of
Posterior Longitudinal
Ligament
Anil Pande  M Vikram  Ravi Ramamurthi
INCIDENCE AND PREVALENCE

•• A high incidence of ossification of posterior longitudinal ligament (OPLL)
has been reported in the Japanese and other Asian populations.
•• OPLL tends to manifest clinically in the 5th to 6th decade of life.
•• Among patients older than 60 years of age, the prevalence of OPLL was
greater than 20%.
•• Most patients with OPLL are asymptomatic.
AETIOPATHOGENESIS
•• The aetiology is multifactorial, in which complex genetic and environmental
factors interact.
•• There are many cascading events like genetic factors of polygenic
character, anatomical stress, age and sex in the formation of OPLL.
Genetics
•• Siblings of patients who share an increased number of human leukocyte
antigen haplotypes are at increased risk of developing OPLL.
•• Specific polymorphisms that may be associated with OPLL occur in several
collagen genes, which encode for extracellular matrix proteins.
•• Polymorphisms in the nucleotide pyrophosphate gene, which is involved
in regulation of calcification in chondrocytes, may also be associated with
OPLL.
Growth Factors and Cytokines

•• Many growth factors and cytokines, including bone morphogenic protein
(BMP) and transforming growth factor-beta, are involved in the pathogenesis
and several transcription factors controlling cellular differentiation may also
have a role.
•• There has also been association of high growth hormone and hypopara
thyroidism in cases of OPLL.
PATHOLOGY
•• OPLL occurs by the process of enchondral bone formation, beginning with
the most superficial layer, progressing to deeper layers and this frequently
involves the dura.
•• There is heterotopic bone formation.
808
•• Fibroblast hyperplasia and cartilaginous proliferation with increased

collagen deposition occurs and this is followed by mineralisation of the
thickened ligament with lamellar bone and Haversian canal formation.
•• The annulus fibrosus remains separate and uninvolved with ossification
at certain levels. The ossified ligament is not always continuous with the
vertebral body.
•• Hypertrophy, calcification and ossification of the ligament occur segmen-
tally. OPLL then extends beyond its posterior margin causing progressive
occlusion of the spinal canal.
•• OPLL involves the cervical spine predominantly followed by the thoracic
and lumbar spine.
•• Multiple level involvement is also commonly noticed with a mean of 2.25
vertebral bodies.
•• OPLL grows with a reported annual increase in size of 0.47 mm
longitudinally and 0.67 mm anteroposteriorly.
•• The enlarging mass may have a round, cuboidal, triangular or polypoid
shape with its base of attachment varying from flat to broad and narrow
to pedunculated.
Pathogenesis
•• The encroachment of the spinal canal causes spinal cord deformation into
a thin, crescent-shaped structure.
•• Neurological symptoms and signs can be expected to develop when the
lesion occupies more than 65% of the neural canal.
•• Two major mechanisms are involved in neural injury, one being mechanical
compression which is both static and dynamic and the other is due to
vascular compromise.
•• Pathological changes in the spinal cord have been observed in the
advanced stages.
•• The extent of gray matter changes and the degree of spinal cord compres-
sion is proportional to the anterior horn deformity.
•• Venous stasis, oedema, ischaemic neuronal necrosis and infarction are
seen leading to cavitations and gliosis in the gray matter and spongiform
atrophy, demyelination and axonal loss in the white matter.
•• The central gray matter and the adjacent dorsal and lateral column are
severely damaged.
•• Progressive myelopathy has been explained by arteriolar degeneration of
the central perforating branches of the anterior spinal artery.
•• Demyelination, axon loss and atrophy have also been noticed in the nerve
roots that have been stretched or compressed.
CLASSIFICATION OF OSSIFICATION OF
POSTERIOR LONGITUDINAL LIGAMENT
•• OPLL is classified as early OPLL and classic OPLL.
•• OPLL in evolution is an early variant and shows focal hypertrophy and
punctuate calcification at the interspaces.
•• On the basis of lateral radiographs, classic OPLL is further classified into
four types: (1) segmental; (2) continuous; (3) mixed and (4) localised (Figs
1A to D).
•• Segmental OPLL is located behind the vertebral bodies and not at the
disc spaces.
Chapter 109 • Cervical Ossification of Posterior Longitudinal Ligament
809
A B C D
Figs 1A to D: Classification of OPLL. (A) Segmental (B) Continuous

(C) Mixed (D) Localised
Fig. 2: Hirabayashi’s CT based classification showing square type,

mushroom type and hill type
•• Continuous type extends from body to body, mixed variety has both
segmental and continuous components and the localised variety is confined
to the disc spaces alone.
•• Hirabayashi et al. suggested a CT based classification and suggested
square, mushroom and hill types of OPLL to reflect its lateral extension
(Fig. 2).
•• Mizuno et al. classified dural ossification in OPLL into three types:
(1) isolated; (2) double layer, and (3) en block type.
MICROSURGICAL ANATOMY OF POSTERIOR

LONGITUDINAL LIGAMENT
•• The posterior longitudinal ligament (PLL) is composed of collagen fibres
with elastin, densely concentrated at its centre and extends from the base
of the clivus to the sacrum.
•• It is attached to the annulus of each inter vertebral disc and the posterior
cortical surface of the vertebral bodies.
•• Its thickness varies from 1 mm to 2 mm.
•• It consists of two layers, a deep ventral layer and a superficial layer.
•• The superficial layer joins the dura at its lateral portion.
•• It is wider at the disc level and is narrow at mid-body level.
•• The longitudinally oriented collagen and elastin fibres are most dense
centrally and thinnest at the site of the most lateral attachment to the
annulus adding substantial strength and stability to the vertebral column
during flexion and, mainly, extension movements.
•• The normal ligament has both type I and type II collagen.
810
•• Ossification involves replacement of the type I collagen matrix with lamellar

bone structure with Haversian canals and a few bone marrow canals.
•• The posterior margin of the vertebral body where the PLL is attached is
the common site of occurrence of OPLL and this extends both rostrally
and caudally.
•• The internal vertebral venous plexus is located in the lateral posterior
longitudinal ligament space.
CLINICAL PRESENTATION AND

NATURAL HISTORY
•• OPLL occurs in association with degenerative disc disease or spondylosis
causing radiculopathy, myelopathy and myelo-radiculopathy.
•• Patients with early OPLL, often in their mid-forties, present with
radiculopathy or mild/moderate myelopathy.
•• Imaging shows hypertrophy of the posterior longitudinal ligament with
punctate ossification opposite multiple disc spaces.
•• Patients with classic OPLL frequently become symptomatic in their mid-fifties.
•• Symptoms include neck pain, radicular pain, dysaesthesia, arm weakness,
leg weakness and urinary incontinence.
•• Hypalgesia below segmental levels on the torso, and radicular sensory
loss is also seen.
•• Subacute development of symptoms over one to two years is common.
•• Acute onset of symptoms or signs and exacerbation of existing neurological
impairment were precipitated after trivial trauma.
•• The pathomechanism of myelopathy in OPLL involves both static and
dynamic factors.
•• The static factors include: spinal canal stenosis and PLL hypertrophy, and
the dynamic factors include: Instability and association with a protruded disc.
•• The axial ossified pattern is classified into two types: (1) a central type and
(2) a lateral deviated type.
•• The incidence of myelopathy in patients with less than 60% spinal canal
stenosis was significantly higher in the lateral deviated-type group than in
the central-type group.
•• All patients in whom there was 60% or greater stenosis of the spinal canal
developed myelopathy, regardless of a history of trauma.
•• The proportion of patients showing motor deficits of the lower extremities
significantly increased when the sagittal canal diameter was narrowed
to less than 8 mm.
•• Myelopathy has been quantified by many authors.
•• The Nurick scale and the Japanese Orthopaedic Association (JOA) scale
are frequently used (Table 1).
Table 1: Nurick scale of myelopathy

Grade 0 Intact, mild radiculopathy without myelopathy
Grade I Mild myelopathy
Grade II Mild to moderate myelopathy
Grade III Moderate myelopathy
Grade IV Moderate to severe myelopathy
Grade V Severe myelopathy, quadriplegic
811
MANAGEMENT
Radiodiagnosis
Plain X-rays
•• Plain X-rays are very useful in diagnosing and classifying OPLL and
dynamic X-rays are useful to check for abnormal mobility.
•• OPLL is visible as retrovertebral calcification on plain films in approximately
one third of cases.
•• The normal spinal canal diameter is 17 mm from C3 to C7 on plain X-rays
taken at a distance of six feet.
•• Absolute stenosis is when the diameter is 10 mm or less and relative
stenosis is when it is 10−13 mm.
•• Occupancy ratio (OR) is obtained by dividing the thickness of the OPLL
by the AP canal diameter.
•• If the OR is greater than 40%, there is an increased risk of myelopathy.
Computed Tomography (CT) Scan and CT Myelography
•• A 2−5 mm thick linear ossified strip along the posterior vertebral margin is
usually seen at the mid cervical (C3 to C5) level.
•• CT more readily identifies the foci of frank ossification.
•• Patients with OPLL frequently show concomitant ossification of the
anterior longitudinal ligament and posterior longitudinal ligament in the
thoracolumbar region and the yellow ligament.
•• OPLL was most frequently observed at C5 and the number of vertebral
bodies on average was 3.1.
•• The thickness of the OPLL ranged from 2.5 mm to 11.5 mm.
•• Canal stenosis was most severe in patients with ‘total’ type of OPLL.
•• Bone window studies may show two signs of dural ossification: (1) the
double layer or (2) the single layer sign.
•• On pre-operative computed tomographic studies, the single-layer sign
characterised by a solid mass of hyperdense OPLL and the double-layer
sign defined by two (anterior and posterior) ossified rims surrounding a
central non-ossified but hypertrophied posterior longitudinal ligament.
•• When the single layer sign is associated with a lateral C-shaped
configuration of ossification, dural involvement is seen more frequently.
•• The double-layer computed tomographic sign is more pathognomonic for
dural penetration than the single-layer sign.
•• The size of the spinal canal is a factor that contributes to the neurological
deficits associated with OPLL.
•• The spinal canal was narrowed by OPLL to 2.9−10.0 mm.
•• CT myelography is recommended, especially when previous surgery has
been performed or in cases of anterior spinal instrumentation with metallic
implants restricting the MRI sequences.
•• The interpedicular distance can be measured and varies from 14 to 20 mm
and helps in deciding upon the width of the corpectomy.
•• Post-operative myelo-CT studies are used to confirm the adequacy of
decompression.
•• MRI provides information on spinal cord structure and associated soft-tissue
abnormalities and is especially useful for evaluating the cervicothoracic
junction.
812
•• The length of the lesion, cervical axial canal area, anteroposterior (AP)
diameter of the cervical canal, spinal sagittal angles, cervical curvature
index (CCI) and signal changes in the cord can be made out.
•• MRI is valuable in studying associated cord damage and associated disc
lesions prior to surgery.
•• The T1-weighted images clearly demonstrate the spinal cord deformity
caused by OPLL.
•• Associated disc protrusion is found to be present at the maximum
compression level in 60% of the patients.
•• A calcified central sequestrated disc is the only condition that may be
mistaken for the segmental and retrodiscal forms of OPLL.
•• The highest incidence of disc protrusion (81%) was found in patients with
segmental OPLL.
•• OPLL appears as a low signal intensity band between bone marrow of the
vertebral body and the dural sac on T1- and T2-weighted images.
•• The continuous type of OPLL is easier to diagnose than the segmental type.
•• Formation of bone marrow is shown by increased signal or intermediate
signal in 56% and 11% of the segmental type.
•• Intramedullary hyperintensity on T2-weighted imaging was noted in 43%
of patients.
•• On T1-weighted and T2-weighted images, ligamentous calcification or
ossification appears as a region of low-signal intensity.
•• A sagittal image details the longitudinal extent and anatomical type of OPLL.
•• Axial images can demonstrate the extent of neural canal stenosis, including
developmental and acquired anterior and posterior components.
•• MRI shows signal intensity changes which may be due to cystic necrosis
of the cord, which is irreversible, but sometimes the signal intensity may be
due to venous infarction and this progression can be halted by early surgery.
TREATMENT
Conservative
•• Acute episodes of pain and the onset or increase of neurological deficits are
treated with rest, external spinal immobilisation with a collar or brace and
administration of analgesics, including anti-inflammatory or antispasmodic
medication.
•• Treating asymptomatic patients surgically or recommending prophylactic
total excision of all OPLL is not advisable as the natural history of the
disease is variable.
Operative
•• Surgery is aimed at enlarging the spinal canal by decompressing the
bony ring and is indicated for patients with acute or chronic progression
of neurological deficit.
•• MRI showing signal intensity changes in the cord suggestive of cord
oedema in T2-weighted sequence indicates sub-clinical dorsal cord
compromise and warrants surgical intervention.
•• Similarly, SSEP responses indicating sub-clinical dorsal cord compromise
may also indicate surgical intervention.
•• Compression by a large bone mass directly on the anterior surface of a
chronically constricted spinal cord causes anterior spinal artery compromise
that leads to vascular myelopathy and neurological deficit, which could be
irreversible.
813
Selection of Surgical Procedure

•• The choice of surgery depends on the age of the patient, location of
the lesion and the extent of OPLL causing spinal cord and nerve root
compression.
•• Developmental size of the spinal canal and the canal diameter compromise
due to OPLL causing spinal cord compression are important factors
influencing clinical management and the neurological state.
•• Being an anterior pathology, anterior procedures offer direct access and
removal of the pathology.
•• Posterior procedures give indirect decompression for multilevel
involvement, leaving behind the progressing anterior pathology untouched.
•• Kyphotic alignment of the cervical spine and a large OPLL are major factors
causing poor surgical outcome after laminoplasty for cervical OPLL.
•• OPLL with disc protrusion causes greater spinal cord compression at the
disc level.
•• The K-line is a simple and practical tool for making decisions regarding the
surgical approach for cervical OPLL patients.
•• The K-line was defined as a line that connects the midpoints of the spinal
canal at C2 and C7.
•• The group of patients in whom the OPLL did not exceed the K-line are the
K-line (+) group.
•• Those in whom the OPLL did exceed it are the K-line (–) group.
•• A sufficient posterior shift of the spinal cord and neurological improvement
was not obtained after posterior decompression surgery in the K-line (–)
group.
Surgical Technique
•• Anaesthetic considerations: Fibreoptic pre-operative intubation is
electively performed by specifically trained anaesthesiologists when
deemed appropriate.
Posterior Procedures
•• Posterior procedures are preferred when the OPLL is continuous, involves
a long segment, in elderly high-risk patients, when the upper limit of OPLL
includes C2 and in cases with a normal spinal sagittal balance.
•• These include laminectomy alone, laminectomy with fusion, laminoplasty
and various newer techniques of laminoplasty, e.g. modified Hirabayashi-
type unilateral open-door laminoplasty (Figs 3A to F).
•• They offer adequate decompression in the presence of adequate cervical
lordosis and the removal of multiple laminae and hypertrophied yellow
ligament allows dorsal migration of the cord.
•• The presence of kyphosis may leave the cord tethered to the anterior
pathology and cause neurological deterioration.
•• A mean dorsal cord shift of greater than 3 mm was co-related with good
clinical outcome.
•• After laminectomy, post-operative progression of kyphotic deformity was
observed.
•• Cervical range of movement (ROM) reduces after cervical laminoplasty.
•• Post-laminoplasty cervical ROM had a positive correlation with extended
motion; however, gradually it became reduced.
•• Surgical outcome was significantly poorer in patients with occupying ratio
greater than 60%.
814
A B C
D E F
Figs 3A to F: Various laminoplasty methods. (A) Open door (B) Bilateral

French door (C) Splitting the spinous process and lamina with a spacer (D)
Modified open door method with a spacer (E) Z-shaped laminoplasty (F)
Laminotomy and fusion with ceramics
•• The most significant predictor of poor outcome after laminoplasty was

hill-shaped ossification, followed by lower pre-operative JOA score, post-
operative change in cervical alignment and older age at surgery.
•• Laminoplasty is effective and safe for most patients with occupying ratio
of OPLL less than 60% and plateau-shaped ossification.
•• OPLL is a progressive disease, and an increase in the area of ossification
following laminoplasty affects the surgical results.
•• Tension band laminoplasty described by Tsuzuki helps to minimise the
severe post-operative contractures seen in laminoplasty. In this technique,
the lamina are reflected unilaterally in an open door fashion keeping the
interspinous and ligamentum flavum intact and these behave as a tension
band.
•• Double door laminoplasty was developed by Kurokawa, and in this the
spinous process and laminae are split centrally and retracted symmetrically
in a double door manner.
•• Increase in segmental motion may lead to deterioration after posterior
approaches which may be aggravated by the progressive atrophy of
nuchal muscles.
•• In patients with either CSM or OPLL with instability, cervical laminectomy
with fusion (arthrodesis) improved the functional outcome.
Anterior Procedures
•• The overall improvement of the neurological status of the patients were
better in the anterior procedures than the posterior procedures.
•• Anterior discectomy, corpectomy and fusion are now considered the optimal
operative treatment.
•• Segmental plate fixation is biomechanically better than end construct plate
fixation.
•• In focal segmental lesions that do not extend above or below the disc,
a simple interbody discectomy, excision of OPLL and fusion may be
adequate.
•• Complete resection of the lesion requires microsurgical removal of the
involved posterior longitudinal ligament and the adjacent osteophytes.
815
•• The technique of resection of OPLL with floating of dural ossification provides

satisfactory decompression and avoids dural defect or neural injury in OPLL
associated with dural ossification.
•• Kamikozzuru and Yamaura developed the original floating method and this
technique requires more extensive corpectomy to free the ossified dura
leading to a ventral migration of the OPLL mass but this procedure does not
remove the OPLL and there is an increased risk to the vertebral artery and
root injury while doing this extreme lateral resection technique.
•• Hida et al. advocated the microfloating technique that makes the OPLL
paper thin by using a high speed drill under a microscope and resecting it.
•• Modifications of corpectomy in the form of open-window corpectomy, oblique
corpectomy and floating methods have been advocated for avoiding instability
and instrumentation.
•• Continuous intra-operative somatosensory evoked potential (SSEP)
monitoring also appears to limit operative morbidity.
•• Open window corpectomy: This operation which involves minimal bone
removal with high-speed drilling, dorsal surface removal after appropriate
microdiscectomy leaving the anterior and lateral parts of the vertebral
bodies intact. This provides a more stable construct with three point fixation
and offers better load sharing.
•• The oblique corpectomy: It preserves the ventral half of the vertebral body
and does not require stabilisation. It avoids a multilevel central corpectomy
that is associated with significant instability often requiring reconstructive
procedures.
•• Goel et al. have elaborated on partial oblique strategic corpectomy involving
extended midline and lateral undercutting of the vertebral body.
•• The skip corpectomy technique: This is characterised by C-4 and C-6
corpectomy, C-5 osteophytectomy and C-5 vertebral body preservation;
the preservation of the C-5 vertebral body provided an additional screw
purchase and strengthened the construct.
•• OPLL often coexists with cervical disc herniation and the disc may be the
more important compressing factor.
•• The area of greatest spinal cord compression is at the disc levels because
of herniated cervical discs. Staged or combined anterior and posterior
decompression may be necessary in a small segment of patients with
mixed or continuous long segment OPLL.
•• Anterior, anterolateral decompression and fusion for ossification of posterior
longitudinal ligament in the thoracic spine by transthoracic trans-sternal
approach is possible with good neurological outcome compared to posterior
decompression and fusion with laminectomy or laminoplasty.
•• Complex cases of thoracic ligamentous ossification involving both the
ligamentum flavum and the posterior longitudinal ligament may require
combined procedures.
Complications
•• Complications of anterior cervical surgery include a risk of quadriplegia,
root injury typically the C5 root, which has been attributed to rapid cord
migration and the so-called “untethering effect”.
•• Temporary paraparesis and new cervical radiculopathy may be caused
due to residual foramen stenosis.
•• CSF fistulas, bone graft displacement, pin site infection, graft site
complication (iliac bone fracture, meralgia paraesthetica) implant failure,
816
restenosis, tethering, wound infection, epidural haematoma, deformity,

respiratory insufficiency, oesophageal perforation, bladder disturbances,
Horner’s syndrome and retropharyngeal abscess have been reported.
•• Temporary recurrent laryngeal nerve and superior laryngeal nerve palsy due
to retraction injury may cause hoarseness of voice and swallowing difficulty.
•• Phrenic nerve dysfunction may be due to bilateral C4 nerve root stretching,
iatrogenic injury of the gray matter in the ventral horn, alteration of blood
circulation related to spinal oedema or re-impingement on the spinal cord
at the cranial part of the decompression site.
•• Phrenic nerve dysfunction should be considered as a possibility when it is
difficult to wean a patient from the ventilator after surgery.
•• Post-operative cerebrospinal fluid leak and pseudomeningocoeles: Patients
with OPLL are especially prone to dural leaks and these are managed with
dural repairs and rarely lumboperitoneal shunting procedure.
•• The surgeon is required to recognise dural ossification and be cautious
during drilling of the OPLL.
•• Hida et al. described the (CT) findings that indicated the association with
dural ossification and suggested that the ‘double-layer sign’ appeared
more specific.
OUTCOME
•• Outcome analysis can be done using tools such as the Odom’s criteria.
•• OPLL thickness, effective canal diameter, anteroposterior cord compression
ratio, the traverse area of the spinal cord, the spinal cord-evoked potentials
(SCEPs), the increase of the range of motion in the cervical spine (ROM),
diabetes, history of trauma, the onset of ossification of the ligament flavum
(OLF) in the thoracic spine, snake-eye appearance (SEA) and incomplete
decompression may be other factors influencing outcome.
•• Age at surgery seems to be closely related to the outcome of the posterior
surgical procedure.
110
CHAPTER
Thoracic Disc Prolapse
INTRODUCTION
•• The incidence of thoracic disc prolapse is about 0.04 of all cases of disc
prolapse.
•• With the increasing use of magnetic resonance imaging (MRI) more cases
with subtle lesions are picked up.
PATHOLOGY
•• It may occur at any age, being most frequent during middle age.
•• Due to the resilient bony thoracic cage which permits only limited move-
ments and the relatively small size of the thoracic disc, actual protrusion
of the intervertebral disc into the thoracic canal is uncommon, although
degenerative changes in the form of Schmorl’s nodes and anterior and
posterior osteophytes are seen frequently.
•• Such changes are more common in people carrying loads on the back.
•• The cause of nucleus pulposus herniations in the thoracic spine is similar
to those occurring in the lumbar and cervical regions.
•• The lower incidence of herniations is ascribed primarily to the reduced
allowable flexion at the thoracic level compared with the lumbar and cervical
levels and, to a lesser extent, the contribution of the ribs to weight bearing.
•• The protrusion is commonly central, but may be centrolateral or lateral.
•• Intradural disc herniation in the thoracic region occurs in less than 5%,
but is a well-recognised entity in the lumbar region, where over 90% of all
intradural herniations are seen.
CLINICAL FEATURES
•• The diagnosis of thoracic intervertebral disc herniation is often missed due
to its complex and variable presentation.
•• The signs and symptoms are often of a relatively long duration, usually
vague and frequently misleading.
•• Pain localised to the back, girdle pains, pain in the abdomen, testicular
pain or limb pain may be present.
•• The symptoms may range from mild paraesthesia to paraplegia.
•• Bladder, bowel and sexual disturbances are late features.
•• Position sense is frequently intact.
•• Mild scoliotic or kyphotic deformities may at times be present and act as a
natural protection in accommodating the prolapsed disc segment.
•• The delay in diagnosis is often a consequence of failure to consider
protrusion of a thoracic intervertebral disc as a diagnostic possibility.
818
•• Ossification of the ligamentum flavum (OLF) and ossification of the posterior
longitudinal ligament (OPLL), occurring in the thoracic region, may simulate
cord compression by thoracic discs.
•• OLF is common in males and occurs at a lower thoracic level, while OPLL
may occur at any level.
•• Plain radiology, myelography, CT myelography and MR are useful for
correct localisation of the pathology.
•• The approach to treatment for OLF is different from that of thoracic disc
prolapse and OPLL.
INVESTIGATIONS
•• Calcification may be seen at the site of disc degeneration on plain X-rays.
•• The affected disc space is narrowed.
•• Bony spurs may be seen along its anterior and posterior surface.
•• MR is the investigation of choice and shows the prolapse clearly, even when
this is minimal. The extent of the prolapse, and the exact relationship of
the bulge to the cord and roots are clearly seen. Extradural tumours can
easily be differentiated from disc prolapse.
•• CT and myelography are less sensitive, when compared to MR.
TREATMENT
Surgical Management
•• Evidence of cord compression is an indication for surgery.
•• Various surgical approaches for the excision of a prolapsed thoracic disc
have been described.
•• When indicated, discectomy may be performed via an anterior, posterior
or anterolateral approach depending on the location of the disc herniation.
•• Posterior routes include the transpedicular, lateral extracavitary approach,
and the more recently described minimally invasive extracavitary approach.
•• Minimally invasive technique via a transpedicular route with the use
of tubular retractors and microscope visualisation. This technique
provides a safe method to identify the thoracic disc space and perform a
decompression with minimal paraspinal soft tissue disruption.
•• The transpedicular approach also appears to be most suitable for
discectomy for dorsolumbar junction disc prolapse.
•• The approach is minimally invasive considering the size of the incision,
minimal bone removal and avoidance of vital structures.
•• Post-operative pain is minimal and ambulation can be begun within 24
hours of surgery.
•• Decompressive laminectomy without dealing with the prolapsed disc has
been described. The results of such an operation are unsatisfactory and
may even be deleterious, as the compressive element persists.
•• Approaching the prolapsed segment through a laminectomy is dangerous
as the thoracic disc prolapse is central or centrolateral and the dorsal cord
tolerates retraction poorly.
•• The thoracic disc is best approached by the anterolateral route through the
lateral costotransversectomy approach, transpedicular approach or by an
anterior route through a thoracotomy (transpleural or retropleural approach).
Chapter 110 • Thoracic Disc Prolapse
819
•• Intra-operative fluoroscopy or plain radiographs are traditionally used to

localise thoracic spine levels during thoracic spine operations.
•• Unfortunately, such localisation can occasionally be difficult in the
midthoracic levels due to lack of landmarks, scapular shadows and the
body habitus of the morbidly obese.
•• For efficient and accurate intra-operative localisation of thoracic spinal
levels during anterior thoracic spine procedures, Hsu et al. have described
a method that uses pre-operative percutaneous placement of polymethyl
methacrylate (PMMA) into the vertebral body using the standard
vertebroplasty technique.
•• Video-assisted thoracoscopic microdiscectomy is gaining acceptance as a
minimally invasive, safe and efficient technique suited for herniated thoracic
discs from T4-T5 up to T11-T12.
•• The transpedicular approach is most applicable for lateral or centrolateral
calcified or soft discs.
•• The more anterior (transthoracic or thoracoscopic) and lateral
(costotransversectomy or lateral extracavitary) approaches may be more
useful for excision of central calcified discs.
•• Newer, minimally invasive techniques with a nearly absent learning curve
are evolving. One of these techniques is the mini-thoracotomy (mini-TTA).
•• To reduce the invasiveness and risk of thoracic disc surgery, endoscopic
approaches have been developed.
•• Thoracic microendoscopic discectomy is a safe and effective treatment for
surgical removal of herniated thoracic intervertebral discs. This approach
allows access through a minimally invasive muscle-splitting posterolateral
approach that does not place the contents of the thoracic cavity at risk.
•• In the lumbar spine, this approach has been proven effective, with a shorter
length of hospital stay, less post-operative pain, decreased blood loss and
shorter recovery time.
•• These same advantages can be expected in the thoracic spine with
appropriate patient selection and proper surgical technique.
•• Jho has described the transpedicular endoscopic approach.
•• The surgical technique of posterior transpedicular thoracic discectomy was
modified to endoscopic transpedicular surgery.
•• Giant herniated thoracic discs (HTDs) can be defined as occupying more
than 40% of the spinal canal.
•• Patients with giant HTDs presented more frequently with myelopathy and
experienced worse functional outcomes than those with smaller HTDs and
recommend open thoracotomy rather than thoracoscopy for the treatment
of midline giant HTDs.
Complications
•• The procedure-related complications include death, neurological deteriora-
tion, post-operative vertebral column instability, incomplete disc resection,
discectomy at the wrong level, cerebrospinal fluid leak and fistula, infection,
pulmonary embolism, pneumothorax, pneumonia and intercostal neuralgia.
•• Unusual complications include chylorrhea. The thoracic duct along with the
cisterna chyli is a major lymphatic pathway near the anterior thoracolumbar
spine.
•• Despite the fragile nature of the lymphatic system and its proximity to the
spinal column, chylorrhea is rarely encountered by spine surgeons.
820
Conservative Management
•• Conservative treatment rarely helps, as the relatively narrow dorsal canal
cannot accommodate intrusions and as the thoracic cord is very sensitive
to mechanical compression and vascular compromise.
•• The herniated discs exhibited marked decrease in size, corresponding
to a favourable clinical outcome within a few months after the initiation of
conservative treatment with prostaglandin E3 and/or steroids in conjunction
with physical therapy.
•• The thoracic herniated discs are capable of undergoing natural resorption
and that conservative treatment could be indicated, even in the presence
of moderate myelopathy, when the myelopathy is not accompanied by
bladder dysfunction or progressive muscular weakness.
111
CHAPTER
Lumbar Disc Disease
Manas Kumar Panigrahi  Rajesh Reddy S
INTRODUCTION
•• The term “lumbar degenerative disc disease” includes a spectrum of
disorders like disc bulge, disc protrusion (central, paracentral, intraforaminal
or far lateral), disc extrusion (with or without migrated fragment) and internal
disc disruption.
•• Patients suffering from this condition present with low-back pain or
radiculopathy of long duration or, acutely, as cauda equina syndrome.
ANATOMY AND BIOMECHANICS OF

THE LUMBAR INTERVERTEBRAL DISC
•• The intervertebral disc (IVD) is composed of three elements which include
the nucleus pulposus, annulus fibrosus and cartilaginous end-plate.
•• The nucleus pulposus is the central portion of the disc which is composed
of cells from the primitive notochord.
•• It is composed of type II collagen and a very hydrophilic polymer called
glycosaminoglycan, which is capable of absorbing a large amount of water
and forming a gel-like matrix.
•• The amount of water absorbed by the nucleus depends not only on the
composition of the polymer matrix but also on the external pressure exerted
on the disc.
•• At a young age and when the disc is healthy, 80% of the nucleus is
constituted by water, even under normal loading conditions, which keeps
the annulus well inflated. It becomes more solid and fibrous with age.
•• The annulus is a fibrous structure composed largely of type I collagen
that restrains lateral forces produced by the compressed nucleus which is
located within it, slightly dorsal to the midline.
•• It is a multilayered structure, much like an automobile tyre, composed
of 10–12 concentric layers of well organised collagen fibres running in
opposite directions in adjacent layers at approximately 30 degree to the
horizontal plane.
•• This arrangement provides the annulus with a high tensile modulus and
strength, as well as equal torsional modulus in either direction.
•• The annular bands are subdivided into inner fibres, which are connected to
the cartilaginous end-plate, and outer Sharpey fibres, which are attached
to the vertebral body.
•• The disc has a low metabolic rate and receives most of its nutrition by
diffusion.
822
•• The majority of the disc nutrition is supplied via the capillary beds of the
cartilaginous vertebral body end-plate.
•• The capillaries receive blood from the lumbar arteries which arise from the
aorta and supply the vertebra in a segmental fashion.
•• Vascular and lymphatic tissue is present in the annulus of young patients but
the nucleus pulposus does not have blood vessels or lymphatics at any age.
•• A meningeal branch of the spinal nerve, known as the recurrent sinuver-
tebral nerve of Luschka, which arises from the posterior ramus of each
nerve root, innervates the dura, PLL and the fibres of the annulus fibrosus.
•• The outer annular regions are innervated but the inner regions and the
nucleus pulposus are not innervated.
•• Degenerated human lumbar discs have been found to contain more nerve
tissue and more vessels than normal discs.
PATHOPHYSIOLOGY OF
DEGENERATIVE DISC DISEASE
•• The IVD performs two important but somewhat conflicting functions, i.e. it
maintains spinal column stability while providing the column with necessary
flexibility.
•• Lumbar disc degeneration and herniation are multifactorial processes to
which both mechanical and biochemical derangements contribute.
•• Degenerated discs show abnormal vascularity, abnormal distribution of
collagen and collagen cross links and, abnormal and non-uniform elastic
modulus that distributes stress to critical portions of the disc.
•• Repetitive or continuous axial overloading is the key determinant in the
pathogenesis of lumbar degenerative disease.
•• Obese individuals, manual labourers, truck drivers and those involved in
athletic activities like weight lifting and gymnastics are at risk of repetitive
axial overloading of the spine.
•• The process of disc degeneration occurs in both the annulus fibrosus and
the nucleus pulposus.
•• With advancing age, the mechanical strength of the annulus decreases
and the nucleus also loses its water binding capacity.
•• As a result, the stress in the vertebral column, which in normal individuals
is transmitted to the centre of the end-plate, is transmitted to the peripheral
portion of the vertebral body and the weakened annulus, resulting in disc
herniation and compression on the adjacent nerve root. This, in turn,
accelerates the degeneration of the facet joints.
•• Radicular pain associated with disc herniation has been attributed, in
part, to the inflammatory response at the site of disc herniation, resulting
in an increase in the number of macrophages and IL 1β with subsequent
release of PGE2.
•• The majority of disc herniations occur in a posterolateral direction, i.e.
corresponding to the region of the spinal canal between the midline and
the neural foramen, because the nucleus pulposus is situated somewhat
posteriorly within the annulus and the PLL reinforces the annulus fibrosus
in the midline posteriorly.
•• A disc bulge is a symmetrical extension of the disc beyond the endplates,
whereas a disc protrusion is a focal area of extension still attached to the disc.
•• An extruded or free fragment disc herniation refers to the part of the
herniated disc that is no longer connected to the disc, and herniated disc
Chapter 111 • Lumbar Disc Disease
823
material that is contained within the PLL is termed a sequestrated or

subligamentous disc herniation.
CLINICAL FEATURES
Symptoms
•• A patient with a herniated lumbar disc may present with radiculopathy,
neurogenic claudication or cauda equina syndrome.
•• The initial symptom is pain, which may be in the back, buttock, thigh, leg or
foot which is present either in all areas or a few of these areas.
•• Radicular pain is aggravated by bending, coughing, sneezing and lifting
a grounded object.
•• The pain is usually relieved by lying down in a hip-knee flexed posture.
•• The back pain often resolves to be replaced later in the course of the
disease by weakness and numbness in the lower extremity.
•• The radiation of pain helps the clinician localise the nerve root that is involved
and, in many but not all cases, the level of the herniated disc (Table 1).
•• A posterolateral disc herniation compresses the ipsilateral nerve root at
its exit from the dural sac (under the pedicle of the lower vertebral body)
rather than in the neural foramen.
•• A patient with posterolateral left L4–L5 disc herniation would present with
left L5 radiculopathy. On the other hand, a far lateral disc herniation often
affects the ipsilateral nerve root exiting through the adjacent neural foramen
(under the pedicle of the upper vertebral body), i.e. a patient with left far
lateral L4–L5 disc herniation would present with left L4 radiculopathy.
•• Paraesthesias in the form of tingling, pins and needles sensation or
numbness is of great value in localising the level of root compression. The
more distal its location, the more reliable it is in helping with root localisation.
•• Patients who have large central disc herniation and resultant spinal canal
stenosis present with neurogenic claudication which is asymptomatic at rest.
•• They experience bilateral lower extremity pain after a variable duration of
exertion, associated with numbness which is relieved with a brief period
of rest.
•• A central lumbar disc herniation may result in cauda equina syndrome with
perineal numbness, loss of bowel and bladder control and some degree
of motor weakness in legs.
Table 1: Common neurologic changes in herniated lumbar disc

Motor weakness Sensory loss Reflex Muscle
depression wasting
L2 Hip flexion and abduction Lateral thigh Nil Thigh
L3 Knee extension Patellar region Knee Thigh
L4 Knee extension, ankle dorsiflexion Medial shin Knee Thigh
below knee
L5 Extensor hallucis longus Dorsum of foot, Tibialis posterior, Calf, minimal
lateral calf lateral hamstrings thigh
S1 Plantar flexion at ankle Lateral border of Ankle Calf
foot, posterior
calf
824
Signs
•• Examination of the sensory system is the most subjective part of the
neurologic examination, while assessment of muscle strength is less
subjective and eliciting the reflexes is the least subjective.
•• It is important to look for paraspinal muscle spasm, range of movements of
the spine and perform a rectal examination when cauda equina syndrome
is suspected.
•• It is important to interpret straight leg raising test of Lasegue—a positive
test implies reproduction of radicular pain and not back pain.
•• Tumours involving the nerves (neurofibroma, Schwannoma, ependymoma)
or metastatic deposits in the pedicle.
•• Peripheral neuropathy in diabetes mellitus and entrapment neuropathies
involving the sciatic nerve in the pelvis.
•• Osteoarthritis of the hip.
•• Fractures involving the vertebra caused by trauma, osteoporosis or
metastatic deposits.
•• Arachnoid cyst and Tarlov’s cysts of the spinal region.
•• Vascular claudication.
INVESTIGATIONS
Radiographs of the Lumbar Spine
•• Manifestations of degenerative disc disease that may be identified on plain
X-ray films include:
–– IVD space narrowing.
–– Accumulation of gas within the disc (vacuum disc phenomenon).
–– Calcification of the disc, sclerosis of the adjacent vertebral body end-
plates (collectively termed intervertebral osteochondrosis).
–– End-plate osteophytes secondary to anterolateral disc protrusion with
traction by Sharpey’s fibres at the site of the osseous attachment of the
disc (spondylosis deformans).
–– Standard anteroposterior and lateral radiographs rule out other causes
of back pain.
–– Dynamic flexion and extension views are needed to rule out associated
spondylolisthesis.
Myelography
•• It is possible to delineate the thecal sac, spinal cord and exiting nerve
roots on myelography.
•• The myelographic signs of disc herniation include:
–– Compression of the nerve root and thecal sac with an angular indenta-
tion on the anterolateral aspect of the thecal sac
–– Compression of the nerve root with fusiform widening of the more distal
end of the involved root
–– Central compression of the thecal sac by a centrally located herniated
nucleus pulposus.
•• Myelographic findings of disc herniation correlate well with operative
findings at the L4–L5 level but are less accurate at L5–S1, owing to the
825
wider epidural space and greater amount of epidural fat at this level, which
minimises deformity or displacement of the sac by a disc herniation.
•• Myelography is insensitive to the detection of lateral disc herniations and
foraminal stenosis.
•• The sensitivity and specificity of myelography have improved considerably
since the introduction of water-soluble contrast agents and the use of
myelography followed by computed tomography.
•• Computed tomography demonstrates both the primary abnormality and
the secondary effects.
•• It is more accurate than myelography in the detection of lumbar disc
herniations, owing to its ability to show lateral disc herniations and to
evaluate the L5–S1 level reliably.
•• The accuracy of computed tomography is greater than 90% in the detection
of lumbar disc herniations.
•• Computed tomography accurately demonstrates the central canal, lateral
recesses, neural foraminal stenosis, facet joint disease, ligamentous
hypertrophy and reactive bone changes associated with disc degeneration,
including end-plate sclerosis, osteophyte formation, and facet joint
narrowing or hypertrophy.

•• The MR imaging is the preferred initial study for the evaluation of
degenerative diseases of the lumbar spine including disc herniations and
central canal, lateral recess and neural foraminal stenosis.
•• The MR imaging findings of a degenerated disc are:
–– Decrease in signal intensity on T2-weighted scans of the nucleus
pulposus, compared with a normal disc, because of desiccation of the
degenerated disc and resultant diminished water content
–– Irregularity of the outline of the nucleus pulposus
–– Decrease in disc height
–– An intense dot like high intensity signal in the posterior annulus signify-
ing an annular tear
–– Modic changes in the cortical end-plate and the adjacent marrow.
•• A disc herniation is best detected on axial images (either computed
tomography or MR imaging) because in this plane the focal, usually
eccentric posterior extension of the disc material is readily visualised.
•• The protruding disc obliterates the epidural fat, displaces the nerve root
sleeve, or both.
•• Sagittal T1-weighted and moderately and heavily T2-weighted images
provide information regarding the level of herniation, presence of extruded
or sequestrated fragments.
•• Gradient-echo imaging provides excellent views of the spinal cord free
from pulsation artifacts, with the high-intensity cerebrospinal fluid (CSF)
and low-intensity spinal cord.
Discography
•• This modality provides radiographic evaluation of the integrity of the nucleus
pulposus and annular rings to determine tears or other lesions that could
be responsible for low-back pain.
826
•• Second, and more important, is its measure of disc nociception and that
targeted therapy directed at that disc is warranted.
•• No more than three discs should be injected during any single study.
•• The primary indication for lumbar discography is chronic low-back pain
with or without radicular pain in the absence of MR imaging–documented
neural compression, i.e. it can be used for identifying disc lesions and pain
generators when MR images are equivocal.
•• Discography is also indicated in the following scenarios:
–– When clinical findings point to one level or one side and myelography
or MR imaging indicates a different level.
–– When the disc protrusion is asymmetrical to the contralateral side of
the patient’s symptom.
Electromyogram/Nerve Conduction
•• This study may sometimes be required to rule out peripheral neuropathy.
MANAGEMENT
•• Progress made in the management of disc ailments can be divided into
four distinct stages:
–– Stage I involved the correct diagnosis of the problem and the selection
of surgical treatment.
–– In Stage II, advances were made in diagnostic methods and in the un-
derstanding of the physiological and biomechanical aspects of the disc.
–– Stage III consists of a period during which both progress made in stage
I and II continued with new trends of disc replacement by prosthetic
devices.
–– In Stage IV, more aggressive research into the field of disc degenera-
tion and possible regeneration with stem cells is being carried on.
–– Summary of the treatment options available for the management of
patients with degenerative disc disease is given in Table 2.
Table 2: Management options for a patient with degenerative disc disease

Non-operative management Operative management
• Bed rest • Open techniques
• Physiotherapy—In the acute phase: Use of • Endoscopic techniques
hot packs, short wave diathermy, microwave
therapy. After the acute phase: Graduated
regime of back exercises is instituted
• Microdiscectomy
• Use of lumbar corset whenever the patient • Minimally invasive techniques
is active – Chemonucleolysis
– Automated percutaneous lumbar discec-
tomy
– Laser assisted percutaneous discectomy
– Arthroscopic microdiscectomy
– Intradiscal electrothermal therapy
– Percutaneous nucleoplasty
• NSAIDs
• Muscle relaxants
• Epidural corticosteroid injections
827
•• An important decision for the clinician is whether to advise bed rest for
patients with low back pain.
•• One rationale for bed rest is that many patients experience relief of
symptoms while in a horizontal position. Another rationale is that the supine
position minimises intradiscal pressure.
•• There is no important difference in the effects of bed rest compared with
exercises in the treatment of acute low-back pain, or 7 days compared with
2–3 days of bed rest in patients with low-back pain of different durations
with and without radiating pain.
Microdiscectomy
•• Microsurgical approach for lumbar discectomy is currently the gold standard
in the management of herniated lumbar disc disease (Table 2).
•• The biggest advantage is the shorter incision and hence reduced post-
operative pain which reduces the hospital stay.
•• The O’Connell technique of aggressive discectomy has been criticised for
causing nucleus and end-plate injury, accelerating degenerative changes at
the operated disc level, leading to disc space collapse with loss of foramen
height, and potentially leading to an increased incidence of post-operative
back and leg pain.
•• The more conservative Williams and Spengler technique of limited
discectomy emphasises removal of the disc fragment alone with little
invasion of the disc space, hence is associated with a higher incidence
of disc reherniation.
•• The extent of disc removal must be based on a case by case decision
regarding the intra-operative appearance of the herniated lumbar disc after
discussing the pros and cons of each procedure with the patient.
•• Potential predictors of poor outcome include misdiagnosis, pre-operative
psychological distress, insufficient rehabilitation, mechanical instability,
impaired fibrinolytic activity, diabetes, obesity and hypertension.
•• The complication rate following microdiscectomy is 15–30%.
•• Intra-operative complications:
–– Exploration of the wrong side or level.
–– Dural tears resulting in post-operative CSF leak, pseudomeningocoele.
–– Injury to the nerve root.
–– Retroperitoneal injury to great vessels and bowel.
–– Facet joint fracture.
–– Haemorrhage.
•• Post-operative complications:
–– Discitis (septic or aseptic).
–– Arachnoiditis.
–– Soft tissue infection.
–– Failure of pain relief.
–– Recurrence of pain due to failed back surgery syndrome.
Minimally Invasive Spinal Surgery

•• The traditional surgical technique of discectomy involves extensive
resection of the posterior bone and muscular structures leading to increased
post-operative pain, intra-operative blood loss and morbidity.
828
•• Extensive paraspinal muscle detachment from the midline osseous

elements can cause weakness secondary to muscle denervation.
•• Damage to the “tension band” consisting of the supraspinous and
interspinous ligaments may lead to increased instability of the spine during
lumbar flexion resulting in failed back syndrome.
•• Hence, minimally invasive spinal surgical techniques have been developed
with the idea of minimising tissue trauma without compromising the goal of
a successful surgical outcome.
•• Long-term prospective controlled data are lacking to establish the success
rates of minimally invasive procedures on the spine compared with the
traditional ones.
Chemonucleolysis
•• Chemonucleolysis with chymopapain is based on the principle that
depolymerisation of the proteoglycan and glycoprotein macromolecules
of the nucleus pulposus reduces the water content of the extracellular
matrix of the nucleus pulposus and reduction in the IVD height and bulge.
•• In addition, chymopapain may also have an anti-inflammatory role in the
nerve apart from the possibility of producing a total or partial neurectomy
like effect by interacting with the sensory fibres of the annulus.
•• It is reserved for patients with soft herniated disc as demonstrated by
imaging.
•• Contraindications include patients older than 60 years of age (poor
response rate due to low mucoprotein content of the disc), migrated disc,
canal stenosis, past history of discitis and allergy to papain.
•• Success rates ranging from 82 to 87.2% have been reported.
•• An inadvertent intrathecal injection results in hemiparesis, paraplegia,
raised intracranial pressure, meningitis and haemorrhage.
•• For all practical purposes this procedure has been abandoned.
Percutaneous Nucleotomy
•• This procedure is most ideal for contained disc fragments. Sequestrated
disc fragments, spinal stenosis, spondylolisthesis and past history of spinal
surgery are contraindications.
•• Success rates reported in literature range from 77.5 to 87% with a
complication rate of 1%.
Percutaneous Laser Assisted Discectomy
•• It involves placement of a needle in the disc space coupled with passage of
laser energy generated by carbon dioxide, Nd YAG, KTP laser or Holmium
YAG laser.
•• A 70–80% rate of long-lasting pain relief has been reported with a
complication rate of 3.5%.
Intradisc Electrothermal Coagulation
•• It is a therapeutic innovation specifically designed to treat discogenic pain.
•• Targeted thermal energy is delivered from an electrosurgery unit into the
disc space by percutaneously threading a flexible heating electrode into
the disc, such that the electrode passes circumferentially around the inner
surface of the disc.
•• The energy thus delivered is thought to reduce discogenic pain either by
thermal coagulation of the nociceptors or by increasing the stability of the
disc via contraction of type I collagen fibres.
•• Successful relief of pain in up to 60% of the patients has been reported.
829
RECURRENT DISC HERNIATION

•• The rate of recurrent disc herniation after lumbar discectomy is 5–15% with
an average pain-free interval of 8 years.
•• The strict definition of recurrent disc herniation is the presence of herniated
disc material at the same level, ipsilateral or contralateral, in a patient who
has experienced a pain-free interval of at least 6 months after surgery.
The clinically more appropriate definition, however, is disc herniation at
the previously operated site and side.
•• The current neuroimaging tool of choice in investigating a patient with
post-discectomy recurrent symptoms is gadolinium enhanced MR imaging.
•• The findings on imaging should be interpreted carefully and should not be
confused with the post-discectomy changes. The nerve root should not
enhance 6 months after the initial procedure.
•• Treatment options include observation and aggressive medical manage-
ment (pharmacological therapy and physical therapy for rehabilitation) or
operative intervention.
•• Revision laminectomy and discectomy are the most commonly performed
surgical therapies, starting at an area known to be intact, finding landmarks,
beginning medially, and working out laterally to locate the pathological
entity.
•• Fusion is not routinely needed, unless spinal instability is demonstrated.
•• Higher recurrence rates and poorer outcomes have been documented in
diabetic patients.
•• Chymopapain, intradiscal electrothermal coagulation therapy and laser-
assisted decompression are contraindicated because the annulus is no
longer intact in revision disc surgery.
RECENT ADVANCES
Artificial Disc Technology
•• One of the major reasons why artificial disc technology has been slow to
develop is the structural and functional complexity of the disc, unlike hip
and knee joints, which are composed mainly of a layer of cartilage tissue
on each articulating surface.
•• In IVD replacement, one can replace either the entire disc or only its
nucleus, the former prosthesis is called an artificial total disc and the latter
an artificial nucleus.
•• Basic design concepts and component material(s) can be divided into
three groups:
–– Metal
–– Non-metal
–– Metal in combination with non-metal.
•• The nucleus prosthesis approach has several obvious advantages over
the total disc prosthesis.
•• By replacing only the nucleus, it preserves the remaining disc tissues—
annulus and end-plates—and therefore preserves their functions.
•• The major limitation of the nucleus prosthesis is that it can be used only
in patients in whom disc degeneration is at an early or intermediate stage
because it requires the presence of a competent natural annulus.
•• Some of the artificial disc and nucleus available for use are the Charite
device, prodisc and Raymedica implant.
830
Stem Cell Therapy

•• Regenerative medicine and stem cell therapy hold great promise for IVD
disease.
•• Mesenchymal stem cells from adults are the best candidates for IVD repair.
•• Although the avascular environment of the IVD poses a challenge for
stem cell–mediated regeneration, neuroprogenitor cells have been
discovered within degenerated discs, allowing scientists to revisit the hostile
environment of the IVD as a target for stem cell therapy.
•• Issues now under investigation include the timing of cell delivery and
manipulation of stem cells to make them more efficient and adaptive in
the IVD niche.
112
CHAPTER
Lumbar Canal Stenosis
Manas Kumar Panigrahi  Debabrat Biswal
•• Lumbar canal stenosis (LCS) most commonly affects the middle-aged and
elderly population and is one of the most common diseases in elderly persons.
•• This refers to the degenerative changes or trauma of the lumbar spine,
resulting in narrowing of the spinal canal and entrapment of the cauda
equina roots by hypertrophy of the osseous and soft tissue structures
surrounding the lumbar spinal canal.
•• It is often associated with incapacitating pain in the back and lower
extremities, difficulty in ambulating, leg paraesthesias and weakness and,
in severe cases, bowel or bladder disturbances.
•• It is caused by a complex process of disc degeneration, facet arthropathy,
ligamentum flavum hypertrophy and spondylolisthesis.
•• Low back pain resulting from degenerative disease of the lumbosacral spine
is a major cause of morbidity, disability and lost productivity.
•• Due to the slow progression of the disease, the diagnosis may be
significantly delayed.
NORMAL ANATOMY
•• The lumbar vertebral canal is roughly elliptical, rounded, triangular or trefoil
in shape and is narrowest in its anteroposterior diameter in the axial plane.
•• The average anteroposterior diameter of the lumbar canal in adults, as
determined by anatomic and radiographic studies, ranges from 15 to 23 mm
and a cross sectional area of about 77 ± 13 mm.
•• The canal is anteriorly bounded by the posterior edge of the vertebral body
including the posterior longitudinal ligament, which is closely apposed to the
posterior vertebral body surface, laterally by the pedicles, posterolaterally
by the facet joints and articular capsules, and posteriorly by the lamina and
ligamenta flava (yellow ligaments).
•• The disc absorbs load and stress, provides support and resists movement.
•• The superior facet and associated ligamentum flavum form the roof of the
lateral recess, where nerve roots exit the canal and enter the foramen.
•• The lumbar facet complex is biplanar with the medial portion oriented in
the coronal plane and the lateral portion in the sagittal plane.
•• The medial portion (coronal) limits forwards translation and the lateral
portion (sagittal) resists lateral rotation.
•• Therefore, the total facet load consists of a component responsible for
sharing axial load bearing with the disc as well as components for resisting
anterior and lateral shear.
•• Ligaments play a primary role in resisting flexion, rotation and posterior shear.
832
•• Biomechanical studies on cadavers demonstrate that the posterior

ligaments, notably the supraspinous and interspinous ligaments, exert a
significant effect on tensile stiffness.
•• The neural foramen is bordered by the superior and inferior articular
processes and pars interarticularis of the superior vertebra dorsally,
sequential pedicles superiorly and inferiorly, and the intervertebral disc and
the posterolateral surface of the vertebral body ventrally.
•• The nerve root exists caudal to the pedicle, and the dorsal root ganglion
lies in the superior and lateral portion of the foramen.
•• Lumbar stenosis has been classified anatomically as central or lateral (or
mixed) and developmentally as congenital or acquired.
•• Central stenosis involves narrowing predominantly of the spinal canal.
•• Coric et al. subdivided lateral stenosis as entrance zone stenosis, mid-zone
stenosis and exit zone stenosis.
•• Lateral stenosis has also been referred to as lateral recess, foraminal
canal, subarticular, subpedicular, intervertebral foramen and lateral gutter
stenosis (Fig. 1).
•• The classification system proposed by Verbiest categorises the multiple
causes of lumbar stenosis into two types: conditions that lead to progres-
sive bony encroachment of the lumbar canal (including developmental,
congenital, acquired and idiopathic causes) or stenosis produced by
nonosseous structures such as ligaments, intervertebral discs and other
soft tissue masses.
•• For practical purposes, however, the aetiology of lumbar stenosis can be
divided into congenital or acquired forms. The two forms of spinal stenosis
are described as follows:
–– Congenital stenosis which is primary and relatively uncommon is
divided additionally into idiopathic and achondroplastic varieties. This
condition is diagnosed more easily because patients are younger and
usually lack other complicating medical problems such as diabetes or
vascular insufficiency. Stenosis may develop at several levels of the
vertebral column and may often lead to serious neurological deficits.
–– Acquired stenosis is a degenerative condition. The vast majority of
patients present with acquired LCS. Patients generally become symp-
tomatic at 50 years of age or older.
–– Degenerative changes of the spine can include osteophyte formation,
facet hypertrophy, bulging disks and hypertrophy of the ligamentum
flavum. Degenerative spondylolisthesis can further compromise the
canal (Fig. 2).
–– In some cases, the patient has acquired degenerative changes that aug-
ment a congenitally narrow canal, which are classified as complex lumbar
stenosis and present concurrently with other spinal deformities such as
spondylolisthesis, scoliosis or lumbar kyphosis (flatback deformity).
–– These lesions may be idiopathic, degenerative or surgery induced.
Fig. 1: Central stenosis versus lateral stenosis

Chapter 112 • Lumbar Canal Stenosis
833
Fig. 2: Acquired stenosis due to hypertrophy of superior and inferior

facets and ligamentum flavum
PATHOPHYSIOLOGY
•• The essential contents of the spinal canal include the spinal cord, the
cerebrospinal fluid (CSF) of the thecal sac and the dural membranes that
enclose the thecal sac.
•• The spinal canal may become narrowed by bulging or protrusion of the
intervertebral disc annulus, herniation of the nucleus pulposus posteriorly,
thickening of the posterior longitudinal ligament, hypertrophy of the facet
joints, hypertrophy of the ligamentum flavum, epidural fat deposition, spon-
dylosis of the intervertebral disc margins, uncovertebral joint hypertrophy in
the neck, or a combination of two or more of the above factors.
•• The spine responds to physiological stresses with bone growth at the
superior and inferior margins of the vertebral body (osteophytes).
•• Osteophytes can form anteriorly or posteriorly.
•• Posterior osteophytes narrow the intraspinal diameter and also cause lateral
recess stenosis. This results in spinal cord or nerve root impingement.
•• Furthermore, arthritic degeneration causes formation of synovial cysts and
hypertrophy of the facet joints, which further compromise the patency of
the spinal canal and the neural foramina.
•• Ageing discs dehydrate and can get compressed and bulge. This process
can cause tilting, slippage or rotation of the vertebral bodies.
•• The ligamentum flavum may also ossify and becomes hypertrophic.
•• The compressed discs result in shortening of the spinal column, which
causes the ligamentum flavum to buckle inwards and compress the
spinal sac and nerve roots.
•• Lumbar intervertebral disc degeneration represents a cascade of events
involving bulging of the disc, disc herniation and ligamentum flavum into the
canal, and resulting chronic facet arthrosis, sclerosis and osteophytic growth.
•• Hypertrophy of the ligamentum flavum is also an important element in
the development of spinal stenosis.
•• Lumbar spinal encroachment induces ligamentum flavum hypertrophy,
which further aggravates stenosis.
SPINAL CLAUDICATION SYNDROME

•• The narrowing of the spinal canal leads to a compression of the cauda
equina and its nerve roots.
•• However, there is no direct relationship between the extent of the stenosis
and the clinical symptoms. This finding remains unexplained.
•• Furthermore, patients are usually asymptomatic when sitting and lying
indicating a strong functional influence.
•• The following two prevailing theories try to explain intermittent claudication:
834
Neurogenic Compression Theory

•• Prolonged compression of a peripheral nerve followed by mechanical
stimulation is known to produce abnormal electrical discharge, thereby
causing pain as observed in experimental animal studies.
•• Long-standing direct mechanical compression of nerve roots leads to
decreased CSF supply to the nerve root.
•• Impaired nutritional supply results in microvascular changes, and causes
oedema, accumulation of noxious substances, deterioration and fibrosis.
•• The combination of these changes may explain neurological dysfunction.
Vascular Compression Theory
•• The vascular compression theory suggests that spinal stenosis has
pathological effects on the blood supply of the cauda equina. Particularly,
multiple-level central stenosis is associated with spinal claudication.
•• It is assumed that venous congestion between the levels of stenosis
compromises nerve root nutrition and results in clinical symptoms.
•• Additionally, the compressed nerve root arterioles may lose the ability
to respond to exercise by vasodilatation. This compromise explains that
walking produces back, buttock and leg pain as well as heaviness and
discomfort in the lower limbs.
•• During rest, the vascular (nutritional) supply may suffice and the patient
may be asymptomatic.
•• Low back pain is often accompanied by asymmetrical, unilateral more than
bilateral, radicular or claudication complaints.
•• Standing and walking, which cause an acute increase in lumbar lordosis
and infolding of the ligamentum flavum, precipitates claudication that can
readily be reversed on flexion (by sitting or lying down).
•• The characteristic syndrome associated with lumbar stenosis is termed
neurogenic intermittent claudication.
•• This condition must be differentiated from true claudication, which is caused
by atherosclerosis of the pelvofemoral vessels.
•• Compression of the microvasculature of the lumbar nerve roots, resulting in
ischaemia, is believed to be a major contributing factor in the development
of neurogenic claudication.
•• Postural neurogenic claudication is induced when the lumbar spine is
extended and lordosis is accentuated, whether at rest or during exercise
in the erect posture.
•• With extension of the spine, degenerated intervertebral discs and thickened
ligamenta flava protrude posteriorly into the lumbar canal, producing
transient compression of the cauda equina.
•• In the ischaemic form, it is hypothesized that transient ischaemia occurs
in compressed lumbosacral roots when increased oxygen demand occurs
during walking.
•• Positive mechanical findings of entrapment are the Lasègue’s sign and
femoral stretch test and these can be elicited in 60% of patients with
absolute and 43% of patients with mixed stenosis.
•• Mild motor dysfunction most frequently involves the extensor hallucis longus
and peroneal muscle groups (L-5), and reflexes may diffusely be diminished
or absent, mostly the ankle reflex.
835
•• Sensory deficits, usually noted in the L-5 or S-1 distributions are rarely seen
in more cephalad L2-4 or more caudad (sacral) distributions.
•• At the initial examination, no neurological deficit may be elicited but a brief
period of exercise often uncovers the deficit.
•• Symptoms and signs are related to the age of the patient but not to the
radiographic data (i.e. site and degree of the narrowest part or number of
stenotic sites).
•• Patients with canal stenosis tend unconsciously to assume a style of gait
that precludes the development of symptoms and this is one reason why
the style of walking noted in these subjects immediately after they start
walking is different from that in normal subjects.
IMAGING STUDIES
•• Older patients in whom spinal stenosis is suspected should be examined
using conventional spinal radiology, including AP, lateral, oblique and lower
lumbar-centred views.
•• Lateral views are most sensitive for central spinal stenosis, while oblique
views of the cervical and lumbar areas demonstrate lateral stenosis
syndromes better.
•• Plain radiographs of the lumbar spine reveal multilevel spondylotic changes
with osteophytes, facet hypertrophy and disk space narrowing.
•• Interpedicular and sagittal measurements of the canal on plain films are
helpful in defining the stenosis.
•• Flexion-extension radiographs help demonstrate motion occurring at a
potentially unstable segment.
•• CT scan helps in viewing facet hypertrophy, especially of the superior
process, leading to constriction of the transverse diameter of the canal.
•• Ventrally located osteophytes and hypertrophied laminae narrowing
the canal in its AP diameter are readily demonstrated. Together, these
changes narrow the lateral angles of the canal, diminishing the height of
the lateral recess.
•• Magnetic resonance imaging studies better delineate the soft tissue
changes laterally, in the foramina and far laterally.
•• MRI with gadolinium DTPA affords a near myelographic view of the entire
subarachnoid space.
•• It also reveals tumours, demyelinating syndromes, adhesive arachnoiditis
and infection, which need to be excluded.
•• CT:
–– The benefits of CT over plain films are that it can provide greater reso-
lution in terms of an increased ability to appreciate density differences.
–– A second advantage of CT is its ability to image in different planes, ei-
ther directly or by multiplanar reconstruction, specially the axial views.
–– On CT, midsagittal lumbar canal diameter less than 10 mm is regarded
as absolute stenosis and canal diameter less than 13 mm indicates a
relative stenosis.
–– Compared to MR imaging, the disadvantage of CT is that it does not
allow good visualisation of the nerve roots and exposes the patient to
radiation.
–– If MRI is not possible (e.g. pacemaker, metallic artefacts), CT myelo
graphy provides the best alternative to confirm nerve root involvement.
–– However, CT myelography may not display foraminal stenosis be-
cause the dural root sheath ends at the entrance of the foramen.
836
MANAGEMENT
•• Decompression of the spinal canal relieves the symptoms of lumbar stenosis
in a considerable proportion of cases, but the results tend to be inconsistent.
•• Medical treatment alternatives, such as bed rest, pain management
and physical therapy, should be reserved for use in debilitated patients
or patients whose surgical risk is prohibitive as a result of concomitant
medical conditions.
•• Favourable indications for non-operative treatment would be mild claudi-
cation symptoms, concomitant back pain, mild to moderate radiculopathy,
minimal interference with lifestyle and absence of motor deficits.
•• Conservative treatment options may consist of medication like analgesics,
NSAIDs and muscle relaxants.
•• The administration of calcitonin has been reported to improve the symptoms
of neurogenic claudication.
•• Some patients may improve functionally as a result of postural education
and physiotherapy.
•• As extension worsens the symptoms by reducing the size of the spinal
canal, it is obvious that extension exercises must be avoided.
•• Epidural injections anecdotally have a temporary beneficial effect and may
be considered as a treatment in elderly patients in whom surgery would be
too risky or who refused surgery.
•• However, the therapeutic value of epidural injections in all lumbar spinal
disorders and particularly in spinal stenosis remains controversial.
•• The administration of intravenous infusion of PGE1 (60 mg/day) for
approximately two weeks has been found to be useful for treating
intermittent claudication in patients with LCS.
•• Surgery for lumbar spinal stenosis is generally indicated when conservative
treatment has failed or if the stenosis substantially impacts on the patient’s
lifestyle.
•• The general goals of operative treatment are to improve quality of life by
reducing symptoms.
•• Indications for surgery are moderate to severe claudication symptoms,
significant interference with lifestyle, progressive neurological deficits and
cauda equina syndrome.
•• With the exception of a cauda equina syndrome or progressive neurologic
deficits, the indication for surgery remains relative and is dominated by the
subjective interference with the patient’s quality of life.
•• The surgical technique is largely dependent on the type of stenosis, which
may be central, lateral recess or foraminal and the presence of concomitant
back pain.
•• The principal surgical options for decompression of central and/or lateral
spinal stenosis are decompressive unilateral or bilateral laminotomy
or laminectomy, decompression with non-instrumented fusion and
decompression with instrumented fusion.
Laminotomy or Laminectomy
•• The objective of decompression is to create more space for the cauda
equina and nerve roots by liberating the neural structures from compressing
soft tissues such as disc herniation, hypertrophied ligamentum flavum,
thickened facet joint capsules and osseous structures like hypertrophied
facet joints and osteophytes.
837
•• Until recently, total laminectomy was the standard method of decompression

in central spinal stenosis.
•• However, the recognition that total laminectomy may increase or cause
segmental instability has led to a more conservative approach, preserving
the lamina and only removing those parts which actually cause the stenosis.
•• Selective decompression is the surgical technique of choice in patients
presenting with neurogenic claudication without associated back pain.
•• One of technical details is related to the preservation of the facet joint
capsules when an undercutting medial facetectomy is required to
decompress the thecal sac.
•• In selected cases, a unilateral approach suffices to bilaterally decompress
the thecal sac (over-the-top technique) by undercutting of the laminae,
preserving the interspinous ligaments and the contralateral muscles.
•• Endoscopic interlaminar decompression in cases of lateral recess stenosis
and its superiority over the microsurgical technique has been claimed.
•• Endoscopic techniques are advantageous in respect to the following:
operative, complications, traumatisation and rehabilitation.
•• Total laminectomy is still indicated in cases in which the thecal sac cannot
be decompressed sufficiently or the access to the foramen is obliterated
(foraminal stenosis).
•• In rare cases of cauda equina syndrome, total laminectomy is indicated to
ensure adequate neural decompression.
•• Laminectomy alone should be avoided in cases with pre-existing instability
such as degenerative spondylolisthesis, isthmic spondylolisthesis with
secondary degenerative changes and degenerative scoliosis.
•• Inverse laminoplasty is a canal enlargement technique with ligamentum
flavum excision, foraminotomy and lateral recess decompression with
preservation of the osseous structures.
•• Inverse laminoplasty has three advantages: (1) prevention of instability
and re-construction of spinal osseous structures, (2) enlargement of the
spinal canal diameter, (3) prevention of neural elements from peridural
scar formation.
•• Disc excision is performed in patients who have disc protrusion or extrusion.
Decompression and Spinal Fusion

•• The addition of fusion, with or without instrumentation, to surgical
decompression is generally recommended when segmental instability is
suspected.
•• Decompression and fusion are considered by many spine surgeons in case
of segmental instability like degenerative spondylolisthesis and scoliosis,
concomitant severe back pain, necessity for a wide decompression and
for patients with recurrent spinal stenosis.
•• In patients who had a concomitant fusion, the results were significantly
better with respect to relief of pain in the back and lower limbs.
•• Use of instrumentation like pedicle screws and rod stabilisation may lead
to a higher fusion rate, but clinical outcome shows no improvement in pain
in the back and lower limbs.
•• There is no evidence in the literature that an additional interbody fusion by
an anterior (ALIF) or posterior (PLIF, TLIF) approach improves outcome.
•• Newer techniques, such as interspinous spacer stabilisation, are still
evolving and conclusions on clinical effectiveness are premature.
838
•• Indications for implantation of the interspinous spacer are:

–– Resistance to conventional medical treatment.
–– Age older than 70 years or, if younger than 70 years, a high operative
risk and inability to tolerate lengthy surgery.
–– Lumbar stenotic symptoms of greater than moderate severity, espe-
cially intermittent claudication.
–– Pain relief in flexed lumbar and exacerbation when in an extended
position.
–– Dural compression, primarily caused by the ligamentum flavum.
•• The advantage of the spacer is its ease of insertion into the interspinous
process space. Many types of spacers are now in use, such as Titanium and
Ceramic, and the overall results with them are early, but quite encouraging.
113
CHAPTER
Spondylolisthesis
TERMINOLOGY
•• Spondylolisthesis is defined as a displacement of one vertebra over the
next lower vertebra in the sagittal plane.
•• Spondyloptosis is an extreme degree of spondylolisthesis, where the
upper vertebral body appears to be not in contact and is placed anterior
to the lower body.
CLASSIFICATION AND AETIOLOGY

•• An aetiological classification that is widely accepted was proposed in 1976
by Wiltse, Newman and MacNab (Table 1).
Table 1: Wiltse-Newman-MacNab classification of spondylolisthesis

Type Aetiology Comments
Isthmic Defect in pars interarticularis (isthmus) Commoner at L5–S1 level and in
Subtype A Bilateral chronic spondylolytic defect in younger patients
the isthmus Type 4 of Aihara classification of
Subtype B Healed spondylolysis with elongated lumbosacral dislocation (Table of
isthmus chapter Sacral Spine Injury in the
Subtype C Acute bilateral fracture of isthmus textbook) Commoner at L4–5 level
and in older patients
Degenerative Abnormal motion due to disc and facet Elongation of pars (mimicking isth-
joint degeneration mic subtype B) or fracture of the
parts (mimicking subtype A) might
occur secondarily. Horizontal ori-
entation of L5–S1 facet joint and
wedging of L5 body help distin-
guish dysplastic spondylolisthesis
Dysplastic Congenital abnormality of neural arch Type 1, 2, 3, 5 of Aihara classifica-
such as malformed L5 inferior or supe- tion (see above)
rior S1 facet, abnormal sacral surface Example: Paget’s disease, Marfan
syndrome, achondroplasia, neu-
rofibromatosis
Traumatic Acute fracture of the neural arch at a
site other than the isthmus
Pathological A. Generalised bone disease Example: Tuberculosis, metastasis.
B. Localised bone disease disrupting Fracture of the pars cephalad to a
the integrity of the neural arch site of surgical posterior (laminar)
fusion is also included (spon-
dylolisthesis acquisita)
840
•• Isthmic spondylolisthesis (ISO) is commoner in the 20−40 age group, while

degenerative spondylolisthesis (DSO) is common above the age of 40.
Isthmic Spondylolisthesis
•• The pars interarticularis is an isthmus of bone that connects the superior
and inferior facets.
•• The pars appears to be the weakest point in the neural arch and yet it
faces the highest stress. Repeated stress fracture of the pars results in
isthmic spondylolysis.
•• A fracture that goes into non-union produces a wide smooth defect with
edge sclerosis resulting in the subtype A of ISO.
•• If there is healing and remodelling at the stress fracture site, the pars
becomes elongated with alteration of the biomechanics of the motion
segment, which leads to the subtype B of ISO.
Degenerative Spondylolisthesis
•• DSO is found most commonly at the L4–5 level, followed with decreasing
frequency by L3–4, L2–3, L5–S1 and L1–2 levels.
•• Women aged 40–60 years exhibit slippage in a 2:1 to 10:1 prevalence
compared with men.
•• Male patients are typically older, in the six to eighth decades.
•• Table 2 lists the factors associated with an increased incidence of DSO.
•• DSO may be associated with translatory slips in the coronal plane or
degenerative kyphoscoliosis.
Dysplastic Spondylolisthesis
•• This spondylolisthesis occurs at L5–S1 level.
•• If L5 is sacralised, dysplastic spondylolisthesis can occur at L4–5 level.
•• Dysplastic spondylolisthesis needs to be distinguished from ISO subtypes
A and B, as there might be a secondary isthmic defect or elongation in
dysplastic cases too.
•• The key is the horizontal orientation of the L5–S1 facet joint in dysplastic
spondylolisthesis.
Table 2: Factors predisposing to DSO

Female sex
• Oophorectomised women—3 times greater incidence
• Osteoporosis—leading to elongation of the pars
• Sagittal orientation of facets (sagittal facet angle > 45° increases risk 25-fold)
• Specific factors for L4–5 level DSO
• Narrow L4 inferior articular process
• Sacralisation of L5
• Horizontalisation of the lamina and the facets
• Specific factors for L5-S1 level DSO
• Slender L5 transverse process
• Greater inclination of sacral table
• Less deep location of the L5 vertebra in the pelvis
Reproduced with permission from Progress in Clinical Neurosciences Vol. 23
Chapter 113 • Spondylolisthesis
841
•• A higher incidence of associated spina bifida is noted with dysplastic

spondylolisthesis.
•• Traumatic and Pathological Spondylolisthesis are mentioned in Table 1.
GRADING
•• Grading describes the severity of the vertebral slip.
•• Meyerding, in 1932, divided the upper surface of the inferior vertebra
into four equal parts and depending on the degree of slip of the superior
vertebra, described four grades of spondylolisthesis (Fig. 1A).
•• Grades 1 and 2 are considered low-grade and grades 3 and 4 as high-
grade spondylolisthesis.
•• It is necessary to specify the percentage of slip to describe slips of
intermediate grades (Fig. 1B).
•• When there is a sagittal plane translation (slip) there must be an
accompanying sagittal plane rotation (roll), which becomes obvious in
high-grade olisthesis. This rotation is measured by the angle between the
posterior or the anterior surfaces of the two vertebrae (Fig. 1C).
•• In high-grade olisthesis, there is rounding off of the anterior border of the
upper surface of the lower body and sagittalisation of the disc space. The
sacrum appears more inclined forward in L5–S1 olisthesis.
•• The subpedicular posterior border in the slipping upper vertebra loses its
height. This results in a wedge-like shape of the slipping vertebra. The
ratio of the anterior and posterior heights of the slipping vertebra is the
lumbar index (Fig. 1D).
A B C D
E F G H
Figs 1A to H: Measuring spondylolisthesis. (A) Meyerding grades. The up-

per surface of the lower body is divided into four equal parts to grade the for-
ward slip: grade I: up to 25%, grade II: 26−50%, grade III: 51−75% and grade
IV: > 75%. (B) Ratio X/Y represented as % gives the percentage slip. (C) The
angle between the posterior borders of the bodies gives the sagittal plane
rotation or roll. (D) The ratio A/B represented as % gives the lumbar index.
(E) Lumbosacral angle of Boxall (normal = 90−110°) becomes more acute
with high-grade olisthesis. (F) Sacral angle measures the inclination of the
sacrum. (G) Sacral slope measures the sagittalisation of the upper surface of
the sacrum. (H) The ratio between the width of the upper and lower endplates
of S1 (called S1 index) is less than 1.35 in high-grade olisthesis
842
•• The remaining measures used in studies on spondylolisthesis are shown

in Figures 1E to H.
CLINICAL FEATURES AND THEIR BASIS

•• Spondylolysis and spondylolisthesis may entirely be asymptomatic.
•• Symptomatic spondylolisthesis presents with various combinations of
low backache, restriction of back mobility, radicular leg pain (sciatica),
neurogenic claudication, postural abnormality and neurological deficits
referable to the caudal roots, roughly in that order of frequency.
•• The back pain is poorly localised, central and sometimes is referred to the
sacral and perineal region. It is worse on standing.
•• Leg symptoms of sciatica and neurogenic claudication arise from
compression or stretch on the spinal roots.
•• DSO is most common at L4–5 level and this again causes L5 root
compression which is the traversing root.
•• The bulging disc or a frank prolapse of the disc also narrows the space in
the lateral canal.
•• The symptoms do not improve on forward bending, unlike in the case of
pure spinal stenosis.
•• The patients tend to support the back of the trunk with their arms.
•• Clinical examination may show wasting of extensor digitorum brevis,
weakness of toe-grip, sensory loss in the L5 and S1 segments and absent
ankle reflexes.
•• Acute worsening of pain and unilaterality of symptoms suggest an additional
disc prolapse in both DSO and ISO.
•• In high-grade L5–S1 olisthesis, the lumbar spine becomes hyperextended
giving a foreshortened appearance of the trunk.
•• The upper surface of the sacrum becomes vertical and the caudal sacrum
juts out. The buttocks appear flat and there is a prominent transverse crease
in the flanks and anterior abdomen.
•• The gait has a characteristic waddle. There may be an associated scoliosis.
•• It is important in clinical examination to feel the leg pulses to rule out an
additional vascular claudication.
•• Neurogenic claudication is brought on by standing or walking; the pain is
associated with numbness of the legs and is not felt while riding a bicycle.
•• The “walk test” may bring about a new sensory, motor or reflex deficit that
was not present at rest in a patient with neurogenic claudication.
•• Vascular claudication is brought on by walking or cycling but not by
standing.
•• Additional diabetic neuropathy is common with DSO which causes
overlapping clinical signs and will need to be ruled in or out prior to surgery
with nerve conduction studies.
INVESTIGATIONS
Plain Radiographs
•• The standard projections are: (1) anteroposterior view, which also covers
the sacroiliac joints and both hip joints; (2) lateral view in the standing
posture in neutral, flexion and extension.
•• Since CT is much better at detecting the break in the pars interarticularis,
now replaced oblique views to display the ‘Scottie dog collar’ sign.
843
•• Worsening or appearance of the vertebral slip in flexion indicates a dynamic

olisthesis.
•• A forward movement of up to 2 mm in flexion is acceptable in normal
persons.

•• CT shows spondylolysis better than oblique X-rays.
•• Multiplanar reconstruction of helically acquired data from a multi-detector
CT done without intravenous or intrathecal contrast is routine.
•• Elongation of the pars and sclerosis/callus arising from healed pars defects
are also seen.
•• CT pediculometry helps to visualise narrow a pedicle or one with a very
wide angle.
•• Sagittal reconstruction can show the subtle slippage at the posterior
vertebral border, without the overlap from the hypertrophic facets or iliac
crests as would happen a lateral X-ray.
•• Measuring the bone mineral density by volumetric quantitative CT can be
done for osteoporosis assessment simultaneously.

•• Coronal plane imaging shows associated vertebral translation.
•• The distended facet sign has been described to be associated with position
dependent spinal stenosis in dynamic DSO.
•• Normally, the marrow signal in the pars is uninterrupted from the superior
to the inferior facet.
•• Spondylolysis is suggested on sagittal MR images by a dark signal on all
imaging sequences in the pars resulting from marginal sclerosis at the
site of the break.
•• If there is a gap at the site of the break then there will also be an increased
signal in the gap resulting from the presence of soft tissue.
•• Presence of oedema in the pars indicates an acute stress fracture.
•• The wide canal sign on midline sagittal MR images is present in ISO but
not in DSO.
•• The paradiscal vertebral marrow changes described by Modic generally,
indicate facetal instability.
•• Large (>1.5 mm) facet effusions are predictive of L4–L5 DSO even though
the slip is not seen in the MRI and only seen in erect dynamic radiographs.
Discography
•• Discography is used to study the internal disruption of the disc by analysing
the contrast diffusion patterns.
•• It also aims to provoke the patient’s pain.
•• The invasiveness, rare chance of infection and poor patient acceptance
of contrast discography have made many centres rely on MRI for the
structural information.
•• Modic type 1 MR changes have a high positive predictive value in the
identification of pain generator and may help avoid discography.
•• Discography might help decide, if fusion surgery needs to be extended
beyond the level of the olisthesis.
844
MANAGEMENT
•• Conservative management is indicated in patients with minimal or no
symptoms.
•• This is offered to young patients with spondylolysis or low-grade
spondylolisthesis and to the older patients with non-disabling DSO.
•• The modalities consist of 3−5 days of rest till the acute episode of back
pain resolves.
•• Longer periods of bed rest are counter-productive.
•• Oral analgesics, bracing, various physical therapies, epidural/facetal steroid
injections and spinal flexion exercises are also prescribed but none of these
have been validated by controlled trials.
•• The wait-and-watch policy for patients without leg pain has been supported
by a 10 to 18-year follow-up study of non-surgically managed patients
with DSO.
•• Limitation of claudication producing activity is all that is needed for some
elderly persons with DSO.
•• Lack of medical fitness for surgery may rarely force one to settle for
conservative treatment.
Surgical Management
•• Surgical management is indicated in patients with disabling symptoms that
are unrelieved by conservative management.
•• Surgery could be offered to asymptomatic olisthetic patients with a high-
risk of progression.
•• Factors such as spina bifida, younger age at detection, higher degree of
slip at detection, female sex and dysplasia in the posterior elements have
all been associated with symptom progression, but none of these are
consistent markers.
•• Hence, it is prudent to wait and watch an asymptomatic patient.
•• Clinical and/or radiological progression occurring during the observation
period constitutes a strong indication for surgery.
•• The twin aims of olisthesis surgery are: (1) to relieve symptoms and
(2) to prevent progressive worsening or recurrence of symptoms.
•• One or more of the following is/are done at surgery for spondylolisthesis,
so as to achieve these twin aims: (1) decompression; (2) reduction;
(3) fusion; and (4) instrumentation.
Decompression
•• Decompression of the nerve roots addresses the spinal stenosis and is
traditionally the most important treatment for DSO and adult ISO.
•• It may not be needed at all in young ISO patients as their neural canals
are wide and they have no neural compression.
•• In fact decompression without fusion (Gill’s procedure) may be hazardous
in a young patient with ISO as it leads to worsening of the olisthesis.
•• The decompression can take the form of unilateral laminofacetotomy,
undercutting mesial facetectomy, foraminotomy, coronal hemilaminec-
tomy (trumpet laminectomy of Kanamori) or complete laminectomy and
facetectomy.
•• Partial pediculectomy, removal of osteophytes from the vertebral edges
and excision of the ossified annulus may be needed.
845
•• Excision of thickened ligamentum flavum or hypertrophic synovium,

drainage of synovial cysts, discectomy and epidural scar release are the
soft tissue manoeuvres to relieve root compression.
•• Restorative laminoplasty has also been described.
•• Refinements, such as use of the operating microscope, endoscope and
high-speed drills, have enhanced the safety and added to operator’s ease.
Reduction
•• Reduction of olisthesis is seldom necessary to achieve the twin aims stated
above for patients with low-grade ISO or DSO.
•• Complete (or at least partial) reduction is a fervently wished for goal in
high-grade olisthesis, but it is rarely achieved in adults.
•• Achieving reduction is an important advantage of using metal instrumentation.
•• Distraction force applied to pedicle screws can help achieve reduction.
•• Precontouring the vertical rod (or even better a plate) into lordosis can also
force some reduction.
•• The vertical connector is fixed firmly to the caudal pedicle screw first and
then the act of tightening the cranial (olisthetic) screw pulls up the slipped
vertebra to at least some degree of reduction.
Fusion
•• The aim of fusion is to obtain a stable spine and a pain-free patient.
•• Fusion addresses the instability caused by the disease and aggravated by
the decompression procedure.
•• Successful fusion avoids motion at that segment and halts progression
of degeneration.
•• One or two level fusion does not greatly reduce the range of whole spine
movements.
•• A variety of fusion procedures are available. These include intertransverse
fusion (ITF), posterolateral fusion (PLF), posterior lumbar interbody fusion
(PLIF), transforaminal lumbar interbody fusion (TLIF), anterior lumbar
interbody fusion (ALIF) and circumferential (270° or 360°) fusion.
•• Autografts, allografts (locally banked cadaveric bone or commercially
available femoral rings) and xenografts (bovine bone) are used in various
combinations.
•• The autograft may be obtained from the lumbar spine during decompression
or separately from the iliac crest.
•• Cages for interbody fusion are made of titanium, carbon fibre, ceramic or
polyethyl ether ketone. They come in various shapes such as threaded
cylinders, spiked cuboids, tapered cuboids or the expandable variety.
•• Anterior interbody fusion relies more on cages as the neural structures do
not come in the way of implanting large cages.
Instrumentation
•• There is no consensus on the use of instrumentation in lumbar fusion.
•• The fusion rate was higher with the use of instrumentation as opposed to
the non-instrumented cases of DSO.
•• The previously used posterior instrumentation using sublaminar wires and
Luque rods or Hartshill rectangles is now supplanted by transpedicular
screws.
•• Since they provide three column support, pedicle screws are the stablest
of devices.
846
•• The vertebral slip can be corrected by distraction-lordosing.

•• It is acceptable to obtain in situ fusion in low-grade olisthesis as long as
the nerve root space is well-decompressed.
•• The decompression and, therefore, the instrumentation and fusion might
need to extend to adjacent stenotic levels in DSO.
•• The recent advances include use of neuronavigation for proper placement
of the screw and percutaneous placement of pedicle screws.
•• Use of navigation helps minimise radiation exposure of the operating room
personnel.
•• In mild grade DSO, interbody cages might even obviate the need for
pedicle screws.
114
CHAPTER
Fluorosis
Raja Reddy D, Srikanth R Deme
INTRODUCTION
•• High incidence of endemic fluorosis in India is due to the fact that large
areas of the country contain water supplies having high levels of fluoride.
•• All states of India except the Northeast and Himachal Pradesh reported
cases of fluorosis and 25−30 million people are exposed to high fluoride
intake and half a million persons suffer from skeletal fluorosis.
METABOLISM OF FLUORIDE
•• Biological effects of fluoride intoxication are related to the total amount of
fluoride ingested whatever the source, be it food, water or air.
Sources of Fluoride
•• Foods: The contribution of food to the total daily intake of fluoride varies
from region to region. Staple diets rich in Sorghum, Ragia or Bajra
containing high silicon besides fluoride which seem to aggravate fluoride
toxicity in some endemic areas of India.
•• Water and beverages: The fluoride intake dependent upon consumption
of drinking water and beverages is determined by their fluoride content and
influenced by such factors as body size, physical activity, food habits and
variations in atmospheric temperature and humidity.
•• Air: The fluoride content of the atmosphere rises wherever there is volcanic
action or industrial activity.
Total Daily Fluoride Intake

•• The estimated range of safe and adequate intake of fluorides for adults
is 1.5−4.0 mg/day and it is less for children and those with renal disease.
•• The daily intake of fluoride in endemic regions varies from 10 mg to 35 mg
and can be even higher in summer months.
ABSORPTION OF FLUORIDES
•• Fluorides are absorbed from the gastrointestinal tract by a process of
simple diffusion without any mechanism of active transport being involved.
•• Various dietary components apparently influence the absorption of fluoride
from the gut.
•• It has been noticed that salts of calcium, magnesium and aluminium, when
added to the diet, reduce the quantum of fluoride absorption on account of
the formation of their less soluble compounds.
848
DISTRIBUTION OF FLUORIDES
•• About 96−99% of the fluoride retained in the body combines with
mineralised bones, since fluoride is the most exclusive bone-seeking
element on account of its affinity for calcium phosphate.
•• Fluoride in plasma exists in free ionic and bound forms, the latter bound to
serum albumin forming about 85% of the total amount of fluoride in plasma.
•• Plasma fluoride in normal individuals in non-fluoridated areas ranges from
0.14–0.19 PPM and is higher in fluorotic patients.
•• Newer methods, which only measure the ionic component of plasma fluoride
levels, show lower values which range between 0.004 PPM and 0.008 PPM
when drinking water contained traces of fluoride and varied from 0.1 to 0.2
when water was fluoridated.
•• The sequestration of fluoride into the skeleton, urinary excretion and loss
sustained through sweat helps in regulation of plasma fluoride.
•• The levels of fluoride in most soft tissues of the body are lower than 1 PPM
but are higher than those of plasma.
•• The fluoride content of the brain is 0.4−0.68 PPM and the concentration in
cerebrospinal fluid (CSF) is 0.1 PPM which is lower than that of plasma.
•• The uptake of fluoride by the skeleton is very rapid and depends upon the
vascularity and the rate of its growth.
•• The fluoride uptake of young bones is faster than that of mature bones.
•• The amount of fluoride present in various bones of the same skeleton differs
from bone-to-bone with the pelvis and vertebrae registering higher fluoride
content than limb bones.
EXCRETION OF FLUORIDES
Faeces
•• Fluoride present in faeces comes from two sources: (1) the ingested fluoride
that is not absorbed and (2) the absorbed fluoride that is excreted into the
gastrointestinal tract.
•• About 10−25% of the daily intake of fluoride is excreted in the faeces.
Urinary
•• The elimination of absorbed fluoride occurs almost exclusively via the kidneys.
•• Urinary fluoride in normal individuals fluctuates widely between 0 PPM and
1.2 PPM with an average of about 0.4 PPM when the fluoride content of
drinking water is 0.3 PPM.
•• Urinary levels of fluoride are higher in individuals exposed to higher intake
of fluoride.
Sweat
•• Some fluoride is also lost from the body through sweat, and so, appreciable
amounts may be lost in situations marked by excessive sweating. Sweat
fluoride concentrations are similar to plasma.
CLINICAL FEATURES
•• Fluoride intoxication presents an extraordinary degree of uniformity in its
clinical manifestations. It occurs in humans as dental and skeletal fluorosis.
•• In its advanced stages, skeletal fluorosis causes crippling deformities and
neurological complications.
Chapter 114 • Fluorosis
849
Dental Fluorosis
•• Dental fluorosis mainly involves enamel but severe intoxication may affect
the dentine as well as the pulp.
•• Enamel fluorosis occurs when fluoride concentrations in or in the vicinity
of the forming enamel are excessive during its pre-eruptive development.
•• Mottling of teeth is one of the earliest and most easily recognisable features
noticed in the first decade of life.
•• The permanent teeth are affected and they lose their normal creamy white
translucent colour and become rough, opaque and chalky white.
Pre-skeletal Stage
•• The duration of this stage may vary with the amount of fluoride ingested
daily.
•• The persons concerned may occasionally complain of pain in the small
joints of the limbs and back, which are often mistaken for rheumatoid
arthritis or ankylosing spondylitis.
Skeletal Fluorosis
•• Early in the development of fluorotic changes in the skeleton, the patients
often complain of a vague discomfort and paraesthesiae in the limbs and
the trunk.
•• Pain and stiffness in the back appear next, especially in the lumbar region,
followed by the dorsal and cervical regions.
•• Restriction of spine movements is the earliest clinical sign of fluorosis.
•• The stiffness increases steadily until the entire spine becomes one
continuous column of bone, manifesting as a condition referred to as
‘poker back’.
•• When the condition becomes severe and chronic, various ligaments of the
spine are involved and it soon spreads to various joints in the limbs owing
to the involvement of the joint capsules, the related ligaments, tendinous
attachments to the bones and interosseous membranes.
•• The involvement of the ribs gradually reduces the movement of the chest
during breathing, which finally becomes mainly abdominal.
•• With the increasing immobilisation of the joints due to contractures, flexion
deformities may develop at the hips, knees and other joints, which make
the patient bedridden.
•• Bony exostoses may also appear over the limb bones, especially around
the knee, the elbow and on the surface of the tibia and ulna.
•• The stage at which skeletal fluorosis becomes crippling usually occurs
between 30 years and 50 years of age in the endemic regions.
NEUROLOGICAL MANIFESTATIONS OF
SKELETAL FLUOROSIS
•• The neurological sequelae in skeletal fluorosis manifesting usually as
radiculomyelopathy arise principally due to the mechanical compression
of the spinal cord and nerve roots brought about by osteophytosis and
sclerosis of the vertebral column.
•• However, it is only in the later stages, owing to pressure on the radicular
vessels in the intervertebral foraminae that vascular complications may
supervene.
850
•• Neural toxicity attributable to fluorides is yet to be established.

•• The largest number of cases with neurological manifestations was reported
from two endemic belts: Punjab, Haryana, Rajasthan and adjacent Uttar
Pradesh in North India and from Andhra Pradesh in South India.
•• The patients suffering from neurological manifestations varied in age from
20 years to 70 years.
•• It was noticed that fluorosis occurred less frequently in areas having low
levels of water fluoride, the lowest ranging from 1.2 to 1.35 PPM.
•• It is the cervical cord rather than the dorsal cord that is commonly affected
by fluorosis.
•• Although the disease develops slowly but progresses relentlessly, the
neurological deficits may sometimes be precipitated by a minor trauma.
•• Such cases present a wide spectrum of neurological deficits, which may
be found manifesting as either lower motor neuron or upper motor neuron
defects or both, which is more common.
Myelopathy
•• Patients suffering from fluorosis usually experience difficulty in walking due
to the progressive weakness in the lower limbs.
•• With the spreading of this weakness to the upper limbs, neurological dis-
abilities occur that makes the patient bedridden. These disabilities are due
to motor and sensory deficits, which are followed by sphincter disturbances.
•• Flexor spasms appear only at the late stage of the illness.
Radiculopathy
•• Nerve root compression leads to atrophy of various muscle groups in both
the upper and the lower limbs.
•• With the onset of fasciculations motor neuron disease may be mimicked.
•• The upper limbs appear to be affected more than the lower limbs which
may be traced to the more common involvement of the cervical region or
even the anatomical features of the cervical spine.
•• In advanced cases, marked cachexia develops on account of disuse atrophy
of limb and trunk muscles.
Cranial Nerve Lesions

•• The skull is not usually affected in fluorosis and basal cranial nerve foraminae
are not encroached upon except in the advanced stages of the disease.
•• Of the cranial nerves, the most frequently affected, in a quarter of the cases
investigated, has been the eighth nerve.
•• A progressive high frequency perceptive deafness is observed. Moreover,
bone conduction is affected more than air conduction.
Peripheral Neuropathies
•• Exostoses, which mainly develop around the knee, elbow and ankle, may
press upon the median, ulnar or lateral popliteal nerves.
•• Pain and paraesthesiae followed by weakness in the limbs may be caused
by such bony growths.
•• Even meralgia paraesthetica has been reported to occur in fluorosis.
•• Fluorotic patients may also manifest entrapment syndromes involving other
peripheral nerves.
•• Degenerative disc disease is very uncommon in fluorotic patients.
851
Cerebral Ischaemia
•• Involvement of the vertebrobasilar circulation caused by compression of the
vertebral artery by cervical osteophytes may occasionally occur.
•• Increased calcifications of major vessels and disturbance of lipid metabolism
that has been reported in fluorosis may lead to cerebrovascular accidents.
•• The occurrence of certain other neurological features, like headache,
tetaniform convulsions, mental depression and electroencephalographic
disturbances, have also been reported.
General
•• A mild degree of anaemia and a decrease in erythropoietic activity of bone
marrow are found in fluorosis, which may be due to associated nutritional
factors or secondary to osteosclerosis and encroachment of medullary
cavities.
•• CSF analysis in cases of fluorotic spinal compression reveals a moderate
rise of protein and the other constituents are normal.
•• Evidence of impaired renal function was reported in a certain proportion
of fluorotic patients. The abnormalities included impaired urea clearance,
decreased glomerular filtration rate and increased blood urea nitrogen.
Electrophysiological Studies
•• Neurophysiological experiments have revealed that sodium fluoride
has anticholinesterase and anticurare like effects on muscle and nerve,
although it has no effect on normal muscle membrane potentials even in
the endplate region.
•• Peripheral nerve conduction velocities in such cases are normal and
compound action potentials are usually within normal range. These findings
suggest that the nerve lesion in fluorosis is located either in the nerve roots
or anterior horn cells in the spinal cord.
•• The nerve conduction velocities are found to be reduced to 30−35 m/sec
in peripheral nerve entrapment on account of the pressure of exostoses
or ligaments around the joints.
Fluoride Estimations
•• Diagnosis of fluorosis depends upon the estimation of fluoride levels of
urine, serum and bone.
•• Several methods are available for the determination of fluoride and the
most widely used involve colorimetry or the fluoride specific ion electrode.
•• Urine Fluoride Estimation:
–– Urinary fluoride levels are the best indicators of fluoride intake.
–– Since fluoride excretion is not constant throughout the day, 24-hour
samples of urine are more reliable than random or morning samples,
for the estimation of fluoride content.
–– In normal individuals urinary fluorides fluctuate widely between 0.1
PPM and 2.0 PPM with an average of about 0.4 PPM when the fluoride
content of drinking water is 0.3 PPM.
–– In general, urinary fluoride rises in relation to fluoride intake and
it fluctuates widely from day-to-day and ranges from 0.5 PPM to
4.48 PPM minimum and from 1.5 to 13.0 PPM maximum in cases of
skeletal fluorosis.
852
•• Serum Fluoride Estimation:

–– Normal values for serum fluoride in non-endemic regions varied be-
tween 0.002 mg/100 mL and 0.008 mg/100 mL.
–– In endemic regions, blood fluoride levels ranged between 0.02 mg/100
mL and 0.15 mg/100 mL, whereas, in patients with skeletal fluorosis,
these were 0.02−0.19 mg/100 mL.
•• Bone Fluoride Estimation:
–– Measurement of bone fluoride content allows the determination of the
extent of bone fluoride retention and is a useful complement to bone
histology for the diagnosis of skeletal fluorosis and could be used for
the management of fluoride treatment of osteoporosis.
–– Bone samples are collected and prepared for subsequent analysis us-
ing the fluoride selective electrode.
•• Bone Biopsy:
–– Histopathological changes of bone in fluorosis show that the Haversian
system is poorly formed and there is disordered lamellar orientation in
the compact bone.
–– Osteoid tissue is found in the spongy bone and some of these irregular
deposits of osteoid tissue extend into the attached muscles.
Scintigraphic Studies
•• Radionuclide bone scans using technetium-labelled methylene diphos
phonate (99mTc-MDP) in fluorosis shows mostly a superscan appearance
and in some cases joint abnormalities.
•• Increased tracer activity between the forearm bones and the diffuse linear
tracer activity along the ligamentous attachments were seen.
Radiology of Fluorosis
•• Radiological changes usually manifest at puberty and in adulthood.
•• However, in some young adolescents, osteopenia of a generalised nature
may be seen along with sclerotic areas at the metaphyseal ends of long
bones simulating renal rickets. In such cases, the epiphyses are also dense.
•• The vertebral bodies may be prone to sclerosis of the endplates.
•• In adults, the radiological findings could be set forth in three stages, each
overlapping the preceding one.
–– The findings are mainly confined to the axial skeleton. The primary
trabeculae appear slightly rough due to sclerosis. In the secondary
trabeculae, however, these are not prominent. The bones assume a
ground glass appearance, an early manifestation.
–– In the next stage, the thick primary trabeculae merge with the second-
ary trabeculae to make the bone homogeneously dense. The bone
contours become uneven due to subperiosteal new bone apposition,
which is prominently present in the ribs, pelvis and vertebral column.
Ligamentous calcification begins most frequently in the paraspinous,
sacrospinous and sacrotuberous ligaments.
–– The bones appear chalk-like with an ill-defined trabecular pattern. With
the loss of cortical and trabecular definition, the bone appears woolly.
The cortices of long bones are dense and thick due to amorphous sub-
periosteal new bone formation. The medullary cavities are encroached
upon by endosteal new bone.
•• X-ray of the forearms show calcification of the interosseous membrane.
853
Computed Tomography
•• Besides proper appreciation of the morphological anatomy and density of
the various parts of the vertebra, it shows the exact location and direction
of the osteophytes compressing the various neural elements and thus helps
in proper surgical planning.
•• The calcified ligaments are visualised earlier and with much more clarity
than by plain roentgenology, so are the indentations of the epidural space
and the alterations in the spinal canal.
•• By reconstruction, CT provides exact dimensions of the ossified intraspinal
ligaments such as the posterior longitudinal ligament and yellow ligaments.
•• Fluorotic vertebrae are seen to be hypointense in both T1- and T2-weighted
images.
•• The localised areas of hypertrophy and ossification of ligaments are
visualised clearly and these give a clue to the surgical approach.
•• Evidence of chronic cord compression producing pathological changes, like
myelomalacia, cavitation and necrosis, is seen as a high intensity signal in
the spinal cord in T2-weighted images.
PATHOLOGY OF FLUOROSIS
Gross Changes in the Skeleton
•• Skeletal changes involving overall increase in bone mass, 2−3 times the
normal is a characteristic feature of fluorosis.
•• The changes will be first noticed in the vertebral column and pelvis and,
thereafter, in the rib cage and limb bones.
•• The bones become whitish and, occasionally, mottled like the teeth.
•• A clear indication of chronic fluorosis is the calcification and ossification
of ligaments and interosseous fasciae occurring along with periosteal
new bone formation and development of exostoses on long bones and
osteophytes in the spine.
•• The spine is converted into a single rigid bone as a result of ossification of spinal
ligaments and fusion of the adjacent bony structures.
Histopathology of Bones
•• The mottled osteone is signified by brownish discolouration and increase
in the number of osteocytes found in a tangled mass on its periphery
synchronising with a reduction of osteocytes in the rest of the osteone.
•• Mottling may be said to result from the action of fluoride on osteoblasts.
•• The final stage is reached when the fluoride levels exceed 5000−6000
PPM, a stage at which even the naked eye could detect abnormality in the
formation of the bone. These changes cause impairment of mechanical
properties of bones.
TREATMENT OF FLUOROSIS
Prevention
Prevention of Endemic Fluorosis
•• The supply of water with permissible levels of fluoride, although desirable,
cannot obviously be made available to the vast number of people nor can
they be shifted from endemic areas.
854
•• The nature of nutritional intake appears to play a crucial role in the incidence
and severity of fluorosis and, hence, a balanced diet having adequate
calcium and vitamins reduces the toxicity of fluoride.
Prevention of Industrial Fluorosis
•• Workers in industries and mining exposed to fluorides should be monitored
and it should be ensured that their fluoride content of urine is below 5 PPM.
Medical Therapy
•• In vitro studies revealed that bone meal, serpentine, dowex, magnesium
compounds, etc. could be effective in the reduction of the fluoride levels
of water having a high fluoride content.
•• In vivo experiments with animals showed that salts of calcium, magnesium
and aluminium acted as a check on fluoride absorption and also increased
its excretion from the body.
•• The use of serpentine resorted to in recent times for increasing the excretion
of fluoride in human fluorosis cases has been successful.
Surgical Management of Skeletal Fluorosis with

Neurological Manifestations
•• Surgery can obviously be of little help to alleviate the neurological deficits in
view of the widespread involvement by the disease. Surgical decompression
is only possible in such of those early cases in which the compression is
confined to a small segment of the vertebral column.
•• However, the results of surgical decompression of the spine undertaken
in a selected group of cases were found to be encouraging in the cervical
region, but discouraging in the dorsal region,which might be attributed to
the peculiarities of the anatomical features of these regions.
•• Lumbar compression rarely necessitates surgical decompression as the
roots get accommodated easily.
•• In recent years, the surgical approach to certain types of lesions of the
cervical spine in fluorosis has changed.
•• Fluorotic compression in the cervical region is due to: (a) cervical canal
stenosis (b) localised calcified ligamentum flavum (c) osteophytes causing
compression anteriorly and lastly (d) ossification of the posterior longitudinal
ligament or a combination of these lesions .
•• The posterior approach is indicated in cases of canal stenosis and in lesions
of the ligamentum flavum.
•• Ossification of the posterior longitudinal ligament, which could be continuous
or segmental, is tackled through the anterior approach with better results
than in the past when the posterior approach was used.
•• Dorsal cord compression in fluorosis is of three types: (1) diffuse, extensive
where surgery is not beneficial (2) localised posterior osteophytic or ossified
ligamentous compression, wherein results are excellent and lastly (3)
localised posterior osteophytes which are spread over many vertebral
levels, although technically feasible to excise them, the results obviously
are not rewarding.
115
CHAPTER
Osteoporosis
Ramakrishna Easwaran  S Sundarrajan
INTRODUCTION
Osteoporosis, a common feature of ageing, is now being recognized with
increasing frequency in younger individuals in our country. As for as the
neurosurgeons are concerned its significance lies in involvement of the
vertebrae frequently resulting in compression fracture.
DEFINITION
•• Osteoporosis is defined as “a disease characterised by low bone mass and
microarchitectural deterioration of bone tissue, leading to enhanced bone
fragility and a consequent increase in fracture risk”.
•• In addition to loss of bone mass or bone mineral density (BMD), other
factors contribute to the loss of bone strength in osteoporosis (Table 1).
AETIOLOGY
•• Normal bone consists of organic (30%) and inorganic (70%) components.
•• The organic osteoid component is mostly made up of type 1 collagen.
•• The inorganic component is mostly made up of hydroxyapatite,
Ca10(PO4)6(OH)2, a macrocrystalline mineral.
•• Bone is a dynamic tissue that keeps on remodelling during a person’s
lifetime.
•• Osteogenetic and osteoclastic activities are continuous and are decided
by local stresses, nutrition and hormonal factors.
•• Loss of bone mass begins after the age of 35 in normal men and women
at the rate of 0.3% per year.
•• At menopause, the rate of trabecular bone loss dramatically increases to
3% per annum for 10−15 years.
•• This postmenopausal (previously called ‘type 1’) osteoporosis appears
to be mainly due to increased osteoclastic activity rather than insufficient
osteogenetic activity.
Table 1: Factors weakening the bone in osteoporosis

Loss of bone mass and reduced mineralisation (reduced BMD)
Altered bone turnover
Alteration in bone microarchitecture
Alteration in bone geometry
Reduced capacity to heal microfractures
856
•• Beyond the age of 70, the loss is slower and the rate of loss is the same
in men and women.
•• Several factors, such as decreased absorption of calcium, reduced
activation of vitamin D, a decline in the lifespan and function of osteoblasts
and decreased concentrations of sex hormones, contribute to age-
associated osteoporosis.
•• The reduction in bone mass and BMD is called osteopaenia when it is
subclinical. When it is severe enough to produce symptoms or increase
the fracture risk it is called osteoporosis.
•• The World Health Organization (WHO) criteria (Table 2) based on the BMD
give a quantitative definition of osteopaenia and osteoporosis.
•• Several secondary causes of osteoporosis are seen in practice, especially
among males with osteoporosis (Table 3).
•• Neurosurgeons are likely to see osteoporosis due to glucocorticoid or
antiepileptic therapy, Cushing syndrome, hypopituitarism and prolonged
immobility.
Table 2: Criteria for osteopaenia and osteoporosis

Category Criteria based on mean bone mineral density (BMD) of
young adult reference population-t score
1. Normal Mean ± 1 standard deviation (SD)
2. Osteopaenia 1−2.5 SD below mean
3. Osteoporosis < 2.5 SD below mean
4. Severe osteoporosis < 2.5 SD below mean + any insufficiency fracture
Table 3: Aetiology of osteoporosis

Primary BF BL
Postmenopausal ↑
Age associated osteoporosis (OP) ↓
Rare: Idiopathic juvenile OP, Transient hip OP, Regional migratory OP
Secondary
Endocrine
Excess of cortisol (Cushing), thyrotoxicosis, hyperprolactinaemia ↑
Deficiency of growth hormone, parathormone, gonadal hormones, in- ↓
sulin
Dietary
Calcium/vitamin D deficiency, malabsorption, alcohol, scurvy ↓
Systemic disease
Inflammatory bowel disease, liver disease ↓
Haemolytic anaemia, myeloma, leukaemia, mastocytosis ↑
Rheumatoid arthritis, chronic obstructive pulmonary disease ↓
Drugs
Glucocorticoids, antiepileptic drugs, anticoagulants, ↓ ↑
antiandrogen therapy
Genetic
Osteogenesis imperfecta, Marfan syndrome, Ehlers-Danlos ↓
syndrome
Others
Prolonged immobility, sedentary life style, smoking, HIV infection ↓ ↑
Note: BF, Bone formation; BL, Bone loss; ¯, Decreased; , Increased.
Chapter 115 • Osteoporosis
857
CLINICAL FEATURES
•• Osteoporosis is essentially asymptomatic until a fracture occurs.
•• Many patients, who are ultimately shown to have osteoporosis, complain
of pain, especially over the low back or lower extremities.
•• While this may be due to microfractures, the pain syndrome overlaps with
the pain caused by degenerative lumbar spondylosis and osteoarthritis,
which are common co-morbidities.
•• Fatigue and pain may also be worsened by the associated depression.
•• Vertebrae (50%), proximal femur (20%) and distal radius (15%) are the
common sites of insufficiency fractures in osteoporosis.
•• The elderly are more prone to fall because of visual impairment, dizziness
or loss of co-ordination.
•• The pain is localised to the site of the vertebral fracture and there is often
a girdle pain.
•• Patients with T12 or L1 fracture may complain of pain over the L5–S1 area.
•• Radicular leg pain is rare and should suggest spondylosis or metastasis.
•• The pain is worsened by sitting, spinal movement or coughing.
•• Painless deformity of the spine may occur due to one or more vertebral
compression fractures.
•• Progressive kyphosis (Dowager’s hump) is a consequence of multiple
compression fractures.
INVESTIGATIONS
Plain Radiography
•• Osteoporosis becomes evident on standard radiographs only when the
bone mass diminishes to nearly 50% and, therefore, it is a poor and
unreliable tool for assessing osteoporosis.
•• Prominent Schmorl’s nodes may be seen.
•• Breaks in the vertebral endplates are also seen.
•• In the advanced stages, ballooning of the discs into the weak vertebral body
may cause the end plates to appear biconcave (fish vertebra).
•• Silent multiple vertebral compression fractures are the hallmark of
osteoporosis. Therefore, it is mandatory to screen the entire vertebral
column by imaging.
•• A difference in height of the vertebra of greater than 4 mm between the
anterior and the posterior borders should be taken as evidence of a
compression fracture.
•• The compression may involve the anterior and the posterior borders equally,
sometimes to the extent of causing a vertebra plana.
•• The compaction of trabeculae due to compression fracture may give a
paradoxical radiodense appearance to the vertebra .
•• CT or MRI may show the intravertebral cleft better, it is often seen on
standard radiographs.
•• Comparison with previous X-rays if available shows the progression of
osteoporotic clefts and loss of vertebral height.
•• Anterior wedging, preserved disc spaces and absence of vertebral
displacement or paraspinous shadows are classical findings of the
osteoporotic compression fracture.
•• Posterior wedging and the ‘wink sign’ on anteroposterior radiographs due
to loss of pedicle suggest metastasis or myeloma.
858

•• CT scan is mainly required to look for retropulsed fragments in the spinal
canal and to demonstrate the intravertebral cavity (fluid content) or cleft
(gas or vacuum) that can be targeted for vertebroplasty.
•• The reconstructed sagittal and coronal CT can detect subtle compression
fractures missed by conventional radiography.
•• The presence of callus may indicate an old fracture.
•• CT is very useful to study the pedicle width and the integrity of the posterior
cortex for vertebroplasty.
•• Primary vertebral lesions, such as haemangioma, show up well on CT.

•• The presence of hyperintense oedema in the bone on T2-weighted images
indicates a recent fracture.
•• Hence MR is useful for picking up the recent fracture for treatment in a
patient with multiple wedge compression fractures.
•• The subtle infiltrates caused by tumours or infections are seen earliest
with MRI.
•• In the absence of a cavity, contrast enhanced MR has been found to show
an area of non-enhancement that corresponds to the cleft which can be
filled up during vertebroplasty.
•• Study of microarchitectural changes can be done with the help of thin
section MRI.
Radionuclide Imaging
•• The advantage of radiotechnetium imaging is the ability to look at the whole
skeleton simultaneously.
•• This is helpful for metastasis screening.
•• Recent osteoporotic fractures appear as hot spots while the clefts may
show up as cold spots.
•• It is also a useful technique for imaging patients with pacemakers, who
cannot undergo MRI.
Quantitative Assessment of Bone Mineral Density

•• Single photon or dual photon absorptiometry utilising radionuclides are
now out of vogue.
•• Since its introduction in 1987, dual energy X-ray absorptiometry (DXA or
DEXA) has become a rapid, reliable and cost-effective method of measur-
ing BMD.
Quantitative Computerised Tomography

•• Quantitative computerised tomography (QCT) gives excellent three-
dimensional (voxel) information on specific parts of the lumbar spine.
•• The technique is more accurate, but it is expensive and carries a greater
radiation exposure than DXA.
Quantitative Ultrasonography
•• Quantitative ultrasonography (QUS) is performed on the calcaneum.
•• The indications for performing bone densitometric studies are given in
Table 4 and are in keeping with the guidelines by the US National Osteo-
porosis Foundation.
859
Table 4: Indications for osteoporosis screening (BMD measurement)

All women > 65 years, (All men > 75 years)
Postmenopausal women < 65 years with 1 additional risk factor
Premenopausal women or men with 2 risk factors
Risk factors:
1. Personal history of fracture (fragility or traumatic)
2. Family history of fragility fracture
3. Low body weight (< 57 kg), recent loss of > 5% body weight
4. Amenorrhoeic women, early menopause, delayed menarche
5. Presence of any secondary cause for osteoporosis listed in Table 2, especially steroid/antie-
pileptic therapy, rheumatoid arthritis and inflammatory bowel disease
6. Smoking, alcoholism, sedentary lifestyle
7. Increased risk for falls
Monitoring osteoporosis therapy (usually 2 years after starting therapy)
•• Osteoporotic fractures occur 10−20 years earlier in Indians as compared

to Caucasians and hence the age criteria have to be lower for the Indian
population.
Assessment of Bone Turnover

•• The markers of bone formation (bone specific alkaline phosphatase,
osteocalcin) and bone resorption (deoxypyridinoline, collagen telopeptides)
have been measured but are clinically not commonly done. They have
been more accurate in the assessment of perimenopausal rather than
postmenopausal women. They may be measured in a serial manner for
monitoring therapy.
TREATMENT
Medical Treatment
•• The two medical strategies for treating or preventing osteoporosis are to
reduce bone resorption and to increase bone formation.
•• Table 5 summarises the drugs currently in use for treatment of osteoporosis.
•• Only sodium fluoride (no longer in use) and synthetic fragment of
parathyroid hormone (teriparatide) work by enhancing bone formation.
All the other drugs in Table 5 act predominantly by preventing excessive
osteoclastic activity.
•• Strontium ranelate has a dual mode of action.
•• Bisphosphonates constitute the first line therapy in those who can tolerate
the drug. Bisphosphonates provide 7% increase in hip and spine BMD and
60% decrease in markers of bone resorption. Bisphosphonates also reduce
the incidence of new vertebral fractures by 50%.
•• Oesophageal ulceration caused by bisphosphonates can be prevented by
taking the dose on an empty stomach in the morning with 200 ml of water.
The patient must be instructed to strictly avoid lying down or taking any
diet for 30 minutes.
•• Pamidronate is an intravenous alternative that can be used for those who
cannot tolerate oral bisphosphonate therapy.
•• Bisphosphonates offer protection against hip, spine and other fractures,
unlike synthetic oestrogen receptor modulators (SERM, e.g. raloxifene)
which mainly act on the vertebral trabecular bone.
860
Table 5: Drug therapy for osteoporosis

Drug Dosage and Adverse effect Proven Recommended
route efficacy in for
risk reduction
Bisphosphonates Prevention and
treatment
Alendronate 5 mg daily or Oesophagitis, Vertebral, non-
35 mg weekly, myalgia vertebral and
oral, for pre- hip fracture
vention. Twice
this dose for
treatment
Risedronate 5 mg daily or Oesophagitis Vertebral, non-
35 mg weekly, incidence same vertebral and
oral as alendronate hip fracture
Ibandronate 2.5 mg Joint pain, fever Vertebral
daily or 150 mg with first dose fracture
monthly, oral of 150 mg
Strontium 1–2 g daily at Diarrhoea, Vertebral and Prevention and
ranelate night, oral venous non-vertebral treatment
thromboem- fracture
bolism
HRT
Low-dose oes- Conjugated Venous Vertebral, non- Prevention and
trogen equine oestro- thromboem- vertebral and treatment
gens 0.625 mg bolism, stroke, hip fracture
daily, oral myocardial
infarct, breast
cancer
SERM
Raloxifene 60 mg daily, Hot flushes, leg Vertebral Prevention and
oral cramps fracture only treatment
Calcitonin 100–200 IU, Vertebral Treatment only
daily, subcuta- fracture only
neous or nasal
Teriparatide 20 µg/day Hypercalcaemia Vertebral, non- Treatment
vertebral and (presently for 2
hip fracture years)
•• Strontium ranelate therapy reduces the risk of vertebral fracture by 40%

and is less effective for preventing other fractures.
•• Recombinant human parathyroid hormone (1−34) (teriparatide) stimulates
bone remodelling by increasing bone formation.
General Measures
•• The importance of maintaining calcium and vitamin D intake throughout life
cannot be overemphasised. The recommended daily intake is summarised
in Table 6.
•• Supplemental calcium must be given in 2−3 split doses.
•• Maintenance of body weight, regular weight bearing activity and physical
exercise are also essential. Preventing falls is desirable.
861
Table 6: Recommended daily intake

Age (years) Calcium (mg) Vitamin D (IU)
3−8 800 200
9−17 1300 200
18−50 1000 400
51−70 1200 400
> 70 1200 600
Conservative Management of Vertebral

Compression Fracture
•• The pain of the recent vertebral compression fracture responds to bed rest
and simple analgesic therapy.
•• Prolonged bed rest is poorly tolerated by the elderly and hence the patients
are mobilised early, usually within a week or two.
•• Anterior spinal bracing may be used in the first 6−8 weeks after the fracture.
•• Calcitonin helps the pain when other analgesics fail.
•• All fractures that remain painful after 3 weeks, selected early fractures and
chronic non-healing fractures greater than 6 weeks old are considered for
percutaneous augmentation.
Percutaneous Intervention for Osteoporotic

Vertebral Compression Fracture
Indications
•• Percutaneous injection of polymethylmethacrylate (PMMA) bone cement
was first done in France for haemangioma of the vertebra in 1984.
•• Over the last 15 years, it has widely been used for relieving the pain of
osteoporotic vertebral compression fractures.
•• The other indications include osteolytic metastasis and myeloma with or
without pathological fracture, vertebral histiocytosis and the painful fractures
of osteonecrosis (Kummell’s disease).
•• Since 1999, correction of kyphosis by a balloon inserted percutaneously
has been available as an adjunct to vertebroplasty.
•• Kyphoplasty opens up the wedged vertebra by means of an inflatable bone
tamp prior to injection of bone cement.
•• This should ideally restore the vertebral height and correct the kyphosis.
Mechanism of Pain Relief
•• Vertebroplasty has been proved by in vitro biomechanical studies to stiffen
the vertebra.
•• Stabilisation of the microfractures is one mechanism of pain relief following
vertebroplasty.
•• The heat produced by the exothermic polymerisation of methylmethacrylate
may damage the nociceptive nerve endings in the bone. The unpolymerised
monomer may directly damage the cells secreting pain mediators.
Contraindications
•• Systemic or local infection, bleeding diathesis and neurological deficits due to
spinal canal compromise may contraindicate vertebroplasty and kyphoplasty.
•• Disruption of the posterior vertebral cortex increases the chance of
intraspinal cement leakage
862
Approach
•• Transpedicular approach is the classical route.
•• The advantages are that the pedicle is a well-recognised radiographic
landmark and that the long intraosseous path prevents nerve root injury
minimising cement leakage into the soft tissues.
•• In this approach, although the needle lies in one half of the vertebra, the
entire vertebra often gets filled.
•• In some cases, bipedicular injection may be needed to fill both halves of
the vertebral body.
•• In small pedicles, such as those seen in the upper thoracic region, the
parapedicular approach may be chosen.
•• For kyphoplasty, the inflatable balloon tamp needs to be placed in the
middle of the vertebral body and hence the parapedicular approach may
be preferred.
Cement Injection
•• Injection of bone cement in a thick soupy consistency is done with 1 mL
syringes using hand pressure.
•• Injection when the mixture is too thin encourages venous embolisation
and must be avoided.
•• The injection is done under lateral image intensifier screening to look for
entry of cement into the spinal canal.
•• The body opacifies with cement in the anterior to posterior direction.
•• The volume needed per level might be 2−6 cc.
•• Cement injection is stopped when the posterior quarter of the body is filled
or when it leaks beyond the vertebra.
•• The patient must lie prone for 15−20 minutes until the cement hardens. The
patient can be ambulated within hours. Pain relief is usually seen within a
day and is long lasting.
Technique of Kyphoplasty
•• The initial steps are similar to vertebroplasty.
•• The needle, placed in a similar manner, is exchanged for a cannula and
introducer system over a guide pin.
•• Through this the balloon tamp is introduced and inflated till the kyphotic
deformity is corrected or the balloon reaches the cortical margin.
•• The balloon is then deflated and bone cement is injected.
•• More viscous cement can be injected under lower pressure into the cavity
created.
•• Kyphoplasty is generally done with bilateral approaches but unipedicular
kyphoplasty has been reported.
Complications
•• Placement of the needle may engender root injury and might fracture the
pedicle or rib.
•• Cement leakage may be seen in 60% of patients and is usually
asymptomatic, especially when it occurs into the anterior or lateral
paravertebral spaces, disc or the perivertebral veins.
•• Small intraspinal leaks may also be asymptomatic.
•• Symptomatic cement leakage may result in either radiculopathy or
myelopathy, and occurs in only 1%.
•• Pulmonary cement embolism is rare.
863
•• Bleeding at the puncture site, transitory worsening of pain and fever in the
hours following injection due to the heat generated during polymerisation
and bone infection have been reported.
•• Complications are more common in patients with tumours undergoing
vertebroplasty.
Surgery for Osteoporotic Compression Fractures

•• Patients with demonstrable instability and significant neurological deficits
may need surgery in the acute stage. Delayed neurological progression
after initial fracture healing also calls for surgery.
•• The techniques of stabilising and fusing the spine are similar to those used
in non-osteoporotic vertebrae.
Instrumentation in Osteoporotic Spine
•• Instrumentation of the osteoporotic spine (Table 7) is rendered difficult by
poor purchase of screws leading to screw pullout, wires cutting through the
Table 7: Recommendations on the methods for internal fixation of the

osteoporotic spine
Level Method of choice Comments
Odontoid 1. Anterior screw fixation Chance of wire cut through high in
fracture 2. Posterior transarticular screw fixation Gallie or Brooks wiring
type 2
Subaxial 1. Anterior constrained plate-screw Lateral mass fixation is prone to fail
cervical construct Interspinous wires may cut through
spine 2. Unconstrained plate with bicortical
screw purchase (Caspar)
3. Rectangular cages sit on the
peripheral thick cortical shell and are
better than porotic autografts
Thoracic 1. Multiple segmental fixation using Spinous process wire cut through,
spine pedicle screw or sublaminar wire con- pedicle screw pullout, pedicle break
struct, 2−3 levels above and below after sublaminar wiring and hook
the injured level, supplemented by failure due to break in pars-pedicle
laminar hooks junction are likely
2. Bicortical purchase and placement of
screws as safely as possible near the
end plates for anterior fixation
3. Claw or staple washers prevent the
screw head from sinking into the soft
vertebral body
Lumbar 1. Multiple segmental fixation using Lower the BMD, greater the chance
spine pedicle screw construct of pedicle screw pullout. Pedicle
2. Under-tapping or no tapping, screws cannot be used in spines with
injecting carbonated apatite BMD < 0.3−0.4 g/sq cm.
cement under pressure,convergent Placing bone graft in a stripped
screw paths, large diameter screws, screw hole does not prevent screw
expanding tip screws help achieve pullout in osteoporotic bone
good pedicle screw placement
3. Placement of a good interbody
construct (bone or cages) lessens the
strain on the pedicle screw system
864
bone, greater tendency for settling of cages and proneness for iatrogenic
fracture.
•• The weakest link in osteoporotic bone is the bone-metal interface.
•• These problems can be solved to an extent by: (1) increasing the points
of fixation to evenly spread out the stresses over many levels; (2) adding
supplementary fixation as for example using laminar hooks, wires or
transverse connectors along with pedicle screws; (3) using PMMA bone
cement to augment fixation; (4) using “escape” methods like larger screws
to thwart loosening; (5) using larger cylindrical or rectangular cages which
maximise the surface area of contact; (6) using implants which are less stiff
and nearer to bone in elasticity; (7) using appropriate orthoses for longer
periods and (8) by careful selection of the method of fixation in individual
cases (see recommendations in Table 7).
Interbody Fusion in Osteoporotic Spine
•• Notwithstanding the generally poor autogenous donor bone quality,
tricortical iliac crest autograft is still the best for fusing the osteoporotic
spine.
•• Cylindrical threaded cages, rectangular cages and femoral ring allografts
are available.
•• Cages made of steel, titanium, PEEK ceramic and carbon fibre are
available.
•• End plate integrity must be maintained to prevent settling of cages or strut
grafts.
•• Bone morphogenic protein improves bone fusion but is very expensive.
Section X: Pathology of Intracranial Tumours
116
CHAPTER
Classification of
Tumours of the
Nervous System
Vani Santhosh
Beginning with the classification of brain tumours by Bailey and Cushing (1926)
a number of classification have been proposed, including those by Penfield,
Cone and Elvidge (1931), Kerrohan, et al. (1949), Zulch (1965), Russell and
Rubinstern (1971), more recently who has reported a series of classification
from time to time.
CLASSIFICATION
•• The 4th edition of the WHO Classification of the nervous system (2007) is
the latest published classification of the tumours of the nervous system.
•• This classification lists several new entities like angiocentric glioma,
papillary glioneuronal tumour, rossette forming glioneuronal tumour of
the fourth ventricle, papillary tumour of the pineal region, pituicytoma and
spindle cell oncocytoma.
•• Some of the histological variants added are—pilomyxoid astrocytoma,
anaplastic medulloblastoma and medulloblastoma with extensive nodularity
(MBEN).
•• The WHO grading scheme and the sections on genetic profiles of CNS
tumours have been updated.
•• In the section of familial tumour syndromes, the entity of ‘rhabdoid predis
position syndrome’ has been included.
•• Table 1 represents the current WHO classification of CNS tumours.
GRADING OF CENTRAL
NERVOUS SYSTEM TUMOURS
•• The goal of any grading system is that tumour grade should predict the
biological behaviour of a neoplasm.
•• It should be sufficiently objective, so as to minimise interobserver variability
and maximise reproducibility.
•• Tumour grade is the key factor that influences and guides adjuvant therapy.
Significance of Grading
•• In the CNS, tumours are graded from I to IV.
•• Grade I tumours are those with low proliferative potential and could possibly
be cured by surgical resection alone.
•• Grade II tumours are usually infiltrative, have a lower proliferative potential,
but often progress to higher grade malignancy and recur, for example,
Section X • Pathology of Intracranial Tumours
866
Table 1
Tumours of neuroepithelial tissue Grade
Astrocytic tumours
• Pilocytic astrocytoma I
– Pilomyxoid astrocytoma II
• Subependymal giant cell astrocytoma I
• Pleomorphic xanthoastrocytoma II
• Diffuse astrocytoma II
– Fibrillary astrocytoma
– Gemistocytic astrocytoma
– Protoplasmic astrocytoma
• Anaplastic astrocytoma III
• Glioblastoma IV
– Giant cell glioblastoma IV
– Gliosarcoma IV
• Gliomatosis cerebri III
Oligodendroglial tumours
• Oligodendroglioma II
• Anaplastic oligodendroglioma III
Oligoastrocytic tumours
• Oligoastrocytoma II
• Anaplastic oligoastrocytoma III
Ependymal tumours
• Subependymoma I
• Myxopapillary ependymoma I
• Ependymoma II
– Cellular
– Papillary
– Clear cell
– Tanycytic
• Anaplastic ependymoma III
Choroid plexus tumours
• Choroid plexus papilloma I
• Atypical choroids plexus papilloma II
• Choroid plexus carcinoma III
• Other neuroepithelial tumours
• Astroblastoma I/II
• Chordoid glioma of the third vertical II
• Angiocentric glioma I
Neuronal and mixed neuronal-glial tumours
• Dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos) I
• Desmoplastic infantile astrocytoma/ganglioglioma I
• Dysembryoplastic neuroepithelial tumour I
• Gangliocytoma I
• Ganglioglioma I
• Anaplastic ganglioglioma III
• Central neurocytoma II
• Extraventricular neurocytoma II
• Cerebellar liponeurocytoma II
• Papillary glioneuronal tumour I
• Rosette-forming glioneuronal tumour of the fourth ventricle I
• Paraganglioma I
Contd...
Chapter 116 • Classification of Tumours of the Nervous System
867
Contd...
Tumours of the pineal region
• Pineocytoma I
• Pineal parenchymal tumour of intermediate differentiation II/III
• Pineoblastoma IV
• Papillary tumour of the pineal region II/III
Embryonal tumours IV
• Medulloblastoma
– Desmoplastic/nodular medulloblastoma
– Medulloblastoma with extensive nodularity
– Anaplastic medulloblastoma
– Large cell medulloblastoma
• CNS primitive neuroectodermal tumour
– CNS neuroblastoma
– CNS ganglioneuroblastoma
– Medulloepithelioma
– Ependymoblastoma
•
Atypical teratoid/rhabdoid tumour
Tumours of cranial and paraspinal nerves
• Schwannoma (neurilemmoma, neurinoma) I
– Cellular
– Plexiform
– Melanotic
• Neurofibroma I
– Plexiform
• Perineurinoma I/II/III
– Perineurinoma
– Malignant perineurinoma
•
Malignant peripheral III
– Nerve sheath tumour (MPNST)
– Epithelioid MPNST
•
MPNST with mesenchymal differentiation II/III/IV
•
Melanotic MPNST
•
MPNST with glandular differentiation
Tumours of the meninges
Tumours of meningothelial cells
• Meningioma I
– Meningothelial
– Fibrous (fibroblastic)
– Transitional (mixed)
– Psammomatous
– Angiomatous
– Microcystic
– Secretory
– Lymphoplasmacyte-rich
– Metaplastic
– Chordoid II
– Clear cell II
– Atypical II
– Papillary III
– Rhabdoid III
– Anaplastic (malignant) III
Contd...
868
Contd...
Mesenchymal tumours I/II/III
• Lipoma
• Angiolipoma
• Hibernoma
• Liposarcoma
• Solitary fibrous tumour
• Fibrosarcoma
• Malignant fibrous histiocytoma
• Leiomyoma
• Leiomyosarcoma
• Rhabdomyoma
• Rhabdomyosarcoma
• Chondroma
• Chondrosarcoma
• Osteoma
• Osteosarcoma
• Osteochondroma
• Haemangioma
• Epithelioid haemangioendothelioma
• Haemangiopericytoma
• Anaplastic haemangiopericytoma
• Angiosarcoma
• Kaposi sarcoma
• Ewing sarcoma—PNET
Primary melanocytic lesions
• Diffuse melanocytosis
• Melanocytoma
• Malignant melanoma
• Meningeal melanomatosis
Other neoplasms related to the meninges
• Haemangioblastoma I
Lymphomas and haematopoietic neoplasms
• Malignant lymphomas
• Plastocytoma
• Granulocytic sarcoma
Germ cell tumours IV
• Germinoma
• Embryonal carcinoma
• Yolk sac tumour
• Choriocarcinoma
• Teratoma
– Mature
– Immature
– Teratoma with malignant transformation
• Mixed germ cell tumour
Tumours of the sellar region I
• Craniopharyngioma
– Adamantinomatous
– Papillary
• Granular cell tumour
• Pituticytoma
• Spindle cell oncocytoma of the adenohypophysis
Metastatic tumours
869
diffuse astrocytoma (DA) (Grade II) which can progress to anaplastic

astrocytoma (Grade III) and GBM (Grade IV).
•• Grade III tumours are malignant and these patients have to receive
appropriate radiotherapy and/or chemotherapy.
•• Grade IV tumours are cytologically malignant, with brisk mitosis, often
associated with necrosis. These patients have a poor prognosis and a
fatal outcome. Examples for Grade IV tumours are GBM and most of the
embryonal tumours.
Predictive Value of Tumour Grades

•• WHO grades reasonably predict response to therapy and outcome.
•• However, several studies have shown that, apart from tumour grading, other
clinical parameters particularly age of the patient, Karnofsky performance
status, location of the tumour, radiological characteristics, especially the con
trast enhancement pattern, extent of surgical resection, tumour proliferation
indices and genetic alterations are the factors that govern the biological be
haviour of brain tumours and the prognosis of patients, particularly in gliomas.
•• Despite all these variables, studies have shown that patients with WHO
Grades II tumours survive for more than 5 years and those with Grade III
tumours survive for 2−3 years.
•• In Grade IV tumours, the prognosis largely depends upon the degree of
response to effective treatment regimens.
•• The prognosis for GBM patients is very poor with the mean survival period
not exceeding 9−12 months.
•• However, in patients with medulloblastoma and germ cell neoplasms (Grade
IV tumours) who have received adequate adjuvant therapy, the 5-year
survival rate exceeds 67% and 80%, respectively.
Grading of Astrocytomas
•• Several grading schemes have been applied to this group of tumours,
notably that of Ringertz, St. Anne-Mayo and the published WHO schemes.
•• Currently, the WHO grading system is the one mostly used for ease and
uniformity.
•• The objective criteria taken into account for grading astrocytomas are:
nuclear atypia, mitotic activity, microvascular proliferation and/or necrosis.
•• Tumours with nuclear atypia alone are graded as II, those with nuclear
atypia and mitosis are graded as III and tumours additionally showing
microvascular proliferation and/or necrosis are graded as WHO Grade
IV neoplasms.
•• Nuclear atypia refers to variation in nuclear size or shape, multinucleation
and hyperchromasia.
•• Mitosis should be unequivocal but there is no importance given to their
number and morphology.
•• Sometimes it is difficult to differentiate a Grade II from a Grade III
astrocytoma, when there is a solitary mitosis in a large tumour.
•• Several authors advocate that MIB-1 labelling indices be used to distinguish
accurately a Grade II from a Grade III astrocytoma.
•• The term ‘endothelial proliferation’ or ‘microvascular proliferation’ refers
to ‘heaping up’ of endothelial cells rather than simple hypervascularity or
glomeruloid vasculature.
•• Necrosis can be either of the ‘field’ type or ‘wreath’ type with perinecrotic
pallisading of tumour cells.
870
•• It is important to know that these four objective criteria (e.g. nuclear atypia,
mitosis in tumour cells, endothelial proliferation and/or necrosis) appear in
a predictable sequence as the tumour grade increases.
Biology/Molecular Genetics/Predictive and

Prognostic Factors
Molecular Genetics
•• Two interrelated concepts of molecular oncogenesis have been developed
over the past three decades and it is now proposed that initiation and
progression of astrocytomas, similar to several other neoplasms, are under
the influence of tumour promoting oncogenes and tumour suppressor
genes.
•• Accordingly, two pathways have been defined in the development of
classical GBM resulting in the formation of primary and secondary GBM.
•• Primary GBM occurs in elderly individuals, presenting with a short clinical
history and no clinical or histological evidence of progression from a lower
grade astrocytic glioma as a precursor.
•• Molecular genetic studies have shown that the majority of these tumours
have amplified oncogenes like the epidermal growth factor receptor (EGFR)
gene on chromosome 7. They also possess deletion in the cell-cycle-related
INK4a-ARF genes, p16INK4a and p19/p14ARF.
•• Mutations of the p53 gene (tumour suppressor gene on chromosome
17p13.1) are infrequent and noted in less than 10% of cases. However,
the other tumour suppressor gene that is often mutated is the phosphate
and tensin homology (PTEN) gene located on chromosome 10.
•• On the other hand, secondary GBMs evolve from a lower Grade II or
Grade III.
•• They occur in younger individuals and show predominantly p53 mutations
along with other genetic alterations such as amplification of CDK-4 or loss
of Rb involved in cell cycle regulation.
•• Tumours in this younger group of patients also tend to express a different
signal transduction alteration-amplification or over expression of platelet
derived growth factor (PDGF).
Parameters of Invasiveness
•• The capability of tumour cells to modify the various extracellular matrices
(ECM) in the CNS which in turn facilitates invasion.
•• Studies on several adhesion molecules, which play an important role in
modifying ECM components, have begun to yield data which ultimately
may be useful in diagnosis and prognostication.
•• Recent gene expression profiling studies have revealed subsets of GBMs
with increased expression of ECM components and intracellular proteins
that are associated with cell motility.
Tumour Angiogenesis
•• Astrocytoma development and progression is always accompanied by the
formation of new blood vessels.
•• GBM is the most vascularised of all human neoplasms.
•• The classical angiogenesis is the sprouting angiogenesis, in which there
is recruitment of endothelial cells by neoplastic astrocytic cells, endothelial
cell proliferation, migration and vasculogenesis.
871
•• Angiogenesis in gliomas is regulated by several factors.

•• Hypoxia is the important underlying factor and this leads to accumulation of
hypoxia-inducible factor 1a (HIF-1a) which in turn leads to transcriptional
activation of several genes that regulate angiogenesis, cellular metabolism,
cell proliferation/apoptosis and migration.
•• An important downstream target of HIF-1a is vascular endothelial growth
factor (VEGF).
•• VEGF is mainly produced by the perinecrotic pallisading neoplastic cells
in GBMs.
117
CHAPTER
Pathogenesis:
Tumours of the
Nervous System
Radhakrishnan VV
•• The pathogenetic mechanisms in CNS tumours are discussed under the

following heads: (1) Molecular pathogenesis (oncogenes and tumour
suppressor genes); (2) Hereditary factors; (3) Oncogenic viruses;
(4) Radiation; (5) Chemical carcinogens; (6) Immunosuppression;
(7) Hormones and (8) Trauma.
MOLECULAR PATHOGENESIS OF GLIOMAS

•• The term ‘glioma’ refers to primary tumours of the brain originating from
the major components of glial tissue, i.e. astrocytes, oligodendrocytes and
ependymal cells.
•• The first morphological consequence of anaplasia may be cell atypia, which,
however, is not a hallmark.
•• With anaplasia, the growth fraction increases and it is very likely that an
oncogene activation or tumour suppressor gene deletion is involved in the
passage of cells from the non-proliferating to the proliferating pool.
•• The increase in cell density, enhanced mitotic response and nuclear
pleomorphism are direct consequences of anaplasia, whereas other
histological signs, such as nuclear pleomorphism, necrosis and endothelial
proliferation, usually regarded as indicative of malignancy, represent indirect
consequences only.
•• Based on these four morphological characteristics, Daumas-Duport et al.
published in 1988 a simple method of grading of gliomas.
•• Tumours are grade I if none of these criteria are met, grade II with one
criterion, grade III when two are met and grade IV if three or four criteria
are present in the sections.
•• In fact, the World Health Organization (WHO) system is a three-tiered
grading system, assigning grade II to astrocytoma (fibrillary, protoplasmic
and gemistocytic), grade III to anaplastic astrocytoma and grade IV to
glioblastoma multiforme.
•• Grade I tumours form a distinct category with tumours such as pilocytic
astrocytomas and sub-ependymal giant cell astrocytomas.
•• The initiation and progression of sporadically occurring human malignant
tumours are a result of genetic alterations, mutation, deletion or
rearrangement in one or more genes.
•• Gross chromosomal aberrations in the form of both numerical and structural
alterations are often demonstrated.
•• Extra copies of the genetic material that encode an oncogene could
increase the expression of the oncogene protein and tilt the balance towards
uncontrolled DNA synthesis.
Chapter 117 • Pathogenesis: Tumours of the Nervous System
873
•• The loss of genetic material that encodes a tumour suppressor gene could
again favour uncontrolled DNA synthesis.
•• Thus at least two types of genes have been implicated in the tumourigenic
process of malignant tumours of the CNS: (1) Proto-oncogenes that
promote cell growth and (2) Tumour suppressor genes (TSG), which
negatively regulates cell growth.
Tumour Oncogenes
•• In 1976, DNA sequences almost identical to viral oncogenes were
discovered in the genomes of all vertebrate and invertebrate cells.
•• These genes, named proto-oncogenes, encode growth factors, growth
factor receptors and components of signal transduction mechanisms that
mediate the cell cycle.
•• In neoplastic cells, such genes are frequently found to be mutated or over
expressed and are, therefore, referred to as oncogenes.
•• Two main groups of oncogenes will be discussed: one involved in growth
factor pathways and the other in cell cycle control.
Growth Factors
Epidermal Growth Factor (EGF)
•• Several growth factors or their receptors have been found to be over
expressed in gliomas. In particular, there is evidence for the amplification
of the EGF gene and epidermal growth factor receptor (EGFR) gene.
•• The EGFR is a multifunctional allosteric transmembrane protein with an
extracellular binding site for EGF, a single transmembrane region and an
intracellular domain that exhibits tyrosine kinase (TK) activity.
•• Activation of this EGFR associated TK results in a number of cellular
activities, including mitogenesis and migration of the cell.
•• The EGFR gene has been localised on the short arm of chromosome 7,
within 7p11–12.
•• Amplification as well as over expression of the EGFR gene has been
demonstrated in many histological types of brain tumours.
•• The EGFR gene has been found to be amplified and over expressed in
1% of low grade astrocytomas, in a cumulative incidence of around 10%
in anaplastic astrocytomas and in about 30−40% of glioblastoma (GBM)
and is, therefore, considered to be a hallmark of malignant transformation
in patients with gliomas.
•• Most individuals, whose gliomas carry an EGFR mutation or amplification,
have a poor prognosis, even when the tumour is classified as a grade II
astrocytoma.
Vascular Endothelial Growth Factor (VEGF)
•• VEGF, a 46-kDa protein, is a dimeric growth factor.
•• VEGF has two principal biological activities: (a) To promote microvascular
permeability and (b) The ability to function as an endothelial cell mitogen
and potentially stimulate angiogenesis.
•• The ability to increase vascular permeability is independent of other
inflammatory mediators such as cytokines.
•• The effect of VEGF on endothelial cells is dependent on the activation of
the receptor protein tyrosine kinase (RPTK).
•• There is strong evidence that VEGF plays a dominant role in the
development of angiogenesis that accompanies the anaplastic progression
874
of astrocytic tumours. There is almost no expression of VEGF in the normal

adult brain.
Tumour Angiogenesis Factor (TAF)
•• This is another growth factor found to be present in high levels in glial
tumours.
•• It may play a role in the proliferation and possible subsequent transformation
of vascular and perivascular mesenchymal elements to the development
of an angiosarcoma.
Other Growth Factors in Gliomas

•• The other growth factors with potential mitogenetic activities include
erythropoietin, found to be active in capillary haemangioblastoma;
progesterone receptors in meningiomas and insulin-like growth factor
receptors in glioblastoma.
•• Certain glioblastomas may also over express the transforming growth
factor-alpha (TGF-a) gene, the protein product of which resembles EGF
and binds to the EGFR stimulating TK activity.
•• Several studies demonstrated over expression of platelet derived growth
factor (PDGF) and PDGF receptor in glioblastoma.The oncogene encoding
PDGF is located on chromosome 22.
•• The basic fibroblast growth factor (bFGF) gene is known to exert a trophic
effect upon a variety of cells of neural origin and is prevalent in the neural
tissue.
Cyclin Dependant Kinases (CDK)

•• Besides the growth factors, another important cell cycle regulator
mechanism consists of the cyclin dependant kinases (CDKs) and their
inhibitors.
•• They regulate a number of target molecules by phosphorylation. Activation
of these CDKs will lead ultimately to DNA replication and mitosis.
•• The CDKs are activated by cyclins and inhibited by a still growing number of
proteins that include factors named after their apparent molecular weights:
p15, p16, p21 and p27, encoded by their respective TSG.
•• The expression and interactions between these three types of molecules,
CDKs, cyclins and CDK inhibitors account to a great extent for cell cycle
control.
•• Over expression of CDK4, therefore, will indirectly stimulate cell growth (by
controlling pRb1) and eventually lead to uncontrolled mitosis.
•• Amplification of the CDK4 gene occurs in 30% of patients with anaplastic
astrocytomas.
Tumour Suppressor Genes (TSG)

•• A second class of genes related to anaplasia is TSG.
•• Indications for the existence of TSG came from observations made during
the study of retinoblastoma, occurring both in sporadic and familial form.
•• The association of loss of genetic material with the development of cancer
is consistent with the idea that the normal allele protecting against the
formation of retinoblastoma must be dominant and, therefore, must be
inactivated or deleted before the mutant, recessive retinoblastoma allele
will give rise to the tumour.
875
•• In the familial form, one mutation (first hit) is already present due to
inheritance. The second hit (mutation or the loss of the other allele of a
TSG) occurs somatically in the target tissue (retina).
•• A high penetrance in the familial form that affects both eyes in very young
children reflects the high probability of the second hit in these patients.
•• In the sporadic form, two somatic events usually occur. Since the somatic
mutation rate is low, only one eye is affected and the children are older
before they develop retinoblastoma.
•• This led to the two hit theory of Knudson where inactivation due to loss of
functional inhibition of both copies of specific allele on two homologous
chromosomes may lead to tumourigenesis.
•• In most instances of TSG inactivation, one allele carries a point mutation
while the other is inactivated by a major structural alteration such as
chromosomal deletion, inversion or translocation.
Retinoblastoma (Rb) Gene and Gliomas

•• The Rb gene, which is the product of pRb1 protein, is involved in the
transition of the cell from G0 or G1 to the S phase in the cell cycle.
•• Inactivation of the Rb gene has been reported in about 20% of anaplastic
astrocytomas and GBM, and it is concluded that the phosphorylated pRb1
is involved in the malignant progression of gliomas.
•• It has been demonstrated that 85% of a series of GBM had one or
the other defect, thereby highlighting that the cell cycle growth control
system determining their progression from G1 to the S phase by the
phosphorylation of pRb1 is defective.
p53
•• Several intracranial tumours including gliomas with loss of chromosome
17 show partial chromosomal deletion with the common region of allelic
loss involving 17p13.
•• The p53 protein, which is the product of the p53 wild-type gene, is involved
in cell cycle control.
•• At least two stages in the cell cycle are regulated in response to DNA
damage—the G1-S and the G2-M transitions.
•• p53 encodes a nuclear protein that suppresses this cell transformation.
•• p53 mediates this effect on cellular growth either by inducing apoptosis
(programmed cell death) or through a transient cellular arrest at the G1
phase.
•• Until now, no grade-specific p53 mutations are identified. Gliomas are
observed with increased prevalence in association with Li-Fraumeni
Syndrome (LFS of breast cancer, sarcomas, autosomal dominant patterns
of inheritance), NF-1, NF-2, tuberose sclerosis and Turcot’s syndrome.
LOH-10
•• Since the loss of alleles is in chromosome 10 in almost 80% of cases
of glioblastoma multiforme, it is presumed that inactivation of a tumour
suppressor gene on this chromosome is a critical step in the transition of
astrocytoma grade III to glioblastoma multiforme.
•• Despite considerable efforts, the common deletion region on chromosome
10 at molecular level remains poorly defined.
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Genetic Instability
•• Genetic instability has been suggested as a possible mechanism in the
development of cancer.
•• The genomic instability can be observed as a change in the length of
microsatellite sequences in the tumour DNA as compared to constitutional
DNA. The genomic instability is the result of replication errors.
•• Microsatellite instability has been found in many tumours including gliomas.
•• It is present in low-grade astrocytomas, but more frequently in glioblastoma,
and appears as a hallmark of a more generalised genomic instability.
HEREDITARY SYNDROMES
•• Familial clustering does not seem to account for a majority of brain tumours.
•• However, a high incidence of brain tumours has been observed in families
with at least one affected member with brain tumour, suggesting that tumour
susceptibility may be inherited in these cases.
•• A number of hereditary syndromes, such as phakomatosis or familial cancer
syndrome, are also associated with an increased risk for brain tumours.
•• The phakomatoses (e.g. neurofibromatosis, tuberose sclerosis, von-Hippel-
Lindau disease) are neurocutaneous disorders, characterised by tumours
of ectodermal and mesenchymal origin, with vascular malformations of the
skin, eyes and the CNS.
•• Neurofibromatosis type I (NF-1) is characterised by café-au-lait spots,
hamartomas of the iris (Lisch nodules) and multiple cutaneous and
plexiform neurofibromas. Other neoplasms associated with NF-1 include
schwannoma, phaeochromocytoma, rhabdomyosarcoma, optic glioma
and astrocytoma.
•• The NF-1 gene has been identified and mapped to chromosome 17q11.
It encodes the protein ‘neurofibromin’, which stimulates a ras-associated
GTPase and may, therefore, exhibit its physiological role as a transducer
for growth factor mediated signals.
•• The NF-2 gene located on chromosome 22q11 encodes the proteins merlin/
schwannomin, a cytochrome-associated protein.
•• The clinical triad of tuberose sclerosis (TSC) consists of adenoma
sebaceum, seizures and mental retardation. The most frequently observed
tumours in this condition are subependymal giant-cell astrocytoma and
ganglioglioma.
•• The disease-causing gene product has been identified only for TSC2,
called ‘tuberin’ and it encodes a GTPase activating protein that may act in
a similar fashion as the NF-1 protein.
•• Patients with Turcot’s syndrome develop gliomas and adenomatous
polyposis coli, which regularly progresses to colorectal carcinoma. The
adenomatous polyposis coli (APC) gene has been cloned and mapped
to chromosome 5.
•• Li-Fraumeni’s syndrome is caused by an inherited mutation of the p53
tumour suppressor gene. Affected patients display a variety of tumours,
most commonly carcinoma of breast, sarcoma, leukaemia and brain
tumours.
ONCOGENIC VIRUSES
•• A large number of oncogenic viruses have been implicated in the
pathogenesis of human brain tumours and these include: simian virus,
877
JC virus, Rous sarcoma virus, adenovirus, polyoma virus and papilloma

virus.
•• Simian Virus-40 (SV-40):
–– Primitive neuroepithelial tumours induced by ‘simian virus-40 (SV-40)
large T-antigen’ are morphologically indistinguishable from that of hu-
man medulloblastoma.
–– SV-40 large T-antigen binds and inactivates several tumour suppres-
sive genes including p53 and Rb gene and is capable of transforming
human cells in vitro.
JC Virus
•• JC virus has an extensive nucleotide sequence homology with SV-40 and
also overlapping antigenicity, but the host range is definitely different.
•• While SV-40 rarely infects human cells, latent JC viral infection is very
common with a seroprevalance of 40−60% in most developed countries
particularly in immunocompromised patients.
•• In the brain, JC virus infection may cause progressive multifocal
Adenovirus 12
•• Human adenovirus 12 has been shown to induce neuroblastoma and
retinoblastoma in rodent models following intracerebral and intraorbital
inoculation.
EFFECT OF RADIATION
•• Radiation has been implicated in the induction of human intracranial
neoplasms for over thirty years.
•• However, the exact incidence of intracranial tumour development following
irradiation is still unknown.
•• Meningiomas have been reported to develop following radiation therapy
for pituitary and glial tumours.
•• Fibrosarcomas are the next common type of tumours to develop after
radiation therapy.
•• However, the following criteria should be fulfilled in order to incriminate
radiation therapy in the development of intracranial tumours:
–– The tumour occurs within the anatomical territory of radiation
–– An adequate latent period exists following radiation, commensurate
with the dose of radiation given
–– No factors predisposing to tumour development exists such as neurofi-
bromatosis or multiple endocrine neoplasia syndrome
–– The tumour would rarely occur spontaneously in a control group of
non-irradiated patients.
Radio Frequency (RF) Radiation

•• In recent years, there is a rapid increase in the use of cellular phones.
•• Data so far gathered is too limited to implicate the biological effects of radio
exposure for the occurrence of brain tumour.
•• However, exposure to higher frequency radio frequency fields is known to
increase local tissue heat and vascularity and these may be expected to
affect the blood-brain barrier.
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CHEMICAL CARCINOGENS
•• Several studies have been undertaken to test the assumption that N-nitroso
compounds play a role in the evolution of human brain tumours.
•• Nitroso compounds have been detected in nitrite-preserved food and in
beer, but they can also be formed in the stomach after the intake of their
chemical precursor, nitrate/nitrite and secondary amines.
•• Experimental data in animals provides evidence that chemical carcinogens,
such as nitroso compounds and polycyclic hydrocarbons, can be used to
induce brain tumours.
•• Druckrey et al. demonstrated that N-methyl-N-nitrosourea (MNU) selectively
induced CNS tumours.
•• Malignant gliomas developed in 90−100% animals within eight months after
regular intravenous administration of MNU.
•• Anaplastic and mixed gliomas along with oligodendroglioma are the
commonest MNU induced CNS tumours. They occur preferentially in the
subcortical white matter, hippocampus and periventricular regions.
•• Ethyl nitrosourea (ENU) is another commonly used alkylating agent.
•• Administration of ENU on the 15th day of gestation results essentially in
CNS tumours, while exposure to ENU on the 21st day of gestation leads
primarily to spinal cord and nerve sheath tumours.
•• Despite sufficient experimental data suggesting that chemical carcinogens
may have a role in animal models, so far no firm evidence of the
carcinogenic effects of these elements in humans has been established.
IMMUNODEFICIENCY STATUS
•• Among all intracranial malignant tumours, association of congenital or
acquired immunodeficiency disorders with primary central nervous system
lymphoma (PCNSL) has been established.
•• Overall PCNSL occurs in as many as 6% of AIDS patients and may
be seen in conjunction with other neurological complications such as
cytomegalovirus or toxoplasmosis infection, or progressive multifocal
•• The Epstein-Barr virus (EBV) is frequently found in lymphomas and in
immunodeficient patients.
•• The EBV sequence has also been consistently found in AIDS-related
PCNSL.
•• In addition, use of highly sensitive PCR to detect EBV genome in the CSF
of AIDS patients may be diagnostic of PCNSL, providing a simple and
non-invasive alternative to stereotactic biopsy.
HORMONAL FACTORS
•• There is some evidence to suggest a role of hormonal factors in the
development of meningioma and possibly acoustic schwannoma and
pituitary adenomas.
•• Steroid hormones can cross the blood-brain barrier and progesterone
is thought to affect the growth of some intracranial tumours, especially
meningiomas, gliomas and vascular tumours.
•• The female preponderance of meningioma and pituitary tumours has
been well established in clinical and population studies, an effect that was
stronger in younger than older women.
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TRAUMA
•• An association between trauma and meningioma/glioma development has
been proposed frequently.
•• Based on their observations, Cushing and colleagues suggested that
one-third of meningiomas were related to previous trauma. More recent
case reports of brain tumours associated with previous trauma sites were
explained by the introduction of carcinogenic compounds into open wounds
or by the activation of dormant tumourigenic cells during repair-related
proliferation.
•• While repeated case reports keep the intriguing relationship in mind,
sufficient data is not there to support an aetiologic role of trauma for primary
brain tumours.
•• Review of larger series did not detect a significant correlation between
trauma and brain tumours.
CONCLUSION
•• Precise pathogenetic mechanisms in the development of human malignant
cerebral neoplasms are still not well defined.
•• Understanding of the processes such as cell-cycle control, programmed
cell death and angiogenesis, together with the discovery of oncogenes and
TSG have provided insight into the mechanisms of initiation, proliferation
and progression of the tumour.
•• Tumourigenesis is a multistep process caused by genetic changes that are
either inherited or acquired.
•• The identification of the genes responsible for hereditary syndromes
associated with tumours such as p53, Rb and NF genes and the
elucidation of their functional role have been extended to understanding the
pathogenetic mechanisms underlying sporadically occurring brain tumours.
•• In addition, analysis of genetic changes, such as gene amplification or loss
of heterozygosity, allow the identification of markers that can be used as
more accurate tools for diagnosis and the assessment of tumour prognosis.
118
CHAPTER Germ Cell Tumours of the
Vani Santhosh
INTRODUCTION
•• The majority of patients are below the age of 25 years and the peak
incidence is 10−14 years.
•• A distinct male preponderance has been observed.
•• They are classified as follows:
–– Germinoma
–– Teratoma—mature teratoma, immature teratoma, teratoma with
malignant transformation
–– Yolk sac tumour
–– Embryonal carcinoma
–– Choriocarcinoma.
CLINICAL FEATURES AND LOCALISATION

•• These tumours preferentially affect midline structures.
•• The majority of tumours arise from structures around the third ventricle-
pineal region followed by the suprasellar compartment.
•• Other sites include: intraventricular, basal ganglionic, diencephalic,
intramedullary and intrasellar.
•• Germinomas have a predilection to arise from the suprasellar region while
other non-germinomatous tumours arise from the other sites mentioned above.
•• Clinical symptoms depend on the anatomical site of the neoplasm.
•• Those in the pineal region present with features of obstructive hydrocephalus
and neuro-ophthalmic paralysis or Parinaud’s syndrome due to infiltration
of the tectal plate.
•• They can also present with features of raised intracranial pressure.
•• Tumours in the suprasellar region produce visual compressive symptoms.
•• They disrupt the hypothalamo-pituitary axis and may produce diabetes
insipidus and features of pituitary failure, which include retarded growth
and sexual maturation.
•• Some tumours that secrete human chorionic gonadotropin (hCG) can
cause precocious puberty.
•• In general, the symptoms are more protracted in germinomas than in other
germ cell tumours.
IMAGING FEATURES
•• On CT and MRI scans, except teratomas, all others are solid masses that
are isointense to hyperintense relative to grey matter and show prominent
Chapter 118 • Germ Cell Tumours of the Central Nervous System
881
contrast enhancement. Intratumoural cysts, areas of calcification and areas

of low signal attenuation characteristic of fat are seen in teratomas.
PATHOLOGY
Germinoma
•• These are composed of large neoplastic cells that resemble primordial
germ cells.
•• The cells are round with a vesicular, centrally placed nucleus with a
prominent nucleolus and abundant glycogen filled cytoplasm.
•• Mitosis is frequent but necrosis is rare.
•• The cells are disposed in sheets and lobules separated by a desmoplastic
stroma.
•• Infiltration of the tumour by a variable number of mature lymphocytes
(T cells) is a characteristic feature.
•• Some tumours can have florid lymphocytic or lymphoplasmacytic infiltrates
along with epithelioid granulomas and giant cells. In such tumours, it is
important to identify primordial germ cell elements to avoid a misdiagnosis
of a granulomatous lesion.
•• Immunohistochemical markers for the germ cell component include cell
membrane staining for placental alkaline phosphatase (PLAP), ckit and
nuclear labelling for OCT4.
Teratoma
•• These tumours contain ectodermal, endodermal and mesodermal elements.
Mature Teratoma
•• These are composed of fully mature ‘adult-type’ tissue elements.
•• The common ectodermal elements include skin and neuroepithelial tissues.
•• Mesodermal elements are represented by cartilage, fat, muscle and bone
and the endodermal elements include respiratory or intestinal type of
epithelium.
Immature Teratoma
•• This variant contains incompletely differentiated components resembling
foetal tissues either as a minor portion of the tumour which is otherwise
composed of mature elements or it can predominate in the tumour.
•• The component that is often immature is the mesenchymal or neuroectodermal
elements and these cells are mitotically active.
Teratoma with Malignant Transformation
•• These are rare tumours exhibiting malignant transformation of one of the
somatic elements.
•• Commonly seen are undifferentiated sarcomas, or regions of squamous
cells or adenocarcinomas within the tumour.
Yolk Sac Tumour

•• This tumour is composed of a loose myxoid matrix within which are primitive
appearing epithelial cells (representing yolk sac endoderm).
•• The cells can be in solid sheets, trabeculae or line delicate fibrovascular
projections to form distinctive papillae known as Schiller-Duval bodies.
•• They can also show a reticular or sinusoidal growth pattern.
882
•• The diagnostic feature, although not always present, is the presence of

PAS positive, diastase-resistant hyaline globules located intracytoplasmic
or freely in the myxoid stroma.
•• The tumour cells exhibit high mitosis and cytoplasmic labelling of alpha
fetoprotein (AFP) which is characteristic.
•• The hyaline globules are also AFP positive.
Choriocarcinoma
•• These tumours contain cytotrophoblastic and syncitiotrophoblastic elements.
•• Ectatic stromal vascular channels and large areas of fresh haemorrhage
characterise this tumour.
•• Cytoplasmic immunoreactivity for βHCG and human placental lactogen
is diagnostic.
Embryonal Carcinoma
•• This rare tumour is composed of large cells arranged in abortive papillae,
gland-like structures and can replicate an early embryo forming the
‘embryoid bodies’.
•• The tumour cells show cytokeratin immunoreactivity along with PLAP and
OCT labelling.
•• Often CNS germ cell tumours are encountered as mixed histological forms.
HISTOGENESIS
•• One of the hypothesis for the origin of CNS germ cell tumours is the
neoplastic transformation of germ cells that either migrate in an aberrant
fashion or ‘home’ to the embryonic CNS.
•• However, immunohistochemical studies on foetal pineal gland for germ
cell markers including PLAP expression have never shown this gland to
harbour primordial germ cells.
•• An alternate hypothesis postulates an origin for CNS germ cell tumours in a
variety of displaced embryonic tissues that can be sometimes incorporated
in the developing neural tube.
•• Another speculation is the involvement of totipotent or pleuripotent stem
cells in the origin of these tumours.
PROGNOSTIC AND PREDICTIVE FACTORS

•• Prognosis depends on the histological sub-type of the tumour.
•• Mature teratomas are curable by complete resection of the tumour.
•• Germinomas are extremely radiosensitive and 10 year survival has been
recorded after craniospinal irradiation.
•• The tumours most resistant to treatment are yolk sac tumours, embryonal
carcinoma and choriocarcinomas.
•• Immature teratomas and mixed germ cell tumours with predominant
teratoma and germinoma components and containing non-germinomatous
components occupy an intermediate position in terms of aggressiveness.
119 Embryonal Tumours of the
CHAPTER
Chitra Sarkar  MC Sharma
INTRODUCTION
•• Embryonal Tumours of the CNS are highly malignant tumours (WHO grade
IV) occurring predominantly in children.
•• The following tumours are included in this group according to the WHO
classification (2007):
–– Medulloblastomas (MBs)
–– CNS primitive neuroectodermal tumours (PNETs)
¾¾ CNS/Supratentorial PNETs (SPNETs)
¾¾ Medulloepithelioma
¾¾ Ependymoblastoma
–– Atypical teratoid/Rhabdoid tumours (AT/RTs).
MEDULLOBLASTOMAS
•• These are the most common malignant brain tumours of childhood
accounting for approximately 12−25% of all CNS tumours in children.
They correspond histologically to WHO grade IV and are subdivided into
the following histological subtypes (WHO 2007):
–– Classic MB
–– Desmoplastic/Nodular MB
–– MB with extensive nodularity (MBEN)
–– Anaplastic MB
–– Large cell MB
–– MB with melanotic differentiation (melanocytic)
–– MB with myogenic differentiation (medullomyoblastoma).
Clinical Features
•• The overall mean and median ages at diagnosis are 13 years and 9 years
respectively with a peak age of occurrence around 7 years.
•• Among the adult patients, 80% are in late adolescence or early adulthood
(median 25 years).
•• MBEN typically occurs in infants less than 3 years of age.
•• The desmoplastic variant, however, shows almost equal distribution
between children and adults.
•• There is a marked male preponderance with approximately two-third of
patients being males.
884
•• MBs are tumours of the cerebellum with 75% of them arising in the
cerebellar vermis.
•• A hemispheric or lateral location is more common among adolescents
and adults.
•• The most common subtypes of MB in a hemispheric location are
desmoplastic/nodular types.
•• The presenting clinical features commonly include gait disturbances and
truncal ataxia.
•• These are often associated with features of raised intracranial pressure
secondary to obstructive hydrocephalus.
•• In the later stages, clinical manifestations may be related to the spread of
tumour through the CSF pathways.
Imaging
•• Imaging (both CT and MRI) reveal most MBs as solid masses with intense
enhancement on contrast injection. Striking “grape like” pattern on MRI is
characteristic of MBEN.
Histopathology
•• The majority of MBs arise in the vermis and appear as pink or grey masses
that can project and fill the fourth ventricle.
•• Foci of necrosis are generally small and extensive necrosis is uncommon.
Classic Medulloblastomas
•• Classic MBs are characterised by sheets of densely packed cells with
hyperchromatic round to oval or carrot shaped nuclei, scant cytoplasm,
numerous mitosis and conspicuous apoptosis.
•• Homer-Wright rosettes are observed in less than 40% of cases.
•• These rosettes are characterised by arrangement of tumour cells around
a fibrillary centre.
•• Varying degrees of neuronal and glial differentiation can be seen in these
tumours.
•• Areas of necrosis and vascular hyperplasia are uncommon.
•• The tumour shows high mitotic activity.
Desmoplastic/Nodular Medulloblastomas
•• Desmoplastic/nodular MBs show a distinctive nodular architecture with
reticulin free pale islands alternating with reticulin rich internodular regions.
•• The cells within the nodules have round uniform nuclei, with evidence of
neuronal differentiation (synaptophysin +ve) and show low mitotic rate (low
MIB-1 labelling index) but high apoptosis.
•• In contrast, the cells in the internodular regions have hyperchromatic
irregular nuclei, show evidence of glial differentiation (GFAP +ve) and have
a high mitotic rate, but a low apoptotic rate.
•• This characteristic pattern may be present either diffusely or focally
throughout the tumour.
•• It is important to emphasise that MBs showing only increased amounts
of reticulin fibres and/or collagen, but lacking the nodular pattern, are not
classified as desmoplastic/nodular variant.
•• The high reticulin/collagen content could be a secondary event to
leptomeningeal invasion.
Chapter 119 • Embryonal Tumours of the Central Nervous System
885
Medulloblastomas with Extensive Nodularity

•• MBEN comprise of nodules having round cells with uniform nuclei arranged
in a laminar/streaming pattern with a fine fibrillary neuropil like matrix (cells
resemble those of central neurocytoma).
•• These cells express synaptophysin while the surrounding undifferentiated
cells are negative.
•• They possibly represent the most differentiated form of desmoplastic MBs
comprising of well-delineated nodules with little or no internodular cellular
component unlike desmoplastic MBs.
Anaplastic Medulloblastomas
•• Anaplastic medulloblastomas (MBs) are characterised by marked nuclear
pleomorphism, nuclear moulding, cell-to-cell wrapping, high mitotic activity
(including abnormal forms) and high apoptotic rate.
•• The above changes have to be pronounced and widespread within a tumour
to label it as an anaplastic MB.
•• If these features are present only focally, then a tumour cannot be labelled
anaplastic MB.
•• Several studies have documented histological progression from non-
anaplastic to anaplastic MB (similar to malignant progression in gliomas).
Large Cell Medulloblastomas
•• Large cell MBs comprise of monomorphic cells with large round vesicular
nuclei, prominent nucleoli and variable amounts of eosinophilic cytoplasm
with abundant mitosis and apoptosis.
•• Large cell and anaplastic MBs show considerable histological overlap and,
hence, in several studies, a combined large cell/anaplastic category (LC/A
MBs) has been proposed.
Melanocytic Medulloblastomas
•• Melanocytic MBs are characterised by the presence of melanin in scattered
tumour cells.
Medullomyoblastomas
•• Medullomyoblastomas comprise of areas of classic MBs admixed with
cells that show rhabdomyoblastic differentiation (spindle or strap cells
with cross-striations of skeletal muscle and immunopositivity for desmin).
Tumour Markers
•• Most MBs are immunopositive for nestin and vimentin.
•• Synaptophysin is also by and large positive, although its expression may take
several forms (from completely negative to patchy positivity to diffuse positivity).
•• The other markers that can be demonstrated, at least focally in many
MBs, include class III beta tubulin, MAP-2, neuron specific enolase and
neurofilament.
•• Most tumours contain GFAP positive reactive astrocytes but there are tumours
in which unequivocal GFAP positivity is noted within the neoplastic cells.
•• Tissue from the undifferentiated areas does not show any specific ultra-
structural features.
•• In the areas of neuroblastic differentiation (rosettes), the cells show neurite
like cytoplasmic processes filled with microtubules.
•• Dense core vesicles and synapse-like structures may also be seen. In
areas of glial differentiation, abundant intermediate filaments are noted.
886
Histogenesis
•• The histogenesis of MBs has remained controversial for over 80 years,
since Bailey and Cushing first recognised it as a distinct clinicopathological
entity in 1925.
•• There are two main hypotheses. One view suggests that MBs arise from
the cells of the external granular layer of the cerebellum.
•• The second hypothesis states that MBs are derived from subependymal
matrix cells, which reside throughout the embryonal CNS, including the
fourth ventricle, which give rise to neuronal and glial cells.
•• Perhaps, most likely, is a combined theory proposing that MBs arise from
more than one cell type.
•• Based on this theory it is suggested that classic MBs are derived from
the periventricular primitive zone while nodular MBs arise from external
granular layer cells.
•• New candidate cells of origin continue to be proposed and one such recent
hypothesis is the origin from CD133+ve stem cells found predominantly in
the white matter of the postnatal cerebellum.
Molecular Genetics
•• These have been divided into three main groups namely: (i) non-random
chromosomal abnormalities; (ii) abnormalities in signal transduction
pathways and (iii) altered expression of neural transcription factors.
Non-random Chromosomal Abnormalities
•• Chromosome 17: Partial or complete deletion of the short arm of
chromosome 17 (17p) is noted in 30−50% of MBs and is the most frequent
non-random chromosomal abnormality.
•• Other chromosomes: Loss of genetic material from chromosome 1q and
10q are demonstrated in approximately 20−40% of MBs.
•• Gene amplification: C-myc gene amplification occurs in 4−17% of MBs,
followed by N-myc.
Abnormalities in Signal Transduction Pathways
•• Sonic Hedgehog SHH-PTCH signalling pathway: Abnormalities in the
SHH/PTCH signalling pathway was first suggested following the observation
that 1−2% of patients developing MB have Gorlin’s syndrome or Naevoid
Basal Cell Carcinoma Syndrome (NBCCS) which are caused by mutations
of the PTCH gene.
•• Wingless (WNT/WG) signalling pathway: Involvement of this pathway in
MB was first suggested because of the association of some MB cases with
type 2 Turcot’s syndrome, a familial cancer syndrome, in which patients
have adenomatous colonic polyps, predisposing to colonic carcinoma,
in association with germ-line mutations of the APC gene (Adenomatous
Polyposis Coli).
•• Neurotrophin signalling pathway: The neurotrophin signalling pathway
comprises of the neurotrophin family along with the tyrosine receptor kinase
family of receptors (Trk receptors A, B and C) and plays a major role in
cerebellar development. Increased expression of Trk receptors, especially
TrkC, has been noted in MBs, especially desmoplastic MBs.
•• ErbB receptor signalling pathway: ErbB receptor signalling pathway is
important in both cerebellar development and MB tumourigenesis. The
ErbB2 receptor especially appears to play a central role in MB.
887
•• Notch signalling pathway: Notch is a pathway that plays a critical role in

regulation of neural stem cells. In the cerebellum, Notch 2 has been shown
to promote proliferation of EGL progenitor cells.
Treatment and Prognosis
•• Before 1970, the overall 5-year survival rate for patients with MBs was
only 2−30%. Since then, with the advancements in diagnosis, imaging
and management (both surgical and radio-chemotherapeutic) the 5-year
survival has markedly improved to 60−70%.
•• MBs spread via the CSF pathways with subarachnoid seeding occurring
in up to one-third of patients at the time of diagnosis.
•• Recurrence, generally local, is unfortunately very common and mostly
occurs within the first 2 years after initial treatment; however, late
recurrences can occur sometimes 10−19 years after diagnosis.
•• Systemic/extraneural metastasis is also described, the most common site
being bone, followed by lymph nodes. They may manifest up to several
years after initial treatment, within a median time of 12−32 months.
Risk Stratification in Medulloblastomas

(Prognostic Factors)
Clinical Factors
•• MBs have been stratified on the basis of age, extent of resection and Chang
et al. metastasis staging into the following two risk groups:
–– Average risk: Patients older than 3 years of age with non-metastatic
disease and total or near total resection (<1.5 cm of residual tumour
on post-operative imaging).
–– High risk: Patients less than 3 years, with incomplete surgical
resection (>1.5 cm residual tumour) or with metastatic disease at
presentation (Chang stages M1 to M4).
Histopathological Factors
Histopathological subtypes
•• The best prognostic outcome is seen with MBEN while large cell/anaplastic
MBs have the worst outcome with high local recurrence, CSF and systemic
metastasis and death within 1−2 years of diagnosis.
•• Prognosis of the desmoplastic variant still remains debatable. They have
been inconsistently correlated with better outcome, worse prognosis or no
relation with survival time.
•• Other variants with poor outcome are melanotic MBs and medullomyo-
blastoma, with survival of 2 months to 2.5 years in the former, to less than
1 year in the latter.
•• Anaplasia: It has been proposed as the criteria associated with aggressive
behaviour and poor outcome.
•• Differentiation: MBs have been shown to differentiate along glial or
neuronal cell types. Different studies have shown variable prognostic
significance for GFAP positivity ranging from better to poor to equivocal.
Proliferation index and apoptotic index
•• The overall significance of cell proliferation and apoptotic index as
prognostic markers is still debatable.
•• Ploidy: Aneuploid tumours have been shown to respond favourably to
treatment as compared to diploid tumours.
888
Molecular, Cytogenetic Factors and

Signalling Pathway Markers
•• Loss of 17p/Isochromsome 17q: Poor outcomes, shortened survival
and metastasis have been demonstrated with 17p deletions and/or
isochromosome 17q.
•• C-myc and N-myc Amplification: Tumours with myc gene amplification
have a significantly worse clinical outcome, shorter survival and resistance
to therapy
•• Gene Profiling: Gene expression profiling of MBs have been studied using
oligonucleotide microarrays. Genes attributed to cerebellar differentiation
and genes encoding extracellular matrix proteins have been correlated
with a better prognosis.
•• TrkC Expression: TrkC is the single most important predictor of favourable
outcome in MBs.
•• ErbB2 Expression: Increased ErbB2 expression is associated with poor
prognosis.
•• Wingless (WNT/WG) Pathway: Nuclear accumulation of beta-catenin,
a marker of activation in the WNT pathway, has been found to be an
independent marker of good outcome.
•• The mainstay of treatment of MBs has been maximal surgical resection,
whole neuraxis radiation and chemotherapy.
•• However, only 60% of children with MBs are cured using the aggressive
regimen and most of them suffer long-term side effects in the form of
neuropsychological sequelae and neurocognitive decline.
•• Hence, new modalities of treatment aimed at lowering the dose
of craniospinal axis irradiation (CSA-RT) combined with adjuvant
chemotherapy (CT) are being tried.
•• New treatment modalities being investigated include new techniques of
three-dimensional conformal RT and intensity modulated radiation therapy
(IMRT) which precisely direct RT to the desired site and minimise the
neurotoxicity of conventional RT.
•• New biological and molecular factors are also being targeted for novel
therapeutic approaches.
•• One of these is cyclopamine, a plant-derivative teratogen that inhibits the
SHH/PTCH1 pathway by binding to and altering the conformation of SMO
gene product.
•• A second class of potential molecular therapeutic agents for MBs is small
molecule inhibitors of receptor tyrosine kinases like ErbB2 and PDGFR.
Very recently, Erlotinib (TM), a dual specific ErbB1/ErbB2 inhibitor, was
shown to selectively inhibit ErbB2 signalling, cell invasion and ErbB2-
dependent prometastatic gene expression in MB cells in vitro and in vivo.
•• Neural stem cells, retrovirally transduced with cytosine deaminase gene
(CD-NSCs) treatment, followed by 5-fluorocytosine administration have
shown to prolong survival periods significantly in experimental animals.
ATYPICAL TERATOID/RHABDOID TUMOUR

•• This is a highly malignant CNS tumour in children, histologically
corresponding to WHO grade IV.
•• It comprises about 1−2% of paediatric brain tumours and about 10% of
CNS tumours in infants.
889
Clinical Features
•• AT/RTs most often present in children less than 3 years of age (mean
age 2 years).
•• They are rare in children older than 6 years and even rarer in adults.
•• Male preponderance is noted.
•• AT/RTs occur both in the supratentorial and infratentorial locations (ratio
of 1.3:1).
•• Infratentorial tumours are commonly located in the cerebellar hemispheres,
cerebellopontine angle and brainstem.
•• Supratentorial tumours are more often located in the cerebral hemispheres
and less frequently located in the ventricular system, suprasellar or pineal
region.
•• About 2% of AT/RTs arise in the spinal cord.
•• Variable clinical presentation is noted depending upon the age of the
patient, location and size of the tumour.
Imaging
•• AT/RTs are isointense to slightly hyperintense with a variable degree of
contrast enhancement, similar to MBs.
Histopathology
•• AT/RTs are soft pinkish and red bulky tumours with foci of haemorrhage
and necrosis. Some regions of tumour may appear firm and grey-white.
•• AT/RTs are histologically heterogeneous lesions.
•• The most conspicuous feature is the presence of rhabdoid cells with
eccentrically placed vesicular nuclei, prominent eosinophilic nucleoli and
abundant eosinophilic cytoplasm containing globular intracytoplasmic
eosinophilic inclusions.
•• In addition to these rhabdoid cells, most tumours contain variable com-
ponents of primitive neuroectodermal, mesenchymal and epithelial cells.
•• Mitotic figures are abundant and necrosis is common.
•• AT/RTs show a wide range of immunoreactivity.
•• Rhabdoid cells are consistently positive for vimentin and epithelial
membrane antigen.
•• Expression of glial fibrillary acid protein, neurofilament protein, synaptophy-
sin, smooth muscle actin and cytokeratin are variably observed.
•• Germ cell tumour markers are never expressed in these tumours.
Histogenesis and Molecular Genetics

•• The histogenesis of AT/RTs is not known.
•• Various hypotheses suggested include origin from pluripotent foetal cells,
neural crest cells, meningeal cells and germ cells.
•• The genetic hallmark of AT/RTs is mutation or loss of the INI1 (hSNF5/
SMARCB1) gene locus at 22q11.2 chromosome.

•• The overall prognosis of AT/RTs is very poor, mean survival being 11
months and median survival 17 months.
•• The majority of patients develop local recurrence and/or neuraxis
dissemination, and die within a year of diagnosis.
890
CENTRAL NERVOUS SYSTEM PRIMITIVE

NEUROECTODERMAL TUMOURS
•• This is a heterogeneous group of malignant tumours occurring predomi-
nantly in children and adolescents and which correspond histologically to
WHO grade IV.
•• The term CNS-PNET has been introduced in the new (2007) WHO
classification and refers to all undifferentiated or poorly differentiated
embryonal tumours that occur at any extra-cerebellar site in the CNS.
•• The following tumours are included in this category:
–– Supratentorial PNET (sPNET)
–– CNS neuroblastoma
–– CNS ganglioneuroblastoma
–– Medulloepithelioma
–– Ependymoblastoma.
Supratentorial Primitive Neuroectodermal Tumour

•• This is an embryonal tumour occurring in the supratentorial location,
composed of undifferentiated or poorly differentiated neuroepithelial cells
with the capacity for divergent differentiation along neuronal, astrocytic,
muscular or melanocytic lines.
•• Supratentorial PNETs with only neuronal differentiation are termed cerebral
neuroblastoma while those with neuronal differentiation with ganglion cells
are termed ganglioneuroblastoma.
•• Since these are rare tumours, their precise incidence is difficult to determine.
Clinical Features
•• The mean age is 5.5 years with a range of 4 weeks to 20 years.
•• Male preponderance is noted.
•• These tumours are found most commonly in the cerebral hemispheres.
•• Rarely, they have been reported from spinal cord and suprasellar regions.
•• Clinical presentation is related to the site of origin of tumour.
Imaging
•• They are isointense to hyperintense and show enhancement on injection
of contrast material.
Histopathology
•• These tumours appear as pink-red soft tumours with or without cysts and
haemorrhage.
•• These supratentorial PNETs are histologically similar to MBs, being
composed of poorly differentiated round to oval cells with high nuclear
cytoplasmic ratio and brisk mitosis.
•• Fibrillary background may be seen in these tumours and Homer Wright
rosettes can also be present.
•• Calcification is a relatively common feature within degenerated areas.
•• Neuronal and glial cells, ependymal canals, striated muscle or melanin
bearing cells, indicating divergent differentiation of tumours may be seen.
•• These supratentorial PNETs express many of the neuronal markers, namely
synaptophysin, class III beta tubulin and neurofilament protein. Variable
degree of GFAP expression may also be seen.
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Histogenesis and Genetics

•• Histogenesis of supratentorial PNETs is controversial.
•• They possibly arise from primitive neuroepithelial cells.
•• The genetic abnormalities in supratentorial PNETs are different from MBs.
•• Although they are histologically similar to MBs, they lack many of the
molecular genetic alterations characteristic of MBs. Thus, losses of 17p
and isochromosome 17q abnormality are rarely seen in sPNETs.
•• In contrast, other genetic abnormalities seen in supratentorial PNETs are
expression of neuroD family of basic helix-loop-helix transcription factors
and RASSF1a promoter methylation.
•• Supratentorial PNETs also express Achaete-Scute, which is another
neurogenic transcription factor with homology to neuroD genes.
•• Recent microarray studies have also revealed that MBs and supratentorial
PNETs can be separated based on their specific pattern of gene expression.
Outcome and Prognosis
•• Children with supratentorial PNETs have a worse overall 5-year survival
rate compared to children with MB.
•• Infants less than 2 years of age have a poorer prognosis than older children.
•• CSF dissemination can be found in nearly one-third of patients.
•• Extraneural metastasis to bone, liver and cervical lymph nodes has also
been reported.
120
CHAPTER
Tumours of Meninges
Sundaram C  Shantveer G Uppin
MENINGIOMA
•• Meningiomas are generally slow growing benign tumours accounting for
13−26% of primary intracranial tumours.
•• The tumours arise from the arachnoid cap cells.
•• Classification of the tumours arising from the meninges is given in Table 1.
Age and Gender

•• Meningiomas are tumours of adults with a peak incidence between 50 years
and 60 years though they also occur in children and the elderly.
•• They are twice as common in women as in men.
Table 1: Tumours of the meninges (WHO 2007)

Tumours of the meningothelial cells meningioma
Meningothelial Metaplastic
Fibroblastic Chordoid
Transitional Clear cell
Psammomatous Atypical
Angiomatous Papillary
Microcystic Rhabdoid
Secretory Anaplastic (malignant)
Lymphoplasmocytic-rich mesenchymal tumours
Lipoma Chondroma
Angiolipoma Chondrosarcoma
Hibernoma Osteoma
Liposarcoma (intracranial) Osteosarcoma
Solitary fibrous tumour Osteochondroma
Fibrosarcoma Haemangioma
Malignant fibrous histiocytoma Epithelioid haemangioendothelioma
Leiomyoma Haemangiopericytoma,
Anaplastic haemangiopericytoma
Leiomyosarcoma Angiosarcoma
Rhabdomyoma Kaposi’s sarcoma
Rhabdomyosarcoma Ewing’s sarcoma—PNET
Chapter 120 • Tumours of Meninges
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Site
•• Meningiomas occur in intracranial, spinal, orbital and ectopic locations.
•• The common intracranial locations include parasagittal, falx, cerebral
convexity, olfactory groove, tuberculum sellae, sphenoid ridge, cerebel-
lopontine angle, optic nerve, parasellar region and within the ventricles.
•• Spinal meningiomas are more common in the thoracic region.
Clinical Features and Associations

•• Meningiomas may present as space occupying lesions, with raised
intracranial pressure, focal deficits or seizures.
•• They may be incidental and asymptomatic.
•• They can occur in association with neurofibromatosis 2 and may be multiple.
Radiological Features
•• Meningiomas are isointense or hyperintense on the T2-weighted image
and enhance with contrast.
•• A short tapered peritumoural extension of contrast material along the inner
surface of the tumour due to its attachment to the dura is called dural tail
and is a helpful diagnostic feature of meningioma.
Gross Pathology
•• Meningiomas are lobulated, well-demarcated tumours attached to the dura
(which may not be obvious in all tumours).
•• Some tumours are flattened and are called the enplaque variety.
•• The tumours compress the adjacent brain parenchyma and may produce
oedema.
•• The peritumoural oedema is related to the size of the tumour, proliferative
activity and histological subtype.
•• The overlying bone may show hyperostosis due to the presence of tumour
cells in the diploic space.
•• The tumour may infiltrate the dura, sinuses, bone, muscle, orbit, soft tissues
and the brain.
•• This infiltration is responsible for local recurrence even after complete
resection.
Microscopy
•• Meningiomas exhibit a wide variety of histological diversity.
•• The common histological varieties include meningothelial, fibroblastic and
transitional forms.
•• Psammomatous meningioma is more common in the spinal canal.
•• However, they are benign and belong to WHO grade I.
Meningothelial Meningioma
•• This is composed of lobules of meningothelial cells with indistinct
cytoplasmic margins and intranuclear pseudoinclusions. Cellular whorls
and psammoma bodies are uncommon.
Fibroblastic Meningioma
•• This is composed of spindle cells in a fascicular architecture with
intercellular collagen.
•• Intranuclear inclusions and psammoma bodies are uncommon but
calcification of the stroma is frequent.
894
Transitional Meningioma
•• This is characterised by cellular whorls usually around a central thin vessel
and is intermediate between meningothelial and fibroblastic meningiomas.
•• Psammoma bodies may be seen.
Psammomatous Meningioma
•• This type of meningioma shows extensive whorl formation and calcification
along the concentric cellular whorls or central vessel forming numerous
calcific psammoma bodies.
•• These meningiomas are common in the spinal canal and olfactory groove.
Angiomatous Meningioma
•• Meningiomas rich in small vascular channels, some densely hyalinised, are
called angiomatous meningiomas and they have no prognostic significance.
Microcystic Meningioma
•• This tumour arises from the arachnoidal trabecular cell.
•• The tumours are associated with peritumoural oedema, and large para
and intratumoural cysts.
•• Microscopically, there is accumulation of extracellular fluid with intercon-
necting cell processes.
•• Whorl formation and psammoma bodies are infrequent.
Secretory Meningioma
•• This meningioma, in addition to a meningothelial and transitional pattern,
demonstrates intracytoplasmic single or multiple brightly eosinophilic,
periodic acid Schiff (PAS) positive globules which are called ‘pseudopsam-
moma bodies’.
•• Immunohistochemically, these globules are positive for epithelial membrane
antigen (EMA), cytokeratin and carcinoembryonic antigen (CEA).
•• Serum or cerebrospinal fluid levels of CEA may also be elevated.
Lymphoplasmacyte-rich Meningioma
•• This type of meningioma is characterised by a dense infiltrate of lympho-
cytes and plasma cells, sometimes forming lymphoid follicles with germinal
centres.
•• This is associated with polyclonal hypergammaglobulinaemia.
•• This lymphoplasmacytic response remits with tumour removal and
reappears with recurrence.
Metaplastic Meningioma
•• These are meningiomas in which bone, cartilage, fat, myxoid tissue or
xanthoma cells may be seen.
•• According to WHO 2007, meningiomas are graded based on certain
histological features (Table 2).
•• Certain histological types, like chordoid, clear cell, papillary and rhabdoid,
and a few other histological features are associated with aggressive
behaviour.
Clear Cell Meningioma (WHO Grade II)
•• These tumours have patternless sheets of polygonal cells with clear
cytoplasm due to glycogen accumulation labelled by PAS stain.
•• The vessels and stroma are hyalinised.
895
•• Immunohistochemistry shows weak EMA positivity.

•• These tumours, in spite of gross total removal, have aggressive behaviour
with multiple recurrences, local spread and spinal metastases.
Atypical Meningioma (WHO Grade II)
•• Any histological subtype of meningioma, which fulfils the criteria of WHO
Grade II 2007 (Table 3), is associated with a greater chance of recurrence.
•• Five-year recurrence rate may be as high as 50%. MIB-1 labelling index
is moderately high.
Chordoid Meningioma (WHO Grade II)
•• These tumours contain trabeculae of vacuolated or eosinophilic cells in a
bluish matrix mimicking a chordoma.
•• Meningothelial or transitional features may be seen in focal areas.
•• Lymphoplasmacytic infiltrates are common.
•• Immunohistochemistry shows scant positivity for EMA and S100.
•• Recurrence is nearly 100% after subtotal resection.
Papillary Meningioma (WHO Grade III)
•• These are rare and tend to occur in children and young adults.
•• They have a perivascular pseudopapillary pattern.
•• The tumours exhibit an identifiable meningioma component and a variable
papillary component.
•• These tumours invade locally and into the brain parenchyma in 75%, tend
to recur in 55% and metastasise in 20% of cases.
Table 2: Histological grading of meningioma (WHO)

Grade Criteria
Grade II (Atypical meningioma) Mitosis 4 or more/10 high power field
or
Three of the following five features:
1. High cellularity
2. Loss of architectural pattern
3. Small cells with high nuclear/cytoplasmic ratio
4. Prominent nucleoli
5. Necrosis
Grade III (Anaplastic meningioma) Mitosis more than 20/10 high power field
or
Features of malignancy of a frank carcinoma or sarcoma
or melanoma
Table 3: Aggressive meningiomas: grade, behaviour and histological type

Grade Behaviour Histological sub-type
WHO grade II Greater chance of recurrence Atypical
WHO grade II (Brain invasive) Greater chance of recurrence Chordoid
Clear cell
Benign/Atypical
WHO grade III i. Greater chance of recurrence Anaplastic
ii. Locally infiltrating growth Papillary
iii. Dissemination to systemic sites Rhabdoid
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Rhabdoid Meningioma (WHO Grade III)

•• These tumours exhibit characteristic rhabdoid cells in diffuse sheets or
focally.
•• These rhabdoid cells have eosinophilic cytoplasm with eccentric nuclei
and prominent nucleoli.
•• The rhabdoid cells may be absent in the primary tumour and appear in
recurrent tumours.
•• MIB-1 index is high and recurrence is frequent.
Anaplastic Meningioma (WHO Grade III)
•• Meningiomas fulfilling the criteria of WHO 2000 of anaplastic features are
usually fatal with a median survival of less than 2 years.
Primary Melanocytic Lesions

•• Diffuse melanocytosis, melanocytoma, malignant melanoma, meningeal
melanomatosis.
Other Neoplasms Related to the Meninges

•• Haemangioblastoma.
Immunohistochemistry
•• The majority of meningiomas stain for EMA, but in atypical and anaplastic
meningiomas, it is less consistent.
•• All meningiomas show vimentin positivity.
•• The S-100 protein is variably expressed.
•• Secretory meningiomas are positive for CEA in pseudopsammoma bodies
and for cytokeratins in the cells surrounding the pseudopsammoma bodies.
Molecular Genetics
•• Chromosomal abnormalities have been described associated with
the evolution of meningioma by Giemsa staining, fluorescent in situ
hybridisation (FISH), comparative genomic hybridisation (CGH) and
spectral karyotypic techniques.
•• The majority of sporadic and familial meningiomas are associated with
abnormalities in chromosome 22.
•• The neurofibromatosis 2 (NF2) gene, on chromosome 22q12.2, a tumour
suppressor gene, is believed to play a central role in the formation of
meningiomas, in addition to Schwannomas in cases of NF2 (Table 4).
•• Production of vascular endothelial growth factor (VEGF) is associated with
peritumoural oedema.
Table 4: Genetic mutations, growth factors and association with

meningioma tumourigenesis and progression
NF2 gene mutations Tumour genesis
1p gene mutations Tumour progression to high grade, recurrence
Large gene mutations Tumour recurrence
MN1 gene mutations Multiple meningiomas
Production of VEGF Peritumoural oedema
Abbreviation: NF2: neurofibromatosis type 2, VEGF: vascular endothelial growth factor
897
•• Higher grade tumours are associated with a decrease in progesterone

receptor staining and an increase in MIB-1 nuclear labelling.
•• Complex cytogenetic and molecular abnormalities including CDKN2A,
CDKN2B, CDKN2C and PTEN gene mutations are identified in higher
grade meningiomas.
•• Microsatellite instability is also described in meningioma.
•• Multiple meningiomas are clonal in origin and 50% exhibit NF2 gene mutations.
•• Paediatric meningiomas, although rare, show NF2, 1p and 14q deletions
and exhibit aggressive behaviour.
Proliferation
•• Meningiomas exhibit increase in proliferative activity from benign to atypical
to anaplastic varieties.
•• This can be assessed by mitotic activity.
•• The mean mitotic counts vary widely.
•• The other markers of cell proliferation include nucleolar organiser regions
(AgNORs), bromodeoxyuridine (BrdU) incorporation and MIB-1/Ki-67.
•• Labelling indices are most commonly used and they show a highly signifi-
cant graded increase correlating with progression from benign to atypical
to anaplastic tumours.
•• The proliferation markers also show an increase in recurrent tumours.
•• Table 5 depicts the increase in labelling index of different proliferation
markers in meningiomas.
•• Diploidy is more common in meningiomas, but the proportion of aneuploidy is
higher in atypical and malignant meningiomas than in benign meningiomas.
•• The proliferation index is high in aneuploidy than in diploidy.
Recurrent Meningiomas
•• Although the majority of meningiomas are benign, recurrence after gross
total resection still remains a problem.
•• Risk stratification based on histological features alone has limitations.
•• Extent of surgical resection, grade and sub-type of tumour, MIB-1/Ki-67
labelling index and loss of short arm of chromosome 1 (1p-) by in situ
hybridisation are important parameters singly or in combination in predicting
recurrence (Table 5).
Hormone Receptors
•• Meningiomas exhibit enhanced growth rate during reproductive life
correlating with elevated sex hormone levels. There is an association with
carcinoma of the breast also.
Table 5: Factors associated with recurrence of meningioma

I. Extent of surgical resection:
a. Skull base
b. Parasagittal
II. Histological subtype Chordoid, clear cell, papillary, rhabdoid meningiomas
III. Grade of tumour Atypical, anaplastic meningiomas
IV. Invasion into adjacent structures Muscle, dura, bone, brain
V. Others MIB-1 LI, ↓ progesterone receptors, loss of expression
of alkaline phosphatase receptors, loss of 1p gene,
Large gene mutations
898
•• Nearly 84% of meningiomas express progesterone receptors and it is

influenced by histological grade, type and site of the tumour.
•• Progesterone receptor levels are low in convexity, fibrous and atypical
meningiomas and also associated with peritumoural swelling.
•• Lack of progesterone receptors is associated with large tumour size, atypia
and anaplasia.
•• Androgen receptors reside in the nuclei suggesting a role for activating
gene expression.
HAEMANGIOPERICYTOMA
Definition and Grading
•• Haemangiopericytoma (HPC) of the central nervous system is a highly
cellular and richly vascular neoplasm, histologically indistinguishable from
its soft tissue counterpart elsewhere in the body.
•• They correspond histologically to WHO Grade II, the anaplastic variant
corresponding to Grade III neoplasms.
Incidence
•• These represent about 0.4% of primary brain tumours.
•• The ratio of meningeal HPC to other forms of meningiomas reported in the
literature has ranged from 1:40 to 1:60.
Age and Gender

•• Meningeal HPC are tumours of adults (mean age 43 years) and are more
common in males (M:F = 1.4:1).
Location
•• The majority are dural based and supratentorial with only occasional reports
of an intraparenchymal location.
•• Multifocality has not been reported.
•• Clinical and neuroimaging features that help in differentiating HPC from
meningiomas are presented in Table 6.
Gross and Microscopic Features

•• Grossly these are lobulated, firm, well-demarcated tumours with a fleshy,
greyish to red brown cut surface.
•• Microscopically, these are highly cellular tumours comprised of spindle
shaped cells arranged around thin walled vascular spaces.
•• These vascular spaces have characteristic “staghorn” configuration.
•• The degree of mitosis is variable.
•• These tumours lack cellular whorls, nuclear pseudoinclusions and
psammoma bodies unlike those noted in meningiomas.
•• These tumours are reticulin rich and have reticulin fibres enveloping
individual cells.
•• The tumours are diffusely positive for vimentin, negative for EMA and
express CD34 in one third of the cases.
Table 6: Differences between meningioma, haemangiopericytoma and solitary fibrous tumour
Meningioma Hemangiopericytoma Solitary fibrous tumour (SFT)
Incidence 13−20% of primary CNS tumours 0−4% of primary CNS tumours Rare
Age in years Peak incidence: 60−80 years 43 years (mean age) 57 years (mean age)
Male:Female 1:2 1.4:1 2:5
Location Cranial-cerebral convexity especially parasagittal, Cranial—most often involves tentorium and Falx, occipital and spinal dura, tentorium,
tentorium and subtentorial space; (11−12%) thoracic, subtentorial space; 1/5th in posterior fossa and cerebellopontine angle
intraventricular (most often lateral ventricle) Spinal—8% Multifocal tumours—not recorded
Multifocal tumours—16% Multifocal tumours—not recorded
Clinical features Signs and symptoms referable to location and Indistinguishable from meningioma, but relatively Indistinguishable from meningioma
compression of adjacent structures shorter duration of symptoms
Neuroimaging Well-demarcated dural based lesion May resemble meningioma May resemble meningiomas
Broad-based dural attachment Narrow based dural attachment—more frequent Hyperostosis—occasionally
Dural tail sign adjacent to main mass Dural tail sign—50%
Hyperostosis of adjacent bone, calcification Hyperostosis of adjacent bone—absent
Calcification—absent
Prominent vascular flow voids on MRI
Angiography—cork-screw like vessels
Microscopic features Wide range of histopathological appearance Characteristic ‘staghorn’ branching vascular pattern Variable cellularity with intervening
Fibrous type needs differentiation from HPC and SFT Whorls, psammoma bodies and intranuclear collagen bands
Lacks ‘staghorn’, vascular pattern of HPC inclusions—absent Staghorn vessels—may be present in some
Collagen sheathed vessels Reticulin around individual cells Reticulin—rich, envelope
Whorls, psammoma bodies and intranuclear Whorls, psammoma bodies and
inclusions seen intranuclear inclusions—absent
Reticulin—Scarce, segregates tumour into lobules
899
Contd...
Contd... 900
Meningioma Hemangiopericytoma Solitary fibrous tumour (SFT)

Immunohistochemistry Vimentin—positive Vimentin—positive Vimentin—positive
(IHC) EMA—positive EMA—negative EMA—negative
S-100—positive (80%) S-100—negative S-100—negative
CD34—positive (60%) CD34—positive (33%) CD34—positive (80−90%)
Factor XIIA—positive (65%) Factor XIIA—positive (78%) Factor XIIA—positive (100%)
Genetic susceptibility, Familial clustering—present No evidence of familial clustering -
cytogenetics and Association with NF2 Rearrangements of 12q13 (common in HPCs),
molecular genetics NF2 gene mutation—60% of sporadic meningiomas 19q13, 6p21 and 7p15
del 22—most consistent abnormality NF2 gene mutations—not reported
Recurrence and Recurrence rate: Recurrence rate: Recurrence rare
metastasis Benign meningiomas—7−20% 65% at 5 years
Atypical meningiomas—29−40% 76% at 10 years
Anaplastic meningiomas—50−78% Extracranial metastasis—64−68% at 15 years
Extracranial metastasis—extremely uncommon (bone, lungs and liver)
901
Genetic Susceptibility, Cytogenetics and

Molecular Genetics
•• There is no evidence of familial clustering in HPCs.
•• Chromosomal rearrangements of 12q13 (common in HPCs), 19q13, 6p21
and 7p15 have been reported in HPCs.

•• These tumours are usually treated with surgery followed by local irradiation
to the tumour bed.
•• Haemangiopericytomas have a high recurrence rate (65%, 76% and 87%
at 5-, 10- and 15-years, respectively).
•• Another unique feature of HPC is their tendency to metastasise to
extracranial sites like lung, liver and bone.
•• Histological features predictive of decreased survival include increased
mitotic rate (≥5/10 HPF), high cellularity, nuclear pleomorphism,
haemorrhage and necrosis.
•• These lesions correspond to WHO Grade III.
SOLITARY FIBROUS TUMOUR

•• Solitary fibrous tumour (SFT) is a rare tumour of the meninges, which is
pathologically identical to similar tumours occurring in the pleura and other
extrapleural sites.
•• These tumours resemble meningiomas in terms of their age of occurrence
and female predominance, and can involve both the cranial and spinal
meninges.
•• The imaging features resemble those of meningioma.
•• Grossly, these are firm, grey-white and circumscribed tumours.
•• Microscopically, the majority of the tumours show moderate cellularity
with spindle cells arranged in fascicles between dense bands of collagen.
•• There may be areas showing increased cellularity and reduced collagen as
well as foci with a vascular pattern reminiscent of haemangiopericytoma.
•• These tumours lack whorls, nuclear pseudoinclusions and psammoma bodies.
•• Mitoses are sparse.
•• Immunohistochemically these tumours show diffuse positivity for CD34 and
are negative for EMA and S-100.
HAEMANGIOBLASTOMA
•• Haemangioblastomas are WHO grade I tumours of uncertain histogenesis.
•• They constitute 1.3% of intracranial neoplasms and 7.3% of posterior
fossa neoplasms.
•• They occur both as sporadic tumours and in association with the inherited
syndrome of Von Hippel Lindau (VHL) disease.
•• Haemangioblastoma is a cardinal feature of VHL disease and about 30−40%
of all cerebellar haemangioblastomas are associated with VHL disease.
Location
•• Sporadic haemangioblastomas occur predominantly in the cerebellum but
VHL associated tumours occur in brainstem and spinal cord.
•• Supratentorial location is rare. They may be single or multiple, the latter
often in association with VHL disease.
902
Age and Gender

•• The sporadic tumours have a peak incidence between 35 years and 45
years and VHL associated tumours occur earlier (mean age of 29 years).
•• There is no gender predilection.
•• Haemangioblastomas are slow growing tumours and present with
symptoms of raised intracranial pressure.
•• The tumours produce erythropoietins and hence, cause secondary
polycythaemia.
Neuroimaging
•• Magnetic resonance imaging (MRI) is the investigation of choice which
has replaced CT and angiography. Various morphological patterns are
described on MRI and CT.
•• For example, (i) pure cystic, (ii) cyst with mural module, (iii) cyst with wall
enhancement, (iv) solid and cystic areas, and (vi) solid.
Pathogenesis
•• Stromal cells, the neoplastic component of the lesion express high levels
of hypoxia inducible transcription factors (HIF)-1 and HIF-2.
•• Stromal cells also express receptors for growth factors like epidermal growth
factor, transforming growth factor alpha, vascular endothelial growth factor
(VEGF) and platelet derived growth factors (PDGF).
•• HIF-1 and HIF-2 in stromal cells lead to upregulation of vascular endothelial
growth factor and erythropoietin at transcriptional level. This explains the
elevated erythrocytosis and also the formation of vascular and cystic
components of haemangioblastomas.
•• The stromal cell protein expression is characteristic and it has been shown
that it is similar to the embryonic progenitor cells with haemangioblastic
differentiation.
Gross Pathology
•• Haemangioblastoma is a circumscribed mass but unencapsulated.
•• It is reddish in colour due to its vascularity and sometimes yellow due to
the lipid content in the stromal cells.
•• It may be solid, cystic or partly solid and partly cystic.
Microscopy
•• The tumour is composed of two components: The capillary sized blood
vessels and the stromal cells.
•• The stromal cells are the neoplastic component.
•• Based on the pattern of arrangement of stromal cells and capillary sized ves-
sels, two patterns in the tumour are described—reticular and cellular patterns.
•• When stromal cells are evenly distributed between capillary blood vessels
it is called reticular pattern and when there are sheets of stromal cells with
random vascular changes, it is called cellular pattern.
•• The stromal cells have abundant cytoplasm with variable amounts of lipid
and glycogen.
903
•• The nuclei may show pleomorphism but mitosis is not a feature.

•• The blood vessels are usually thin walled but sometimes thick walled
vessels may be seen.
•• Haemorrhages, haemosiderin-laden macrophages, hyalinisation and
microcyst formation may be seen.
•• Reactive astrocytes with Rosenthal fibres at the periphery of the tumour
may be seen.
•• Infiltration into adjacent cerebellar tissue is rarely noted.
•• Necrosis and calcifications are usually absent.
•• Reticulin fibres are seen around blood vessels and groups of stromal cells.
•• Stromal cells stain positive with oil red O reflecting the lipid content.
•• The clear cell appearance of stromal cells may lead to a diagnostic problem
mimicking metastatic renal cell carcinoma.
•• Ultrastructurally, the stromal cells contain electron-lucent cytoplasm
containing lipid droplets and bundles of delicate filaments.
•• Immunohistochemically, the stromal cells lack endothelial cell markers
(von Willibrand factor and CD34) and endothelium associated adhesion
molecule (CD31).
•• Stromal cells express neuron specific enolase (NSE) and the neural cell
adhesion molecule transthyretin.
•• Vimentin is expressed and glial fibrillary acidic protein (GFAP) is not
expressed by the stromal cells.
•• The stromal cells have no consistent antigen expression profile.
•• The Ki-67 labelling index is less than 1%.
Prognosis
•• The outcome following surgical resection is favourable for sporadic tumours
compared to VHL associated tumours.
•• Mortality is low and permanent neurological deficits are extremely rare
with improved microsurgical techniques in sporadic haemangioblastomas.
•• In cases of VHL associated haemangioblastoma, haemorrhage is the most
common cause of death.
•• The histological sub-type of cellular variant is associated with more chances
of recurrence.
•• Recurrence is common when the tumour occurs in young age, associated
with VHL syndrome and in multicentric tumours. Solid tumours with less
cystic spaces and tumours with lower proportion of lipid laden cells have
higher chances of recurrence.
•• Risk of spontaneous haemorrhage is extremely low in haemangioblastoma
of size smaller than 1.5 cm.
•• In VHL associated haemangioblastomas, neuroradiologic screening and
lifelong follow-up are necessary for identification of new lesions before
they become symptomatic.
121
CHAPTER
Pituitary Tumours,
Sellar and Suprasellar
Lesions
Geeta Chacko
INTRODUCTION
•• The sella turcica in which the pituitary gland is housed is an intricate assembly
of anatomical structures representing elements of neural, endocrine,
vascular, osseous and meningeal tissues being in close proximity to the
cavernous sinus, hypothalamus, and major blood vessels, nerves, bone
and connective tissue.
•• Lesions in the sellar region are, therefore, remarkably diverse, originating
from varied tissues in the region (Table 1).
PITUITARY ADENOMA
•• Pituitary adenomas are benign tumours that comprise 10% of all intracranial
neoplasms and are a preventable cause of blindness.
•• It is the most common neoplasm of the sellar region and may even be
detected incidentally as frequently as 5–20%.
•• They are derived from adenohypophyseal cells, are most often confined to
the sella turcica, grow slowly, enlarge by expansion and are demarcated
from the normal pituitary tissue by a pseudocapsule.
•• Pituitary adenomas can be a part of the multiple endocrine neoplasia
syndromes.
•• Clinical features are related to mass effect and include visual symptoms,
headache and hypopituitarism.
•• In the case of secretory adenomas, the symptoms are related to the
hormone secreted.
•• Growth hormone (GH) excess is associated with acromegaly or gigantism;
overproduction of prolactin (PRL) is associated with amenorrhoea,
galactorrhoea, infertility, hypogonadism, decreased libido and impotence;
increased secretion of adrenocorticotropic hormone (ACTH) causes
Cushing’s disease; follicle stimulating hormone (FSH) and luteinizing
hormone (LH) oversecretion leads to hypogonadism or are clinically silent
and hypersecretion of thyrotropin (TSH) leads to hyperthyroidism.
Gross
•• The tumour is a well circumscribed brown-coloured mass in the sellar-
suprasellar region.
Chapter 121 • Pituitary Tumours, Sellar and Suprasellar Lesions
905
Table 1: Lesions of the sella turcica

I. Neoplastic lesions of the sella turcica
Sellar, suprasellar region:
Pituitary adenomas Craniopharyngioma
Germ cell tumours Spindle cell oncocytoma
Infundibulum and neurohypophysis:
Granular cell tumour Pituicytoma
Optic chiasm and hypothalamus:
Astrocytoma Ependymoma
Gangliocytoma Ganglioglioma
Ganglioneuroma
Bone and connective tissue:
Post-irradiation sarcoma Chordoma
Haemangiopericytoma Chondroma
Chondrosarcoma Fibroma
Fibrosarcoma Lipoma
Plasmacytoma Giant cell tumour of bone
Schwannoma Paraganglioma
Vascular:
Haemangioma Glomangioma
Haemangioblastoma Haemangiopericytoma
Olfactory groove:
Meningioma
Miscellaneous:
Lymphoma Langerhan’s cell histiocytosis
Leukaemia Melanoma
Metastatic tumours
II. Non-neoplastic lesions of the sella turcica
Sellar, suprasellar region:
Pituitary hyperplasia Rathke’s pouch cyst
Empty sellar syndrome Giant cell granuloma
Lymphocytic hypophysitis Granulomatous hypophysitis
Xanthogranuloma Rosai-Dorfman disease
Erdheim-Chester disease Xanthoma disseminatum
Epidermal cyst Dermoid cyst
Sarcoidosis Abscess
Tuberculosis Mucocoele
Infundibulum, neurohypophysis, optic chiasm and hypothalamus:
Hamartoma
Bone and connective tissue:
Fibrous dysplasia Cholesteatoma
Vascular:
Aneurysms
Miscellaneous:
Malformative tumours and cysts
906
Microscopic Features
•• The tumour is composed of sheets of monomorphic cells with uniform
round to oval nuclei, evenly dispersed chromatin and moderate amounts
of cytoplasm.
•• The tinctorial properties of the latter vary from acidophilic to amphophilic
or even basophilic.
•• Cells within the same tumour have similar tinctorial properties, except in
plurihormonal tumours.
•• A delicate capillary network traverses the tumour.
•• A pseudorosette arrangement is seen if a papillary pattern is present.
Normal Adenohypophysis
•• A monomorphous population of cells is seen in adenomas, whereas the
normal adenohypophysis has a mixture of cell types with different tinctorial
properties.
•• The acinar pattern of the normal adenohypophysis is disrupted in adeno-
mas, which is best appreciated on a reticulin stain.
Metastatic Carcinoma
•• These usually have brisk mitotic activity and show epithelial features with
prominence of nucleoli.
•• Intra-operative diagnosis is rarely requested for the straight forward
adenomas.
•• In certain circumstances when the dura appears firm or abnormal, an intra-
operative consult is sent to exclude other pathologies.
•• It is imperative that the specimen be sent rapidly and preferably on
moistened gelfoam or a smooth surfaced material so as to avoid drying.
•• Pituitary adenomas smear easily and hence, this method, smear or squash
preparation of rapid processing, are preferred to frozen sections.
•• Adenomas form cellular smears of uniform monomorphic cells.
•• Differentiation from normal gland requires a reticulin stain and this is not
optimal in an intra-operative setting.
•• Hence, in the case of a microadenoma (such as in ACTH secreting tumours
when the surgeon wishes to determine whether the entire tumour has
been removed) it is preferable that all material be submitted for routine
processing, so that, serial sections can be examined with both hematoxylin
and eosin, as well as reticulin stains to detect the microadenoma.
ADENOMAS OF SPECIFIC CELL TYPE

•• Table 2 summarise the current WHO classification of pituitary adenomas.
•• The salient features that are special to the different subtypes are discussed
below.
Growth Hormone Cell Adenoma

•• GH tumours constitute 15–20% of pituitary adenomas.
•• These tumours are often plurihormonal and show secondary immunoreac-
tivity for PRL, alpha-subunit (a-SU), TSH, FSH and LH.
•• Cytokeratin paranuclear dot-like positivity is seen in the sparsely granulated
variant and corresponds ultrastructurally to paranuclear intermediate
filament known as “fibrous bodies”.
Table 2: WHO classification of pituitary adenomas: clinical and pathological characteristics
WHO classification– Incidence Clinical features Staining Hormone (localised by
adenoma type characteristics immunohistochemistry in tumour cells)
Lactotropic adenomas:
Sparsely granulated 25% Amenorrhoea and/or galactorrhoea C Prolactin (PRL)
Densely granulated 1% in females/impotence/non-functional A PRL
Amenorrhoea and/or galactorrhoea in females/impotence
Somatotropic adenomas:
Sparsely granulated 5% Acromegaly or gigantism C/A Growth hormone (GH)
Densely granulated 5% Acromegaly or gigantism A GH
Adenomas with combined 5% Acromegaly or gigantism ± A/C GH/PRL
lactotropic and somato- 3% Hyperprolactinaemia A GH/PRL
tropic features 1% Acromegaly or gigantism ± C GH/PRL
Mixed GH cell/PRL cell Hyperprolactinaemia
Mammosomatotroph Hyperprolactinaemia or “non-functional”; only
Acidophil stem cell occasional acromegaly
Corticotropic adenomas:
Cushing (densely/sparsely 10% Hypercortisolism B Adrenocorticotropic hormone (ACTH),
granulated) 2% Pigmentation; mass symptoms B/C b-lipotropic hormone (LPH), endorphins and
Nelson <1 Hypercortisolism B/C propiomelanocortin (POMC)
Crooke cell 3% Mass symptoms; hypopituitarism B/C ACTH, b-LPH, endorphins and ACTH, b-LPH,
Silent corticotropic endorphins and POMC ACTH, b-LPH, endor-

phins and POMC
Contd...
907
Contd... 908
WHO classification– Incidence Clinical features Staining Hormone (localised by

adenoma type characteristics immunohistochemistry in tumour cells)
Glycoprotein adenomas:
Gonadotropic 7–15% Hypogonadism; functionally silent; mass effects silent; mass C/B Follicle stimulating hormone and luteinizing
Thyrotropic 1% effects C/B hormone thyrotropin (TSH)
Plurihormonal adenomas 10% Hypothyroidism or hyperthyroidism C/A Usually GH, PRL and TSH, b–subunit; includes
Silent sub-type 3 3% Usually acromegaly ± hyperprolactinaemia; glycoprotein hor- C/A other unusual combinations
Null cell adenomas 20% mone production rarely expressed C No specific hormones
Non-oncocytic 14% Mass effects; hyperprolactinaemia or GH effects A None ± mild hyperprolactinaemia
Oncocytic 6% Visual symptoms; hypopituitarism; as a result of pituitary stalk compression
headache None ± mild hyperprolactinaemia as a result of
Visual symptoms; hypopituitarism; headache pituitary stalk compression
Abbreviation: A—Acidophil, B—Basophil, C—Chromophobe
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•• The sparsely granulated variants are clinically aggressive.

•• Growth hormone-releasing hormone (GRH) overexpression correlates with
the level of GH as well as the aggressiveness of the tumour.
•• The GH excess due to adenomas is not restricted to the sparsely and
densely granulated variants of GH adenomas, but as described below, is
also seen with mixed GH-PRL, mammosomatotrophic and acidophil stem
cell adenoma, as well as with plurihormonal adenomas.
Prolactin Cell Adenoma (Prolactinoma)

•• The frequency with which this tumour is seen by pathologists is on the
decline as medical therapy with dopamine agonists is effective in the vast
majority of cases obviating the need for surgery.
•• These tumours are seen in the reproductive age group.
•• There is a female predominance, with females in the reproductive age group
presenting with amenorrhoea and galactorrhoea, while they are functionally
silent in post-menopausal women and in men.
•• Other causes of hyperprolactinaemia such as primary hypothyroidism and
antipsychotic drug use need to be ruled out.
•• Hyperprolactinaemia due to stalk effect needs to be recognised as distinct
from that due to an adenoma. The latter usually results in biochemical
values greater than 150 ng/mL.
•• Psammomatous calcification and amyloid deposition are features that are
peculiar to prolactinomas.
•• Immunoreactivity corresponds to the Golgi zone with secondary
immunoreactivity for a-SU.
•• Prolactinomas have abundant rough endoplasmic reticulum and the
presence of “misplaced exocytosis”, which is the presence of secretory
granules between neoplastic cells.
•• These tumours can be aggressive in both males and females in the post-
reproductive age group.
•• Morphology after medical treatment: The dopamine agonist, bromocriptine,
has a dramatic effect on the histology and ultrastructural features of
prolactinomas with cells undergoing atrophy.
•• There is significant stromal fibrosis. The changes are reversible and
cessation of therapy results in regrowth of the adenoma.
Adenomas Producing Growth Hormone and Prolactin

•• There are three principal subtypes of adenomas producing both GH and PRL.
Mixed Growth Hormone Cell-Prolactin Cell Adenoma
•• These are rare indolent neoplasms that manifest with acromegaly and
have serum PRL elevation.
•• The bimorphous nature is evident on ultrastructure.
Mammosomatotroph Cell Adenoma
•• These tumours present with acromegaly and hyperprolactinaemia.
•• The tumour has a single cell type with reactivity for both hormones.
•• Key features include densely granulated cells resembling somatotrophes,
but exhibiting both large granules and misplaced exocytosis, a feature of
lactotrophes.
•• By double labelling immunoelectron microscopy both hormones can be
localised within the same cell and often within the same granules.
910
Acidophil Stem Cell Adenoma

•• These tumours are rare and are usually non-functional.
•• Hyperprolactinaemia may be present.
•• Immunoreactivity for PRL generally exceeds that for GH.
•• Secondary immunoreactivity is seen for a-SU and TSH.
•• The cells show some features of both GH and PRL producing cells.
•• Oncocytic change is a common feature due to the presence of numerous
mitochondria, some of which are giant. The tumours show progressive
growth and invasive behaviour.
Adrenocorticotropic Hormone Cell Adenomas

•• There are three principal subtypes of ACTH-producing adenomas:
Adenomas of Cushing’s Disease
•• These tumours constitute 10% of all pituitary adenomas and are
predominantly microadenomas.
•• The male to female ratio is 1:5.
•• The ACTH immunoreactivity is variable.
•• These tumours are densely granulated with electron dense, teardrop
secretory granules and perinuclear bundles of intermediate (cytokeratin)
filaments.
•• Reticulin and periodic acid-Schiff (PAS) stains are helpful in identifying
the adenoma.
•• Crooke’s hyaline change is a conspicuous finding in the non-neoplastic
pituitary surrounding an ACTH-producing adenoma.
•• It is seen surrounding the nucleus as a pale zone and consists of perinuclear
accumulation of keratin microfilaments within the corticotroph.
Adenomas of Nelson’s Syndrome
•• Adrenalectomy for undetected microadenomas was performed in the past
to treat adrenocortical hyperplasia. This lead to unsuppressed growth of
the microadenoma, with progression to invasive macroadenomas.
•• Nelson’s adenomas underlie a significant proportion of pituitary carcinomas.
Silent Corticotroph Cell Adenomas
•• Approximately 5% of corticotroph cell adenomas are unaccompanied by
elevations in ACTH or clinical evidence of Cushing’s disease.
•• These are usually invasive macroadenomas.
•• There are two subtypes of silent corticotroph cell adenomas:
–– Subtype I.
–– Subtype II.
Glycoprotein Adenomas
•• These tumours produce hormones that have two amino acid chains.
•• The a-SU is common to all these hormones and a beta that has functional
specificity.
•• They include gonadotropic (FSH-LH) and TSH adenomas.
Gonadotroph Cell Adenoma

•• These represent 10% of pituitary adenomas.
•• They are seen primarily in elderly individuals, most often in males.
•• These are macroadenomas with a low invasion rate.
911
•• These adenomas show perivascular pseudorosette or ribbon formation.

•• Oncocytic change is seen in approximately 50% of adenomas.
•• Staining for FSH and/or LH and the a-SU is highly variable and patchy,
with secondary immunoreactivity for PRL, GH and ACTH.
•• These tumours have small (200 nm) secretory granules that are peripherally
located.
•• A “honeycomb” Golgi complex is seen in female patients.
Thyrotroph Cell Adenoma

•• These tumours are the least common (1%) of pituitary adenomas.
•• They manifest as hypothyroidism in individuals of all ages.
•• There is an equal gender distribution.
•• The majority are invasive macroadenomas.
•• TSH positivity and variable staining for a-SU, GH and PRL typify these
adenomas.
•• Secretory granules are few, small (200 nm) and peripherally located
beneath the plasma membrane.
Plurihormonal Adenomas
•• Adenomas that produce both amino acid hormones (GH, PRL, ACTH) and/
or glycoprotein hormones (LH, FSH, TSH, a-SU) are termed plurihormonal
adenomas.
•• Acromegaly is a common feature with GH, PRL or TSH. Other plurihor-
monal adenomas that are reported are: PRL-TSH; PRL-FSH/LH and
ACTH-LH-a-SU.
Silent Adenoma, Subtype III

•• These tumours are clinically silent or non-functional and are seen in the
second and third decades in females, and at any age in males.
•• Immunoreactivity is seen for any of the pituitary hormones; however, some
adenomas are entirely immunonegative.
•• The adenomas are aggressive in behaviour.
Null Cell Adenomas

•• These adenomas constitute one-fifth of all pituitary adenomas.
•• These tumours are clinically silent or non-functional and indolent in
behaviour.
•• They are macroadenomas with 40% being invasive.
•• The tumours are negative for pituitary hormones, or show scant glycoprotein
hormone or a-SU production.
•• There is a paucity of organelles and only few small secretory granules on
electronmicroscopy.
INVASION AND MALIGNANCY IN

PITUITARY ADENOMAS
Invasive Adenoma
•• A subset of tumours demonstrates a propensity for infiltrative and destruc-
tive growth.Termed invasive adenomas they represent a group between
the well-demarcated benign adenomas and the metastasising pituitary
carcinomas.
912
•• Routine histological tests fail to reliably distinguish aggressive and locally

invasive pituitary adenomas from those that are biologically indolent.
•• Morphological markers of aggressiveness in most tumour systems, namely
nuclear pleomorphism, cytological atypia, high cellularity, necrosis and brisk
mitotic activity are of limited usefulness in pituitary neoplasms, particularly
in the assessment of their invasive tendency, growth rate, potential for
recurrence and general biological behaviour.
Atypical Adenoma
•• Atypical adenomas are adenomas that are in a category intermediate
between benign adenomas and the pituitary carcinomas.
•• These adenomas have mitotic activity, a MIB-1 labelling index of greater
than 3% and immunoreactivity for p53.
Pituitary Carcinoma
•• This tumour is defined as one which has either craniospinal spread or
metastasis to lymph nodes, liver or bone.
•• These tumours are by and large functional, but may not show overt
histological signs of atypia.
Pituitary Apoplexy
•• Surgical specimens from cases of apoplexy can range from haemorrhagic
material to infarcted tumour and combinations of these.
•• On occasion there may be old haemorrhage as evidenced by the presence
of cholesterol crystals and haemosiderophages.
•• Viable tumour may also be present.
•• In the absence of viable tumour, immunostaining is not advised as
ambiguous results may be obtained.
•• The reticulin framework of an adenoma is usually preserved and, hence,
a stain to highlight this is helpful in diagnosis.
MARKERS OF BIOLOGICAL BEHAVIOUR OF

PITUITARY ADENOMAS
DNA Analysis
•• The clinical relevance of DNA analysis in pituitary tumours is still to be con-
clusively established, with variable results on secretors and non-secretors.
•• Karyotypic studies on pituitary adenomas have shown abnormalities in
chromosome 1, 4, 7 and 19 in functional tumours and numerical abnormali-
ties in non-functioning tumours.
•• There are no reported differences in karyotype between functional and
non-functional tumours.
Proliferation Markers
•• It has been shown that pituitary adenomas with histologically proven dural
invasion have a statistically significantly higher Ki-67 index compared with
non-invasive adenomas.
p53 Tumour Suppressor Gene

•• In a study by Thapar et al. expression of p53 gene mutation was present
in 100% of pituitary carcinomas, 15.2% of invasive adenomas and none
of the non-invasive adenomas.
913
•• Data from other studies have, however, failed to confirm the validity of
the p53 gene as a clinical predictor of the aggressiveness of pituitary
adenomas.
Apoptosis
•• The B-cell lymphoma-2 was moderately expressed in all groups of tumours
and normal pituitary, and was much weaker in pituitary carcinomas.
•• The Bax, Bad and Bcl-X were expressed in most pituitary tissues with
less intensive staining in carcinomas, indicating that both pro-apoptotic
and anti-apoptotic proteins are expressed concurrently in the same cells.
Angiogenesis
•• Pituitary adenomas show a lower microvascular density than normal
pituitary tissue with the exception of invasive prolactinomas and pituitary
carcinomas.
Growth Factors
•• Many growth factors are expressed in normal pituitary and pituitary
adenomas.
•• There is, however, no evidence for using the expression of growth factors
or their receptors as prognostic markers.
MOLECULAR PATHOLOGY: ONCOGENES AND

TUMOUR SUPPRESSOR GENES
•• Amplification of oncogenes H-ras and c-Myc and inactivation of tumour
suppressor genes Rb, p53, nm has been thought to play a role in initiation
and adenoma progression.
•• Pituitary oncogenes gsp, cyclin D1 and PTTG are frequently found in
pituitary adenomas.
•• Cyclins A, B and E are expressed in all adenomas and are significantly
higher in macroadenomas compared to microadenomas.
•• The allelic loss of a RB1 intragenic marker on chromosome 13q loss is
more frequent in invasive adenomas.
•• All cases of pituitary adenoma require a hematoxylin and eosin section
and preferably reticulin and PAS stains. This together with the clinical and
biochemical profile helps in diagnosis of most pituitary adenomas.
•• Reticulin stain helps in detection of microadenomas.
•• Immunohistochemistry is imperative in the detection of mixed GH-PRL
adenomas, acidophil stem cell adenomas, silent corticotroph adenomas,
gonadotrophic adenomas, and null cell adenomas and in confirming PRL
production when serum PRL levels are not markedly elevated.
•• Immunohistochemistry for the MIB-1 monoclonal antibody and p53 are
helpful in diagnosing atypical adenomas.
•• Electron microscopic examination is useful in the diagnosis of mixed
GH-PRL adenomas, acidophil stem cell adenomas, female gonadotroph
adenomas, null cell adenomas and silent subtype III adenomas.
•• Potentially aggressive adenomas are sparsely granulated GH adenomas,
acidophil stem cell adenoma, PRL adenomas in the post-reproductive age
group, ACTH adenomas associated with Nelson’s syndrome and silent
subtypes I and II, TSH adenomas and silent subtype III.
914
CRANIOPHARYNGIOMA
•• These are epithelial neoplasms which arise in the sellar and/or third
ventricle region.
•• Craniopharyngiomas manifest with hypothalamo-pituitary dysfunction and
•• There are two histological subtypes:
–– Adamantinomatous
–– Papillary.
Adamantinomatous
•• The tumours are thought to arise from Rathke’s cleft, squamous metaplasia
of adenohypophyseal cells of the pituitary stalk or embryonic rests with
odontogenic potential.
•• These tumours are seen in the first two decades of life, although they can
also be seen in adults.
•• They are cystic, contrast enhancing, partly calcified masses in the sellar
or third ventricular region.
•• The tumour is ill circumscribed with a poor interface with adjacent brain.
•• They are partly cystic with calcific material and “machine–oil” fluid rich in
cholesterol particles.
•• Chemical meningitis results if the contents spill into the cerebrospinal fluid
space.
•• They are similar to odontogenic tumours like adamantinoma of the jaw with
anastomosing trabeculae of epithelial cells that exhibit peripheral palisading
of columnar epithelial cells and enclose in their central portions loosely
arranged epithelium known as “stellate reticulum”.
•• Amorphous masses of keratin (wet keratin) with secondary calcification
are seen.
•• The cyst contents incite an inflammatory reaction that is usually xanthoma-
tous. Cholesterol granulomas are also a feature.
•• Adamantinomatous craniopharyngiomas have a propensity to recur owing
to their infiltrative nature and, especially, if they are subtotally excised.
•• Sometimes biopsy material is scant and consists of the cyst contents or wet
keratin without any epithelial elements. In such a case only a presumptive
diagnosis of craniopharyngioma can be made.
•• Adamantinomatous craniopharyngiomas often infiltrate the adjoining
parenchyma as nests and incite a rim of piloid gliosis.
•• Differential Diagnosis: Epidermoid cyst, these cysts have lamellated keratin
instead of wet-keratin nodules, gradual keratinisation of the epithelium and
the presence of keratohyaline granules.
Papillary Craniopharyngioma
•• Papillary craniopharyngiomas are seen primarily in adults in the third
ventricle or suprasellar space.
•• The sella may hence, be normal.
•• They are solid tumours that have papillary fronds.
•• A discrete tumour with simple squamous epithelium covering fibrovascular
cores without adamantinomatous features typifies this tumour. “Wet”
keratin, machine-oil fluid and calcification are not features of this neoplasm.
915
•• Complete excision is possible due to their well circumscribed nature.

•• Reported recurrence rates are low after radical excision, however, more
recent reports suggest that these tumours too have a propensity to recur
similar to adamantinomatous craniopharyngiomas.
•• Differential Diagnosis: Epidermoid cyst and adamantinomatous
craniopharyngioma.
PITUICYTOMA AND GRANULAR

CELL TUMOUR
•• These tumours are seen in adults, usually in the fourth and fifth decades of life.
•• Their cell of origin is the pituicyte, which is a modified glial cell of the
infundibulum, and neurohypophysis.
•• They are well circumscribed contrast enhancing tumours, isointense on
T1-weighted and T2-weighted images seen in the sellar/suprasellar region
in relation to the neurohypophysis and infundibulum.
•• These are firm, tan-coloured masses that can be vascular.
•• Granular Cell Tumour: The tumour is composed of sheets of polygonal
cells with granular, eosinophilic PAS-positive, diastase resistant cytoplasm
with eccentrically placed round nuclei with uniform nucleoli. Perivascular
lymphocytic infiltrates are sometimes present.
•• Pituicytomas: These tumours are composed of fascicles of spindle-shaped
cells with an astrocytic morphology and fibrillary cytoplasm, uniform bland
nuclei and distinct small nucleoli.
–– Mitotic activity is sparse.
–– Granular cell tumours are CD68 positive and rarely S-100 protein and
GFAP positive.
–– Pituicytomas are S-100 protein positive and variably reactive to GFAP
–– Ultrastructural Features are numerous intracytoplasmic lysosomes
are seen.
–– Differential diagnosis: Pilocytic astrocytoma. These are large tu-
mours seen mainly in childhood with a biphasic histological pattern
with rosenthal fibres and eosinophilic granular bodies.
–– These tumours are reported to have a variable prognosis with recurrences.
NON-NEOPLASTIC LESIONS OF THE

SELLA TURCICA
Rathke’s Cleft Cyst
•• They arise from Rathke’s cleft rests.
•• These cysts are rarely symptomatic.
•• They are often an incidental finding at autopsy or present as cysts that
cause visual symptoms, hyperprolactinaemia, diabetes insipidus, growth
retardation or other endocrinal dysfunction.
•• They are intrasellar cysts with suprasellar extension with a high signal on
T1-weighted images. Calcification is absent.
•• The cyst is lined by a single to pseudostratified layer of columnar, mucin-
producing or ciliated cells with a few goblet cells.
•• Squamous metaplasia is seen occasionally. They are rarely associated
with adenomas.
•• Recurrences have been reported.
916
Empty Sella Syndrome

•• It is of two types, primary or secondary.
•• In the primary form, arachnoid herniates into the sella through an
incompletely formed sellar diaphragm resulting in displacement of the
infundibulum and compression of the pituitary gland.
•• In the secondary form the herniation is secondary to loss of the intrasellar
contents, either secondary to surgical resection, apoplexy or necrosis.
Giant Cell Granuloma

•• Giant cell granuloma is thought to be of autoimmune in origin.
•• Clinical Features: They manifest with pituitary insufficiency and diabetes
insipidus, occasionally.
•• Gross: In the early stages an enlarged gland is seen and later one sees
a shrunken gland.
•• Microscopic Features: Discrete non-caseating granulomata containing
several giant cells, with associated fibrosis are seen within the
adenohypophysis.
•• Behaviour: It is a self-limiting condition.
•• Differential Diagnosis:
–– Tuberculosis, fungal infections and sarcoidosis.
–– Necrotising granulomas are usually of infective aetiology. Sarcoidosis
usually involves the neurohypophysis or hypothalamus.
Lymphocytic Hypophysitis
•• This is secondary to an autoimmune response which is both cellular and
humoral, most often directed against pituitary hormones.
•• Clinical Features: These manifest with pituitary insufficiency and hyper-
prolactinaemia. There is a female predominance usually in late pregnancy
or post-partum.
•• Radiographic Features : A symmetric enlargement of the pituitary is seen
with contrast enhancement.
•• Gross: A firm gland is seen macroscopically.
•• Microscopic Features:
–– Lymphocytic hypophysitis is characterised by pituitary acini extensively
infiltrated by lymphocytes, as well as occasional plasma cells and
histiocytes.
–– Lymphoid follicles with germinal centres are seen.
–– There is extensive fibrosis.
–– An inflammatory infiltrate may also be seen in other endocrine organs.
•• Treatment: A biopsy is followed by hormone replacement as this can be
fatal if untreated.
Pituitary Hyperplasia
•• Pituitary hyperplasia occurs in response to stimulation by hypothalamic
releasing hormones either as a physiological response to end-organ failure
or due to a neoplasm.
•• Microscopic Features:
–– Hyperplasia is either nodular or diffuse in pattern and usually involves
one cell type.
917
–– The reticulin stain plays a pivotal role in the diagnosis of hyperplasia.

–– Nodular hyperplasia is seen as expanded acini.
–– Cell counts are required for the diagnosis of diffuse hyperplasia.
•• Growth Hormone Cell Hyperplasia: It is seen with GRH-producing
tumours, such as carcinoids and pheochromocytomas. These cells are
immunoreactive for GH.
•• Prolactin Cell Hyperplasia: It is seen as a constant feature in association
with pregnancy and lactation. It is also seen in long standing cases of
primary hypothyroidism, secondary to increase in TSH releasing hormone
as well as in Cushing’s disease.
•• Corticotroph Hyperplasia: Corticotroph hyperplasia is seen in the
adenohypophysis adjoining a corticotroph adenoma. It is also seen in
untreated Addison’s disease as well as in association with tumours that
produce corticotropin-releasing hormone.
•• Gonadotroph Hyperplasia: It is seen in early onset primary hypogonadism
such as in Klinefelter’s or Turner’s syndrome.
•• Thyrotroph Hyperplasia: It is seen in patients with long-standing primary
hypothyroidism.
122
CHAPTER
Lymphomas and
Metastatic Tumours of
Nervous System
Sundaram C  T Roshni Paul
LYMPHOMAS OF THE CENTRAL

NERVOUS SYSTEM
•• Non-Hodgkin’s lymphomas of the central nervous system (CNS) can be
primary or secondary.
•• Systemic lymphomas can spread to the CNS in about 10% cases, usually
in advanced or relapsing phase.
•• Certain primary sites, like testis, bone marrow, bone, paranasal sinus, are
more likely to seed the CNS.
•• High grade lymphomas spread to the brain more frequently than others,
and the involvement is usually leptomeningeal.
•• Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin’s
lymphoma that is confined to the brain, leptomeninges, eye or spinal cord
without evidence of involvement of other parts of the body.
•• Involvement of the brain is uncommon in Hodgkin’s lymphoma and plasma
cell dyscrasias. They can, however, present with spinal cord compression.
PRIMARY CENTRAL NERVOUS

SYSTEM LYMPHOMA
Predisposing Conditions
•• PCNSL occurs in both immunocompetent and immunosuppressed
individuals.
•• The immunodeficiency states associated with PCNSL may be acquired
or congenital.
•• The immunodeficiency states include AIDS and immunosuppressive therapy
for organ transplantation (especially cardiac and renal transplantations).
•• The congenital immunodeficiency states include: Wiskott-Aldrich syndrome;
severe combined immunodeficiency syndrome; immunoglobulin A
deficiency; ataxia-telangiectasia; X-linked lymphoproliferative syndrome
and Chediak-Higashi syndrome.
•• PCNSL is diagnosed in at least 2% of human immunodeficiency virus (HIV)
infected individuals and is an AIDS defining illness.
•• The relative risk of PCNSL in HIV infected individuals was 3600 fold
when compared to the general population before the use of highly active
antiretroviral therapy (HAART).
•• In India, the majority of PCNSLs are reported in immunocompetent indi-
viduals.
Chapter 122 • Lymphomas and Metastatic Tumours of Nervous System
919
Age and Gender

•• PCNSL occurs in all age groups, but age differs significantly depending
on the immune status.
•• The mean age of PCNSL in India varies from 39 years to 44 years in
immunocompetent individuals, significantly lower than that reported from
the West.
•• There is a male predominance in both AIDS patients (> 95%) and in
immunocompetent patients with PCNSL (2:1).
•• The clinical features depend on the neuroanatomical location of the lesions.
•• The patients present with focal neurological deficits, neuropsychiatric
symptoms, raised intracranial pressure, seizures or ocular symptoms.
•• The leptomeningeal lesions may be asymptomatic and spinal cord lesions
are usually discrete intramedullary nodules.
Pathogenesis
•• The pathogenesis of PCNSL is unclear as the CNS does not contain any
lymphatic system.
•• Three hypotheses have been put forwards but none of them can explain
the pathogenesis completely:
1. A systemic B cell lymphoma develops and spreads to all organs, but
lymphoma cells are eradicated by an intact immune system in all
organs. The CNS being an immunologically privileged site, the cells
proliferate and develop neoplasia there. However, there is no evidence
of concomitant lymphoma at other immunologically privileged sites like
testis.
2. B cell lymphomas that arise elsewhere in the body develop particular
adhesion molecules permitting homing to the CNS, where such cells
proliferate and develop into lymphomas in the absence of immune
regulation.
3. An intracerebral inflammatory lesion with polyclonal inflammatory
infiltrate may progress to a neoplastic monoclonal B cell proliferation
similar to mucosa-associated lymphoid tissue (MALT) lymphoma
evolving from gastritis induced by Helicobacter pylori.
•• In the majority of immunosuppressed patients, PCNSL is associated with
latent infection of B cells by Epstein Barr virus.
•• Virtually all PCNSLs in AIDS patients contain EBV DNA.
•• Clinical or subclinical infection with EBV results in both humoral and cellular
immunity and EBV persists despite the immune effector responses and
results in latent infection of B cells.
•• The proliferation of B cells is controlled by T cell immunity.
Gross Pathology
•• Four forms of involvement have been described in PCNSLs:
1. Discrete or diffuse intracranial mass lesions that are solitary or multi-
ple, often in contact with ventricular or meningeal surface
2. Leptomeningeal lesions
3. Ocular lesions with or without other lesions and rarely
4. Spinal cord lesions.
920
•• Majority of the intracranial lesions are supratentorial (85%) in the

periventricular zone and areas in thalamus, basal ganglia and corpus
callosum and the lobar lesions in the frontal, parietal, temporal and occipital
lobes in the descending order of frequency.
•• Primary leptomeningeal lymphoma, without parenchymal involvement and
primary intraocular lymphoma are rare forms of PCNSL and spinal cord
involvement is very uncommon.
•• Leptomeningeal involvement is common in PCNSL either in mass lesions
or primary leptomeningeal form, but majority are asymptomatic.
•• However, it provides an important aid in diagnosis by CSF cytological
examination.
Histology
•• PCNSL are most often high grade diffuse large B cell Lymphoma (DLBCL)
according to REAL and WHO classifications.
•• All types of lymphoma including the rare ones with signet ring cell
morphology or anaplastic large cell (Ki-1) type have been reported in the
brain.
•• The PCNSL in AIDS frequently include immunoblastic and small non-
cleaved Burkitt-like cell type.
•• The round to oval cells infiltrate the cerebral parenchyma diffusely and
aggregate in the Virchow Robin spaces with infiltration of the vessel walls.
•• The tumour cells are angiocentric, pleomorphic, discohesive and infiltrative.
•• There is no associated endothelial proliferation or thrombosis.
•• The cells show high mitotic index.
•• The vessels show perivascular cuffing and the reticulin stain shows splaying
of reticulin fibres.
•• The AIDS related PCNSL shows atypical features, areas of necrosis and
EBV genome by in situ hybridisation, and EBV associated latent membrane
protein by immunohistochemistry.
•• More than 95% of NHL in the brain are of B cell lineage and show CD 20
and CD 79a positivity.
•• A few reactive T cells can be seen in B cell PCNSLs.
•• Primary T cell lymphomas including anaplastic large cell variant, constitute
a small minority of PCNSL, especially in the cerebellar and leptomeningeal
examples.
Diagnosis
•• The diagnosis of PCNSL may be suggested by several radiological findings.
•• They are angiographically avascular.
•• On CT scans, they are either isodense or hyperdense in relation to the
normal cortex, as opposed to glial tumours and metastasis, which are
hypodense.
•• They tend to cause less oedema than gliomas.
•• More than 90% are contrast-enhancing.
•• The radiographical appearance of PCNSL differs significantly between
AIDS and non-AIDS setting.
•• In immunocompetent patients, PCNSL appears multifocal in one-third of
patients, enhance uniformly with contrast, and lack ring enhancement,
whereas in AIDS associated PCNSL, the lesions are multifocal in 30−75%,
may be cortical or subcortical and enhance after contrast administration.
921
•• On MRI, PCNSL is typically hypointense or isointense on T1-weighted

images with variable enhancement pattern on Gadolinium, especially ring
enhancement.
•• It is difficult to reliably distinguish AIDS associated PCNSL from AIDS
related infections, especially Toxoplasmosis on CT or MRI.
•• Diffusion weighted MRI and metabolic imaging hold promise in this direction.
•• It should be performed in all patients with suspected PCNSL, unless
contraindicated by a large posterior fossa mass lesion, elevated intracranial
pressure or coagulopathy.
•• Cytological examination may provide useful information and eliminate the
need for surgery.
•• CSF shows raised protein, low sugar, may be positive for tumour markers
such as β2 microglobulin and LDH.
•• Flow cytometry improves sensitivity of detecting occult leptomeningeal
disease.
•• Polymerase chain reaction (PCR) for EBV DNA in CSF has a sensitivity of
80−100% and specificity for lymphoma of 93−100%. It is also positive in
EBV associated systemic lymphoma in AIDS patients.
•• Combining CSF-EBV analysis with metabolic imaging improves the
accuracy of diagnosis of AIDS-PCNSL.
Role of Stereotactic Brain Biopsy
•• Stereotactic Brain Biopsy (SBB) is the standard procedure for obtaining
tissue for a pathological diagnosis of cerebral lymphoma.
•• The centre of the suspected lesion should be targeted for biopsy.
•• The advantages of SBB over open biopsy include minimal skin incision,
option of local anaesthesia, short post-operative recovery period, and low
rate of morbidity and mortality.
•• Surgical excision of a parenchymal PCNSL confers no survival benefit.
•• They may be associated with a worse survival along with a risk of seeding
the leptomeninges with tumour cells.
•• The morbidity and mortality of SBB is higher in AIDS patients due to the
high frequency of haemorrhagic complications.
•• Stereotactic biopsy is particularly useful to obtain tissue in PCNSLs
involving deep structures like thalamus, periventricular area and corpus
callosum.
•• Use of steroid therapy before biopsy can obscure histopathological features
due to tumour cell apoptosis to the point that lesional cells disappear
completely.
•• As most patients with PCNSLs have relapses if treated with steroids
alone and there are difficulties in establishing subsequent diagnosis,
corticosteroids should not be administered before biopsy.
Prognostic Markers
•• Age more than 60 years, performance status more than one; elevated
serum LDH, high CSF protein concentration and involvement of deep
regions of the brain (periventricular regions, basal ganglia, brainstem and/
or cerebellum) were significantly and independently associated with bad
prognosis and low survival rate.
•• Combined modality approach with chemotherapy and whole brain
radiotherapy has improved survival, but relapses occur in almost all PCNSL.
922
Spinal Cord Compression Due to

Haematological Malignancies
•• Spinal cord compression due to haematological neoplasm is a serious
complication requiring immediate diagnosis and treatment.
•• It can occur due to involvement of spinal cord, spinal leptomeninges, dura
or vertebra.
•• The spinal involvement is common with multiple myeloma (MM), followed
by NHL, but rare in Hodgkin’s lymphoma, leukemia and extramedullary
myeloid cell tumour (EMCT).
•• Patients with myeloma or lymphoma have a good prognosis even if they
present with cord compression, when treated appropriately and promptly.
Non-Hodgkin’s Lymphoma
•• Cord compression has been noted at presentation in 2.2% of cases of NHL.
•• Back pain and weakness are the commonest presenting symptoms.
•• All histological grades of NHL have been reported.
•• Surgery to provide a tissue diagnosis followed by combined radiotherapy
and chemotherapy is indicated for all cases.
Hodgkin’s Lymphoma
•• Hodgkin’s lymphoma presenting with spinal cord compression is very rare
and occurs in only 0.2% cases of Hodgkin’s lymphoma.
•• The thoracic spine is the most commonly involved site.
•• Histopathology of the lesion along with detailed clinical evaluation with
history of previous biopsy, lymph nodal status and organomegaly is required
to make a definitive diagnosis.
Multiple Myeloma and Solitary Plasmacytomas

•• Involvement of spinal cord and/or nerve root by myeloma is a serious
complication and is secondary to involvement of vertebrae.
•• It occurs in about 10% of patients of multiple myeloma and may be the
initial manifestation.
•• Solitary plasmacytomas can also present with spinal cord compression.
•• Recognition of paraspinal mass by CT/MRI is useful in diagnosis and early
recognition is important.
•• Histology is diagnostic and immunohistochemistry for kappa and lambda
light chains of immunoglobulins can be carried out.
•• Associated amyloidosis carries a poor prognosis.
•• Clinical, imageological and biochemical evaluation including serum and
urine immunoelectrophoresis along with bone marrow examination is
necessary for instituting therapy.
•• Myeloma involving skull bones of the vault do not usually produce
neurological symptoms but those involving base of the skull can produce
cranial nerve involvement.
•• Solitary plasmacytomas are rare and account for less than 10% of plasma
cell tumours and are morphologically indistinguishable from multiple
myeloma on immunohistochemistry.
•• Skeletal survey and bone marrow evaluation are necessary to rule out
multifocal lesions.
923
•• Although the prognosis for solitary plasmacytoma is significantly better than

that of multiple myeloma, solitary plasmacytoma eventually progresses to
multiple myeloma.
METASTATIC TUMOURS OF THE

CENTRAL NERVOUS SYSTEM
Pathogenesis
•• Brain metastases exhibit considerable clinical and neuropathological
heterogeneity. This cannot be explained only by the pattern of regional
blood flow.
•• Tumour cells have marked genetic, biochemical and cytological diversity.
•• The metastatic tumour cells use specific adhesion molecules to attach to
microvessel endothelial cells.
•• They then respond to endothelial cell derived motility factors and invasion
factors, like neurotrophins and basement membrane degradative enzymes,
which facilitate brain invasion by metastatic cells locally destroying blood-
brain barrier.
•• The tumour cells proliferate in response to local paracrine and autocrine
growth factors.
•• Receptors to paracrine growth factor, like transferrin (a glycoprotein), are
expressed in greater numbers on the surfaces of cells that are metastatic
to brain.
•• Transferrin-like factors are important for invasion, colonisation and growth
of metastatic cells in CNS and probably explain why certain tumours, like
melanoma, lung carcinoma and breast carcinoma, metastasise to brain.
Spread of the Tumours

•• Systemic tumours spread to brain by three routes: (i) haematogenous; (ii)
contiguous and (iii) perineural.
•• Haematogenous spread is the commonest route by which the tumour cells
reach the brain and spinal cord.
•• The tumour cells reach nervous system via systemic circulation through
pulmonary vasculature or through a patent foramen ovale in the heart rarely.
•• Metastases may occur anywhere in the brain, but in general, the distribution
is proportional to the blood supply to specific areas of the brain.
•• Hence, grey matter is more commonly involved than white matter, and
metastases occur with equal frequency to both hemispheres.
•• Eighty per cent occur in cerebral hemispheres, 10−15% in cerebellum,
2−3% in brainstem.
•• Multiple metastases are seen in 50% of patients and numerous military
metastases are described as miliary carcinomatosis.
•• Tumours in CNS that develop by invasion of a primary tumour in the
adjacent structures, like paranasal sinuses or bone, are not actually
considered as metastases because they remain in continuity with the
primary neoplasm.
•• Tumours that spread by contiguous invasion include carcinomas of
nasopharynx, paranasal sinuses, skull bone and middle ear. Of these,
nasopharyngeal carcinoma is the commonest.
•• Osseous tumours of the skull and vertebrae also spread by contiguous
invasion.
924
•• Metastases to skull bones can occur from primary tumours-like

neuroblastoma in children and tumours of prostate, breast, kidney, thyroid,
lung and myeloma in the adult.
•• Perineural metastases are the least common and this type of spread is
supposed to be the mechanism for meningeal carcinomatosis.
Tumours Metastasising to Brain

•• The incidence of brain metastases and the spectrum of metastasising
primary tumours vary with patient’s age.
•• In general, brain metastases occur more frequently in adults than in children.
•• In adults, primary tumours metastasising to brain include lung, breast,
kidney, gastrointestinal tract and melanoma in descending order.
•• Apart from the cerebral hemispheres, cerebellum and brainstem, other
intracranial sites of metastases include pituitary, pineal and choroid plexus.
•• The metastases can also involve pre-existing lesions like glioma,
meningioma, schwannoma, arteriovenous malformations and infarcts.
•• In children younger than 15 years, osteosarcoma and rhabdomyosarcoma
produce solid brain metastases, while in older children germ cell tumours
produce metastatic deposits.
•• Melanoma, although constitutes only 4% of all cancers, has the highest
propensity to result in brain metastases.
•• Genitourinary tumours and sarcomas do not frequently metastasise to brain.
•• Metastases from melanomas and lung carcinomas tend to be multiple while
tumours from breast, colon and kidney tend to be single.
•• Metastases from melanoma and choriocarcinoma are usually haemorrhagic.
•• Metastatic choriocarcinoma should be considered in the differential
diagnosis of haemorrhagic intracranial masses in women of child
bearing age and the surgically resected blood clots should be examined
histologically for determining the aetiology.
•• Systemic lymphomas and leukaemias involve leptomeninges and do not
involve parenchyma and leptomeningeal carcinomatosis is usually due to
an adenocarcinoma.
•• Primary brain tumours, like germinoma and medulloblastoma, also spread
by CSF pathway.
•• Histology of primary tumour also influences the metastasising potential.
•• Small cell carcinoma and adenocarcinoma of lung along with breast
carcinoma are found to metastasise to brain twice more frequently than
other histological types.
Tumours Metastasising to Spine

•• Metastases affecting the spinal cord may involve the epidural space,
leptomeninges or intramedullary spinal cord.
•• Epidural metastases are the commonest and usually present as the initial
manifestation of malignancy. They arise by extension from a metastatic
deposit in the vertebra.
•• Thoracic spine followed by lumbosacral and cervical spine are involved
by the metastases.
•• Lung is the most common primary affecting area followed by breast,
prostate and lymphoma.
•• In children, leukaemia and lymphoma involve the leptomeninges.
925
Diagnosis
•• Following clinical evaluation, the size, location and number of metastases
can be assessed by CT and MRI.
•• High index of clinical suspicion is required to make a diagnosis of leptome-
ningeal involvement as the neurological manifestations can be protean.
•• The diagnosis should be suspected when symptoms and signs suggest
involvement of multiple anatomic sites in CNS.
•• These include headache, altered sensorium, cranial nerve palsies, back
or radicular pain, lower motor neuron weakness, sphincter incontinence
and sensory abnormalities.
•• The cerebrospinal fluid examination has to be repeated two to three times
with more volume of CSF (up to 10 mL) when the clinical suspicion is high
to get a positive yield and it has to be supplemented with special stains
and immunohistochemical stains.
•• Gadolinium enhanced T1-weighted MRI complements CSF cytology in
suspected leptomeningeal metastases.
•• Approach to evaluation of a patient with brain metastasis is represented
in Flow chart 1.
Prognostic Factors
•• Outcome in patients with metastatic brain disease depends on four
parameters that include; age less than 60 years, unknown or controlled
primary cancer, Karnofsky performance scale score greater than 70 and
metastatic spread limited to the brain.
Flow chart 1: Approach to evaluation of a patient with brain metastasis

926
•• Patients with all the four favourable factors had a predicted 200 day survival
of 52% while the patients with none of the favourable factors had a predicted
survival time of 54 days.
•• Patients with carcinoma breast, who have CNS involvement, whether occult
or symptomatic, have an impaired survival.
•• The institution of systemic chemotherapy was a positive prognostic factor
in patients with subarachnoid lesions detected by neuroimaging or with
extra CNS tumour deposits.
123
CHAPTER
Cerebral Oedema in
Relation to Neoplasias of
Nervous System
Shankar SK
•• In normal human adults, the intracranial volume includes intracellular

(1100−1300 mL), interstitial (100−150 mL), CSF (75−100 mL) and blood
(75−100 mL) spaces.
•• Exchanges of fluid amongst these compartments take place in response
to osmotic and hydrostatic forces at the interphase between:
–– Intracellular and extracellular compartments (cell membranes)
–– Blood-brain barrier (BBB)
–– CSF and brain (ventricular ependyma and glia limitans at the surface
of the brain) and
–– Blood and CSF (choroid plexus and arachnoid granulations).
•• In addition, nearly 30 mL of water in brain is produced daily from glucose
metabolism.
•• As the skull in the adult is rigid, any increase in brain parenchymal volume
by tumour or haemorrhages would result in replacement of fluid from the
low pressure CSF (approximately 10 mmHg in man) and venous (about
10 mmHg) compartments initially followed by the high pressure arterial
compartment (approximately 100 mmHg mean), as enunciated in the
Monroe–Kellie doctrine.
•• The volume of cerebrum and cerebellum, the space available in the
supratentorial and infratentorial cranial cavity and the ventricular size
cause differential pressure gradients by occlusion of the subarachnoid
space at the tentorial incisura or between the intracranial cavity and the
spinal subarachnoid space following the obliteration of communication at
the level of the foramen magnum.
•• This explains why, at times, the lumbar spinal fluid pressure may be within
normal limits in patients with raised intracranial pressure.
•• Other modifying factors could be elderly age of the patient with pre-existing
cerebral atrophy and infants with pliable cranial fontanelle and sutures that
provide compensatory capacity for accommodating a space-occupying lesion.
•• The reciprocal relation between the volume of the space-occupying lesion
and the resultant increase in intracranial pressure is particularly important
in causing clinical symptoms.
•• In the later stages of growth of mass lesions, uniform increment of volume
causes an exponential increase in intracranial pressure, rendering the
patient vulnerable to minor changes in intracranial pressure with serious
clinical consequences.
•• These pressure changes are the consequence of distribution of intracellular,
interstitial, intravascular and intraventricular fluid volume manifesting as
oedema, a subject of extensive clinical and experimental research.
928
•• Association of water with electrolytes determines the osmotic regulation of

cell volume and transmembrane ionic gradient essential for excitation and
impulse transmission in the nervous system.
•• The normal BBB is relatively permeable to water but considerably less to
ions and principal electrolytes.
•• Brain fluid regulation takes place within the context of systemic fluid
volume control, which depends on mutual interaction of osmotic, volume
and pressure regulatory receptors in the hypothalamus, heart and kidney,
hormones like vasopressin, renin-angiotensin, aldosterone, atriopeptins,
immunoreactive substances and their respective sites of action.
•• The concentration of Na+, K+ ATPase activity and the presence of Na+ and
K+ antiporter at the abluminal (external) surface of cerebral capillaries than
in other vascular beds in the body suggest that cerebral microvessels play
an active role in brain volume regulation and ion homeostasis.
•• The normal brain extracellular space (ECS) amounts to 12−19% of brain
volume and is markedly reduced following anoxia, ischaemia, metabolic
poisoning and spreading depression of electrical activity.
•• The asymmetric distribution and ionic gradient of Na+, K+ and Ca++ between
the intracellular space (ICS) and the ECS underlie the role of these cations
in nerve excitation, conduction and signal transduction.
•• Under normal conditions, the extracellular compartment within the brain
has two fluids—the interstitial fluid and CSF and the ECS extending from
the BBB, through a series of 100−150Å wide intricate intercellular spaces,
anatomically continuous with CSF spaces.
BLOOD–BRAIN BARRIER
•• The blood–brain barrier maintains a stable environment for neurons to
function effectively.
•• It excludes many toxic substances and protects neurons from circulating
neurotransmitters, like norepinephrine and glutamate, following stress
response.
•• This exclusion is mediated by specialised anatomic barrier properties of
cerebral capillaries.
•• The brain in addition is considered a relatively immunologically privileged
site, thereby abrogating the immune-mediated and inflammation-mediated
oedema in contrast to extra-CNS sites.
•• Specific examples of immunomodulatory factors include:
–– Transforming growth factor-b (TGF-b) present in CSF, which endows
macrophages with a capacity to induce antigen-specific suppression
of delayed type hypersensitivity reaction.
–– Low concentration of complement in extracellular fluid of brain reduces
the possibility of antibody mediated inflammatory reactions in CNS that
can cause oedema.
–– The highly selective membrane at the capillary endothelium has low
permeability to hydrophilic compounds and has a selective carrier
mediated transport system instead of passive diffusion.
–– Factors produced in this immunologically privileged site on the contrary
can distribute widely in the CNS microenvironment without significant
diffusional loss into the capillary plasma because of an intact barrier.
•• In addition, the barrier membrane may control, by selective expression of
homing receptors and other mediators of transmembrane passage, the
movement of lymphocytes and macrophages in and out of the CNS.
Chapter 123 • Cerebral Oedema in Relation to Neoplasias
929
•• Dynamic gradients may be superimposed by neoplasms and inflammatory

mass lesions (abscess, granulomas) altering the equilibrium in both halves
of the brain by local production of cytokines and immune mediators.
Anatomy of Blood–Brain Barrier

•• The structural blood–brain barrier is formed by specialised brain capillary
endothelial cells and the astroglial processes that ensheath more than 95%
of the abluminal (external) microvessel surface.
•• The endothelial cells in the brain microvessels have tight junctions imper-
vious to hydrophilic compounds (but permeable to lipophilic compounds
like alcohol, addiction-forming drugs like morphine and anaesthetics) and
relative lack of a pinocytic vesicular transport system.
•• Microvessels in the posterior pituitary, area postrema, subforniceal organ,
lamina terminalis, subcommisural organ, pineal gland, median eminence
and neurohypophysis lack the BBB.
•• The subforniceal organ is a chemoreceptive area that monitors blood
angiotensin level to regulate water balance and other homoeostatic functions.
•• During the development of the brain, not all capillaries develop the BBB
at the same time, the barrier in the spinal cord forming earlier than in the
telencephalon.
•• The neural analogue of the brain is vascularised by invagination of prolif-
erating vessels from an extraneural vascular plexus in the leptomeninges.
•• Soon after penetration into neural tissue, the interendothelial fenestrations
are lost and they mature into brain capillaries with a BBB. This BBB property
is induced in the microcirculation by chemical signals from the brain.
•• These barrier properties will develop in peripheral endothelial cells that
invade the brain tissue, but are lost in the brain endothelial cells that invade
the peripheral extraneural tissues.
•• Astrocyte foot processes in conjunction with cyclic adenosine mono
phosphate agonists, specifically increase interendothelial tight junctions
and their complexity, but not the neurons and oligodendroglia.
•• This feature has an implication in the evolution of cerebral oedema and contrast
enhancement on MRI/CT imaging and consequent clinical implications of
respective tumours like oligodendrogliomas and gangliogliomas.
•• In capillaries of peripheral organs and in sites of brain lacking BBB
(circumventricular organs), blood borne polar molecules diffuse passively
across vessels through interendothelial fenestrations and by passive fluid
phase or receptor mediated endocytosis.
•• Anticonvulsants, like phenobarbitone and phenytoin, bind to plasma protein
and thus, reduce their delivery to the brain.
•• Glucose, L-DOPA, large neutral amino acids and vinca alkaloids are
delivered by non-energy dependent selective endothelial transport and
enzyme systems, thus increasing permeability for them.
•• Glucose is transported selectively by a hexose transporter (glucose
transporter isotype-1 Glut-1 located on chromosome 1) which is facilitative
and saturable and stereospecific glucose is driven across the luminal and
abluminal surface of the endothelium, using a higher concentration gradient
in the plasma.
•• Multiple drug resistance (MDR) transporter, a transmembrane protein
is found in the microvessels of the BBB, which is involved in delivery of
chemotherapeutic drugs like vinca alkaloids, actinomycin D and steroid
930
hormones. MDR genes expressed at the BBB interphase protect the brain
from circulating toxins.
•• The external membrane of brain capillary endothelial cells have a high
concentration of Na+ K+ ATPase that exchanges intracellular Na+ with
extracellular K+ in an energy dependent manner, thus removing the extra-
cellular K+ in conjunction with astrocytes following neuronal depolarisation.
•• The catecholamine, vasoactive leukotrienes and glutathione bound
products are inactivated by various enzyme systems of the barrier
endothelium. These features represent the ‘biochemical blood–brain barrier’
in addition to the ‘physical barrier’.
•• To deliver chemotherapeutic agents, the BBB can be opened by
hyperosmolar mannitol. This opening of the BBB by mannitol is reversible
after about 4 hours, but the major disadvantage is the breach of BBB
is random and disseminated, thus neurotoxic drugs cause widespread
damage.
CEREBROSPINAL FLUID AND

HYDROCEPHALUS
•• The CSF communicates with brain interstitial fluid and acts as a conduit
for polypeptide hormones secreted by hypothalamic neurons that act at
remote sites in the brain.
•• The pH of CSF affects both pulmonary ventilation and cerebral blood flow.
•• Small solutes diffuse freely between the interstitial fluid and CSF in the
perivascular space (Virchow-Robin spaces) and across the ependymal
lining of the ventricular system, the pia glial membrane at the surface
facilitating movement of metabolites from deep brain parenchyma to the
cortical surface and ventricular system.
•• The total CSF volume is approximately 140 mL (lateral and third
ventricle—12 mL; spinal subarachnoid space—30 mL, brain subarachnoid
space and major basal cisterns containing most of the CSF), as measured
by dynamic CT studies.
•• Every day 500 mL of CSF is formed.
•• The choroid plexus, which is structurally similar to the distal collecting
tubules of the kidney produces CSF by capillary filtration and an epithelial
secretory mechanism, and maintains the chemical stability of the CSF.
•• The capillaries traversing the choroid plexus are freely permeable, but the
blood-CSF barrier exists along the apex and sides of the epithelial cells
of the choroid plexus.
•• The barrier is responsible for carrier mediated active transport.
•• The secretory capacity of the choroid plexus epithelium is bidirectional,
facilitating continuous CSF production into the ventricles and active
transport of metabolites out of the CNS into the blood.
•• Under normal conditions, the blood plasma and CSF are in osmotic
equilibrium, although CSF is low in K+, Ca++, bicarbonates and glucose
and is more acidic than plasma.
•• The normal pressure of CSF is 65−195 mm water (5−15 mmHg).
•• The formed CSF is drained by a directional movement to the subarachnoid
space and into the cerebral venous sinuses by hydrostatic gradient, passing
through the arachnoid granulations functioning as unidirectional valves.
•• In view of continuity between the ventricles and the interstitial space, a
limited amount of fluid is drained into brain capillaries passing through
931
the Virchow-Robin space and to the superolateral subarachnoid space

traversing the pia glial membrane.
•• The hydrocephalus has the following three possible causes:
1. Although rare, enhanced secretion is considered to occur in some
functional tumours like choroid plexus papilloma. These tumours are
usually associated with high CSF protein content, thus impairing the
absorption as well.
2. Impaired absorption of CSF may result from conditions that raise
intracranial pressure like parasagittal meningioma compressing the
veins, thrombosis of cerebral veins and cortical venous sinuses or
due to tumour associated hypercoagulable states. Impaired CSF
absorption causing communicating hydrocephalus occurs following
subarachnoid haemorrhage and bacterial meningitis clogging the
channels. Impaired CSF absorption is believed to be the cause of
normal pressure hydrocephalus.
3. Obstruction to CSF pathways can result from tumours like septal and
medial thalamic gliomas, subependymal giant cell astrocytomas, col-
loid cyst and ependymomas obstructing the foramina of Monro. An
anatomical site vulnerable for all the three mechanisms is the narrow
aqueduct of Sylvius. Tectal gliomas projecting into the pathway, glio-
sis due to intrauterine infections and haemorrhage, fourth ventricular
ependymomas, choroid plexus papillomas and medulloblastomas
cause obstruction to free flow causing ventricular dilatation proximally.
•• The accumulated CSF in the hydrocephalic ventricles, due to transient
or continuous hydrocephalic attacks with a raised hydrostatic pressure
gradient, backtracks into subventricular brain tissue by breaching the
ependymal barrier and the subependymal gliotic tissue by bulk flow.
•• The periventricular nuclear zones offer resistance to the spread as also
low-grade thalamic gliomas with a glial fibre mesh work.
AQUAPORINS IN THE BRAIN

•• With the recognition of water channel proteins (aquaporins, AQPs) in
Xenopus oocytes for the first time in 1992, the AQP family of at least 11
subtypes has been identified in biological tissue.
•• The AQP family is grouped according to their selectivity characters: water
selective channels (AQP 1, 2, 4, 5 and 8), channels transporting glycerol
and small solutes (AQP 3, 7, 9 and 10) and channels transporting chloride
at low pH (AQP6).
•• Each subtype has its own cellular distribution and distinct regulatory
mechanism in its expression.
•• AQP1 is expressed in the apical surface of choroid plexus epithelium
facilitating CSF formation, capillary endothelial cells throughout the body
and a few microvessels in the human brain, in human astrocytoma and
metastatic carcinoma.
•• In the spinal cord AQP1 is involved in water recycling and neural signal
transduction for pain.
•• AQP4 is the predominant type in the brain, expressed abundantly in
perivascular glial processes and ependymal cells, but absent in neurons,
oligodendroglia and microglia.
•• AQP4 is expressed also in the abluminal and luminal aspects of microvessel
endothelial cells. This protein is anchored by α-syntrophin (an adapter
932
molecule associated with dystrophin) and this interaction is essential for

localisation of AQP4 on the foot processes of astrocytes in contact with
the vessel for fluid transport.
•• Water transport via AQP4 is essential for normal neural activity. These
glial water channels may modulate brain excitability and the initiation and
generalisation of seizure activity.
•• In the hypothalamus, the astrocytes express AQP4 and have an
osmoregulatory role.
•• AQP9 is expressed in the ependymal lining of the ventricle and tanycytes
of the mediobasal hypothalamus and less, so in astrocytes and endothelial
cells, suggesting a role in extrachoroidal production and resorption of CSF.
•• Upregulation of AQP4 is observed in the oedematous zones of cerebral
contusion, bacterial meningitis, glioblastoma and reactive astrocytes around
metastatic tumours.
•• After focal transient ischaemia, AQP9 expression is increased on AQPs
in peri-infarct areas. These observations suggest that AQPs play a role
in regulation of post-ischaemic oedema, clearance of lactate from the
ischaemic tissue and water transport in tumours.
CEREBRAL OEDEMA
Cytotoxic Oedema
•• This is the result of deranged cellular metabolism resulting in inadequate
functioning of the Na+ and K+ pumps in the glial cell membrane.
•• As a consequence, Na+ and water are retained in the astrocytes.
•• These swollen astrocytes accumulate in grey and white matter, secondarily
affecting neuronal and oligodendroglial function and intracellular fluid
homeostasis.
•• Cytotoxic oedema is caused by various intoxications (dinitrophenol,
triethyltin, hexachlorophene, isoniazide), Reye’s syndrome and ischaemia.
•• In this form of cerebral oedema, the BBB is intact still (intact barrier
oedema).
•• This needs to be distinguished from focal cytotoxic injuries or abnormal
accumulation of metabolic substances (as they cannot be cleared) due to
enzyme defects (inborn errors of metabolism).
•• Hydro-oncotic changes due to electrolyte and protein build-up accruing
within the cells and in the ECS leads to obligatory movement of water and
water logging.
•• The cellular oedema occurs (cytotoxic brain oedema) through intracellular
hyperosmolarity and extracellular hypotonicity and a deranged ATP
dependent Na+/K+ pump at the cell surface.
Vasogenic Oedema
•• Disruption of the cerebral capillary barrier (BBB) mechanism by structural
and functional alterations of the cerebral capillary endothelium and astrocyte
foot process forms the underlying mechanism for vasogenic oedema.
•• This form of oedema is found in response to trauma, tumours, focal
inflammation and the later stages of cerebral ischaemia.
•• The amount of oedema is greater in the white matter than grey matter, with
a widened ECS, accumulation of water and Na+ and decreased K+ and
swollen astrocyte foot processes reflecting initial glial cytotoxicity (closed
barrier progressing to open barrier oedema).
933
•• The interendothelial fenestrations are widened and transendothelial vesicle

trafficking is enhanced.
•• Most of the time, combined cytotoxic and vasogenic oedema manifest,
one progressing to the other or they can manifest together from the onset,
based on pathophysiological events.
Hydrostatic Oedema
•• Vasogenic oedema has to be differentiated from two other types of brain
bulk enlargement like vascular swelling caused by vascular dilatation and
venous obstruction.
•• Brain oedema can be the first event in the initial stages of intracranial
hypertension.
•• Following acute and transient systemic hypertension beyond 160 mmHg,
the ‘BBB’ and ‘blood-CSF’ barriers are opened transiently due to hydrostatic
pressure and transudation occurs through interendothelial fenestrations and
transendothelial fluid trafficking occurs through vesicles.
•• At this stage, initially, there is no significant change in Na+ and K+ content
of the brain, CSF and muscle with no measurable cerebral oedema, but
with progression, the tendency is enhanced.
•• Following venous compression and stasis proximal to the compression,
the water with plasma proteins move out as a transudate by hydrostatic
pressure through veins and venules which are devoid of a barrier.
•• Later, the extracellular protein accumulation causes an osmotic gradient,
drawing the fluid out of the vessels.
•• Red blood lysis contributes to brain oedema formation after intracerebral
haemorrhage. RBC haemolysate (oxyhaemoglobin) has been found to be
a spasminogen in subarachnoid haemorrhage. Lysed RBCs alter the blood-
brain barrier more than packed RBC’s in a haematoma. These effects are
evident 72 hours after the event.
•• The cellular mechanisms related to high altitude (mountain sickness)
oedema is not clear.
•• Nitric oxide (NO) induced vasodilatation and altered cerebral circulation
as a response to hypobaric oxygen status is considered to cause cerebral
oedema.
Osmotic Oedema
•• The usually marginally higher osmolality of the CSF and extracellular fluid
as compared to plasma is reduced by an abnormal hypo-osmolar oncotic
gradient created in the circulation following SIADH, water intoxication and
haemodialysis.
•• As a consequence water flows into the ECS causing cerebral oedema.
•• In this form, the BBB is relatively intact. In the dynamics of events this form
resembles oedema due to venous stasis.
•• The extracellular brain oedema (interstitial) appears as a result of build-
up of oedema fluid in the ECS and can be due to hydrostatic extracellular
brain oedema (through enhanced ultrafiltration and formation of CSF),
oncotical (osmotic) extracellular brain oedema (vasogenic oedema) and
hydrocephalic extracellular brain oedema.
•• Most of the times, combined brain oedema manifests, one progressing
to the other type or they can manifest together from the onset based on
pathophysiological events.
934
Hydrocephalic Extracellular Oedema

•• This form of oedema is essentially paraventricular, following a breach in the
ependymal barrier leading to backflow of CSF into the brain parenchyma.
•• Subependymal gliosis and the nuclear areas around the ventricle resist
this movement of fluid.
•• The hydrostatic fluid accumulation in the ventricles could be due to the
rare enhanced production of CSF by ultrafiltration by choroid plexus, or
continuous and longstanding stasis due to defective drainage at different
levels.
•• In this form of oedema the BBB is intact till the late stages.
•• The oedema is essentially due to hydrostatic pressure and without a
significant oncotic gradient.
•• The precise mechanism underlying such oedema-induced neuronal
dysfunction is not clear.
Brain Oedema Following Trauma

•• Brain oedema leading to expansion of brain volume has a critical impact
on morbidity and mortality following traumatic brain injury (TBI).
•• Two major types of traumatic brain oedema exist; vasogenic due to a breach
in the blood-brain barrier and fluid accumulation in the interstitial space
and, cytotoxic oedema due to sustained intracellular water accumulation.
•• Following TBI, various kinins and mediators of inflammation are released,
which enhance vasogenic and cytotoxic oedema.
•• In addition, osmotic brain oedema is caused by extravasation of plasma
products and thus, a local imbalance in blood and tissue products and
hydrocephalic oedema occur due to obstruction of CSF outflow.
•• Cytotoxic oedema is of decisive pathophysiological importance following
TBI as it develops early and persists, while the BBB is gradually restored,
reducing vasogenic oedema.
•• Avoiding cerebral anaerobic metabolism and acidosis is beneficial to control
lactate and H+ ion.
•• For therapy, both cytotoxic and vasogenic oedema need to be managed
simultaneously in traumatic brain injury.
BRAIN TUMOURS AND OEDEMA

•• Oedema associated with a brain tumour often exceeds the mass effect
induced by the tumour itself resulting in raised intracranial pressure,
destruction of tissue homeostasis and neurological disturbances.
•• All aggressive brain tumours, like malignant gliomas, metastatic tumours
and many benign tumours, like meningiomas, produce oedema regardless
of the cell of origin.
•• All focal lesions, including primary and metastatic tumours, abscesses,
encephalitides and radionecrosis produce cerebral oedema.
•• Brain swelling associated with long-term therapy of tumours remains to be
an important issue in cases of recurrent tumours and lesions treated by
radio/chemotherapy and radiosurgery rather than resection.
•• In contrast to perilesional oedema and reactive astrocytosis associated with
meningiomas and metastatic tumours, oedema around high-grade gliomas
is characterised by extensive infiltration by tumour cells, thus distinguishable
by histological and clinical properties.
935
•• Metastatic and non-glial tumours produce angiogenic factors, promoting

new capillary formation with significant ultra structural abnormalities like
more frequent pinocytic vesicles in the endothelial cells, and an irregular
basal lamina.
•• In human glial tumours, the endothelial junctions are either short or
elongated. The endothelial cells display hyperplasia, irregular basal lamina
and a large extravascular space.
•• In malignant gliomas, the endothelial cells have defective tight junctions,
fenestrations, increased pinocytic vesicles and incomplete ensheathment
by the basal lamina.
•• The morphologically disrupted tight junctions in the newly formed vessels in
malignant gliomas are associated with paucity or lack of occluding claudins
and junctional adhesion molecules.
•• The decreased expression or function of these proteins results in opening
of interendothelial junctions and initiation of oedema, and this feature is
found in high-grade gliomas (Grade III−IV).
•• VEGF, a cytokine, has a mitogenic and chemotactic action on the endothelial
cells facilitating angiogenesis and also enhances the permeability of the
endothelium, which is more potent than histamine.
•• VEGF exerts its effect on venules and capillaries, but not on smooth muscle
cells or fibroblasts of vessels.
•• VEGF impairs the function of occludin and thus opens the tight junctions
and enhances fenestration of the endothelium.
•• Upregulation of VEGF is found in gliomas, meningiomas and metastatic
tumours.
•• In meningiomas (WHO Grade I) the upregulation of VEGF is mediated
by platelet derived growth factor (PDGF), epidermal growth factor (EGF)
and oestrogens.
•• Transitional, meningotheliomatous and secretory meningiomas are
associated with oedema.
•• The peritumoural brain oedema in cases of meningiomas is found to
be related to pial blood supply following a breach in the arachnoid and
adherence to the brain.
•• Secretory meningiomas and anaplastic meningiomas are frequently found
to be associated with extensive pial blood supply and hence severe oedema
while fibrous and psammomatous meningiomas, either in the cranium or
spinal canal, are rarely fed by pial blood vessels and produce only mild
oedema.
•• In terms of pathophysiology, small tumours with significant oedema and
large tumours with minimal oedema appear to correlate with the amount
of pial blood supply from the superficial cortex.
•• Induction of nitric oxide synthase (NOS) following anoxia and the modulating
role of NO in vasodilatation, peritumoural oedema and angiogenesis have
been found more commonly with metastatic tumours than primary brain
tumours.
•• Serotonin, thromboxanes and platelet activating factors are the other
vasogenic substances involved in the pathophysiology of tumour associated
oedema, especially with a coexisting cerebral infarct adjacent to a tumour
and associated macrophage response.
•• The spread of vasogenic oedema fluid by hydrodynamic bulk flow is
determined by anatomic barriers like the nuclear areas and long fibre tracts
which can be splayed apart.
936
•• Diffusion tensor imaging by MRI has not only provided an insight into this
pathophysiology, but also opened a new avenue of convection enhanced
(bulk flow of fluid against gradient) drug delivery as a therapeutic modality.
•• Malignant thalamic gliomas with perilesional oedema use the ventricular
surface to drain off the fluid by bulk flow, depending on cell density and
intercellular spaces below the ependyma.
•• As a consequence of hydrocephalus and raised CSF pressure, spontaneous
but intermittent cerebrospinal rhinorrhoea is seen in some cases.
•• Cisternography reveals alterations in the flow dynamics of CSF. Now CT
and MRI can offer similar information.
•• In normal individuals technetium labelled albumin injected into the lumbar
subarachnoid space can be traced by a gamma camera up to the cortical
convexities and the CSF may reflux into the ventricles only, if the pressure
dynamics are altered.
•• Dexamethasone not only reduces VEGF expression but also interferes
with the effect of VEGF on capillary endothelial cells, acting through a
glucocorticoid receptor.
•• As thrombin, a protein involved in the coagulation cascade is implicated
in angiogenesis, cell proliferation and oedema formation, thrombin
antagonists, like argatroban, have been found to be useful in reducing
oedema and the occurrence of tumour related neurological deficits.
SECONDARY EFFECTS OF CEREBRAL

OEDEMA-RAISED INTRACRANIAL PRESSURE
Papilloedema
•• This is caused by compression of the central retinal vein as it traverses the
subarachnoid space of the optic nerve sheath.
•• The compression results in fluid exudation from the engorged veins and
capillaries.
•• The fluid accumulation is minimal in the optic nerve as the enhanced
venous pressure is countered by the transmitted increased intracranial
pressure around the nerve and the fluid accumulation is maximal in the
unsupported disc zone.
•• Reduced blood flow in the region of the disc and lamina cribrosa further
contributes to axonal swelling interfering with rapid axonal flow and
increasing swelling.
Intracranial Herniations
•• Laterally placed tumours in frontoparietal areas result in depression of the
corpus callosum on the same side and herniation of the supracallosal gyrus
beneath the free edge of the falx resulting in indentation along the medical
surface of the cingulate gyrus.
•• It may compress the branches of the anterior cerebral artery resulting in
infarction.
•• With downwards displacement of the brain, the lesser wing of the sphenoid
causes grooving on the inferior surfaces of the orbitofrontal lobes.
•• Raised intracranial pressure due to supratentorial tumours either in the
midline or laterally placed, causes downwards displacement of the brain, im-
pacting the uncus and parahippocampal gyrus through the tentorial hiatus.
937
•• The characteristic early sign is the wedge shaped pressure necrosis in

one or both parahippocampal gyri and in severe cases haemorrhagic
necrosis occurs.
•• Rapidly growing temporal gliomas usually result in ipsilateral uncal
herniation.
•• More centrally located tumours cause bilateral herniation, compressing
and deforming the mid-brain and aqueduct.
•• Lateral displacement of the brain following unilateral herniation pushes the
contralateral cerebral peduncle against the rigid free edge of the tentorium
leaving a groove referred to as Kernohan’s notch.
•• Rarely, there may be bilateral lesions of this kind on the crura suggesting
torsion and swelling of the brainstem.
•• Obliteration of the lumen of the aqueduct by the herniation can result in
raised intraventricular pressure supratentorially, but not transmitted to
the spinal subarachnoid space paradoxically resulting in normal spinal
pressure.
•• Decompression of the supratentorial tumour and lowering the pressure
in the cranial cavity may cause caudal displacement of the brainstem
either along the midline or laterally, thus stretching the paramedian or
long circumferential perforators and causing their rupture or avulsion and
pontine tegmental haemorrhages.
•• Kinking of the posterior cerebral artery along the tentorial free edge can
cause necrosis of the medial occipital cortex, especially the calcarine cortex,
with punctate haemorrhages.
•• Similarly, caudal displacement of the brainstem and kinking of the posterior
cerebral artery can cause secondary compression of the ipsilateral
oculomotor nerve.
•• Following unilateral hippocampal herniation and concomitant lateral
pressure on the tegmental part of the midbrain may cause circulatory
disturbances in the third cranial nerve nuclei leading to ‘paralysis like loss
of upwards movement’ of the eyes and pupillary asymmetry.
•• With cerebellar tumours, the roots of the sixth cranial nerve may get
compressed against the anterior inferior cerebellar artery, causing sixth
nerve paresis.
•• Lateral displacement of the cerebrum may cause circulatory disturbances
in the stalk of the pituitary with secondary hormonal disturbances.
•• Similarly, caudal displacement of the brainstem and the drag may cause
bruising of the pituitary stalk against the dorsum sellae or its avulsion.
•• Expanding lesions in the posterior fossa may cause upwards herniation of
the cerebellar vermis through the tentorial hiatus and cause compression
of the superior cerebellar arteries leading to ischaemic infarction.
•• Similarly, a downwards thrust can cause compaction of the cerebellar
tonsils into the foramen magnum with grooving and necrosis of the tonsils.
•• Severe tonsillar herniation, especially sudden, can cause compaction of the
medulla with fatal consequences, while a mild degree of cerebellar tonsillar
herniation may not be of any clinical consequence.
•• The surgical opening in the vault of the skull provides an outlet for the
oedematous brain to fungate out with necrosis due to compression of
meningeal vessels along the edge of the bone. This is usually seen in
herniation of the cerebrum through a burr hole or craniotomy wound in
cases of glioblastoma.
938
•• The herniated parenchyma is usually necrotic and haemorrhagic.

•• Persistent intracranial pressure can cause erosion of posterior clinoid
processes and enlargement of the sella and thinning along the lesser wing
of the sphenoid and orbital plates.
•• Ionising radiation and chemotherapy to brain tumours and haemopoietic
malignancies cause damage to the vessel walls.
•• The brain tissue contiguous to the neoplasm is more vulnerable to radiation
injury than the normal CNS.
•• Primary injury to the brain vasculature with an early effect on cerebrovascular
endothelium is an important cause of oedema following radio/chemotherapy
and radionecrosis, manifesting with a mass effect.
•• The fibrinoid necrosis of the vessel walls and resultant exudation of the
protein rich serum into the necrosed brain results in oncotic brain oedema.
•• In addition, enhanced vascular permeability and an impaired blood-brain
barrier causes exudation of fibrin into the white matter followed by oedema
and demyelination.
CONCLUSION
•• Brain tumour oedema and the associated structural changes in the
surrounding brain are a complex event and multifactorial.
•• It is the result of imbalance between water moving in and out of the brain.
•• Molecular abnormalities of tumour endothelial tight junctions enhancing
blood-brain barrier permeability and identification of water channels, the
AQPs and their molecular diversity have enhanced our understanding of
pathophysiology.
•• Many dynamic events are yet to be understood in order to optimise the
therapeutic approach at the bedside.
124
CHAPTER Tumour Markers in
Tumours of Nervous System
Chitra Sarkar  Vaishali Suri  MC Sharma
•• A tumour marker is defined as “any substance that makes possible either

a qualitative diagnosis of neoplasia or a quantitative estimate of tumour
burden”.
•• Hence, a tumour marker is also broadly defined as any cell product related
to any event during tumour formation and/or growth such as malignant
transformation, proliferation, differentiation/cell lineage and metastasis.
USES OF TUMOUR MARKERS

•• The following are the uses of tumour markers:
–– Diagnosis: Improves diagnostic capability.
–– Characterisation of tumour in terms of cell lineage/degree of
differentiation and maturation.
–– Assessment of aggressiveness of tumour.
–– Helps selection of treatment strategies
–– Helps prediction of prognosis/outcome.
–– Evaluation of treatment response:
¾¾ Success of surgery—complete/incomplete surgical resection of
the tumour.
¾¾ Effectiveness of chemotherapeutic drug.
¾¾ Guide for selection of most effective drug for each case.
–– Detection of primary tumour metastasising to nervous system.
–– Detection of recurrence of neoplastic lesion.
–– A tool for screening asymptomatic population—for early detection of
malignant disease.
CHOICE OF TUMOUR MARKERS

•• The most important criteria for the selection and use of tumour markers are
their high sensitivity and specificity to identify the neoplastic nature, cell of
origin and molecular fingerprint of neoplasia.
CLASSIFICATION OF TUMOUR MARKERS

•• Markers detected in serum/CSF as a screening modality.
•• Markers detected in cells/tissues (immunohistochemical markers) to identify
tumour cell lineage (Table 1).
•• Molecular markers.
940
Table 1: Immunohistochemical markers for identifying cell lineage in

CNS tumours
Glial tumours • Glial fibrillary acidic protein (GFAP)
• S-100 protein
Neuronal tumours • Synaptophysin
• Neurofilament
• Beta-tubulin
• Microtubule associated protein (MAP 2)
• Neuron specific enolase (NSE)
• Alpha-internexin
• Peripherin
• GFAP +/- (aberrant expression)
Choroid plexus tumours • Cytokeratin
• S-100
• Transthyretin
• GFAP (20%)
Meningeal tumours • Epithelial membrane antigen (EMA)
• Vimentin
• S-100
• Cytokeratin
Schwann cell tumours • S-100
• Leu 7
Melanocytic tumours • S-100
• HMB 45
• Meland D
Lymphomas • Leucocyte common antigen (LCA)
• B and T Cell
• B (CD-20) and T cell (CD 3)
Germ cell tumours • Alpha foetoprotein (AFP)
• Human chorionic gonadotropin (HCG)
• Placental alkaline phosphatase (PLAP)
• Human placental lactogen
Tumours of vascular origin • Factor VIII
• CD 34 (also stem cell)
• VEGF
• Ulex Europeus
Neuroendocrine tumours • Synpatophysin
• Chromogranin
• NSE
Stem cell • Nestin, CD-133
USE OF TUMOUR MARKERS DETECTED

IN SERUM/CSF
Oncofoetal Proteins
•• The only group of CNS tumours wherein detection of tumour markers in
serum/CSF is useful at present is the germ cell tumours (Table 2).
•• Detection of tumour markers, such as AFP, HCG, PLAP, CEA and HPL, in the
serum/CSF is more reliable and sensitive for diagnosis than CSF cytology.
•• Further, in this group of tumours, markers help to monitor response to
therapy and to identify early tumour recurrence.
Chapter 124 • Tumour Markers in Tumours of Nervous System
941
Table 2: Immunoreactivity of some common CNS tumours

Tumour GFAP S-100 Synaptophysin NFP EMA CK
Astro/Oligo/Ependymal + + - - - -
Neurocytoma +/- - + + - -
Neuroblastoma/ +/- +/- + +/- - -
medulloblastoma
Ganglioglioma + + + + - -
Choroid plexus +/- + - - +/- +/-

Meningioma - +/- - - + +/-
Schwannoma +/- + - - +/- -
Metastatic carcinoma - +/- - - + +
Table 3: Immunohistochemical markers of germ cell tumors

Diagnosis PLAP AFP b-HCG HPL CK
Germinoma + - +/- - 10%
Teratoma + +/- - - +/-
Embryonal carcinoma + - - - +
Yolk sac tumor +/- + - - +
Choriocarcinoma +/- - + + +
Use of Oncofoetal Markers

•• The use of oncofoetal markers is chiefly for the diagnosis of intracranial
germ cell tumours, both primary and metastatic.
•• The various immunohistochemical markers for the diagnosis of germ cell
tumours are enumerated in Table 3.
•• The only drawback is that the absence of tumour markers in serum/CSF
does not exclude a diagnosis of germ cell tumours.
TUMOUR MARKERS IN CELLS/TISSUES

(IMMUNOHISTOCHEMICAL MARKERS)
•• The development of reagents to identify epitopes associated with cell
lineage, cell cycle, cell activation, oncogene and tumour suppressor gene
products have helped to clarify the nature of cellular maturation, tissue
differentiation, tumour progression and metastasis.
•• All this has resulted not only in improving diagnostic accuracy, but also in
clarifying developmental pathways within and between cell lineages involved.
•• It has also lead to revision of tumour classification, prognostication and
prediction of clinical outcome.
Types of Tumour Markers in Cells/Tissues

Tumour Markers for Diagnostic Use
1. Cell lineage/differentiation markers:
a. Structural/cytoskeletal proteins, cytokeratin, glial fibrillary acidic
protein (GFAP), neurofilament, desmin, vimentin, nestin, actin, tubulin,
microtubule associated proteins (MAPs)
942
b. Cell surface antigens: Lymphoid markers—leucocyte common antigen

(LCA), T cell markers (CD3), B cell markers (CD20)
c. Secretory products: Hormones, immunoglobulins
d. Neuroendocrine markers: Synaptophysin, chromogranin, neuron
specific enolase (NSE).
2. Oncofoetal markers
–– Alpha foetoprotein (AFP)
–– Placental alkaline phosphatase (PLAP)
–– Human chorionic gonadotropin (HCG)
–– Carcinoembryonic antigen (CEA)
–– Human placental lactogen (HPL).
3. Miscellaneous
–– S-100, epithelial membrane antigen (EMA).
Tumour Markers Useful for Prognostic Evaluation
•• Cell cycle/proliferation markers
•• Oncogene/tumour suppressor gene proteins
•• Growth factors/receptors
•• Hormones/receptors
•• Adhesion molecules
•• Angiogenic factors.
Cell Proliferation Markers
•• Various stages of cell proliferation in neoplastic cells can be detected to
get an insight into cell biology and evolve methodologies in cancer therapy
(Table 4).
•• Uses of cell proliferation markers:
–– These are very useful to measure the growth rate of tumours and
hence these are markers of prognostic significance.
–– Correlate with histological tumour grades and indicate aggressiveness
–– Correlation with prognosis.
–– It is essential to realise that some cells, like vascular endothelial
cells, intestinal epithelial cells and germinal cells, have inherent high
proliferative activity as a reparative process.
Molecular Genetic Markers
•• The clinical significance of molecular parameters for diagnostic and
prognostic assessment of gliomas is just emerging. Some are elaborated
below:
Table 4: Methods of detection of cell proliferation on tissue sections

Marker Technique
Mitotic figure Routine histology M Phase
AgNOR staining Silver stain Nucleolar organising region
[3H] – Thymidine Autoradiography S Phase
BrdU/IdU Immunohistochemistry S Phase
Ki-67/MIB-1 antibody Immunohistochemistry G1, S, G2, M Phase
PCNA antibody Immunohistochemistry G1, S, G2, M Phase
Topoisomerase II Immunohistochemistry G1, S, G2, M Phase
Fluorescent antibody labelling Flow cytometry All phases
of cell membrane
Chapter 124 • Tumour Markers in Tumours of Nervous System
943
•• Loss of 1p/19q
–– The presence of 1p/19q deletion supports a diagnosis of oligodendro-
glioma.
–– This molecular signature of oligodendrogliomas has also become very
important in diagnostic assessment of these tumours, e.g. for differential
diagnosis of oligodendroglioma from neurocytoma, DNET, etc.
•• p53 mutations and prognosis
–– TP53 is a tumour suppressor gene and in tumours it is expressed in
mutated form.
–– The presence of TP53 mutations may simply indicate occurrence of
the glioma in a younger age group and slow progression, and does not
reflect the survival period and prognosis.
–– Presence of p53 mutations are of diagnostic help in a few situations,
e.g. for differential diagnosis between grade II and pilocytic astrocytoma.
–– If p53 mutation is present, it favours a diagnosis of grade II diffuse
astrocytoma as p53 mutations are rarely seen in pilocytic astrocytomas.
•• EGFR amplification/overexpression and prognosis: EGFR amplification
was associated with poorer survival in patients with a glioblastoma.
•• Loss of 10q/PTEN mutations and prognosis: Losses involving
chromosome 10 are quite frequent in astrocytomas, limited mainly to
high-grade tumours. LOH 10 is the most frequent genetic alteration in
glioblastomas and occurs in 60−80% of cases.
•• C-myc/N-myc amplification, Erb-B2 overexpression and Trk-C
expression in prognosis of medulloblastomas:
–– Chromosomal gains of MYCC and MYCN locus has been identified in
medulloblastoma in 4−17% of cases.
–– The MYCC or MYCN amplification is associated with the aggressive
large cell tumour variant and a poor clinical outcome.
•• Over expression of ErbB2 receptors has been proposed as an independent
indicator of aggressive behaviour, while high TrkC receptor expression
indicates a favourable outcome.
125
CHAPTER Tumours of Cranial and
Peripheral Nerves
Sundaram C  Anita Mahadevan
The current WHO classification is provided in Table 1.
SCHWANNOMA
•• Schwannomas are benign, slow growing neoplasms of the central and
peripheral nerve sheath that arise anywhere distal to the oligodendroglial-
Schwann cell myelination junction.
•• They are defined by WHO as encapsulated benign tumours composed
exclusively of Schwann cells.
•• They have been variously referred to in literature as “neuromas”,
“neurinomas” (Verocay, 1910) and “neurilemmomas” (Stout, 1935).
•• The majority of Schwannomas are solitary, sporadic tumours although
syndromic associations are seen particularly when multiple.
Syndromic Associations
•• Neurofibromatosis type 2 (NF2) is associated with bilateral vestibular
Schwannomas and multiple peripheral nerve Schwannomas.
Table 1: WHO classification of peripheral nerve sheath tumours

Benign tumours of peripheral nerve
Schwannoma
Conventional
Cellular
Plexiform
Melanotic
Neurofibroma
Cutaneous (diffuse/nodular)
Plexiform
Perineurioma
Intraneural perineurioma
Soft tissue perineurioma
Malignant peripheral nerve sheath tumours (MPNSTs)
Epithelioid
MPNST with divergent mesenchymal and/or epithelial differentiation
Melanotic
Melanotic psammomatous
Chapter 125 • Tumours of Cranial and Peripheral Nerves
945
•• Schwannomatosis, a rare genetically distinct disorder is associated with

multiple peripheral Schwannomas in the absence of bilateral vestibular
Schwannomas.
•• Carney’s complex is associated with psammomatous melanotic
Schwannomas.
Incidence and Site

•• As neoplasms of the nerve sheath, they may arise intracranially,
intraspinally or in the periphery.
•• They constitute 5−10% of all intracranial tumours.
•• Sensory roots are more often affected than motor or autonomic roots.
•• The peak incidence is in the third to sixth decade although no age is exempt.
•• The intracranial tumours have a female predilection.
•• Ninety per cent of intracranial Schwannomas arise from the vestibular
division of the eighth cranial nerve. Other cranial nerves combined account
for only 10% of all intracranial Schwannomas.
•• Trigeminal Schwannomas are the second most frequent and may take
origin from the ganglion, root or rarely the divisions of the trigeminal nerve.
•• Glossopharyngeal, vagal and spinal accessory nerve Schwannomas are
recorded while involvement of other cranial nerves, such as oculomotor,
trochlear, abducens and hypoglossal, that are purely motor nerves are
extremely rare. Intraparenchymal Schwannomas (intracerebral and
intramedullary) are extremely rare.
•• The clinical and radiographic features vary according to the parent nerve
involved.
•• In general, these tumours present as mass lesions, produce neurological
dysfunction by distorting the parent nerve and compressing the surrounding
cranial nerves, brainstem and cerebellum.
•• They cause widening of the bony foramina and scalloping or erosion of
bone at the skull base that are recognised on plain radiographs.
•• They arise as extra-axial masses in the subdural space and widen the
cisterns within which they are located, which is how they are recognisable
on cisternography or pneumoencephalography.
•• Angiographically, they are detected to receive their blood supply from
branches of the external carotid system.
•• On CT, they appear as isodense to slightly hyperdense, well circumscribed
lesions which enhance on contrast administration.
•• On MRI, they remain slightly hypointense on T1W1 and hyperintense on
T2W1 and enhance uniformly and intensely on contrast administration.
•• Degenerative change, particularly cystic change, is readily detectable on
MR imaging.
Gross Pathology
•• Schwannomas are typically discrete, solitary and well encapsulated.
•• They tend to displace the parent nerve eccentrically and have a smooth
lobulated appearance.
•• The cut surface is glistening and interrupted by bright yellow areas
(xanthomatous change), cysts and haemorrhage.
•• In tumours arising from the peripheral nerves, the parent nerve of origin
can usually be identified.
946
Conventional Schwannomas
•• Microscopically, conventional Schwannomas are classically described as
being composed of alternating compact zones (Antoni A pattern) and less
cellular, loose textured (Antoni B) regions.
•• The Antoni A regions have well ordered arrays of elongated spindle
shaped cells with tapering, buckled nuclei and eosinophillic cytoplasm. The
nuclei may line up in palisades with intervening nuclei-free zones forming
characteristic structures called Verocay bodies.
•• The Antoni B regions are poorly organised clusters of large vacuolated
cells with small round nuclei. Cystic change and xanthomatous change are
common in these zones, as are hyalinisation of vessel walls with thrombosis
and perivascular haemosiderin deposits. The Antoni B regions, therefore,
probably represent degenerative changes.
•• The prominent vascular hyalinisation may be responsible for intense
contrast enhancement on imaging.
•• Cystic change in the tumour contributes to hyperintensities on T2W1.
•• The classic histology is more prominent in intraspinal and peripheral
tumours, while the intracranial tumours typically lack the prominent
palisades and show more prominent Antoni B regions with prominent
xanthomatous changes.
Ancient Schwannomas
•• This refers to large tumours of long duration that have undergone extensive
degenerative changes.
•• They commonly demonstrate bizarre pleomorphic nuclei that represent
degenerative atypia and do not connote malignancy.
Cellular Schwannomas
•• These are defined as hypercellular Schwannomas composed exclusively
of Antoni A areas, and devoid of Verocay bodies.
•• Mitotic activity is readily identifiable (not exceeding 4 per 10 high power
fields).
•• They are found most often in paravertebral sites in the pelvis, retroperitoneum
and mediastinum. Intracranially, they are described in facial and trigeminal
nerves.
•• The clinical presentation does not differ, but the finding of hypercellularity,
fascicular growth pattern, nuclear atypia and mitosis may lead to a mistaken
diagnosis of malignancy.
•• The Ki-67 labelling index ranges from 5.6% to 6% and p53 staining is found
in a significant proportion, although with only few positive cells.
•• Cellular Schwannomas are benign and may tend to recur, particularly the
intraspinal examples, but no tumour has been reported to metastasise or
show a malignant transformation.
Melanotic Schwannoma
•• These are grossly pigmented tumours that have cells that both ultra
structurally and immunophenotypically have Schwannian characteristics
but contain melanosomes and are reactive for melanoma markers.
•• They are extremely rare and occur a decade earlier than conventional
Schwannomas.
947
•• They may be psammomatous or non-psammomatous.

•• The former involve nerves of the intestinal tract or heart and rarely cranial
nerves.
•• The majority of non-psammomatous tumours are seen in the spinal nerves.
•• The distinction is of importance as approximately 50% of patients with
psammomatous tumours have Carney complex (that includes cardiac
myxoma, lentigenous facial pigmentation and endocrine hyperactivity,
most commonly Cushing syndrome with multinodular adrenal hyperplasia
or acromegaly due to pituitary adenoma).
•• Slightly over 10% of melanotic Schwannomas follow a malignant course.
Plexiform Schwannoma
•• This refers to the growth of the tumour in a plexiform or nodular manner.
•• It is more often seen in the skin or subcutis of an extremity, head and neck
or trunk where it arises from a nerve plexus.
•• The cranial and spinal nerves are usually spared and the tumour is
associated with NF2 (not NF1) or Schwannomatosis.
•• Tumour cells exhibit strong and diffuse positivity for S100 protein.
•• They may also be positive for myelin-associated glycoprotein (Leu 7) and
focally express GFAP.
•• They are usually negative for myelin basic protein and EMA (marker of
perineurial cell).
Ultrastructure
•• Ultrastructural features are diagnostic and demonstrate long entangled cell
processes that enclose the intervening stroma analogous to normal axon-
Schwann-cell-axon sheathing arrangement (pseudomesaxon).
•• This is in contrast to a neurofibroma in which true axons are found within
the tumour surrounded by Schwann cell processes (mesaxons).
•• A well defined continuous basal lamina separates the cell processes from
the stroma.
•• The cells are devoid of pinocytotic vesicles and cell-cell junctions are rare.
Syndromic Association
•• Most Schwannomas are sporadic but, when multiple, occur in association
with two inherited tumour syndromes—neurofibromatosis 2 (NF2) and
Schwannomatosis.
•• Bilateral vestibular Schwannomas are pathognomonic of NF2 while
multiple peripheral Schwannomas in the absence of other NF2 features is
characteristic of Schwannomatosis, a newly recognised syndrome.
•• The gene product of NF2 Merlin/Schwannomin is believed to perform a
tumour suppressor gene function. Merlin is probably a novel type of tumour
suppressor that co-ordinates the processes of growth-factor receptor
signalling and cell adhesion.
•• Psammomatous melanotic Schwannomas are associated with Carney
complex.
948
NEUROFIBROMA
•• These are defined as well demarcated intraneural or diffusely infiltrative
extraneural tumours that are composed of an admixture of neoplastic
Schwann cells, perineurial-like cells and fibroblasts.
•• Like Schwannomas they are most often single when sporadic but, when
multiple, are associated with neurofibromatosis 1 (NF1).
•• There is no age or gender predilection.
•• They have three distinct growth patterns: (1) localised; (2) diffuse and
(3) plexiform.
•• In the localised form, they present as cutaneous nodules (localised
cutaneous neurofibroma) or as a mass arising from a peripheral nerve
(localised intraneural neurofibroma). Unlike Schwannomas, they are
occasionally seen in the spinal nerves but are virtually unknown in the
cranial nerves (Table 2).
•• The diffuse growth pattern is rare and can present with localised
involvement of skin and subcutis (diffuse cutaneous neurofibroma) or
extensive involvement of soft tissue of an entire limb (elephantiasis
neuromatosa). The diffuse form, despite its extensive involvement, never
shows malignant transformation.
•• The plexiform variant on the contrary is virtually pathognomonic of NF1
and, although rare (2−3%), is the most frequent form to show malignant
transformation. They arise from large nerve trunks or plexuses.
•• The cutaneous tumours are either circumscribed or diffuse, and appear
gelatinous and grey-tan on sectioning.
•• Those confined to nerves are fusiform and well circumscribed while
the plexiform variant that arises from nerve trunks or a plexus appears
multinodular causing expansion and matting together of involved trunks
producing a characteristic “bag of worms” appearance.
Table 2: Differences between neurofibroma and Schwannoma

Features Neurofibroma Schwannoma
Cell of origin Unidentified, mixture of Schwann cell
Schwann cell, axons,
perineurial-like cell and
fibroblast
Parent nerve Fusiform enlargement/ Compressed
infiltration
Capsulated No Yes
Growth pattern Localised, diffuse, plexiform Localised, plexiform (rare)
Degenerative changes Uncommon Common (cystic change,
xanthomatous change,
hyalinisation, haemorrhage)
Immunohistochemistry for Focal Diffuse
S100
Ultrastructure Mesaxons Pseudomesaxon
Syndromic association NF1 NF2
Carney’s complex
Schwannomatosis
Malignant transformation 2−3% (NF1) Exceptional
949
Histological Features
•• Neurofibromas are characterised by both cellular and stromal components.
•• The former is an admixture of neoplastic Schwann cells, perineurial-like
cells and fibroblasts that typically proliferate in a haphazard fashion
dispersed in a stroma rich in collagen and mucopolysaccharides.
•• If arising from a medium sized nerve, the tumour remains confined within
the epineurium.
•• If arising in small nerves, they spread diffusely into soft tissues.
•• Large diffuse neurofibromas often show tactile differentiation with Wagner-
Meissner like corpuscles and pigment containing melanotic cells.
•• In the plexiform variant, the nerve bundles are matted together by tumour
and commonly demonstrate residual recognisable nerve fibres at the centre
and may infiltrate the dorsal root ganglia.
•• Unlike Schwannomas, degenerative changes (cystic change and xan-
thomatous change) as well as vascular hyalinisation are lacking.
•• Immunohistochemically, S100 staining is present but less diffuse than in
Schwannomas.
•• Variants of neurofibromas have been described.
Atypical Neurofibroma
•• Presence of nuclear atypia (degenerative) in the absence of cellularity
and mitotic activity in an otherwise typical neurofibroma is termed atypical
neurofibroma.
•• No risk of malignancy is identified in this variant.
Cellular Neurofibroma
•• Similar to cellular Schwannomas, these demonstrate increased cellularity
and appreciable mitotic activity, but do not connote malignant transformation.
•• They need to be differentiated from malignant peripheral nerve sheath
tumour (MPNST) by their low mitotic activity, lack of necrosis and absence
of significant cellular atypia.
PERINEURIOMA
•• A benign tumour composed exclusively of neoplastic perineurial cells, they
occur as intraneural lesions producing expansion of the involved nerve or
as soft tissue lesions with no demonstrable origin from a nerve.
•• They are extremely rare with just over 30 cases reported in the literature.
•• They are unassociated with any syndromes.
•• Monosomy of chromosome 22 has been demonstrated in both types.
•• The intraneural perineuriomas most often affect peripheral nerves of the
extremities causing nerve thickening, and progressive muscle weakness
and atrophy closely mimicking hypertrophic neuropathies.
•• Intraneural perineuriomas are benign and do not show any tendency to
recur or metastasise.
•• Biopsy is sufficient for a diagnosis and resection should be avoided to
retain neurological function.
MALIGNANT PERIPHERAL NERVE

SHEATH TUMOURS (MPNST)
•• The term incorporates lesions that arise from specialised cells of the
endoneurium and perineurium.
950
•• It encompasses the previously used terms—malignant Schwannomas and

neurofibrosarcoma.
•• To define a tumour as MPNST it must satisfy one of the following criteria:
–– Arise from an identifiable peripheral nerve trunk and have histological
features consistent with recognised types of MPNST.
–– Arise in a patient with NF1 and have a histological type conforming to
MPNST.
–– Arise from a pre-existing benign nerve sheath tumour (Schwannoma,
neurofibroma or ganglioneuroma).
–– Show histological features corresponding to a recognised type of
MPNST with morphological evidence of Schwann cell or perineurial
cell differentiation.
–– These types of MPNST recognised by WHO are depicted in Table 1.
Predisposing Factors
•• NF1 is the most important risk factor for MPNST and accounts for 50% of
all these tumours.
•• Risk of a patient with NF1 developing MPNST varies in various series from
2−29% with a lifetime risk of 10%.
•• In general, patients with NF1 develop tumours a decade earlier.
•• Tumours associated with NF1 show a loss of NF1 expression and high
levels of Ras, but additional genetic events that inactivate key cell cycle
regulators are required for malignant transformation.
•• Radiation is another important risk factor seen in 10% of cases with a long
latent period between exposure and tumour development.
Incidence and Localisation

•• These are uncommon neoplasms and almost two thirds arise from
neurofibromas, often of the plexiform type in the setting of NF1.
•• Development from a pre-existing Schwannoma is extremely rare.
•• MPNSTs occur most often in adults in the third to sixth decade.
•• Large and medium nerves are more prone to involvement with the most
common sites being the brachial plexus in the upper arm and the sciatic
nerve in the buttock and thigh.
•• They are large and often demonstrate foci of haemorrhage and necrosis
on sectioning.
•• Cranial nerve involvement is extremely rare with the fifth nerve being most
frequently involved.
Histopathology
•• MPNSTs grow within a nerve fascicle in fibrosarcoma-like pattern and
commonly invade through the epineurium into the soft tissues.
•• Large areas of geographical necrosis and brisk mitotic activity are common.
•• Perivascular accentuation of tumour and haemangiopericytic growth pattern
is a common feature.
•• About 15% exhibit unusual histological features such as epithelioid
morphology and divergent differentiation.
•• Epithelioid MPNST does not show any association with NF1 and carry a
better prognosis.
•• Divergent differentiation may produce glandular epithelium (Glandular
MPNST), while neuroendocrine and squamous differentiation is uncommon.
951
•• Association with NF1 in glandular MPNST is high as is the mortality.

•• MPNSTs showing rhabdomyosarcomatous differentiation (Malignant triton
tumours) are more common than glandular MPNST and 60% of patients
have NF1.
Prognosis
•• The prognosis is extremely poor with overall 5-year and 10-year survival
rates being only 34% and 23%.
•• Recent studies suggest that positron emission tomography and
glucose analogue 18-fluorodeoxyglucose might be useful in presurgical
differentiation between benign and malignant nerve sheath tumours.
KEY POINTS
•• Benign nerve sheath tumours include Schwannoma, neurofibroma and
perineurioma.
•• Solitary tumours are often sporadic while multiple tumours are associated
with familial tumour syndromes particularly neurofibromatosis 1 and 2 and
a newly recognised entity, Schwannomatosis.
•• Schwannomas more commonly involve cranial and spinal nerves while
cranial nerve involvement is very uncommon in neurofibromas.
•• Sensory nerves are preferentially involved by Schwannomas with the
vestibular division of the eighth nerve and the trigeminal nerve being most
frequent.
•• Cellular Schwannomas tend to recur with predilection for paravertebral
regions (pelvis, retroperitoneum and mediastinum).
•• Malignant transformation in Schwannomas is exceedingly rare.
•• The plexiform variant of neurofibroma has a higher risk of malignant
transformation.
•• Advances in imaging techniques (positron emission tomography and use
of 18-FDG) allow presurgical detection of malignant transformation.
•• Newer surgical options are being evolved in treatment particularly
stereotactic radiosurgery allowing more precise treatment with retained
function of the involved nerve.
•• Molecular advances have revealed novel modes of tumourigenesis in
producing sporadic tumours and development of neurofibromatosis that
may have an implication in developing targeted therapies.
126
CHAPTER Tumours of the
Choroid Plexus
Yasha TC
•• Choroid plexus tumours (CPTs) are intraventricular neoplasms arising from

the lining epithelium of the choroid plexus and comprise of the following:
–– Choroid plexus papilloma (CPP) WHO Grade I
–– Atypical papilloma (APP) WHO Grade II
–– Choroid plexus carcinoma (CPC) WHO Grade III
INCIDENCE
•• Tumours of the choroid plexus are rare neoplasms accounting for
0.36−0.6% of all intracranial tumours.
•• They are more frequent in children and account for 2−3.69% in them.
•• Twenty per cent of patients present during the 1st year of life and 50% in
the first decade.
•• In infants less than 2 years of age CPT are the third most common CNS
tumours following medulloblastoma and ependymoma.
•• Papillomas occur approximately 3−5 fold more often than carcinomas, and
the latter are more common in children less than 2 years of age.
SITE
•• In children, CPT most frequently arise in the lateral ventricle, followed
by the fourth and third ventricle, while in adults the fourth ventricle is the
commonest site followed by the lateral ventricles.
•• CPCs occur more often in the lateral ventricles of children less than 2
years of age.
•• CPT also present at the cerebellopontine angle as an extension of the
tumour through the foramen of Luschka where they are often benign and
rarely bilateral.
•• Diffuse hyperplasia of the choroid plexus associated with communicating
hydrocephalus is an entity now categorised as bilateral CPP.
•• Rare intra-parenchymal examples with no attachment to the ventricle have
also been reported in the cerebral cortex and in the brainstem.
AETIOLOGY
•• Choroid plexus tumours are usually sporadic.
•• They have been associated with Li-Fraumeni and Aicardi syndromes and
a possible association with SV 40 virus has also been suggested.
Chapter 126 • Tumours of the Choroid Plexus
953
Association with SV 40 Virus

•• Human polyomaviruses (e.g. BK and JC viruses) are tumourigenic in animal
models and cause ependymomas and choroid plexus neoplasms in them.
•• In humans, the presence of viral DNA signature of a closely related monkey
virus, SV40 was noted in 50% of choroids plexus tumours and in almost
all ependymomas.
•• Transgenic mice expressing SV40 large T antigen and SV11(+), develop
spontaneous tumours of the choroid plexus.
•• The viral T antigen binds to cellular protein targets that favour tumourigenesis.
Role of p53
•• There is increasing evidence for the role of p53 involvement in CPT
tumourigenesis.
•• CPTs are seen in patients of Li-Fraumeni syndrome (LFS) with p53 germline
mutations.
•• Loss of heterozygosity, other chromosomal alterations and possibly
association with SV 40 virus are likely mechanisms of inactivation of wild
type p53.
Aicardi Syndrome
•• CPTs also occur in association with Aicardi syndrome, an X-linked dominant
disorder with a triad of corpus callosal agenesis, infantile spasms and
chorioretinal lacunae.
•• Recurrent chromosomal abnormalities in CPT are gains of chromosome
7 and region 12q.
•• Gains of 9p and loss of 10q have correlated with a more favourable
prognosis in CPCs.
CLINICAL FEATURES
•• Choroid plexus tumours are usually slow growing and cause symptoms by
mass effect and obstructive hydrocephalus.
•• Occasionally, communicating hydrocephalus is caused by excessive CSF
production by the functional tumour cells particularly in bilateral lateral
ventricular CPP.
•• Lesions in infancy may cause enlargement of the head.
•• In children, the median age at presentation is 17 months (1–138) for CPP
and 13 months (2–102) for CPCs.
•• Congenital tumours have also been identified on antenatal sonography.
NEUROIMAGING
•• CT scans reveal isodense to hyperdense lesions.
•• On MRI, CPP are brilliantly enhancing intraventricular, lobulated masses,
isointense on T1W and well-defined, and hyperintense on T2W images.
•• MRI features commonly associated with CPC are a large intraventricular
lesion (approximately 4−5 cm), with irregular enhancing margins;
heterogeneous signal, oedema (73%), hydrocephalus and the presence of
disseminated tumour (45%). The latter is associated with a poor prognosis.
•• MR spectroscopy shows a higher level of myo-inositol in CPP compared
to CPCs.
954
•• On the other hand, markedly elevated levels of choline are noted in

malignant tumours of the choroid plexus.
•• Metastatic spread to lung and bone has also been reported.
•• On occasion, CPP exhibit ‘drop’ metastases into the thecal sac and
rarely a more diffuse subarachnoid spread can be seen, even after a long
asymptomatic period. Hence, total neuraxis imaging at the time of initial
diagnosis as well as periodic follow-up examinations after resection is
recommended.
PATHOLOGY
Macroscopy
•• Papillomas are generally circumscribed, greyish red, soft tumours with a
characteristic granular, cauliflower like surface, with focal gritty areas due
to calcification.
•• On sectioning, the tumour has variably compact and loose grey white
areas with haemorrhage and cystic change. Choroid plexus carcinomas
can be infiltrative, less circumscribed and show areas of haemorrhage
and necrosis.
Microscopy
•• CPP are benign papillary neoplasms resembling the normal choroid plexus
and are composed of delicate papillary fronds with central fibrovascular
cores lined by a layer of benign cuboidal to columnar epithelium.
•• The vessels are thin walled or variably hyalinised.
•• Histological features of anaplasia are not seen and mitotic activity is very
low.
•• Rarely, oncocytic change of the epithelial cells with abundant eosinophilic
cytoplasm rich in mitochondria, focal clear cell, mucinous change or
melanisation may be observed.
•• These changes do not have any prognostic significance.
•• Rarely, a mucinous adenoma pattern or tubulo-glandular pattern may be
noted.
•• Psammomatous and non-psammomatous calcification, xanthomatous
change, lymphocytic infiltrates in the stroma, cystic change and
haemorrhage are often present.
•• Extensive psammomatous calcification may be associated with aggressive
behaviour and a higher proliferative index.
•• Cartilage, ossified bone and, rarely, adipose tissue may also be seen as
a metaplastic change.
•• Occasionally, large angioma-like aggregates of thin walled vessels can be
observed in the core.
•• Ultrastructurally apical microvilli, basement membrane, tight junctions and
interdigitating cell membranes characterise the tumours.
Atypical CPP
•• Tumours with one or more atypical features in focal areas, namely,
loss of papillary pattern, increased cellularity, necrosis and nuclear
pleomorphism, but without frank anaplasia fall into this intermediate
histological grade.
Chapter 126 • Tumours of the Choroid Plexus
955
•• Mitotic activity of greater than or equal to 2 per 10 high power fields is

found to be the sole atypical feature associated with recurrence and is the
defining criteria for this grade in the WHO 2007 classification.
Choroid Plexus Carcinoma
•• It is characterised by overt features of malignancy, namely, solid growth with
loss of papillary architectural pattern, nuclear anaplasia, high mitotic activity
(often more than 5 per 10 high power fields) and parenchymal infiltration.
•• The tumour may show both solid and papillary areas and necrosis is often
present.
•• Infiltration by singly dispersed tumour cells has a more ominous connotation
and is seen in CPC.
IMMUNOHISTOCHEMISTRY
•• Almost all choroid plexus neoplasms, both papillomas and carcinomas,
express cytokeratin and vimentin.
•• The majority (80−90%) of CPP and less frequently the malignant form are
labelled by antibody to transthyretin (TTR) and S-100.
•• Developmentally, the choroid plexus cells normally express GFAP, a glial
marker, which persists in very few cells in adulthood.
•• This is reflected in the plexus tumours, and GFAP is present in a small
number of tumour cells in 25−55% of CPP and 20% of CPC.
•• Lack of or reduced S-100 staining has been associated with a poorer
prognosis in CPC.
•• The normal choroid plexus shows an MIB labelling index of 0.01−0.4%,
while in CPP it ranges from 0.2% to 6% (mean of 1.9%).
•• Following chemotherapy, some CPC have shown a reduction in MIB-1
labelling index, suggesting that chemotherapy may work in part in reducing
the proliferative potential.
•• Adhesion molecules, like CD44, markers for invasive growth and
metastasis, are found in atypical CPP and CPC.
•• Altered p53 expression, a tumour suppressor gene, was found in all CPC
and in one fourth of papillomas.
•• Aggressive papillary tumour of the endolymphatic sac or duct of the middle
ear (also known as endolymphatic sac tumour, ELST) is histologically
identical to CPP and explains the earlier reports of CPP in the temporal
bone, close to the internal acoustic meatus. These tumours, unlike CPP,
do not express TTR and are often a component of von Hippel Lindau
(VHL) disease.
•• Anaplastic papillary ependymomas may mimic CPC. Perivascular
pseudorosettes and strong perivascular GFAP fibre positivity serve to
identify the former.
PROGNOSIS
•• For choroid plexus tumours histological features and complete surgical
resection are the most important prognostic factors.
•• In CPP, complete resection is more frequently possible than in atypical or
malignant forms.
956
•• Management is influenced by several factors like resectability, vascularity,

presence of craniospinal spread and treatment of associated hydocephalus.
•• After gross total resection in papillomas recurrences are rare and the
functional outcome is excellent in 92%.
•• The median survival for CPP is 75.5 months.
•• In the small proportion of cases where resection of CPP is incomplete a
wait-and-watch policy is advocated.
•• In case of plexus carcinomas, gross total resection is possible in about 33%
of cases and the median survival is only 6 months (range 1−90 months).
•• For CPCs, adjuvant chemotherapy and craniospinal radiation following
surgery should be considered although its uniform efficacy in all cases
remains to be established.
•• The excessive vascularity of the CPT lends itself to peri-operative morbidity
and mortality and infants have a higher risk of massive bleeding and
coagulation disturbances.
127
CHAPTER Pineal Parenchymal
Tumours
Vani Santhosh
•• Neoplasms occurring in the pineal region are very rare, comprising 0.5−1%
of all intracranial neoplasms in adults.
•• Among these, pineal parenchymal tumours are a small group, ranging from
15 to 30% of pineal region tumours.
•• According to the revised WHO 2007 classification of central nervous system
tumours, pineal parenchymal tumours (PPTs) are classified as pineocytoma
(PC-grade I), pineal parenchymal tumour with intermediate differentiation
(PPT-ID grade II/III) and pineoblastoma (PB-grade IV) and papillary tumour
of the pineal region.
•• Papillary tumour of the pineal region is now recognised as a distinct entity
in this group.
PINEOCYTOMA (WHO GRADE I)

•• This is a slowly growing, relatively demarcated tumour occurring in the
pineal region.
•• Patients often present with neuro-ophthalmic paralysis or Parinaud’s
syndrome.
•• They can also present with features of raised intracranial pressure.
•• The tumour is relatively well demarcated with foci of calcification.
•• It tends to be isointense on T1W images of MRI and hyperintense on T2W
images.
•• There is intense homogeneous contrast enhancement. Associated
hydrocephalus is always seen.
•• These are well differentiated neoplasms composed of uniform mature cells
resembling pineocytes, arranged in sheets or ill-defined lobules.
•• Mitotic activity is either absent or very low.
•• Calcification is evident in some cases.
•• Pineocytomatous rosettes are often seen.
•• These are composed of pineocytic cells arranged around a fine meshwork
of neuropil-like stroma.
•• Occasional tumours exhibit foci of pleomorphic binucleate or multinucleate
ganglionic cells and have been termed as pleomorphic variant of
pineocytoma with ganglionic differentiation.
•• The tumour cells strongly express neuronal markers such as neurofilament
protein, synaptophysin, neuron specific enolase and others.
•• They also express retinal s-antigen and rhodopsin indicating a photosensory
differentiation of tumour cells.
958
PINEAL PARENCHYMAL TUMOUR OF

INTERMEDIATE DIFFERENTIATION
(PPT-ID; WHO GRADE II/III)
•• This is a pineal parenchymal tumour of intermediate grade malignancy
which comprises about 20% of all pineal parenchymal tumours.
•• The tumour occurs at all ages.
•• The clinical features are very similar to that of pineocytoma and distinct
imaging features are seen.
•• The tumour exhibits varied histomorphological features.
•• The majority are moderately cellular neoplasms exhibiting a lobular or
sheet-like arrangement.
•• Some of the neoplasms exhibit a neuroendocrine or papillary pattern.
•• There is a moderate degree of nuclear atypia and mitotic activity.
•• There has been some attempt at sub-classifying these tumours according
to the extent of mitotic activity.
•• Neuronal differentiation in the form of Homer-Wright rosettes or ganglion
cells are seen occasionally.
•• This tumour has a similar immunohistochemical marker profile as
pineocytoma.
PINEOBLASTOMA (WHO GRADE IV)

•• This is the most malignant of all pineal parenchymal neoplasms and is a
form of primitive neuro-ectodermal tumour (PNET).
•• The tumour most often affects children and has a predilection for CSF
dissemination in view of its proximity to the CSF cisterns behind the
mesencephalon.
•• The clinical presentation is similar to other pineal parenchymal tumours
but the duration of symptoms is shorter than the others.
•• On CT scan, pineoblastoma is a lobulated or poorly demarcated,
homogeneous mass which is hyperdense after contrast enhancement.
•• The tumour is hypointense to isointense on MRI scan and exhibits
significant heterogeneous contrast enhancement.
•• Calcification and extensive cystic change are rare.
•• Infiltration of the surrounding structures and CSF dissemination is
commonly seen.
•• Pineoblastomas are poorly differentiated neoplasms with features in
common with other central primitive neuroectodermal tumours.
•• They are composed of densely packed small cells with a hyperchromatic
nucleus and scanty cytoplasm.
•• Characteristic Homer-Wright and Flexner-Wintersteiner rosettes are seen.
The latter indicates a retinoblastic differentiation.
•• Rarely fleurettes are also seen.
•• All tumours exhibit a very brisk mitotic activity (more than 6 mitoses in
10 high power fields).
•• In addition, apoptosis is also detectable on Hematoxylin and Eosin stained
sections.
•• Necrosis is also seen in several tumours.
•• Rarely, a mixed tumour with alternating areas of pineocytoma and
pineoblastoma has been reported.
Chapter 127 • Pineal Parenchymal Tumours
959
•• Pineoblastomas with mesenchymal or melanotic differentiation are referred

to as ‘Pineal anlage’ tumours.
•• The immunophenotype of pineoblastomas is similar to other pineal
parenchymal tumours.
•• The tumour exhibits a high MIB-1 index.
HISTOGENESIS OF PINEAL PARENCHYMAL

NEOPLASMS
•• The pineocyte is a cell with photosensory and neuroendocrine functions in
lower animals and is believed to be the cell of origin of pineal parenchymal
tumours.
•• Ontogenically the pineal gland resembles the phylogeny of the human
retina.
•• During the late foetal gestational and early postnatal period, the pineal gland
contains primitive cells arranged in small rosettes similar to developing
retina.
•• Later, the cells differentiate along neuronal lineage.
•• The pineocyte is a differentiated cell and appears before 1 year age.
PROGNOSTIC AND PREDICTIVE FACTORS OF

PINEAL PARENCHYMAL NEOPLASMS
•• In general, some of the factors affecting survival in pineal parenchymal
tumours are the morphological sub-type of the tumour, mitotic and MIB-I
labelling index, presence of necrosis and neurofilament immunolabelling.
PAPILLARY TUMOUR OF THE PINEAL REGION

•• This is an uncommon tumour of the pineal region in adults composed of
cells with an epithelial morphology arranged as papillary structures.
•• These cells exhibit cytokeratin immunoreactivity and ultrastructurally show
features suggesting ependymal differentiation.
•• The tumour grade is variable and may correspond to grade II or III.
128
CHAPTER Neuronal and Mixed
Neuronal Glial Tumours
Sharma MC  Chitra Sarkar
GANGLIOGLIOMA AND GANGLIOCYTOMA

•• These are well differentiated slow-growing neuroepithelial tumours
consisting of neoplastic mature ganglion cells alone (gangliocytoma) or in
combination with neoplastic glial cells (ganglioglioma).
•• Both gangliocytoma and ganglioglioma correspond to WHO Grade I
(Table 1) but, rarely, the glial component in ganglioglioma can be WHO
Grade III.
•• The criteria for Grade II tumours are controversial.
•• Ganglion cell tumours are found throughout the neuraxis, but the favoured
sites are the cerebral hemispheres, especially the temporal cortex, followed
by the cerebellar hemispheres, brainstem, spinal cord, optic chiasm,
pituitary and pineal glands.
•• Children and young adults are most commonly affected.
•• The most common presentation is with seizures but, sometimes, these
lesions remain subclinical for decades.
Neuroimaging
•• CT scan shows a well circumscribed mass lesion with a cyst and mural
nodule.
•• Calcification in the tumour and scalloping of the overlying bone can also
be seen, but features of mass effect are absent.
Table 1: The following tumours are included in the group of neuronal and
mixed neuronal-glial tumours as per WHO classification (2007)
S.No. Name of the entity WHO grade
1. Dysplastic gangliocytoma of cerebellum (Lhermitte- Hamartomatous/
Duclos disease) Grade I if neoplastic
2. Desmoplastic infantile astrocytoma and ganglioglioma Grade I
3. Dysembryoplastic neuroepithelial tumour Grade I
4. Gangliocytoma and ganglioglioma Grade I
5. Papillary glioneuronal tumour Grade I
6. Rosette forming tumour of the fourth ventricle Grade I
7. Central neurocytoma and extraventricular neurocytoma Grade II
8. Cerebellar liponeurocytoma Grade II
9. Spinal paraganglioma Grade I
Chapter 128 • Neuronal and Mixed Neuronal Glial Tumours
961
•• On MRI, this tumour is hypointense on T1WI and hyperintense on T2WI

and the mural nodule will enhance.
•• The other brain tumours which show a cyst with mural nodule are pilocytic
astrocytoma, pleomorphic xanthoastrocytoma, haemangioblastoma and,
sometimes, papillary glioneural tumour (PGNT).
Histopathology
•• Ganglion cell tumours are typically well circumscribed with expanding
margins, and infiltration of the surrounding parenchyma is unusual.
•• Gangliocytoma is composed of nodular aggregates of ganglion cells in a
fibrillary background.
•• The individual cell has distinct cellular outline, eosinophilic cytoplasm and
large nucleus with prominent nucleolus.
•• Cytoplasmic vacuolation, irregular distribution of Nissl substance, nuclear
pleomorphism and binucleation differentiates a neoplastic cell from a normal
neuron in the cortex.
•• Perivascular lymphocytes are common and, sometimes, occur in large
numbers to form a lymphoid follicle.
•• Areas of dystrophic calcification are common. Mitosis, necrosis and vascular
proliferation are typically absent.
•• Gangliogliomas are composed of a dual population of cells consisting of
neoplastic ganglion cells admixed with neoplastic astrocytic cells. These
two elements may be admixed intimately, or be present separately, any of
the two components dominating.
•• The ganglionic component is composed of lobules of large cells with
eosinophilic cytoplasm with vacuolation and paucity of Nissl substance.
•• Nuclear dysplasia and binucleation favour the neoplastic nature of the cell.
•• The glial component comprises of reactive looking astrocytes, at times a
perfect caricature of pilocytic astrocytoma or oligodendroglioma.
•• Perivascular lymphocytic inflammation and calcification are frequent
findings.
•• Some cases show abundant eosinophilic granular bodies and microcystic
change as observed in pilocytic astrocytomas.
•• The tumours which show frequent mitoses, necrosis or vascular proliferation
in the astrocytic component are designated as anaplastic ganglioglioma
of WHO Grade III.
•• The stroma with desmoplasia is commonly seen and this is better
appreciated with a special reticulin stain or Masson trichrome stain. This
feature is extremely useful in the diagnosis and differentiation from other
tumours.
•• Subarachnoid spread is not indicative of aggressiveness of this tumour
and is commonly seen in benign tumours.
•• The ganglionic component is immunopositive for neurofilament proteins
(NF), synaptophysin, MAP-2 and NeuN. CD34 positivity is demonstrated
in 70% of the cases, especially in the temporal lobe tumours. The glial
component is positive to glial fibrillary acidic protein (GFAP), but is negative
to MAP-2 protein.
•• Patients with neurofibromatosis-1 (NF-1) and Peutz-Jeghers syndrome are
more prone to have ganglioglioma.
•• Genetic abnormalities commonly found in gangliogliomas include gain of
chromosome 7 and loss of chromosome 9p.
962

•• Surgical excision is the treatment of choice and is curative.
•• Good prognosis is associated with temporal lobe location, long history of
epilepsy and complete resection.
•• Seizures may persist in cases associated with cortical dysplasia.
•• Anaplastic transformation is a bad prognostic indicator.
LHERMITTE-DUCLOS DISEASE/DYSPLASTIC
GANGLIOCYTOMA OF THE CEREBELLUM
•• It is a benign cerebellar tumour composed of dysplastic ganglion cells.
•• The exact grade has not been assigned to this lesion in the WHO
classification of tumours, as its exact nature is not clear.
•• This lesion was described by Lhermitte and Duclos and by Spiegel in the
same year.
•• This entity is also called cerebellar granular cell hypertrophy, diffuse hy-
pertrophy of the cerebellar cortex and gangliomatosis of the cerebellum.
•• Recently, it has been shown that it has a strong association with Cowden
disease.
•• The majority of patients are adults at the time of presentation, although it
may present in the age range of 3−74 years.
•• Most of the patients present with cerebellar dysfunction and obstruction
of the CSF pathway.
•• Mass effect, associated macrocephaly and seizures are common.
•• MRI shows diffuse thickening of the cerebellar foliae.
Histopathology
•• Under low power magnification the cerebellum looks distorted and enlarged,
and still maintains the architecture.
•• The lesion causes diffuse enlargement of the molecular and internal
granular layers of the cerebellum which are filled by large pleomorphic
ganglionic cells.
•• A layer of abnormally myelinated axon bundles in parallel arrays is observed
in the outer molecular layer and extends from the granular layer through
the molecular layer, and is better appreciated with myelin stains.
•• Scattered small cells, morphologically consistent with granular neurons, are
seen in the subpial region or in the molecular layer. This whole appearance
is referred to as inverted cerebellar cortex.
•• Purkinje cells are either absent or markedly reduced in numbers.
•• The associated findings include abnormally ectatic vessels, calcification
and vacuoles in the molecular layer or cerebellar white matter.
•• The neurons are immunopositive for synaptophysin, chromogranin and
neurofilament, but are negative for GFAP.
•• Immunohistochemistry also shows loss of PTEN protein and increased
expression of phosphorylated-Akt and S6 in the dysplastic neurons. Mitotic
response in the cells is low.
•• The exact origin of this condition is not known but a hamartomatous origin
is favoured. If neoplastic, then it corresponds to WHO Grade I tumour.
963
DESMOPLASTIC INFANTILE
GANGLIOGLIOMA/ASTROCYTOMA
•• Desmoplastic infantile ganglioglioma (DIG)/astrocytoma (DIA) are large
cystic tumours occurring in infants.
•• They involve the superficial cortex, or leptomeninges, are often attached
to the dura, show marked desmoplasia and correspond to WHO Grade I.
•• DIG and DIA differ only with respect to the presence of ganglion cells in
the former and their absence in the latter.
Clinical Features
•• Desmoplastic astrocytoma was variously described as meningocerebral
astrocytoma attached to the dura with desmoplastic reaction or superficial
cerebral astrocytoma attached to the dura.
•• Desmoplastic supratentorial neuroepithelial tumours of infancy with
divergent differentiation probably belong to the category of DIG.
•• These are rare tumours of childhood, predominantly seen during the 1st
year of life.
•• Males are more commonly affected than females, but this male predominance
is stronger when they occur between the ages of 5 years and 25 years.
•• Most of the children present with marked enlargement of the head, bulging
fontanelles, lethargy and ‘setting sun’ sign of short duration. Seizures and
neurological deficits are uncommon.
Neuroimaging
•• CT scan shows a large cystic lesion with a solid isodense or hyperdense
superficial portion.
•• MRI shows the cystic component to be hypointense on T1WI and hyper
intense on T2WI, the superficial solid portion being contrast enhancing.
•• Some authors have described five cardinal diagnostic signs namely: (1)
massive size; (2) cystic architecture; (3) superficial position; (4) contrast
enhancement and (5) dark desmoplastic component on T2WI, which are
helpful in pre-operative diagnosis.
Histopathology
•• The most important feature of these tumours is desmoplasia which varies
in extent from region to region and from tumour to tumour.
•• The lesions have three components: desmoplastic leptomeningeal, poorly
differentiated neuroepithelial and cortical components.
•• The leptomeningeal component is composed of fibroblast, like spindle
shaped cells and pleomorphic cells, with an eosinophilic cytoplasm
arranged in fascicles derived from the glial component.
•• These areas are reticulin rich and mimic mesenchymal tumours.
•• GFAP positive astrocytes are the sole component of DIA, but DIG, in
addition, contains neuronal components ranging from small neurons to
large ganglionic cells.
•• The poorly differentiated neuroepithelial component comprises reticulin
poor nodular aggregates of small cells with deeply basophilic nuclei and
minimal pleomorphism.
964
•• Mitoses may be seen in these cells.

•• A multinodular cortical component with microcystic changes may be seen
which is devoid of desmoplasia. Areas of calcification may be seen.
•• There is sharp demarcation between the tumour and the underlying cortex,
but perivascular invasion along the Virchow-Robin spaces may be seen.
•• The desmoplastic component is immunopositive for GFAP, vimentin and
rarely smooth muscle actin indicating a possible origin of this tumour from
glial progenitors or subpial astrocytes.
•• Neuroepithelial cells are positive for GFAP while the neuronal cells are
positive for synaptophysin, NF and class III b tubulin.
•• The poorly differentiated neuroepithelial component shows positivity for
GFAP, vimentin, MAP-2 and rarely desmin.
CENTRAL NEUROCYTOMA
•• WHO defines central neurocytoma as a neuronal tumour comprising of
uniform round cells, typically located in the lateral ventricle in the foramen
of Monro region and corresponds to WHO Grade II.
•• The term central neurocytoma was coined in 1982 by Hassoun, et al.
•• They used this term to describe an intraventricular tumour which mimics
morphologically an oligodendroglioma but after ultrastructural studies and
immunohistochemistry was found to be of neuronal nature.
•• Earlier these tumours were misdiagnosed as intraventicular oligodendro-
gliomas or ependymomas of the foramen of Monro.
•• Tumours which occur in the lateral, third or fourth ventricle are designated
as central neurocytoma (CN), but those which are outside the ventricular
system are designated as extraventricular neurocytomas (EVN).
•• They comprise about 0.1−0.5% of all intracranial tumours.
Clinical Features
•• Central neurocytomas are typically located in the supratentorial ventricular
system near the foramen of Monro in the lateral or third ventricle.
•• The most common locations are the anterior portion of the lateral ventricle
with attachment to the septum pellucidum with or without biventricular
extension or extension into the third ventricle.
•• No gender predilection is noted and the majority of the tumours occur in
the second and third decades of life.
•• The duration of symptoms is usually long and patients present with
headache, vomiting and visual disturbances.
•• Rarely, an acute presentation due to haemorrhage has been reported.
Imaging
•• Radiologically these tumours are isodense to hyperdense on CT scanning
with cystic areas and contrast enhancing areas.
•• Foci of calcification are commonly seen in about half of the patients and,
sometimes, these tumours are densely calcified.
•• On MRI, these tumours are isointense on T1WI but hyperintense on T2WI
and uniformly to heterogeneously enhancing with contrast.
Histopathology
•• Intraventricular tumours are well demarcated, greyish and friable with
areas of calcification.
965
•• On light microscopy, neurocytoma is a perfect caricature of an

oligodendroglioma.
•• Neurocytoma is a tumour of variable cellularity and classically shows cellular
areas alternating with fibrillary areas.
•• The cellular areas are composed of uniform cells with perinuclear clearing
of cytoplasm, and a central, round to oval nucleus with speckled chromatin.
•• The background shows a fine fibrillary neuropil-like matrix and intervening
thin walled blood vessels, at times hyalinised or dilated and congested.
•• At places, the cells are arranged around the fibrillary areas giving the
appearance of vague rosette formation.
•• The fibrillary areas, at places, project on to the blood vessels mimicking
the perivascular rosettes of ependymomas.
•• Mitoses are usually absent or occasional.
•• Microscopic foci of calcification are seen in 50% of the cases.
•• Some tumours with extensive ganglionic differentiation are labelled as
ganglioneurocytomas.
•• Tumour cells are positive for synaptophysin and neuron specific enolase
(NSE), but negative for GFAP except for focal positivity mainly at the tumour
periphery or around blood vessels.
Histogenesis
•• Central neurocytoma supposedly arises from the nuclei of the septum
pellucidum and is of neuronal origin, but the presence of reactive looking
astrocytic components in the tumour and tissue culture studies support the
hypothesis that this tumour arises from primitive neuroglial cells with the
capacity to differentiate towards both neuronal as well as astroglial lines.

•• Surgical excision is the treatment of choice but total excision may not be
possible due to attachment to the surrounding structures. Some tumours
remain stable even after partial excision.
•• Radiotherapy should be reserved for recurrent or partially excised tumours
or when surgery is not possible, or for atypical neurocytomas.
DYSEMBRYOPLASTIC
NEUROEPITHELIAL TUMOUR
•• Dysembryoplastic neuroepithelial tumour (DNET) is a benign, usually
supratentorial tumour, occurring in childhood or in young adults,
characterised by a cortical location, drug resistant partial seizures and
characteristic morphology (WHO Grade I).
Clinical Features
•• In the tissues excised during epilepsy surgery, the incidence of DNET is
12% in adults and 13.5% in children.
•• Among all neuroepithelial tumours diagnosed in a single institution, DNET
occurs in 1.2% of patients below 20 years of age and in 0.2% beyond 20
years of age, with a male preponderance.
•• Most patients present with pharmacoresistant partial seizures with or
without secondary generalisation.
966
•• The most common location is the temporal lobe, but it may occur in the
caudate nucleus, septum pellucidum, lateral ventricle, floor of third ventricle,
brainstem and cerebellum.
Neuroimaging
•• MRI shows a well defined cortical lesion which is nodular or triangular in
appearance with its apex towards the white matter.
•• They are hypointense on T1WI and hyperintense on T2WI and show single
or multiple ring enhancements on contrast injection.
•• Scalloping of the inner table of the skull is a common finding.
Pathology
•• These tumours are located in the superficial cortex forming nodular
expansions indenting the subcortical fibres.
•• Extension into the underlying white matter is extremely rare. Grossly, they
are mucoid in appearance.
•• The histological hallmark is the ‘specific glioneuronal element’ (SGE)
described by Dumas-Duport.
•• SGE shows columns formed by bundles of axons lined by oligodendroglial-
like cells (OLC), oriented perpendicular to the cortical surface. The lining
cells are small with perinuclear clear cytoplasm simulating oligodendroglial
cells.
•• The scattered cells are positive for NeuN, NSE, synaptophysin,
neurofilaments and class III b tubulin.
Histogenesis
•• Association with cortical dysplasia, cortical location and young age at the
onset of symptoms favours the theory of the malformative nature of this
lesion, supposedly arising from the secondary germinal layers.
•• A malignant progression in an occasional case indicates the neoplastic
nature.

•• Surgical resection is the treatment of choice and is rewarding, as these
tumours are benign and the prognosis is excellent.
•• The tumours which are associated with diffuse cortical dysplasia may
continue to produce seizures even after surgery.
•• Malignant progression has been described only twice in the literature and
both of them presented with atypical features. In one patient, this malignant
progression was seen after radiotherapy and chemotherapy.
Section XI: Cranial and Intracranial Tumours
129
CHAPTER Clinical Features of
Intracranial Tumours
Ravi Ramamurthi  Santosh Mohan Rao K
•• The term ‘intracranial tumours’ includes, in a loose fashion, all space-

occupying lesions within the cranial cavity including non-neoplastic lesions
like cysts, granulomas, chronic abscesses and haematomas.
•• ICSOL cause clinical symptoms by:
–– Raising the ICP
–– Interfering with the function of the area involved by the lesion
–– Disturbing the function of neighbouring structures due to oedema or
vascular disturbances and
–– By displacement and distortion of remote structures due to various
herniations.
RAISED INTRACRANIAL
PRESSURE—PATHOGENESIS
•• Except in infants and young children, the cranial cavity is not expansile and
thus any addition of matter inside the cranial cavity results in an increase
in pressure.
•• In the early stages, some amount of adjustment may occur by displacement
of a small quantity of CSF and venous blood.
•• If the lesion increases in size, it has to accommodate itself by compressing
the brain and the other intracranial structures with a resultant increase in
ICP.
•• The factors that determine the rise in ICP are:
–– The bulk of the tumour and rapidly of its growth:
¾¾ A slow growing lesion, like a meningioma, may grow to a large size
without manifesting any symptoms or signs of raised ICP.
¾¾ On the contrary, a rapidly growing tumour, even when small in size,
raises the ICP early in its evolution.
¾¾ Any event, like haemorrhage or cystic degeneration that may sud-
denly increase the size of a slow growing lesion, may also lead to
decompensation and result in raised ICP.
–– Associated cerebral oedema:
¾¾ Some space occupying lesions have a tendency to break down
the blood-brain barrier and cause extensive oedema, e.g. glioblas-
toma, some varieties of metastases, meningioma, tuberculoma,
cysticercus and abscess. In these cases, the ICP may show a rapid
rise, even though the tumour may be small in size.
Section XI • Cranial and Intracranial Tumours
968
–– Proximity to CSF pathways:

¾¾ Tumours occurring near the midline tend to obstruct the CSF flow
and thus lead to hydrocephalus and increased ICP. Tumours aris-
ing in the medial temporal region, in the suprasellar region in the
third ventricle and in the posterior fossa near the fourth ventricle are
such examples. In these locations, even a small lesion may lead to
an early rise of ICP.
–– Compression of the major venous channels:
¾¾ A tumour arising near a major venous channel may compress it and
lead to venous stasis.
EFFECTS OF RAISED INTRACRANIAL PRESSURE

ON VARIOUS STRUCTURES
•• The skull and the scalp:
–– Due to the free communication between the scalp veins, the diploic
channels and the dural and subdural veins, increasing ICP may be
transmitted to the veins of the skull and scalp.
–– The scalp veins may become dilated and prominent when the patient
bends forward.
–– They may appear especially prominent on the side of the tumour when
the tumour is near the surface.
–– The enlarged diploic veins become apparent on plain X-rays.
–– The posterior clinoid processes get demineralised and may get ab-
sorbed and the pituitary fossa may get enlarged.
–– In children and young adults separation of the sutures and beaten
silver appearance are common.
•• The dura mater:
–– As the ICP rises, the dura mater gets stretched. The basal dura being
sensitive, the patient develops headache, which may be frontal, occipi-
tal or generalised. Stretching of either the falx cerebri or the tentorium
may also result in localised or generalised headache.
–– The dura, if stretched over the surface of a tumour, may get thinned
out.
•• Veins:
–– The intracranial veins are one of the earliest structures to suffer the
effects of increased ICP.
–– The walls of the veins near the tumour get stretched and compressed
and the veins get obliterated leading to back pressure.
–– As the ICP rises, a large number of veins get occluded but as the
venous sinuses are enclosed in rigid dura, pressure on the sinuses is
not common except when there is direct pressure by a tumour arising
near the sinus.
–– Pressure on the veins leads not only to retrograde congestion but also
interferes with the absorption of CSF.
–– Blockage of the venous flow from the orbit may result in a mild unilat-
eral or bilateral proptosis.
–– Tumours occurring in the middle cranial fossa or the temporal lobe
may lead to a mild but perceptible proptosis on the side involved due
to pressure on the veins draining through the superior orbital fissure.
•• Cerebrospinal fluid:
–– The subarachnoid spaces along the base of the brain and over the
convexity gradually get obliterated.
Chapter 129 • Clinical Features of Intracranial Tumours
969
–– A tumour adjacent to the CSF pathway may exude proteins into the
CSF which may further increase the ICP.
–– A spinal neurofibroma which elevates the protein levels in the CSF
may raise the ICP and cause papilloedema.
•• Major arteries:
–– In the initial stages, there are no alterations in the major cerebral
arteries. However, as the tumour enlarges, local distortion of the neigh-
bouring arteries may take place.
–– The patient may complain of frontal headaches due to stretching of the
vessels of the circle of Willis.
–– In the late stages, the ICP may rise as high as the arterial pressure;
this causes a reflex rise of blood pressure in an attempt to keep up the
cerebral blood flow (CBF).
–– In an acute and severe rise in ICP, when the ICP equals the arterial
blood pressure, carotid and vertebral arterial flow into the brain may
stop. At this stage, the patient is deeply unconscious and without spon-
taneous respiration and is a prelude to “Brain Death”.
–– Angiography shows a ‘carotid stop’ or total circulatory failure. This
phenomenon is more often seen terminally in cases of acute massive
increase in pressure, as in sudden severe subarachnoid or intracer-
ebral haemorrhage, fulminating post-traumatic brain swelling and only
rarely in brain tumours.
–– Reduction of ICP by diuretics or hyperventilation may help to restore
the blood flow for a short while.
•• Cranial nerves:
–– Owing to their pliability, the cranial nerves may get stretched without
any apparent deficit.
–– The nerves most liable to be involved in rising ICP are the sixth nerves,
because of their long intracranial course and their angulation over the
petroclinoid ligament and passage through Dorello’s canal. Increased
ICP may result in unilateral or bilateral external rectus palsy. In gen-
eral, this is not of localising value.
–– The third nerve is likely to be compressed in supratentorial lesions
when there is transtentorial herniation. The pupillary fibres being more
superficial in the nerve, dilatation of the pupil is more frequently en-
countered than ptosis or ocular muscle weakness.
–– Raised ICP can produce impairment of hearing may be either conduc-
tive or sensorineural type.
–– When the ICP rises further or in posterior fossa lesions when the
cerebellar tonsils herniate through the foramen magnum, the first and
second spinal nerves get stretched leading to spasm of the suboccipi-
tal muscles, as well as pain and paraesthesia over the occipital region.
–– Tumour of the temporal lobe may produce trigeminal neuralgia by
pressing on the Gasserian ganglion or a tumour in the CP angle may
present with hemifacial spasm.
•• Cerebral blood flow:
–– When the ICP is marginally raised, there is no change in the CBF.
–– However, enlarging lesions may cause alterations in the blood flow of
circumscribed areas depending on the local pressure and the pathol-
ogy of the lesion.
–– A very vascular growth or an arteriovenous malformation causes a
considerable reduction in the blood flow to the surrounding areas due
to the phenomenon of steal.
970
–– As the ICP rises further, there is a gradual reduction in CBF leading to

incipient cerebral anoxia.
–– The rapid clinical improvement, often seen after the administration of
diuretics or CSF diversion procedures, can be attributed not only to the
reduction in ICP but also to improved CBF.
–– On the other hand, when the ICP rises rapidly there may be a paraly-
sis of autoregulation, resulting in a sudden increase in CBF which is
responsible for the rapid deterioration in the condition of the patient.
•• Effects on the brain:
–– The white matter is liable to be affected by a dilating ventricular system.
–– In long standing hydrocephalus, signs of pyramidal tract involvement
in the legs appear due to stretching of the white matter of the corona
radiata by the enlarging ventricles.
•• Secondary phenomena:
–– Increasing pressure on the brain, the blood vessels and the CSF re-
sults in the secondary phenomena of herniations, false localising signs
and systemic disturbances.
SIGNS AND SYMPTOMS OF RAISED

•• The elastic skull of the infant and young child can accommodate the
increase in intracranial contents by a slow expansion secondary to
separation of the sutures.
•• A tense fontanelle or a progressive increase in the size of the head may
be the only sign of raised ICP for months in infants and young children
with brain tumours.
•• Percussion of the head elicits a cracked pot sound (MacEwen’s sign) in
some children.
•• Young children often do not complain of headaches and the presenting
symptoms may be abdominal discomfort, vomiting, irritability or listlessness.
•• The optic fundus is often normal; papilloedema is uncommon but pallor of
the disc may be seen in some children with raised ICP.
•• In old people, the brain shrinks a little due to atrophy and thus there is more
space for the lesion to grow before causing an increase in pressure. Thus,
slow growing lesions may attain a considerable size in elderly persons
before pressure effects begin to appear.
Headache
•• Headache occurs frequently in patients with increased ICP and acquires
special significance if it occurs in a person not previously subjected to
headaches.
•• The brain itself is insensitive to pain but the dura mater, especially at the
base of the skull as well as the major blood vessels in the brain, are pain
sensitive structures.
•• Headache, in increasing ICP results from stretching of the dural coverings,
shifting of the dural partitions and stretching and kinking of the major blood
vessels.
•• The headache may be frontal, bitemporal or occipital.
•• The anterior parts of the dura are supplied by the trigeminal nerve and the
posterior half by the second cervical nerve, frontal headache may indicate
an anterior lesion and an occipital headache a more posterior tumour but
this is often not true.
971
•• Only occasionally the site of headache has any localising value.

•• Anterior basal tumours often cause retro-orbital pain for months, before
generalised headache appears.
•• Pain over the vertex is uncommon, except in cases of parasagittal tumours
arising near the vertex.
•• Surface tumours, like meningiomas, may present with localised pain and
tenderness.
•• Headache caused by raised ICP has certain features which may arouse
suspicion of the possibility of a space occupying lesion.
•• The headache is throbbing in character and gets aggravated by stooping,
straining or exertion.
•• It is common in the early hours of the morning and towards late in the
evening.
•• A characteristic feature of the headache due to raised ICP is its occurrence
when the patient is sleeping.
•• The throbbing headache often wakes up the patient in the early hours of
the morning.
•• Such headaches coincide with REM sleep (dream sleep) during which
normally the ICP shows a tendency to rise due to cerebral vasodilatation.
•• In patients whose ICP is already high, a further increase in pressure, during
sleep, causes an increase in the severity of headache.
•• Intake of alcohol or other vasodilating drugs tend to increase this headache.
•• Pain in the suboccipital region has a serious import and requires urgent
action.
•• Suboccipital pain, occurring in a patient who has already been diagnosed
as suffering from raised ICP, indicates tonsillar herniation.
•• The herniating cerebellar tonsils irritate the C1 nerve root causing spasm
of the suboccipital muscles which causes headache. The head may be
tilted or rotated to one side and this is often seen in children.
•• At a later stage, the C2 nerve root is similarly stretched leading to
muscular pain. Such pain is often mistaken for upper cervical pathology
both in children as well as in adults. Cough syncope may occur with
herniated cerebellar tonsils.
Localised Tenderness of the Skull

•• This has a localising value in tumours involving the cranium or the dura
mater.
•• More commonly, inflammatory lesions underlying these structures cause
localised tenderness over the affected area.
•• Some patients with cerebellopontine angle (CPA) lesions will give a history
of transient severe ear ache or retromastoid pain on the side ipsilateral to
the lesion.
Vomiting
•• This is a frequent symptom of raised ICP and is caused by irritation of the
vomiting centre in the medulla.
•• Usually, vomiting occurs sometime after the headache sets in.
•• Vomiting is a common and early symptom of increased ICP in children
and may be the only symptom of a space-occupying lesion for a long time.
Unexplained vomiting in a child has to be taken seriously and investigated.
•• Generally, the vomiting is described as projectile without any feeling of
nausea but this is not always so.
972
•• As the vomiting is not due to gastric causes, it is often possible to feed a

patient with small amounts of nourishment soon after the vomiting. This
must be remembered as otherwise the patient may get dehydrated and
malnourished in a very short time.
Vertigo
•• This is often seen in intracranial tumours, especially in posterior fossa
lesions.
•• The patient will complain of an unsteady feeling and a disturbance of the
sense of balance in space.
•• This may occur with or without alteration in posture.
•• Giddiness may be due to vestibular disturbances, pressure on the brainstem
or visual disturbances like diplopia or transient blurring of vision.
Visual Changes
•• When ICP has existed for sometime, the function of the optic nerves is
affected.
•• Ophthalmoscopic examination is essential while examining a patient
suspected of harbouring a brain tumour.
Papilloedema
•• A blockage of the venous return from the retina results in papilloedema.
•• This occurs in the majority of cases of raised ICP, except in young children,
in whom raised ICP is compensated for a long period of time by separation
of the sutures.
•• Papilloedema is also late in appearance in benign low grade gliomas,
epidermoids, meningiomas and in frontoparietal tumours, whereas posterior
fossa lesions cause papilloedema early.
•• Very rarely, papilloedema may not occur in raised ICP if the venous drainage
of the retina is embryologically different, draining chiefly into the inframaxillary
venous plexus.
•• In pituitary and parapituitary lesions, the optic nerve gets compressed initially
leading to primary optic atrophy; in such cases, even when the ICP increases
later on, papilloedema does not develop in the eye with optic atrophy.
•• The earliest change in the optic fundus secondary to rise in ICP is loss
of spontaneous venous pulsations (SVP). The presence of the pulsations
indicates that the ICP is less than 200 mm H2O. In about 10−20% of normal
patients the SVP may be absent.
•• The earliest indication of papilloedema is the enlargement of the blind spot.
This is a useful diagnostic sign and should be carefully looked for whenever
there is any doubt about the existence of papilloedema.
•• The size of the blind spot corresponds to the area of exit of the optic nerve
from the retina, i.e. the optic nerve head; hence the size of the blind spot
increases when the optic nerve head begins to swell.
•• Another early sign of increasing ICP is the enlargement and congestion
of the retinal veins.
•• The normal optic disc is slightly pink and circular, with the temporal side
being slightly paler than the nasal side.
•• Normally, the optic nerve head is depressed below the surface of the retina
by about two or three millimetres, thus forming the optic cup.
973
•• From the centre of the depression, the retinal arteries and veins may be
seen coursing in four directions.
•• In papilloedema the disc projects forwards in relation to the retina, the
projection being more obvious on the nasal side when seen through the
ophthalmoscope.
•• Pigment is often seen at the edge of the optic cup.
•• An initial change that may often be observed in raised ICP is the obliteration
of the optic cup, with the margins of the optic cup becoming ill defined.
•• A little later, the origin of the retinal vessels from the optic cup cannot be
visualised.
•• As the swelling of the optic disc progresses further, the retinal vessels get
narrowed and obliterated near the optic disc. At this stage, haemorrhages
may develop and a generalised congested picture of the retina will become
obvious.
•• A small cupless disc is vulnerable to anterior ischaemic optic neuropathy
(AION). This is termed “disc at risk”.
•• Examination of the fields may show only a mild concentric contraction.
•• In the late stages, when the papilloedema is advanced, there may be attacks
of transient dimness of vision.
•• Transient obscuration of vision may be complained of when the patient
straightens himself after bending down or on getting up from bed. This is
a danger signal and should be understood as a sign of impending visual
failure. This picture may be contrasted with that of optic neuritis.
•• It is essential to differentiate between the two conditions, as early
papilloedema may be mistaken for optic neuritis.
•• In optic neuritis or retrobulbar neuritis, the changes in the optic discs are
minimal compared to the degree of loss of vision.
•• The failure of central vision occurring in optic neuritis leads the patient
to complain of severe loss of vision, whereas the optic disc itself may be
normal or may show mild congestion or slight pallor.
•• It is uncommon to have retrobulbar pain in papilloedema.
•• Papilloedema has also to be distinguished from pseudopapilloedema.
•• Hypermetropia, congenital anomaly of the disc or deposits of Drusen
may simulate papilloedema. Drusen is an inherited anomaly occurring in
about 0.3% of the population. Deposits occurring deep to the disc give
an appearance simulating disc swelling. There is no visual loss and the
prognosis is good.
•• Papilloedma may occur in only one eye if the subarachnoid space around
the optic nerve in the other eye is obliterated due to direct pressure by a
tumour. In such cases, the patient presents with primary optic atrophy in
the eye on the side of the tumour and papilloedema in the opposite eye
(Foster Kennedy syndrome).
•• When papilloedema has been persistent for a long time, visual failure may
occur even after the ICP has been reduced. In other words, onset of visual
failure may occur after successful surgery for a tumour and the unfortunate
patient may attribute this visual failure to the surgery.
•• The stages of papilloedema as graded by Frisen, et al. are as follows:
–– Grade 0 : Normal
–– Grade 1 : Minimal papilloedema characterised by a C-shaped halo
–– Grade 2 : Mild papilloedema which is characterised by a complete
halo
974
–– Grade 3 : Moderate papilloedema which is characterised by obscura-

tion of disc vessels off the disc
–– Grade 4 : M arked papilloedema characterised by obscuration of
vessels on the disc
–– Grade 5: Severe papilloedema characterised by mushroom disc with
cup obliteration
Optic Atrophy
•• Long standing papilloedema leads to blindness with secondary optic
atrophy.
•• The disc becomes white, the vessels attenuated and the disc margins
continue to be indistinct (as contrasted with primary optic atrophy).
Abducens Palsy
•• The patient may complain of diplopia and on examination show evidence
of unilateral or rarely bilateral, external rectus paralysis.
•• Owing to the long course of the nerve inside the cranial cavity, both in the
posterior fossa as well as in the middle fossa, space occupying lesions and
increased ICP tend to interfere with the function of this nerve more often
than any other cranial nerve.
•• Diplopia may be a presenting symptom of intracranial tumours.
Proptosis
•• A mild proptosis may be seen in raised ICP.
•• Unilateral proptosis of a mild degree is of localising value.
•• The lesion is often in the region of the lesser wing of the sphenoid bone or
the middle cranial fossa of the concerned side.
Disturbance of Higher Functions

•• The higher functions of the brain, like concentration, judgement and
memory, get impaired to a varying degree when ICP rises.
•• In the early stages, the patient is often aware of these defects; occasionally
the impairment may be reported by friends and relatives.
•• In frontal tumours such symptoms occur early, commonly preceding the
signs of increased ICP. On the contrary, most children who develop raised
ICP due to tumours are well behaved, quiet and remarkably mature in
their actions.
•• Generalised epilepsy may occur as a sign of raised ICP without localising
significance. This has been attributed to anoxia, venous congestion or
oedema in a brain with a low threshold for convulsions.
•• Sleep rhythm is occasionally disturbed when ICP increases, the patient
being restless and sleepy alternatively during the day and night.
Systemic Changes
•• Paroxysmal hypertension may be seen in the late stages of intracranial
tumours, especially in posterior fossa lesions.
•• Palpitation, perspiration and headache may be present with the acute rise
in blood pressure and may be mistaken as due to a phaeochromocytoma.
•• Bradycardia is a late sign of raised ICP and may also be caused by cerebral anoxia.
•• In the late stages, stupor, bradycardia and rising blood pressure are
apparent along with respiratory depression.
975
•• Increased ICP may result in abnormal impulses being transmitted to the

kidneys, resulting in renal ischaemia and leading to a rise in blood urea,
non-protein nitrogen and extracellular potassium.
•• The urinary output is normal.
•• The patient becomes drowsy and irritable and may develop tachycardia,
fits or generalised oedema.
•• The urine may show albumin with marked decrease in sodium and chlorides.
As the urine volume remains normal, the diagnosis may be missed.
•• Pulmonary oedema may be produced by increased ICP. The mechanism is
mediated through the upper cervical cord. The severe ICP leads to systemic
vasoconstriction, systemic arterial hypertension, pulmonary venous
hypertension and pulmonary oedema. Even in such a stage, a reduction
of ICP by proper therapy leads to a reversal of the signs.
•• It will thus be noted that the non-specific signs of increased ICP may
resemble systemic disease in their earlier stages.
•• Hypertension may cause headaches similar to those of a brain tumour
and in the late stages the ophthalmoscopic findings also may be similar.
•• Cerebrovascular disease also simulates the symptoms of brain tumour
in elderly people, the convulsions and deterioration in personality being
attributed to cerebral ischaemia.
•• Toxic and metabolic encephalopathy, especially lead encephalopathy and
also incipient uraemia may mimic symptoms of raised ICP.
Signs of Interference with Local Functions

•• In early cases, various combinations of signs and symptoms or syndromes
can be recognised.
•• In late cases, secondary phenomena, like, neighbourhood effects and
increasing ICP, distant effects confuse the clinical picture.
•• Hence, a careful recording of the history of the onset and of early symptoms
of the illness greatly contributes to localisation.
•• The local effects of the tumour may be either irritative or paralytic.
•• Irritation results in abnormal increase of function, e.g. generalised or focal
fits, flashes of light, tinnitus and in other bodily sensations.
•• Depending upon the site of the lesion, paralysis of local areas of the brain
manifests itself by negative signs like loss of motor power, sensation,
speech and hearing.
•• In addition, there may be positive signs of increased activity of the lower
levels of the nervous system due to release phenomena, e.g. spasticity,
grasp reflex.
Epilepsy and Brain Tumour

•• Epilepsy is a common symptom of intracranial tumours occurring in about
a third of all patients with tumours.
•• Supratentorial tumours, both extracerebral and intracerebral, manifest
epileptic seizures as a symptom in about 50% of cases.
•• These may be focal or generalised, presenting as the initial symptom and
remaining as the only symptom for a long time.
•• Convulsions may also occur in the late stages of the disease due to
increased ICP.
•• When epilepsy heralds the presence of a tumour, it occurs early in the
course of the disease. It was the first symptom in 50% of temporal tumours,
78% of frontal tumours and 93% of central tumours.
976
•• Focal epilepsy often suggests the site of the lesion.

•• Postictal weakness (Todd’s paralysis) is common and clears in a short time.
When it occurs consistently and persists for a long time, the chances of an
organic lesion being the cause of the fit are much higher.
•• Variation in the pattern of the fits with passage of time or the occurrence
of fits in clusters favours the possibility of a tumour.
Regional Signs
Subfrontal Tumours
•• Tumours in the subfrontal region grow upwards into the under surface of
the frontal lobe and may exist for a long time without causing any apparent
neurological signs.
•• In larger tumours, lack of inhibition and impulsive laughter or crying may
occur, as also pointless silly joking (moria) associated with euphoria.
•• Rage attacks may also occur.
•• There may be impairment of recent memory.
•• Excitement or hallucinations may occur due to irritation of the frontobasal
region.
•• Epilepsy may be generalised or adversive in onset.
•• Subfrontal midline lesions cause anosmia in the absence of rhinitis, as
seen in olfactory groove meningioma.
•• When the lesion extends posteriorly, optic atrophy results from pressure on
the optic nerve or chiasma or there may be a Foster Kennedy syndrome.
Frontal Lobe Tumours
•• These may exist for a long time without any physical or mental sign or
symptom, resulting in delay in diagnosis.
•• The patient may be able to carry on routine work without impairment. When
the lesion begins to spread posteriorly and involves the connections with the
opposite frontal lobe, symptoms appear, commonly termed frontal lobe signs.
•• The signs progress rapidly if the lesion is intra-parenchymal, whereas, with
extrinsic tumours the symptoms progress more slowly.
•• Lack of drive or reduction in initiative may be the first symptom and a failure
to observe accepted social norms becomes obvious.
•• There may be undue jocularity (‘Witzelsucht’).
•• There is an absence of inhibition naturally expected of a normal person in
a particular social environment.
•• This may manifest itself in an unnaturally familiar behaviour which may
be mistaken for taking liberties or for impertinence. Later, the capacity for
insight is impaired. These symptoms become more pronounced when the
lesion extends backwards to involve the association fibres of the corpus
callosum.
•• Visual inattention, confabulation and apathy may be observed.
•• There are three distinct prefrontal lobe dysfunction syndromes. They
are: (1) Dorsolateral prefrontal lobe dysfunction which is important for
working memory and adjusted behaviour; (2) medial prefrontal syndrome
which is concerned with initiation of activity and causes akinetic-abulia
syndromes and (3) orbital pre-frontal syndrome which is characterised
by hyperactivity.
•• The motor signs of frontal lobe lesions are a manifestation of impairment
of voluntary motor control, e.g. difficulty in performing serial alternating
977
tasks, motor perseveration and ataxia of the contralateral leg.

Apraxia of gait, occasionally seen in these patients, may be mistaken for
ataxia.
•• Psychoses may be simulated by a long standing frontal lesion like a
meningioma.
•• Involutional depression or presenile dementia may be diagnosed when
the patient has incontinence, apathy and dementia due to a frontal lesion.
•• Basal frontal lesions may cause excitement or hallucinations which may
lead to a mistaken diagnosis of hypomania or schizophrenia.
•• When the lateral surface of the frontal lobe is irritated, adversive fits may
occur with the head and eyes turning to the opposite side.
•• In acute frontal lesions, conjugate deviation of the eyes to the opposite side
occurs. In some chronic lesions, the eyes may tend to turn ipsilaterally.
•• Bilateral frontal lobe lesions may uncover primitive reflexes, e.g. grasp
reflex in the hand or the tonic foot response.
Tumours in the Sensorimotor Region
•• Tumours involving the sensorimotor strip are more easily diagnosed
because of the obvious impairment of motor and sensory function in the
contralateral limbs.
•• Epilepsy is a common symptom of such lesions.
•• This may be focal motor or focal sensory with or without the Jacksonian
march or generalisation.
•• Loss of power or sensation, lasting for some time after a focal attack, is
suggestive of local pathology.
•• When the function is further affected, paralysis occurs which is more
pronounced in one limb (monoplegia), or in one part of a limb.
•• Isolated digit palsies may occur. Such circumscribed pareses are common
in cortical lesions.
•• Superior and medial lesions cause weakness of the hand or face, or
dysphasia if the tumour is on the dominant side.
•• Initially, this weakness may be flaccid with diminished reflexes but soon
becomes spastic.
•• When the lesion is deep seated, even a small tumour may cause hemiplegia
with exaggerated reflexes.
•• Primitive reflexes are unmasked, e.g. grasp reflex, the bulldog reflex,
i.e. involuntary hold on an object placed between the teeth and the tonic
plantar reflex.
•• When the supplementary motor area of the dominant hemisphere is
involved, the rare clinical phenomenon of dysphonia may be observed
due to interference with the circuits linking the cortical speech area with
the thalamus.
•• Involvement of the sensory cortex is indicated by a feeling of tingling,
dysaesthesia or numbness in the contralateral limbs.
Parietal Lobe Tumours
•• The cortical sensory area forms the anterior boundary of the parietal lobe.
When the lesion spreads posteriorly, parietal lobe signs become more obvious.
•• Discrete areas of sensory loss may be detected in small focal lesions.
•• In anterior parietal lesions, tactile localisation, two point discrimination and
light touch are affected, as also joint sense, vibration sense, stereognosis
and appreciation of form and weight.
978
•• Spontaneous pain and dysaesthesia of the opposite half of the body may
be seen in some parietal lobe lesions and may resemble thalamic pain.
There will be difficulty in tactile localisation.
•• The patient is not able to appreciate differences in texture of materials,
e.g. between cotton and silk. There is also an impairment of appreciation
of differences in temperature. While a normal person can appreciate
differences between 2°C and 5°C, in parietal lobe lesions differences of
10°C may not be appreciated.
•• There is difficulty in recognising numbers written on the skin (graphaesthesia),
as also difficulty in appreciating differences in weight (abarognosia).
•• An early sign of a parietal lobe lesion is the fall of the outstretched arm.
If the patient is asked to keep both his arms stretched out in front with
the eyes closed, the arm opposite to the side of the lesion will slowly drift
downwards and outwards.
•• In pure parietal lobe lesions, inattention is an early feature. This sensory
inattention can be detected by simultaneous stimulation of identical areas
on both sides of the body.
•• Somatoagnosia leads to non-recognition of one half of the body, not shaving
one half of the face or difficulty in dressing.
•• Apraxia is often seen, especially in lesions of the left side, leading to
difficulty in writing (agraphia). Copying is not difficult.
•• Apraxia of eye movements may be observed in bilateral parietal lesions.
•• Apraxia of gait or apraxia of dressing may be an important manifestation.
•• Gerstmann described a syndrome with the chief components of: (1) finger
agnosia; (2) agraphia-apraxia of writing confined to single letters or words,
(while copying is not affected) (3) dyscalculia—difficulty in calculations; (4)
right-left disorientation. Gerstmann believed that this syndrome was due to
a lesion in the dominant (left) angular gyrus.
•• Parietal lobe dysfunction can be summarised as follows:
–– The dominant lobe is concerned with spatial motor skills while the non-
dominant lobe is concerned with spatial orientation skills.
–– Left superior parietal lobule lesions cause aphasia, agnosia, astereog-
nosis and agraphaesthesia.
–– Right superior parietal lobule lesions cause spatial agnosia, sensory
neglect, astereognosis, agraphaesthesia and dressing apraxia.
–– Left inferior parietal lobule lesions cause ideomotor/ideational apraxia
and Gerstmann’s syndrome (angular gyrus-Geschwind’s area lesion—
area 39) while right IPL lesions cause aprosody.
–– Bilateral parietal lesions cause Balint’s syndrome and movement
agnosia.
Temporal Lobe Lesion
•• Lesions in Broca’s area (posterior part of the inferior frontal gyrus) result
in non-fluent aphasia with difficulty in naming objects and with good
comprehension.
•• Lesions in Wernicke’s area (posterior superior temporal lobe) cause fluent
aphasia, with poor naming and impaired comprehension.
•• In Jargon aphasia, the tone, inflection, etc. resemble speech but the words
and phrases carry no meaning.
•• Conduction aphasia (resulting from lesions in the arcuate fasciculus
connecting Broca’s area with Wernicke’s area) resembles Wernicke’s
aphasia except that comprehension in these patients is good.
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•• Paroxysmal disturbances of speech may also be observed. Auditory

disturbances are rare with unilateral temporal lobe lesions.
•• When the medial temporal lobe is affected, the most common manifestation
is complex partial seizures (temporal lobe epilepsy). The patient may have
a cephalic or a visceral sensation as an aura.
•• There may be psychosensory or psychomotor disorders like déjà vu
phenomenon and a dreamy state.
•• Hallucinations of taste or smell are a common feature of limbic lobe epilepsy
and are more often seen in patients with tumours as compared to the more
common medial sclerosis.
•• Lesions of the medial temporal region may lead to loss of memory,
especially for recent events.
•• When the lesion is in the more posterior part of the temporal lobe, the optic
radiations are affected. As the optic radiation makes a loop (Meyer’s loop)
into the temporal lobe before proceeding to the occipital lobe, posterior
temporal lesions result in a superior quadrantanopia. (Note inferior
quadrantic defect in parietal lesions.)
•• In more medial temporal lobe lesions, the optic tract could be affected
leading to typical homonymous hemianopia.
•• Temporal lobe tumours, especially in the non-dominant side may exist for
a long time and may even raise the ICP without any apparent localising
sign. They show a greater tendency for uncal herniation than other tumours.
Occipital Lobe Lesions
•• The characteristic sign of an occipital lobe lesion is loss of vision in the
opposite visual field, the extent of the defect varying with the site and size
of the tumour.
•• Tumours compressing the outer surface of the occipital lobe usually spare
the fixation area.
•• These may also cause impairment of follow-on conjugate movement of the eyes.
•• In occipital lesions causing homonymous hemianopia, the patient can detect
moving objects but not stationary objects in the visual field.
•• Homonymous hemianopia is diagnosed at the bedside by the patient failing
to look at persons on one side of his bed. During conversation the patient
turns his head to one side to see well. Thrusting a finger near the eyes on
the hemianopic side fails to elicit the menace reflex.
•• Occipital lobe lesions may also show the phenomenon of visual inattention
or extinction. When two objects are placed on either side simultaneously,
the object in the defective field is not recognised. But as soon as the object
in the normal field is removed, the object in the defective field becomes
visible and is also recognised.
•• Seizures are less common in occipital lobe lesions compared to the other
lobes. Seizures with uniform visual hallucinations like flashes of light may
present as an early symptom of occipital lobe lesions and there may be an
adversive element at the onset of fits.
•• Unlike temporal lobe fits, these hallucinations are crude and not organised.
Distortions of images and objects (metamorphopsia) may form the visual
aura.
Lesions Near the Falx
•• These lesions compress the medial surface of the hemispheres and may
cause bilateral signs.
980
•• Spastic paraparesis occurs if the lesion is near the motor strip.

•• Similarly, focal epilepsy irregularly involving either lower limb may be
observed.
•• Irritation of the supplementary motor area may result in focal seizures with
adversion and tonic posturing of the limbs or generalised convulsions with
loss of consciousness as the initial phenomenon.
•• When the pressure is chiefly on the supplementary motor area of the
dominant hemisphere, the patient may have the rare clinical phenomenon
of spastic dysphonia.
Lesions of the Corpus Callosum
•• Being an extensive structure connecting the two hemispheres, the corpus
callosum is involved in about a third of all cerebral gliomas.
•• Being essentially a commissure between the two hemispheres, symptoms
of corpus callosum involvement depend upon the areas of the brain that
are ‘disconnected’ by the lesion.
•• In anterior lesions, frontal lobe symptoms appear more pronounced. In this
area, the tumours may extend into both the hemispheres as a butterfly growth.
•• Lesions in the middle of the corpus callosum result in impairment of sensory
and motor functions.
•• Posterior lesions cause early pressure on the third ventricle and the
brainstem.
•• Pressure on the colliculi may result in symptoms simulating a pineal tumour.
•• The common sign of callosal dysfunction is a unilateral left tactile anomia.
•• The subjects are unable to name objects placed in the left hand although
they are able to describe their features. There is also a difficulty in the cross
replication of finger positions.
Assessment of Lobar and Higher Cognitive Functions
•• The basic initial step in the assessment of higher functions is the mini-
mental state examination (MMSE).
•• Score features:
–– Orientation
–– Registration
–– Attention and calculation
–– Recall
–– Language.
•• The MMSE is 80% sensitive and 98% specific. The average score adjusted
for age and level of education is 25−30.
Frontal Lobe Dysfunction
•• Frontal lobe dysfunction is not easily picked up on psychological testing.
The patients may have a normal MMSE.
•• The Luria fist-edge-palm pattern repetition test is of value.
•• Digit repetition is the best test for attention span.
•• Cord-sorting test was found to be consistently abnormal by Brenda Milner.
Parietal Lobe Dysfunction
•• The clock drawing test which tests for constructional apraxia is a very
sensitive test for detecting cognitive disturbance.
•• It is based on the principle that to draw a clock showing a particular time,
one must know what a clock is and should have the motor co-ordination
to draw the object and also have an ability to understand the examiner;
981
which in effect tests the frontal, temporal, parietal and occipital lobes in
one test.
•• Those with left parietal dysfunction are unable to get the form right and
those with right parietal lesions are unable to place the numbers in the
correct spatial orientation.
Temporal Lobe
•• Language and memory are important functions to be tested.
•• The Babcock sentence (nonsense sentence) is useful for assessing
language.
•• Wertheim’s test is useful for assessing non-dominant temporal lobe
function-non-verbal language.
•• Lesions of the dominant temporal lobe result in impairment of intelligence
quotient (IQ) while those in the non-dominant side affect the performance
quotient (PQ).
Lateral Ventricle Tumours
•• These lesions are often silent till they grow to a large size.
•• Meningiomas, ependymomas, choroid plexus papillomas and epidermoids
occur inside the lateral ventricles.
•• Cushing and Eisenhardt described the syndrome produced by tumours in
the lateral ventricles, which is characterised by headache on the side of the
tumour, contralateral homonymous hemianopia, often with macular splitting,
contralateral hemiparesis with pronounced sensory loss sometimes
associated with trigeminal numbness, cerebellar symptoms and paralexia
when the tumour is on the left side (as it commonly is).
•• All or any of these symptoms may be present.
•• Posterior hemispheral signs are pronounced, because the majority of lateral
ventricle tumours occur in the trigone.
•• Signs due to raised ICP may occur alone without any of the above
lateralising signs.
•• The most common false localising signs are those that point to a posterior
fossa lesion.
Lesions Involving the Basal Ganglia
•• These may result in abnormal movements, rigidity or tremors.
•• Unilateral tremors may closely resemble those of Parkinson’s disease.
•• Chorea, athetosis and dystonia have been reported as the presenting
symptoms of basal ganglia tumours in children.
•• It is seldom possible to clinically suspect extension of hemispherical gliomas
to the basal ganglia, a fairly common occurrence.
•• Due to the close association with the internal capsule, these tumours often
cause contralateral motor, sensory or visual field defects.
•• Pupillary inequality and impairment of conjugate movements have been
described and are due to pressure on the midbrain.
•• Seizures may occur as drop attacks, with or without accompanying
disturbances in the eyes and limbs.
•• Loss of mirror movements is considered to be an early sign of basal ganglia
dysfunction.
Middle Cranial Fossa Lesions
•• These may be divided into sellar lesions, parasellar lesions, lesions near
the cavernous sinus and lesions of the temporal fossa.
982
•• Parasellar lesions:
–– The common parasellar lesions are meningiomas, carotid aneurysms
and tumours of the base of the skull.
–– In medial lesions, obstruction of the cavernous sinus leads to a mild
proptosis.
–– A complete or incomplete ophthalmoplegia follows due to involvement
of the III, IV and VI nerves. Often, the pupillomotor fibres are not af-
fected and thus the pupils may remain normal.
–– Involvement of the ophthalmic division of the trigeminal nerve causes
hyperaesthesia or anaesthesia of the forehead.
–– Anterior parasellar lesions in the carotid region (aneurysms) press on
the optic nerve leading to loss of vision and optic atrophy.
•• Temporal fossa lesions:
–– This being a fairly large fossa containing numerous structures, various
disturbances may arise depending on the location and direction of
growth of the tumour.
–– Anterior lesions of the middle cranial fossa may be asymptomatic for a
long time and attain a large size (meningioma).
–– Fits due to irritation of the cortex may be the only sign, followed much
later by papilloedema.
–– Of these lesions, the medial ones cause pressure on the optic nerve,
while lateral lesions may cause early bony changes, at times visible
and palpable externally.
–– Lesions in the middle may cause only a mild proptosis for a long time,
due to obstruction of the venous outflow from the orbit through the
orbital fissure.
–– In posterior lesions of the middle cranial fossa, the motor division of the
trigeminal nerve is affected with resulting weakness of the masseter,
temporalis and pterygoids on the affected side.
–– Pain and paraesthesia may be present over the trigeminal distribution.
–– The optic tract may be affected by lesions extending medially, resulting
in visual changes.
–– All middle cranial fossa lesions, if they extend superomedially, may
cause temporal lobe seizures.
–– Large lesions compressing the temporal lobe may produce temporal
lobe signs in the later stages.
Midline Lesions of the Brain
•• Tumours of the third ventricle region can be conveniently divided into five
groups: (1) anterosuperior; (2) anteroinferior; (3) inferior; (4) posterior and
(5) lateral.
•• The onset and progress of symptoms vary in these groups, although there
may be a lot of overlap in the latter.
•• Anterior third ventricle tumours (e.g. craniopharyngioma or a colloid cyst)
extending superiorly, often block the foramen of Monro. This blockage is
usually intermittent in the case of a colloid cyst and thus the patient may
suffer from intermittent bouts of headache, which in a few, gets dramatically
relieved by a change in the position of the head. The dilating anterior horn
may lead to dementia in adults. In children, anterior third ventricle tumours
may be associated with mental retardation, memory loss, weakness of the
lower limbs and occasional somnolence.
983
•• Anteroinferiorly, the lesions compress the hypothalamus and cause

endocrine symptoms. Hypersomnia, diabetes insipidus and hyperthermia
have been noted and are more common in infiltrating tumours of the third
ventricle. Pressure on the chiasma leads to field defects in such inferior
lesions. Disturbances of micturition or defaecation may occur in anterior
diencephalic lesions.
Posterior Third Ventricle Tumours

•• These infiltrate the thalamus and cause symptoms of contralateral pain,
tremors, rigidity or weakness.
•• Laterally placed tumours may simulate an early case of Parkinsonism.
•• Pinealomas and posterior third ventricle tumours may present with the
classical sign of difficulty in conjugate upward deviation of the eyes with or
without other ocular nerve paralysis (Parinaud’s syndrome). This is seen
only in about 50% of the cases and is due to pressure on the superior
colliculi by the tumour.
•• Pressure on the inferior colliculus may cause tinnitus.
•• Posterior pressure on the cerebellar peduncles may cause incoordination
and ataxia, simulating a cerebellar tumour.
•• Cysts of the third ventricle have been reported to result in to and fro
movement of the head and trunk in children: ‘bobble-head doll syndrome’.
Tumours Involving the Hypothalamus

•• Hypothalamic signs may be seen in patients with posterior fossa tumours
due to pressure on the hypothalamic nuclei by the dilating third ventricle.
•• Thus, children and adolescents with posterior fossa lesions may present
with symptoms suggestive of hypothalamic involvement.
•• A chubby child, too well behaved for his age, may be the early clinical
picture of a posterior fossa lesion.
•• The hypothalamus may also get compressed by tumours of the third ventri-
cle and adjacent lesions like a craniopharyngioma and other sellar lesions.
•• An increase in the subcutaneous fat, docility leading on to lethargy and
lack of growth of hair over the body may be seen.
•• Puberty is delayed in both boys and girls. In adults, libido is decreased and
amenorrhoea may occur. These symptoms often simulate hypopituitarism.
•• Other signs of serious interference with function may also occur like
diabetes insipidus.
•• The syndrome of inappropriate ADH secretion (SIADH) may occur.
•• In some cases, fat metabolism is disturbed leading to fat depletion, resulting
in marasmus or progeria (premature ageing).
•• A typical diencephalic syndrome characterised by marasmus, euphoria and
nystagmoid eye movements has been described in infants.
•• The failure to thrive is obvious, the child is cachectic, but the sensorium is
normal and the child remains active and playful.
Lesions of the Midbrain

•• Being situated in a strategic area between the edges of the tentorium, the
midbrain is often involved in tumours of the cerebral hemispheres due to
brain shifts and herniations.
•• Intrinsic tumours may extend into the midbrain from the hemispheres above
or from the pons below.
984
•• When the lesion arises in the ventral part of the midbrain, the oculomotor
nerve is affected as well as the crus. This leads to an ipsilateral ptosis with
contralateral hemiparesis (Weber’s syndrome).
•• The signs become bilateral as the tumour spreads to the opposite side.
•• Involvement of the tegmentum may result in coarse tremors on the
contralateral side; occasionally, when the subthalamic nucleus gets
affected, hemiballismus may result.
•• Dorsal tumours will involve the superior colliculus leading to disturbances
in upward gaze and pupillary reaction. This is also seen in tumours dorsal
to the midbrain, e.g. pineal tumours.
•• Intrinsic lesions of the brainstem occurring lower down will cause internu-
clear ophthalmoplegia. Occasionally peduncular hallucinosis may occur.
Tumours of the Posterior Fossa
•• Posterior fossa lesions may be situated in six different locations: (1) poste-
rior midline; (2) laterally, in the cerebellar hemisphere; (3) anterolaterally,
in the cerebellopontine angle; (4) anterior midline, in front of the pons
and the medulla; (5) intrinsic, inside the brainstem or (6) inside the fourth
ventricle or aqueduct.
•• Cerebellar functions may be affected by lesions of the vermis, of the
cerebellar hemispheres or of the cerebellopontine angle.
•• Cerebellar disturbances may also be seen in brainstem lesions if the fibre
connections passing through the cerebellar peduncles get involved.
•• All the manifestations of motor cerebellar dysfunction, whether of the
lobes or of the vermis, are attributable to asynergia, ataxia, dysmetria and
hypotonia of the muscles.
•• Based on these basic disturbances, many symptoms and signs appear, and
numerous tests have been devised to reveal early dysfunction.
Posterior Midline Lesions
•• The vermis of the cerebellum occupies the posterior midline and is involved
in lesions of this region, e.g. vermian astrocytomas, ependymomas,
medulloblastomas, a dilating fourth ventricle, posterior midline cysts,
tuberculomas and dermoids.
•• The vermis of the cerebellum is concerned mainly with the control of the
muscles of the trunk and the muscles of posture, whereas the cerebellar
lobes exert control over the muscles of the ipsilateral limbs, chiefly of the
upper limb.
•• In lesions of the vermis an early symptom is truncal ataxia and difficulty in
controlling the lower limbs.
•• The first evidence of such a disability in a child may be its tripping over
steps which it could previously negotiate easily.This may be followed by
mild unsteadiness of gait, leading to an inability to walk or stand.
•• At the same time it will be apparent that the child can use its upper limbs
effectively, e.g. while sitting it can take its hand or a spoon to its mouth.
The finger-nose test is normal. Such pure midline vermis syndromes are
seen in early cases, before the tumour extends to the cerebellar lobes.
Nystagmus is usually absent, but when seen, is rapid, fine and symmetrical.
•• Large tumours of the vermis extend into the cerebellar lobes producing
signs in the upper limb. They also compress the fourth ventricle resulting
in increased ICP, headache and vomiting. When extending higher up,
functions of the fourth cranial nerve may be involved.
985
Cerebellar Hemisphere Lesions

•• The common symptom of a cerebellar lobe lesion is the difficulty in using
the ipsilateral upper limb, although the lower limb may also be involved.
•• The patient complains of clumsiness of movement of the upper limb.
•• In a right handed individual, this may manifest itself early as difficulty in writing.
•• The letters become bigger than usual (macrographia).
•• There is difficulty in picking up objects or in holding them steady.
•• On examination there is a drift of the outstretched hand.
•• The cerebellar disturbance is obvious only when the limb is put to action
(action tremor) and disappears if the limb is supported or is resting.
•• The finger-nose test reveals intention tremors and past-pointing.
•• In early cases, an involuntary closure of the eyelid as the finger reaches
the nose may indicate a cerebellar dysfunction.
•• There is an inability to make rapid alternate movements of the limb
(dysdiadochokinesia).
•• The heel-knee test is impaired.
•• The knee jerk is pendular and all the deep tendon reflexes are intact.
Hypotonia is evident on testing the muscle tone.
•• If the forearm is jerked quickly up and down, the hand will flap, indicating
lack of tone in the forearm muscles.
•• In an unconscious patient, the way in which an upheld limb drops on the
bed can indicate hypotonia.
•• Until the lesion begins to invade the vermis or the brainstem all the
symptoms are confined to the ipsilateral limb.
•• Asynergia of the pharyngeal and tongue muscles leads to slurred (words
running into each other) or staccato or scanning speech (words split
syllable by syllable).
•• Nystagmus, evidence of asynergia of eye muscles, is seen in cerebellar
lesions only when the vestibulo-cerebellar connections (dentate nucleus)
begin to get affected. Nystagmus is not seen in laterally placed cerebellar
hemisphere lesions.
•• In unilateral cerebellar lesions, the nystagmus is slower and coarser when
the eyes are directed towards the side of the lesion than towards the
opposite side. Such nystagmus disappears in a few weeks. If persistent, it
will indicate pressure on or invasion of the vestibular nuclei.
•• The cerebellum has a role in cognition as well. Diseases of the cerebellum
are known to cause attention deficits and disturbed executive function,
visuospatial disorganisation and impaired visuospatial memory, personality
change and linguistic difficulties such as dysprosodia, agrammatism and
mild anomia.
•• Lesions of the cerebellum in children have been reported to produce
mutism.
Cerebellopontine Angle Tumours
•• The structures in this region are the V, VII and the VIII nerves anteriorly,
the cerebellum posteriorly, the brainstem medially and the lower cranial
nerves inferiorly.
•• Any one or all these structures get involved gradually as the lesion enlarges.
•• When the tumour arises primarily from the eighth nerve, tinnitus and impairment
of hearing are early symptoms. Disturbances of vestibular function, like
giddiness or vertigo, are usually transient phenomena, compensation taking
place very early.
986
•• An early sign of trigeminal affection is the loss of corneal sensation as

shown in a diminution or abolition of the corneal reflex.
•• If there is a fully established seventh nerve palsy preventing closure of the
ipsilateral eyelid, the efficacy of the corneal reflex is judged by observing
the rolling up of the ipsilateral eyeball (Bell’s phenomenon) and closure of
the opposite eyelid.
Prepontine or Clival Tumours
•• Anterior midline tumours, especially when slow growing, may exist for a
long time without any apparent clinical signs.
•• The lesions located anterior to the brainstem are chordomas, chondromas,
clivus meningiomas, nasopharyngeal growths and basilar aneurysms).
•• Unprovoked, uncontrolled laughter is a characteristic symptom of
prepontine tumours.
•• Pressure on the anterior aspect of the brainstem may lead to bilateral
pyramidal or bilateral cerebellar signs.
•• As the tumour enlarges, multiple cranial nerves may be involved bilaterally.
Intrinsic Lesions of the Brainstem
•• The most common lesion is a glioma, rarely a metastatic lesion or an
angioma may be seen.
•• In India, the possibility of a brainstem tumour being a tuberculoma must always
be kept in mind. These constitute more than 10% of all brainstem tumours.
•• Likewise, it must be remembered that tuberculous meningitis may mimic
a brainstem tumour.
•• Headache is uncommon in brainstem gliomas, whereas it is a predominant
symptom in tuberculous meningitis.
•• Exacerbations and remissions of symptoms have been noted in some
brainstem gliomas, thus mimicking multiple sclerosis.
•• Gaze palsy, multiple cranial nerve involvement, cerebellar signs and
bilateral long tract signs, in various combinations, constitute the clinical
features of brainstem lesions.
•• An early sign of an intrinsic brainstem tumour is external rectus weakness
in one eye followed by facial palsy, swallowing difficulty and unsteadiness.
•• Examination shows a combination of multiple lower cranial nerve palsies
and motor and sensory long tract signs. This is specially seen in exophytic
brainstem tumours.
•• Unilateral or bilateral horizontal conjugate gaze palsy is characteristic of
a lesion at this site.
•• Internuclear ophthalmoplegia due to involvement of the medial longitudinal
fasciculus, when seen, is diagnostic of an intrinsic brainstem lesion. On
attempted gaze towards either side, there is paresis of adduction and an
associated nystagmus of the abducting eye.
•• Another ocular phenomenon seen in brainstem lesions is vertical
nystagmus. This sign is always indicative of nervous system involvement,
especially of the caudal brainstem, as labyrinthine disease cannot produce
vertical nystagmus.
•• Papilloedema is seen in only 15% of cases.
Tumours of the Fourth Ventricle
•• These tumours usually grow to a large size and fill up the ventricle before
causing signs and symptoms of increased pressure.
•• Small tumours may obstruct the aqueduct early.
987
•• A common and early symptom, especially in children, is vomiting unas-

sociated with abdominal discomfort or nausea. An otherwise healthy child
that begins to vomit without reason and falters in its gait must immediately
be suspected of harbouring a midline vermis lesion encroaching onto the
fourth ventricle.
•• Unsteady gait, giddiness or vertigo, nystagmus and lower cranial nerve
palsies become evident much later.
Tumours at the Craniovertebral Junction
•• These are difficult to diagnose, being in the borderline between the brain
and the spinal cord.
•• In the absence of symptoms and signs of raised ICP, lesions at the CV
junction may masquerade as disseminated sclerosis, amyotrophic lateral
sclerosis or spinocerebellar degeneration. They may mimic the clinical
picture of craniovertebral anomalies.
•• Lesions at this level may exist for a long time without causing any apparent
neurological deficit.
•• A large cisterna magna provides a lot of space for the growth of such
tumours.
•• Those arising intracranially cause obstruction to the CSF flow and raise
the ICP without producing localising signs.
•• They may also cause lower cranial nerve palsies.
•• Occasionally, the hypoglossal nerve may be involved leading to wasting
and weakness of one-half of the tongue.
•• Pressure on the brainstem may lead to bilateral pyramidal signs.
•• Cerebellar signs are occasionally seen.
•• If the tumour is inferior, occipital neuralgia with a stiff neck, often mistaken
for a long time for tension headache, may be the only symptom.
•• Numbness over the occipital nerve distribution with signs in the upper and
lower limbs that occur later, give a clue to localisation.
•• Varying degrees of signs and symptoms of upper cervical cord involvement
confuse the clinical picture.
Neighbourhood Signs
•• In addition to the local signs, neighbourhood effects are often seen in
ICSOL.
•• As the lesion grows in size, the neighbouring structures get compressed
or infiltrated, the resulting symptomatology depending on the direction of
growth of the lesion.
•• The neighbourhood effects may also be caused by secondary phenomena,
the most common being oedema.
•• Oedema surrounding a space-occupying lesion varies in its intensity and
severity depending upon the nature of the original lesion.
•• Oedema around a tuberculoma, a glioblastoma or a metastasis could be
pronounced and thus lead to neurological symptoms far more extensive
than could be caused by the actual size of the tumour.
•• Neighbouring structures may also suffer from a steal of blood supply as may
happen in an arteriovenous malformation or in a highly vascular tumour.
Herniation
•• Owing to the softness and compressibility of the brain a growing tumour
is able to displace the brain substance. This displacement modified by
988
the presence of dural partitions inside the cranial cavity results in brain
herniations.
•• Depending on the site of the tumour and the direction of the pressure,
the herniation may take place under the falx, through the tentorium or the
foramen magnum.
•• In very acute and severe rise of ICP, brain matter may herniate through
the exit foramina of the cranial nerves.
Subfalcine Herniation
•• In supratentorial space occupying lesions, the ipsilateral cerebral
hemisphere is compressed and pushed against the falx cerebri.
•• The portion nearest the dural partition, namely the cingulate gyrus, herniates
under the free edge of the falx. Although, on rare occasions, this may result
in occlusion of the anterior cerebral artery, such herniation does not cause
any serious problem.
Tentorial Herniation
•• As the supratentorial lesion grows in size, the brain not only gets pushed
across the midline but herniates downwards through the tentorial hiatus.
•• The structures (close to the tentorial edge) that herniate are the uncus and
hippocampal gyrus which insinuate themselves between the brainstem
and the tentorial edge.
•• On the other hand, instead of the temporal lobe, the brainstem may itself
be pushed down.
•• Depending on the site of the causative lesion and the direction of the
pressure, tentorial herniation may chiefly be in its anterior or posterior part
and in advanced stages may be complete.
•• In anterior herniation, the third nerve and the crus are involved leading to
a dilating pupil and a contralateral hemiplegia.
•• In some cases, when the brainstem is pushed against the opposite tentorial
edge, an ipsilateral hemiplegia may result (Kernohan’s notch).
•• The shift of the brainstem also leads to a kinking of the aqueduct with
secondary blockage of the CSF flow, which further aggravates the
supratentorial pressure.
•• A complete bilateral tentorial herniation may block the CSF pathways
around the brainstem and further disturb the CSF flow and absorption.
•• In rare instances, the posterior cerebral artery may get compressed,
resulting in occipital infarction and hemianopia or cortical blindness if both
arteries are involved.
•• In posterior lesions, the anteromedial portion of the occipital lobe (the
precuneus) herniates into the cisterna ambiens and presses on the colliculi
and the midbrain. This may lead to varying degrees of oculomotor palsy,
progressive deafness and decerebrate rigidity. There may also be paralysis
of upward gaze, as well as hemianopia.
Cerebellar Herniation (Tonsillar Herniation)
•• In generalised increased ICP, as well as in posterior fossa lesions, the
ICP may force the posterior fossa structures down through the foramen
magnum.
•• The cisterna magna gets obliterated.
•• The tonsils of the cerebellum, which are situated near the margin of the
foramen magnum, are pushed down through it and may reach the level of
the second cervical vertebra.
989
•• The crowding of structures in the foramen magnum aggravates the ICP by

a secondary blockage of the exit of CSF.
•• Pressure on the upper cervical nerves leads to neck rigidity and torticollis.
•• In the presence of a persistent herniation, a sudden rise in ICP precipitated
by coughing or sneezing may quickly squeeze the medulla resulting in rapid
respiratory failure followed by cardiac failure and death.
•• Usually the stage of respiratory failure lasts for some minutes before
cardiac failure sets in.
•• Even at this stage, it is possible to save the patient by energetic treatment
to reduce the ICP.
•• Mild degrees of tonsillar herniation are seen in most cases of increased ICP.
•• In unilateral cerebellar lesions, only the tonsil of the affected side may be
found herniated.
Retrograde Tentorial Herniation
•• In some cases of posterior fossa tumours, when the pressure in the posterior
fossa is much higher than the pressure in the supratentorial compartment,
the structures near the tentorial hiatus may be pushed upwards.
•• This may cause secondary pressure on the brainstem.
•• Such an emergency sometimes arises as a consequence of a CSF diversion
procedure for hydrocephalus.
•• The patient may suddenly go into decerebrate rigidity with autonomic
disturbances, followed later by respiratory failure.
False Localising Signs

•• Neighbourhood or distant effects may present themselves as primary
symptoms, before any localising sign of the tumour becomes obvious.
•• Practically, all possible neurological signs have been reported as false
localising signs.
•• Only a few common ones are mentioned here:
–– Ipsilateral hemiplegia lateralising the lesion to the wrong side. Ipsilat-
eral hemiplegia may also occur due to: (a) direct pressure acting on the
opposite internal capsule due to the configuration of the falx cerebri;
(b) longitudinal stretching of the opposite internal capsule (c) dilatation
of the opposite lateral ventricle, especially when there is a block of the
foramen of Monro and (d) uncrossed pyramidal tracts.
–– The presence of frontal lobe signs in cerebellar tumours and cerebellar
signs in frontal lobe tumours have already been mentioned.
–– A highly vascular lesion of the temporal lobe may steal blood from the
frontal region leading to the appearance of frontal lobe localising signs.
–– Cerebellar signs in a craniopharyngioma.
•• In summary, therefore, a patient with an intracranial space occupying lesion
may present with one or more of the following:
–– Symptoms and signs of raised ICP
–– Focal neurological deficit
–– Focal or generalised epilepsy
–– Psychiatric symptoms
–– Endocrine disturbances
–– Visible deformity of the head
–– A combination of any or all of these.
130
CHAPTER Supratentorial
Astrocytomas
INTRODUCTION
•• Gliomas constitute 35–50% of all intracranial neoplasms.
•• Gliomas are seen at all ages from the just born to the nonagenarian.
•• Nearly two-thirds of all cases of supratentorial gliomas occur in the third
to fifth decade.
•• With the exception of meningioma, all brain tumours occur more frequently
in males.
•• The increased incidence in men is mainly due to increased frequency of
malignant astrocytoma and glioblastoma.
•• Children of mothers residing within a mile of certain toxic chemical factories
during pregnancy have been shown to have a risk of brain cancer.
•• Ionising radiation exposure (therapeutic, occupational or accidental) has
been proved to increase the risk of malignant glioma.
PATHOLOGY
Location of Gliomas
•• The majority of cerebral gliomas are located in the frontal, temporal and
parietal lobes and the incidence is proportional to the size of each lobe.
•• Tumours often transcend anatomical boundaries, though in the early
stages many tumours are confined to the area of the gyrus and grow in
size expanding the gyrus.
•• The corpus callosum is often invaded by a lobar tumour but it may be the
site of origin too.
•• The thalamus, corpus striatum, pineal gland and pituitary fossa are the
less frequent sites of origin.
•• Rarely, gliomas are multicentric in origin or may occur in the same patient
at two different sites after a long time interval.
Gross Pathology
•• The low-grade tumours tend to be poorly demarcated from the surrounding
brain.
•• They are relatively less vascular and appear grey.
•• There is hardly any oedema in the surrounding white matter. In fibrillary
astrocytomas, the consistency is tougher than the normal white matter.
•• The subtle colour difference between the tumour and the normal brain
is more apparent under the lighting and magnification of the operating
microscope than to the naked eye.
Chapter 130 • Supratentorial Astrocytomas
991
•• A single large cyst or a honeycombed appearance due to multiple small

cysts may be seen.
•• The more malignant tumours may be more granular, pinkish and vascular.
•• As the tumour grows, the central part becomes necrotic.
•• The term “angioglioma” is used to describe a low-grade tumour with
vascularity mimicking a cavernous angioma or arteriovenous malformation.
•• The glioblastoma shows a variegated appearance, true to the tag of
“multiforme” in its name.
•• Pale yellow areas of necrosis or lipid accumulation, black areas of old
haemorrhages, purple thrombosed vessels and cystic areas containing
bright yellow fluid are interspersed in a soft pinkish-grey mass that is
deceptively well circumscribed.
•• The swelling and peritumoural oedema are disproportionately more for the
size of the tumour.
•• Involvement of an entire frontal or temporal lobe is characteristic.
•• A glioblastoma that starts de novo and grows rapidly is called primary
glioblastoma.
•• A pre-existing low-grade astrocytoma may turn anaplastic and this gives
rise to the secondary glioblastoma.
Spread
•• Gliomas spread within the neuraxis through the subarachnoid,
subependymal, intraventricular or direct brain penetration routes in the
descending order of frequency.
•• If extensive, such a spread is called “leptomeningeal gliomatosis”.
•• Superficial gliomas may invade the meninges. This invokes a fibroblastic
proliferation and the tumour then simulates a meningioma at surgery.
•• Biopsies from the superficial part of such a tumour may mistakenly be
reported as meningioma.
•• Spread along the subarachnoid cerebrospinal fluid (CSF) pathways as
happens in an ependymoma or a medulloblastoma is rare.
Extracranial Metastases
•• Extracranial metastases of brain tumours are uncommon because of the
absence of lymphatic drainage.
•• They may occur after a craniotomy that opens paths of exit from the brain.
Extracranial metastases in the absence of a previous craniotomy have
been reported in a few cases.
CLASSIFICATION AND GRADING

•• Bailey and Cushing (1926) put forth the classification of gliomas on the
basis of possible histogenesis.
•• Penfield, Cone and Elvidge (1931) retained some of the 14 terms from
this terminology (such as medulloblastoma) but replaced others (e.g.
spongioblastoma multiforme was changed to glioblastoma multiforme).
•• The criteria of a grading system of gliomas are:
–– The grade should predict clinical behaviour
–– The system must be objective and should not allow inter-observer
variation.
•• Kernohan at Mayo Clinic divided astrocytomas in to grades 1 to 4 in the
increasing order of malignancy.
992
•• Zulch (1979) authored the World Health Organization (WHO) classification

of brain tumours.
•• The Russell and Rubinstein school slightly modifies the 1993 WHO revised
scheme of Kleihues, Burger and Scheithauer.
•• The fourth edition of the WHO classification (2007) adds several new tumour
types and recognises genetic profiling.
•• The new glial-neural tumours added in this edition are pilomyxoid astrocytoma,
papillary glioneuronal tumour, angiocentric glioma and pituicytoma.
MICROSCOPIC PATHOLOGY
Histological Variants
Pilocytic Astrocytoma
•• It occurs in the cerebellum and hypothalamus-optic pathway.
•• Pilocytic astrocytomas with identical radiological appearance, histological
findings and good prognosis are seen in the temporal and parieto-occipital
lobes in the first three decades of life.
•• Adult pilocytic astrocytomas might recur frequently and may not behave in
a benign fashion unlike the juvenile cases.
Protoplasmic Astrocytoma
•• It has not been accorded a separate status in the recent classification.
•• It is composed of process-poor astrocytic cells and a microcystic background.
•• It is a rare variant occurring in about 5% of low-grade astrocytomas affecting
mainly young males.
•• Complete excision may be beneficial, but adjuvant therapy appears to have
no effect on outcome.
Subependymal Giant Cell Astrocytoma
•• This type of astrocytoma is characteristic of tuberose sclerosis.
•• The lesions arise in the lateral ventricle near the foramen of Monro.
•• Cellular pleomorphism, mitosis and foci of necrosis are seen, but do not
indicate a worse prognosis for this tumour.
•• Immunohistochemistry often shows negativity for glial fibrillary acidic protein
(GFAP) and positivity for neuron specific enolase (NSE) or synaptophysin.
•• Adjuvant therapy is not needed and recurrence free survival is long.
Desmoplastic Infantile Astrocytoma
•• It appears to arise from the subpial astrocyte.
•• The tumour is seen in the frontal or parietal lobe and grows to a large size
with a big cyst.
•• The cyst wall, even if enhancing, does not contain tumour.
•• Additional neuronal differentiation is possible and then it is called
desmoplastic infantile ganglioglioma.
•• They are usually resectable and the prognosis is favourable.
Angiocentric Glioma
•• It has been recently included in the WHO classification.
•• It occurs in the cortical-subcortical areas of the temporal or parietal lobes
and presents with refractory epilepsy from childhood.
•• The characteristic feature is prominent perivascular tumour cell
arrangements with features of astrocytic/ependymal differentiation, but
lacking neoplastic neuronal features.
•• Mitosis, necrosis and vascular proliferation are not seen.
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Pilomyxoid Astrocytoma
•• It is a recently described solid, circumscribed tumour occurring in the
hypothalamic region of young children.
•• It is composed of a monomorphous population of bipolar tumour cells within
a rich myxoid background, with a conspicuous angiocentric arrangement.
•• This tumour is graded as WHO grade II.
•• It behaves more aggressively than pilocytic astrocytomas in the same
location.
Chordoid Glioma
•• It is an uncommon low-grade tumour arising in the third ventricular region, in
middle-aged women.
•• It shows chordoma-like histologic features including lymphoplasmacytic
infiltrates and Russell bodies.
•• Immunohistochemically, the tumour cells are positive for GFAP, neurofilaments
and NSE, suggesting a divergent neuronal and glial differentiation.
•• The Ki-67 index is low.
Pleomorphic Xanthoastrocytoma
•• It is seen in the second decade of life.
•• Most of these are located in the temporal lobe and involve the cortex,
accounting for their presentation with epilepsy.
•• The radiological findings are similar to the cystic pilocytic astrocytoma.
•• Their well-circumscribed nature allows total excision.
•• The tumour shows a high degree of cellular pleomorphism.
•• Their characteristic yellow colour is due to lipid accumulation.
•• Therefore, it needs to be differentiated from the lipidised glioblastoma.
•• An abundant reticulin network is produced due to infiltration of the meninges.
•• The GFAP positivity proves its astrocytic origin.
•• Demonstration of a basal lamina by electron microscopy suggests that the
tumour might arise from the subpial astrocyte.
•• The clinical behaviour is like a low-grade astrocytoma in spite of the
pleomorphic and strikingly “malignant” histological appearance.
Gliofibroma
•• It is a rare glio-mesenchymal tumour composed of astrocytic and benign
mesenchymal components, usually seen in the first two decades of life.
•• It has not been accorded a separate status in the recent WHO classification.
•• On imaging and at surgery it mimics a meningioma.
Gemistocytic Astrocytoma
•• It consists entirely of large astrocytes with no or short, thick or no processes
called gemistocytes.
•• The cell bodies rather than the processes are GFAP positive.
•• Often they are only a component within a fibrillary astrocytoma.
Giant Cell Glioblastoma
•• It is a variant of glioblastoma that seems to have a better prognosis than
the garden variety glioblastoma multiforme.
•• A few multinucleated giant cells may be seen in any glioblastoma, especially
after radiotherapy.
•• In the giant cell glioblastoma variant practically every cell is a giant cell.
•• The giant cells are GFAP positive and sometimes they are lipidised.
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Gliomatosis Cerebri
•• It involves a whole hemisphere or even both hemispheres and spinal cord.
•• The areas of enhancement are the foci of higher grade of malignancy.
•• Gliomatous change occurring simultaneously over a wide field and extreme
motility of the transformed cells has been held as the cause of a very wide
area of involvement.
•• Stereotactic biopsy and initial temozolomide therapy have been
recommended to delay radiation therapy in those patients who are often
young children.
Gliosarcoma
•• It is a rare malignancy consisting of gliomatous and sarcomatous elements.
•• It shares the aggressive clinical behaviour and genetic similarities with
glioblastoma.
•• The tumour is reported to invade outside the dura directly.
AETIOLOGY AND PATHOGENESIS

•• The aetiology of the majority of gliomas is not known.
•• The known causes include exposure to ionising radiation and genetic
predisposition, but these are rare.
•• Viral aetiology has been suggested but not proved.
Radiation Therapy Induced Gliomas

•• Radiotherapy for other scalp, brain or head and neck lesions has been
reported to cause glioma.
•• They generally arise after a latency of 8–25 years and are within the
previous field of radiation.
•• They are generally anaplastic and carry a poor prognosis.
•• Children treated for acute lymphoblastic leukaemia with craniospinal
irradiation have been reported to develop malignant glioma.
Hereditary Syndromes and Glioma

•• There are hereditary neurological tumour syndromes associated with
gliomas.
•• Children with trisomy 21 (Down’s syndrome) have been reported to have a
higher incidence of gliomas.
•• Though rare, the heritable neurological tumour syndromes are important, as
they throw light on glioma genesis.
Cytokinetic Studies and Labelling Index

•• The factors determining the growth of the tumour are the cell cycle time,
the growth fraction, tumour doubling time and cell loss.
•• The parameter most commonly studied is the labelling index (LI), which
reflects the proportion of cells in the DNA synthesis phase.
•• The initial studies showed LI < 1% in low-grade glioma and LI > 5% in
glioblastomas.
•• The malignant tumours show greater degree of aneuploidy or polyploidy
and greater proportion of cells in S phase of mitosis.
•• Increasing values of Ki-67/MIB-1 LI with increasing grade of malignancy
in astrocytoma has been noted.
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Genetic Abnormalities in Non-Syndromic Glioma

•• Tumour results when tumour promoter genes are over-expressed or when
tumour suppressor genes are under-expressed.
•• The genetic alterations are recognised from the losses or gains in the
chromosomal arms and loss of heterozygosity (LOH).
•• Glial tumours are genetically heterogeneous.
•• Primary glioblastoma, which occurs predominantly in elderly males, has a
short evolution and a rapidly fatal course.
•• The secondary glioblastoma that arises from a previous low-grade
astrocytoma is seen in younger patients, has no gender predilection,
presents with a longer history and runs a slower course.
•• Though histologically the primary and secondary glioblastomatous areas
are indistinguishable, their genetic makeup is quite different.
•• The primary glioblastoma shows LOH on chromosome 10q, epidermal
growth factor receptor (EGFR) amplification, p16INK4a deletion, and
phosphatase tensin homology gene on chromosome 10 (PTEN) mutations.
•• The secondary glioblastomas show p53 mutations and LOH on 10q.
•• The tumour suppressor gene p53, located on chromosome 17p, is known
as the “guardian of the genome”.
•• The normal (wild) p53 product is a protein that has a very short half-life
and cannot be detected routinely.
•• The abnormal (mutated) p53 product is stable and can be detected. Hence,
immunoreactivity to p53 product (TP53) indicates a mutated abnormal gene.
•• The p53 protects cells from cancer by preventing cells with damaged DNA
from proliferating wantonly.
•• This is achieved by cell-cycle arrest, which facilitates cell repair; and
apoptosis, which ensures the death of cells too severely damaged to be
repaired.
•• The p53 also has an important role in angiogenesis and tumour invasion,
processes fundamental to malignancy.
•• Over-expression of p53 has been correlated with adverse prognosis in
childhood malignant glioma.
•• Another important gene is the Bc12 proto-oncogene located on
chromosome 18.
•• The Bc12 product is antiapoptotic.
•• Over-expression of Bc12 gene product found in primary central nervous
system tumours is known to make tumours resistant to chemotherapy or
radiotherapy.
Role of Growth Factors

•• The mutations in glioma cells cause amplification and over-expression of
epidermal, platelet derived and fibroblast growth factor receptors.
•• In addition, the vascular endothelial growth factor (VEGFR) amplification
causes angiogenesis.
•• The LOH in 10q causes inactivation of PTEN, a gene downstream of focal
adhesion kinase, which controls cell migration and invasiveness.
•• Cyclo-oxygenase 2 (COX-2) is an enzyme that is over-expressed in glioma
cells as compared to normal astrocytes. This over-expression is associated
with angiogenesis and resistance to apoptosis.
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Role of Stem Cells

•• The malignant gliomas retain a small number of brain tumour stem cells
(BTSC), which are derived from the neural progenitor/stem cells.
•• These are responsible for recurrence of tumour.
•• The BTSC progresses in to tumour due to changes in signalling and control
pathways such as ras, retinoblastoma (Rb), Notch and sonic hedgehog
(Shh).
Role of Environmental Factors

•• Recently, human cytomegalovirus (HCMV) antigen and DNA have been
demonstrated in glioma cells.
•• This herpes virus exhibits glial tropism.
•• Tumour hypoxia is known to promote tumour recurrence and decreases
the efficacy of radiotherapy or chemotherapy.
•• This effect may be mediated by erythropoietin.152 Vitronectin in CSF
promotes glial tumour cell mobility.64
CLINICAL FEATURES
•• The signs and symptoms of supratentorial glial tumours depend upon the
site, the size, the histological nature and the rate of growth of the tumour.
•• The onset of symptoms is usually insidious and the course progressive.
Duration and Progression

•• The duration of symptoms is usually 2–3 years for low-grade tumours,
1–2 years for the intermediate grades and a few months or weeks for
glioblastomas.
•• It is much longer for oligoastrocytomas and oligodendrogliomas.
•• Stepwise deterioration may be observed with anaplastic astrocytomas.
•• Sudden deterioration may set in during an otherwise gradual course, due
to haemorrhage in the tumour or rapid necrosis or onset of oedema. These
are seen more frequently in glioblastomas.
•• A slow growing astrocytoma may suddenly change its character and turn
into a glioblastoma, resulting in a rapid downhill course in a patient with
an otherwise slow course.
•• Slow growing tumours in the so-called silent areas of the brain, (the frontal
lobes and the non-dominant temporal lobe) may acquire a large size without
producing any symptoms and then show rapid deterioration and present
with a short history due to decompensation of the intracranial pressure
(ICP) dynamics.
•• On the other hand, a small strategically located astrocytoma may, by
manifesting an epileptic attack or early focal deficit, be associated with
a short history. Thus, the duration of the illness may not provide a true
indication of the histological nature.
•• Supratentorial gliomas may manifest themselves by symptoms and signs
of raised ICP, epilepsy, progressive neurological deficits and cognitive/
behavioural dysfunction.

•• Headache and vomiting are the initial symptoms in about one-third of
patients with supratentorial gliomas.
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•• The headache is generalised and progressive, sometimes lateralised to

the side of the tumour.
•• The frequency and severity of symptoms of raised ICP is greater in patients
with more malignant tumours and with gliomas situated nearer the midline.
•• Signs of ICP like papillooedema and abducens palsy are less common
nowadays, due to earlier diagnosis with the widespread use of imaging.
Epileptic Seizure
•• Two-thirds of patients with a supratentorial glioma are likely to get a seizure
sometime during the course of their illness.
•• Low-grade tumours also tend to present with seizure as their only mani-
festation.
•• Adult onset focal seizures, changing character of seizure over time,
prolonged postictal (Todd’s) paralysis, and onset with status epilepticus
have been traditionally held to arouse the suspicion of a tumour.
•• Postictal paralysis may be prolonged or may not recover fully and may
increase with every seizure.
•• Generalised epilepsy of long duration and seizure history in childhood do
not rule out the possibility of an underlying tumour.
•• Simple partial seizure, with or without generalisation, is the most frequent
type accounting for 47% of patients with glioma presenting with seizure.
•• Generalised tonic-clonic seizure was seen in 35% of patients and complex
partial seizure in 10% of patients.
•• Tumour is the most likely cause of seizures in patients with olfactory or
gustatory aura.
•• The recurrence of attacks after a long seizure free interval in a treated
patient generally indicates recurrence of tumour.
Focal Neurological Dysfunction

•• Neurological deficit is not a common initial symptom, since a large
percentage of hemispheric gliomas are located in the “silent” frontal and
temporal lobes.
•• It is predominantly a feature of tumours located in or near the sensorimotor
cortex. Here, it generally starts as postictal deficit.
•• Comprehension dysphasia is often overlooked or confused with memory
impairment or a psychiatric illness. Patients developing hemianopia are
often unaware of the deficit but bump in to objects on the hemianopic side.
Similarly, the patient also ignores sensory symptoms due to parietal lobe
involvement. Dressing apraxia or the neglect of the contralateral half of the
body or visual field may be observed by others rather than the patient. While
a neurological deficit, as the initial symptom, is observed in 3% of cases
only, nearly 60% of patients have some deficit at the time of presentation.
Motor weakness is more common with malignant glioma than low-grade
glioma. Incontinence, when awake, may be the presenting symptom in
frontal or midline tumours.
Cognitive Dysfunction
•• Apathy, change in personality, impairment of memory, inattention,
inappropriate social behaviour, irritability, verbal-motor perseveration and
psychomotor retardation are common symptoms. This is especially true
for tumours of the frontal lobe and temporal lobe.
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•• Basal frontal tumours present with pseudomania, lateral frontal tumours

with pseudodepression and medial frontal lesions with pseudodementia
and akinetic state.
•• Impairment of memory is seen with frontal and temporal lobe tumours.
Uncommon Presentations
•• Enlarging size of the head, irritability and a delay in achieving developmental
milestones may be the presenting features of gliomas in children.
•• Temporal lobe tumours may present in to the orbit or infratemporal fossa.
•• Hemiatrophy of the contralateral half of the body (seen in slow-growing
parietal lobe tumours occurring at a young age) is a rare manifestation.
INVESTIGATIONS
Imaging
•• Till the advent of CT plain X-ray skull was the initial investigation for a patient
suspected to harbour a brain tumour. The plain X-ray findings of these
patients (detailed else where) could provide valuable diagnostic information.
•• The CT is generally the first investigation done for a patient with a suspected
intracranial mass lesion, as it is more rapid, less expensive and generally
available.
•• The CT can be done more easily than MRI in demented, restless or
intubated patients.
•• It can also be done in claustrophobics and patients with pacemakers.
•• Calcification, fresh haemorrhage and bony anatomical landmarks are well
made out in CT.
•• Contrast CT study may be avoided if gadolinium enhanced MRI is going
to be done.
•• The MRI is more sensitive to pathological changes in the tissue and superior
in assessing tumour volume or tissue characteristics.
•• Patients presenting with seizures alone are generally investigated directly
with MRI.
Low-Grade Astrocytomas
•• Low-grade astrocytomas take on one of two morphologies on imaging.
•• The diffuse infiltrative low-grade astrocytoma is seen as a homogeneous
hypodense (about 20 HU) area with indistinct borders on non-contrast CT.
•• They are hypointense in T1W and hyperintense in T2W, PD and fluid-
attenuated inversion recovery (FLAIR) MR images.
•• There is little or no peritumoural oedema.
•• Since both the tumour and the oedema appear hypodense on CT, the judgment
about the absence of oedema is made from the lack of much mass effect.
•• There is usually no contrast enhancement.
•• Focal hyperdensities on CT may be due to calcium or blood.
•• Calcification is seen more frequently in about 20% of astrocytomas. It is
better appreciated on CT and generally indicates slow growth.
•• Haemorrhage is seen if there is an oligodendroglial component.
•• Attenuation values approaching that of water may indicate a cystic area,
but even such hypodense tumours may be solid. This is because the “solid”
area is in fact made up of microscopic cysts containing fluid.
•• The isodense non-enhancing tumour is invisible on CT (about 5% of low-
grade gliomas) and requires MRI for diagnosis.
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•• The closest imaging mimic is infarction.

•• The other imaging variety of low-grade astrocytoma is the circumscribed
one (e.g. pilocytic astrocytoma), which is sharply marginated. The circum-
scribed astrocytomas show contrast enhancement as globular masses
or thick irregular rings on CT or MR. Macrocystic change is common in
these tumours.
Anaplastic Astrocytoma
•• It is marked by the heterogeneity in appearance on imaging.
•• There are areas of low density, isodensity and even areas of hyperdensity
on non-contrast CT.
•• The cystic and necrotic areas both appear hypodense in CT.
•• Delayed contrast CT may show contrast-fluid levels in cysts while this sign
is absent in necrotic areas.
•• The border of the lesion may be apparently better defined than in a low-
grade tumour.
•• The enhancement on CT or MR takes the form of a thick ring or a nodule.
•• There is more oedema than in a low-grade tumour.
•• This lesion needs to be distinguished from granuloma, abscess and
metastasis.
•• It has been found that an abscess appears hyperintense on diffusion-
weighted MR images, whereas a tumour is hypointense. The apparent
diffusion coefficient (ADC) values are lower in an abscess than tumour cysts.
•• The size of the lesion may increase in a few months.
•• Enhancement alone does not predict the malignant nature.
Glioblastoma Multiforme
•• It is marked by its variegated appearance and mass effect.
•• The secondary glioblastoma retains the imaging characteristics of the
low-grade tumour from which it developed and adds the imaging features
of neovascularity, haemorrhage or necrosis.
•• The primary tumours on the other hand show a thick, shaggy and
serpigenous pattern of enhancement all over the tumour.
•• Infiltration of the opposite frontal lobe through the corpus callosum produces
the famous “butterfly” glioma.
•• In glioblastoma, and to some extent with anaplastic astrocytomas, the tumour
cells have been detected in radiologically normal brain around the tumour.
Recent Trends in Imaging

Proton Magnetic Resonance Spectroscopy
•• Proton magnetic resonance spectroscopy (MRS) has been employed to
predict tissue characteristics.
•• The molecules studied are N-acetyl aspartate (NAA), that reflects loss of
neuronal integrity; creatinine (Cr), a measure of energy stores; lactate (Lac),
that reflects anaerobic metabolism; and choline (Cho), that is elevated in
tumours and inflammatory processes, reflecting rapid cell turnover.
•• Generally, in highly metabolic tumours, including glioblastoma, the levels
of NAA and Cr are decreased, and the rapid growth results in elevated
Cho and Lac levels.
•• Thus, in comparison with normal tissues, glioblastoma demonstrates an
increase in Cho/Cr and Cho/NAA peak ratios, an increased Lac/Cho peak
ratio, and a decreased NAA/Cr ratio.
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•• MRS is useful for distinguishing infarcts or inflammatory lesions that mimic

a glioma on MR imaging.
•• Cho appears to correlate best with the degree of tumour infiltration.
•• MRS appears more accurate than conventional MRI in defining the tumour
boundary and quantifying the degree of tumour infiltration.
•• The relative levels of Cho and NAA correlated with the cell density in grade
2 and grade 3 gliomas. The association was irrespective of the presence
of contrast enhancement.
Perfusion and Diffusion Magnetic Resonance
•• The blood flow in the tumour can be assessed with perfusion MRI.
•• Glioblastoma shows higher regional cerebral blood flow (rCBF) than lower
grade tumours or lymphomas.
•• The pre-operative ADC in diffusion-weighted MR has emerged as a
prognostic factor. Low ADC carries a poor prognosis.
•• Diffusion tensor imaging is a new modality that can delineate fibre tracts
and depict their displacements or infiltration by gliomas.
•• It can also be used for delineating accurately the tumour margin and
oedema from the surrounding healthy white matter.
Positron Emission Tomography
•• Its spatial resolution is poor but, since it can be combined with CT, the
resolution is improving.
•• The advantage is that it is able to show the areas of active tumour growth
by demonstrating hypermetabolism.
•• PET using 18 F-fluorodeoxyglucose (FDG) has been shown to correlate with
survival in anaplastic astrocytomas, those with higher uptake succumbing
earlier.
•• PET studies using L-(methyl-11C) methionine have shown that methionine
uptake was heterogeneous even among the homogeneous tumour areas
demonstrated on MRI. Malignant pathological features were detected in
the areas with the highest methionine uptake.
Serum and Cerebrospinal Fluid Markers

•• GFAP has been detected by enzyme linked immunosorbent assay test in
serum samples of 80% of patients with glioblastomas.
•• The levels are higher in those with larger tumours, larger areas of necrosis
and greater tumour cell positivity for GFAP.
•• Though CSF cytology may prove positive for tumour cells in glioblastomas,
it is not advisable to obtain lumbar CSF in patients with large mass lesions.
•• Ventricular CSF may be obtained during shunt surgery or endoscopy.
TREATMENT
Goals of Therapy
•• The goals of management of an individual patient can be summarised as:
–– To establish an unequivocal diagnosis
–– To determine the degree of malignancy
–– To relieve distressing symptoms
–– To prolong useful survival without inflicting unacceptable neurological
deficits
–– To achieve as complete an excision of the tumour as possible
–– Improve the effectiveness of adjuvant therapy like radiotherapy,
chemotherapy and immunotherapy by cytoreduction.
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•• To achieve these objectives the following alternatives are available:

–– Image guided stereotactic biopsy (frame based or frameless)
–– Tumour removal: partial; subtotal; macroscopically total; lobectomy
–– Procedures for relieving ICP: drainage of cyst; CSF diversion (shunt or
ventriculostomy); craniectomy for external decompression
–– Procedures to facilitate adjuvant therapies (implanting catheters for
intralesional therapy, radioactive material for brachytherapy, etc.).
Biopsy
Need for Biopsy
•• It is not always possible to ensure that the lesion seen on imaging is a
glioma and not some other lesion such as infarction, abscess, granuloma
or demyelination.
•• Even if the imaging characteristics strongly suggest a glioma, its grading
can only be suggested but not confirmed by the most sophisticated
neuroradiological technique.
•• Hence, in all cases, it is necessary to obtain a histological diagnosis before
deciding on further therapy.
•• If the tumour is in a resectable region and the patient is fit for surgery,
there is no need to do a preliminary biopsy before proceeding with tumour
excision.
•• Similarly, in a patient who needs a resectional procedure for relieving
symptoms, there would be no need for a preliminary biopsy.
Indications for Biopsy
–– Biopsy-alone approach will be indicated in the following cases:
–– Deep-seated lesions
–– Small lesions
–– Lesion associated with a large cyst
–– Lesions affecting eloquent areas
–– Multiple lesions
–– Lesions where there is a differential diagnosis with a medically
treatable lesion such as tuberculoma
–– Patients who are not fit to undergo major surgery.
Accuracy
•• Stereotactic biopsy is generally accurate.
•• About 80% accuracy on comparing with the subsequent resection specimen
has been reported.
•• The CT is usually used for stereotactic biopsy while MRI has proved to be
as accurate in the axial plane coordinates and may be used for lesions
not seen well on CT.
•• It is possible to obtain accurate samples with frameless stereotaxy also.
Rationale of Biopsy
•• Several surgeons have favoured the biopsy-followed-by-radiotherapy
approach for malignant tumours.
•• It is claimed that there is no survival difference between those who undergo
biopsy alone and those who undergo major resections for malignant gliomas
as long as the patient undergoes radiotherapy.
•• They also point to the morbidity of major resections.
•• However, in the recent years, the safety of resectional surgery has
increased and resection has been shown to confer a survival advantage.
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•• While most radiotherapists believe that cytoreduction is a prerequisite for

radiation therapy, some have cast a doubt on the role of cytoreduction in
glioblastoma.
•• Patients with large tumours who have marked increase in ICP are obviously
not suitable for this line of management.
Tumour Removal
Differences Between Radical Cancer Surgery
Elsewhere and in the Brain
•• Radical cancer surgery in other areas of the body has aimed at complete en
bloc excision with surrounding normal tissue to assure a tumour free margin.
None of these goals is possible to achieve in malignant brain tumours.
•• The technique of neurosurgery involves intralesional decompression before
piecemeal excision and so en bloc excision is generally not possible.
•• The en bloc removal technique using spoon retractors may not ensure
prevention of tumour spillage.
•• It is important to recognise that a malignant glioma, even if it appears to
be well circumscribed, is an infiltrating tumour.
•• During surgery, the bulk of the tumour can be differentiated from the normal
brain tissue by its colour, consistency and texture.
•• However, even when using microsurgical techniques, it is impossible to be
sure of the precise extent of tumour infiltration. Thus, the microsurgical limit
of the tumour is well within the histological limits revealed by pathological
examination.
•• Resection of surrounding brain to assure a tumour free margin is only rarely
possible in small tumours in silent areas of the brain.
•• Hence, though gliomas may be resectable, they are not amenable to
oncologically radical excision. “Radical” or “aggressive” glioma removal is
tantamount to a gross or macroscopic total removal.
•• It should be considered a cytoreductive procedure and as the first step in
a multimodality treatment regime.
Strategies to Maximise the Resection
•• Use of a 7–10 MHz ultrasound probe can show up the higher echogenicity
of the glioma tissue (irrespective of its contrast enhancing property) and
can help in detecting residual tumour in the bed of an apparently complete
excision.
•• Stereotactic craniotomy involves performing the craniotomy in the stereotaxy
frame.
•• Neuronavigation [image guided resection (IGR)] achieves the same purpose
and has been demonstrated to result in more complete excision and
longer patient survival as compared to conventional microsurgery without
navigation. Addition of PET data to the MR data for IGR improves the extent
of resection. The problem with neuronavigation is the shift of targets that
occurs after CSF drainage, brain shrinkage, displacement during removal
of large lesions or ventricular opening.
•• Intraoperative MRI to assess completeness of excision is logical, but is
expensive and available in a very few centres only.
•• 5-aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular
accumulation of fluorescent protoporphyrin IX in malignant gliomas. This
fluorescence, visible under violet-blue light distinguishes tumour from
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normal tissue and results in a better resection than with conventional white
light. This requires appropriate modifications of the operating microsope.
Strategies to Minimise the Risk to Neurological
Function in Glioma Surgery
•• Blood oxygen level dependent imaging is known as functional MRI (fMR)
and it can be used to map the eloquent areas preoperatively.
•• Motor pathway monitoring with motor evoked potentials (MEP) is especially
needed for insular glioma surgery.
•• Preoperative MR tractography to identify the pyramidal tract, integration of
fibre tracking data with neuronavigation and MEP monitoring helped avoid
motor deficit in removing tumours up to 1 cm of the pyramidal tract.
•• Intraoperative navigated 3D ultrasound angiography identifies hidden blood
vessels and helps save them during resection.
•• Ultrasound data can be easily updated and hence brain shift is not a problem
in using ultrasonographic navigation.
Low-Grade Gliomas
•• Low-grade glioma presents a therapeutic dilemma.
•• The patients are often in the prime of life.
•• The sole symptom is seizures in about two-thirds of patients.
•• The lesion might not show growth over several years.
•• Early complete excision gives a reasonable chance of cure without any
adjuvant therapy and avoids progression to an anaplastic tumour.
•• In fact 82% of low-grade gliomas (compared with 54% of glioblastomas)
were situated within functional regions in one study.
•• The supplementary motor area and insula alone accounted for 52% of the
sites for low-grade gliomas.
•• Injudicious surgery in these critical areas might make the patient worse off.
•• Total excision is sometimes not possible because of the difficulty in defining
the edge of the tumour from normal brain.
•• The key questions that the neurosurgeon faces in dealing with a
supratentorial non-optic pathway, non-enhancing lesion that is consistent
with a non-pilocytic astrocytoma are:
–– Should the patient be observed without a tissue diagnosis?
–– Should biopsy be done?
–– Should tumour resection be done? If so should it be subtotal or gross
total?
–– Should radiation therapy be given?
Observation
•• Observation seems to be a reasonable option with smaller non-enhancing
lesions in neurologically intact, young patients who are imaged immediately
after a seizure.
•• This option is often exercised when the lesion is in an eloquent area.
•• The possibility of a postictal evanescent imaging lesion necessitates that
a repeat imaging is done in 3–12 weeks.
•• Only if the lesion persists, one can be sure that it is not a mere postictal
change.
•• The observation period can be extended to years in patients who remain
neurologically normal with adequate seizure control and have no increase
in tumour volume on follow-up.
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•• This conclusion is bolstered by a retrospective comparison of “wait” and

“no wait” groups of patients with suspected low-grade glioma.
•• The MRI occasionally discloses an entirely asymptomatic brain glioma
(not even a single seizure) while looking for cervical spine disease. Such
patients are also best managed by watchful expectancy.
Biopsy
•• It is an essential requirement before radiotherapy without resection.
•• The tendency would be to choose biopsy for lesions in eloquent or deep
areas and resection for silent areas.
•• The biopsy related morbidity and mortality is much less (near-zero) for
low-grade tumours than for the malignant ones.
Resection
•• Resection has been shown to give a survival advantage.
•• The 5-year survival was 80% for total resection, 50% for partial resection
and 45% for biopsy in low-grade astrocytomas.
•• The seizure control is also better after resection.
•• The current practice is to choose early surgical resection for patients
presenting with raised ICP, the older patients, those with enhancing or
large lesions and tumours in non-eloquent areas.
•• The strategies to maximise the excision and minimise the collateral damage
are all the more relevant to low-grade gliomas.
•• In general, age below 40 years, good KPS, seizure as a presenting
symptom, imaging findings of circumscribed or homogeneous enhancement,
hypometabolism on PET and microcystic or pilocytic histology predict a
good prognosis.
Radiotherapy
External Radiotherapy
•• Radiotherapy has the advantage of tackling the “unseen” tumour infiltration
inaccessible to the surgeon’s tools.
•• Conventionally, 40 Gy of whole brain radiation (20 fractions in 4 weeks)
has been followed by 20 Gy (10 fractions in 2 weeks) of booster to the
tumour site.
•• Radiation planning for the booster is ideally done with a mid-treatment T2W
MRI as the tumour might have changed in size by then.
•• Accelerated hyperfractionation (1.2 Gy twice daily) allows the treatment
to be completed faster.
•• Hypofractionation (5 doses) is the standard technique of stereotactic
radiotherapy.
•• Treatment planning with MRI is better than that with CT.
•• The efficacy of radiotherapy for low-grade tumours is less certain.
•• For tumours such as pilocytic astrocytoma that are totally excised there is
no need for radiotherapy.
•• Early radiotherapy (immediately after surgery) is preferable to delayed
radiotherapy (at the time of demonstrable progression).
•• In eloquent areas, radiotherapy is the usual option for low-grade
astrocytomas.
1005
Brachytherapy
•• It has been used along with external radiotherapy in an effort to increase
the glioblastoma dose without increasing normal brain dose.
•• Radioactive iodine (125I) seeds and temporary iridium (192Ir) wires have
been used to improve the survival by about 6 months.
•• Since, it requires a second operation for implantation, it can be considered
an option for recurrent glioma requiring surgery.
•• Methods to enhance radiation response have been surgical cytoreduction
and the use of radiosensitisers.
•• Most attempts with misonidazole and paclitaxel as radiation sensitisers
have failed to improve the prognosis in glioblastoma.
•• The COX-2 inhibitors are being tried now to enhance apoptosis induced
by radiotherapy.
Risks of Radiotherapy
•• Risks of radiotherapy that need to be highlighted are radiation necrosis
and cognitive dysfunction.
•• Radiation necrosis typically appears 1–3 years after therapy.
•• The risk increases significantly with higher radiation dose, fraction size and
the subsequent administration of chemotherapy.
•• Radionecrosis has a predilection for the periventricular white matter and
may be distant from the original tumour site.
•• The imaging findings of radionecrosis can mimic enhancing tumour regrowth.
•• The MRS, PET and pMRS may be useful in distinguishing tumour from
radionecrosis.
•• The differential diagnosis might need stereotactic biopsy.
•• Radionecrosis might cause enough mass effect to warrant surgical excision
if it does not respond to steroid therapy.
Stereotactic Radiosurgery
•• SRS involves delivering the radiation dose on a single day with stereotactic
precision to the tumour and its margin.
•• The radiation can be from gamma ray sources (gamma knife radiosurgery)
or from a linear accelerator (X-knife radiosurgery).
•• SRS is a potential alternative in the management of small-volume low-grade
astrocytomas in unresectable areas.
•• It avoids the risks of larger-field fractionated radiotherapy.
•• SRS has been done before and after external radiotherapy.
Chemotherapy
•• The initial attempts at chemotherapy with nitrosoureas [parenteral bis-
chloroethylnitrosourea (BCNU) or oral chloroethyl-cyclohexyl-nitrosourea
(CCNU)] did not add much to improve the bleak outlook of malignant glioma
and posed significant toxicity risks.
•• Combination therapy with procarbazine, CCNU and vincristine (PCV
regime) was the next to be tried.
•• There is a high incidence of haematotoxicity with this regime used for
recurrent glioblastoma.
•• Carboplatin-vincristine therapy has been used for low-grade gliomas in
children who cannot be given radiotherapy.
1006
•• In order to reduce the systemic toxicity, intra-arterial chemotherapy and

interstitial therapy have been tried.
•• Intra-arterial cisplatin-etoposide chemotherapy (with or without osmotic
opening of blood-brain barrier) administered prior to radiotherapy appears
to be better than concomitant radiation and chemotherapy.
•• “Gliadel” is a BCNU impregnated wafer, implanted surgically in to the tumour
resection bed that provides interstitial chemotherapy. This approach carries
the risk of brain oedema.
Temozolomide
•• It is an oral alkylating agent that received Food and Drug Administration
approval in 1999 for recurrent anaplastic astrocytoma and in 2005 for newly
diagnosed glioblastoma.
•• The dose used was daily temozolomide (75 mg/m2/day, all seven days
of the week from the first to the last day of radiotherapy), followed by six
cycles of adjuvant temozolomide (150–200 mg/m2 for 5 days during each
28–day cycle).
•• This resulted in prolongation of median survival time from 12 months with
radiation alone to 14.6 months when temozolomide was added.
•• More significant was the rise in the 2-year survival rates (from 10 to 27%).
•• Severe haematotoxic side effects occurred only in 7% of these
chemoradiotherapy patients.
•• The efficacy and relative safety of temozolomide has been shown in children
and in elderly patients.
•• Since children and the elderly tolerate radiation poorly, temozolomide alone
has been used in these groups.
•• Chemotherapy-alone approach has been used for low-grade gliomas in
the hope of avoiding long-term side effects of radiotherapy.
•• Temozolomide has been tried as sole adjuvant therapy for the
chemosensitive low-grade tumours with 1p/19q deletion.
•• Topotecan, a topoisomerase inhibitor, has been used with some success
in childhood high-grade gliomas.
PROGNOSIS
•• The prognosis of glioblastoma and anaplastic astrocytoma remains poor
despite significant recent advances.
•• In retrospective studies reporting multivariate analysis, the universally
agreed predictors of prognosis are the age of the patient, pre-treatment
Karnofsky performance score and the use of radiotherapy for both
glioblastomas and anaplastic astrocytomas.
•• The less consistent predictors are sex (females carry better prognosis),
extent of surgical resection, pre-operative seizure as a symptom, imaging
variables, histological grade, proliferation index and molecular markers.
RECURRENCES
•• The most common cause of death of a patient treated for a supratentorial
glioma is recurrence.
•• It is easy to imagine a glioblastoma recurring, but even low-grade tumours
may recur after imaging proved complete excision and after a considerable
time lag.
•• Recurrence generally occurs at the site of the original tumour or within
4 cm from it.
1007
•• Occasionally, the tumour may spread along the CSF pathways and present
at a different site in the neuraxis.
•• Technically, a tumour might be deemed to have recurred only when there
is evidence of complete excision in the early post-operative contrast
imaging study.
•• If there had been a residue, the more appropriate term is re-growth or
progression.
Clinical Features of Recurrence

•• A recurrence manifests with recurrent seizures, symptoms of raised ICP
or progressive neurological deficit.
•• Epileptic fits occurring for the first time following treatment, or recurring after
a seizure free post-operative period, indicate a recurrence.
•• Recurrence of neurological deficits that had improved post-operatively
or appearance of new neurological deficits should arouse suspicion of
tumour recurrence.
•• Clinical deterioration does not necessarily imply tumour recurrence.
•• In one-third of the patients clinically suspected to have a recurrence, there
may be other factors such as reactive oedema following chemoradiotherapy,
postictal weakness, infection, haemorrhage or radionecrosis that mimic
symptoms of tumour recurrence.
Imaging of Recurrence
•• The MR is better than CT in investigating a possible recurrence.
•• Most recurrent tumours are more T1 hyperintense than the original tumour
and enhance with gadolinium.
•• PET demonstration of hypermetabolism indicates recurrence, but this is
not as infallible as it was thought to be.
•• The MR and CT signs of radiation necrosis may be indistinguishable from
recurrent tumour.
•• The similarities and differences are enumerated in Table 1.
•• The difficult case might require stereotactic biopsy.
•• It has been recently found that increased CSF matrix metalloproteinase
(MMP-9) activity could be a marker of recurrent malignant glioma, before
any changes are detectable on MRI.
Treatment of Recurrence
•• The choices for recurrent glioma are re-operation, radiosurgery, radio-
therapy, chemotherapy and comfort therapy.
Re-operation
•• Re-operation is considered under the following conditions:
–– Young age
–– Low-grade of initial tumour
–– Progression free survival of at least 1 year or longer
–– KARNOFSKY performance score greater than 70
–– Tumour causing a mass effect
–– Tumour in non-eloquent area.
–– Biopsy is occasionally required for differentiating true recurrence
from imaging mimics. Except in this situation, the surgery is always
resective and it aims at maximising tumour removal without provoking
new neurological deficit.
•• Surgery also allows interstitial chemotherapy and brachyradiotherapy.
1008
Table 1: Imaging comparison of recurrent glioma and radionecrosis

Modality Recurrent/residual glioma Radionecrosis
Location At previous tumour site, At previous tumour site,
rarely at distant site not uncommonly distant or
contralateral side
Contrast enhanced Ring enhancing Ring enhancing, soap bubble
Computed tomography or Swiss-cheese
or contrast enhanced appearance
Magnetic resonance
Oedema and mass effect Present Present
Central necrosis Present Present
Serial imaging Growth Growth, stabilisation or
regression
Magnetic resonance Decreased Increased
spectroscopy- N-acetyl
aspartate/creatinine ratio
Perfusion magnetic Increased Decreased
resonance-regional
cerebral blood flow
Positron emission Hypermetabolism Hypometabolism
tomography
Radiosurgery
•• Radiosurgery is usually reserved for small recurrences and it can be done
for those who have already had external radiotherapy.
•• Most radiotherapists would desist from giving a second course of radiation
to the same brain field.
•• In cases where the recurrence occurs after 1 or more years of the initial
therapy and for those in whom an adjacent field needs radiation, re-radiation
therapy may be considered.
Chemotherapy
•• It is offered to patients who have recurrence within the 1st year of initial
treatment and those in whom re-operation is not a choice (older age,
poorer Karnofsky performance score, location in eloquent area, lack of
mass effect).
•• Temozolomide is the choice for those who have not had this drug earlier.
•• Cyclophosphamide has been used for temozolomide resistant recurrences.
•• Multi agent chemotherapy does not confer an advantage and poses a
significant toxicity.
EMERGING THERAPIES
Molecularly Targeted Therapies
•• The past decade has seen a spate of novel approaches to treating
malignant gliomas. Broadly, they target growth promoting factors or stop
the signalling pathways.
•• These include EGFR tyrosine kinase inhibitors (gefitinib and erlotinib),
mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and
everolimus), and VEGFR, protein kinase C-beta, and other angiogenesis
pathways inhibitors (vatalanib, bevacizumab and enzastaurin).
1009
Convection Enhanced Delivery

•• Convection enhanced delivery of therapeutic macromolecules through a
stereotactically implanted catheter in to the tumour ensures coverage for
a 2 cm margin of brain around the tumour. This is far more than the 2 mm
penetration of drugs from implanted wafers.
•• The chimeric macromolecule delivered is a conjugate consisting of a
monoclonal antibody that specifically attaches to the tumour cells in
preference to normal cells and another portion that is tumouricidal.
•• The tumouricidal portion may be a biotoxin (modified pseudomonas/
diphtheria toxin or plant derived ricin) or a radioisotope (131I).
•• This delivery method circumvents the blood brain barrier, provides high
local drug concentrations and minimises systemic exposure.
Gene Therapy
•• It has been explored for malignant gliomas.
•• One concept is to deliver a cytotoxic gene in to the tumour cell through a
viral vector.
•• Retrovirus, adenovirus and herpes simplex virus have been tried as the
vectors.
•• The virus can be redirected in such a way as to specifically attach to tumour
specific sites such as fibroblast growth factor receptor on the tumour cells
and the endothelial cells in the tumour.
•• The cytotoxic effect can then be increased with the antiadenoviral drug,
ganciclovir.
131
CHAPTER
Cerebellar Astrocytomas
INCIDENCE
•• Cerebellar astrocytoma is predominantly a tumour of childhood, 75%
occurring in the first two decades of life.
•• The youngest reported case of cerebellar astrocytoma was in a 5-week-old
infant, which raises the possibility of origin in utero.
•• The median age at presentation has dropped to 6–8 years in most modern
series, indicating that these tumours are being diagnosed earlier.
PATHOLOGY
Gross Pathology
•• Cerebellar astrocytoma is described classically as arising from one
cerebellar hemisphere with a well-defined cyst containing yellow-brown
fluid and a mural nodule.
•• In different series, the location was 28% in the cerebellar hemisphere, 30%
in the vermis and the rest were tumours involving both the hemisphere
and the vermis.
•• The tumours can be divided into the true cystic, false cystic and solid types.
The differences between the two cystic types are set out in Table 1.
•• Brainstem infiltration is more common in the solid and midline tumours, a
reflection of their more malignant histology.
Microscopic Pathology
•• Pilocytic astrocytes, which are “hair-like” elongated bipolar astrocytes, are
the histological hallmark of the paediatric cerebellar astrocytoma (Table 2).
Table 1: True and false cystic cerebellar astrocytoma

True cystic False cystic
Mural tumour nodule within a glial cyst Tumour lining the wall of the cyst
No tumour in the wall, which is thin Wall is thicker, varies in thickness from part
to part
Wall does not enhance with contrast Wall enhances with contrast but to a varying
degree
Wall shiny and translucent Wall shaggy and opaque
Cyst content clear Cyst content not always clear, usually
xanthochromic
Chapter 131 • Cerebellar Astrocytomass
1011
Table 2: Histological subtypes of cerebellar astrocytic tumours

Pilocytic astrocytoma (juvenile)
Diffuse fibrillary astrocytoma (low-grade)
Oligoastrocytoma
Anaplastic (malignant) astrocytoma (high-grade)
Glioblastoma multiforme
Lipidised glioblastoma
Pleomorphic xanthoastrocytoma
•• However, the most abundant cells in these tumours are the fibrillary
astrocytes, arranged in alternating compact and loose areas resembling
a honeycomb.
•• Rosenthal fibres, the stout eosinophilic cytoplasmic rods made of heat
shock protein, are more common in the compact zones.
•• The absence of nuclear pleomorphism, mitotic figures, endothelial
proliferation, necrosis and haemorrhage ensures that these tumours are
graded as World Health Organisation (WHO) grade 1.
•• The tumour cells are positive for glial fibrillary acidic protein.
•• About 20% of the paediatric cerebellar astrocytomas are histologically
classified as the diffuse fibrillary astrocytoma.
Malignant Astrocytomas
•• Anaplastic (WHO grade 3) astrocytomas account for 9–12% of cerebellar
astrocytomas.
•• Malignant astrocytom may either arise de novo or may result from malignant
progression of a pilocytic astrocytoma.
•• Such a progression may occur even after three decades of original diagnosis.
•• Anaplasia may be localised to a focal region within the pilocytic astrocytoma
and this focus appears radiologically distinct.
•• The solid nature and the tendency to infiltrate the brainstem or peduncle limit
the extent of resection of anaplastic astrocytomas.
Other Histological Types
•• Primary oligoastrocytoma is recognisable by the calcification pattern.
•• Pleomorphic xanthoastrocytomas are rare in the cerebellum, but have been
reported in a wide range of ages.
•• The surgeon should be aware that these tumours are harder in consistency
(due to desmoplasia) and that they may involve the overlying dura or
venous sinus.
•• Glioblastoma multiforme is rare in the cerebellum, but carries as poor a
prognosis as its supratentorial counterpart.
Tumour Biology
•• Vascular endothelial growth factor (VEGF) expression and changes in the
blood-brain barrier have both been proposed as mechanisms for the cystic
change in pilocytic cerebellar astrocytomas.
•• The occurrence of cerebellar astrocytoma in association with ataxia-
telangiectasia, Albright’s disease, von Hippel-Lindau disease and
neurofibromatosis suggests a genetic mechanism of causation, quite unlike
the sporadic cerebellar astrocytoma.
1012
•• The gene expression profiles of pilocytic astrocytomas differ significantly

from those of diffusely infiltrating low-grade gliomas and their benign
biologic behaviour may be related to up-regulation of immune defence-
associated genes.
•• The symptoms and signs vary with the age of the patient and the site of
the tumour.
•• In infancy, cerebellar tumours present with enlarging head size due to
hydrocephalus, irritability and vomiting. The tense fontanel, rather than
papilloedema, indicates raised pressure at this age.
•• Older children and adults complain of headache, seen in about 80% of
patients.
•• The headache is usually frontal, but may later become generalised.
•• Localised headache in the occipital region is rarely an early symptom.
•• Headache occurring in the early morning hours has been attributed
to sleep induced hypoventilation causing hypercarbia and postural
cerebrospinal fluid (CSF) accumulation in the intracranial compartment
during recumbency.
•• The headache may be accompanied by vomiting, diplopia or irritability.
•• Vomiting relieves the headache, probably due to the associated
hyperventilation.
•• Amaurosis fugax, especially on rising from the stooped posture, is a symp-
tom of advanced papilloedema and may indicate impending loss of vision.
•• Vomiting alone, without headache, is also seen, though this story is more
typical of a fourth ventricular tumour such as ependymoma.
•• “Robin’s rule” states that if the vomiting occurs before the headache, it is
an ependymoma but, if the headache occurs before the vomiting, it is a
medulloblastoma or astrocytoma.
•• Some children arrive at the emergency department with brief episodic loss
of consciousness and tonic stiffening of the limbs during the height of the
headache—the so-called “hydrocephalic fit”.
•• Torticollis to the side of the tumour may be a symptom, sometimes a sole
symptom. This symptom indicates tonsillar herniation.
•• Clinical examination reveals signs of raised intracranial pressure (ICP)
(80%) and those of cerebellar dysfunction (70%).
•• Neck stiffness without Kernig’s sign in an afebrile patient indicates tonsillar
herniation.
•• Gait and stance ataxia denote a vermian lesion while unilateral appendicular
ataxia is seen in the deeper hemispheric masses.
•• Horizontal nystagmus is found in midline or lateral cerebellar lesions while
vertical nystagmus or gaze palsy is caused by anterior vermian lesions
compressing the collicular region.
NEURORADIOLOGY
•• Dilatation of the third and lateral ventricles is seen in the majority of patients,
as the tumours tend to be large enough to cause compression of the fourth
ventricle at the time of diagnosis.
•• Periventricular lucencies suggest high intraventricular pressure.
•• The solid part of the tumour is hypodense in non-contrast CT as compared
to the cerebellum.
1013
•• The cystic part is hypodense compared with the cerebellum or the solid
part, but it shows a higher attenuation coefficient as compared to the CSF
due to its protein content.
•• The tumour shows a varying degree of demarcation with the surrounding
normal tissue.
•• Calcific foci are uncommon.
•• Calcification is displayed more graphically by CT than MRI and extensive
calcification should suggest oligoastrocytoma.
•• Pilocytic astrocytomas enhance well, while the more fibrillary variety may not.
•• The enhancement may be non-uniform due to the presence of microcysts
in the solid part of the tumour.
•• The cyst wall enhances in the false cystic tumour due to the presence of
tumour in the wall.
•• The cystic and solid parts of the tumour appear hypointense in T1-weighted
magnetic resonance images and hyperintense in proton density or T2-weighted
images.
•• The solid part is hyperintense to the cerebellum in T2-weighted images and
the cystic part slightly hyperintense to the CSF in T1-weighted images.
•• Presence of haemosiderin causes a rim of hypointensity in the cysts suggesting
an old bleed.
•• Gadolinium enhancement patterns are similar to CT contrast enhancement.
•• Haemangioblastoma, ependymoma, medulloblastoma, dermoid tumour,
choroid plexus papilloma, metastasis, tuberculoma and cerebellar abscess
must be considered in the differential diagnosis.
•• Magnetic resonance spectroscopy (MRS) may help in narrowing the
differential diagnosis. Taurine detection by short-echo proton MRS is present
in medulloblastoma and absent in cerebellar astrocytoma.
MANAGEMENT
•• In the past, it was a routine practice to place a ventriculoperitoneal shunt
a week or so before resecting cerebellar astrocytomas.
•• The current opinion is against pre-operative routine shunting for all the
disadvantages given in Table 3.
•• Pre-operative dexamethasone preparation suffices in most cases.
•• Endoscopic third ventriculostomy seems to be a better option when relief of
hydrocephalus is needed before or after posterior fossa tumour extirpation.
Table 3: Pre-operative shunting for cerebellar astrocytoma

Advantages Disadvantages
Rapid symptom improvement Upward transtentorial herniation
Life/vision saving in an emergency Tumour dissemination through the shunt
Lax brain during resective surgery Shunt block/infection prior to resection
Luxury of converting an emergency into an Increased risk of infection after posterior fossa
elective operation surgery
Supratentorial subdural haematomas
Shunt no longer necessary in the long-term
Higher cost
A rare patient may refuse resec tional surgery,
as the patient is relieved of symptoms by the
shunt
1014
Surgery
Goal
•• Total excision of the tumour is the goal of cerebellar astrocytoma surgery.
•• It used to be advocated that removal of the mural nodule in case of a
cystic astrocytoma was all that was necessary if the cyst wall was thin
and transparent.
•• Invasion of the brainstem by the tumour is the only reason for partial or
subtotal excision in current neurosurgical practice.
Approach
•• The surgical approach to a cerebellar astrocytoma is decided by the location
of the tumour as summarised in Table 4.
•• Positioning of the patient is a matter of the surgeon’s preference.
•• The sitting position is not favoured in many departments nowadays due to
its inherent complications such as air embolism, tension pneumocephalus,
supratentorial haematoma, etc.
Tumour Excision
•• For midline tumours a vertical vermis incision through the avascular midline
is well tolerated and does not worsen the gait ataxia permanently.
•• A paravermian vertical incision is to be avoided as it carries a higher risk
of post-operative mutism.
•• For lateral tumours, it is preferable to incise the cerebellar hemisphere
horizontally along the direction of the folia.
•• The mural nodule, all solid parts and contrast enhancing or cyst walls are
excised. Small mural nodules can be excised en masse.
•• The bigger solid masses may require internal debulking (done with
ultrasonic aspirator) before dissection of the plane between the tumour
and the surrounding normal cerebellar tissue.
•• The plane is well defined in pilocytic astrocytomas but may not be so in the
fibrillary or, the rare malignant varieties.
•• Attachment to the pons or major invasion of the middle cerebellar peduncle
may limit the completeness of excision.
Complications
•• The CT must be done emergently if the patient becomes less responsive
or drowsy or complains of severe headache in the post-operative period.
•• Possible causes include tumour bed haemorrhage, supratentorial subdural
or extradural haemorrhage, infratentorial subdural haemorrhage, unrelieved
hydrocephalus, pneumocephalus and venous or arterial infarction in the
cerebellum.
Table 4: Choosing the surgical approach according to the location of

cerebellar astrocytoma
Location Approach Position
Inferior vermian, medial hemispheric Midline suboccipital Prone
Lateral hemispheric Lateral suboccipital Prone
Cerebellopontine angle Retromastoid Lateral
Superior vermian Infratentorial supracerebellar Concorde
Anterosuperior Occipital transtentorial Sitting
1015
•• As with any posterior fossa surgery, complications such as pseudo-

meningocoele, aseptic or infective meningitis and external CSF leak can
occur.
•• A complication that requires special mention is transient cerebellar mutism.
•• In this condition, the child or young adult, who has a relatively normal
speech for becomes mute 1 or 2 days after posterior fossa tumour surgery.
•• These patients, additionally, may have long tract signs or behavioural
abnormalities.
•• Routine imaging fails to reveal any specific abnormality that can explain
the deficits.
•• The deficit is not nearly as transient as the name suggests; recovery is a
slow and incomplete process taking several months. Fortunately this is an
uncommon complication.
•• Bromocriptine has been anecdotally reported to be of help.
•• Many patients are left behind with speech and cognitive abnormalities.
•• The cause is believed to be damage in the region of the dentate and
interpositus nucleus.
•• The finding of contralateral cerebral hemispheric hypometabolism
(diaschisis) by F18 fluorodeoxyglucose positron emission tomography study
in a patient who had undergone cerebellar astrocytoma excision suggests
that such vascular events may also be responsible.
Adjuvant Therapies
•• Radiotherapy is not indicated for pilocytic astrocytoma as these can be
“cured” by total excision.
•• Even when a tumour residue has been left behind, radiotherapy may not
prevent regrowth.
•• In case a residue has to be left behind, it can be observed with periodic
imaging.
•• Re-operation or adjuvant therapy can be advised for remnants documented
to be progressing.
•• Stereotactic radiosurgery has been used for remnants and those pilocytic
astrocytomas exhibiting progression.
•• The more malignant varieties must be subjected to adjuvant radiotherapy
and/or chemotherapy.
•• Chemotherapy is the only possible adjuvant method for children younger
than 2 years.
PROGNOSIS
•• The extent of surgical resection is the strongest determinant of prognosis.
•• Cerebellar astrocytomas often behave in a benign fashion and total surgical
excision has been the mainstay of therapy since Cushing’s times.
•• Even after complete excision, recurrence can be seen several decades
later.
•• Re-operation and total excision again is feasible in such cases.
•• The recurrence may be malignant.
•• CSF shunting is less often needed in today’s practice.
132
CHAPTER
Brainstem Gliomas
Sarat Chandra P  VS Mehta
INTRODUCTION
•• Intrinsic brainstem tumours are common in childhood, comprising
approximately 20% of all paediatric brain tumours, but are not uncommon
in adults.
CLASSIFICATION
•• A number of classifications have been proposed based on location, imaging
and histopathology, but most of them overlook the fact that there exist
basically two categories of brainstem tumours:
1. Focal, discrete and sometimes exophytic lesions associated with a
favourable prognosis.
2. Classic diffusely infiltrative lesions known for their relentless growth,
resistance to radiotherapy and chemotherapy, and a bleak prognosis.
•• The focal tumours are particularly amenable to total excision, and the
patients have a good prognosis provided the surgery has been performed
by an experienced surgeon who has had enough exposure in operating
upon such lesions.
•• Brainstem gliomas have been classified by site, imaging and pathology.
•• Location: The terms applied include midbrain tumour, tectal tumour, pontine
glioma, focal medullary tumour and cervicomedullary tumour.
•• Imaging: Diffuse gliomas, intrinsic gliomas, pencil gliomas, exophytic
tumours (dorsal; ventral and lateral), focal and cystic tumours.
•• Histopathology: Low grade or benign tumours (pilocytic and grade II) and
high grade tumours (World Health Organization Grades III and IV).
•• These classification systems by various authors are mentioned in greater
detail in Table 1.
•• Currently, the most commonly used classification in clinical practice is
based on imaging and location.
•• This includes focal (solid or cystic), diffuse, exophytic (ventral, lateral or
dorsal), tectal plate and cervicomedullary.
•• However, as mentioned above, for practical purposes there are two
categories of tumours mentioned above (a) focal (b) classic.
•• The surgical plan is still difficult to decide in many cases as most of the
classifications are usually based on their anatomical location only.
•• The difference between a diffuse brainstem glioma and large focal intrinsic
brainstem glioma is not clearly differentiated in most of the classifications.
•• Thus, it is sometimes possible that a large focal intrinsic tumour, which
is actually a benign lesion is not subjected to surgery but submitted to
radiotherapy directly.
Chapter 132 • Brainstem Gliomas
1017
Table 1: Different forms of classification systems

Author Classification system
Epstein Intrinsic
Diffuse
Focal
Cervicomedullary
Exophytic
Anterolateral into cerebellopontine angle
Posterolateral and into pontine brachium
Disseminated
Positive cytology
Positive myelography
Epstein and Diffuse
McCleary Focal
Cervicomedullary
Stroink, et al. Group I—dorsal exophytic glioma
Group IIA—intrinsic brainstem glioma
Group IIB—intrinsic brainstem glioma, hyperdense, contrast enhancing,
exophytic
Group III—focal cystic tumour with contrast enhancement
Group IV—focal intrinsic isodense, with contrast enhancement
Barkovich, et al. Location (midbrain, pons, medulla)
Focality (diffuse or focal)
Direction and extent of tumour growth
Degree of brainstem enlargement
Exophytic growth
Haemorrhage or necrosis
Evidence of hydrocephalus
Allbright, et al. Focal (midbrain, pons, medulla)
Diffuse
Fischbein, et al. Midbrain
Diffuse
Focal
Tectal
Pons
Diffuse
Focal
Medulla
Diffuse
Focal
Dorsal exophytic
Choux, et al. Type I—diffuse
Type II—intrinsic, focal
Type III—exophytic, focal
Type IV—cervicomedullary
•• Expanding variety: These tumours have the following characteristics:

–– Well delineated as seen on gadolinium contrast MRI, located posteri-
orly, posterolaterally or ventrolaterally.
–– They have a slow progression of neurological deficits with a relatively
long clinical history of approximately 6 months.
–– Motor function is usually well preserved with the patient being inde-
pendent for all activities of daily living.
1018
•• Infiltrating diffuse variety: Here, the margin between the tumour and the
brainstem parenchyma is not well defined. Patients usually have a short
clinical history and there is a rapid progression of symptoms.
•• Ventrally located tumours:
–– The tumour is located completely ventrally without any lateral or pos-
terolateral extension.
–– They have been included in a different subset because of the “very
difficult to access” surgical location.
•• Only the “expanding variety” of tumours should be subjected to surgery.
•• If surgery is undertaken, a radical removal should be done.
•• Radiotherapy is given only if the tumour is found to be malignant on histology.
•• Thus, a more important approach would be to try to remove the tumour
as radically as possible, yet remaining within the tumour, provided the
radiological image reveals such a possibility.
•• It should be remembered that this is a for surgical management of
strategical classification only “intrinsic” brainstem gliomas. Surgery is
anyway indicated for all exophytic tumours (Table 2).
PATHOLOGY
•• Most astrocytomas of the brainstem are infiltrative tumours of the fibrillary
type, similar to diffuse cerebral astrocytomas.
•• Macroscopically, they are usually characterised by a symmetrical
enlargement of the pons (diffuse hypertrophy).
•• The expanding lesion encroaches posteriorly and superiorly upon the fourth
ventricle. Occasionally, there may be anterior enlargement.
•• The medulla is often spared.
•• Histologically, there is a diffuse replacement of nerve tissue by small and
large astrocytic cells (stellate, pilocytic and gemistocytic), either randomly
dispersed or arranged in small or large groups.
Diffuse
•• These neoplasms present with a short history and with multiple cranial
nerve palsies along with involvement of long tracts.
•• The MRI is virtually diagnostic of these lesions.
•• The tumour is invariably malignant and the only form of therapy advisable
is radiotherapy or chemotherapy.
•• Surgery is not indicated.
•• Even stereotactic biopsy is not advised as the procedure may cause
additional morbidity, and the biopsy may not contain representative tissue.
Focal
•• These more commonly involve the medulla and are often associated with
a relatively long clinical history.
•• Neurological examination usually reveals focal deficits, i.e. either a VI or
VII nerve palsy.
•• These neoplasms are commonly low-grade astrocytomas and are amenable
to surgical excision.
•• Cervicomedullary Tumours
•• These are usually low-grade astrocytomas and gangliogliomas with well
defined tumour margins and thus amenable to radical excision.
Table 2: The classification proposed by the authors for intrinsic brainstem tumours
Type of brainstem glioma Features Comparison with other classifications Surgery
I. Intrinsic only The tumour is well within the brainstem axis without any breach of the parenchyma
A. Expanding variety • Well delineated on gadolinium-magnetic resonance imaging (Gd-MRI) Epstein, et al. [1985]: Yes
• Slow progression of clinical symptoms (> 6 months) Focal (< 2 cm)*, cervicomedullary Radical excision
• Well preservation of motor function with independent activities of daily living Stroink, et al. [1987]†:
• Size may be > 2 cm Group III, IV
Choux, et al§. [2000]: Type II, IV
B. Diffuse infiltrative • No margin of delineation on Gd-MRI Epstein, et al. [1985]¶: diffuse No
variety • Rapid progression of symptoms Stroink, et al. (1987)**: IIA
Choux, et al. (2000): Type I
C. Ventrally located Pure ventral location May be kept as focal in other classifications, No
but authors prefer not to operate in view of
the difficult location and associated high risk
of complications
II. Exophytic brainstem The tumour breaches the bordering brainstem parenchyma to become exophytic Yes
glioma
A. Focal with exophytic Has a well defined focal component with a dorsal or dorsolateral exophytic component The exophytic portion removed
radically. The intrinsic part may
or may not be removed radically

B. Diffuse with exophytic The intrinsic component is not well defined and the tumour has a dorsal or dorsolateral The exophytic portion removed
exophytic component radically. The intrinsic part may
not be removed radically
*
Tumours > 2 cm could still be expanding variety.
†
Based on contrast enhancement and radiology only; clinical features not taken into consideration.
§
Based more on anatomical localisation, clinical features not mentioned again.
¶
Tumour looking focal but > 2 cm is still considered diffuse.
**
Clinical features not taken into account.
1019
1020
Cystic Tumours
•• These are usually low-grade pilocytic astrocytomas and highly amenable
for surgical excision.
Exophytic Tumours
•• These tumours are characterised by exophytic growth either ventrally,
laterally into the cerebellopontine (CP) angle or dorsally into the fourth
ventricle.
•• Of these, the dorsally exophytic tumours have the best prognosis,
are amenable for radical excision and are associated with long-term
neurological recovery.
•• The other variants have a poor prognosis.
Tectal Plate Gliomas

•• These are uncommon in the paediatric age group.
•• The main presenting feature is hydrocephalus.
•• These may be simply followed up and if they increase in size may be
subjected to radiotherapy.
•• Radiosurgery has also been used recently.
•• Endoscopic third ventriculostomy or aqueductal stenting may be a better
alternative to shunt surgery.
CLINICAL FEATURES
•• It is now widely recognised that brainstem tumours are a very heterogeneous
group with regard to their clinical, histopathological and biological features,
and it is essential that they be therefore regarded as distinct entities.
•• Vomiting is a common symptom and is usually due to involvement of the
area postrema and the other medullary nuclei by the tumour.
•• Ataxia is usually due to involvement of the cerebellar peduncles.
•• Motor weakness due to involvement of the pyramidal tracts is common.
•• Extraocular motor palsy is characterised by squint usually noticed by the
parents or school teachers.
•• Additional signs include nystagmus, skew deviation and internuclear
ophthalmoplegia.
•• The latter sign is a hallmark of intrinsic brainstem involvement characterised
by failure to adduct the eye on the side of the lesion and presence of
nystagmus of the abducting eye on the opposite side. This occurs due to
involvement of the medial longitudinal fasciculus.
•• Other signs of cranial nerve involvement include facial weakness, dysarthria
and swallowing difficulties.
•• Features of raised intracranial pressure may occur due to obstruction of
cerebrospinal fluid (CSF) pathways in dorsally exophytic tumours.
•• Focal intrinsic tumours from the tectum can cause obstruction of CSF
pathways early in the course of illness.
•• The following features are characteristic of an intrinsic brainstem neoplasm:
–– Internuclear ophthalmoplegia
–– Horner’s syndrome
–– Cranial nerve involvement with crossed motor involvement, e.g. ipsilat-
eral III nerve paresis with contralateral hemiparesis (Weber’s syndrome)
1021
–– Combination of certain cranial nerve nuclei, e.g. VI and VII cranial

involvement on one side indicates an intrinsic pathology
–– Partial involvement of some large sized cranial nerve nuclei, e.g. III
cranial nerve nucleus. This has many components, so a diffusely
infiltrative tumour may cause bilateral ptosis (involvement of bilateral
levator palpabrae superioris), or bilateral superior rectus palsy (in-
volvement of unilateral superior rectus nucleus can still cause bilateral
superior rectus palsy as the tract of the opposite superior rectus cross-
es contralaterally and passes through the opposite superior rectus
nucleus) or unilateral complete III nerve palsy and opposite partial III
nerve palsy.
•• Patients with tumours at the cervicomedullary junction exhibit lower cranial
nerve dysfunction and pyramidal tract signs, similar to those occurring in
the upper cervical spinal cord lesions.
•• Intrinsic tumours of the pons are infiltrative in nature and are mostly
malignant. Symptoms at the time of admission are usually cranial nerve
palsy, pyramidal tract signs and ataxia.
NEURORADIOLOGY
•• Tumours should be assessed for location, signal intensity, focality, extent
of infiltration, degree of brainstem enlargement, presence of cyst, necrosis
or haemorrhage, or an exophytic component.
•• Following this the morphology should be categorised, whether it comes
under focal, diffuse, cervicomedullary or exophytic type.
•• First categorise whether the tumour is “intrinsic” or a “tumour with an
exophytic component”.
•• In the former, identify whether the tumour is an “expanding variety”, “diffuse
infiltrative” or a “pure ventral type” of tumour.
•• Exophytic, cystic and expanding tumours should be subjected to surgery,
while direct radiotherapy and/or chemotherapy is preferable for diffusely
infiltrative and pure ventral type of tumours.
MANAGEMENT
•• The surgical approach should be according to the location and projection
of the tumour.
•• Most of the tumours in the pons, medulla and cervicomedullary junction
can be approached through a midline suboccipital craniectomy/craniotomy
in the prone position with or without vermian splitting.
•• Tumours in the midbrain are approached in sitting position through a midline
suboccipital craniectomy/craniotomy through a vermian splitting approach.
•• Tumours with an exophytic component laterally are preferably removed
through a paramedian or a CP angle approach.
•• The sitting position was preferred for dorsal midbrain or upper pontine
lesions.
•• The prone position was used in dorsally situated lower pontine, medullary
or cervicomedullary lesions.
•• The lateral position was preferred in ventrolateral lesions of the lower
pons, while the supine position was used for ventrolateral midbrain or
thalamic lesions.
1022
Mapping of the Cranial Nerve Nuclei

•• Because the rhomboid fossa and the brainstem are densely packed
with cranial nerve nuclei and neural tracts, surgery in this area carries a
substantial risk of new or increased neurological deficits.
•• For the same reason, neurosurgeons have long considered lesions in this
so-called “no-man’s land” at least among the most difficult to manage and
even inoperable.
•• However, new diagnostic and surgical techniques have reduced the risk
of neurological deficit resulting from such surgery, and surgeries are being
performed more frequently to treat intrinsic brainstem lesions.
•• Recent anatomic studies have identified safer approaches to the brainstem
via the fourth ventricle, but because disease often distorts the anatomy,
landmarks may be difficult or impossible to identify with the aid of the
operating microscope alone.
•• Thus, electrophysiological techniques need to be developed to help
distinguish the neural structures so that surgeons can avoid manipulating
or injuring these structures.
•• Two kinds of monitoring methods are commonly used.
–– Intraoperative Motor Nucleus Mapping:
¾¾ During motor mapping in the brainstem, electrical stimulation of the
hypoglossal or the vagal triangle elicits continuous motor action
potentials (CMAP) from the tongue muscles and the soft palate,
respectively. Stimulating the facial colliculus, which contains facial
and abducens nerve fibres, elicits CMAPs simultaneously from the
lateral rectus and facial muscles.
¾¾ Stimulating other ocular motor pathways elicits CMAPs from cor-
responding extraocular muscles.
–– Continuous Intraoperative Electromyographic Monitoring:
¾¾ Because muscles amplify the electrical activity in the individual motor
units, continuous monitoring of the electromyographic (EMG) activity
from certain muscles of the head can provide information about the
status of the respective motor cranial nerves.
¾¾ Use of this technique has been described for monitoring the motor
function of the facial nerve and other motor cranial nerve nuclei.
¾¾ For dorsally located lesions, we usually use electrodes connected
to the orbicularis oris, orbicularis oculi and the tongue muscles with
either intermittent or continuous stimuli.
¾¾ A single stimulus of 0.1–1 mA or a continuous stimulus of 10 Hz
(50–400 mS) is generally used.
Surgical Approaches
•• Surgery is indicated for focal solid or cystic tumours, cervicomedullary
tumours and exophytic (particularly dorsal) tumours.
•• The patients need to be followed up with regular neuroimaging.
•• Patients with focal cystic tumours may undergo decompression of the
cyst, which is a fairly easy procedure. However, focal radiotherapy may
be required to prevent recollection of the cyst.
•• In patients with dorsally exophytic tumours, decompression may be carried
out till the tumour is shaved off flush with the floor of the fourth ventricle.
•• A large number of patients with low-grade astrocytomas and gangliogliomas
will have a good outcome.
1023
•• Patients with tectal plate tumours may be subjected to a shunting procedure

followed by direct radiotherapy or radiosurgery.
•• Recently endoscopic third ventriculostomy and stenting of tectal plate
gliomas along with simultaneous biopsy is being recommended. This has
an advantage of performing a biopsy and a shunting procedure at the
same sitting.
•• All the patients should be started on methylprednisolone just before making
an incision on the brainstem and this should be continued for 24–48 hours
in doses of 30 mg/kg for the 1st hour followed by 5.4 mg/kg/hour for the next
24 hours.
•• All patients should be electively ventilated with sedation for 24 hours.
Management of Diffuse Tumours

•• The diffuse tumours carry the worst prognosis and the survival is usually
not more than 18 months after diagnosis.
•• Parts of the tumour may start off as a fibrillary astrocytoma but, by the time
of death, usually the entire tumour is either a malignant astrocytoma or a
glioblastoma multiforme. Thus, a stereotactic biopsy is totally unreliable
for diagnosis, while the imaging characteristics are almost diagnostic
of this dreadful condition. These patients may be directly subjected to
radiotherapy.
•• The type of radiotherapy is undergoing a change. The standard therapy
has been 55 Gy to the tumour area with a weekly dose of 800–1000 cGy.
•• In hyper-fractionated therapy, higher doses up to 76 Gy may be tolerated
and has improved short-term survival without obvious toxicity.
CONCLUSION
•• The identification of various subgroups of brainstem tumours has led
to more rational treatment strategies and allows for a more accurate
assessment of prognosis.
•• The focal tumours with paucity of neurological signs are a distinct subgroup
of brainstem tumours.
•• Most of them are low-grade astrocytomas and are amenable to radical
surgical resection, but this should be performed by an experienced surgeon
in a set-up with adequate intraoperative and postoperative facilities.
•• Surgical intervention in this subgroup of brainstem tumours may be
associated with a good long-term prognosis.
•• Exophytic tumours, particularly those associated with diffuse brainstem
enlargement, should undergo a limited decompression.
•• Purely diffuse tumours should preferably undergo direct radiotherapy.
133
CHAPTER Hypothalamic-Optic
Nerve Gliomas
INTRODUCTION
•• Optic pathway gliomas (OPGs) are unique in many ways.
•• They occur commonly in children and young adults.
•• They may show little growth over years.
•• Their location makes them a surgical challenge.
•• Controversy surrounds the optimal management.
INCIDENCE
•• Optic pathway gliomas are rare.
•• They account for 1% of all intracranial tumours, 3–5% of paediatric brain
tumours and 6% of all orbital tumours.
•• Gliomas account for two-thirds of all tumours in the optic nerve.
•• About 25% of OPGs are in the optic nerve [optic nerve glioma (ONG)] and
60% involve the chiasm (optic chiasm glioma).
•• Nearly one-third of patients with OPG have neurofibromatosis-1 (NF-1).
•• Symptomatic OPG occurs only in 5% of patients with NF-1, but imaging
series report a 15–20% incidence, as computed tomography (CT) and
magnetic resonance imaging (MRI) are able to detect several asymptomatic
OPGs in NF-1 patients.
•• The OPGs in NF-1 differ in many ways from the non-NF-1 OPGs and these
differences are summarised in Table 1.
•• The mean age at diagnosis was 8.8 years.
•• About 60% of OPGs are diagnosed before the age of 5 years, 75% before
the age of 10 years and 90% before the age of 20 years.
•• The male:female ratio is nearly equal but pure optic nerve tumours are
commoner in girls.
PATHOLOGY
Macroscopic Appearance
•• ONG can be purely intraorbital or purely intracranial.
•• Often the tumour starts in one compartment and spreads to the other
through the optic foramen causing a dumb-bell pattern with smooth
enlargement of the bony optic canal and foramen.
Chapter 133 • Hypothalamic-Optic Nerve Gliomas
1025
Table 1: Differences between optic pathway gliomas in those without and

with neurofibromatosis-1
Characteristic Non-neurofibromatosis-1 OPG in NF-1
(NF-1) Optic pathway
glioma (OPG)
Demographic
Incidence 3–5% of childhood tumours 10–15% of patients with NF-1

Male: Female ratio 1:1 2:3
Mean age ± SD 6 ± 3.3 years 4.3 ± 2.1 years
Gross pathology
Involvement
Orbital optic nerve 32% 66%
Chiasma 91% 62%
Hypothalamus 70% 36%
Beyond optic pathway 68% 2%
Bilaterality 7% 24%
Average size 4.5 cm 2.5 cm
Shape Globular mass 90% conform to optic pathway
shape
Cystic areas 66% 9%
Growth pattern Intraneural Perineural
Microscopic pathology
Infiltration of leptomeninges Rare Florid

Arachnoid hyperplasia Absent 50% of cases
Non-pilocytic histology Rarely reported Not reported
Malignant transformation Seen in adults Not seen
Clinical features
Progression 60% 12%

Asymptomatic 0% 32%
Visual symptoms 84% 21%
Proptosis 5% 21%
Hypothalamic symptoms 33% Rare, but precocious puberty
occurs
Raised pressure symptoms 66% Rare
Hydrocephalus 75% Not seen
Regression Not likely Reported
Imaging features
Diffuse enlargement of optic

nerve or chiasma 27% 91%
Vessel encasement 32% 2%
Prognosis
5-year survival 83% 93%

10-year survival 76% 81%
Time to progression 2.3 years 8.3 years
1026
•• The nerve is expanded by the tumour and also by the extension of the
tumour into the subarachnoid space.
•• The chiasmal variety may diffusely infiltrate the hypothalamus and the floor
of the third ventricle.
•• There is difficulty in distinguishing whether the primary site of origin is in the
chiasma or in the hypothalamus and so they are dubbed as hypothalamic-
chiasmatic glioma.
•• The non-NF-1 OPG in the chiasma may become a large mass and show
areas of cystic change. Large cysts have been reported to extend to the
middle fossa or third ventricle.
Microscopic Pathology
•• The histology of OPG is almost always a pilocytic astrocytoma.
•• Of all pilocytic astrocytomas, 11% occur in the optic pathways.
•• The astrocytes in the tumour have hair-like long processes, which give the
tumour the appellation “pilocytic”.
•• The pilocytic growth is compact in some areas and loose-textured in others
(biphasic pattern).
•• Rosenthal fibres and eosinophilic granular bodies are characteristic.
•• Microcystic change is seen.
•• The cells are positive for glial fibrillary acidic protein.
•• The typical pilocytic astrocytoma is graded as World Health Organization
(WHO) grade 1.
•• The majority of pilocytic astrocytomas have a very low growth potential but
undoubtedly a few show aggressive clinical behaviour.
•• Pilomyxoid astrocytoma has been recently recognised as a separate entity.
–– It is a solid, circumscribed tumour that occurs in the chiasma-hypothal-
amus area of very young children.
–– It is composed of a monomorphous population of bipolar tumour cells
within a rich myxoid background, with a conspicuous angiocentric ar-
rangement.
–– This tumour is graded as WHO grade 2 and shows more aggressive
behaviour than pilocytic astrocytoma, with 14% spreading through the
cerebrospinal fluid (CSF) pathways.
–– The presumed cell of origin of pilomyxoid astrocytoma is the embryonic
radial glial cell in the chiasma.
•• Chordoid glioma may be an asymptomatic lesion detected incidentally on
imaging.
•• Fibrillary astrocytoma is rare and is seen in the chiasma/hypothalamus
only in non-NF-1 patients.
•• Adult patients may harbour anaplastic astrocytoma or glioblastoma
multiforme which might mimic a cystic craniopharyngioma or pituitary
adenoma on imaging.
•• Ganglioglioma of the optic nerve is rare.
1027
CLINICAL FEATURES
Visual Dysfunction
•• Visual impairment occurs in about 85% of cases of OPG.
•• It may escape being noticed, as the onset is insidious and the tumour occurs
in children too young to discern the symptom.
•• Drop in visual acuity occurs before field cuts are detected.
•• The differential diagnosis is with retrobulbar neuritis.
•• Primary optic atrophy takes time to set in, but is seen in about 60% cases
of OPG.
•• Rarely the visual loss stops progressing and indeed regresses.
•• Bitemporal hemianopia progressing to bilateral visual loss occurs in adults
due to chiasmal involvement.
•• Acute visual loss might occur due to intratumoural haemorrhage.
Proptosis
•• Painless axial proptosis is commoner in NF-1 patients with OPG, due to
the frequent location of the tumour in the orbit.
•• This may be the only symptom in young children.
•• Painful proptosis is seen only with large tumours and may be due to
compression of branches of the ophthalmic division of the trigeminal nerve
or orbital venous occlusion.
Hypothalamic Dysfunction
•• The symptoms of hypothalamic dysfunction in OPG are commoner in
non-NF-1 patients.
•• Emaciation despite normal caloric intake in an alert child is known as the
“diencephalic syndrome of infancy”. This has been found to be associated
with dissemination of the hypothalamic pilocytic astrocytoma.
•• The somatic growth rate is normal in spite of the emaciation and so is the
pituitary hormonal function.
•• Ironically, some of these children become very obese in later years.
•• The diencephalic syndrome has been attributed to the dysfunction of the
leptin-ghrelin system.
•• Gigantism due to OPG has been reported.
•• Spasmus nutans consists of disconjugate nystagmus, torticollis and
titubation. While OPG can cause spasmus nutans, the prevalence of glioma
in patients presenting with spasmus nutans is very low.
•• Precocious puberty is common in NF-1 children with OPG.
•• Adult patients may present with hypersomnolence due to involvement of
the posterior hypothalamus.
•• Diabetes insipidus is rare as a presenting symptom of OPG and must raise
the suspicion of germinoma or craniopharyngioma.
1028
Symptoms of Increased
Intracranial Pressure
•• Due to the larger size of the mass and association with hydrocephalus,
symptoms of raised intracranial pressure are commoner with OPGs in
non-NF-1 patients.
•• Papilloedema is seen in about 38% of patients.
•• Foster Kennedy syndrome due to optic glioma presents with unilateral optic
atrophy first followed by contralateral papilloedema, the third component
of this syndrome, anosmia, described with olfactory groove meningioma
is never seen with OPG.
INVESTIGATIONS
•• The CT scan and MRI are the currently used modalities for imaging OPG.
•• On CT the tumour is hypodense and shows variable enhancement.
•• The MRI has the advantage of showing the extent of optic pathway
involvement in all three planes without bone artifacts.
•• Fat suppressed T1-weighted (T1W) images with contrast must be obtained.
•• In the orbital ONG, the tubular or fusiform enlargement of the nerve is seen
well in axial images.
•• Since the small tumours may be isointense with the nerve in T1W and T2-
weighted (T2W) images, the diagnosis might rest solely on detecting the
smooth enlargement of the nerve that is well appreciated on comparing
with the opposite nerve in coronal images.
•• Most lesions are T1 hypointense and T2 hyperintense.
•• There is usually good but non-uniform enhancement with gadolinium.
•• The “tram track” sign on MRI refers to a hyperintense core on T1W images,
surrounded by lower signal intensity. On T2W images, the exact opposite
is seen. This is due to perineural arachnoidal gliomatosis.
•• The tram track sign is not specific for glioma and is seen with optic sheath
meningioma, pseudotumour or optic neuritis.
•• The dumb-bell extension in to the intracranial compartment is well seen
in axial or oblique reformatted images. Extension into the optic tracts,
lateral geniculate bodies and to the optic radiation may be detected with
T2W images.
•• The bony optic canal enlargement is better appreciated with CT. Similarly,
the calcification pattern of meningioma (which is the closest differential
diagnosis of OPG) is also better appreciated on CT.
•• The non-NF lesions tend to be larger and have cysts. Calcification is rare.
•• The non-uniform enhancement differentiates the mass from suprasellar
germinoma, which is a common differential diagnosis in children.
•• The larger tumours fill the third ventricle, extend to the subfrontal region
and may encase the vessels of the circle of Willis.
MANAGEMENT
•• The management of OPG is influenced by several variables such as age,
presence or absence of NF-1, location in optic pathway, size and symptoms
(visual acuity, proptosis, raised pressure).
•• The available methods of management are observation, surgery, chemo-
therapy and radiotherapy.
1029
•• Since OPGs are slow growing lesions, any one or more of these modalities
may be needed during the course of management.
Observation
•• Since the growth rate of most OPGs is low, mere watchful expectancy is
an acceptable choice of initial management.
•• The wait-and-watch approach applies to the incidentally detected
asymptomatic tumours, small tumours, patients who have well-preserved
vision with little proptosis and those with NF-1.
•• The surgeon has to instruct the family about the signs of progression and
maintain a meticulous clinical, neuro-ophthalmic and imaging follow-up.
Surgery
•• In contrast to the cerebellar juvenile pilocytic astrocytoma, surgery plays
only a limited role in the tumour with the same histology occurring in the
optic pathway.
•• The indications for surgery are listed in Table 2. Radical surgery has not
been proved to increase the length or quality of survival.
•• Biopsy of intraorbital tumours can be performed by lateral orbitotomy or
by fine needle aspiration.
•• Resection of ONG requires transcranial superior orbitotomy and cannot be
done adequately through the lateral orbitotomy approach.
•• Transcranial orbitotomy can be done through an eyebrow incision but the
traditional method is to raise a frontal flap from behind the hairline.
•• Removing the superior orbital rim allows a lower trajectory and reduces
frontal lobe retraction.
•• The orbital rim may be taken with the frontal bone flap or as a separate
osteotomy piece.
•• Extradural approach is reserved for lesions that do not extend to the optic
canal.
•• Intradural approach is done for gliomas that reach into the canalicular or
the intracranial portions of the optic nerve.
•• The periorbita is opened medial to the superior rectus and the annulus of
Zinn must be sectioned to approach the canalicular part.
•• The approaches to chiasmal-hypothalamic gliomas are listed in Table 3.
•• The infiltrative chiasmal gliomas cannot be radically excised.
Table 2: Indications for surgery in optic pathway glioma

Biopsy for tumours with atypical imaging findings
Mass reduction by cyst drainage and tumour decompression for relieving raised pressure
symptoms or neighbourhood compression syndromes
Disfiguring or painful proptosis
Total excision for orbital optic nerve tumours with total visual loss, so as to prevent
intracranial extension and to provide cure without adjuvant therapies
Excision of exophytic masses (mainly chiasmal)
Ventricular shunt placement for hydrocephalus
1030
Table 3: Approaches for chiasmal hypothalamic glioma

• Subfrontal
– Lateral (pterional)
– Anterior
• Transventricular
– Interhemispheric transcallosal
– Anterior interhemispheric, translamina terminalis
– Endoscopic transventricular
•• Biopsy and sufficient decompression to open the CSF pathways can be

done for big masses.
Chemotherapy
•• The risks of irradiating young children have caused a swing towards the
“chemotherapy-first” approach.
•• Carboplatin based regimes are the most studied.
•• The Packer regimen of concurrent carboplatin and vincristine in a 10-week
induction phase, followed by 48 weeks of maintenance carboplatin/
vincristine resulted in progression-free survival of 75% at 2 years and
50% at 5 years. Imaging evidence of tumour shrinkage was seen in 63%
of patients with this regimen.
•• Children 5 years of age or younger had a more favourable rate of response.
•• Recently, single agent temozolomide therapy has also been found to be
successful.
Radiotherapy
•• Radiotherapy was the initial treatment modality until a decade back.
•• The recognition of endocrine and cognitive side effects of radiotherapy
in young children has made chemotherapy the choice in this age.
•• Radiotherapy is the initial modality in older children and adults.
•• The standard prescription is 45–50 Gy in 2 Gy daily fractions to the
tumour and the surrounding 0.5–1 cm margin.
•• Fractionated stereotactic radiotherapy and Gamma knife radiosurgery
have been recently reported.
PROGNOSIS
•• Spontaneous regression (involution) of OPG has been recorded well in
the literature. Regression may manifest either as an overall shrinkage in
tumour size, or as signal intensity change on MRI. A variable degree of
improvement in visual function may accompany regression.
•• It is recommended that OPGs should not be treated unless they
demonstrate clear disease progression. There is a two-fold difference in
the visual deterioration rates of ONG (21%) and chiasmatic glioma (42%).
•• The tumour related mortality is 0–5% for optic nerve tumours, 29% for
chiasmal tumours and 43% for hypothalamic tumours.
•• Visual improvement after therapy is often not seen but complete recovery
has been occasionally reported.
•• Endocrine defects in survivors are mainly due to therapy and growth
hormone deficiency is the commonest.
1031
Flow chart 1: Management for suspected intraorbital optic nerve glioma
Flow chart 2: Management for suspected chiasmatic/hypothalamic glioma
CONCLUSION
•• Optic pathway gliomas are slow growing tumours but may behave erratically.
•• The treatment recommendation is to observe the course and intervene
only when one is forced to.
•• Chemotherapy for younger children and radiotherapy for older patients is
effective in achieving long-term tumour control.
•• Surgery does little to alter the natural course of the tumour.
•• The management is summarised in Flow charts 1 and 2.
134
CHAPTER
Oligodendrogliomas
CLASSIFICATION
•• Oligodendrogliomas are now generally accepted as a distinct pathological
entity with special clinical features.
•• These are divided into two groups: (1) oligodendroglioma and (2)
oligodendroblastoma.
•• Kernohan further elaborated the morphological characteristics of these
two subgroups.
•• Attempts were later made by the Mayo Clinic group to grade these tumours
on the same lines as astrocytomas (grade 1–4).
•• Based on the presence, absence and degree (high or low) of the following
criteria, viz. endothelial proliferation, necrosis, nuclear/cytoplasmic ratio,
cell density and pleomorphism, they graded these tumours into four groups:
A to D.
•• The WHO classification recognises three subgroups: (1) oligodendroglioma;
(2) mixed oligoastrocytoma and (3) anaplastic (malignant) oligodendroglioma.
•• A more recently used classification is the one proposed by the Sainte-
Anne Hospital (SA). The SA classification is based on the distinction
of two patterns of tumour growth, solid tumour tissue versus isolated
tumour cells and also relies on imaging and clinical features.
•• Difficulties and discrepancies regarding the diagnosis of oligodendrogliomas
are in part due to the lack of an immuno-marker for the identification of
tumoural oligodendrocytes.
INCIDENCE AND SITE

•• Oligodendrogliomas constitute approximately 5–7% of all primary brain
tumours.
•• Most of these tumours are supratentorial, predominantly affecting the
frontal lobes.
•• Lesions that are close to the ventricles or the subarachnoid spaces may
spread along the CSF pathways.
•• Intraventricular oligodendrogliomas are very rare.
•• Oligodendrogliomas of the spinal cord are uncommon.
PATHOLOGY
Gross Morphological Features
•• The tumour is a pinkish red, vascular and friable mass with a rather
deceptive pseudoplane of demarcation.
Chapter 134 • Oligodendrogliomas
1033
•• Central foci of necrosis and cystic degeneration occur in the larger lesions.
•• There is a propensity for calcification and a marked tendency to infiltrate
the cortex.
•• It consists of a monotonous pattern of small round nuclei, with perinuclear
halos, scanty cytoplasm and a prominent cell wall.
•• Like any other glioma, these neoplasms form a spectrum from the
cytologically well differentiated to the anaplastic.
Ultrastructural Features
•• Oligodendroglial tumour cells may have either scanty or abundant
cytoplasm, rich in organelles, including microtubules, free ribosomes,
mitochondria and prominent Golgi apparatus.
•• Polygonal intracytoplasmic crystalline inclusions have been described,
but are not specific.
•• Laminated cell processes overlying the cell body are commonly present
and are typical of oligodendroglioma.
•• Angiogenesis has been proposed as essential for the growth of solid
tumours.
•• The determinants of this process, the growth factors and the vascular
endothelial receptors have a role in determination of tumour prognosis, as
well as perspectives of “targets” for antiangiogenic therapy.
Cytogenetic and Molecular Studies

•• Oligodendrogliomas show distinct genetic alterations, allowing us to distinguish
them from other types of gliomas.
•• The loss of heterozygosity (LOH) on chromosomes 1p and 19q were
reported to be the most frequently observed alterations.
•• While loss of heterozygosity on chromosome 1p is a statistically significant
predictor of chemosensitivity, combination with deletions on chromosome
19q was reported to be associated with both chemosensitivity and longer
recurrence-free survival after therapy.
AGE AND SEX

•• Characteristically it is a tumour of middle-aged persons, although the age
range has been recorded from 3 years to 76 years, with a biphasic peak
between the ages of 6–12 years and a second peak between the ages of
26-46 years.
•• Only 5–6% of tumours occurred in the paediatric age group.
•• Males are more frequently affected (60–65%).
CLINICAL FEATURES
•• These tumours tend to grow relatively slowly.
•• The average duration of symptoms has been reported to vary from 33
months to 43 months.
•• Due to the predominantly frontal location and a relatively slow growth rate,
the tumour attains a large size before symptoms occur.
1034
•• Epileptic fits constitute the most common initial symptom.

•• The highest incidence of epilepsy in patients with supratentorial gliomas
was observed in oligodendrogliomas.
•• The other presenting symptoms include headache, visual disturbances,
papilloedema and focal neurological deficits.
•• There are no characteristic clinical features attributable to this tumour,
except a high propensity for calcification, seen in 25–30% even in plain
X-rays of the skull.
RADIOLOGY
•• The age of the patient, the location of the tumour in the frontal lobe and
the presence of calcification in plain X-rays of the skull should arouse the
suspicion of an oligodendroglioma.
•• On CT scan, the lesion appears as a heterogeneous mass, isodense to
hypodense, as compared with normal brain.
•• With contrast, the tumour may show variable enhancement, usually to a
mild to moderate degree.
•• Low-grade oligodendrogliomas usually do not enhance with contrast.
•• More malignant lesions are characterised by more intense, irregular
enhancement, associated with vasogenic oedema and mass effect.
•• Linear or nodular calcification has been reported in 50–90% of
oligodendrogliomas on CT.
•• On MR they are usually heterogeneous and isointense to grey matter on
long TR images.
•• Calcification, which cannot be seen on conventional spin echo MR, can be
demonstrated on gradient echo imaging.
•• Fifty percent show contrast enhancement.
•• Positron emission tomography (PET) has the ability to differentiate low-grade
oligodendroglioma from astrocytoma, based on the methionine uptake.
•• Low-grade oligodendrogliomas have a high methionine uptake, while in
astrocytomas it can be decreased, moderately increased or may be normal.
•• The dysembryoplastic neuroepithelial tumour (DNET) is a tumour which
contains foci similar in appearance to oligodendrogliomas.
•• Dural based oligodendrogliomas may be confused with meningiomas.
•• Intraventricular oligodendrogliomas must be differentiated from central
neurocytomas which histologically can be very similar in appearance.
•• Clear cell variant of ependymoma is a rare entity which morphologically
mimics oligodendroglioma and poses a diagnostic dilemma.
•• High-grade oligodendrogliomas should be differentiated from other
anaplastic gliomas and metastatic carcinoma.
TREATMENT
General Management Plan
•• It is becoming increasingly apparent that oligodendrogliomas are a distinct
disease on a molecular level and that key genetic derangements can signify
a response to treatment and favourable outcome.
•• The combination of improved imaging techniques, molecular profiling and
new therapies should result in improved outcome with reduced treatment-
Chapter 134 • Oligodendrogliomas
1035
related morbidity for patients with newly diagnosed, progressive and

recurrent oligodendrogliomas.
•• It is necessary to obtain a histological diagnosis in all cases of suspected
oligodendroglioma.
•• This can be achieved by a stereotactic biopsy or excisional biopsy.
•• Subsequent treatment options available are surgical resection of the lesion,
followed by post- operative radiotherapy and/or chemotherapy.
Surgical Management
•• Oligodendrogliomas are managed like any other glioma, with as radical
a removal as possible.
•• However, the role of resection on prognosis, the most appropriate time
for surgery along the natural history of these tumours and the best
operative strategy remain debatable.
•• Surgical or stereotactic biopsy is the first surgical procedure which
enables confirmation of the diagnosis suggested on imaging, assessment
of extension of tumour cell infiltration beyond the abnormalities limit
defined on imaging and currently available molecular biology studies.
•• Biopsies may be the only surgical procedure in patients having a deep-
seated tumour with minimal mass effect or prior to a surgical resection
or a “wait and watch” strategy.
•• Surgical resection may be indicated for the other patients. However, it
has not been demonstrated that time for resection has any influence
on survival, except in patients with rapidly growing tumours with mass
effect causing increased intracranial pressure.
•• The present trend is for maximal safe resection, preserving ‘eloquent’
cerebral areas, since truly large or complete resection of the tumour based
on imaging is not associated with significantly longer survival.
•• Neuronavigation guidance, intra-operative imaging and cortical stimulation
techniques are helpful neurosurgical techniques enabling maximal safe
resection with preservation of functional areas.
Radiation Therapy
•• The 5-year survival for the group who had surgery plus irradiation was 36%,
as compared to 26.5 for surgery alone.
•• Radiation doses between 40 Gy and 50 Gy were as effective as doses
between 50 Gy and 60 Gy.
•• It has been suggested that selected patients who undergo gross total
resection, particularly younger patients with low-grade tumours, may not
require post-operative radiation therapy.
Chemotherapy
•• Fifty to seventy percent of patients with recurrent oligodendroglial tumours
may respond to chemotherapy.
•• Genetically, 60–70% of oligodendroglial tumours are characterised by the
loss of the short arm of chromosome 1 (1p) and the loss of the long arm
of chromosome 19 (19q).
•• Virtually all tumours with the combined loss of 1p/19q respond to chemo-
therapy, which has been the first demonstration of the clinical usefulness
of the genotyping of brain tumours.
1036
•• Two independent large Phase III trials on adjuvant procarbazine, lomustine

and vincristine chemotherapy in anaplastic oligodendroglial tumours have
shown improvement in progression-free survival, but not overall survival,
regardless of 1p/19q status.
•• Temozolomide is a methylating agent that is typically administered once
daily.
PROGNOSIS
•• The median duration of disease from the onset of symptoms to death was
14 months in nine untreated cases.
•• The median post-operative survival period was 14 months longer in those
patients who were considered to have gross total removal of the tumour.
•• Histopathologically five prognostically significant factors, in order of
decreasing importance are: mitoses, necrosis, nuclear cytologic atypia,
vascular hypertrophy and vascular proliferation.
•• Postoperative radiotherapy improved the 5-year survival rate of patients
who had subtotal tumour removal.
•• The presence of calcification and the absence of CT enhancement were
associated with longer survival.
135
CHAPTER
Ependymomas
Harjinder S Bhatoe
DEFINITION
•• Ependymoma is a slow-growing tumour arising from the wall of the cerebral
ventricles or from the ependymal lining of the central canal of the spinal
cord and filum terminale and is composed of neoplastic ependymal cells.
•• The tumour is of neuroectodermal origin and corresponds histologically to
WHO grade II (Table 1).
INCIDENCE
•• Of all neuroepithelial tumours, 3–9% are ependymomas.
•• Ependymoma is a tumour of childhood and accounts for 6–12% of all
paediatric intracranial tumours.
•• Nearly 30% of intracranial tumours in children less than 3 years of age
are ependymomas.
•• Ependymoma is the most common spinal cord tumour, comprising 50–60%
of glial tumours of the spinal cord.
•• Supratentorial ependymomas constitute about 30% of all intracranial
ependymomas.
•• The tumours may be intra- or extraventricular.
•• Of the intraventricular tumours, the ones in the lateral ventricles are more
common.
Table 1: Classification of ependymal tumours

1. Ependymoma
Cellular
Epithelial
Papillary
Clear cell
Mixed
2. Anaplastic ependymoma
3. Myxopapillary ependymoma
4. Subependymoma
5. Ectopic ependymoma
Parasacral
Intra-abdominal
1038
ORIGIN
•• Ependymomas arise probably from a differentiated ependymal cell,
although there is another view of their origin, being from a less differentiated
ependymoglial precursor cell.
•• Rare, familial cases have been reported.
•• Adult tumour cells show allelic losses of chromosome 22, suggesting the
presence of a tumour suppressor gene.
LOCATION
•• Although these tumours can occur at any site where there is an ependymal
lining, nearly two-thirds of the ependymomas are infratentorial, while one-
third are above the tentorium.
•• Most infratentorial ependymomas occur in the midline, often involving
the floor of the fourth ventricle, particularly in the region of the obex, and
hypoglossal and vagal triangles.
•• These infratentorial tumours are solid and can grow laterally into the lateral
recesses and foramina of Luschka.
•• Rarely, extraventricular ependymomas may be seen in the supratentorial
region, especially in children. These probably originate from embryonic
remnants in the brain parenchyma.
•• In adults, infratentorial and spinal ependymomas occur with equal
frequency, while infratentorial ependymomas are predominant in children.
•• In the spinal cord, the cervical and cervicothoracic segments are most
frequently affected.
•• The conus and cauda equina regions are the preferred sites for occurrence
of myxopapillary ependymoma.
CLINICAL PROFILE
•• Ependymomas, as with other posterior fossa tumours of childhood, often
present with features of raised intracranial pressure due to obstructive
hydrocephalus.
•• Generally, this manifests as headache and repeated vomiting.
•• Infants can present with lethargy and macrocephaly.
•• Symptoms are worse in the morning, as recumbency and raised carbon
dioxide blood levels during sleep cause an increase in cerebral blood flow
and a consequent rise in intracranial pressure.
•• Vomiting may precede other symptoms in case the tumour originates in
the caudal part of the fourth ventricular floor and these children may often
undergo initial evaluation by a paediatric gastroenterologist.
•• Gait or truncal ataxia may be seen with involvement of the cerebellar vermis.
•• Nystagmus, papilloedema and ocular cranial nerve palsy may be seen, and
lower cranial involvement may be seen in tumours with lateral extension.
•• Neck pain, head tilt and nuchal rigidity can occur if the tumour extends
caudally through the foramen magnum.
•• Intraventricular tumours present more often with obstructive hydrocephalus,
while extraventricular tumours may manifest as seizure disorder with raised
•• Seizures occur in one-third of patients with supratentorial tumours.
Intraspinal Ependymomas
•• These are intramedullary, at filum terminale or sacral in location and often
have a long history spanning several years.
Chapter 135 • Ependymomas
1039
•• The intramedullary tumour extends over several segments, is usually

discrete, elongated and sausage-like with a clear plane between it and the
cord tissue, causing fusiform expansion of the cord.
•• Backache is often the only symptom for some time and sphincter dysfunc-
tion occurs late.
•• Clinical features reveal myelopathy and there may be a suspended zone
of sensory impairment.
•• There may be a syrinx above or below the tumour.
•• Tumours involving the filum terminale arise from ectopic ependymal cell
rests and may attain a large size before detection.
•• Presentation is in the form of cauda equina syndrome, wasting of calves
and talipes deformity of the feet and ankles.
IMAGING
•• Ependymomas are generally solid tumours.
•• CT shows calcification in nearly 50% of cases and areas of haemorrhage
and cyst formation may be seen.
•• On MRI, these tumours are circumscribed, and appear isointense or
hypointense on T1-weighted images and intensely enhance with contrast.
•• They appear hyperintense on T2-weighted and proton-density images.
•• They appear heterogeneous on MRI due to the presence of cyst formation,
calcification, haemorrhage and necrosis.
•• Cyst formation is often seen in supratentorial tumours.
•• Spinal ependymomas may appear like astrocytomas on MRI.
•• A “tumour cap” at either pole of the intramedullary tumour is highly
suggestive of an ependymoma.
•• On administration of intravenous Gadolinium, tumoural contours are
clearly defined in ependymomas, unlike that of astrocytomas.
•• Besides astrocytoma, an intramedullary ependymoma should be
distinguished from sarcoidosis, a rare condition which responds to
corticosteroids.
MANAGEMENT
•• Surgical excision is the mainstay in the management of these tumours—
whether supratentorial, infratentorial or spinal intramedullary.
•• In patients with supratentorial tumours, a craniotomy is performed and the
tumour—intraventricular or extraventricular—is approached.
•• Real-time ultrasound can reliably demarcate the tumour and a cystic
component can be tapped to relax the brain.
•• Gross total excision is the desired goal, so as to achieve satisfactory
cytoreduction.
•• Infratentorial tumours often lead to hydrocephalus by the time treatment is
sought. Although hydrocephalus can resolve with excision of the tumour, it
is preferable to divert the CSF pre-operatively. This will reduce intracranial
pressure and improve the general well-being of the patient.
•• CSF diversion can be achieved by ventriculoperitoneal shunt (with a filter
device to prevent tumour seeding) or by endoscopic third ventriculostomy.
•• Alternatively, a ventricular catheter can be placed at the time of surgery to
release CSF and reduce brain swelling and intracranial pressure.
•• Treatment with parenteral glucocorticoids for several days helps in reducing
intracranial pressure pre-operatively.
1040
•• Posterior fossa lesions occurring in the fourth ventricle can be exposed by

suboccipital craniectomy or craniotomy.
•• Complete vermis section and excessive lateral retraction should be avoided
to prevent post-operative cerebellar mutism.
•• Intramedullary spinal cord ependymomas are best treated by surgical
excision.
•• The MRI data in three planes should be analysed and it is essential to
define the length and depth of the tumour.
•• Most ependymomas are centromedullary, although uncommonly, they
may be exophytic.
•• Limits of the tumour’s solid portion will determine the extent of laminectomy/
laminotomy.
Adjunctive Therapy
Radiotherapy
•• The role of radiotherapy in ependymomas has been difficult to validate,
although these tumours are radiosensitive.
•• Local field irradiation is the treatment recommended.
•• The recommended dose is 4500–6000 cGy over 5–6 weeks.
•• Prophylactic irradiation of the spinal cord is not advised, since the incidence
of spinal seeding is low.
•• However, for adults, craniospinal irradiation has been advocated in case
of incomplete resection.
•• Children below three years do not receive radiotherapy and in the presence
of anaplastic tumours, have a lower progression-free-survival.
•• Efficacy of chemotherapy is still not established in ependymomas.
ANAPLASTIC EPENDYMOMA
•• As with other glial cell tumours, ependymomas can show aggressive
behaviour in their malignant forms.
•• Anaplastic ependymoma is a high grade malignant tumour (WHO III) with
an aggressive course and unfavourable outcome.
•• Histologically, they exhibit high mitotic activity, microvascular proliferation,
perivascular rosettes of narrow width and pseudopalisading necrosis.
•• GFAP expression is reduced but other immunohistochemical markers of
ependymomas are positive.
•• Anaplastic tumours in children less than three years of age with evidence
of CSF metastases have an adverse outcome.
PROGNOSIS
•• Recurrence rate is high in incompletely resected ependymomas.
•• Deterioration after initial treatment occurs due to local recurrence and
subarachnoid seeding.
•• Seeding of ependymal tumours through the cerebrospinal fluid pathways
is reported with varied frequency
•• Autopsy studies have revealed 30% incidence of seeding of the spinal
subarachnoid space in infratentorial tumours, while no such seeding was
observed in supratentorial tumours.
•• Extraneural metastases, usually to the cervical lymph nodes and lungs,
are seen in high grade tumours.
Chapter 135 • Ependymomas
1041
•• As with subarachnoid seeding, most of the cases of extraneural metastases

occur after surgical excision of the primary tumour.
•• Overall 5-year-survival with surgery and post-operative radiation therapy is
about 50–60%, and long-term survival drops to 40% or less.
•• Prognosis is poor in children with high grade anaplastic lesions in the
posterior fossa.
•• Supratentorial lesions, unless they are high-grade extraventricular tumours,
carry a better prognosis.
•• Spinal ependymomas have a better prognosis with a 5-year-survival of 83%.
•• Thus, the overall prognosis in ependymomas is determined by a matrix of
variables comprising age, location, completeness of surgical resection and
histological type and grade.
MYXOPAPILLARY EPENDYMOMA
•• This tumour is listed as an independent subgroup of ependymal tumours
in the WHO classification.
•• The tumour preferentially involves the filum terminale and is known for its
striking histological appearance.
•• The overall incidence is about 5% of all ependymal tumours and in the
region of the cauda equina, they account for nearly 50% of ependymomas,
most of them arising from the filum terminale.
•• They arise from ependymal glia of the filum terminale and can grow to a
large size.
•• Rarely, they involve the nerve roots or the sacrum, where they may be
extradural.
•• Rare occurrences have been reported in the cervicothoracic cord, lateral
ventricle or brain parenchyma.
•• Subcutaneous sacrococcygeal and presacral myxopapillary ependymomas
represent a distinct subgroup. They probably arise from ectopic ependymal
remnants.
Histopathology
•• These tumours are characterised by radially arranged cuboidal cells in a
papillary manner around a vascular stroma, with a background of mucoid
matrix that forms microcysts.
•• The mucoid matrix can be deposited by tumour cells and vascular
extravasation via endothelial fenestrations.
•• There is low mitotic activity.
•• The tumour cells are positive for GFAP, S-100 and vimentin with lack of
reactivity for cytokeratin.
Clinical Features
•• Myxopapillary ependymomas typically present with back pain, often of
long duration.
•• Large tumours cause pressure and stretching of nerve roots causing
wasted legs, foot drop and sphincter dysfunction with saddle anaesthesia
and absent tendon jerks in the lower limbs.
•• Small tumours can be suspected by virtue of their intradural location on MRI,
while large, sacral and subcutaneous tumours can be mistaken for chordoma.
•• In contrast to other ependymomas, myxopapillary tumours are hyperintense
on T1-weighted images.
1042
Management
•• Intradural tumours need excision through a laminectomy.
•• Total excision with preservation of neural function is the goal of surgery.
•• Large tumours involving the sacrum may need spinopelvic stabilisation, if
involvement of the sacroiliac joints causes instability.
Prognosis
•• Myxopapillary ependymomas show good outcome with more than 10-year-
survival after total or even partial excision.
•• Sacrococcygeal ependymoma, however, can recur early and distant
metastases may appear.
PARASACRAL EPENDYMOMAS
•• These can occur in an anterior or posterior (subcutaneous) location.
•• They originate from ependymal cell nests and present from infancy to the fifth
decade of life.
•• Posterior lesions generally present as a subcutaneous mass, while anterior
lesions present as an abdomino-pelvic mass with sphincter disturbances.
•• Imaging studies show a sacral mass and the diagnosis of an ependymoma
is often made only after surgery.
•• These tumours are well circumscribed and histologically are typical of
myxopapillary ependymomas.
•• These tumours have to be distinguished from other mucinous or myxoid
lesions, such as chordomas, chondroid tumours and mucinous metastatic
adenocarcinomas.
136
CHAPTER
Medulloblastomas
BS Sharma
•• The term medulloblastoma was first used by Bailey and Cushing in 1925.
•• Medulloblastomas account for approximately 20% of all childhood brain
tumours and 40% of all paediatric posterior fossa tumours.
•• Medulloblastomas occur more frequently in children with 70% of all cases
occurring below 10 years of age.
•• The peak age of incidence is 5 years. Twenty per cent of all medulloblastomas
may occur in adults, of which 80% are paramedian (i.e. cerebellar
hemisphere) and 40% desmoplastic.
PATHOLOGY
•• Stevenson and Echlin postulated that a medulloblastoma arises from the
foetal external granular layer of Obersteiner—a sub-pial layer of small,
primitive cells present throughout the cerebellar cortex at birth, which
gradually disappears during the 1st year of life.
•• This external granular cell layer provides cells which ultimately give rise
to the definitive, internal granular layer as well as basket cells and stellate
cells.
•• Alternative cells of origin include the subependymal cells of the medullary
velum and possibly the internal granular cell layer.
GROSS APPEARANCE
•• The tumour is soft, greyish-purple, granular and deceptively circumscribed,
with areas of necrosis.
•• Cyst formation and calcification are rare.
•• The desmoplastic form of the tumour seen more commonly in adults is
darker in colour, firmer and often occupies a lateral cerebellar location.
•• Medulloblastomas have also been reported in the cerebellopontine angle
and rarely in the supratentorial region.
HISTOLOGY
•• The tumour is composed of small blue cells.
•• It is highly cellular with frequent mitoses, occasional necrosis and clustering
in Homer-Wright rosettes.
•• The cells have a high nuclear-cytoplasmic ratio, coarse chromatin and
angular/carrot-shaped nuclei.
•• Five histological variants are recognised.
1044
•• Neuronal, as well as rhabdomyomatous or melanocytic differentiation, may

point to a multipotential, undifferentiated precursor cell, which suggests that
medulloblastomas may have a PNET origin.
•• The WHO classification of brain tumours (1979) prefers to designate it as
a primitive neuroectodermal tumour (PNET).
•• Neuronal differentiation is indicated by immunohistochemical positivity for
beta 3 tubulin, MAP 2, TAO, synaptophysin, somatostatin, substance P
and bombasin.
•• Astrocytic differentiation may reveal areas of GFAP positivity.
•• Neuronal differentiation may reduce the malignant potential and show a
decrease in cellular proliferation, as indicated by a low Ki-67 labelling index.
MOLECULAR GENETICS
•• Medulloblastomas may also arise in association with the naevoid basal
cell carcinoma syndrome (Gorlin’s syndrome), the Li Fraumani syndrome
associated with a germline p53 mutation on chromosome 17p, familial
Wilms’ tumour and the APC form of Turcot’s syndrome.
•• Molecular markers, such as amplification of MYCC, ERB B2 and a low
apoptotic index, have been shown to have a poor prognosis.
•• Tumours with high TRKC (neurotrophin-3 receptor) have a better outcome.
•• Aberrant signal transduction in medulloblastomas has been implicated in
its tumourigenesis and has opened exciting avenues for development of
newer chemotherapeutic regimens and risk stratification. These are:
–– Wingless (WNT) signalling: The WNT pathway, when activated, in-
activates the adenomatous polyposis coli (APC) complex, resulting in
the transcription of genes, such as Cyclin D1 and MYCC.
–– The Sonic Hedgehog (SHH) pathway is implicated in Gorlin’s syn-
drome, which is a familial predisposition to basal cell carcinomas,
medulloblastomas and rhabdomyosarcomas. Medulloblastomas that
carry mutations in the SHH pathway preferentially show a nodular,
desmoplastic morphology.
–– ERB B2 pathway Upregulation of the tyrosine kinase 1 ERB B2 recep-
tor signalling results in cell transformation and may be seen in 80% of
paediatric medulloblastomas. These may amplify the metastatic and
angiogenetic cascade, resulting in a poor prognosis.
CLINICAL FEATURES
•• Medulloblastomas characteristically arise from the cerebellar vermis and
grow into the fourth ventricle obstructing the flow of CSF.
•• The clinical features, therefore, consist of headache, vomiting, enlarging
head truncal ataxia and other cerebellar signs.
•• They frequently infiltrate the brainstem and, hence, produce clinical features
attributable to it.
INVESTIGATIONS
•• Medulloblastomas on CT scans appear as hyperdense, intensely enhancing,
well-defined vermian masses, usually accompanied by hydrocephalus.
•• Twenty per cent of tumours may show calcification.
Chapter 136 • Medulloblastomas
1045
•• MRI reveals a vermian mass usually separate from the floor of the fourth
ventricle on axial and sagittal (sign of the superior medullary velum)
sequences, which is homogeneously hypointense on T1-images.
•• On T2-weighted images, the signal is intermediate between grey matter
and white matter, while it is isointense to grey matter on FLAIR sequences.
•• These findings are in contrast to other CNS tumours which are mostly
hyperintense to grey matter on T2 and FLAIR sequences.
•• Magnetic resonance spectroscopy (MRS) is nonspecific indicating high
choline and lactic acid with low N-acetyl aspartate levels.
STAGING
•• Tumour staging, based on surgical findings was proposed by Chang
et al. in 1969.
•• Langston proposed an MRI-based modification of Chang’s system with the
main difference being that the T stage did not account for hydrocephalus
or the number of structures involved.
•• The T stage has not been as powerful a prognostic factor for disease free
survival, as has the M stage.
•• Currently, children are divided into two risk groups:
–– Standard risk—includes patients with non-disseminated (MO) disease
with less than 1.5 cm2 of residual tumour and >3 years of age.
–– High risk—includes all cases with disseminated disease and with re-
sidual tumour greater than 1.5 cm2 and children <3 years.
•• Medulloblastoma is the most common CNS tumour with a propensity for
extraneural spread to the bone, bone marrow, liver and lymph nodes.
•• These may occur in approximately 1–2% of all cases at the initial
presentation itself.
PROGNOSTIC FACTORS
Age
•• Very young children less than 3 years of age represent 25–30% of the case
load and their 5-year survival rate is 12%.
•• Poor prognosis may be linked to larger tumours at presentation, as this
age group tends to be relatively clinically silent.
•• More aggressive tumours, a low rate of complete surgical resection, higher
proportion of CNS dissemination and the inability of the immature brain to
tolerate radiotherapy may also account for the poor outcome in this age
group.
•• Adults with medulloblastomas have a better prognosis than the less than 3
year population, but have a shorter median survival than children.
Histology
•• The prognostic significance of a desmoplastic component amongst tumours
remains uncertain with variable results emanating from a search of the
literature.
Glial Differentiation
•• The risk for relapse was also directly proportional to the amount of GFAP
expressed.
1046
ERB-B2 Expression
•• Multicentre analysis of molecular defects in paediatric medulloblastomas
reveals that children with standard risk ERB-B2 negative disease had a
median survival of 100% at 5 years, compared to 54% of children with
average risk ERB-B2 tumours.
•• In summary, children less than 3 years old, amplification of MYCC, ERB-B2,
a low apoptotic index, distant metastases, partial resection, brainstem
infiltration and glial differentiation are poor prognostic indicators, whereas
adults and patients whose tumours are desmoplastic or have neuronal
differentiation fare better.
MANAGEMENT SURGERY
Microsurgical Anatomy
•• The fourth ventricle is roughly a pyramid with its floor formed by the pons
and the medulla.
•• The superior and inferior medullary vella form the roof.
•• The superior, middle and inferior cerebellar peduncles form the lateral
boundaries.
•• Inferior apex opens into the cisterna magna through the foramen of Magendi
•• The superior apex opens anteriorly into the cerebral aqueduct; and the
lateral apices open into the cerebellopontine angle.
•• The floor is divided by the transverse medullary stria and the vertical
median sulcus.
•• Cranially, the median sulcus is flanked by the facial colliculi and inferiorly
by the hypoglossal trigone, the vagal trigone and the area postrema.
They derive their blood supply from the tonsillohemispheric branch of the
posterior inferior cerebellar artery.
•• Medulloblastomas arise commonly from the superior medullary vellum and
may invade the cerebellar peduncles and the dorsal brainstem in about
one-third of cases.
Surgical Strategies
Management of Hydrocephalus
•• Some centres believe that ventriculoperitoneal shunting may decrease
operative mortality, by affording time to perform diagnostic tests, prepare the
patient and schedule a major neurosurgical procedure electively. Reduction
in intracranial pressure also permits safer resection.
•• The other stratagem is a course of preoperative steroids, external
ventricular drain placement and emergent surgery.
•• If the patient is stabilised with steroids alone, surgery may be scheduled
at the next elective operating date.
•• This latter approach prevents the need for shunting and, therefore, all
the possible shunt related complications, such as infection, migration,
intracranial haematomas, shunt block, dissemination of malignant cells
into the peritoneal cavity, delaying definitive treatment, reverse herniation
and tumour haemorrhage.
•• Either strategy is acceptable.
•• Intermediate stratagems involve the use of Millipore filters to prevent tumour
dissemination and endoscopic ventriculostomy.
Chapter 136 • Medulloblastomas
1047
Definitive Surgery
•• The tumour is soft, suckable and highly vascular with the blood supply
derived from the branches of the PICA.
•• In very young children, even a small amount of blood loss during tumour
decompression could cause serious hypotension. All efforts must be made
to reduce blood loss and promptly replace the amount lost.
•• As the tumour collapses, a plane is usually evident along the cerebellar
vermis, the hemispheres, the cerebellar peduncles and most importantly
the ivory white floor of the fourth ventricle.
•• The ventral plane of the tumour is breached first at that portion where the
tumour is free from the brainstem. The rest of the tumour is subsequently
removed.
•• Medulloblastomas are not truly encapsulated and are highly vascular.
•• The aqueductal section of the tumour is the last to be removed, to
prevent blood from entering the third ventricle and producing obstructive
hydrocephalus or shunt dysfunction.
•• Medulloblastomas may infiltrate the brainstem and cerebellar peduncles.
Attempts at removal can permanently harm the child.
•• Small bits of tumour adherent to the brainstem or vessels should be left
behind and have not been shown to diminish survival or increase relapse.
•• CO2 laser can help in removing the tumour adherent to the brainstem and
in achieving haemostasis.
•• Perioperative Complications are:
–– Pressure sores
–– Air embolism
–– Delayed anaesthetic arousal
–– Pseudobulbar palsy
–– Cerebellar mutism
–– Aseptic meningitis
–– Stress ulcers
–– Postoperative pseudomeningocoele
–– Cervical spine instability.
RADIATION THERAPY
Historical Perspective
•• The initial attempts at irradiation with a 3,600 cGy craniospinal dose
coupled with a posterior fossa boost of 5,000 cGy yielded survival rates
of 50% at 5 years.
•• This, however, resulted in tremendous cognitive decline and hence, a
combined Children’s Cancer Group/Paediatric Oncology Group randomised
trial (CCG 9014/POG9331) was undertaken to compare standard dose
neuraxis radiation (3600 centigrade/20 fractions) with reduced neuraxis
radiation(2340 centigrade/30 fractions) in patients with standard risk
medulloblastoma, along with the use of adjuvant chemotherapy.
•• Chemotherapy consisted of weekly vincristine during radiotherapy followed
by seven cycles of cisplatin, vincristine and cyclophosphamide.
•• Intensity modulated radiation therapy, which involves conformal radiation
delivery, using multileaf collimators, multiple beam angles, varied exposure
times and fused digital imaging helps deliver stereotactic radiation, while
reducing normal brain exposure. Its main benefit would appear to be reduced
cochlear radiation and hearing loss.
1048
CHEMOTHERAPY
•• Chemotherapy include vincristine with radiotherapy followed by post-
radiation vincristine, prednisone and CCNU.
•• Other regimens include methotrexate, carboplatin, iproplatin, etoposide,
cyclophosphamide, cisplatin, in addition to CCNU and vincristine.
•• At present, chemotherapy allows greater survival in high-risk
medulloblastomas and helps reduce the craniospinal radiation dose for
paediatric patients with standard risk.
•• Chemotherapy has not been proven to better outcome in adult
medulloblastoma patients, as tolerance is poor.
Neuroendocrinologic Dysfunction
•• Growth failure: Decreased growth velocities remain the most common
form of neuroendocrinologic dysfunction. Growth hormone replacement
therapy can be employed safely, but 2 years should elapse after completion
of therapy.
•• Hypothyroidism: It may be due to either irradiational damage to
the hypothalamus or thyroid gland. Routine screening and hormone
replacement is essential.
•• Secondary malignancies
–– As survival improves, secondary malignancies occurring in the fringes
of the radiational fields have assumed greater importance.
–– Meningiomas and high-grade gliomas may occur in survivors of medul-
loblastomas.
–– Secondary acute myeloid leukaemia may occur in patients who have
undergone chemotherapy, as can cancer of the salivary glands, cervix,
central nervous system, thyroid and acute lymphoblastic leukaemia.
•• Hearing loss: Ototoxicity may be secondary to either whole brain irradiation
with cochlear exposure or may be cisplatin induced. Consequently,
oxaloplatin, a cisplatin derivative may be preferred, since it has no
ototoxicity and nephrotoxicity.
Newer Chemotherapeutic Agents

•• These include erlotinib, an ERBB2 receptor inhibitor.
•• SCH66336 is an oral farnesyl transferase inhibitor that blocks the ras
pathway.
•• Gefitinib, a PDGF inhibitor is also undergoing trials.
137
CHAPTER Metastatic Brain
Tumours
Ravi Ramamurthi  Harinivas
DEFINITION
•• Metastasis is defined as the spread of malignant tumour cells from a primary
neoplasm to distant tissue to form a new growth.
•• A solitary metastasis is a single brain lesion without evidence of metastatic
spread elsewhere in the body.
INCIDENCE OF BRAIN METASTASIS

•• Metastatic brain tumours are the most common intracranial neoplasms
found of autopsy in adults.
•• The incidence of metastases is thought to be rising due to better detection
and treatment of systemic malignancy.
•• It is more common in adults compared to children.
•• Among adults the highest incidence is seen in the fifth to seventh decades.
•• Approximately 75–85% of lesions are supratentorial and 15–25% are
infratentorial.
FACTORS GOVERNING THE

METASTATIC PROCESS
•• The first phase of pathogenesis is invasion of cancer cells into blood, lymph
or cerebrospinal fluid (CSF).
•• In the second phase, there is dissemination with transport of cancer cells.
Most of the cells are killed and only viable cells which reach the target
organs develop into micrometastasis.
•• The final phase involves the growth of these viable cells into either single
or multiple metastases.
•• The factors which determine the detachment of tumour cells from the
primary tumour are growth rate of the tumour, tumour necrosis, enzymes
and stress.
CLASSIFICATION DEPENDING ON
SITE OF ORIGIN
Skull and Dura
•• The deposits are mainly located in the vertex or low occiput.
•• They are seen commonly secondary to prostate carcinoma, lymphoma,
breast carcinoma, melanoma, neuroblastoma and osteosarcoma.
1050
Leptomeninges
•• The spread is usually via the CSF pathways.
•• Obliteration of the subarachnoid space with development of hydrocephalus
is more common.
Parenchyma
•• Most common Cerebrum—80%
•• Cerebellum—16%
•• Brainstem—3%.
PATHOPHYSIOLOGY
Pagets Seed and Soil Theory
•• The first process in the formation of metastasis is tumour cell adhesion
to the local extracellular matrix, cell locomotion and proteolysis, which is
followed by invasion into lymphatics, venules and capillaries.
•• This is followed by haematogenous embolism to distant sites and the
tumour cells interact with various blood components to survive the hostile
environment of circulation.
PATHOLOGY
•• On gross examination a secondary deposit is usually well circumscribed
and spheroidal in shape.
•• The cut surface is pinkish-grey, granular and soft.
•• Cystic degeneration and necrosis may be seen on CT scan.
•• Choriocarcinoma secondaries are haemorrhagic.
•• Calcification has been noted in some metastases usually from the
gastrointestinal tract and these have a relatively benign course.
Histopathology
•• Histopathology of the lesion usually reflects the tissue of origin, i.e. the
primary site.
•• Occasionally, in anaplastic and undifferentiated metastases, the differential
diagnosis will be highly anaplastic glioma, lymphoma, amelanotic melanoma
and a small round-cell tumour like a medulloblastoma.
•• The chemokine/receptor system CXCL12/CXCR4 plays a key role in
multiple biological functions including homing of neoplastic cells from the
primary site to the target and metastasis progression.
•• CXCL12 is expressed in tumour cells and in tumour vessels.
•• CXCR7 is expressed by tumour and endothelial cells (both within the tumour
and in the adjacent brain tissue).
•• CXCR4 showed positivity in all samples with a nuclear pattern.
CLINICAL FEATURES
•• In a solitary cerebral metastasis, symptoms and signs of the cerebral lesion
may precede those of the primary malignancy. In such cases, only after the
tumour is removed at surgery, its true nature becomes apparent.
Chapter 137 • Metastatic Brain Tumours
1051
•• Symptoms and signs depend on the site and size of the metastasic deposit.
•• Metastases in the brain become symptomatic more often and earlier than
in other organs such as liver and lungs, though the incidence is much
higher in these organs.
•• Increased intracranial pressure or focal signs may be the presenting feature.
•• The usual symptoms are headache, decrease in cognitive function, nausea
and vomiting.
•• Seizures occur less commonly than in primary neoplasms.
•• Papilloedema is also common.
•• Features of raised intracranial pressure are usually caused by cerebral
oedema, but it can be present due to ventricular obstruction secondary
to cerebellar and brainstem metastasis, and also obstruction of venous
sinuses by the neoplasm.
•• Neuropsychological disturbances are common as the frontal lobe is a
common site for secondary deposits (33%).
•• Stroke like picture may also result from haemorrhage in the metastasis.
•• Metastasis from the highly vascular choriocarcinoma may present as
a cerebrovascular accident due to tumour emboli dislodging from the
pulmonary secondary, where the pulmonary lesion may be misdiagnosed
as a primary lesion.
•• The duration of symptoms is often short with rapid progression. This can
be explained on the basis of extensive oedema associated even with small
subcortical lesions.
INVESTIGATIONS
•• On CT metastases are isodense with abundant hypodense perilesional
oedema disproportionate to their size.

•• On the non-enhanced T1-weighted magnetic resonance (MR) image
metastases are hypointense to isointense compared to grey matter and
are surrounded by vasogenic oedema.
•• They are hyperintense in T2 images.
•• Usually metastases are located at the grey-white junction, often in the
watershed territories such as in the parieto-occipital regions.

•• Proton MR spectroscopic imaging is a non-invasive diagnostic tool for the
investigation of cancer metabolism.
•• As an adjunct to morphologic and dynamic magnetic resonance imaging
(MRI), it is used for the staging, assessment of treatment response, and
therapy monitoring in brain, breast and prostate cancer.
Positron Emission Tomography

•• High-grade and low-grade tumours, recurrence and radionecrosis can
be distinguished by using positron emission tomography (PET) with
fluorine–18.
•• The PET does not distinguish secondary from primary neoplasms.
1052
•• Several clinical reports have suggested that 18F-fluorodeoxyglucose PET

is useful for detecting unknown primary tumours in patients with brain
metastasis.
Whole-Body Magnetic Resonance Imaging

•• The advent of whole-body MRI (WB-MRI) has introduced tumour imaging
with a systemic approach compared to established sequential, multi-modal
diagnostic algorithms.
•• Assessment of individual organs with various soft-tissue contrast, spatial
resolution and contrast media dynamics can be combined with whole-body
anatomic coverage in a multi-planar imaging approach.
•• The WB-MRI has shown advantages for the detection of distant metastatic
disease, especially from tumours frequently spreading to the liver or brain.
It is especially useful as a radiation-free alternative for the surveillance of
tumour patients with multiple follow-up exams.
•• Primary brain tumour: Meningioma, the most common primary intracranial
tumour to be associated with breast carcinoma
•• Brain abscess
•• Infarction and haemorrhage
•• Encephalitis
•• Demyelinating lesion
•• Resolving haematoma
•• Radiation necrosis.
TREATMENT
•• To select the appropriate therapy, one must consider the extent of the
systemic disease, primary histology, and patient age and performance
status, as well as the number, size and location of the BMs.
•• A tissue diagnosis is necessary when the primary tumour is unknown or
the findings on CT/MRI are atypical.
•• Ideal management of BMs requires simultaneous control of the existing BM
(local brain control), prevention of future BM and control of the systemic
cancer (systemic control).
•• The available modalities include whole brain radiation therapy (WBRT),
surgery, stereotactic radiosurgery (SRS), and systemic therapies, such as
chemotherapies, biologic agents and radiosensitising agents.
Medical Management
•• Dexamethasone is the corticosteroid of choice for cerebral oedema
associated with metastasis as it has high glucocorticoid potency and
minimal mineralocorticoid effect.
•• Anticonvulsants should not be prescribed prophylactically.
•• Treatment must be directed not only at the BM (definitive care), but also at a
multitude of other symptoms that plague patients with BMs (supportive care).
Surgery
•• The incidence of solitary metastasis varies from 50 to 89%.
•• Surgical excision of a solitary lesion also helps in diagnosis, especially in
cases where the primary has not been detected.
1053
•• Surgical excision of solitary metastases offers a good chance for reducing

intracranial pressure and improving neurological deficits.
•• The ideal candidates for surgical excision are:
–– Patients with good performance status [Karnofsky performance scale
(KPS)]
–– Minimal or no evidence of extracranial disease
–– Surgically accessible single BM amenable to complete excision.
•• To reduce the risk of tumour recurrence for patients who have undergone
resection of a single BM, postoperative WBRT should be considered.
•• The optimal dose and fractionation schedule for WBRT is 3,000 cGy in 10
fractions or 2,000 cGy in 5 fractions.
•• Surgical adjuncts such as bischloroethylnitrosourea (carmustine) wafers
and the glia site radiation system may be useful in the future in achieving
optimal local tumour control.
•• Factors influencing the risk of local recurrence after resection of a single
BM are:
–– Biological factors (such as tumour volume)
–– Treatment (such as the resection method).
•• Alternatives to surgical excision in solitary metastasis: WBRT followed by
SRS should be considered.
•• Surgical resection followed by WBRT represents a superior treatment
modality in terms of improving tumour control at the original site of the
metastasis and in the brain overall, when compared to surgical resection
alone.
•• Surgical resection plus WBRT and stereotactic radiosurgery (SRS) plus
WBRT, both represent effective treatment strategies, resulting in relatively
equal survival rates.
•• Stereotactic biopsy of a solitary deep lesion in an eloquent area may be
helpful in achieving the diagnosis.
•• The prognosis for long-term survival of patients operated upon for solitary
cerebral metastasis depends on the site of the metastasis, the extent of
removal, the age of the patient and the tissue of origin, the kidney being
the most favourable.
•• WBRT alone is the treatment of choice for patients with single or multiple
BMs not amenable to surgery or radiosurgery.
Chemotherapeutic Regimen
•• In the TP regimen paclitaxol 175 mg/m2 on day 1 and cisplatin 20 mg/m2
on days 1–5 are given.
•• The NP regimen consists of navelbine 25 mg/m2 on days 1 and 8 and
cisplatin 20 mg/m2 on days 1–5.
•• Gemcitabine 1 g/m2 on days 1 and 8 and cisplatin 20 mg/m2 on days 1–5
are given in the GP regimen.
•• All regimens were repeated every 3 weeks. Each regimen must be given
for at least two cycles and but not more than four cycles.
•• SRS using the gamma knife or cyberknife has been employed for solitary
cerebral metastasis.
•• Lesions less than 3 cm in size can be targeted using 1,600–3,500 cGy
in a single session and may be a safe alternative to surgical excision in
elderly frail patients with associated medical conditions like diabetes and
hypertension.
1054
•• Short hospital stay and lower steroid requirement is an added advantage.

•• SRS provides good tumour control for small BMs from various primary
cancers, with minimal untoward effects on surrounding normal brain.
•• The cyberknife can greatly raise the fractional dose of SRS, thus improving
its clinical efficacy. Cyberknife has produced perfect clinical outcomes by
using a higher dosage per fraction. It is an appropriate and valid treatment
shortcut for BM.
•• Radiosurgery is an effective and safe minimally invasive option for patients
with BMs from an unknown primary site.
•• Image-guided radiosurgical treatment of BMs resulted in high rates of
tumour control comparable to control rates reported for frame-based
methods.
•• The combined treatment of SRS and WBRT is effective in the control of
brainstem metastasis, improving the neurological symptoms and, therefore,
early diagnosis and treatment is important.
•• Gamma knife SRS is a safe and feasible strategy for treatment of patients
with a single radioresistant BM.
•• Radiosurgery alone is a reasonable treatment option, but may carry a
greater likelihood of distant brain recurrence.
•• Surgery is indicated in patients with a single lesion located in an accessible
zone and SRS is indicated for lesions up to 3 cm in diameter, and in patients
with up to three or four metastasis, no matter their location.
PROGNOSIS
Prognostic Factors Associated with Better Survival
•• KPS higher than 70
•• Solitary BM
•• Age less than 65 years
•• Controlled primary tumour and no extracranial metastasis.
MULTIPLE METASTASES
•• The decision to treat or not, and how to treat metastases when multiple
is difficult.
•• One of the large life-threatening symptomatic metastasis in a young patient
may be removed, followed by WBRT if the primary neoplasm is known to
be radiosensitive.
•• Steroids and diuretics are helpful in alleviating symptoms by reducing the
oedema surrounding the lesions.
•• In terminal cases, steroids can be used with good effect; of course the
side effects may dictate the cessation of therapy. This may be followed by
remission for a few months.
•• The radiation therapy is quite effective in palliation. This is based on the
assumption that even if primary investigations have revealed a single lesion
and the operative removal of a solitary lesion has been complete, there
always exist multiple microscopic undetected metastases.
•• When the primary is unknown in a patient with multiple cerebral metastases,
stereotactic biopsy will be required to confirm the diagnosis.
MENINGEAL CARCINOMATOSIS
•• Meningeal carcinomatosis refers to diffuse metastasis in the leptomeninges
by systemic cancer.
1055
•• Meningeal carcinomatosis is characterised by a diffuse widespread

involvement of the meninges by carcinomatous infiltration.
•• The most frequent primary sites are the breast and lung.
•• This condition is distinct from both metastatic deposits that occur in the
substance of the brain and spinal cord and nodular deposits in the dura.
•• The leptomeninges appear thickened over a wide area both at the base of
the brain as well as the vault.
•• This may occasionally cause occlusion of the CSF circulation leading to
hydrocephalus.
Aetiopathogenesis
•• Meningeal carcinomatosis is a better term than neoplastic meningitis.
•• The aetiopathogenesis of this condition is not clear; the CSF may be
involved via the choroid plexus which may be affected by the malignancy.
•• A deposit in the nerve root or the surface of the brain may spread along
the leptomeninges.
•• Spread may occur via the venous route from the Batson’s plexus.
Clinical Features
•• Because the symptoms resemble a meningeal infection, it has also been
referred to as carcinomatous meningitis.
•• There may be cranial nerve palsies and if the spinal dura is involved, the
patient may present with paraparesis.
•• They may antedate any symptoms of malignancy and, therefore, may be
confused with tuberculous meningitis, cysticercosis, cryptococcal meningitis
or sarcoidosis.
Investigations
•• The diagnosis is confirmed by CSF examination, sometimes with the help
of multiple filters to filter the CSF, or examining a centrifugate revealing
carcinomatous cells will clinch the diagnosis.
•• The MRI shows nodular contrast enhancement lining the CSF pathways.
•• There may be associated hydrocephalus.
•• Gadolinium-enhanced MRI will show neoplastic spread involving the spinal
cord and spinal nerves.
•• Unenhanced fluid-attenuated inversion recovery (FLAIR) images are of
greater value than SE T2-weighted images for the diagnosis of intracranial
meningeal carcinomatosis.
•• Contrast-enhanced FLAIR images are more useful than contrast-enhanced
T1-weighted images in their quality.
•• Meningeal biopsy is helpful when the diagnosis is strongly suspected and
clinical and other investigations fail to support it.
•• Staging of leptomeningeal metastasis requires contrast-enhanced brain
and spine MRI and radionuclide CSF flow study.
Treatment
•• Irradiation of part or of entire neuraxis.
•• Chemotherapy (methotrexate, cytosine arabinoside and thiotepa).
•• Intra-CSF drug therapy primarily utilises one of three chemotherapeutic
agents (e.g. methotrexate, cytosine arabinoside and thiotepa) administered
1056
by a variety of schedules either by intralumbar or intraventricular drug

delivery.
•• A good prognosis is possible in the following:
–– Lymphomatous or leukaemic meningitis
–– Chemosensitive tumours such as breast cancer
–– Low tumour burden
–– Minimal neurological deficits
–– Good performance status
–– Controllable systemic disease.
138
CHAPTER Radiation Therapy for
Malignant Brain Tumours
Julka PK  Haresh KP  Rath GK
INTRODUCTION
•• Surgery is the primary modality of treatment for the majority of primary
brain tumours.
•• Radiotherapy is an essential component in the management in most of
them after a maximal safe surgical resection.
•• Radiotherapy can be delivered by fractionated external beam irradiation,
small field stereotactic irradiation or by interstitial implantation.
•• Current regimens generally use 50–60 Gy delivered in 25–30 fractions
over 5–6 weeks.
•• Regimens with either higher dose or more than 2 Gy per fraction are
associated with late neurotoxicity.
•• The volume of normal brain irradiated should be kept to a minimum, in
order to decrease the late side effects.
•• The tolerance of normal brain (and spinal cord in the case of cord tumours)
is the major limiting factor in achieving local control and cure.
•• Tolerance dose is usually expressed as TD 5/5 and TD 50/5.
•• “TD 5/5” is the dose that leads to 5% risk at 5 years.
•• “TD 50/5” is the dose that leads to 50% risk at 5 years.
•• TD 5/5 and TD 50/5 values for whole-brain fractionated radiotherapy at
2 Gy per fraction are 60 Gy and 70 Gy, respectively. With partial brain
irradiation, the corresponding values are 70 Gy and 80 Gy, respectively.
•• For tumours with high-risk to spread to the CSF space, elective irradiation
of the whole craniospinal axis with localised boost to the area of gross
tumour is necessary.
•• Adverse reactions associated with cranial irradiation include: (1) acute
reactions; and (2) late reactions.
•• Acute reactions: A transient worsening of pre-treatment symptoms
can occur due to peritumoral oedema. This is very well managed by
corticosteroids. Other acute side effects include nausea, vomiting, skin
discolouration, alopecia, otitis externa, serous otitis media, fatigue,
mucositis, oesophagitis (last two only in craniospinal irradiation) and
haematologic toxicity.
•• The late sequelae include:
–– Radiation necrosis, which can mimic a recurrent tumour both sympto-
matically and on radiology.
–– Auditory apparatus damage can occur due to the inclusion of the mid-
dle or inner ear in the field.
1058
–– Visual disturbance can occur due to damage to the eye, optic nerve
or chiasm.
–– Endocrine dysfunction due to damage to the hypothalamo-pituitary
axis.
–– Neuropsychological changes.
RADIOTHERAPY TECHNIQUES
•• It involves the combined work of the neurosurgeon, radiation oncologist
and physicist.
•• SRS can be delivered using a Gamma Knife or a linear accelerator.
•• Gamma Knife contains 201 cobalt-60 (60Co) sources and it is collimated
using a helmet with circular apertures ranging from 4 mm to 18 mm focusing
a single point.
•• Linac based radiosurgery can be either cone-based or multileaf collimator-
based.
•• The treatment is delivered using multiple non-coplanar arcs that intersect
at a single point to treat a tumour of less than 4 cm in diameter.
Stereotactic Radiotherapy
•• It is delivered using a linear accelerator.
•• A fractionated schedule is followed maintaining the precision targeting
techniques of SRS.
•• Either cone or MLC with non-coplanar beams are used as in the case of
SRS.
TREATMENT OF INDIVIDUAL TUMOURS

Gliomas
High-Grade Gliomas (Anaplastic Astrocytoma,
Glioblastoma Multiforme)
•• They account for 35–45% of adult brain tumours.
•• Of the high-grade gliomas, glioblastoma multiforme (GBM) constitute 85%
and anaplastic astrocytoma (AA) constitute 10–15%.
•• Excision is never complete in high-grade gliomas.
•• Even macroscopic complete removal is possible in 10–20% of cases only.
•• One needs to add post-operative radiotherapy in these cases.
•• The less the residual tumour after surgery, the better is the prognosis.
•• Radiotherapy has been used in malignant gliomas for the last six decades.
•• RT can only delay the disease progression or recurrence.
•• Dose of Radiotherapy: The MRC trial compared 45 Gy with 60 Gy and
suggested a statistically significant prolongation of median survival from 9
months in the 45 Gy group to 12 months in the 60 Gy group.
•• Role of Chemoradiation:
–– Chemotherapy is mainly added as a radiosensitiser.
–– The main concern in brain tumours is that to be active, the chemother-
apeutic agents must reach the brain crossing the blood-brain barrier.
–– The chemotherapeutic agents that are used include the nitrosoureas-
CCNU, BCNU, Procarbazine, etc.
Chapter 138 • Radiation Therapy for Malignant Brain Tumours
1059
–– The newer drug is temozolomide, which is a lipophilic second-generation

alkylating agent.
–– Stupp et al. conducted an open-label, phase II trial in GBM in which
Temozolomide (75 mg/m2/d × 7 d/wk for 6 weeks) was administered
orally concomitant with fractionated radiotherapy (60 Gy total dose: 2
Gy × 5 d/wk for 6 weeks), followed by temozolomide monotherapy (200
mg/m2/d × 5 days, every 28 days for six cycles).
–– They observed that concomitant radiation plus temozolomide therapy
was safe and well tolerated.
–– Median survival was 16 months and the 1-year and 2-year survival
rates were 58% and 31%, respectively.
–– Based on randomised data available, chemotherapy has consistently
failed to improve the outcome of patients with anaplastic astrocytoma,
while a meta-analysis showed a small, but significant improvement in
survival favouring the use of chemotherapy.
•• Brachytherapy:
–– Permanent or temporary I-125 or temporary Ir-192 sources can be
after loaded into catheters placed in the tumour bed.
–– The catheters can be placed either during craniotomy or stereotactically.
–– This can be used as a boost dose after external beam radiation in
glioblastoma.
–– Most trials are limited to supratentorial tumours less than 6 cm and that
do not involve the corpus callosum.
Low-Grade Gliomas
•• Low-grade gliomas account for approximately 20% of gliomas and
approximately 10% of all primary intracranial tumours in adults.
•• This is constituted by low-grade astrocytomas 67%, mixed oligoastrocytomas
19% and oligodendrogliomas 13%.
•• Astrocytomas are well differentiated tumours. They show increased
cellularity and mild to moderate pleomorphism. The presence of microcysts
differentiates it from reactive gliosis.
•• The different subtypes of astrocytomas include the fibrillary, protoplasmic,
gemistocytic and pilocytic ones.
•• They are differentiated by the intracytoplasmic fibrillary processes, which
stain with GFAP.
•• With time, 50% of the fibrillary and protoplasmic types transform to more
anaplastic ones.
•• Since the majority of the gemistocytes transform to highly anaplastic ones
and behave in an aggressive fashion, they should be treated like anaplastic
astrocytomas.
•• Pilocytic astrocytomas have a long natural history and rarely dedifferentiate
into more malignant ones.
•• The majority of low-grade gliomas present with seizures without any
neurologic symptoms.
•• Other presentations include headache, vomiting, motor deficit, visual or
sensory loss, language deficit or personality changes.
•• Pilocytic astrocytomas grow by expansion, while non-pilocytic ones diffusely
infiltrate the surrounding structures like malignant gliomas.
•• Complete resection is the treatment of choice for pilocytic astrocytomas.
•• Postoperative radiotherapy is indicated only in incompletely resected
tumours.
1060
•• Complete resection is associated with excellent survival with more than

90% cured of the disease, whereas incomplete resection is associated with
10-year cure rates of 70–80%.
•• In non-pilocytic astrocytomas (Grade 2 gliomas), the initial treatment is
surgery. Since, these tumours are diffusely infiltrative, complete resection
is rarely possible.
•• The dose and timing (immediate versus delayed) of post-operative
radiotherapy in grade 2 gliomas is debated.
•• Deliver immediate postoperative radiotherapy for Grade 2 gliomas with
a dose of 50 Gy in 25 fractions over 5 weeks delivered to the Flair or T2
abnormality on MRI with a margin of 1–1.5 cm, followed by a boost of 6
Gy in three fractions to the gross tumour without margin.
Brainstem Gliomas
•• About two thirds of brainstem gliomas occur in children.
•• The survival and prognostic factors are entirely different for adults compared
with children.
•• The tumour may contiguously involve the cerebellar peduncles, cerebellum
and/or thalamus.
•• The majority of childhood brainstem gliomas are diffuse pontine gliomas,
which have a very poor prognosis.
•• Focal pilocytic astrocytomas have a better prognosis.
•• They most frequently arise in the tectum of the midbrain, focally, within the
pons or at the cervicomedullary junction.
•• Generally, the diagnosis is made radiologically and biopsy is not mandatory.
•• The tumours of the midbrain, especially in the tectal plate region, are usually
low-grade and have a greater likelihood of long-term survival (approximately
80% 5-year progression-free survival vs less than 20% for tumours of the
pons and medulla).
•• The standard treatment for children with diffuse intrinsic pontine glioma is
radiation therapy to involved areas, but 90% of patients will die within 18
months of diagnosis.
•• The conventional dose of radiation therapy ranges between 5,400 cGy and
6,000 cGy given locally to the primary tumour site in daily fractions of 1.8 Gy.
•• The utility of chemotherapy in the treatment of patients with newly
diagnosed diffuse pontine gliomas is unproven.
•• In focal or low-grade brainstem gliomas, maximal surgical resection should
be attempted, followed by adjuvant radiotherapy.
•• Mehta et al. classified focal intrinsic brainstem tumours into three types:
Expanding, diffuse infiltrative and pure ventral varieties.
•• Surgical intervention in the expanding variety was associated with excellent
long-term prognosis.
•• The other two varieties were associated with poor outcome and the authors
recommended that they should be subjected to radiotherapy only.
•• Patients with small tectal lesions and hydrocephalus but no other
neurological deficits may be treated with cerebrospinal fluid diversion alone
and have follow-up with sequential neuroradiographic studies, unless there
is evidence of progressive disease.
Ependymomas
•• Ependymomas occur in both adults and children.
•• The peak incidence is at 5 years and 34 years.
1061
•• In adults, approximately 33% of ependymomas arise infratentorially and

66% arise supratentorially; the opposite is true in children.
•• It is classified into ependymomas (low-grade) and anaplastic ependymomas
(high-grade) according to WHO classification.
•• The 5-year survival ranges from 60 to 80% in low-grade versus 10 and
47% in high-grade tumours.
•• They usually originate in the ependymal linings of the ventricles in the
posterior fossa or supratentorial region and have access to the cerebral
spinal fluid (CSF) and, therefore, may spread throughout the entire neuraxis.
•• These tumours can cause hydrocephalus and increased intracranial
pressure, mimic brainstem lesions, cause multiple cranial nerve palsies,
produce localising cerebellar deficits and cause neck stiffness and head
tilt if they infiltrate the upper portion of the cervical cord.
•• Every patient with ependymoma should be evaluated with diagnostic
imaging (CT/MRI) of the spinal cord and whole brain.
•• In addition, CSF cytological evaluation should be conducted.
•• Patients with totally resected tumours tend to have the best prognosis.
•• Surgery should be performed in an attempt at maximal tumour reduction.
•• Supratentorial ependymomas generally have a poorer prognosis than their
infratentorial counterparts.
•• Radiotherapy significantly improves tumour control and survival.
•• The volume of CNS to be irradiated is controversial.
•• Many authors recommend the inclusion of the entire craniospinal axis or
whole brain in the treatment of anaplastic ependymomas.
•• Spinal metastases are not prevented by prophylactic spinal irradiation,
regardless of tumour grade and site.
•• With the availability of MRI to detect involvement of the spine, it is
generally agreed that one can go ahead with local RT even in anaplastic
ependymomas, unless the spine or CSF are involved.
•• The treatment algorithm for adult ependymomas revolves around histology,
extent of surgical resection and extent of disease in the craniospinal axis.
•• Patients with a well differentiated ependymoma who have undergone a
gross total resection and have a negative screening spinal MRI scan, may
be treated by limited-field radiation.
•• However, if a contrast enhanced spinal MRI scan reveals disease,
craniospinal irradiation should be administered.
•• In patients with anaplastic ependymoma, if the spinal MRI scan is negative,
limited-field RT is normally given. However, if the spinal MRI scan is
positive, craniospinal irradiation is indicated.
•• Based on dose-response analyses for ependymomas, the typical radiation
dose is between 50 Gy and 55 Gy locally using 1.8–2.0 Gy per fraction.
•• For a low-grade ependymoma, the usual dose is 54 Gy to tumour plus 2
cm margin.
•• For a high-grade ependymoma, it is 60 Gy to tumour plus 2–3 cm margin.
•• Ependymomas do not appear particularly responsive to chemotherapy.
However, chemotherapy is sometimes considered as a salvage option to
best supportive care in cases of recurrence.
Medulloblastoma
•• Medulloblastoma is the most common type of malignant brain tumour in
childhood (peak 5–10 years).
•• About 15–20% of cases occur in adults.
1062
•• It belongs to the group of tumours known as primitive neuroectodermal

tumour, which is a highly malignant, small round blue cell tumour of the
central nervous system.
•• This tumour usually originates in the cerebellum. It may spread contiguously
to the cerebellar peduncle, floor of the fourth ventricle, into the cervical
spine or above the tentorium.
•• In addition, it may spread via the cerebrospinal fluid intracranially and/or
to the spinal cord.
•• The incidence of CSF spread at diagnosis is 10–15%.
•• The work up investigations include contrast enhanced MRI of the brain and
whole spine and CSF cytology.
•• A bone scan as well as a bone marrow aspiration and biopsy may be
useful in symptomatic patients or in those with abnormal blood cell counts
at diagnosis.
•• Two major risk categories are now being used:
–– Average risk: Children older than 3 years with posterior fossa tu-
mours; tumour is totally or near-totally (<1.5 cc’s of residual disease)
resected; no dissemination.
–– Poor risk: Children 3 years old or younger or those with metastatic
disease and/or subtotal resection (>1.5 cc’s of residual disease) and/
or non-posterior fossa location.
•• The patients should undergo maximal resection.
•• The traditional post-surgical treatment for these patients has been
radiation therapy consisting of 5,400–5,580 cGy to the posterior fossa
and approximately 3,600 cGy to the entire neuraxis (i.e. the whole brain
and spine).
•• In poor-risk patients, the addition of chemotherapy has improved the
duration of disease-free survival.
•• Children younger than 3 years are particularly susceptible to the adverse
effect of radiation on brain development. Debilitating effects on growth
and neurologic development have frequently been observed, especially
in younger children.
•• For this reason, chemotherapy is administered to delay the administration
of radiation therapy.
•• Different chemotherapeutic regimens have been employed and most have
utilised an alkylator (cyclophosphamide or ifosfamide), cisplatin and/or
carboplatin, oral or intravenous etoposide and vincristine.
•• High-dose chemotherapy and autologous stem cell rescue is also tried in
children less than 3 years.
•• The treatment of medulloblastoma in adults is similar to that of children.
The management is by surgery followed by radiotherapy to the neuraxis.
•• Chemotherapy is added for poor-risk patients.
•• The 5-year survival ranges from 46 to 78% and the 10-year rates from
38 to 55%.
Primary Central Nervous System Lymphoma

•• Primary central nervous system lymphoma (PCNSL) is a rare form of
non-Hodgkin’s lymphoma (NHL) that is restricted entirely to the brain,
leptomeninges, eyes and rarely the spinal cord, without systemic disease.
•• It accounts for 0.5–2% of all primary brain tumours.
1063
•• This disease is seen more commonly among patients with acquired

immunodeficiency syndrome (AIDS) and other immunocompromised states.
•• Primary central nervous system lymphoma is probably a substantially
different disease in persons with and without AIDS with regard to patient
characteristics, clinical and radiographic presentation and prognosis.
•• More than 50% of the lesions on computed tomographic (CT) scans in
patients with AIDS are ring-enhancing and multifocal, a pattern rarely
described in immunocompetent patients.
•• Patients without AIDS almost always show only homogeneous
enhancement.
•• A periventricular, diffusely enhancing lesion on magnetic resonance
imaging (MRI) is suggestive of primary CNS lymphoma.
•• Tumours are often periventricular and may involve ependymal lining cells
or, if more peripherally located, may extend to the leptomeninges.
•• Leptomeningeal involvement may remain localised to adjacent parenchymal
sites or can be more diffuse with positive CSF cytology.
•• Ocular involvement may develop independently in 10–20% of primary CNS
lymphoma patients with primary brain disease.
•• Less often, the tumour arises within the eye as the initial manifestation of
primary CNS lymphoma.
•• In rare cases, the spinal cord parenchyma may be an initial or secondary
site of primary CNS lymphoma.
•• The work up investigations include haemogram, liver and kidney function
tests, HIV, chest X-ray, MRI of brain and spine, and a biopsy from the lesion
(preferably a stereotactic biopsy).
•• If there is no risk of herniation, a lumbar puncture with evaluation of CSF
is recommended.
•• An ophthalmologic evaluation including a slit-lamp examination should be
done to exclude an obvious malignant uveitis.
•• If there is a reasonably high suspicion of primary CNS lymphoma, it is
preferable not to start therapy empirically with steroids, unless medically
indicated.
•• Because of the diffuse nature of central nervous system (CNS) lymphomas,
aggressive surgical decompression with partial or gross total removal of
the tumour is of no benefit to the patient.
•• Systemic treatment is compromised by the blood-brain barrier, which is
impermeable to several cytostatic agents.
•• The role of RT for patients with primary CNS lymphoma continues to evolve.
•• Early studies demonstrated that these tumours were radiosensitive and
that complete and partial responses could be obtained using doses ranging
from 3,000 cGy to 5,000 cGy.
•• However, the responses were brief and patients often developed recurrent
disease within a matter of months.
•• The currently recommended dose of RT for cerebral primary CNS
lymphoma is between 4,000 cGy and 5,000 cGy (whole brain), without
a boost.
•• However, RT should be avoided in patients older than 60 years.
•• For patients with ocular lymphoma, irradiation is the treatment of choice;
3,600 cGy should be administered to both eyes.
•• Median survival times for studies with pre-irradiation CHOP (cyclophos-
phamide, doxorubicin, vincristine and dexamethasone) were no better than
for radiation therapy alone.
1064
•• High-dose methotrexate (≥ 3 g/m2) is the single most active agent against

primary CNS lymphoma and should be a part of any chemotherapy regimen.
•• For healthier patients (i.e those 60 years or younger with a KPS ≥ 40 and
a creatinine clearance ≥ 50; those older than 60 years with a KPS > 50),
some type of pre-radiation chemotherapy is generally recommended; a
high-dose methotrexate based regimen is most commonly used.
•• In patients older than 60 years, RT may be omitted to avoid neurotoxicity.
•• For patients with extremely poor KPS (< 40) or creatinine clearance less
than 50, it is recommended that treatment consist of whole brain irradiation
(45 Gy), in order to rapidly induce a response, diminish neurologic morbidity
and optimise quality of life.
139
CHAPTER Adjuvant Therapies for
Malignant Brain Tumours
Raj Kumar R  Ashok Kumar Mahapatra
•• A variety of adjuvant therapies specially chemotherapeutic agent are

recommended for management of malignant brain tumours. Their
therapeutic potential is dependent upon a number of factors mentioned
below.
BLOOD-BRAIN BARRIER
•• The highly effective blood-brain barrier (BBB) is one of the main reasons
for the relative inaccessibility of the brain.
•• The continuity of this barrier is maintained by the tight junctions of the
capillary endothelial cells, lack of fenestrations with the endothelial cells,
limited pinocytosis, normal astrocytes and the presence of ‘P’ glycoprotein.
•• The capillary permeability, the molecular weight of the drug and its
lipophilicity regulate drug penetrance in the CNS.
•• Drugs with a molecular weight greater than 450 kDa cannot cross the BBB,
despite being lipophilic.
•• The BBB may get partially disrupted by malignant gliomas.
•• Similarly, higher doses of chemotherapeutic agents increase BBB
penetration.
•• The intrathecal route of drug administration is an effective route for
bypassing the BBB.
Tumour Heterogeneity
•• Following BBB penetration, the availability of the drug at the tumour site is
dependent upon the transcapillary flow of the drug to the tumour.
•• This is restricted due to the heterogeneity of the tumour seen more
commonly in brain tumours.
•• The tumour cells are in various stages of the cell cycle which is another
factor in limiting drug efficacy, since the sensitivity varies in different portions
of the tumour, hence resulting in the variable response.
Drug-Drug Interaction
•• Drugs which induce hepatic cytochrome 450 enzymes reduce the efficacy of
the chemotherapeutic aspects, by altering and increasing drug metabolism
and clearance of the drugs.
•• This in turn allows suboptimal dosage at the tumour site, resulting in
treatment failure (Fig. 1).
1066
Fig. 1: Cell cycle

Tumour Resistance
•• Over the years, inherent tumour resistance to chemotherapy has been
noticed, resulting in a low response rate.
•• Glioblastoma has been shown to have the least response rate.
•• Some anaplastic oligodendrogliomas, especially those with LOH at 1p/19q,
have been shown to have a higher response rate.
•• Sometimes it has been noticed that tumours which were initially responsive
demonstrate progressively decreasing levels of response. This indicates that
the tumour had certain resistant cells, the population of which has grown rapidly.
Chemotherapeutic Agents
Table 1: Chemotherapeutic agents

Group Agent Mechanism
Nitrosourea Carmustine (BCNU) DNA cross links,
Lomustine (CCNU) carbamoylation of
Nimustine (ACNU) amino groups
Alkylating Procarbazine (P) DNA alkylation,
(methylating) interferes with protein
Agents Temozolamide (TMZ) Synthesis
Carboplatin Chelation via intrastrand
Cisplatin crosslinks
Nitrogen Cyclophosphamide DNA alkylation,
mustard Isofamide carbonium ion
Cytoxan formation
Vinca Vincristine Microtubule formation
alkaloids Vinblastine inhibitor
Pacilataxel
Epidophy- Etoposide (ETOP) Topoisomerase II
llotoxins Teniposide (VM26) inhibitor
Miscellaneous Topoteca Topoisomerase I
Irinotecan (CPT11) inhibitor
Tamoxifen Protein kinase inhibitor
Hydroxyurea
Bleomycin
Methotrexate
Chapter 139 • Adjuvant Therapies for Malignant Brain Tumours
1067
Newly Diagnosed Glioblastoma

Neo-adjuvant chemotherapy
•• Neo-adjuvant refers to administration of chemotherapy prior to radiotherapy.
•• Repeated trials have failed to demonstrate any benefit of neo-adjuvant
therapy, despite using different combination regimes.
Concurrent radiotherapy and chemotherapy
•• This is the widely accepted treatment of choice following surgical
cytoreduction.
•• Trials using temozolamide at 75 mg/m2 orally for 42 days, concurrently with
external beam radiotherapy have shown promising results with survival up
to 16 months.
•• Presently, radiotherapy followed by TMZ (100 mg/m2) for 5 days every 28
days for 6 cycles is the standard treatment.
•• Carmustine (BCNU) is the other agent for which a standard protocol
has been described. This involves surgical cytoreduction followed by
radiotherapy and then BCNU at 6 weeks intervals at 110 mg/m2.
Local delivery of chemotherapeutic agent
•• Agents used for local delivery of chemotherapeutic drugs to the tumour
cavity are in the form of biodegradable polymer wafers.
•• These are loaded with BCNU (Gliadel® wafers) and are designed to release
the drug over 2–3 weeks after their placement within the surgical cavity.
•• Trials have shown them to be more effective than placebos.
•• Gliadel® wafers are, however, not appropriate for use in deep, multifocal
bilateral disease, tumour in eloquent areas and in a juxtaventricular location.
Treatment of Recurrent Gliomas
•• The treatment involves the use of first line drugs and if they fail to have
an adequate response this can be followed-up with the second line drugs.
•• The first line drugs are temozolamide, BCNU and CCNU. Patients who have
already received TMZ should undergo treatment with a nitrosourea, such
as BCNU or CCNU. Sometimes they may also be used in combination.
•• The second line drugs are carboplatin, etoposide and irinotecan.
Carboplatin alone or in combination with tyrosine kinase inhibitors have
been used. Hydroxyurea is used for its radiosensitising properties, along
with cell specific cytotoxic activity.
Anaplastic Astrocytomas
•• Neo-adjuvant therapy has not shown any beneficial result.
•• Trials have been conducted using PCV and BCNU, following surgery and
radiotherapy. Patients undergoing treatment with the PCV regime have
shown higher response rates.
•• The outcome of patients with recurrent anaplastic astrocytoma is dismal
with a maximum survival period of 47 weeks, despite adoption of aggressive
measures.
•• Although nitrosoureas are the most frequently used, agents development
of resistance with myelosuppression limits their use in recurrent cases.
•• Irinotecan has recently been shown to give encouraging results in recurrent
malignant gliomas.
Anaplastic Oligodendroglioma
•• Ongoing trials have reported high response rates to chemotherapy, most
commonly using PCV regimes.
•• It has been demonstrated that patients with LOH (1p/19q) have much
better response rates.
1068
•• Presently the use of PCV as adjuvant therapy has become the treatment
of choice.
•• Temozolamide has been increasingly used due to a better toxicity profile.
•• PCV is effective as salvage therapy in patients having recurrence following
temozolamide administration.
Low Grade Gliomas
•• Low grade gliomas include WHO grade II tumours mainly oligodendrogliomas,
astrocytomas and oligoastrocytomas.
•• The role of chemotherapy in these tumours is still under scrutiny and many
ongoing trials are evaluating their usefulness.
•• So far, trials using PCV/TMZ for recurrent/previously untreated oligoden-
drogliomas and astrocytomas have reported higher response rates.
•• Observation alone without any adjuvant therapy is recommended in patients
younger than 40 years and patients having low grade gliomas.
IMMUNOTHERAPY
•• Immunotherapy has been recognised to be a potent weapon against
gliomas for many years, but research in this field has only gained
momentum during the past decade.
•• Various modalities of treatment which result in enhancement of the immune
response have been developed to enhance the armoury against gliomas.
•• Over the years, it has been noted that patients with gliomas are
immunosuppressed.
•• Several factors have been studied in this regard: TGB-β, IL-10 and PGE2
have been found to be responsible for the immunosuppression (Flow
chart 1).
•• The immunosuppressive state results in defects which have been
enumerated in the Table 2.
Flow chart 1: Mechanism of immune response

Chapter 139 • Adjuvant Therapies for Malignant Brain Tumours
1069
Table 2: Causes for immunosuppressive state

Decreased CD4 ‘T’ cell activity
Increased CD4 suppressor T cells
Low reticulocyte count
Decreased delayed type hypersensitivity
Diminished immunoglobulin synthesis by B cells
Classification of Immunotherapeutics
Agents (Flow chart 2)
Cellular
•• This involves the isolation of immune effector cells from a patient, following
which they are multiplied using stimulating factors and are then activated.
Finally, they are injected back into the patient to cause tumour lysis.
•• The immune effector cells are lymphokine activated natural killer cells,
lymphokine activated lymphocytes, tumour infiltrating lymphocytes and
dendritic cells (Flow chart 3).
•• Dendritic cells have been studied with great interest recently to evaluate their
efficacy and have been giving promising results.
•• Dendritic cells are loaded with acid-eluted peptides, tumour homogenates
or tumour specific antigen EGFR VIII and are then stimulated and matured.
Flow chart 2: Classification of immunotherapeutics agents
Flow chart 3: Cellular mechanism

1070
Antibody-guided Therapy
•• Antibodies can be used either as delivery vehicles for chemotherapeutic
agents or as apoptosis inducers themselves.
•• Tenascin, the extracellular matrix glycoprotein expressed in malignant
gliomas has often been targeted.
•• 81C6 monoclonal antibody binds to the epitope within the spliced fibronectin
type III region of Tenascin.
•• The survival of newly diagnosed GBMs was 19.9 months and for recurrent
GBMs was 12 months.
Vaccination
•• This method of therapy involves utilising the patient’s own immune system
to counter high grade gliomas.
•• Theoretically speaking, this is the ideal method of treatment.
•• Poly ICLC, a double stranded RNA has been investigated for these
purposes.
•• The trials have reported significant improvement in survival rate of patients
with anaplastic astrocytomas.
•• This has, however, not been demonstrated in patients with GBM.
GENE THERAPY
•• Better understanding of the molecular genetics of brain tumours has
opened new options.
•• Attempts have been made to manipulate the molecular biology of tumours
by making alterations in the genome of tumour cells.
•• This, in turn, either inhibits the growth of the tumour or makes the tumour
cells more susceptible to the other modes of adjuvant therapy.
•• It is important to ensure that these alterations in the genome are restricted
to the tumour cells and do not affect the normal neural tissue.
•• These alterations in the genome are carried out by the use of genetically
engineered viruses which are inserted into the tumour cells.
•• The retrovirus and the herpes virus have been the most popular agents
to be used.
•• The genome of the retrovirus has been mapped in detail and has the
advantage that it tends to integrate only in the dividing cells, thereby not
affecting the normal neural tissue which is in the post-mitotic state.
•• Retrovirus that carries the thymidine kinase gene tends to render the cell
sensitive to ganciclovir, resulting in the death of the cells containing this gene.
•• Herpes virus has the advantage of having a large genome and retains
replication competence. However, it does not differentiate between dividing
and non-dividing cells.
140
CHAPTER
Colloid Cyst
Nigel Peter Symss  Ravi Ramamurthi
REGIONAL EMBRYOLOGY OF
THIRD VENTRICLE
•• The third ventricle develops from the diencephalic vesicle at the rostral end
of the neural tube during the third week of gestation.
•• Soon it is surrounded by the rapidly developing cerebral vesicles except
at its roof.
•• The roof of the third ventricle then begins to invaginate and forms the pia
mater that eventually covers the floor of the third ventricle.
•• Rathke’s cleft pouch forms an invagination of the distal end of the
stomodeum into the overlying mesoderm.
•• This eventually gives rise to the anterior pituitary.
•• The posterior pituitary and pituitary stalk are derived from the cerebral
vesicle posterior to Rathke’s cleft pouch.
•• This invagination of mesodermal tissues into the neuroepithelium may
give rise to a number of developmental anomalies and tumours that are
characteristic of the third ventricle.
INCIDENCE
•• These constitute less than 1% of all intracranial tumours.
•• Although colloid cysts have been reported in all age groups, they more
commonly present between the age of 20 and 40 years.
•• The incidence is equal in both sexes.
•• Isolated case-reports suggest a genetic predisposition in certain cases.
•• Familial cases have also been reported.
Incidental Colloid Cyst

•• Colloid cysts have been found incidentally.
•• The rapidly increasing availability of CT and MRI scanning for the
investigation of patients with unrelated symptoms and minor trauma has
resulted in an increase in the frequency of diagnosis of a colloid cyst.
•• The management of incidental colloid cysts is a topic of debate.
•• The rate of growth of the cyst is uncertain and whether these cysts
eventually become symptomatic is unclear.
•• Sudden deterioration followed by death has not been reported in patients
with a colloid cyst of less than 1 cm in size.
•• Patients with colloid cysts larger than 1.5 cm should be considered for
surgical excision, as these cysts are more likely to become symptomatic.
1072
PATHOLOGY
•• The wall of a colloid cyst usually consists of a single layer of columnar
epithelial lining and a collagenous connective tissue stroma.
•• Although electron microscopy suggests a secretory function for these cells,
there is some controversy regarding their development.
•• A neuroepithelial origin is suggested by most authors, although some
believe that it originates from the ependymal epithelium. Others believe
that it derives its origin from the epithelium of the choroids plexus.
•• On the basis of light microscopy, its origin from ectopic epithelium of the
upper respiratory tract has been suggested.
•• A recent immunohistochemical study of colloid cyst suggests that it is not a
derivative of the ependyma or the choroid plexus, but that it is derived from
the primitive neuroectoderm, involved in the formation of the tela choroidea.
•• A non-epithelial origin has also been proposed.
•• Ultrastructural studies show that colloid cysts are endodermal in origin.
•• The cyst contents may consist of soft suckable pultaceous material or could
be firm, non-suckable and hyaline.
•• This PAS positive material is presumably derived from the secretory activity
and desquamation of the lining epithelium.
LOCATION
•• Except in rare instances, colloid cysts are located in the anterior third
ventricle and the wall of the cyst is often firmly adherent to the walls of
the foramen of Monro, the fornix or the lateral wall of the third ventricle.
•• They are located in the roof of the third ventricle, usually attached to the
tela choroidea or rarely to the choroid plexus by a narrow pedicle and are
located just behind the fornices and between the foramina of Monro.
•• Occasionally, they are found more posteriorly and obstruct the posterior
segment of the third ventricle.
•• Intrasellar occurrence of a colloid cyst has also been reported.
•• Rarely, a colloid cyst may grow to a large size, compressing the surrounding
structures and simulating a glioma clinically and on CT.
•• Rarely colloid cyst occur in the fourth ventricle. Intracerebellar colloid cyst,
colloid cyst located in anterior surface of the pons has been reported.
CLINICAL FEATURES
•• Colloid cysts display a typical constellation of symptoms because of their
strategic location in the anterior third ventricle.
•• They act as pure mass lesions, possessing no intrinsic pathologic properties
and they cause symptoms by acting as inert masses.
•• Most of the symptoms are related to hydrocephalus secondary to
obstruction of cerebrospinal fluid (CSF) flow within the middle or posterior
third ventricle, as evidenced by the symmetrical dilatation of both the
lateral ventricles.
•• More than 75% of patients report with headache due to raised intracranial
pressure, as the presenting complaint.
•• It may be insidious in onset and progressive in nature or it may be intermittent
or of sudden onset.
•• The second common pattern of presentation has been “the classical
story”which is characterised by the intermittent and postural nature of the
attacks with remissions.
Chapter 140 • Colloid Cyst
1073
•• The postural component of the classic headache invokes the “ball valve”
theory, implying a movable mass that dislodges from the foramina when
the patient is recumbent.
•• These paroxysmal attacks are generally considered to be due to intermittent
obstruction and disimpaction of the cysts in the third ventricle.
•• A drop attack due to sudden weakness of the lower limbs accompanied
with features of raised intracranial pressure may be the presenting feature.
•• Progressive or fluctuating dementia may be seen or there may be a normal
pressure hydrocephalus syndrome.
•• Seizures may occur in about 20% of cases.
•• The dangers of asymptomatic colloid cysts have been underestimated.
•• There have been several reported instances of sudden death in patients
with colloid cyst, but the reasons are not clear.
•• The sudden elevation of intracranial pressure, with the subsequent
decreased cerebral perfusion pressure induces a vigorous cerebroprotective
neuroendocrine system activation that can lead to the neurogenic stunned
myocardium.
•• Sudden death in patients with colloid cysts may be related to acute
neurogenic cardiac dysfunction and not necessarily cerebral herniations,
as previously thought.
•• Another explanation for the acute deterioration of patients is haemorrhagic
changes in the cysts.
•• Neither the size of the cyst, the degree of dilatation of the ventricles, nor
the duration of symptoms seem to provide reliable prognostic indications
for this fatal complication.
•• As the dangers cannot be underestimated, surgical excision may be
advisable even for asymptomatic colloid cysts specially these larger than
1 cm.
INVESTIGATIONS
•• When the cyst is situated at its usual location, the venous phase of the
cerebral angiogram shows elevation of the anterior part of the internal
cerebral vein, resulting in a curve which is concave downwards.
•• The posterior part of the internal cerebral vein is flattened and depressed
due to the dilated lateral ventricles.
•• The CT appearance is of a lesion located at the foramen of Monro, varying
from hypodensity or isodensity to moderate or marked hyperdensity on
the plain scan.
•• This hyperdensity is secondary to a combination of desquamated material
within the cyst, haemosiderin and calcium. However, the colloid cyst is
frequently isodense or only slightly hyperdense.
•• It enhances with contrast to a mild degree in some cases.
•• Enhancement may be secondary to blood vessels in the wall of the cyst or
leakage of contrast into the cyst cavity.
•• MR findings are very variable, ranging from hypo-to-iso to hyperintense
in all sequences.
•• The signals may be homogenous or heterogenous.
•• High signals on short TR/TE sequences are correlated with high cholesterol
content.
•• MR venography gives a better visualisation of the adjacent venous
structures, including the internal cerebral vein.
1074
•• The differential diagnosis of third ventricular lesions may be divided into:
–– Intraventricular extra-axial lesions: Colloid cyst, cysticercal cysts,
meningiomas, haemangioblastomas, xanthogranulomas and cavern-
ous angiomas
–– Intraventricular intra-axial lesions: Gliomas, choroid plexus tu-
mours, teratomas, ependymomas and subependymal giant cell
astrocytomas and
–– Lesions with basal origin but third ventricular extension: Menin-
giomas, craniopharyngiomas, giant basilar aneurysms and pituitary
adenomas.
TREATMENT
•• The various microsurgical approaches to colloid cysts are:
–– Transfrontal/transventricular
¾¾ Transforaminal
¾¾ Subchoroidal
–– Transcallosal/transventricular
¾¾ Transforaminal
¾¾ Interforniceal
¾¾ Subchoroidal
–– Subfrontal translamina terminalis.
•• Opening the CSF pathway obstruction is the goal of treatment.
•• Total surgical excision would be the ideal therapy, provided that the
complications are kept to a minimum.
•• A transcallosal transventricular approach, when the lateral ventricle is
small and an anterior transcortical (middle frontal gyrus) transventricular
approach, when the ventricle is dilated, are the options available to reach
the foramen of Monro.
•• The transcallosal approach allows safer access if the ventricles are normal
sized or small and has greater flexibility in exploring the entire extent of the
third ventricle. There is no cortical incision, the ventricular size is irrelevant
and an excellent unobstructed view of the third ventricle may be obtained.
•• The disadvantages of the transcallosal approach include less familiarity with
the anatomy for some neurosurgeons, thereby increasing possible injury
to frontal draining veins and the sagittal sinus, injury to the pericallosal
arteries, problems related to corpus callosal section and forniceal damage.
•• Dandy first used the transcortical approach for lateral ventricular and third
ventricular lesions.
•• It is useful, if the ventricles are enlarged and access to the foramen of
Monro and third ventricle is readily obtained.
•• The transcortical approach avoids injury to the frontal draining veins of the
sagittal sinus and decreases the chance of injury to the pericallosal arteries.
•• However, in the presence of small or normal sized ventricles, it may be
difficult to enter the lateral ventricles without undue trauma and retraction,
thereby increasing the incidence of postoperative morbidity.
•• The transcortical-transventricular approach has been associated with
the following complications: Seizures, hemiparesis, memory loss usually
transient, subdural fluid collection, meningitis, ventriculitis, confusion and
mutism.
Chapter 140 • Colloid Cyst
1075
•• The reported complications in the transcallosal approach have been

hemiparesis, transient memory loss, transient akinetic mutism, impairment
of interhemispheric transfer of sensory information, bacterial meningitis and
aseptic meningitis, confabulation, aphasia and obtundation.
•• Transient hemiplegia, drowsiness, mutism and haemorrhagic infarction of
the basal ganglia have been found with the subchoroidal and the trans-
velum interpositum approach.
•• Palliative ventricular shunting, although a simple way of avoiding surgical
complications, is not advisable because there is no tissue confirmation, the
signs due to the tumour mass per se are not alleviated and it exposes the
patient to the risks of infection, epilepsy and shunt blocks.
•• Unilateral shunting of the ventricles may lead to sudden enlargement of the
opposite ventricles resulting in coma or even sudden death.
•• CT-guided stereotactic aspiration should be routinely used for the
management of colloid cysts.
•• The advantage of this procedure is the low morbidity and mortality rates.
•• The disadvantages are the occasional inability to aspirate the cyst contents
and recurrence 6−15 years after successful aspiration.
•• The aspirability of the cyst may be predicted by its CT appearance. When
the preoperative CT showed a hypodense or isodense lesion, it was
possible to aspirate the cyst successfully.
•• In view of the risks of open surgery and failure to aspirate the colloid
cyst with CT- guided stereotactic techniques, stereotactic microsurgical
approach and total removal of the colloid cyst by laser has been advocated.
•• Stereotactic-guided endoscopic laser therapy has also been employed.
The advantages claimed for this technique are:
–– Limited cortical dissection.
–– Avoidance of callosal or forniceal injury.
–– Ease of localisation of the lesion, regardless of ventricular size.
–– Good haemostasis achieved by bipolar cautery or LASER.
–– Possibility of total resection.
•• Neuroendoscopic treatment of colloid cysts has gained increasing
acceptance and is being used more widely. Endoscopes have also been
used with interactive image-guided methodology.
141
CHAPTER
Choroid Plexus Tumours
Vasudevan MC
•• Tumours of the choroid plexus are rare neoplasms of neuroectodermal

origin, accounting for less than 1% of all intracranial tumours.
•• These tumours primarily occur in children but they are also observed in
adults and infants.
•• Prenatal occurrence has also been reported.
•• Choroid plexus tumours are among the more frequent tumours in children
under the age of 3 years.
•• Among 245 patients of all ages, the distribution was as follows: Lateral
ventricle 43%, third ventricle 9%, fourth ventricle 39%, CP angle 9% and
multiple sites 3.7%.
•• In children, tumours of the choroid plexus are located most often in the
lateral ventricle but they can also be found in the third ventricle and in the
posterior fossa.
•• Choroid plexus tumours of the posterior fossa in adults are likely to be
benign, whereas, in children, tumours occurring in the lateral ventricle
tend to be anaplastic.
•• Third ventricular tumours are usually prevalent in adults and children and
most such tumours are benign.
•• Lateral ventricle tumours occur equally on either side, though some reports
indicate a preference for the left lateral ventricle.
•• A predominance of males has also been reported.
•• Malignant changes occur in less than 20% and a majority of such tumours
are found in infants and children less than 4 years of age, mostly in the
lateral ventricle.
•• The papilloma appears as a pink or reddish grey globular mass with a
rough irregular surface resembling a cauliflower and is usually attached to
the plexus at the trigone.
•• The consistency is firm and occasionally, significant calcification may be
present.
•• These tumours are very vascular.
•• Although evidence of leptomeningeal spread has been reported on post-
mortem examination, there are no symptoms to indicate this during life.
•• The microscopic appearance of choroids plexus papilloma resembles the
normal architecture of the choroid plexus and shows papillae composed
of a single layer of columnar or cuboidal epithelium lining a stroma of
vascularised connective tissue.
•• It is important to differentiate it from an ependymoma where the stroma
contains neuroglial tissue, epithelial cells with cilia and blepharoplasts.
Chapter 141 • Choroid Plexus Tumours
1077
•• Features of microscopic invasion, especially mitotic activity and

pleomorphism should raise the possibility of malignancy, even when the
general architecture indicates a well differentiated papilloma.
•• The two characteristics that are suggestive of malignancy in choroid plexus
tumours are:
1. Invasion of the brain by malignant-looking cells and
2. Loss of the regular papillary architecture of the tumour in the region
where the normal brain has been invaded.
•• In young patients, in whom metastatic adenocarcinoma is highly unlikely, it
may be difficult to distinguish these tumours from medulloepithelioma, an
embryonal carcinoma or an endodermal sinus tumour. Immunohistochemistry
may be useful.
•• Leptomeningeal spread is common in choroid plexus carcinoma and
extraneural metastasis has also been reported.
•• Hydrocephalus in choroid plexus tumours is due to following factors:
–– Overproduction of CSF
–– Obstruction of the CSF pathways due to tumour and
–– Recurrent occult bleeding from the tumour resulting in subarachnoid
fibrosis and adhesions.
•• From their attachment to the choroids plexus, the tumours frequently extend
from one ventricular compartment to another and to the subarachnoid
space.
•• Lateral ventricular tumours may extend through the foramen of Monro into
the third ventricle and to the quadrigeminal cistern or to the contralateral
ventricle through the choroidal fissure.
•• Third ventricular tumours are usually situated posterosuperiorly.
•• Tumours in the fourth ventricle may, occasionally, burrow into the
cerebellum or the floor of the fourth ventricle or may extend to the CP angle.
CLINICAL COURSE
•• The symptoms are insidious in onset.
•• Acute symptoms appear when brain herniation occurs secondary to
hydrocephalus or when the tumour bleeds into the ventricle.
•• Headache is the most common symptom and is later associated with
vomiting and visual disturbances.
•• Headache is the result of raised intracranial pressure secondary to the
tumour mass or due to obstructive hydrocephalus.
•• In supratentorial tumours, headache could be positional and intermittent.
•• Seizures, hemisyndromes and mental changes may also occur.
•• Progressive enlargement of the head is present in the majority of infants
and young children.
•• Choroid plexus tumours of the anterior third ventricle present with
obstructive hydrocephalus and posterior third ventricular tumours have
tectal syndromes in addition.
•• In fourth ventricular tumours, headache, gait ataxia, nystagmus, cerebellar
signs, loss of vision, vomiting and diplopia are seen.
INVESTIGATIONS
•• Plain X-ray shows only non-specific signs of raised intracranial pressure
and tumour calcifications are generally not apparent.
1078
•• Angiograms may show an enlargement of the corresponding arteries,

depending on the location and a tumour blush is often seen.
•• A CT scan shows a lobulated hyperdense intraventricular mass which
enhances brightly with contrast.
•• Finely speckled calcification is often present within the tumour.
•• MR shows a hypointense or isointense lesion which is hyperintense relative
to CSF in T1-weighted images and a hyperintense mass in T2-weighted
images.
•• Following gadolinium injection the tumour becomes hyperintense in T1-
weighted images.
•• Magnetic resonance spectroscopy (MRS) is a novel in vivo technique
to identify biochemical features of choroid plexus tumours that facilitate
diagnosis and treatment.
•• Both, the choroid plexus papilloma and carcinoma characteristically
contain high levels of choline compounds (CHO), and a complete absence
of creatine and the neuronal/axonal marker N-acetyl aspartate (NAA).
However, a choroid plexus carcinoma demonstrates higher levels of choline
compared to the papilloma and in addition, it also has elevated lactate.
•• The myo-inositol (mL) level is significantly higher in choroid plexus
papillomas (10 mmol/kg), uniquely distinguishing these tumours.
TREATMENT
•• The majority of patients are younger than 3 years of age at the time of
presentation. This makes management of their disease challenging.
•• Total excision of the tumour is the surgical goal and the treatment of choice.
•• Choroid plexus tumours tend to be large, fragile and very vascular. This
presents a particular challenge in a baby with a small total circulating blood
volume, risking intra-operative death from uncontrollable haemorrhage.
•• This complication occurs more commonly in carcinomas than in papillomas.
•• The critical aspect of the surgical approach is to expose the vascular pedicle
during the initial stage of the procedure, to avoid avulsion of the feeding
arteries, which can occur when manipulating these large lesions.
•• Endoscopy can be used as an adjunct to microsurgery to get at the vascular
pedicle in the early stages of surgery.
•• Preoperative angiographic evaluation and embolisation can be extremely
useful in cases of highly vascular lesions. Hypertrophy of one of the
choroidal arteries is a usual angiographic feature and a tumour blush
is commonly seen, occasionally with several minor feeding vessels
contributing.
•• Gross total resection of tumour is possible in 60–90% of cases.
•• The mortality rate in a relatively recent series has been reported to be 20%.
•• Hydrocephalus is generally relieved following removal of the tumour but
in certain cases it may persist and is attributed to subarachnoid fibrosis. A
ventriculoperitoneal shunt may then be necessary.
•• Preoperative radiation to reduce the vascularity is not advisable, as it may
produce adhesions that hinder resection.
•• Postoperative radiation therapy has been recommended for patients with
incomplete excision, although its validity is doubtful.
•• In choroid plexus papilloma, it is accepted that complete excision is curative.
•• Choroid plexus carcinomas have a high propensity for recurrence and
despite some reports adjuvant treatment has not been found to be very
effective in these tumours.
Chapter 141 • Choroid Plexus Tumours
1079
Table 1: WHO classification of choroid plexus tumours

Tumours of the choroid plexus Grade
Choroid plexus papilloma I
Atypical choroid plexus papilloma II
Choroid plexus carcinoma III
•• In older children, radiotherapy can be effective against recurrence.

•• Unfortunately, radiotherapy is not an option in the majority of cases because
of the young age of the patients and the size of the field to be irradiated.
•• Total excision is the major predictor of long-term survival in patients with
CPC, the 5-year-survival rates range from 26% to 50%.
•• At present, total surgical excision is the main predictor of long-term survival
and achieving total excision should be the goal of any treatment strategy.
142
CHAPTER
Pineal Region Tumours:
Clinical Features and
Management
INTRODUCTION
•• The human pineal gland retains its phylogenetic link to the visual system
by connections with the retina by a circuitous route (optic chiasma →
suprachiasmatic nucleus → medial forebrain bundle → intermediolateral
column of the upper thoracic spinal cord → superior cervical sympathetic
ganglion → pericarotid sympathetic fibres → nervi conarii on the tentorium
→ pineal gland).
•• The pineal output is mediated through the release of melatonin into the
vascular system. Serotonin and several neuropeptides are also produced
by the pineal.
•• Through these afferent and efferent mechanisms, the pineal has now
been proved to play a central role in the modulation of circadian rhythms,
sleep-wake cycles, growth and puberty, reproduction, ageing, immune
responses, cancer inhibition, epilepsy inhibition, mood, behaviour and
even motor activity.
PATHOLOGY
•• Pineal tumours account for 1% of all brain tumours and about 3% of
childhood brain tumours.
•• Pineoblastomas may be associated with bilateral retinoblastoma in children
and is known as ‘trilateral retinoblastoma’. Trilateral retinoblastoma is
genetically determined and is associated with inactivation of the tumour
suppressor gene (rb1) in the chromosome 13q14.
•• Germinoma may appear synchronously or metachronously in the pineal
and suprasellar regions.
•• Germ cell tumours (GCTs) of the pineal have a strong male preponderance.
•• Klinefelter’s syndrome and Down’s syndrome may predispose to intracranial
GCTs.
•• Gliomas are known to arise in the pineal gland but the majority of the glial
tumours in this region arise in the neighbourhood structures such as the
posterior third ventricle or dorsal midbrain.
•• The histological type of tumour in the pineal region depends on the age of
the patient is presented in Table 1.
SYMPTOMS AND SIGNS

•• The mechanisms of production of symptoms are:
–– Raised intracranial pressure due to obstruction of the posterior third
ventricle or aqueduct or both
Chapter 142 • Pineal Region Tumours: Clinical Features and Management
1081
Table 1: Frequency of pineal mass lesions at different ages

Age group Most common Next so common
Infants Pineoblastoma Arachnoid cyst, aneurysm of
vein of Galen
Childhood Germinoma, germ cell tumour Pineoblastoma, glioma,
(GCT) tuberculoma
Young adults GCT, glioma Pineocytoma, pineal cyst
Older adults Pineocytoma, glioma Meningioma, epidermoid,
metastasis
–– Direct compression or infiltration of the neighbourhood neurological

structures such as the tectum and the midbrain nuclei or white matter
tracts
–– Endocrine dysfunction.
•• Raised intracranial pressure syndrome is the most common presentation
of pineal masses across the ages.
•• Older children or adults with raised pressure syndrome present mainly
with headache.
•• Vomiting or rapidly increasing head size is the symptom in younger children.
•• Lethargy and obtunded mentation are seen in the later stages.
•• Three fourths of the patients have papilloedema at presentation.
•• Spells of loss of consciousness with limb rigidity might occur and is known
as hydrocephalic attack.
•• Sudden neurological deterioration may also be due to intratumoral
haemorrhage (pineal apoplexy), which seems to be common in
pineoblastoma and choriocarcinomas of children.
•• The intratumoural haemorrhage can also be precipitated by shunt or
endoscopic procedures.
•• Ocular signs are seen in about 50% of patients with pineal tumour.
•• The differentiation of the ocular syndrome into Parinaud’s syndrome, dorsal
midbrain syndrome, pretectal syndrome and syndrome of the aqueduct of
Sylvius (Koerber-Salus-Elschnig syndrome) appears to be a mere hair-
splitting academic exercise.
•• Paralysis of vertical gaze (up gaze alone or both and down gaze), deficiency
of convergence, convergence-retraction nystagmus, disjunctive horizontal
eye position, pupillary light-near dissociation, lid retraction (Collier’s sign)
and ptosis are seen in descending frequency.
•• Parinaud’s syndrome is not pathognomonic of a pineal mass, as stroke,
demyelination and hydrocephalus account for about 75% of the causes
of the syndrome.
•• The other eye signs reported with pineal tumours are reverse Parinaud’s
syndrome (paralysis of downgaze alone instead of upgaze), unilateral
supranuclear abducent paresis (lack of abduction during saccadic or pursuit
volitional movements but preserved reflex abduction while performing
oculocephalic manoeuvre or caloric testing), bilateral superior oblique palsy,
contralateral relative afferent pupillary defect, isolated vertical diplopia, and
paroxysmal tonic upgaze of childhood.
•• Neurological signs are less common than signs of raised pressure or
ocular signs.
•• Involvement of the superior cerebellar peduncles can cause the ataxia-
dysmetria syndrome even when hydrocephalus is absent.
1082
•• Gait ataxia is mostly due to hydrocephalus.

•• Inferior collicular involvement may present with tinnitus or hearing
impairment.
•• Vivid, coloured, formed visual or multi-sensory, long-lasting, non-epileptic
hallucinations known as “peduncular hallucinosis” have also been reported
with pineal tumour.
•• Endocrine dysfunction is a childhood phenomenon restricted to pineal
GCTs.
•• Precocious puberty is seen in 10% of boys with pineal GCTs due to secretion
of human chorionic gonadotrophin (b-hCG) from the syncytiotrophoblastic
(choriocarcinomatous) elements in the tumour.
•• Asymptomatic patients with pineal masses are being increasingly detected
with widespread use of neuroimaging.
•• Asymptomatic small glial cysts are found in routine autopsies in about
25−40% but, until recently, they were seen only in less than 10% of cases
on neuroimaging.
NEUROIMAGING
•• Calcification of the pineal is a physiological phenomenon. It is readily seen
in plain radiographs and CT.
•• Calcification increases with age; below the age of 6 years calcification is
seen in only 1% of glands and by 14 years, 40% of glands are calcified
as seen on CT.
•• In the days of plain radiographs, calcification larger than 1 cm in any one
diameter, or any calcification before the age of 4 years were considered
pathological.
•• MRI gives information on the size, content, intratumoural haemorrhage or
necrosis, degree of invasion and vascularity of the tumour and also shows
the degree of ventriculomegaly.
•• The sagittal and coronal images help to depict the slope of the tent and the
relation of the tumour to the neighbourhood brain structures/deep venous
system. This information is invaluable in planning the operative approach.
•• MR imaging of the entire spinal cord is recommended to detect spinal
seeding in children with malignant pineal tumours.
•• Purely cystic lesions in the pineal region include pineal cysts, pineocytomas,
arachnoid cyst, cysticercal cyst, low-grade astrocytoma and, rarely,
teratoma.
•• Magnetic resonance imaging can generally distinguish pineal cyst from
pineocytoma.
•• Highly cellular tumours such as germinomas and childhood pineoblastomas
may appear isointense or hypointense in T2-weighted images.
•• In spite of the advances in neuroimaging, an exact histopathological
diagnosis for most tumours can be made only by obtaining tissue.
TUMOUR MARKERS
•• Pineal GCTs declare their presence by characteristic cell products that are
found in the ventricular or lumbar CSF and in the serum.
•• Alpha-fetoprotein (AFP), an oncofetal glycoprotein, is a marker for tumours
with yolk sac elements, while b-human chorionic gonadotrophin (b-hCG)
indicates a tumour with trophoblastic elements.
1083
Table 2: Tumour markers in pineal tumours

AFP b-hCG PLAP
Normal serum level 0–8.5 ng/mL 0-7 mIU/mL 0.2 IU/L
Normal lumbar CSF level < 5 ng/mL < 2 mIU/mL 0.11 IU/L
Test CLIA CLIA ELISA
Germinoma Normal Mild elevation < 770 Highly elevated 1-9
mIU/mL IU/L
Endodermal sinus tumour Highly elevated > Normal Normal
1000 ng/mL
Embryonal carcinoma Moderately elevated Mild elevation Slight elevation
< 1000 ng/mL < 770 mIU/mL
Choriocarcinoma Normal Highly elevated > Normal
2000 mIU/mL, CSF
level > serum level
Immature teratoma Rarely and mildly Normal Normal
elevated
All other pineal tumours Normal Normal Normal
Systemic choriocarcinoma Normal Highly elevated > Normal
2000 mIU/mL CSF
level < serum level
Abbreviation: AFP = Alpha fetoprotein, b-HCG = b-human chorionic gonadotrophin, PLAP = placental alkaline
phosphatase, CLIA = chemiluminescence immunoassay, ELISA = enzyme linked immunosorbent assay
•• Placental alkaline phosphatase (PLAP) is a marker for germinoma, but

this is less widely used.
•• The normal levels and the extent of elevation of these markers in various
tumours are given in Table 2.
•• The CSF levels are more sensitive than serum levels.
•• In a small subset of patients with characteristic imaging and elevated tumour
markers, surgical biopsy may be avoidable.
•• The analysis of tumour markers helps in follow-up and in detecting
recurrence or spinal seeding.
MANAGEMENT
•• The goals of management of pineal tumour are:
–– Establishing a firm diagnosis, preferably from tumour tissue
–– Excision or mass reduction
–– Management of hydrocephalus
–– Avoidance of surgical morbidity and complications
–– Effective adjuvant therapy.
•• The main factors that impact the decision-making are:
–– Age of the patient
–– Neurological status
–– Imaging characteristics
–– Presence of hydrocephalus
–– Available technology; and
–– Experience of the surgeon.
•• Young children with pineal masses are likely to have a pineoblastoma
or germinoma and these tumours do not lend themselves to aggressive
excision. These tumours which are hypointense in T2-weighted images
1084
are homogeneous except for areas of haemorrhage and only rarely show
calcification. Both these tumours are not associated with elevation of AFP
or b-hCG.
•• Ventricular diversion, preferably by endoscopic third ventriculostomy (so
as to avoid seeding along the shunt tract) is often necessary.
•• Endoscopic biopsy enables one, nowadays, to establish the tissue
diagnosis at the same time as the third ventriculostomy, thus providing a
basis for adjuvant therapy.
•• Older children and young adults, especially males, have a higher likelihood
of harbouring other GCTs. Marked heterogeneity on imaging suggests a
teratoma and surgical excision is needed.
•• A pre-operative ventricular diversion procedure may be needed only in
patients presenting as an emergency with visual failure (from papilloedema)
or altered sensorium.
•• In non-emergent situations, one can directly proceed with microsurgical
excision of the tumour.
•• The immature teratomas and teratomas with malignant transformation
need adjuvant therapy.
•• On the other hand, an enhancing tumour that shows only some
inhomogeneity on imaging in a young male may be: (1) Embryonal
carcinoma; (2) Endodermal sinus tumour; (3) Choriocarcinoma; or (4) Mixed
GCT. All these four tumours carry a poor prognosis.
•• Elevation of AFP suggests endodermal sinus tumour or mixed GCT with
yolk sac elements.
•• Very high levels of b-hCG would indicate choriocarcinoma or mixed GCT
with syncytiotrophoblastic element
•• Moderate elevations of both the markers might mean an embryonal
carcinoma.
•• Among older adults, meningiomas and epidermoids have characteristic
imaging appearances and need microsurgical excision. However,
pineocytomas and gliomas are the most likely lesions in this age group.
•• Masses larger than 2 cm can directly be accessed and excised using the
most appropriate microsurgical route.
•• Total excision is possible in many cases, but not all.
•• Adjuvant therapy then is based on the histology and the post-operative
residue on imaging.
•• Smaller masses can be excised or at least biopsied by endoscopy.
•• Stereotactic biopsy is more accurate in the smaller lesions.
SURGICAL APPROACHES
•• Pineal tumours are located in the geometric centre of the head and this
makes them equidistant from the surface regardless of the site of surgical
entry into the skull.
•• The depth of location, the proximity to the deep veins and the malignant
nature of some of the tumours have deterred generations of surgeons from
approaching pineal tumours.
•• The various approaches are:
–– Infratentorial supracerebellar approach (Krause)
–– Translateral ventricular approach (van Wagenen)
–– Parafalcine trans-splenial approach (Dandy) and
–– Occipital approach (Poppen)
1085
Surgical Anatomy
•• The pineal gland is attached to the posterior wall of the third ventricle and
is between the posterior commissure below and the habenular commissure
above.
•• The suprapineal recess located above the habenular commissure is larger
than the tiny pineal recess.
•• Anteroinferior to the posterior commissure is the opening of the cerebral
aqueduct and these structures are well seen through the endoscope
introduced through the foramen of Monro, after passing the massa
intermedia (interthalamic adhesion).
•• The paired choroid plexus in the roof of the third ventricle and the dark
internal cerebral veins shining through the ependyma of the roof are also
seen.
Endoscopic Approach
•• Indications:
–– The primary indication for endoscopy for a pineal mass is for perform-
ing third ventriculostomy to relieve hydrocephalus.
–– If the foramen of Monro is large enough and if the mass is visible in
the posterior wall of the third ventricle, a biopsy of the tumour can also
be performed.
–– Lesions less than 2 cm or larger cystic lesions can adequately be man-
aged endoscopically, if they are not highly vascular.
–– A second open microsurgical procedure may not be necessary in the
smaller, radiosensitive malignant lesions such as germinoma, NGGCT
and pineoblastoma.
–– Endoscopic biopsy has also been used for differentiating recurrent
tumour from radionecrosis.
–– Bleeding from the tumour can be a significant problem during endo-
scopic biopsy or decompression.
–– Inadequate tissue sampling by endoscopy has made some prefer the
open or stereotactic approach.
–– Damage to the fornix, resulting in memory loss, is possible after ex-
cessive manipulation of the endoscope thorough a minimally dilated
foramen of Monro.
Stereotactic Approach
Indications
•• CT guided stereotactic biopsy has been viewed as being risky due to the
surrounding major veins in the pineal region.
•• The larger tumours need excision and do not need a preliminary stereotactic
biopsy.
•• If a malignant radiosensitive lesion is clinically thought to be likely,
stereotactic biopsy and radiotherapy, without tumour resection, is a viable
alternative.
•• Since endoscopy is not recommended for those without hydrocephalus,
stereotactic biopsy is a good choice in such patients.
•• Aspiration of cystic lesions can be done by the stereotactic approach.
•• Stereotaxy is also employed for implanting radioactive material (iodine-125)
for brachytherapy.
1086
–– Haematoma formation is a much feared but rare complication.
–– Implantation metastasis is distinctly rare but has been reported in a
case of pineoblastoma.
Microsurgical Approaches
•• All benign pineal lesions that can be diagnosed with reasonable certainty
on imaging would certainly require open microsurgical excision.
•• These include meningiomas, cavernomas, epidermoids and mature
teratomas. Such lesions account for about 15% of all lesions in the pineal
region.
•• Some malignant lesions are radiosensitive and they can be diagnosed by
tumour marker study, endoscopic biopsy or stereotactic biopsy. Examples
are germinomas and some NGGCTs (choriocarcinoma, endodermal sinus
tumour, embryonal carcinoma).
•• All the remaining lesions do not have a distinctive imaging appearance and
cannot be diagnosed by tumour marker study.
•• The histological heterogeneity of the immature or mixed teratomas makes
limited, minimally invasive biopsies unreliable.
•• A more complete histological diagnosis can be expected with the entire
resected tumour specimen.
•• The poor radiosensitivity of the low-grade pineal parenchymal tumours and
gliomas necessitates gross total resection.
•• A preliminary ventriculoperitoneal shunt or endoscopic third ventriculostomy
is often necessary, before definitive surgery for the pineal tumour in patients
with severe raised intracranial pressure.
•• Posterior third ventriculostomy that naturally occurs or is intentionally done
after resecting the pineal mass may also provide relief of hydrocephalus.
STEREOTACTIC RADIOSURGERY
•• Stereotactic radiosurgery (SRS) of pineal tumours is a new therapeutic
choice.
•• The highly conformal nature of therapy makes SRS ideal for irradiating
deep targets in the brain and yet allows for sparing of radiation damage to
the vital structures in the neighbourhood.
•• Performing SRS for a radiosensitive tumour, such as a germinoma, seems
to be overkilled and it also does not prevent ventricular recurrence that is
common with this tumour.
•• SRS has been used:
–– As an alternative to surgical excision for the smaller low-grade lesions
–– For treatment of tumour residue after resection
–– As an alternative to external beam radiotherapy so that radiotoxicity
can be reduced
–– As an adjunct to external radiotherapy in the form of tumour boost dose
for the more malignant lesions.
RADIOTHERAPY
•• Radiotherapy is the principal method of tumour control for the radiosensitive
tumours such as germinoma.
•• Limited field external beam radiation therapy (24−40 Gy) suffices for pineal
germinoma, even when it involves the suprasellar region.
1087
•• NGGCTs require 50−54 Gy and craniospinal axis radiation is recommended.

•• In a child younger than 3 years, radiotherapy can be deferred until that age
by using chemotherapy.
•• Pre-radiation chemotherapy has been used to reduce the dose of radiation
in the responders.
•• The totally excised low-grade lesions, such as a pineocytoma, do not need
radiotherapy.
•• The side effects of radiotherapy are cognitive dysfunction, growth failure,
endocrine changes, radionecrosis and development of new neoplasms
after decades.
CHEMOTHERAPY
•• The success of chemotherapy for gonadal GCTs suggests that the results
might be similar with intracranial GCTs.
•• Carboplatin-etoposide regimen or ifosphamide-cisplatin-etoposide
combinations have been used in GCTs.
•• Chemotherapy has also been used to salvage recurrences at the radiation
field margin.
•• Pineoblastoma has a poor prognosis but recent reports show a fairly
good survival with gross total resection, radiotherapy and multimodality
chemotherapy.
PROGNOSIS
•• CSF Shunting followed by surgical excision resulted in most of the patients
being in good or excellent condition.
•• The 20-year survival rate was 80% for germinoma, the 10-year survival
rate was 70% for malignant teratoma and 3-year survival rate was
27% for malignant NGGCTs (embryonal carcinoma, yolk sac tumour or
choriocarcinoma).
•• Endoscopic management of pineal region tumours produces improved
post-operative quality of life in all health domains.
143
CHAPTER Pituitary
Tumours Overview
Ravi Ramamurthi
INTRODUCTION
•• Tumours in the sellar and parasellar regions constitute 12−15% of all
brain tumours.
•• The most common of these are pituitary tumours, which constitute 8−12% of
all intracranial neoplasms and are found in 2.7−27% of unselected routine
autopsies in humans who had no symptoms of pituitary disease.
•• Incidentalomas or lesions of the pituitary, picked up by imaging in
asymptomatic patients, have been reported in 10−37% of patients and on a
follow-up, 40% of these lesions increased in size, 20% became symptomatic
and 9.5% of these incidental tumours developed apoplexy.
•• In children and adolescents, these tumours are rare and in a large series
of these tumours, children accounted for 2−3.5 per cent.
•• Pituitary tumours are more common among women.
•• Among the elderly (65 years and above), pituitary adenomas are mostly non-
functional and the incidence of gonadotrophic tumours increases with age.
ANATOMY OF THE PITUITARY

GLAND AND ITS SURROUNDINGS
•• The pituitary gland or hypophysis cerebri lies in the pituitary or hypophyseal
fossa of the sphenoid bone.
•• It is basically made up of two divisions, viz. the adenohypophysis and the
neurohypophysis, which have different embryological, morphological and
functional characteristics.
•• It is continuous with the infundibulum, which is a horizontal conical
projection from the inferior aspect of the tuber cinereum.
Pituitary Gland
•• The normal adult hypophysis or pituitary gland is a horizontally positioned
extra-arachnoid ovoid body measuring about 12−15 mm in transverse
diameter, 8−10 mm in anteroposterior diameter and 5−7 mm in height.
•• It weighs about 0.5−0.7 g in an adult male.
•• The weight in a non-pregnant woman is about 100 mg more than in a man.
•• During pregnancy, its weight increases to an average of 0.8−1.0 g.
•• The infundibulum or the hypophyseal stalk contains an inner core, called
infundibular stem, which contains the neural connections of the hypophysis.
It is continuous with the median eminence of the tuber cinereum.
Chapter 143 • Pituitary Tumours Overview
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•• The neurohypophysis is normally taken to include the median eminence,

the infundibular stem and the posterior lobe of the pituitary gland.
•• The adenohypophysis is made up of the pars tuberalis (which surrounds
the neural infundibular stem) and the anterior lobe of the pituitary gland,
which is divisible into pars anterior and pars intermedia.
Blood Supply
•• The pituitary gland has a dual blood supply.
•• There is a direct arterial supply common to the anterior and posterior lobes
and a portal supply exclusive to the anterior lobe.
•• The arterial supply to the anterior lobe of the pituitary gland may be divided
into two groups in relation to the diaphragm sella.
•• The infradiaphragmatic supply to the gland is a capsular network which
also vascularises the diaphragm. This network is made up of branches of
the inferior hypophyseal artery, which arises from the meningohypophyseal
trunk and direct branches from the intracavernous internal carotid artery
(the inferior and the anterior capsular arteries).
•• The supradiaphragmatic supply is through the middle hypophyseal artery,
which is a branch of the superior hypophyseal artery. The vessel is paired
and runs on the anterior surface of the stalk.
•• There are two groups of portal vessels, the long and the short, each with
their own area of supply. The blood flowing in these two groups of veins
does not mix.
•• The long portal vessels supply approximately 90% of the parenchyma of
the anterior lobe, mainly the anterior and the central portions.
•• The short portal vessels supply a small part of the anterior lobe lying
adjacent to the posterior lobe.
•• The blood derived from the portal vessels reaches the sinusoids, which form
the vascular bed of the gland and lie between secretory cells.
•• The significance of the portal system is in that it carries the hypothalamic
regulating hormones to the anterior lobe, thus controlling the secretion of
the anterior pituitary hormones.
•• The venous drainage of the neurohypophysis is to the inferior hypophyseal
veins, the portal system and the hypothalamus via small capillaries, which
pass between it and the median eminence.
Sella Turcica
•• The pituitary gland is housed in the hypophyseal or pituitary fossa of the
body of the sphenoid bone.
•• The pituitary fossa is delineated in front by the tuberculum sella and
chiasmatic sulcus.
•• The dorsum sella and the posterior clinoid processes form the posterior
boundary.
•• The sellar floor, which separates the sellar contents from the underlying
sphenoid sinus, extends from the tuberculum sella in front to the base of
the dorsum sella posteriorly.
•• The pituitary fossa has a depth of 10−12 mm with an upper limit of 13 mm;
an anteroposterior diameter of 5−16 mm with an upper limit of 17 mm and
a width of 10−15 mm.
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•• DiChiro and Nelson have found the mean sellar volume to be 594 mm3
using their simplified mathematical formula:
0.5 (length x width x depth in mm)
Volume in mm3 = ____________________________________________
1000
•• Sellar bridges are bony structures running between the anterior and the
posterior clinoid processes. When present they are bilateral, although they
may be incomplete.
•• The carotico-clinoid foramen is demarcated by a bony bridge between
the lateral border of the pituitary fossa and the apex of the anterior clinoid
process. It transmits the internal carotid artery.
•• The sellar spine is an osseous spine, which is a remnant of the anterior
end of the notochord and protrudes from the dorsal side of the pituitary
fossa into the fossa itself.
Diaphragma Sella
•• The diaphragma sella forms the roof of the pituitary fossa.
•• It is a fold of dura mater, more often rectangular than circular and has a
central opening, which transmits the infundibulum.
•• Anatomical variations of the diaphragma sella are frequent.
•• These have been classified by Busch into:
–– Type I—Funnel shaped depression of the diaphragma sella
–– Type II—Incomplete closure of the diaphragm around the pituitary stalk
–– Type III—A wide defect in the diaphragm, so that there is only a pe-
ripheral rim of tissue measuring less than 2 mm in width. This may
leave the pituitary gland completely exposed and covered only with
arachnoid (III a) or may be associated with symmetrical or asym-
metrical indentation of the pituitary gland by the herniated arachnoid
pouch (III b) or there may be a complete remodelling or flattening of
the pituitary gland (III c).
Sphenoid Sinuses
•• The sphenoidal sinuses are described as paired cavities lying side by side
in the body of the sphenoid bone.
•• They are separated by a bony septum, which is commonly deflected to
one side or the other.
•• The cavities vary in shape and size, are usually asymmetrical and are
subdivided by minor septae.
•• The position of the septum can be located by tomograms and by CT scan
and if located near the midline, can be used as a guide during the trans-
sphenoidal approach to the pituitary fossa.
•• However, the major septum has been seen to be away from the midline.
•• In 43%, only the anterior part lies in the midline, while the rest of the septum
is S, C or L shaped.
•• Hamberger, et al. classified the sphenoid sinus into three main anatomical
types:
–– The conchal type is usually found in children but may be seen in up to
3% of adults. In this type, the sinus does not extend into the body of the
sphenoid. It is small, and between it and the pituitary fossa is spongy
bone, which may be as thick as 10 mm.
1091
–– The presellar type is found in 11−20% of adults. The sphenoid sinus

does not penetrate the body of the sphenoid bone beyond a plane
perpendicular to the planum sphenoidale. The anterior wall of the sella,
therefore, does not bulge into the sphenoid sinus
–– Sellar type of sphenoid sinus occurs in 80−86% of adults. In this type,
the sella has a thin floor and bulges into the sinus and occasionally, the
sinus can extend from the dorsum sella to the upper clivus.
Carotid Arteries
•• The proximity of the carotid arteries to the midline is extremely important
in pituitary surgery.
•• The carotid arteries bulge into the superolateral wall of the sphenoid sinus
in 71%.
•• These are usually covered by bone but in 4%, there may be no bone
between the carotid arteries and the mucosa of the sinus.
•• The average distance between the intracavernous portions of the two
carotid arteries is 12−14 mm.
•• The intercavernous venous connections traverse the anterior surface of
the pituitary gland in 76−85% of cases or the posterior surface in 37%.
Optic Chiasm
•• The position of the optic chiasma varies.
•• Schaeffer found that it lies in the sulcus chiasmaticus in 5% and over the
diaphragma sella in 12%. These two positions are termed prefixed.
•• The chiasma lies over the dorsum sella, which is its normal position in 79%.
•• In the postfixed position the chiasma lies over and behind the dorsum sella
and is found in 4%.
SYMPTOMS AND SIGNS

•• The symptoms and signs of pituitary tumours depend on the endocrine
activity (hyper or hypo), the size of the tumour (micro, macro or invasive)
and the effect on the neighbouring structures due to growth and expansion
of the tumour.
•• Visual manifestations occur when the tumour grows into the cranial cavity
and compresses the optic nerve, chiasm or tract.
•• The optic chiasm is situated 8−13 mm above the diaphragma sella and
therefore, there should be considerable growth of the tumour before vision
is affected. Visual examination, therefore, is not of much use in following-up
microadenomas.
•• Pituitary tumours, by compressing the optic apparatus, may produce: (1)
Reduction or loss of visual acuity due to compression of fibres subserving
central vision; (2) Various types of field defects; (3) Positive visual
phenomena in the form of hallucinations.
•• The visual field defects that commonly occur due to pituitary tumours are:
(1) Bitemporal hemianopia either incomplete or complete; (2) Temporal field
defect in one eye with loss of vision in the other eye; (3) Central scotoma;
(4) Junctional scotoma; (5) Homonymous hemianopia.
•• Visual hallucinations may occur in pituitary tumours. They may be formed,
consisting of recognisable shapes, or unformed, and may include sparks,
flashes or coloured lights.
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•• Some may have photophobia. Amaurosis fugax, lasting 5−45 minutes, has
been reported in a patient with a large pituitary tumour.
•• Foster Kennedy syndrome may be found in large tumours with compression
of an optic nerve, producing optic atrophy and the mass of the tumour
raising the ICP and producing papilloedema in the other eye.
•• The visual field defects may develop or worsen during pregnancy and
regress after delivery. This may be due to the compression of the chiasma,
secondary to an increase in size of the tumour due to the pregnancy.
•• Sudden visual loss and field defects may occur due to pituitary apoplexy,
which at times may be catastrophic, leading to total blindness in both eyes.
Effect on Neighbouring Structures

•• Except for headache most of the clinical features described below develop
only association with very large tumours—so called ‘giant’ pituitary
adenomas.
•• Headache:
–– Headache is initially caused by stretching of the diaphragma sella,
which is innervated by the ophthalmic division of the trigeminal nerve.
–– When the tumour expands further, it may lead to raised ICP and head-
ache as a result of the mass effect itself or by hydrocephalus due to
third ventricular obstruction. The latter is, however, rather uncommon.
•• Ocular Palsies and Ptosis:
–– Paralysis of the extraocular muscles either partial or total may occur;
the III nerve being the most commonly involved there may be ptosis
and the pupil may or may not be involved. This is due to invasion or
compression of the cavernous sinus or due to lateral extension of the
tumour.
–– The onset of III nerve palsy may be preceded by retro-ocular pain.
–– Unilateral proptosis may also occur and indicates the side of lateral
extension of the tumour.
–– The incidence of ocular palsies reported in the various series ranges
from 0% to 25%.
•• Fifth Nerve Involvement:
–– The first and second divisions of the trigeminal nerve may be involved.
–– It is essential to test the corneal reflex.
–– Facial hypoaesthesia may be present.
–– Rarely, facial pain resembling trigeminal neuralgia occur.
•• Hypothalamic Involvement:
–– This occurs when the tumour expands upwards and compresses the
hypothalamus.
–– This may further aggravate the existing endocrinological symptoms.
–– There may be disturbances of consciousness.
•• Hydrocephalus:
–– This can develop either unilaterally or bilaterally, as one or both the
foramina of Monro may get obstructed. This may lead to headache,
vomiting, papilloedema, lethargy and coma.
•• Psychological Changes:
–– Dullness, apathy, loss of memory, confusion, confabulation, irrability,
delusion and hallucinations may be seen. These may result from pres-
sure effects on the frontal and temporal lobes, the third ventricle and
the hypothalamus.
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•• In 1940, Jefferson made an extensive study of extrasellar extensions of

pituitary tumours and described the following varieties:
–– Hypothalamic extension by massive tumours growing behind a pre-
fixed chiasma
–– Extension under the frontal lobes producing personality changes
–– Parasellar extension compressing the temporal lobe and producing
temporal lobe epilepsy
–– Extension into the sphenoid sinus and the nasopharynx. Large tu-
mours may also extend through the tentorial hiatus and grow into the
posterior fossa.
•• Endocrine:
–– The endocrine symptoms and signs may be due to hypersecretion or
hyposecretion.
–– Hyposecretion can be of individual hormones or there could be pan-
hypopituitarism.
–– There may be diabetes insipidus, hypogonadism, hypothyroidism and
abnormalities of secretion of ACTH, GH and PRL.
–– In panhypopituitarism, there is a pale waxy pallor, prominent fine wrin-
kles around the eyes and mouth, a reduction in axillary and pubic hair,
diminished growth of the beard in men with a corresponding diminution
in the need to shave and anaemia as a result of diminished function of
the bone marrow. There may be truncal obesity.
–– A reduction in function of the pituitary adrenal axis (Addison’s disease)
may produce nausea, vomiting, postural hypotension and hyperthermia.
–– Complete failure produces an Addisonian crisis and collapse.
–– Reduction in thyroid function leads to myxoedema with the manifesta-
tions of sluggishness, relative inactivity, cold intolerance, dryness of
the skin and in severe cases, coma.
–– Gonadal dysfunction produces amenorrhoea, decreased libido and
uterine and vaginal atrophy in women. In men, the testes become
atrophic; there is reduction in libido and potency, as well as azoo-
spermia.
144
CHAPTER
Prolactinomas
Ravi Ramamurthi  Prasad AN
INTRODUCTION
•• Prolactinomas are the most common pituitary tumours and account for
25−40% of such pesions.
•• Trisomy of chromosome 12 is a non-random chromosomal change in
pituitary adenomas, particularly prolactinomas.
•• They may be seen as micro or macrotumours.
•• The symptoms and signs are either due to hypersecretion of prolactin or
related to the size of the tumour.
SIGNS AND SYMPTOMS

•• The endocrinopathy produced in women is the galactorrhoea-amenorrhoea
syndrome (Forbes-Albright syndrome).
•• There may be various menstrual disorders like amenorrhoea, oligomenor-
rhoea and irregular periods.
•• About 30% of women have frank galactorrhoea. There is also associated
infertility.
•• In men, there may be loss of libido, oligospermia and, occasionally,
galactorrhoea.
•• The tumours are likely to be larger in men when they seek medical help,
as the mild endocrine symptoms may be overlooked, whereas in women,
generally, the endocrinopathy predominates and, therefore, a larger
proportion of tumours are seen as microadenomas.
•• In men, the signs and symptoms of mass effect generally predominate.
•• The predominance of large prolactinomas in men may also be due to a
high frequency of rapidly growing tumours, which are often invasive and
frequently bromocriptine resistant.
•• Prolactinoma has been associated with obesity.
•• As opposed to ACTH- and GH-secreting adenomas, the mechanism by
which macroprolactinoma causes obesity has not been fully understood.
ENDOCRINOLOGY
•• Elevations in serum prolactin can occur due to secretion by the tumour itself
or from compression of the pituitary stalk or hypothalamus.
•• Hyperprolactinaemia can also occur in several other conditions which
include pregnancy, renal failure, hypothyroidism, other sellar and
parasellar tumours and ingestion of drugs, such as phenothiazines, tricyclic
antidepressants and centrally acting antihypertensives.
Chapter 144 • Prolactinomas
1095
•• The normal range of serum of prolactin (PRL) is 10−20 ng/ml.

•• Elevation of the fasting PRL level above 150 ng/ml is strongly suggestive
of a prolactinoma, preferably, if observed in two different samples tested
at different times.
•• Values between 30−100 ng/ml may be due to other causes which have to
be ruled out before a diagnosis of prolactinoma is made.
•• A PRL level higher than 1000 ng/ml is indicative of an invasive adenoma,
especially invasion of the cavernous sinus.
•• Pituitary tumour transforming gene (PTTG) abundance is a molecular
marker for invasiveness in hormone-secreting pituitary tumours.
•• Macroprolactinaemia, defined as hyperprolactinaemia with a predominance
of, or only the big big prolactin (bbPRL) isoform, is considered idiopathic
and poorly symptomatic.
•• There is a common group of patients with a pituitary adenoma who secrete
PRL and GH unsynchronously. Some of these patients have clinical
acromegaly at diagnosis and some patients diagnosed as prolactinomas
will develop acromegaly.
•• An annual IGF-I measurement should be used as a screening test.
•• It is necessary to have a baseline evaluation of T3, T4, TSH, cortisol, LH,
FSH, oestrogen and testosterone. This helps in diagnosis, in determining
the need for therapy and in the follow-up.
MANAGEMENT
•• Medical therapy is now accepted as the first line of treatment in
microprolactinomas and macroprolactinomas.
•• Medical treatment with dopaminergic compounds is effective and safe in
patients with prolactinoma with onset in childhood, allowing preservation
of anterior pituitary function.
•• The drugs available are: bromocriptine, pergolide, cabergoline and
quinagolide (CV 205-502).
•• Bromocriptine (2 bromo-ergocryptine) is an ergot alkaloid and a dopamine
agonist, which acts by stimulating the dopamine receptors on the lactotrophs
in the pituitary gland and is considered a potent analogue of dopamine.
•• Bromocriptine is given in a dosage of 5−20 mg/day in three divided doses.
•• The dosage should be increased gradually, as this reduces the side effects.
•• A long acting depot injection of bromocriptine, which is given once in 28
days, has been developed and is in use (Parlodel LAR).A slow release
oral preparation (Parlodel SRO) is also available and helps in avoiding
repeated medication and ensuring patient compliance. In patients who are
unable to tolerate the orally administered drug, it can be given per rectum
with good effect.
•• Bromocriptine lowers the PRL level in patients with or without pituitary
tumours, significantly reduces the size of a macroprolactinoma and restores
normal gonadal function.
•• Pronounced visual improvement also occurs due to reduction in the size
of the tumour.
•• Bromocriptine is effective in restoring normal menstruation in 80% of
women, abolishing galactorrhoea in 90% and reversing the hypogonadal
state in 80% of men.
•• Serum-prolactin levels revert to normal in 65−75% of patients with
macroprolactinomas, and there is significant reduction in tumour size in
50−60%.
1096
•• In microadenomas, there is a reduction in symptoms and in serum PRL

levels in over 90%.
•• The most conspicuous pathological changes that occur in a prolactinoma
after dopamine agonist therapy are a decrease in the size of tumour cells
and interstitial and perivascular fibrosis. In some tumours, connective tissue
accumulation is pronounced.
•• The large cells contain immunoreactive PRL and express the PRL gene,
indicating resistance to dopamine agonists.
•• In the small cells, PRL immunoreactivity and PRL gene expression are
decreased, indicating that both PRL synthesis and release are blocked.
•• The side effects of bromocriptine include nausea and vomiting, which may
occur initially in 30% of patients, although it may be troublesome in only
about 10%. Numbness and tingling of the toes and fingers, weakness
in the legs and muscle pains may be complained of by some patients.
Hypotension may occur.
•• In macroprolactinomas, CSF rhinorrhoea may occur during therapy due
to shrinkage of the tumour unblocking a dural rupture in the sellar floor.
•• Most patients require bromocriptine indefinitely, because discontinuation
of therapy may result in rapid expansion of the tumour, especially in
macroprolactinomas.
•• A special problem arises with regard to continuation of bromocriptine
therapy during pregnancy. The tumour, especially a macroadenoma, may
expand during pregnancy if the drug is stopped. This occurs in 1% of
microadenomas and 5−20% of macroadenomas.
•• There have been no known teratogenic effects of bromocriptine in a large
series of pregnancies.
•• Pregnancy is safe in patients with hyperprolactinaemia and can frequently
be beneficial, inducing a decrease in prolactin levels.
•• It is therefore wise to continue bromocriptine during pregnancy, especially in
macroprolactinomas, provided close surveillance is possible with repeated
CT examination.
•• If there is rapid growth of the tumour with visual compromise or apoplexy,
trans-sphenoidal surgery has to be undertaken, with the attendant risks of
major surgery during pregnancy.
Pergolide
•• This is a synthetic ergoline derivative with highly potent long acting PRL
lowering activity.
•• It is administered as a once daily dose of 50−100 micrograms.
•• The effectiveness and side effects were the same as bromocriptine but with
the advantage of a once-daily administration with pergolide.
Cabergoline
•• This is a long acting dopamine agonist.
•• It is administered orally at a weekly dose of 0.2−3.5 mg which may also be
given in divided doses, twice or thrice a week.
•• Long-term low dose of the D2 receptor agonist CAB significantly reduced
tumour volume and normalised serum PRL levels in a great majority of
patients bearing macroprolactinoma.
•• CAB can be used as a first choice drug treatment in macroprolactinomas,
microprolactinomas and idiopathic hyperprolactinaemia.
Chapter 144 • Prolactinomas
1097
Quinagolide
•• CV 205–502 is a potent, long acting non-ergot D2-dopamine agonist.
•• It is administered orally in a single daily dose of 75−300 micrograms.
•• Side effects are mild and include mainly headache, nausea and dizziness.
•• The efficacy of this drug in reducing PRL level and tumour size is similar
to that of bromocriptine.
Surgery
•• The present indications for surgery, either trans-sphenoidal or transcranial
are limited to:
–– Patients in whom the tumour is unresponsive to dopamine agonist
treatment, especially cystic prolactinomas.
–– Patients who are unable to tolerate dopamine agonist medication.
–– Patients in whom there is rapid progression of visual loss.
–– Patients in whom the tumour grows while on dopamine agonist therapy.
–– Pituitary apoplexy.
•• The use of a dopamine agonist, prior to surgery, has not been shown to
be of much benefit in prolactinomas.
•• Long-term administration of a dopamine agonist may lead to tumour fibrosis
and cause difficulties in surgical removal.
•• Surgery for prolactinomas, when indicated, is best performed within twelve
months of starting dopamine agonist therapy.
•• Radiation therapy has a limited role in treatment of resistant prolactinomas
and should be reserved for patients in whom medical and surgical therapy
has failed.
•• Gamma knife radiosurgery should be a part of the armamentarium for
treating refractory prolactinomas.
145
CHAPTER Growth Hormone
Secreting Adenomas
INTRODUCTION
•• Disorders of growth hormone (GH) secretion can result in its excess or
decrease.
•• Reduction in GH is significant in children.
•• Gigantism results when hypersecretion occurs before the epiphyses have
fused, and acromegaly after fusion of the epiphysis.
PATHOGENESIS
•• The excess secretion of GH can be primary or due to an excess of growth
hormone releasing hormone (GHRH) from hypothalamic disease.
•• Primary hypersecretion of GH is most commonly due to a GH secreting
adenoma.
•• Of the adenomas that secrete GH, 80% are somatotrophs and the rest are
mammosomatotrophs with accompanying hyperprolactinaemia.
•• GH may also be secreted ectopically by malignant tumours of the breast,
lungs, pancreas or ovaries.
•• GHRH increase may occur as a result of involvement of the hypothalamus
by hamartoma, glioma, ganglioglioma or choristoma.
•• Ectopic GHRH secretion may occur in carcinoids of the lungs, GI tract and
pancreas, carcinoma lung, islet cell tumours, phaeochromocytomas and
adrenal adenomas.
•• Acromegaly can occur both sporadically and in the setting of familial
conditions, such as multiple endocrine neoplasia type 1 (MEN1), Carney
complex (CNC) and isolated familial somatotropinomas (IFS).
CLINICAL FEATURES
•• The mean age of diagnosis of acromegalic patients is 45 years with a slight
female predominance.
•• In gigantism, the limbs and long bones uniformly enlarge and there is a
proportionate enlargement of the other organs too.
•• This results in increased height, enlargement of hands and feet, progna-
thism, prominent frontal sinuses and puberty may be delayed, due to the
associated hypogonadism, causing a further delay in closure of the epiphyses.
•• The usual age of onset of acromegaly is in the third to fifth decade.
•• In the early stages, the changes in appearance may be subtle.
•• Headache occurs in 50−75% of patients with acromegaly and gigantism.
•• The mechanism of the headaches is not clear. In large tumours, stretching
of the diaphragma sella may be responsible.
Chapter 145 • Growth Hormone Secreting Adenomas
1099
•• Changes take place in the bones and soft tissues, especially of the hands,
feet, face and skull.
•• The fingers and the hands thicken and take on a ‘spade-like’ appearance.
•• Overgrowth of the mandible leads to prognathism and malocclusion of
the jaws.
•• In association with an enlarged tongue, it may lead to respiratory distress.
•• The frontal bone and sinuses, malar and nasal bones and the soft issues
of the face enlarge, leading to a ‘beetle brow’ appearance and the char-
acteristic facies.
•• The cartilages in the joints, nose, ear and larynx overgrow.
•• There is visceromegaly involving the kidneys, lungs, liver, heart, spleen,
stomach, intestines and salivary glands.
•• Skin changes occur in the form of hyperhidrosis and oiliness of the skin with an
abnormal odour. Multiple and excessive sebaceous cyst formation may occur.
•• Body hair may be increased.
•• Entrapment of peripheral nerves may occur, leading to entrapment
neuropathies, the commonest being the carpal tunnel syndrome. Fibrous
thickening of the joint capsule and ligaments may occur, as in the wrist,
which leads to carpal tunnel syndrome.
•• The peripheral neuropathy may also be related to diabetes mellitus.
•• Multiple joint pains leading to severe arthritis may occur as a result of bony
overgrowth and distortion of the articular surfaces.
•• Muscle weakness and easy fatigue may occur due to myopathy.
SYSTEMIC CHANGES
•• Cardiac disease is common and the exact mechanism is not known.
•• Hypertension, coronary artery disease, valvular heart disease and
compensatory hypertrophy due to generalised splanchnic hypertrophy are
some of the proposed aetiological factors.
•• Concentric hypertrophy (biventricular) is the most common feature of
cardiac involvement in acromegaly found in more than two-thirds of patients
at diagnosis.
•• Hepatomegaly and renal enlargement may cause hepatic and renal
insufficiency.
•• The best characterised respiratory disease is sleep apnoea.
•• Ventilatory dysfunction occurs as a result of bony changes of the thoracic
cage, and lung overgrowth.
•• About 50% of acromegalics have impaired glucose tolerance and about
10% have diabetes mellitus.
•• The diabetes is usually reversible after treatment of acromegaly.
•• Menstrual disturbances and galactorrhoea in women and decreased
libido and impotence in men may occur, as a result of associated
hyperprolactinaemia, pituitary stalk effect or reduction in FSH and LH.
•• Low serum IGF-I/GH ratio was associated with abnormal glucose tolerance
in acromegaly.
•• IGF-I/GH ratio is a useful marker to understand the metabolic status in
acromegaly.
•• Factors accounting for the increased mortality rate in acromegaly are:
–– Age at the time of diagnosis. Older patients have higher mortality.
–– Male gender.
–– Disease duration. Exposure to GH excess is associated with increased
cardiovascular risk due to cardiac hypertrophy, diastolic dysfunction, myo-
cardial valve insufficiency, insulin resistance, dyslipidaemia and obesity.
1100
–– Lowest levels of GH (less than 2−2.5 ng/mL) are associated with the
lowest mortality rates.
–– IGF-I concentrations were found to be related to mortality.
–– Active disease.
–– Hypopituitarism, present in 10−40% of patients with acromegaly, is
associated with increased mortality.
–– Increased association of systemic cancers.
–– Increased mortality seen in patients having received irradiation.
TREATMENT
Surgery
•• Surgery is the primary mode of treatment in all patients.
•• Transsphenoidal microsurgery is ideal for microadenomas and macroad-
enomas.
•• Surgery offers the best chance for cure and normalisation of endocrine status.
•• Following surgery, there is rapid clinical improvement, the beneficial
changes in the hands being often apparent within a day or two and in the
facies within a week. The persistent headache disappears rapidly.
•• The criteria for cure and successful therapy should be:
–– GH level less than 5 ng/mL
–– GH level less than 2 ng/mL, following a glucose tolerance test
–– Normalisation of somatomedin C levels (SM-C)
–– A normal response to LHRH stimulation.
•• The best results are obtained when the tumour is a microadenoma and the
basal GH level is less than 40 ng/mL.
•• Complete removal of the pituitary tumour inevitably included a portion of
normal tissue (microsurgical pseudocapsule).
•• The complications that occur after transsphenodial microsurgery are very
low, transient and permanent DI, excessive bleeding, CSF rhinorrhoea
requiring reoperation, infection, meningitis, panhypopituitarism and, oc-
casionally, reduction in vision.
Medical Treatment
•• Octreotide and bromocriptine are the drugs that are used as adjuvants to
surgery, when the GH levels remain high after surgery or when there is
recurrence of tumour.
•• GH induced cardiomyopathy may not allow safe anaesthesia and surgery
and Octreotide and Sandostatin-LAR treatment dramatically improves
ejection fraction in these patients.
Somatostatin Analogues
(Octreotide, Lanreotide and Pasireotide)
•• Octreotide is a cyclic octapeptide analogue of somatostatin, and has been
used extensively for the treatment of acromegaly.
•• It is given subcutaneously in a dose of 300 micrograms per day in three
divided doses.
•• The GH levels normalise in about 25−60% of patients.
•• Incremental doses up to 1500 micrograms have been found useful in a
few patients.
•• It is well tolerated, but reduces gall bladder contractility and predisposes
to the formation of gall stones.
•• Surgical debulking of the pituitary tumour causing acromegaly improves
the effectiveness of somatostatin analogues.
Chapter 145 • Growth Hormone Secreting Adenomas
1101
Dopamine Agonists (Bromocriptine,

Quinagolide, and Cabergoline)
•• It is useful in mild cases.
•• Bromocriptine is less effective than octreotide.
•• Reduction of GH levels to below 5 ng/mL has been reported in 5−40% of
patients on bromocriptine therapy.
•• Larger doses than those used for prolactinomas are necessary and may
lead to increased side-effects.
•• Cabergoline can be used in patients with adenomas cosecreting GH and
prolactin, even in patients with large tumours.
•• Dopamine agonists are generally not effective in reducing the size of pure
GH-secreting pituitary tumours.
Growth Hormone Receptor Antagonists
•• The GH receptor antagonist was first developed in the late 1980s by Chen
et al. to enhance the half-life of the GHR antagonist (from 30 minutes to
more than 100 hours), several were added to the molecule.
•• A nine amino acid residue was added to polyethylene glycol (PEG) mol-
ecules which resulted in a molecule PEG-hGH G120K (with pegvisomant
as the generic name).
•• Pegvisomant has increased affinity to binding site 1 and inactivates binding
site 2, blocking the GH receptor and eliminating the adverse effects of
elevated GH levels.
•• Both GHR antagonists and somatostatin analogues are useful in preventing
long-term diabetic complications.
•• Combined treatment using a somatostatin analogue with pegvisomant
appears to be an effective and rational approach.
Radiotherapy
•• The indications for radiotherapy are: Non-curative surgery; poor response
or inaccessibility to medical treatment; growth restraining of aggressive
macroadenomas; comorbidities that contraindicate surgery and surgery
refusal.
•• Conventional radiotherapy and radiosurgery are two radiation treatment
modalities that can be offered to these resistant patients.
•• Reported rates of remission for conventional radiotherapy range between
50% and 60% in patients with acromegaly, with a time to remission
delayed by several years, and adverse effects including high rates of
hypopituitarism.
•• Radiation can be delivered in a single sitting by stereotactic radiosurgery
or in fractionated form of smaller doses delivered over typically 5−6 weeks
in 25−30 treatments.
•• This treatment could be proposed to patients with aggressive adenomas,
in whom surgery does not lead to biochemical control.
•• In contrast, studies on stereotactic radiosurgery reported faster GH
hypersecretion decline, and a lower risk of adverse effects.
•• Tumour shrinkage in 90% and biochemical remission in 80% have been
reported.
•• More than 95% of pituitary adenoma patients have either tumour shrinkage
or stabilisation after radiosurgery.
•• Gamma knife (GK) radiosurgery is being accepted as an adjuvant form
of treatment.
146
CHAPTER
Cushing’s
Disease and Syndrome
Deepu Banerji  Sanjay Behari
NORMAL HYPOTHALAMIC-PITUITARY-
ADRENAL AXIS
•• The hypothalamic-pituitary-adrenal axis is meant to respond to any
exogenous stress by an appropriate stress reaction.
•• These inputs are transmitted to the paraventricular nucleus of the
hypothalamus by a neuronal network from the suprachiasmatic nucleus,
amygdala, hippocampus, locus coeruleus and median raphe nuclei of the
brainstem.
•• The summation of these signals results in the release of corticotropin
releasing hormone (CRH) into the hypophyseal portal system and from
there via the infundibulum to the pituitary gland.
•• Stimulation of corticotrophs in the pituitary gland by CRH results in the
release of ACTH.
•• Normal ACTH secretion from the pituitary gland into the circulation is in
discrete pulses.
•• Secretion of ACTH, cortisol and CRH follows a circadian rhythm, the highest
levels being around at 04:00 am, which decrease throughout the day to a
nadir between midnight and 02:00 am.
•• This circadian rhythm is due to high amplitude ACTH pulses in the morning
and decreased pulses in the night.
•• In stressful conditions, although the secretions of ACTH, CRH and cortisol
are increased, the normal circadian rhythm is maintained. This circadian
rhythm is disturbed in Cushing’s syndrome which aids in its diagnosis.
•• ACTH has a trophic effect on the adrenal gland and stimulatory effects on
adrenal glucocorticoid and androgen synthesis and release.
•• Due to its trophic effect, increased ACTH secretion in patients with
Cushing’s syndrome results in bilateral adrenal cortical hyperplasia.
•• The regulation of CRH and ACTH is by a negative feedback loop.
•• Cortisol inhibits the synthesis and release of CRH, blocks the action of CRH
and other secretagogues (vasopressin, central catecholamines, angiotensin
II, serotonin, cholecystokinin and vasoactive intestinal peptide) of ACTH on
corticotrophs and inhibits release of ACTH.This normal feedback inhibition
is lost in patients with Cushing’s syndrome.
AETIOPATHOLOGY
•• The aetiopathological causes of Cushing’s syndrome are classified on the
basis of whether it is ACTH dependent or ACTH independent for further
endocrinal evaluation (Table 1).
Chapter 146 • Cushing’s Disease and Syndrome
1103
Table 1: Classification of Cushing’s syndrome

Cushing’s syndrome
ACTH-dependent ACTH-independent Pseudo-Cushing’s
(80%) (20%) syndrome
Pituitary lesion in 85% Adrenal adenoma in 50% Obesity
Corticotroph adenoma Adrenal carcinoma in 50% Major depression
Corticotroph-carcinoma Micronodular hyperplasia Alcoholism
Corticotroph hyperplasia Macronodular hyperplasia Polycystic ovary syndrome
Syndrome X
Ectopic ACTH syndrome—15% Exogenous corticosteroids Others
Small cell CA—Lung (50%)
Foregut tumours—(35%)
Bronchial carcinoid
Thymic carcinoid
Medullary thyroid CA
Islet cell tumour
Phaeochromocytoma (5%)
Other tumours (10%)
Ectopic CRH—<1%
•• Cushing’s syndrome has an estimated prevalence of 5−10/100,000

population.
•• Corticotroph adenomas comprise 15% of pituitary adenomas in adults.
•• Corticotroph adenomas account for 70−85% of ACTH-dependent causes
of Cushing’s syndrome in adults.
•• They are four to eight times more common in females and occur commonly
between 20 and 60 years of age.
•• The less common causes include the syndrome of ectopic ACTH
secretion by tumours originating in the lung, bronchus, thymus, pancreas,
phaeochromocytoma, medullary thyroid carcinomas and rare ovarian
tumours.
•• Rarely ectopic CRH secreting tumours may originate from hypothalamic
gangliocytomas, paragangliomas, thyroid medullary carcinoid, bronchial
carcinoids and small cell lung cancers.
•• The ACTH independent causes of Cushing’s syndrome include adrenal
adenoma, adrenal carcinoma and rarely adrenal hyperplasia.
CLINICAL FEATURES
•• Clinical features are mainly due to a hypercortisolaemic state and hence
common to all causes of Cushing’s syndrome. However, certain features,
like hyperpigmentation, are specific for elevated levels of ACTH and due
to its melanotrophic effect.
•• Stimulation of the adrenal androgens by ACTH may manifest as hirsutism
in women; however, it is also common in polycystic ovary syndrome.
1104
•• Most of the common presenting signs, like central obesity, hirsutism,

abdominal striae and abnormal glucose tolerance are not very specific.
The more specific signs/symptoms like hypokalaemia, ecchymosis and
osteoporosis are uncommon (Table 2).
•• CD is more common in females (8:1), while ectopic ACTH syndrome is
more common in men (3:1).
•• Increased fat deposition is the most common feature of Cushing’s syndrome
and is due to glucocorticoid excess. Unlike generalised obesity, the fat
deposition is typically ‘Centripetal’, i.e. more on the trunk and less or nil in
the extremities which may even be wasted.
•• Increased fat deposition is typically seen in the subcutaneous areas of
the face (moon facies), neck and shoulder (buffalo hump) and in the
mediastinum and peritoneum.
•• Proximal muscle weakness is a prominent feature and is due to cortisol-
induced catabolism of muscle, stimulation of muscle glycogenolysis and
inhibition of muscle protein synthesis. The typical clinical presentation is
difficulty in getting up from the sitting or recumbent position and climbing
stairs.
•• Osteoporosis and fractures are due to increased resorption of osteoclasts,
impaired osteoblast function, impaired calcium absorption and secondary
hyperparathyroidism.
•• In children linear growth is often arrested; however, weight continues to
increase.
Table 2: Clinical features of Cushing’s syndrome

Fat distribution Skin manifestation
Centripetal obesity Purple stria
Moon facies Plethora
“Buffalo Hump” Hirsutism
Supraclavicular fat pads Acne
Bruising
Musculoskeletal Pigmentation
Proximal muscle weakness
Osteoporosis/fractures
Mental changes
Irritability Hypertension
Psychosis Glucose intolerance
Metabolic/circulatory
Hypokalaemic alkalosis
Pituitary dysfunction
Menstrual disorder
Decreased libido/impotence
Hypothyroidism
Dwarfism (children)
1105
•• Hypercalcaemia is rare in spite of increased bony resorption; however,

there may be hypercalciuria and nephrolithiasis.
•• Cutaneous manifestations include ecchymosis, telangiectasias, purpura,
central facial erythema and plethora. Perioral dermatitis and acne may
also be present. These cutaneous changes are due to atrophy of the
epidermis, weakening of supporting muscles and fascia, and exposure of
the subcutaneous vasculature.
•• Violaceous striae larger than 1 cm in diameter are highly specific for
Cushing’s syndrome.
•• Acanthosis nigricans may be seen in patients with Cushing’s syndrome,
as with any condition that causes insulin resistance.
•• The hair of a Cushing’s patient may show soft pale villous hypertrichosis.
•• Hirsutism is a common feature of ACTH dependent disease and adrenal
carcinoma due to secretion of androgens.
ENDOCRINE EVALUATION
•• Endocrine evaluation starts with clinical assessment and to rule out
exogenous intake of steroids, especially from some indigenous form of
medicine and for differentiation from causes of pseudo-Cushing’s syndrome.
•• Different sets of laboratory investigations are done to establish first the state
of hypercortisolaemia, followed by differentiation between ACTH dependent
and independent forms and finally the establishment of CD.
Confirmation of Cushing’s Syndrome

•• The aim is to establish the hypercortisolaemic state and to differentiate it
from pseudo-Cushing’s syndrome.
•• The normal range of basal cortisol levels in an 8 AM serum sample is
110−520 nmol/L, while a level of more than 530 nmol/L in an 11 PM sample
is highly suspicious.
•• Twenty-four Hour Urine Free Cortisol Excretion:
–– The test is very reliable if radioimmunoassay (RIA) or high perfor-
mance liquid chromatography (HPLC) is available.
–– The normal range of urine free cortisol excretion (UFC) in HPCL is
up to 1380 nmol/L (50 µg/dL) or by RIA up to 2,480 nml/L (90 µg/dL).
•• One Milligram Overnight Dexamethasone Suppression Test:
–– This is a simpler test to perform with high sensitivity with false negative
results being less than 1%.
–– One milligram of dexamethasone is given orally at 11 PM. Serum lev-
els are estimated in the next 8 AM sample.
–– A normal response will be suppression of serum cortisol to less than
140 nmol/L (>5 µg/dL).
–– Serum cortisol concentrations greater than 10 µg/mL (>275 nmol/L)
are strongly suggestive of Cushing’s syndrome.
–– False positive tests could result from diseases like severe stress, alco-
holism, depression and medications with oestrogen.
–– False negative results could be due to renal failure and use of
medicines like phenytoin, phenobarbital and rifampicin, which affect
dexamethasone metabolism due to increased hepatic enzyme activity.
–– The normal response of suppression is highly sensitive and a good
screening test to rule out Cushing’s syndrome.
1106
•• Midnight Plasma Cortisol or Salivary Cortisol Level Determination:

–– One of the earliest biochemical abnormalities in Cushing’s syndrome
of any cause is the failure to fully suppress plasma cortisol at or near
its late-night circadian nadir.
–– Patients with Cushing’s syndrome fail to decrease cortisol secretion
during the normal nadir.
Establish ACTH-dependent versus

ACTH-independent State
•• It is very important that once Cushing’s syndrome has been established,
one should differentiate between ACTH-dependent (pituitary corticotrophs,
ectopic ACTH syndrome or rarely ectopic CRH secretions) from ACTH-
independent (adrenal adenoma, adrenal carcinoma, micro-macro adrenal
hyperplasia and exogenous glucocorticoid) causes.
•• A two day midnight plasma ACTH level of more than 10 pg/mL (2 pmol/L)
definitely confirms ACTH-dependent disease.
•• Plasma ACTH levels provide an initial clue, because levels are suppressed
in primary adrenal disease but are elevated in the case of corticotroph
adenomas, ectopic ACTH syndrome and in some CRH-producing tumours.
Cushing’s Disease versus Ectopic ACTH Syndrome

•• The CD is the cause of ACTH dependent Cushing’s syndrome in 85−90%
of cases. The rest are due to ectopic ACTH secreting tumours.
•• The latter usually present clinically with rapid progression of symptoms or
with hypokalaemia.
•• High Dose Dexamethasone Suppression Test (HDDST):
–– It is based on the assumption that in CD, the pituitary corticotrophs
will still have an intact negative feedback and will respond to HDDST
(dexamethasone—2 mg every 6 hours for 48 hours or overnight 8 mg
at bedtime) with 50% or more reduction in UFC or plasma cortisol in
the morning 8 AM sample, while an ectopic ACTH tumour is independ-
ent of negative feedback and will not suppress cortisol secretion even
with higher doses of dexamethasone.
DIAGNOSTIC EVALUATION
•• Magnetic resonance imaging (MRI) is the diagnostic investigation of choice
in CD and has replaced CT scan.
•• An ACTH-dependent patient with positive MRI for a microadenoma (>5 mm)
should straight away undergo trans-sphenoidal surgery.
•• If MRI is inconclusive, a dynamic MRI will pick up a fair number of adenomas
utilising the differential enhancing characteristics of the normal gland and
the adenoma over a time frame.
•• The normal pituitary enhances earlier than the adenoma.
•• If brain MRI is still negative, one should exclude an ectopic ACTH producing
adenoma by doing a high resolution contrast-enhanced CT scan of the
chest and abdomen.
Inferior Petrosal Sinus Sampling

•• It can help in lateralising the side of an adenoma for surgical removal in
an equivocal MRI.
1107
•• It is based on the physiological secretion of ACTH from the pituitary gland,

which then drains into the bilateral cavernous sinus and then into the
bilateral inferior petrosal sinus.
•• Bilateral micro-catheters are placed through the transfemoral route into
both inferior petrosal sinuses.
•• Baseline blood samples are drawn from both the sinus and peripheral veins.
•• A gradient of two or more between central (B/L petrosal) and peripheral
ACTH indicates a pituitary origin of an ACTH adenoma. CRH stimulation
helps in inducing a pulse ACTH secretion and enhances the accuracy.
MANAGEMENT
•• Management of CD is trans-sphenoidal excision of adenoma as a first
choice, once diagnosis is established.
•• If the adenoma is well seen on MRI, selective adenomectomy is done after
exposure of the pituitary gland with good results.
•• Additionally, sector-wise incisions are made in the rest of the gland and
any abnormal tissue is removed and biopsied.
•• If MRI is inconclusive and IPSS shows a side preference, ipsilateral
hemihypophysectomy is planned along with a sectorial search on the
opposite side.
•• However, if MRI and IPSS are inconclusive and the patient is a female
who has completed her family, a pre-operative discussion regarding
total hypophysectomy should be made or else a plan for subtotal
hypophysectomy leaving a small central mucoid core to the pituitary stalk
is made.
•• Laterally placed adenomas as they are likely to be adherent to the
cavernous sinus wall and dura are likely to lead to surgical failure. In such
a situation, an endoscopic approach or at least endoscope assistance may
help in a complete removal.
•• A 3rd to 5th day post-operative serum cortisol level gives a prognostication
of completeness of removal.
•• The patient needs to be put on steroid replacement till the remaining gland
regains its function, usually 5 mg and 2.5 mg of prednisolone or 10 mg and
5 mg of hydrocortisone per day.
•• At 6 weeks to 3 months, a review for hormonal assessment is done.
•• If cortisol remains within normal range, a further 6 monthly follow-up is
necessary.
•• However, if cortisol is near the upper range of normal or high, a
dexamethasone suppression test is done to look for recurrence.
•• Failure of remission/recurrence is usually due to the following reasons:
–– Macroadenoma or invasive tumour with incomplete removal
–– Failure to identify and remove the tumour either due to pre-operative
inconclusive MRI findings or failure to establish a pituitary source of
cortisolaemia
–– Multinodular corticotroph cell hyperplasia and
–– Multifocal corticotroph adenoma.
•• If second surgery is not acceptable or feasible, radiation can be given and
the patient put on medical therapy in the interim period till radiation becomes
effective, usually in 2−3 years.
•• Bilateral adrenalectomy is always the last resort and usually reserved for
failure of multiple pituitary exploration or very invasive tumour with very
high ACTH levels, where waiting for radiation-induced remission is going
1108
to take a long time and the patient is profoundly debilitated due to high
cortisolaemia.
•• Radiation therapy is a useful adjunct in failed or recurrent disease with
approximately 50% achieving remission over a long period of 5−10 years.
•• Radiosurgery is much safer and with good outcomes and approximately
1/3rd achieving remission by 12 months and 2/3rd by 3 years.
•• Gamma knife radiosurgery (GKRS) achieves about 55−65% remission in
the first year itself. For the sellar region, GKRS is more precise with less
risk to nerves including the optic nerves.
•• Medical management is needed as palliative treatment in the interim period
of evaluation of disease or during the phase of radiation to be effective.
•• Usually the drugs are classified as peripherally acting (adrenostatic) or
centrally acting, i.e. suppressing ACTH secretion.
•• Adrenostatics, like ketoconazole, metyrapone or aminoglutethemide are
most commonly used as effective drugs. They competitively inhibit adrenal
enzyme activity and decrease cortisol secretion.
147
CHAPTER
Other Secreting
Adenomas of the Pituitary
Deepu Banerji  Archana Juneja
PHYSIOLOGY OF THE PITUITARY

THYROID AXIS
•• The production of TSH by the pituitary is under control by TSH-releasing
hormone (TRH), produced by the periventricular nucleus of the hypo-
thalamus.
•• TSH is a 280 kD glycoprotein composed of two subunits, the α-and
β-subunits, each coded by separate genes.
•• The α-subunit is common to other glycoprotein hormones like LH, FSH
and hCG.
•• The β-subunit is unique and confers specificity of action of the particular
hormones.
•• The binding of TSH to its receptor on the thyroid follicular cells is influenced
by the degree of glycosylation of the α-and β-subunits.
•• TSH secreting tumours secrete heterogeneous isoforms of TSH which
differ in the extent of oligosaccharide residues and the degree of sialylation
and fucosylation.
•• Tumours tend to have TSH isoforms with increased fucosylation and
decreased or normal sialylation.
•• TSH causes enlargement of the thyroid follicular cells and promotes
synthesis of thyroxine (T4) which gets deiodinated in the periphery to
triiodothyronine (T3).
•• T4 and T3 have negative feedback effects on both the production and the
release of hypothalamic TRH and pituitary TSH.
PATHOLOGY
•• The thyrotroph cells account for about 5% of the functional anterior pituitary
cells and are the cells of origin of a TSH-oma.
•• Most TSH-omas are benign, and malignant transformation is extremely
uncommon. These are invasive macroadenomas with a fibrous consistency
even in the absence of prior surgery or radiotherapy.
•• The adenomatous cells are mostly chromophobic and monomorphous.
•• The only hallmark of a pituitary carcinoma is the presence of distant
metastasis.
•• TSH-omas occur with equal frequency in males and females and are more
common in the third to sixth decade of life.
1110
•• Patients with TSH-omas present with symptoms and signs of either

hormone hypersecretion or mass effect from an expanding sellar lesion.
•• Presentation with thyroid goitre is the rule and is seen in more than 90% of
patients, even in those who have had a partial thyroidectomy.
•• Most patients have a history of long standing thyroid dysfunction with typical
features of hyperthyroidism, including heat intolerance, tremors, weight
loss, palpitation and diarrhoea.
•• The severity of symptoms varies but most have mild degrees of hyper-
thyroidism in relation to their hormone levels, probably due to the slow
development of the hyperthyroidism, leading to compensatory mechanisms
like receptor down regulation.
•• Severe features, like exophthalmos, cardiac failure and periodic paralysis
are very rare.
•• Most patients seek medical attention because of mass effects of the
expanding sellar lesion.
•• Headaches, visual field defects and cavernous sinus involvement are
common.
•• In fact, previous thyroid ablative treatment worsens the invasiveness of
the tumour.
•• Symptoms of hypopituitarism occur due to involvement of the other pituitary
cells by the tumour.
•• Signs of acromegaly, galactorrhoea, menstrual disorders and reduced
libido may be associated.
EVALUATION
•• High levels of T3 and T4 in the presence of detectable levels of TSH are
characteristically seen in patients with TSH secreting tumours.
•• Increase in levels of TSH transport proteins (thyroxine binding globulin
or transthyretin or albumin) caused by drugs or oestrogens; familial
dysalbuminaemia; drugs, like amiodarone and acute psychiatric disorders,
can cause elevation in total T4 levels.
•• Increased levels of free thyroid hormones are documented in the
presence of detectable TSH levels (i.e. central hyperthyroidism) by the
immunoradiometric assays.
•• The α-subunit levels are elevated in two-thirds of patients with a TSH-oma.
•• Calculating the molar ratio of α-subunit to TSH, improves the sensitivity
of detection to 80%.
•• A ratio of more than 1 indicates a TSH-oma, although similar values have
been observed in menopausal women.
DYNAMIC TESTING
•• Several stimulatory and inhibitory tests have been described to evaluate
a TSH-oma.
•• The stimulatory test includes the TRH-induced TSH secretion, which is
absent or blunted in a majority of patients with TSH-omas.
•• The inhibitory test includes the T3 suppression test, which checks for the
degree of TSH suppression following T3 administration.
•• Both basal and TRH stimulated TSH levels are not suppressed, following
T3 administration in patients with TSH-omas.
Chapter 147 • Other Secreting Adenomas of the Pituitary
1111
•• This test is especially useful to diagnose a TSH-oma in patients who have

undergone a prior thyroid ablation and to predict long-term cure in patients
with TSH secreting tumours.
•• In summary, the combination of TRH test, α-subunit and α-subunit to TSH
ratio is diagnostic in the majority of untreated patients.
RADIOLOGICAL DIAGNOSIS
•• The advent of MRI has made the diagnosis of pituitary tumours easier. It
demonstrates the extent of the tumour with greater accuracy.
•• Gadolinium contrast scans are excellent tools to demonstrate micro
adenomas.
•• Nuclear scintigraphy using 111I labelled octreotide are more useful in
ectopic tumours.
THERAPY
•• Surgery is recommended as the first line of management.
•• Most of these tumours are hard, have a fibrous consistency and are locally
invasive, making complete excision difficult.
•• Complications include transient or permanent diabetes insipidus, syndrome
of inappropriate secretion of antidiuretic hormone and permanent central
hypothyroidism.
•• Radiotherapy is mainly employed as an adjunctive therapy to surgery and
not used as a primary modality of therapy.
•• As most TSH-omas are macroadenomas that extend into the suprasellar
cistern, they typically do not meet the criteria for safe use of stereotactic
radiosurgery.
Medical Treatment
•• Antithyroid drugs should not be used as a treatment for patients with
TSH-omas, as they increase the tumour growth and invasiveness. Their
probable role is only in the preparation of the patient prior to neurosurgery.
•• Beta-blockers can be given to control the hyperthyroid symptoms.
•• Somatostatin analogues like octreotide or lanreotide, are the current drugs
of choice for patients with TSH secreting adenomas.
•• Tumour shrinkage occurs in 50% and vision improvement in 75% of patients
treated with octreotide. A reduction in α-subunit, T3 and T4 confirms
efficacy of the drug.
•• Normal TSH dynamics is restored and the suppression of TSH secretion
with octreotide with consequent central hypothyroidism requires thyroxine
supplementation.
•• Tachyphylaxis is seen in about 25% patients necessitating dose increase.
•• Patients need to be monitored for side-effects like cholelithiasis and glucose
intolerance.
•• Lanreotide, the new long-acting formulation of somatostatin is a better
alternative, as it can be given once or twice a month.
•• Thus no single therapy is expected to be curative for a TSH-oma. A
combination of the above modalities is frequently required in a majority of
patients to achieve clinical remission and cure.
1112
Criteria of Cure
•• Cure is not defined by mere euthyroidism and absence of visible tumour
on imaging.
•• The most sensitive and specific test to document cure remains the complete
inhibition of both basal and TRH-stimulated TSH secretion, following T3
administration.
•• Recurrence rates, although not available, seem to be low at least for a
year, following documenting a cure.
•• Patients should be followed up at 3−6 monthly intervals in the first year
and then yearly.
•• Pituitary imaging needs to be performed every 2−3 years.
148
CHAPTER Non-functioning
Pituitary Adenomas
Manas Kumar Panigrahi  Naveen Mehrotra  Amit Kumar T
INTRODUCTION
•• Approximately 25−30% of patients who present with pituitary adenomas
have no clinical evidence of hormone hypersecretion, such tumours are
classified as non-functioning adenomas.
•• A pituitary adenoma can be differentiated from the normal pituitary gland,
both in gross and microscopic appearance.
•• Grossly, a normal pituitary gland is firm in consistency and an adenoma
is soft to semi-solid.
•• Microscopically, in a pituitary adenoma, the cells are monomorphous, but
they lack acinar arrangement whereas, in a normal pituitary gland, the cells
are of different size, shape, types and are arranged in an acinar pattern.
•• The loss of acinar pattern is one of the pathological hallmarks of pituitary
adenoma.
PATHOLOGY
•• Pituitary adenomas have long been classified according to their tinctorial
affinity for acidic or basic dyes into acidophilic, basophilic or chromophobic
adenomas.
•• Acidophil adenomas were traditionally associated with acromegaly,
basophil adenomas with Cushing’s syndrome and chromophobe adenomas
were thought to be non-functioning.
CLASSIFICATION OF PITUITARY
ADENOMAS
•• Prolactin cell adenomas
–– Sparsely granulated
–– Densely granulated.
•• Growth hormone cell adenomas
•• Mixed prolactin cell-growth hormone cell adenomas.
•• Acidophilic stem cell adenomas.
•• Mammosomatotroph cell adenomas.
•• Corticotroph cell adenomas
•• Gonadotrop cell adenomas.
1114
•• Thyrotroph cell adenomas.

•• Plurihormonal adenomas.
•• Null cell adenomas.
•• Oncocytomas.
IMMUNOHISTOCHEMISTRY
•• With the advent of immunohistochemical techniques and the use of specific
antisera, we can identify the hormones stored within the cells.
•• All the hormones have been found in non-functioning adenomas by
immunohistochemistry.
•• Apart from immunohistochemistry, the secretory activity of non-functioning
adenomas have been established by other in vitro studies like tissue culture,
analysis of pituitary hormone gene expression and the reverse haemolytic
plaque assay.
•• Immunocytochemical data suggests that many of these non-functioning
tumours produce subunits of glycoprotein hormones, which are
endocrinologically inactive.
•• The glycoprotein hormones include follicle stimulating hormone (FSH),
luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and the
placental hormone chorionic gonadotropin (CG).
•• They contain two subunits: (1) The alpha-subunit, which is common to each
of them, and (2) a beta-subunit (β-FSH, β-LH, β-TSH and β-CG), which
confers biological and immunological specificity.
•• Apart from immunohistochemistry, on electron microscopy of cells of non-
functioning tumours are seen to contain secretory granules despite their
apparent lack of assayable hormone product.
CLINICAL PROFILE
•• Patients with non-functioning tumours lack a characteristic clinical syndrome
or serum tumour hormone marker.
•• They present with symptoms related to tumour mass effect such as
headache, visual loss or symptoms of hypopituitarism.
•• In its most recognisable form, vision is impaired first in the upper outer
quadrants of the visual fields (bilateral superior temporal quadrantanopia),
which may progress to involve the entire temporal fields bilaterally
(bitemporal hemianopia).
•• The visual field impairment may be asymmetric and, when the chiasmal
compression is severe, central visual acuity is also affected.
•• The visual deficit may be so gradual that many patients are not aware
of their visual loss, until it is demonstrated on a routine eye examination.
•• The mechanisms responsible for visual field impairment may be direct
mechanical compression of the optic nerve or chiasm, ischaemia or a
combination of the two.
•• Headache may be due to stretching of the diaphragma sellae, elevation of
intracranial pressure due to obstructive hydrocephalus or an excruciating
type of headache due to pituitary apoplexy.
•• Diplopia with sudden severe headache may suggest apoplexy.
•• Rarer presentations may include epileptic seizures and CSF rhinorrhoea.
•• LH deficiency is the most common and results in reduced testosterone
secretion, resulting in decreased energy and libido and in pre-menopausal
women results in amenorrhoea.
•• Symptoms of hypothyroidism and hypoadrenalism may also occur.
Chapter 148 • Non-functioning Pituitary Adenomas
1115
ENDOCRINE DIAGNOSIS
•• The most common endocrinological abnormality observed in non-
functioning pituitary macroadenomas is hypopituitarism clinically manifested
as gonadal hypofunction.
•• Baseline serum levels of prolactin, growth hormone, T3, T4, TSH, cortisol,
FSH and LH should be ascertained.
•• The serum prolactin levels may be elevated because of stalk effect.
•• A large sellar suprasellar tumour with prolactin levels less than 200 ng/mL is
more likely to be a non-functioning adenoma than a prolactinoma.
•• The serum levels of TSH, FSH and LH may be elevated, as a majority
of pituitary adenomas that are clinically non-functioning are gonadotroph
adenomas and a significant minority are thyrotroph adenomas.
•• GH and cortisol levels will usually be normal but, if on provocative testing,
the levels of these hormones fail to rise, it is suggestive of hypofunctioning
of the pituitary.
IMAGING
•• MRI is currently the best technique for imaging the pituitary gland, due to
its superior resolution and ability to demonstrate the optic chiasm.
•• In addition, MRI is able to demonstrate blood, so an aneurysm can be
distinguished from other intrasellar lesions and haemorrhage into pituitary
adenomas.
•• A pituitary microadenoma is usually hypointense compared with the normal
gland on T1W images.
•• After contrast injection, the tumour typically does not enhance to the same
extent as the normal pituitary gland and thus stands out as an area of
relative hypointensity.
•• Focal hypointensity within the pituitary is the most reliable indicator of a
microadenoma.
•• Important secondary signs of microadenoma include asymmetric upwards
convexity of the gland surface, deviation of the infundibulum and focal
erosion of the sellar floor.
•• The preferred imaging planes are coronal and sagittal.
•• A pituitary macroadenoma is generally isointense to the normal gland and
brain parenchyma, unless there are cystic and haemorrhagic components.
•• Homogeneous contrast enhancement permits clear demarcation of the
tumour from normal suprasellar structures.
•• MRI is ideal for demonstrating extension of the tumour to the cavernous
sinus, optic chiasm, third ventricle and hypothalamus.
•• Upwards extension of a pituitary adenoma through the diaphragma sella
accounts for one-third to one-half of all suprasellar masses in adults.
•• Pituitary adenomas with suprasellar extension typically have a “figure of
eight” appearance and the mass is indistinguishable from the pituitary gland.
•• CT scan with or without contrast may be done when the patient is unable
to undergo an MRI. CT scan can demonstrate adjacent bone erosion and
extension of tumour beyond the confines of the sella.
•• On a CT scan, a pituitary adenoma typically appears to be well circumscribed,
lesion isodense to the brain and with homogeneous contrast enhancement.
•• Regions of necrosis or cyst formation in the tumour produce internal areas
of low density.
•• Microadenomas are usually less dense than the normal pituitary gland.
1116
•• Plain X-ray of the skull has limited value in the diagnostic evaluation of
patients with sellar/parasellar lesions. It reveals:
–– An enlargement of the sella also known as ballooning of the sella
–– Undercutting of the anterior clinoid process in which the processes are
thinned and sharp
–– Erosion of the sellar floor
–– Unequal downwards displacement of the sellar floor called as double
floor
–– Thinning and erosion of the dorsum sella
–– Degree of pneumatisation of the sphenoid sinus as presellar, sellar or
conchal and
–– Supra/intrasellar calcification.
TREATMENT
•• The goal of therapy for a non-functionary tumour is directed towards
reduction of tumour mass, rather than treatment of hypersecretory
syndrome.
•• The dopamine agonists so far been successful in reducing excessive
secretion by the adenoma than in reducing its size.
•• The presence of somatostatin receptors on the cell membrane of clinically
non-functioning and alpha-subunit secreting pituitary macroadenomas,
provides the possibility of treating these tumours with octreotide.
•• Bromocriptine has also been reported to cause reduction in tumour size.
•• Clinically non-functioning adenomas could include treatment with dopamine
agonists or a combination of octreotide and dopamine agonists.
SURGERY
•• Trans-sphenoidal surgery is currently accepted as the procedure of choice
for the initial management of most clinically non-functioning adenomas.
•• The trans-sphenoidal approach is preferable to transcranial approaches, as
it helps to preserve normal pituitary function and allows recovery of visual
function avoiding manipulation of the brain itself.
•• The immediate indication for surgery is visual field loss and with decom
pression of the optic chiasm, improvement in visual field abnormalities is
seen in the majority of patients.
•• The principle of treatment differs between functioning and non-functioning
adenomas.
•• The primary goal of surgery for non-functioning adenomas is gross total
or subtotal removal of the tumour, with preservation of normal pituitary
function.
•• Secreting adenomas must be removed completely for an endocrinological
cure, although prolactinomas or growth hormone producing adenomas can
be treated with bromocriptine or octreotide.
•• The patient is positioned supine with the head elevated by 30 degrees with
the neck flexed and the head turned contralaterally by about 20 degrees,
so that the nasal septum is parallel to the visual axis.
•• The normal pituitary gland is firmer than the tumour tissue and is yellowish-
orange in colour.
•• The pituitary gland with the stalk has to be preserved as far as possible.
•• After removal of the macroadenoma, the sinus is packed with abdominal
fat and the sellar floor is reconstructed with the autogenous bone graft
obtained at the time of sphenoidotomy.
Chapter 148 • Non-functioning Pituitary Adenomas
1117
•• Use of abdominal fat may not be necessary, if there is no CSF leak and in
case of a microadenoma.
Transcranial Surgery
•• Rarely, transcranial surgery should be considered in patients with giant
macroadenomas, where the bulk of tumour is suprasellar and parasellar,
and symptoms are arising from tumour compression of the brain.
•• Patients with recurrent tumours with failed multi-staged transsphenoidal
excision may require transcranial surgery.
•• Evidence of sphenoid sinusitis.
Complications of Surgery
•• Trans-sphenoidal surgery has low morbidity.
•• CSF rhinorrhoea is one of the most common complications.
•• Injury to the cavernous sinus/carotid artery are serious complications.
•• Cranial nerve injury may occur, especially of the III and VI nerves, if the
tumour is extending into the cavernus sinus.
•• Visual deterioration may occur after trans-sphenoidal surgery, either
because of direct operative trauma, compression due to a haematoma,
ischaemia or prolapse of the chiasm.
•• Hypopituitarism, diabetes insipidus (DI) and hypothalamic damage are
also known to occur.
•• Meningitis and nasal/sphenoidal problems are other complications.
RADIATION
•• Radio-surgery/stereotactic radiotherapy is indicated, when there is
inadequate tumour resection at the time of surgery and post-operative CT/
MRI show evidence of residual tumour, and the patient is symptomatic.
FOLLOW-UP
•• All patients with large non-functioning pituitary adenomas should be
evaluated for the presence of residual tumour with a CT/MRI scan
approximately 1 month following surgery, then at 6 months, 12 months
and, if stable, at yearly intervals.
•• Neuro-ophthalmological evaluation should include determination of visual
acuity and field.
•• Recovery of pituitary function following management of non-
functioning adenomas:
–– Partial or complete hypopituitarism is commonly found in patients with
non-functioning adenoma at the time of presentation.
–– The majority of patients with normal anterior lobe function pre-opera-
tively have preserved function following surgery.
–– Patients with a selected deficiency in anterior pituitary hormones often
showed no change or improvement following surgery.
149
CHAPTER
Pituitary Apoplexy
Ravi Ramamurthi  Vikram M  Goutham Cugati
INCIDENCE
•• The incidence varies in different series from 1 to 21%.
•• The incidence varies depending on the criteria used for diagnosis.
•• The incidence of subclinical pituitary adenoma apoplexy was higher than
acute pituitary apoplexy.
•• When subclinical presentations and patients with evidence of haemorrhage,
cyst or necrosis on imaging or at surgery are also included, the incidence
increases.
•• There are also incidences of post-operative pituitary apoplexy reported,
following surgery for giant pituitary adenomas.
PATHOGENESIS
•• Various mechanisms have been postulated for the occurrence of apoplexy.
•• The growth of the tumour may outstrip the blood supply and lead to necrosis
and haemorrhage. This is more likely in tumours growing in an enclosed
place like the sella turcica.
•• The other proposed mechanism is compression of the infundibulum by
an expanding mass, thus compromising the blood flow from the portal
vessels, resulting in necrosis of the entire gland with haemorrhage as a
secondary occurrence.
•• Prolactin (PRL) adenomas were the most common tumour type (56.2%).
•• Subclinical pituitary apoplexy usually occurs in patients with big or giant
adenomas.
•• The blood supply is also limited, with the main supply to the anterior lobe
being through the hypothalamo-hypophyseal portal circulation.
•• An expanding tumour may compress the infundibulum against the rigid
dural opening in the diaphragma sella, leading to acute necrosis and
infarction in the tumour.
•• Pituitary apoplexy usually occurs de novo, but some precipitating factors
may be responsible for producing the haemorrhage.
•• Head injury, chronic coughing and sneezing, radiotherapy, idiopathic
thrombocytopaenic purpura, lymphocytic hypophysitis, spinal anaesthesia,
intensive thrombolytic therapy and open heart surgery have been reported
to be associated with apoplexy.
•• Medications like leuprolide, clomiphene, goserelin, GnRH and CRH
administration and oestrogen administration, have been reported to
precipitate apoplexy.
•• Bromocriptine therapy and cabergoline administration have also been found
to precipitate apoplexy.
Chapter 149 • Pituitary Apoplexy
1119
•• Hypertension and diabetes mellitus were the possible predisposing factors.

•• In post-operative apoplexy, the proposed mechanisms are sudden release
of tumour vessels from the internal carotid artery due to reduced tumour
burden and compromise of the venous drainage of the tumour during
surgery, tumour manipulation during surgery and swelling and subsequent
compression of the hypophyseal arteries causing haemorrhagic necrosis.
CLINICAL FEATURES
•• Haemorrhage into a pituitary tumour may be subclinical and do not produce
any symptoms or signs, or may produce signs and symptoms of varying
severity, ranging from sudden onset of headache, rapid onset of visual
loss, unconsciousness or death.
•• The most common features are headache (85−90%), visual disturbances
(70−80%) and nausea and vomiting (50−60%).
•• Meningismus, seizures, frontal lobe syndrome, ocular nerve palsies and
signs resembling subarachnoid haemorrhage may occur.
•• Altered mental status, stupor and coma have also been seen.
•• Rarely, the presentation can be of non-ketotic hyperglycaemic coma or
diabetes insipidus.
•• The combination of headache, acute visual loss and ipsilateral Horner’s
syndrome without ophthalmoplegia, mimicking carotid artery dissection has
been reported as an unusual presentation.
•• The onset of apoplectic symptoms may be the first indication of an
underlying pituitary tumour.
•• Endocrinologic manifestations of pre-existing hypersecretion like
acromegaly, Cushing’s or galactorrhoea and amenorrhoea may be present.
Severe and acute hypopituitarism result either due to destruction of normal
pituitary tissue or due to compression of the stalk.
•• The hypopituitarism may be mild.
•• The visual defects that may occur are diminished visual acuity, blindness
in one or both eyes or field defects like central scotomata, bitemporal or
binasal hemianopia or generalised constriction.
•• Ocular movement disorders occur when the tumour expands and
compresses the cavernous sinus.
•• III, IV and VI nerve palsies can occur in various combinations producing
ptosis, dilated pupil and diplopia.
•• Trigeminal signs involving the first and second division may be found.
•• The differential diagnosis should include SAH due to aneurysmal rupture,
stroke, meningitis, encephalitis and uncal herniation, due to an expanding
intracranial mass lesion.
INVESTIGATIONS
•• When the clinical presentation suggests pituitary apoplexy, plain skull
films are valuable, as in the majority of patients changes consistent with
an intrasellar mass are likely to be seen.
•• CT scan is useful, and plain and contrast-enhanced scans must be done.
CT is better than MR in the acute stage.
•• A hyperdense non-enhancing lesion will be seen in the acute stage,
representing blood.
•• Surrounding enhancing tumour tissue may be seen.
•• The mass usually extends into the suprasellar cistern and may displace
the third ventricle producing hydrocephalus, which will be seen on the CT.
1120
•• When the CT is done weeks later or when there is necrosis without

haemorrhage, a central isointense or hypointense lesion may be seen
surrounded by a rim of contrast enhancement.
•• MR is useful, especially in the detection of silent or subclinical haemorrhage
and in following up patients with apoplexy.
•• The MR changes due to haemorrhage will vary depending on the age of
the haematoma in days and weeks.
•• Endocrine assessment is essential to decide on immediate and long-term
replacement therapy.
•• Levels of GH, PRL, cortisol and thyroid hormones should be done
immediately.
•• If necessary, provocative tests are done to evaluate the functioning of the
hypothalamic-pituitary axis and to know the reserve capacity.
•• Lumbar puncture to rule out meningitis or SAH should be done only when
the plain X-rays and the CT are inconclusive.
MANAGEMENT
•• The first step after diagnosis of pituitary apoplexy is to administer
corticosteroids.
•• When there is visual involvement, progressive decrease in the level of
consciousness or involvement of the cranial nerves, emergency surgery
must be undertaken to save life and vision.
•• When there are only mild symptoms and no visual problems, the patient
may be investigated further and the treatment options exercised as in any
other patient with a pituitary tumour.
•• Trans-sphenoidal surgery is indicated in patients with diminished levels of
consciousness, hypothalamic dysfunction and visual deterioration.
•• Trans-sphenoidal excision and decompression of the optic nerve and
cavernous sinus is the ideal.
•• Occasionally, transcranial surgery may be indicated when the sella is not
enlarged or a dumb bell tumour is suggested.
•• Hydrocephalus will be relieved with tumour decompression, but occasionally,
a CSF diversion procedure may be required.
•• Conservative management for patients with isolated cranial nerve palsies
has been advocated but remains controversial.
•• Post-apoplexy long-term endocrine deficits are quite common.
•• Improvement in endocrine status may take place after surgery and this
is probably due to release of stalk compression, which occurs during the
apoplexy.
•• Endocrine replacement therapy as appropriate must be instituted post-
operatively, depending on the post-operative endocrine profile.
•• Visual improvement usually occurs following decompression. Visual
outcome depends on the duration and severity of compression prior to the
apoplexy and also on the time lag between the apoplexy and the surgery.
•• Useful recovery of vision has been reported after total bilateral blindness and,
therefore, it is necessary to take urgent action even when the patient is blind.
•• Recovery of cranial nerve dysfunction occurs usually and may take 8−12
weeks.
•• Some patients are left with permanent devastating neurological deficits like
blindness, hemiplegia or a chronic vegetative state.
150
CHAPTER Giant Invasive
Pituitary Adenomas
INTRODUCTION
•• Pituitary adenomas are the most common intrasellar tumours and account
for 10% of all intracranial tumours.
•• Of these tumours, approximately 5−6% behave aggressively and grow to
gigantic sizes.
•• Tumours measuring less than 10 mm are termed microadenoma and those
measuring more than 10 mm are termed macroadenoma.
•• Pituitary tumours with size in excess of 40 mm, or those extending less than
6 mm from the foramen of Monro are referred to as giant pituitary adenomas.
•• These tumours although benign, occasionally pose difficulty in management
due to technical problems in surgical resection and invasion of surrounding
structures.
EXTENSION
•• Extension of pituitary adenoma can occur in various directions and results
in various signs and symptoms, depending on the structures compressed.
•• Wilson has classified suprasellar extension of pituitary tumours into:
Type A: Tumour occupying suprasellar cistern
Type B: Tumour obliterating the recess of the third ventricle
Type C: Tumour grossly displacing the third ventricle and having
parasellar extension
Type D: Tumour having intradural extension
Type E: Tumour extending into the cavernous sinus.
•• Fahlbusch has classified parasellar tumour extension into:
Type 1: Localised lateral
Type 2: Basal
Type 3: Massive lateral extension without invasion
Type 4a: Localised lateral invasion
Type 4b: Generalised lateral invasion
Type 5a: Supracavernous and subtemporal extension
Type 5b: Extrasellar extension with generalised invasion.
•• These tumours have reported to extend even into the posterior fossa.
INVASION
•• Although pituitary adenomas grow to a very large size, they usually maintain
a plane of cleavage from the surrounding tissues.
•• When the adenomas are seen infiltrating the dura, bone, blood vessel,
adventitia or nerve sheath, they are termed invasive adenomas.
1122
•• The evidence of invasion may be detected radiologically or seen peri-

operatively.
•• Endocrinologically functional tumours are more invasive than the non-
functioning adenomas.
•• Compared to non-invasive adenomas, invasive adenomas more often
appear cellular, demonstrate mitotic activity and exhibit some degree of
nuclear atypia.
MOLECULAR BIOLOGY
•• Loss of heterozygosity is associated with aggressive behaviour of the tumour.
•• Expression of the P53 gene in more than 15% of invasive tumours as
compared to non-invasive tumours.
•• Protein kinase C alpha-isoform was over expressed in invasive pituitary
adenomas.
•• Excessive expression of the proliferative marker MIB-1, which is an
antibody to cell cycle specific nuclear antigen Ki-67, is associated with
invasive adenomas.
•• Cytokine interleukin 6, heat shock protein-27, type IV collagenase and matrix
metalloproteinase-9 were also found to be increased in invasive adenomas.
•• An increased incidence of invasiveness was observed in those patients
with onset of symptoms during the pubertal years, compared to patients
whose symptoms first occurred during the post-pubertal years.
•• The majority of these patients present with visual symptoms, the
predominant visual symptom being bitemporal hemianopia.
•• Others like progressive or sudden visual loss in one or both the eyes are
also seen.
•• Sudden visual loss may be due to apoplexy.
•• Pituitary adenomas are softer than other tumours in this region and,
therefore, they present with cranial nerve paresis at later stages, resulting
in weakness of ocular movements.
•• In most giant pituitary adenomas, features of mass effect are more common
than endocrine disturbances.
•• Hyposecretion in the form of hypothyroidism and hypocortisolaemia is more
common than hypersecretion of prolactin.
•• The sellar floor may be eroded resulting in CSF rhinorrhoea.
INVESTIGATION
•• Plain skull radiographs have been proven to be insensitive and non-specific
for pituitary lesions.
•• On CT scans, pituitary adenomas appear as hypodense lesions. CT scan
provides better details about the bony erosion and calcification. The pituitary
gland and the adjacent soft tissues like the carotids and optic chiasma, are
not well visualised. Coronal views will be required.
•• MRI is now the imaging technique of choice.
•• MRI shows the relation of the gland to the surrounding structures like the
cavernous sinus, floor of the third ventricle and optic pathways with more
clarity and has the advantage of multiplanar imaging.
•• The tumours that are soft and easily aspirated at surgery, mostly appear
hyperintense on T2W and those tumours that are firm appear isointense.
Chapter 150 • Giant Invasive Pituitary Adenomas
1123
Fig. 1: Intercarotid lines which are drawn from intracavernous to supracavernous

portions of the internal carotid artery. (A) Medial intercarotid line: Along the
medial walls. (B) Median intercarotid line: Along the median walls. (C) Lateral
intercarotid line: Along the lateral walls
•• Features suggesting aggressive behaviour in imaging:

–– Extensive invasion of the cavernous sinus
–– Extensive suprasellar and parasellar extension
–– Erosion of the skull base and invasion into the sphenoid sinus.
•• The most sensitive sign of cavernous sinus invasion is an asymmetry in
the signal intensity between the two sides.
•• Encasement of the cavernous carotid artery is a specific but insensitive
sign of cavernous sinus invasion.
•• Knosp-Steiner classification of cavernous sinus invasion based on MRI
(Fig. 1):
Grade 0: When the adenoma does not cross the medial intercarotid line.
Grade 1: When the tumour passes the medial intercarotid line but does not
cross the median intercarotid line.
Grade 2: When the tumour passes the median intercarotid line but does
not cross the lateral intercarotid line.
Grade 3: When the adenoma passes the lateral intercarotid line.
Grade 4: When the ICA is totally encased by the tumour.
•• The most useful sign to predict cavernous sinus invasion is encasement
of the internal carotid artery greater than 30%.
TREATMENT
•• The clinical course and surgical outcome in patients with giant pituitary
adenomas have generally been reported to be poor.
•• Treatment of giant invasive adenomas by the conventional transsphenoid
approach, followed by adjuvant therapy, leads to a relatively high recurrence
rate.
•• Radical surgery by a trans-sphenoidal route in grade I–III pituitary tumours
and biopsy of the tumour, followed by radiotherapy in grade IV tumours.
•• Except for fibrous and dumb-bell-shaped adenomas, the trans-sphenoidal
approach is a safe and effective way to remove large pituitary adenomas.
•• It allows rapid and adequate decompression of the optic nerves and chiasm,
avoids major pituitary insufficiency and is associated with low morbidity-
mortality rates.
•• Simultaneous trans-sphenoidal and pterional approach for resection of
giant pituitary tumours with dumb-bell shape, where the surgeon cannot
achieve complete resection by a single approach.
1124
•• Combined treatment with initial surgical debulking followed by radiotherapy

yields tumour control rates in giant pituitary adenomas similar to those of
smaller pituitary adenomas without undue morbidity.
•• In patients with cavernous sinus invasion, the extended transnasal trans-
sphenoidal approach and contralateral subfrontal approach have been
described.
•• In giant prolactinomas, medical management is considered to be the first
choice. Many of these tumours respond to drugs.
•• Decrease in the serum prolactin level can be noticed within hours of starting
the medication.
•• Surgical intervention is indicated only if there is progressive visual loss or
if the tumour is resistant to medical therapy.
•• In young patients with significant parasellar extension, transcranial surgery
with radical excision is to be aimed.
•• Patients with GH and ACTH secreting tumours have a significant morbidity.
Long-term tumour control is rarely achieved by medical management.
•• With modern skull base techniques, most of these tumours have become
surgically accessible and direct radiotherapy is to be avoided.
•• Although non-functional pituitary adenomas have a relatively benign
course, radical excision is to be aimed at in younger patients with a long-
life expectancy.
•• A partial or a subtotal resection can lead to infarction and oedema of the
residual tumour, termed as post-operative pituitary apoplexy.
•• Other complications are worsened visual status, pituitary and hypothalamic
dysfunction, cerebral ischaemic attacks, coma and mortality.
•• High surgical mortality has been attributed to the breach of subarachnoid
spaces, and ischaemia within the hypothalamus, brainstem or cerebral
hemisphere caused by small and large vessel traction.
RADIATION
•• Radiotherapy is given to all the patients with grade IV tumour.
•• In grade III with significant post-surgical residue, radiotherapy is given in
spite of the patients being asymptomatic, while only symptomatic patients
with grade II tumours received radiotherapy.
•• In grade I cases, radiotherapy was generally avoided and re-exploration
of the tumour was preferred in patients with large or symptomatic residual
or recurrent tumours.
•• Combined modality treatment with initial surgical debulking followed by
radiotherapy in the dose range of 4500−5000 cGy over 25 fractions yields
adequate tumour control rates, although normalisation of the secretory
function is seen in a much less number of patients.
•• Conventional radiotherapy is not as effective as expected.
•• The increased side-effects of radiotherapy in patients with supra-parasellar
extension, especially to the optic pathway and hypothalamus, limit its benefits.
•• Clinical and neuroradiological signs of radiogenic encephalopathy are
encountered.
•• Complications of radiotherapy like hypopituitarism, have seriously affected
the quality of life in these patients.
•• Late onset of worsening in endocrine function, seen in a significant number
of patients, is attributed to delayed onset of radiation effect.
151
CHAPTER
Perioperative Endocrine
Management of
Pituitary Adenomas
Murthy S
PRE-OPERATIVE ASSESSMENT
•• Evaluation should include a complete blood count to assess the presence
of anaemia or other haematologic abnormalities.
•• A metabolic panel to evaluate possible hyponatraemia, hypercalcaemia,
hyperglycaemia and other metabolic abnormalities is also indicated.
•• Patients with hypercalcaemia are evaluated for the possible diagnosis of
multiple endocrine neoplasia, type I.
•• The endocrine evaluation of each patient should include a thyroid panel
(T3, T4, TSH), serum levels of cortisol, adrenocorticotropic hormone,
growth hormone, IGF1, insulin-like growth factor-1, testosterone, luteinizing
hormone, follicle-stimulating hormone and prolactin.
•• The frequency of deficiency among the anterior pituitary hormones at the
time of diagnosis of a pituitary tumour presents a spectrum of prevalence
with GH > LH > FSH > TSH > ACTH and PRL.
Pituitary-thyroid Axis
•• Secondary hypothyroidism is strongly suggested by low levels of free T4 in
association with low, normal or minimally elevated levels of TSH.
Pituitary-adrenal Axis
•• Under normal circumstances, ACTH secretion shows a marked circadian
rhythm with highest levels in the early morning and lowest at around
midnight.
•• Measurement of the target hormone cortisol is common to all tests of the
HPA axis and cortisol has the advantage of being a more stable hormone
in serum/plasma than ACTH.
•• Exogenously administered hydrocortisone or prednisolone interferes with
the measurement of endogenous cortisol secretion.
•• Dexamethasone administration will render cortisol measurements un
interpretable, both during treatment and for several days after steroid
withdrawal depending on the dose and duration of therapy.
•• Total cortisol levels are significantly raised in patients taking oral oestrogens.
•• Ideally, basal cortisol should be measured between 8.00 AM and 9.00
AM since HPA axis activity is maximal at this time. Random cortisol
measurements, for example, during afternoon clinics are much less useful
and often difficult to interpret.
•• If the basal morning cortisol is lower than 3.5 µg/dL, it strongly suggests
ACTH deficiency and glucocorticoid replacement should be commenced.
1126
•• If basal cortisol is higher than 15 µg/dL, adrenal insufficiency is very unlikely.

An intermediate value requires interpretation based on the clinical setting.
•• Stimulation tests, like insulin tolerance test or ACTH stimulation test, are
rarely required to assess the pituitary-adrenal axis.
Serum Prolactin
•• It is important to exclude pregnancy, PRL-elevating drugs, primary
hypothyroidism and polycystic ovarian syndrome in all patients with
hyperprolactinaemia.
•• In hyperprolactinaemic patients with a pituitary mass lesion, the main
challenge is to distinguish between tumoural secretion of PRL and pituitary
stalk interruption.
•• The basal PRL is of considerable diagnostic value.
•• A value greater than 200 ng/mL is usually diagnostic of macroprolactinoma.
•• A serum PRL level lower than 80 ng/mL in a patient with a pituitary
macrolesion usually indicates pituitary stalk interruption rather than tumoural
secretion.
•• An intermediate PRL level of 80−200 ng/mL is usually diagnostic of a
microprolactinoma.
Growth Hormone—IGF-1 Axis

•• Basal GH levels and serum IGF-1 levels are assayed.
•• Rarely, stimulation or suppression tests are done when there is growth
hormone deficiency or excess.
Pituitary-gonadal Axis
•• Basal measurements of gonadotrophins (LH and FSH) and sex steroids
(oestradiol and testosterone) will assess the hypothalamo-pituitary-gonadal
axis.
Vasopressin
•• Central diabetes insipidus is rarely a presenting feature in patients with
pituitary adenomas, even if the tumour is very large.
•• However, diabetes insipidus occurs commonly in patients with
craniopharyngioma or other hypothalamic pathologies.
•• The diagnosis can usually be established by measuring serum sodium
(more than 145 mEq/L) and osmolality (more than 300 mOsm/kg), together
with urine output (often more than 3L/day) and urinary osmolality (less
than 300 mOsm/kg).
•• Vasopressin deficiency may be masked by adrenal insufficiency.
•• After glucocorticoid replacement, central diabetes insipidus may get
unmasked.
Pre-operative Management
•• Glucocorticoid therapy before and during trans-sphenoidal pituitary surgery
has been the conventional treatment in the past. The rationale for this
practice has been the assumption that ACTH secretion is compromised
by the trauma of surgery.
•• Current data and available literature indicates that patients with normal
pre-operative adrenal functions do not require glucocorticoid therapy before
or during pituitary microsurgery.
Chapter 151 • Perioperative Endocrine Management of Pituitary Adenomas
1127
•• The recommendation is that glucocorticoid therapy is not administered

before or during selective pituitary surgery.
•• The argument in favour of this hypothesis is that exogenous steroid
administration inhibits endogenous ADH release and precipitates diabetes
insipidus.
•• Serum cortisol levels are measured twice daily during the immediate post-
operative period. Those with levels above 15 µg/dL do not require therapy.
If serum cortisol is below 5 µg/dL therapy is started.
•• For those with documented pre-operative glucocorticoid therapy, oral
hydrocortisone 30 mg daily in three divided doses is started at the time of
diagnosis. It is switched to injection hydrocortisone 50 mg IM twice daily the
day before surgery and hydrocortisone 100 mg as an IV drip administered
during surgery.
•• Most patients with macroadenomas do not manifest signs and symptoms
of hypopituitarism until after treatment with surgery/irradiation.
•• Deficiency of other pituitary hormones except TSH need not be addressed
in the peri-operative period.
•• If hypothyroidism is detected, thyroxine replacement (50−200 µg/day) is
started immediately. It takes 3 weeks for the patient to become euthyroid.
•• Unless the hypothyroidism is severe, surgery need not be delayed in those
requiring immediate surgery. In this situation, the management team should
be aware of the potential impact on anaesthesia, as well as fluid and pain
management.
•• Dosages of all medications, particularly narcotics need to be decreased in
hypothyroid patients because of lower metabolic rate.
•• Blood pressure, blood sugar levels, serum electrolytes, and fluid intake and
output should closely be monitored in the post-operative period.
EARLY POST-OPERATIVE EVALUATION/

MANAGEMENT (1–2 WEEKS)
General Principles of Pituitary Function Assessment
•• Monitoring of anterior pituitary function is crucial to the peri-operative care
of patients who undergo surgery for pituitary tumours.
•• Pre-operative hypopituitarism should always be treated in the early post-
operative period as this rarely resolves immediately after surgery. In
addition, the suspicion of new hypopituitarism should be heightened in
patients with partial hypopituitarism pre-operatively.
•• When the surgical procedure is more extensive, haemorrhage or necrosis
within the tumour are seen or other complications occur at the time of
surgery, concern for new hypopituitarism should be heightened.
•• In particular, the likelihood of post-operative adrenal insufficiency is
increased fourfold in patients who develop post-operative diabetes
insipidus, which may be a consequence of more extensive surgery.
•• Non-pituitary lesions, such as craniopharyngiomas, are more likely to be
accompanied by hypopituitarism or diabetes insipidus.
Diabetes Insipidus
•• The most common pattern is a transient abnormality which affects most
cases.
•• It consists of abrupt onset of polyuria within 24 hours of surgery, with
resolution in 1−3 days.
1128
•• It may be secondary to the release of bio-inactive arginine vasopressin

(AVP) precursors, local oedema of ADH producing neurons with a
temporary functional impairment or a disruption of the inferior hypophyseal
artery that supplies the ADH transport and storage structures.
•• Proximal damage to the pituitary stalk or hypothalamus can cause a
second variant of DI. After previously formed ADH is used up in 1−3 days,
permanent DI ensues, with a minimal or only partial decrease in urine
volume over several days.
•• The partial improvement sometimes seen is likely caused by resolution
of oedema.
•• The third pattern of post-operative DI is triphasic in nature.
•• The first phase is marked by the abrupt onset of DI within 24 hours of
surgery, which then lasts 1−3 days and is thought to be caused by neuronal
shock and diminished or absent hormone release.
•• An interphase then follows, during which AVP escapes from degenerating
neurons. Urine output comes down and urine osmolality rises, making the
patient vulnerable to hyponatraemia if intravenous fluid administration is
not tapered.
•• This interphase may last 1−14 days and is followed by a return of DI, which
is often permanent owing to the loss of magnocellular neurons by retograde
axonal degeneration. Polyuria in mild DI is usually 4−6 L/24 hours and in
severe DI up to 18 L/day.
•• A urine flow of 150−200 mL/h maintained for several hours is highly likely
to result from DI, although in any situation in which urine output exceeds
fluid intake an abnormal cause of polyuria should be suspected.
•• Polyuria of DI is associated with abnormally high serum osmolality (more
than 200 mOsm/kg), an elevated serum Na level (more than 145 mEq/L)
an inappropriately dilute urine (less than 300 mOsm/L).
•• In a clinical setting measuring urine specific gravity, serum Na and blood
glucose could differentiate causes of polyuria.
•• Patients who are not very sick and who can take oral fluids should be
allowed to regulate their own intake and water balance.
•• Patients with DI prefer ice-cold fluids as this elicits a strong oropharyngeal
reflex, compared to warm fluids promptly suppressing ADH release. If not,
5% GDW could be given intravenously.
•• As soon as possible intravenous fluids should be stopped and glucocorticoid
dosage tapered.
•• By the second or third post-operative day, the polyuria and polydipsia have
usually attenuated to several litres a day and do not require any treatment.
•• Only when adequate fluid intake cannot be maintained because of lethargy
or an impaired thirst mechanism is specific drug therapy instituted in the
early post-operative period.
•• The preferred agent is DDAVP orally 0.5 mg once or twice daily increased
up to 0.4 mg every eighth hourly.
•• If oral medications cannot be taken, DDAVP 2−4 mg (0.5−1 mL) intravenous
or subcutaneous or aqueous vasopressin (20 U/mL) in a dose of 0.1−0.3
mL every 4−6 hours could be used.
•• In case of severe water loss and hypernatraemia, intravenous fluids in
addition could be administered.
•• Short acting preparations are preferred since DI may be transient and
recovery occurs early.
1129
•• Permanent DI is unusual with microadenoma surgery but may occur in

patients with macroadenomas.
•• Patients with unrecognised coexistent adrenal insufficiency may not
develop symptoms of DI, as glucocorticoid deficiency is a stimulus for
release of ADH. The polyuria of DI may follow when steroids are withdrawn.
Hyponatraemia
•• Post-operative hyponatraemia is a relatively common disorder.
•• The presenting signs and symptoms are nausea, lethargy, confusion and
headaches.
•• It can be seen in patients irrespective whether they are hypovolaemic,
euvolaemic or hypervolaemic.
•• The causes are SIADH, hypothyroidism, hypocortisolism and hypergly-
caemia.
•• SIADH is rare and occurs in 1% of patients who have undergone pituitary
surgery and usually presents 1−2 weeks after surgery.
•• The clinical features, pathophysiology, diagnostic features and treatment
modalities are listed in Table 1.
Pituitary Adrenal Insufficiency

•• For those on pre-operative hydrocortisone therapy, injection. hydrocortisone
50 mg x 8 hourly is administered on the first post-operative day, followed
by 25 mg x 8 hourly for 2 days, and 25 mg x 12 hourly for 2 days, followed
by oral hydrocortisone 30 mg/day in three divided doses (physiological
replacement).
•• Since oral hydrocortisone is expensive and not easily available, the
alternate would be oral prednisolone 5 mg in the morning and 2.5 mg in
the evening.
•• In patients with macroadenomas where hypopituitarism is not permanent
and bound to recover pituitary functions, it is recommended that
glucocorticoid is withdrawn abruptly after 3−4 days after surgery.
•• Serum cortisol is measured 24 hours after withdrawal.
•• If serum cortisol at 8.00 AM is 15 µg/dL or more, it indicates recovery of
the HPA axis and further steroid therapy is not required.
•• If serum cortisol at 8.00 AM is less than 5 µg/dL recovery of the HPA axis
has not occurred and glucocorticoid therapy has to be restarted.
•• Patients with intermediate values are monitored carefully until a determina-
tion is made, whether there has been recovery of pituitary function.
•• If surgical adenomectomy is complete, signs and symptoms of
glucocorticoid deficiency develop within 24−48 hours and are associated
with 8.00 AM serum cortisol levels below 5 µg/dL. These patients are
started on glucocorticoid therapy; injection. hydrocortisone 50 mg × 6
hourly tapered down and later switched over to oral hydrocortisone 30−50
mg in three divided doses.
Functioning Tumours
•• Follow-up management of patients with Cushing’s disease is directed
towards tapering and discontinuing glucocorticoid replacement.
•• Patients who do not have evidence of early cure are obviously not treated
with steroids.
Table 1: Differential diagnosis of hyponatraemic state in the post-operative pituitary patients
1130
Disorder Clinical features Hydration Pathophysiology Diagnostic features Treatment

SIADH Asymptomatic to neurological Normal Increased ADH release Hyponatraemia Acute
symptoms Serum Na < 130 mEq/L Fluid restriction if Na+ = 120
Urine Na > 40 mEq/L mEq/L or more if Na+ <120 mEq/L
Serum Osm < 275 3% NaCl + Diuretics
Urine Osm > 100
Chronic
Demeclocycline 600−1200 mg/day
Hypothyroidism Bradycardia, slow mentation, Normal Impaired water excretion Low T4 Thyroid hormone replacement
coarse voice Low or normal TSH
Hypocortisolism Weight loss, malaise, nausea/ Dehydrated Impaired water excretion Hypoglycaemia Steroid replacement
emesis, hypotension Low serum cortisol
Hyperglycaemia diabetes mellitus Polyuria, polydipsia Normal or Dilutional (Pseudohyponatraemia) Hyperglycaemia Lowering blood sugar
Cushing’s acromegaly dehydrated
1131
•• Tapering protocols vary greatly and depend largely on an individual patient’s

symptoms.
•• For patients taking hydrocortisone, a reasonable approach would be to
decrease the dose by 5 mg/d every week and to obtain a fasting serum
cortisol level 24 hours after the last dose.
•• A serum cortisol value less than 3 µg/dL would indicate a persistent defect
in corticotrophin secretion and resumption of glucocorticoid therapy would
be indicated, followed by repeating the tapering and testing process again
after an interval.
•• Most patients do not require post-operative steroid replacement after
approximately 3 or 4 months and, indeed, the longer the requirement for
glucocorticoid therapy, the greater is the likelihood of cure.
•• A fasting serum cortisol level of greater than 20 µg/dL after cessation
of steroid therapy would raise the concern of early recurrence; in such
circumstances, obtaining a 24-hour urine collection for free cortisol would
be indicated.
•• One should be cautious about tapering of steroid dosage, as due to chronic
suppression of the HPA axis, acute adrenal insufficiency or crisis could
be precipitated.
•• In GH secreting tumours/prolactinomas or other functioning tumours, GH,
prolactin, FSH, LH, oestradiol or testosterone need not be measured in the
early post-operative period, as early intervention is not required.
LATE POST-OPERATIVE EVALUATION/MANAGEMENT

(AFTER ONE MONTH)
•• Hormone deficiencies associated with pituitary adenomas are often
reversible with surgical resection of the adenoma.
•• Similarly, the surgical procedure/radiotherapy itself can, at times, result in
partial or complete loss of pituitary hormone function.
•• It is important to document hormone deficiency before long-term
replacement therapy is established.
•• From a practical standpoint, pituitary function can be assessed easily
through outpatient services and dynamic testing can often be avoided.
•• A practical and clinically valuable approach commonly used in evaluating
pituitary function is the determination of serum levels of pituitary hormones
as well as hormones secreted by peripheral glands such as the thyroid,
adrenal and gonadal steroids.
•• In some patients, especially those with mild adrenal insufficiency, dynamic
testing may be necessary to accurately define pituitary function.
Pituitary-adrenal Axis
•• Patients with persistent or acquired glucocorticoid deficiency in the
immediate post-operative period are more likely to maintain similar function
months after surgery.
•• If there is a doubt about the integrity of the pituitary-adrenal axis and if the
patient is on oral steroids (hydrocortisone or prednisolone), it is stopped
for 48 hours and serum cortisol measured.
•• If basal cortisol at 8.00 AM is below 3 µg/dL, the diagnosis of adrenal
insufficiency is confirmed; if above 20 µg/dL, it indicates normal function.
•• Intermediate values may require further evaluation. In a situation like this,
dynamic testing with ACTH would be useful.
1132
•• During periods of stress the dose should be appropriately increased.

•• The usual replacement dose should be doubled or tripled during fever,
infection, invasive diagnostic procedures, minor surgeries (cataract,
laparoscopic, dental) and radiotherapy.
•• For those with severe infections and major surgeries, parenteral steroids
and IV fluids will be required.
•• Once they get over the stress period, it could be changed to the
physiological replacement dosage.
•• For patients who have undergone pituitary surgery for Cushing’s disease,
it would take 6–18 months for recovery of the HPA axis and steroid cover
over this period is required.
CHRONIC DI/SIADH
•• Persistence of DI beyond the immediate post-operative period presages a
poor long-term outlook for recovery.
•• It is unusual to see permanent DI in a patient following trans-sphenoidal
pituitary surgery.
•• The treatment of choice for chronic DI is DDAVP, either an intranasal
preparation (100 mcg/0.1 mL/spray) starting with 0.05−0.1 mL once or twice
a day or oral tablet (0.1 mg) 0.1–0.4 mg in divided doses twice or thrice daily.
•• Chronic SIADH is managed with fluid restrictions and demeclocycline
600–1200 mg/day in divided doses (Table 2).
Pituitary-Thyroid Axis
•• Central hypothyroidism is associated with low T4 and low or normal TSH,
and requires lifelong replacement therapy (100–200 µg/day).
Pituitary-Gonadal/Prolactin Axis
•• Serum FSH, LH assay, prolactin and testosterone/oestradiol are useful
guides to treatment.
•• The most sensitive tests of fertility are the sperm count in the male and
menstrual cycles with evidence of ovulation in the female.
Table 2: Syndrome of inappropriate secretion of

antidiuretic hormone versus diabetes insipidus
SIADH DI
Presentation Hyponatraemia Polyuria
Plasma osmolality Hypotonic (< 275 mOsm/L) Hypertonic (> 310 mOsm/L)
Serum sodium Hyponatraemia (< 135 mEq/L) Hyponatraemia (> 145 mEq/L)
Urine volume Low Polyuria (4−18 L/d)
Urine osmolality Relatively high (> 100 mOsm/L) Relatively low (< 200 mOsm/L)
Urinary sodium > 20 mEq/L > 20 mEq/L
Treatment Fluid restriction DDAVP

If Na < 120 mEq/L, consider 3%
hypertonic saline
Demeclocyline 600−1200 mg/day
1133
•• The concentrations of gonadotrophins (luteinizing hormone, follicle-

stimulating hormone) are frequently in the normal range in pituitary
hypogonadism.
•• It may be necessary to enquire specifically about sex drive, because many
patients hesitate to complain about decreased libido, believing that this is
an effect of their illness for which there is no treatment.
•• Elevated serum prolactin levels also result in decreased libido.
•• Hyperprolactinaemia results from disruption of the pituitary stalk.
•• For males who have low testosterone and elevated prolactin levels,
testosterone replacement alone will not restore normal libido; it is also
necessary to lower the serum prolactin level, for example, by using a
dopamine agonist like bromocriptine/cabergoline.
•• Chronic replacement therapy consists of 200−300 mg testosterone
propionate intramuscularly every 2−4 weeks in men and cyclical hormonal
therapy (oestrogen + progesterone) in pre-menopausal women.
•• Successful treatment of infertility, using sequential combinations of human
menopausal gonadotrophin (hMG) and human chorionic gonadotrophin
(hCG) in patients who have undergone hypophysectomy is now well
established, so that hypophyseal deficiency need not preclude the
possibility of parenthood.
Pituitary-Growth Hormone Axis

•• Most patients with growth hormone secreting pituitary microadenoma are
cured by trans-sphenoidal surgery and those with larger tumours have
partial cure.
•• They may require additional stereotactic radiosurgery.
•• Serum GH and IGF1 should be assessed one month after surgery and
repeated every 6−12 months.
•• Criteria for cure are normal serum IGF1 level and growth hormone levels
less than 0.4 ng/mL 1 hour after oral administration of 100 gm glucose.
•• Children with growth hormone deficiency confirmed by dynamic studies
will benefit from growth hormone therapy.
CONCLUSION
•• Patients undergoing pituitary surgery are a heterogeneous group and
management requires a multidisciplinary team approach, involving
neurosurgery, anaesthesiology and endocrinology.
•• Protocols for evaluation and monitoring have to be individualised by the
centre taking into consideration practicality, financial implications and
patient compliance.
152
CHAPTER
Empty Sella Syndrome
Ravi Ramamurthi  Murali Mohan S
•• An empty sella is defined as a sella, which, regardless of its size, is

completely or partially filled with cerebrospinal fluid (CSF).
•• The pituitary gland is compressed and lies posteriorly and inferiorly in the
sella.
•• The term empty sella is, in fact, a misnomer as the sella is not completely
empty, but the pituitary is always present both anatomically and functionally,
although often it is displaced downwards and compressed by CSF pressure.
•• Empty sella syndrome can be primary or secondary.
•• Primary empty sella (PES) syndrome is that which occurs in the absence
of pituitary surgery or irradiation for pituitary disease and secondary empty
sella is that which occurs following these procedures.
•• Although the sella is empty in both these conditions, they form two distinct
entities with differing aetiology, symptomatology and prognosis.
PATHOGENESIS
•• The diaphragma sella forms the roof of the pituitary fossa.
•• It has a central opening which transmits the infundibulum.
•• The diaphragm separates the cranial subarachnoid space from the pituitary
fossa.
•• Defects in the diaphragm may lead to herniation of the arachnoid into the
sella and accumulation of CSF.
•• These defects are more common in women than men, in a ratio of 5:1.
•• Busch classified the diaphragma sella into the following categories, which
were later referred to by Kaufman.
Type 1-A: The diaphragma sellae forms a complete seal.
Type 1-B: A slight tunnel-shaped depression is present in the intact
diaphragma sellae.
Type 2-A: An opening about 3 mm or smaller in the diaphragma sellae
exists around the hypophyseal stalk.
Type 2-B: A slight funnel-shaped indentation towards the middle of the
diaphragma sellae is present.
Type 3-A: The diaphragma sellae is composed of a 2 mm or smaller
peripheral veil, leaving the pituitary gland freely exposed and covered with
arachnoid.
Type 3-B: The diaphragma sellae is as described for Type 3-A but the
pituitary gland is indented, often eccentrically.
Type 3-C: The deficient diaphragma sellae is as described in Type 3-A;
however, indentation of the pituitary gland is marked.
Chapter 152 • Empty Sella Syndrome
1135
•• An incomplete sellar diaphragm is an essential prerequisite for the

development of the empty sella. All other factors are only predisposing to
the development of intrasellar subarachnoid herniation, whether by causing
increased pressure in the suprasellar subarachnoid space or by reduction
in the size of the pituitary gland.
Congenital Factors
•• Deficiency of the diaphragma sellae.
Suprasellar Factors
•• When the diaphragma sellae is incomplete, CSF pulsations act directly on
the upper aspect of the pituitary gland.
•• In addition, a posteriorly placed optic chiasma may also expose the upper
surface of the pituitary gland and thereby increase the CSF pressure on it.
•• The suprasellar cistern pressure is accentuated when the intracranial
pressure is raised, secondary to hydrocephalus, brain tumours , Arnold-
Chiari malformation, periorbital venous vasculitis, superior sagittal sinus
thrombosis with a dural arteriovenous malformation, etc.
•• Impaired CSF circulation was demonstrated in more than 80% of patients
by Brismar and Bergstrand, who also pointed out the similarity between
empty sella syndrome and normal pressure hydrocephalus, in their
symptomatology.
Intrasellar Factors
•• Any reduction in size of the pituitary gland favours intrasellar extension
of the suprasellar subarachnoid space. Such reductions may be due to:
•• Physiological involution:
–– This often occurs in women. Pregnancies bring about a large variation
in the size of the pituitary gland and after delivery there is an involution.
–– Similarly, after menopause there is a reduction in the pituitary volume.
–– Replacement of the deficient hormone results in feedback suppression
of the pituitary tropic hormone secretion and involution of the hyper-
plastic pituitary gland, resulting in an ‘empty sella’.
•• Pathological involution:
–– Shrinkage of the pituitary gland may occur after post-partum pituitary
necrosis (Sheehan’s syndrome) or pituitary infarction in patients with
vascular diseases, diabetes, increased intracranial pressure, head
injury, meningitis or cavernous sinus thrombosis.
•• Pituitary apoplexy:
–– Pituitary adenomas undergoing spontaneous necrosis (ischaemia or
haemorrhage).
–– The arachnoid descends into the sella, to occupy the space created by
resolution of the tumour.
•• Rupture of an intrasellar or parasellar cyst:
–– Fluid-filled cysts of the sellar region are well known and may cause
visual or endocrine symptoms, as well as changes in the contour of
the sella.
–– Rupture of such a cyst allows intrasellar extension of the subarachnoid
space.
1136
Systemic Factors
•• Hypertension: PES may be associated with systemic hypertension, which
may cause an intermittent rise in intracranial pressure.
•• Obesity: It is proposed that morbid obesity may induce hypercapnia, which
can be the cause of chronic CSF pressure elevation and in turn may lead,
in subjects with hypoplastic diaphragma sellae, to the intrasellar herniation
of the suprasellar subarachnoid space.
PRIMARY EMPTY SELLA

•• On routine MR screening of patients without any pituitary disease or
symptoms of empty sella, a significant number had been found to have
empty sella.
•• The incidence of empty sella increases with age.
•• It has been suggested that an empty sella found on routine MR scanning
is usually of no clinical significance.
•• PES may be seen anatomically and radiologically without producing any
symptoms or signs.
•• Large defects in the diaphragm without herniation of the arachnoid have
also been seen.
•• Raised ICP is an important factor in the pathogenesis of PES syndrome.
•• Empty sella is commonly symptomatic in middle aged obese women and
resembles the occurrence of benign intracranial hypertension (BIH) in this
respect.
•• An empty sella has been found in 10−12% of patients with BIH.
•• The causal relationship between ESS and BIH can be explained by two
mechanisms.
–– Raised intracranial pressure could produce a herniation of the sub-
arachnoid cistern into the sella turcica if the diaphragma sellae is
incomplete.
–– Alternatively, infarction in a pituitary adenoma could result in both an
ESS and a CSF flow obstruction, which could lead to BIH.
•• In summary, the factors that lead to PES syndrome are insufficiency or
absence of the diaphragma sella, increased CSF pressure due to various
causes and pituitary involution.
Symptoms and Signs

•• These may be divided into systemic, neurological and endocrine.
•• A majority of patients who exhibit symptoms form a fairly homogeneous
group.
•• About 80% are females in the fourth and the fifth decades of life with
predominant obesity.
•• About 30% have systemic hypertension.
•• The most common neurological symptom is headache, which occurs in
50−70% of these patents. The pulsations of the CSF against the dura have
been thought to be the cause of the headache.
•• Visual disturbances may occur and visual field defects that are seen are
bitemporal and binasal haemianopia. The defects are due to the descent
of the optic chiasm into the sella producing traction on the optic apparatus.
•• Decreased visual acuity and papilloedema may be seen when there is
raised ICP.
1137
•• Memory disturbances, imbalance, dizziness, convulsions and CSF

rhinorrhoea are the other neurological manifestations that may occur.
•• CSF pulsations inside the sella cause bony erosions in the sellar floor and
lead to dural deficiencies and CSF leak into the sphenoid sinus, leading
to rhinorrhoea.
•• Endocrine symptoms are not common, most common being deficiency
of growth hormone and reduced response of GH to insulin-induced
hypoglycaemia.
•• The pituitary stalk gets kinked against the diaphragm, as it descends into
the sella, giving rise to pituitary stalk effect.
•• Hyperprolactinaemia is not as high as in a prolactin secreting adenoma,
unless the partially empty sella is associated with a prolactinoma. The
prolactin level is usually below 100−125 ng/mL.
•• Hypopituitarism may occur and this is most likely due to compression of
the infundibulum as it descends into the sella and not due to flattening and
compression of the pituitary gland.
•• Precocious puberty has been reported in a young girl with empty sella.
•• Hypogonadotrophic hypogonadism has been seen in association with
empty sella.
Radiology
•• Radiographs of the skull show an enlarged sella and this may lead to a
diagnosis of empty sella.
•• There may be uniform remodelling of the sella which assumes a globular
shape.
•• The globular shape occurs early and further enlargement follows that
pattern.
•• The lamina dura is intact.
•• There is thinning of the dorsum sellae and slight bowing posteriorly.
•• Displacement of the dorsum sellae does not occur.
•• The floor of the sella is concave in the AP projection.
•• Double contour of the floor and erosion, which are characteristic of
intrasellar tumours, may be seen in PES.
•• Before the advent of CT and MR, pneumoencephalography was the
procedure of choice. It demonstrated entry of air into the intrasellar space
in the sitting or brow-up position.
•• On the CT, low density similar to that of CSF is seen in the sella. It may be
difficult to differentiate an empty sella from other conditions due to artefact.
•• CECT and thin high resolution coronal sections make identification of the
infundibulum easier.
•• The “infundibulum sign” differentiates empty sella from other similar CSF
density lesions like a cystic tumour.
•• The infundibulum will be seen to traverse a low density space and end in
the posteroinferior aspect of the sella.
•• Water soluble contrast or air cisternography may be used when MR is
not available.
•• In the differential diagnosis, one should bear in mind cystic intrasellar
tumours, intrasellar cyst and dilated intrasellar third ventricular recess.
•• MR will clearly delineate the infundibulum and the flattened pituitary gland.
•• The normally high signal seen in the posterior lobe may be absent due to
compression.
1138
•• Herniation of the optic nerves and chiasm can be seen very clearly and
the degree of descent assessed. This is especially important in secondary
empty sella when a differentiation has to be made between empty sella,
recurrence of tumour or radiation necrosis, when there is delayed visual
impairment.
SECONDARY EMPTY SELLA

•• Secondary empty sella occurs after surgical and/or radiation therapy of a
pituitary tumour.
•• The arachnoid descends into the sella through a congenitally deficient
diaphragm or due to destruction of the diaphragm by tumour.
•• Secondary empty sella occurs when the tumour shrinks and leaves an
empty space.
•• The predominant clinical finding in these patients is visual abnormality,
occurring due to arachnoidal adhesions and traction on the optic apparatus.
•• They may have initial improvement in visual symptoms with surgery,
followed by recurrence of symptoms due to the development of empty sella.
•• The presenting symptom will usually be visual deterioration, which may
occur even years after the initial treatment.
•• Bitemporal and binasal haemianopia are common, but other defects, like
peripheral field constriction, central scotoma or segmental defects, can occur.
•• These have to be differentiated from the visual defects that arise due to
recurrence of pituitary tumours, arachnoidal adhesions around the optic
nerve and chiasm and radiation necrosis.
•• Endocrine symptoms due to hypersecretion or hyposecretion are more
common in secondary empty sella than in the primary variety.
•• CSF rhinorrhoea can occur due to shrinkage of the tumour.
Treatment
•• Empty sella syndrome is usually a benign condition.
•• The majority of cases do not require treatment, except symptomatic, for
headache.
•• Hypertension must be treated and weight reduction advised in obese
patients.
•• Endocrine tests should be done and appropriate replacement given, if
there is hyposecretion of any of the hormones including gonadotrophins.
•• Hyperprolactinaemia is easily controlled with bromocriptine and smaller
doses are required, when compared to doses used in the treatment of
prolactinomas.
•• CSF rhinorrhoea requires prompt surgical treatment, as the fistula rarely
closes spontaneously.
•• When associated with hydrocephalus or BIH, an initial CSF diversion
procedure, like ventriculoperitoneal or lumboperitoneal shunt should be
done and, if the leak persists, definitive surgery must be undertaken.
•• When the fistula is from the sella into the sphenoid sinus, the trans-
sphenoidal route is ideal.
•• While operating inside the sella, care should be taken to avoid injury to the
infundibulum, especially while exploring for a possible recurrence of tumour.
•• The infundibulum descends into the sella bringing with it the median
eminence and, therefore, damage to the infundibulum can occur close to
the median eminence, producing permanent diabetes insipidus.
1139
•• When visual symptoms are present, especially in secondary empty sella,

the cause should clearly be identified.
•• On MR, if there is a clear demonstration of descent of the optic apparatus
into the sella and there is kinking of the optic nerves or chiasm, chiasmapexy
is indicated.
•• This involves elevation of the optic apparatus and is ideally done through
the trans-sphenoidal route.
•• The dura should be elevated and the space between the dura and the bone
packed with autologous tissues such as muscle, fat, fascia, bone and car-
tilage. Fat and muscle may get absorbed over the long-term after surgery.
Cartilage is more suitable due to the rigidity and resistance to absorption.
•• Synthetic materials, such as silicone balloons and tubings, have been used
with good success.
153
CHAPTER
Diencephalic Syndrome
Anil Pande  Murali Mohan S
DIENCEPHALON
•• The brain develops from the expanded cephalic part of the neural tube
(encephalon) and the caudal part (myelon) forms the spinal cord.
•• Two constrictions first appear in the encephalon, dividing it into three
primary vesicles:
1. The forebrain (prosencephalon)
2. The midbrain (mesencephalon) and
3. The hindbrain (rhombencephalon).
•• At approximately 2 months of gestational age, these three primary vesicles
differentiate into five cerebral vesicles.
•• The prosencephalon divides into two vesicles—the telencephalon (the end
brain) and the diencephalon (the inter-brain).
•• The mesencephalon does not divide.
•• The rhombencephalon divides to form two vesicles—the metencephalon
and the myelencephalon.
•• The telencephalon further differentiates and separates to form two
telencephalic vesicles, which eventually become the cerebral hemispheres
and encircle the underlying diencephalon, making the latter, the central
region of the vertebrate brain.
•• The lateral walls of the diencephalon later differentiate to form the
thalamus on either side, the ventral floor forms the hypothalamus and the
dorsal wall gives origin to the pineal body (the epithalamus), but remains
undifferentiated for a considerable distance to form the lamina epithelialis.
•• The thalamus is separated from the hypothalamus by a prominent sulcus
called the hypothalamic sulcus.
•• The median telocoele and the cavity of the diencephalon transform to form
the third ventricle.
•• The diencephalon is thus the central region of the vertebrate brain, where
the thalamic nuclear complex, pretectum and anterior tegmental structures
are generated.
•• Table 1 represents the structures comprising the diencephalon. It comprises
of the synencephalon, dorsal and ventral thalamus.
•• The hypothalamus is the ventral part of the alar derived diencephalon.
•• The median telocoele and the cavity of the diencephalon form the third
ventricle.
•• The diencephalon is derived solely from the alar plate and a hypothalamic
sulcus divides the alar diencephalic area into a dorsal region of thalamus
and ventral hypothalamus.
Chapter 153 • Diencephalic Syndrome
1141
Table 1: Structures comprising the diencephalon

1. Derivatives of dorsal thalamus
a. Thalamus
b. Metathalamus—medial and lateral geniculate bodies
2. Derivatives of ventral thalamus
a. Zona incerta
b. Nucleus reticularis thalami
3. Derivatives of hypothalamus
a. Dorsal nuclear group—globus pallidus, subthalamic nucleus, interstitial nuclei of the infe-
rior thalamic peduncle and the entopeduncular nucleus
b. Ventral nuclear group—hypothalamus
c. Evaginations—neurohypophysis and the optic stalk derivatives
4. Derivatives of epithalamus
a. Habenular nuclei and the commissure, stria medularis and taenia tectae
b. Evagination—pineal body
DIENCEPHALIC SYNDROME
•• Russel’s diencephalic cachexia (always) indicates the involvement of the
hypothalamus by compression or invagination by lesions arising from the
floor of third ventricle or adjacent area.
•• There is a uniform loss of body fat with normal linear growth, pallor,
hyperkinesis, hypertension, hypoglycaemia, hyperhydrosis, increase in
the size of hands and feet, precocious puberty, emesis, headache and
increasing head circumference due to hydrocephalus.
•• Ocular signs include nystagmoid rotary eye movements, optic atrophy
and visual loss.
Clinical Features
•• This syndrome is a disease of childhood, usually seen in children less than
2 years of age, with an age range of 14−26 months.
•• There is a slight male preponderance.
•• Failure to thrive and progressive emaciation with normal linear growth is
the characteristic clinical presentation of this syndrome.
•• Nystagmoid eye movements are described to be present in up to 60% of
these patients, and may be the first sign of a CNS cause for failure to thrive.
•• Other common presentations includes lid retraction, increased vigour,
euphoria , pallor, hydrocephalus with features of raised ICP, optic atrophy,
hyperhidrosis, precocious puberty and polydipsia.
Pathophysiology
•• The “failure to thrive” is seen in up to 25% of children with hypothalamic
lesions.
•• This is due to failure of inhibition of GH and LHRH secreting mechanisms
in the anterior hypothalamus.
•• The growth hormone levels are elevated with no diurnal rhythm and are
non-responsive to hyperglycaemic or hypoglycaemic changes.
•• The Somatomedin C and IGF levels are normal in these patients.
•• Lipolysis is attributed to elevated GH levels, acquired partial GH resistance,
low level of leptin and impaired metabolic regulation of adiposity.
•• This lipolysis causes the look of profound emaciation with complete loss
of subcutaneous fatty tissue.
1142
•• Leptin is an adipocyte hormone, deficiency of which causes severe obesity

in children. Loss of weight in these patients is believed to be due to the effect
of dysregulation of leptin secretion on transient hypothalamus-pituitary-
gonadal axis activation in the 1st year of life.
Pathology
•• Lesions causing diencephalic syndrome are mostly astrocytic tumours
(80%).
•• Less commonly ependymomas, craniopharyngiomas, germinomas,
suprasellar epidermoids, hamartomas and cysts may produce this
constellation of signs and symptoms.
•• Astrocytomas which manifest the diencephalic syndrome are larger, occur
at a younger age and have a more aggressive behaviour.
•• Juvenile pilocytic astrocytomas and the recently described chondroid
astrocytoma which is a glioma variant are unique to the hypothalamus and
anterior third ventricle.
•• Gross appearance of the tumour is usually soft, translucent and gelatinous;
rarely it maybe large, reddish, fleshy, firm and vascular.
•• The molecular biology of these paediatric astrocytic tumours is very different
from the tumours adults, with only 15% showing 17p mutation, and p53
mutation is very rare.
•• Many low grade tumours often demonstrate no genetic abnormality.
•• MIBI labelling index correlates positively with survival.
•• Histologically, these tumours have moderate cellularity with biphasic pattern
of compact pilocytic zones that stain for GFAP, which are centred round the
blood vessels and loosely arranged microcystic protoplasmic cellular areas
with associated open honeycomb background.
•• There are brightly eosinophillic rounded or elongated fusiform or sausage
like Rosenthal fibres, which are considered to be of degenerative origin.
MANAGEMENT
Imaging Studies
•• X-ray of the skull can show enlarged optic foramina in cases of optic nerve
gliomas, suprasellar calcification in craniopharyngiomas and features of
raised ICP in the form of erosion of dorsum sella, silver beaten appearance
and sutural diastases.
•• Cranial ultrasound, in children with an open fontanel, may reveal a third
ventricular lesion with or without hydrocephalus.
•• Juvenile pilocytic astocytoma occurs in the region of the diencephalon,
including the hypothalamus, visual pathway and the basal ganglia.
–– These are usually solid infiltrating masses but may have an associ-
ated cyst.
–– These are usually hypodense on plain CT and seldom enhance with
contrast.
–– MRI is the investigation of choice and can be supplemented by MR
spectroscopy, which is extremely useful for a non-invasive probable
histological diagnosis.
–– On MRI, these are hypointense to isointense on T1 images and mildly
hyperintense in T2 images with ill defined margins and irregular patchy
contrast enhancement, with or without associated hydrocephalus.
Chapter 153 • Diencephalic Syndrome
1143
•• Suprasellar germinomas are rare and only 20% of these lesions occur in
this area; most of them occur in the pineal region where these are isodense
to slightly hyperdense and enhance homogeneously with contrast.
–– On MRI they are hypointense or isointense on T1 and isointense to
hyperintense on T2 images, with homogeneous enhancement.
•• Craniopharyngiomas are seen as well circumscribed and multilobulated
tumours and 90% may have an associated cystic component.
–– Both cysts and calcification are common in children.
–– On MRI, the hyperintensity correlates with protein and methaemo-
globin components on T1 images.
–– T2 images will show a typically hyperintense lesion, with calcification
seen as signal void areas.
•• Ependymomas are heterogeneous lesions and may have associated
intratumoural cysts.
–– These tumours are usually contrast enhancing.
–– Fifty per cent of these lesions may have calcification, which can be
small and flecky or less commonly large and lumpy.
–– On MRI, they have heterogeneous intensity, with the cystic part being
slightly hyperintense to CSF.
–– The heterogeneous hyperintensity on T2 images is due to necrosis,
calcification, blood degradations and intratumoural cysts.
•• Hamartomas of the tuber cinereum are seen as isodense masses in the
suprasellar region, with no enhancement with contrast.
–– In MRI, they are isointense on T1 images and isointense to slightly
hyperintense on T2 images and are non-enhancing with contrast.
–– Hydrocephalus has been associated with these lesions with an inci-
dence of 55−58%.
–– Leptomeningeal spinal and cranial seeding has been reported in these
lesions and requires clinical suspicion and may warrant a screening of
the whole neuraxis.
Endocrine Assessment
•• A complete endocrine immunoassay profile is performed.
•• The T3, T4 and TSH are within normal range.
•• ACTH stimulation and metyrapone test are abnormal and point towards an
abnormal hypothalamic-hypophyseal-adrenal axis.
•• Somatomedin levels are usually low.
•• The growth hormone levels are usually elevated and are not influenced by
change in blood glucose levels. On administration of propranolol and L-dopa
there is an inappropriate fall in the levels of growth hormone.
•• Germinomas may present with diabetes insipidus and precocious puberty,
which can occur in the male child due to elevated levels of beta-hCG.
•• Female children do not present with precocity, as the beta-hCG requires
the priming effect of oestrogen on the ovary for its action.
Treatment
•• The treatment modalities include observation, biopsy using CT or MRI based
stereotaxy, surgery, radiotherapy and chemotherapy.
•• MR spectroscopy will perhaps play a large role in the histological
characterisation of these lesions non-invasively.
1144
•• Pre-operatively inadequate caloric and malabsorption problems have to

be excluded along with proper imaging and endocrine and electrolyte
evaluation.
•• Surgery for the lesions causing diencephalic syndrome is difficult due to a
varied spectrum of pathology, younger age group, large size of the tumour
at presentation, diffuse and infiltrating nature of these lesions, eloquence of
the area and lastly, the problem of finding a safe corridor to these lesions.
•• The extent of surgical resection is the only reliable prognostic factor, but
this has to be taken into consideration along with a much higher morbidity,
associated with aggressive surgery in diffuse and infiltrating lesions.
•• Surgical approaches are tailored according to the experience of the
surgeon, the clinical features and imaging.
•• Conventional frame based stereotactic surgery may be difficult in these
small children and frameless stereotaxy has a much larger role to play.
•• CSF diversion procedures like endoscopic third ventriculostomy or
ventriculoperitoneal shunt may be required for the management of
hydrocephalus.
•• Chemotherapy has now proved to be useful in these children and can delay,
if not replace, radiotherapy.
•• In very young children, the first option is a combination of actinomycin D
and vincristine.
•• Carboplatin along with vincristine and vincristine with lomustine and
prednisolone are other combinations, which have been tried and have
demonstrated significant disease control.
•• However, for ependymomas and germ cell tumours, chemotherapy has
a limited role.
•• Radiotherapy is beneficial in the treatment of residual and recurrent
tumours and even as a primary treatment for unresectable tumours of the
hypothalamus and optic pathway.
•• The use of radiation is limited, due to its adverse effect on the developing
brain.
•• Long-term complications of radiotherapy in children include CNS necrosis,
myelopathy, leucoencephalopathy, vascular injury, neuropsychological
defects, hormonal imbalance, bone and teeth abnormalities, ocular toxicity,
ototoxicity and secondary malignancies.
•• Recently, stereotactic radiosurgery has been advocated.
154
CHAPTER Other Tumours of the
Sellar Region
Sanjay Behari  Anooj Chatley  Abrar Ahad Wani  Manoj Jain
INTRODUCTION
•• The sellar region is a small but complex area with neural, vascular,
endocrine, osseous and meningeal structures.
•• Although pituitary adenomas, craniopharyngiomas, meningiomas
(tuberculum sellae, planum sphenoidale, diaphragma sellae, etc.),
gliomas (optic nerve, infundibulum, posterior lobe and hypothalamus) and
epidermoids/dermoids form the majority of tumours arising in the sellar and
juxtasellar region, there is an impressive list of other rare tumours which
may involve this area.
•• The differential diagnosis of the many tumours and tumour-like conditions
occurring in the sellar region is listed in Table 1.
PITUITARY CARCINOMA
•• It is a rare entity.
•• Pituitary carcinoma is defined as any tumour of adenohypophyseal
origin with demonstrated craniospinal and/or extracranial metastatic
dissemination.
•• Diagnosis is based on tumour behaviour, rather than histology as features
like nuclear atypia, mitotic activity, necrosis and haemorrhage, may also
be seen in pituitary adenomas.
Table 1: Differential diagnosis of sellar region masses

The most common tumours in this region—pituitary adenoma, craniopharyngioma, meningioma.
This chapter deals with uncommon lesions in the sellar region.
Tumours of adenohypophyseal origin
• Pituitary adenoma
• Pituitary carcinoma
Tumours of neurohypophyseal origin
• Granular cell tumours
• Neurohypophyseal gliomas
• Tumours of non-pituitary origin
• Craniopharyngiomas
• Gliomas
• Meningiomas
• Haemangiopericytomas
Contd…
1146
Contd…
• Germ cell tumours
• Chordomas
• Chondromas/Chondrosarcomas
• Haemangioblastomas
• Giant cell tumours of the bone
• Lipomas
• Fibrous dysplasia
• Sarcomas
• Gangliogliomas
• Ganglioneuromas
• Paragangliomas
• Schwannomas
• Glomangiomas
• Esthesioneuroblastomas
• Primary lymphomas
• Melanomas
Metastatic tumours
• Carcinomas
• Lymphomas
• Leukaemia
• Plasmacytomas
• Sarcomas
Cysts, hamartomas and malformations
• Rathke’s cleft cyst
• Arachnoid cyst
• Ependymal cysts
• Epidermoid cyst
• Dermoid cyst
• Gangliocytomas/Choristomas
• Hypothalamic hamartomas
• Empty sella syndrome
Tumour-like conditions
Inflammatory
• Infections/Abscesses
• Lymphocytic hypophysitis
• Mucocoeles
• Sarcoidosis
• Giant cell granuloma
• Histiocytosis X
Infiltrative
• Amyloidosis
• Haemochromatosis
• Mucopolysaccharidosis
Vascular lesions
• Internal carotid artery aneurysm
• Cavernous angiomas
Chapter 154 • Other Tumours of the Sellar Region
1147
•• Craniospinal metastasis occurs by dissemination via cerebrospinal fluid.

•• Extraneural metastases to bone, liver, lymph nodes, lungs, kidney and
heart have been seen.
•• The criteria that need to be fulfilled for classifying a lesion as pituitary
carcinoma are:
–– The primary tumour must be identified as a pituitary tumour at
histology.
–– An alternative primary tumour has to be excluded.
–– Discontinuous spread in the form of single or multiple, nodular
subarachnoid metastatic deposits, occasionally invasion of underlying
brain or overlying dura, may be seen.
–– Single or multiple systemic deposits broadly similar to and grossly
indistinguishable from metastases of carcinomas, arising in other
organs, may be seen.
–– The structural features or marker expressions of the metastases
should correspond or be similar to those of the pituitary tumour.
•• Less than 0.5% of all pituitary tumours turn out to be malignant.
•• They usually affect adults with a slight female preponderance.
•• They may be hormonally active or inactive.
•• Most common are the adrenocorticotropic hormone (ACTH) producing
tumours. Next in frequency is prolactin producing tumours.
Pathology
•• The mode of spread of these carcinomas is by means of local invasion and
through the venous system, the cerebral spinal fluid (CSF) pathways and
the lymphatics.
•• It is thought that venous spread occurs through the cavernous sinus initially.
From here, spread occurs to the internal jugular vein through the petrosal
system. It has also been postulated that retrograde spread through the
cortical draining veins may affect the superior sagittal sinus.
•• Spread occurs through the CSF pathway once the subarachnoid space
is invaded and may involve the supratentorial, infratentorial or spinal
compartment.
•• Although the pituitary gland lacks lymphatic drainage, spread through
lymphatics may occur once the tumour invades the skull base, which
provides access to a rich lymphatic network.
•• Systemic spread through the bloodstream may involve the lungs, liver,
bones, kidney and the heart.
•• Pituitary carcinomas that spread to the craniospinal axis are often non-
functional, while those that metastasise to extracranial sites are usually
functional.
•• Most of the tumours which spread systemically are ACTH producing
tumours.
•• Microscopically, pituitary carcinomas originate from and are composed of
adenohypophyseal cells.
•• The histological criteria for malignancy, like hypercellularity, nuclear
pleomorphism, mitotic figures, necrosis, haemorrhage and even invasion,
are not reliable indicators of the malignant nature of the tumour.
Clinical Features
•• The age of onset of symptoms is similar to that of patients harbouring
pituitary adenomas.
1148
•• The rate of progression of these symptoms depends upon the biological

behaviour of the tumour.
•• The initial course may be indistinguishable from that of a pituitary adenoma.
•• However, patients may have multiple recurrences and then disseminated
disease may eventually manifest.
•• Alternately, the clinical course may be fulminant with rapid deterioration
of vision, multiple cranial nerve palsy and evidence of metastatic disease.
•• In addition, features of endocrine hyperactivity may be present.
•• Tic like facial pain due to involvement of the Gasserian ganglion and early
onset of diabetes insipidus are poor prognostic indicators.
•• Features of central nervous system or systemic metastasis may be present,
depending upon the site of metastasis.
•• There are no characteristic radiological features which distinguish pituitary
carcinoma from a pituitary adenoma.
•• Scintigraphy with 111I-labelled octreotide has been used to establish the
diagnosis of a metastatic GH-secreting carcinoma and has revealed
additional lesions in an ACTH-secreting carcinoma and/or tumour
recurrences at follow-up.
•• More recently, positron emission tomography (PET) scan using 18F-labelled
deoxyglucose has revealed unsuspected pituitary macroadenomas and
also identified metastases from a pituitary carcinoma.
•• Other radiotracers, such as radiolabelled 5-hydroxytryptamine, are
considered to be more sensitive than 18F-labelled deoxyglucose and may
lead to the recognition of additional lesions.
Treatment
•• The treatment of pituitary carcinoma is similar to that of large and aggressive
pituitary tumours and includes surgery (usually via the trans-sphenoidal
route), external beam radiotherapy and adjuvant medical treatment.
•• The treatment of pituitary carcinomas is mainly palliative and may not
prolong survival to any major extent.
•• Medical treatment is directed against hypersecretory syndromes.
•• Dopamine agonists have successfully been used for the treatment of
prolactin-secreting tumours.
•• Tamoxifen has also been given to achieve a synergistic effect.
•• Dopamine agonists have been used in ACTH-secreting and TSH-secreting
carcinomas, but with only minimal benefit.
•• Somatostatin analogues such as octreotide, have been used to control the
hypersecretory syndrome in GH- and TSH-secreting pituitary carcinomas,
usually with a variable response.
Chemotherapy
•• 5-fluorouracil and methotrexate have been used.
•• However, there is limited experience in the use of chemotherapeutic agents
in the treatment of pituitary carcinoma.
•• Newer agents, like paclitaxel, are under investigation.
1149
GRANULAR CELL TUMOURS

•• The generally accepted hypothesis regarding their histogenesis suggests
that they are derived from supporting glial elements of the infundibulum
and posterior lobe of the pituitary.
•• They may be incidentally detected at autopsy in as many as 17% of cases,
usually as barely visible aggregates of tumorettes.
•• Symptomatic granular cell tumours occur as a result of enlargement of
these tiny tumorettes.
•• Symptomatic patients usually present in the fourth or fifth decade of life.
•• Women are affected almost twice as often as men.
•• They may present with diabetes mellitus, visual disturbance or other
symptoms of a sellar/suprasellar expanding mass lesion.
•• Despite the neurohypophyseal origin of these tumours, diabetes insipidus
may not always be present.
•• Histologically, these tumours consist of large polygonal or round cells with
eccentric nuclei.
•• There are abundant eosinophilic cytoplasmic granules that are PAS positive
and diastase resistant.
•• On immunohistochemistry, they may be positive for S-100, usually negative
for GFAP and uniformly negative for all anterior pituitary hormones.
•• Radiographically, they appear as small rounded masses which are generally
isointense on T1- and hyperintense on T2-weighted MR images.
•• They may be mistaken for a meningioma on radiological evaluation, as they
enhance intensely on contrast administration due to their high vascularity. How-
ever, they are primarily intrasellar and do not invade surrounding structures.
•• Calcification is generally not seen in these tumours.
•• As granular cell tumours are benign slow growing neoplasms, the prognosis
of patients with these tumours is generally favourable following total or
subtotal resection, although recurrences are known to occur.
•• Recurrences may be treated with reoperation or radiotherapy.
NEUROHYPOPHYSEAL GLIOMAS
•• These are rare tumours, generally pilocytic astrocytomas which arise
from the infundibulum or the posterior pituitary. They are also known as
infundibulomas or pituicytomas.
•• These tumours probably arise from the heterotopic glial tissue which may
be present in the subarachnoid space.
GERM CELL TUMOURS

•• Intracranial germinomas account for 0.3−3.5% of all intracranial tumours
and generally arise in the midline.
•• They are commonly located in the pineal region, although a minority of them
may be seen in the sellar/suprasellar region in isolation or in combination
with a pineal lesion.
•• Germ cell tumours are broadly classified into germinomas and non-
germinomatous germ cell tumours which include teratomas, embryonal cell
carcinomas, endodermal sinus tumours and choriocarcinomas.
•• Germinoma is the most commonly occurring germ cell tumour in the
suprasellar region and generally affects patients in the paediatric age group.
1150
Pathology
•• Suprasellar germinomas are generally infiltrative lesions, which may involve
the hypothalamus, pituitary stalk, third ventricular floor, posterior pituitary
and the optic chiasm, nerves or tracts.
•• In most cases, the tumour is located on the under surface of the hypo-
thalamus and is intimately related to the pituitary stalk and optic chiasm.
•• Intrasellar extension occurs in approximately 20%. Rarely, a pure intrasellar
lesion may be seen.
•• All germ cell tumours, except benign teratomas, are known to metastasise.
•• However, most instances of metastasis are within the neuraxis. Non-
germinomatous lesions are more likely to metastasise.
•• Macroscopically germinomas are generally soft, greyish, homogeneous
and at times, may resemble lymphomas on gross examination.
•• The cut surface is granular and usually solid.
•• Haemorrhage and necrosis is uncommon, the presence of which indicates
a high-grade tumour like embryonal cell carcinoma, endodermal sinus
tumour or a choriocarcinoma.
•• Teratomas have solid and cystic components.
•• Mature teratomas are grossly well defined and the cut surface has a
variegated appearance.
•• Derivatives of all three germ layers may be seen. Mucin, hair, bone,
cartilage and occasionally, teeth may be recognisable.
•• Microscopically germinomas are composed of large round to oval cells
with large nuclei and prominent nucleoli, arranged in islands or trabeculae
separated by fibrovascular stroma, containing bands of lymphocytes.
•• In 50%, syncytiotrophoblastic giant cells may be seen and in such cases,
human chorionic gonadotropin levels in CSF and/or serum are elevated.
•• Embryonal cell carcinomas are composed of cuboidal/columnar cells
arranged in varied patterns.
•• These lesions may have focal differentiation into extraembryonic or
embryonic structures leading to expression of alpha fetoprotein (AFP) or
human chorionic gonadotropin (HCG) in body fluids (serum/CSF/urine).
•• Endodermal sinus tumours are generally composed of cuboidal cells
with intracellular and extracellular globules, which contain AFP and
alpha-1 antitrypsin, respectively, which can be demonstrated on
immunohistochemistry.
•• Elevated levels of AFP may be found in serum, CSF or urine in these cases.
•• Choriocarcinomas are composed of large cytotrophoblastic cells surrounded
by syncytiotrophoblastic cells, which are multinucleated.
•• Human chorionic gonadotropin levels may be increased in CSF, serum or
urine and may be demonstrable by immunohistochemistry in tissue sections.
Clinical Features
•• Characteristically, these tumours appear in childhood and usually present
with diabetes insipidus and only later with features of hypopituitarism and
visual loss.
•• Hyperprolactinaemia is often present.
•• Suprasellar germinomas are typically midline lesions, which are centred at
or just behind the pituitary infundibulum.
1151
•• On MRI, they appear mildly hypointense on T1-weighted images and

hyperintense on T2-weighted images. They enhance brightly on post-
contrast images.
•• Other germ cell tumours may display more heterogeneity, due to more
diverse histological elements forming the tumours.
Treatment
•• Due to the anatomical location of these tumours and their infiltrative nature,
total surgical excision is generally not possible.
•• Germinomas are very radiosensitive.
•• It is necessary that the subarachnoid cisterns and ventricular system are
included in the radiation field to prevent recurrence from CSF spread.
•• Radiotherapy is not very effective in the treatment of other germ cell
tumours.
•• Chemotherapy with cisplatin combined with bleomycin and vinblastin is
used, in addition to radiotherapy, for disease control.
CHORDOMAS
•• Chordomas derived from notocordal remnants, are uncommon tumours of
the bone which may arise from any site along the axial skeleton.
•• The preferred location is the sacrococcygeal spine.
•• Intracranial chordomas constitute about 35% of all chordomas and 0.2%
of all intracranial tumours.
•• They are typically midline lesions originating in the region of the clivus.
•• They expand the clivus and may extend intracranially to compress adjacent
anatomical structures.
•• Extension may occur laterally into the cavernous sinus, anteriorly into the
sella and inferiorly into the nasopharyngeal region.
Pathology
•• Cranial base chordomas are slow growing, histologically benign lesions,
which cause expansile bone destruction at the site of origin and later
infiltrate the dura and extend intradurally to displace and compress intra
cranial structures.
•• They usually arise extradurally but may rarely extend intradurally as well.
•• Although they are histologically benign, due to their osteodestructive nature,
progressive course, tendency to recur and capacity to metastasise, they
are included among malignant neoplasms.
•• Metastatic dissemination occurs in 10−20% and is generally a late
occurrence.
•• Sites most commonly involved are liver, lungs, bone, heart and lymph
nodes.
Clinical Features
•• The clinical manifestations of these tumours depend upon the direction
of growth.
•• Lesions which are limited to the midline cause varying degrees of
hypopituitarism and chiasmal syndrome due to compression of the pituitary
and the optic chiasm, respectively.
•• Lateral extension leads to involvement of the cavernous sinus with proptosis
and multiple cranial nerve palsies.
1152
•• CT scan may reveal foci of sequestrated bone or irregular calcifications
amid the destroyed clival marrow.
•• On MRI, the lesion appears isointense to hyperintense on T1-weighted
images and heterogeneously hyperintense on T2-weighted images.
Variable post-contrast enhancement is seen.
•• Foci of calcification are seen as dark foci in the soft tissue component of
the tumour.
Treatment
•• The aim of treatment is to increase the likelihood of recurrence free survival.
•• Options include surgery alone or surgery/biopsy, followed by radiotherapy.
•• Radiotherapy may consist of conventional fractionated radiotherapy, proton
beam radiation, brachytherapy or radiosurgery.
METASTATIC TUMOURS TO THE

SELLAR REGION
•• A variety of systemic and haemopoietic malignancies may metastasise to
the sellar region.
•• In many cases, pituitary involvement may be subclinical and the patients
may succumb to their advanced systemic disease, before the pituitary
metastasis become manifest.
•• Most of the pituitary metastases involve the posterior pituitary. This is due
to the fact that the posterior pituitary has a direct arterial blood supply, as
compared to the portal circulation of the anterior pituitary.
•• Therefore, diabetes insipidus is the most common presenting feature in
these patients.
•• Amongst the systemic malignancies which metastasise to the sellar
region, the most common are lung, breast, prostate, stomach and bladder
carcinomas.
•• The general pattern of metastasis is that of osseous involvement of
the sella turcica with contiguous deposits in the pituitary, especially the
posterior lobe.
•• Hypothalamic involvement may occur by contiguous involvement from the
sellar region.
•• Patients with metastatic systemic malignancies to the sellar region most
commonly present with diabetes insipidus.
•• Suprasellar metastasis may present with rapidly progressive visual loss
due to chiasmal compression.
•• Ophthalmoplegia may be seen due to involvement of the cavernous sinus
region.
•• Hypopituitarism occurs infrequently due to the remarkable functional
reserves of the pituitary.
•• Among the haemopoietic malignancies, leukaemias, lymphomas and
plasmacytomas may metastasise to the sellar region.
•• Most primary CNS lymphomas involve the brain parenchyma.
•• Sellar region lymphomas usually originate in the hypothalamus and infiltrate
the pituitary stalk and posterior pituitary. They may present with hypotha-
lamic dysfunction, chiasmal syndrome or secondary hypopituitarism.
1153
•• Secondary lymphomas involving the sellar region are generally non-

Hodgkin’s lymphomas.
•• The deposits of the lymphomatous lesion are generally periglandular,
limited to the pituitary capsule with infrequent involvement of the pituitary
substance.
•• Lymphocytic and myeloblastic leukaemias may also metastasise to the
sellar region with primarily a periglandular distribution.
•• Patients with secondary lymphomatous deposits or leukaemic deposits
in the periglandular region have diabetes insipidus as the most common
presentation.
•• Metastatic lesions in the sellar region usually appear homogeneous on
the CT scan and enhance intensely with contrast. They are isointense to
brain on T1-weighted MR images, moderately hyperintense on T2-weighted
images and enhance intensely.
•• Surgery is indicated either for diagnostic reasons or when decompression
is required to relieve mass effect.
•• Prognosis is poor in patients with metastatic disease and the average
survival is approximately 8−9 months.
•• Radiotherapy may be an option mainly for palliation.
RATHKE’S CLEFT CYST

•• These are epithelium-lined cysts derived from remnants of the Rathke’s
pouch.
•• Rathke’s pouch appears during the 4th week of gestation as a stomodeal
ectodermal evagination, which extends cranially to form the craniopharyn-
geal duct.
•• The proximal end of the duct obliterates by the 11th week of gestation,
while the cranial part comes in contact with the infundibulum.
•• The anterior wall of the pouch forms the anterior lobe of the pituitary and
the pars tuberalis, while the posterior wall forms the pars intermedia.
•• The residual lumen of the pouch involutes.
•• Cystic remnants of the pouch may persist mainly at the anterior and
posterior pituitary interface. These may be seen in up to 20% of autopsy
cases. Rarely, they may be large enough to cause symptoms.
•• There are secretory cells in the walls of the cyst and the cyst enlarges due
to accumulation of the secretions.
Pathology
•• On pathologic examination, the cysts vary in size from 2 to 40 mm.
•• The cystic capsule frequently is described as thin and transparent.
•• The cystic fluid commonly is thick or gelatinous but it also can be watery,
serous or similar in consistency to motor oil.
•• The cystic fluid most often is yellowish in colour.
•• At histological examination, the cysts typically are composed of vascularised
stroma of connective tissue and three types of epithelial cells: (1) ciliated;
(2) non-ciliated epithelial and (3) mucous secreting.
•• Non-ciliated cells appear as a single layer of flat cells or as stratified
columnar cells.
•• The presence of ciliated epithelial and mucous-secreting cells in a pituitary
gland is pathognomonic for Rathke’s cleft cyst.
1154
•• The patient’s age at presentation ranges 4−73 years (mean age, 38 years).
•• The greatest frequency is in persons aged 50−60 years.
•• RCCs often produce no symptoms and so are usually discovered
incidentally, when radiographic or necropsy findings are reviewed.
•• Symptomatic RCCs are uncommon but cysts can enlarge and cause
symptoms secondary to compression of the pituitary gland, pituitary stalk,
optic chiasm or hypothalamus.
•• The most common presenting symptoms are pituitary dysfunction, visual
field defects and headache.
•• Endocrinal abnormalities include gonadotropin failure, which manifests
early.
•• Features of hyposecretion of growth hormone, hypothyroidism and
hypoadrenalism occur late.
•• Hyperprolactinaemia is common and diabetes insipidus may also occur,
although late.
•• Infrequently, hydrocephalus due to obstruction at the foramen of Monroe,
aseptic meningitis due to leakage of cyst contents into the subarachnoid
space and pituitary apoplexy from haemorrhage into the cyst may manifest.
•• RCCs frequently appear as well-circumscribed, hypodense sellar mass
that may have a suprasellar extension.
•• As a result of the different cystic contents, RCCs may appear isodense or
hyperdense relative to the brain parenchyma.
•• RCCs usually have a thin wall that may enhance.
•• Variability in CT scan contrast enhancement among individual cysts may
reflect squamous metaplasia in the wall or a peripherally displaced rim of
pituitary tissue.
•• Calcification characteristically is not seen on CT scans.
•• MRI appearances of RCCs are highly variable. It can be hypointense/
hyperintense on T1-weighted images and hyperintense on T2-weighted
images.
•• The cystic contents of the group resemble those of cerebrospinal fluid
(CSF).
•• In the second group are RCCs with hyperintensity on T1-weighted images
and variable signal intensity on T2-weighted images.
•• An increase in the signal on T1-weighted images has been related to the
high content of mucopolysaccharides, which is believed to result from an
increase in the number of mucin-secreting cells in the cyst wall, as well as
from an increase in the activity of these cells.
•• RCCs usually have a thin wall that may enhance with contrast. Variability
in the gadolinium enhancement, among individual cysts, may reflect
squamous metaplasia in the wall or a peripherally displaced rim of pituitary
tissue.
Treatment
•• The most common approach in the treatment is trans-sphenoidal surgery,
in which the cyst is partially excised and drained. This method is effective
and helps to preserve pituitary function.
1155
•• Radical excision can cause additional and unnecessary pituitary damage.

•• In trans-sphenoidal surgery, the cyst is opened, a biopsy specimen is
obtained from the wall and the cyst is drained into the sphenoid sinus.
•• Patients in whom this approach is not appropriate because of an
inaccessible cyst, craniotomy is performed.
•• The recurrence rate after craniotomy is twice as high as that after trans-
sphenoidal surgery.
•• In cases with recurrence, extensive removal of the cyst wall is most
appropriate to be followed by latter’s external beam pituitary radiation
therapy, although its role in preventing further recurrence remains unclear.
HAMARTOMAS, CHORISTOMAS AND

GANGLIOCYTOMAS OF THE SELLAR REGION
•• These are a group of histologically similar lesions, which consist of mature
neurons which are clustered within a stroma of axons and astroglial
elements.
•• Various terms, like hamartomas, choristomas and gangliocytomas, have
been used to describe these tumour-like lesions.
•• Such lesions arising in the hypothalamus are known as hypothalamic
hamartomas and those arising in the sella without attachment to the
hypothalamus are called choristomas.
Hypothalamic Hamartomas
•• Minute nodular hamartomatous foci of hypothalamic tissue are a common
incidental finding on autopsy. These hamartomatous nodules are clinically
insignificant.
•• However, they may be large enough to compress surrounding structures
and cause symptoms.
•• These lesions are commonly found in the region of the suprasellar cistern
or the interpeduncular cistern.
•• In most cases, they retain some anatomic continuity with the hypothalamus.
•• Others may have a wide attachment by a distinct stalk to the ventral surface
of the hypothalamus or may even lie embedded in the parenchyma of the
hypothalamus.
Pathology
•• Hamartomas usually resemble normal grey matter.
•• Microscopically, they contain neurons which are indistinguishable from
normal hypothalamic neurons and may contain secretory granules.
•• These secretory granules may contain luteinising hormone releasing factor
(LH-RF), beta-endorphin, corticotropin releasing factor or oxytocin.
•• Immunohistochemistry reveals positivity for hypothalamic hormones in the
neurons of these lesions.
Clinical Features
•• Hypothalamic hamartomas are rare tumours affecting young children below
the age of 3 years.
•• Characteristically, these children present with precocious puberty, which
may be as a result of either simple hypothalamic compression or due to
release of gonadotropin-releasing hormone (GnRH).
•• Patients may present with behavioural or intellectual disturbances.
1156
•• There may be a variety of autonomic disturbances including abnormalities

of thermoregulation, behavioural disorders, somnolence and hyperphagia.
•• Gelastic epilepsy and complex partial seizures are also known to occur
in these patients.
•• Hemiparesis or nystagmus may occur occasionally.
•• Occasionally, these children may present with cachexia.
•• Plain X-ray of the skull is often unremarkable. However, it may show erosion
of the dorsum sellae.
•• On CT scan, a hypothalamic hamartoma appears as an isodense, non-
enhancing suprasellar or interpeduncular cisternal mass.
•• On MRI, it appears isointense on both T1- and T2-weighted images with
attachment to the tuber cinereum or posteromedial hypothalamus by a
distinct stalk, giving it the so-called collar button shape.
•• The lesion may lie entirely within the substance of the hypothalamus and
may, therefore, be easily missed if small.
Treatment
•• Surgery is indicated in most symptomatic cases.
•• Radiotherapy is ineffective in the treatment of these lesions.
•• Total removal may not be possible, due to risk of hypothalamic injury in
cases where there is broad-based attachment to the hypothalamus or when
the tumour lies within the substance of the hypothalamus.
•• However, subtotal removal may result in regression of precocious puberty
in some cases.
•• Surgical treatment is useful to confirm the diagnosis and to regress or abolish
precocious sexual features and skeletal growth. It also results in better seizure
control and improvement in behavioural and intellectual disturbances.
•• Drugs such as medroxyprogesterone acetate and cyproterone acetate have
been used to inhibit gonadotropin production in patients with precocious
puberty.
Intrasellar Choristomas (Gangliocytomas)

•• These lesions are histologically similar to hypothalamic hamartomas.
•• However, they differ from hypothalamic hamartomas in that they are
primarily intrasellar lesions with no attachment to the hypothalamus.
•• They are generally associated with a functional pituitary adenoma.
•• Intrasellar choristomas are seen in association with a GH producing
pituitary adenoma.
•• It has been hypothesised that the development of pituitary adenoma may
be a secondary phenomenon, as these choristomas release hypothalamic
hormones, which may induce adenomatous transformation of adjacent
adenohypophyseal cells.
•• Corticotroph-releasing factor producing choristomas have also been found
in association with Cushing’s disease.
TUMOUR-LIKE CONDITIONS
Pituitary Abscess
•• Pituitary abscess may be the result of direct extension or haematogenous
spread of infection from sphenoid sinusitis, meningitis, cavernous sinus
thrombophlebitis or a contaminated cerebrospinal fluid (CSF) leakage.
1157
•• When pituitary abscess does not coexist with meningitis or an adjacent

sinus infection, it is difficult to determine the original site of infection.
•• Pituitary abscesses may also develop, although rarely, as a result of
generalised sepsis or haematogenous dissemination from a variety of
distant septic foci like pneumonia, osteomyelitis, endocarditis, etc.
•• They may complicate pre-existing lesions, usually adenomas,
craniopharyngiomas and Rathke’s cleft cyst.
•• Tumours are possibly vulnerable to infection because of impaired
circulation, areas of necrosis or local immunological impairment.
•• The incidence of intrasellar abscess is low after trans-sphenoidal pituitary
surgery. These abscesses may be due to intra-operative contamination or
due to CSF leakage (secondary abscesses).
•• When culture is positive, the most commonly identified pathogens are
Staphylococcus species, Streptococcus species, Neisseria species, E.
coli, Corynebacterium species and Diphtheroids.
•• Cases of mycotic abscesses have been reported due to aspergillus,
candida, coccidioidomycosis, histoplasmosis and blastomycosis.
•• In contrast to bacterial pituitary abscesses, most fungal infections occur
when some type of immunosuppression coexists in the patients.
•• Parasitic pituitary infection have also been reported, including cysticercosis
and echinococcosis.
•• Clinical features of pituitary abscesses resemble those of pituitary
adenomas.
•• Pituitary abscesses usually present either with endocrinologic disturbance
or with symptoms related to mass effect.
•• Headache is the most common presenting complaint.
•• Signs of meningitis may be associated in up to 90% of cases.
•• Fever is present in 50% of cases.
•• No pre-operative investigation is specific for the diagnosis of a pituitary
abscess.
•• A past history of meningitis, sepsis and sinusitis may suggest the diagnosis.
•• Rapid neurological deterioration in a patient with sellar tumour after a
presumed bacteraemia should point to the possibility of abscess formation.
•• CSF examination may be useful even when there are no signs of meningitis.
It may reveal increased cell count, elevated protein content or depressed
glucose concentration.
•• Standard X-rays of the skull, centred on the sella may show widening of the
sella turcica, erosion of the sellar floor and opacity of the sphenoid sinus.
•• CT scan shows presence of hypodensity in the pituitary gland with
enhancement of its outline by contrast injection.
•• Extension into filling the sphenoid sinus with destruction of the sellar floor
is also non-specific.
•• The differential diagnosis of rim enhancement would include cystic lesions
with or without superimposed infection.
•• Pituitary abscess appears hypointense on T1-weighted images and
hyperintense on T2-weighted images in MRI.
•• Two important signs may lead to a correct diagnosis.
–– The first includes disparity between the important sphenoid features
(effusion within the sinus, wide sellar floor destruction) and the rela-
tively small volume of the pituitary lesion.
1158
–– The second sign is the enhancement of the sellar lesion outline by both
CT and MRI contrast, with simultaneous extensions to the sphenoidal
sinus.
•• Pituitary abscess is usually treated by antibiotic and corticosteroid therapy,
followed by surgery.
•• The trans-sphenoidal approach is usually chosen for drainage of the
abscess so as to protect the cerebrospinal fluid from contamination and to
avoid post-operative infection.
LYMPHOCYTIC HYPOPHYSITIS
•• It is a rare destructive inflammatory disorder affecting the anterior pituitary
and is presumed to be of autoimmune origin.
•• It occurs almost exclusively in female patients and commonly affects them,
either during pregnancy or within the first year of parturition.
•• It may coexist with other autoimmune diseases including Hashimoto’s
thyroiditis, idiopathic adrenalitis, pernicious anaemia and parathyroiditis.
Pathology
•• Lymphocytic hypophysitis is thought to be an autoimmune disease which
may be precipitated following a viral infection.
•• Prior or concurrent lymphocytic meningitis/meningoencephalitis has been
considered to be an aetiological factor.
•• The pathological process starts as an acute inflammation and enlargement
of the gland.
•• In chronic cases, the gland becomes atrophic and fibrotic.
•• Microscopically, the normal glandular architecture of the anterior pituitary
is replaced by infiltration of lymphocytes, plasma cells, macrophages and
eosinophils.
•• Occasionally, lymphoid follicles and germinal centres may be seen.
•• Varying degree of diffuse interstitial fibrosis is present.
•• Patients may present with headache, vomiting, emotional disturbances or
visual field defects.
•• The hormonal disturbances which may occur include single hormonal
disturbance like hyperprolactinaemia, hypoadrenalism and hypothyroidism
or panhypopituitarism.
•• As the posterior pituitary is not involved, diabetes insipidus is rare.
•• Plain X-ray skull is usually normal but may demonstrate an enlarged sella
with occasional erosion of the dorsum sellae.
•• On CT scan, lymphocytic hypophysitis appears as an enhancing intrasellar
mass which may extend to the suprasellar region with enlargement of the
sella.
•• MRI is the investigation of choice and reveals a lesion in the sella which is
either hypointense or isointense on T1-weighted images and hyperintense
on T2-weighted images.
•• It enhances uniformly on contrast injection. The pattern of signal
enhancement after contrast may be helpful to differentiate this lesion from
a macroadenoma.
1159
•• A strong and homogeneous enhancement of the anterior pituitary, similar to

the cavernous sinus, is more suggestive of an inflammatory process such
as lymphocytic hypophysitis rather than a macroadenoma.
Treatment
•• The aim of surgery should be to reduce the pituitary mass and associated
compressive effects on surrounding structures, without introducing new
endocrinal or neurological deficits.
•• This is best achieved by the trans-sphenoidal approach.
•• Supraphysiological doses of glucocorticoids can be effective in the
treatment of lymphocytic hypophysitis. It helps both by reducing the mass
of the pituitary by its anti-inflammatory effect and as replacement for
defective adrenal function.
•• Other immunosuppressive drugs, such as azathioprine, methotrexate and
cyclosporine, have been used with some success in patients responding
poorly to corticosteroids.
MUCOCOELE
•• These are benign, cystic lesions arising in the paranasal sinuses.
•• Sphenoethmoidal mucocoeles are relatively rare lesions which may erode
the sellar floor to present as intrasellar, parasellar or suprasellar masses.
•• Mucocoeles are filled with mucus and their wall consists of psuedostratified
or low columnar epithelium, which contains goblet cells.
•• Isolated involvement of the sella is very rare.
•• Hypopituitarism rarely occurs.
•• More often, involvement of the sella may just be a small component of a
much wider intracranial extension involving the orbital apex and superior
orbital fissure, wherein oculomotor palsies and exophthalmos may be the
presenting features.
SARCOIDOSIS
•• Sarcoidosis is a multi-system inflammatory disorder which may involve the
nervous system in approximately 5% of cases.
•• Neurosarcoidosis is considered as a great imitator of intracranial lesions.
•• Intracranially, it generally involves the base of the brain with infiltrative
arachnoiditis, which causes entrapment of cranial nerves and may also
involve hypothalamic-pituitary structures.
•• Often it results in polyneuritis cranialis, manifesting as fluctuating or
recurring paralysis of cranial nerves, specially the facial.
•• Histological appearance of these lesions is characterised by non-caseating
granulomas consisting of lymphocytes, giant cells and macrophages.
•• Clinical manifestations are generally due to hypothalamic or infundibular
damage.
•• MRI demonstrates enhancement of the hypothalamus, thickening of the
infundibulum and meningeal enhancement, especially in the region of the
suprasellar cistern.
•• Neurosarcoidosis has no known cure.
•• Immunosuppression is the principal method of controlling the disease and
corticosteroids are the mainstay of therapy.
1160
•• Alternative medications, including azathioprine, cyclophosphamide,

cyclosporine, chloroquine and methotrexate have been used with variable
success.
•• Some patients demonstrate symptomatic benefits from low-dose radiation.
•• Surgical intervention is indicated in cases of hydrocephalus or when an
expanding mass lesion causes an increase in intracranial pressure.
HISTIOCYTOSIS X (LANGERHAN’S
CELL HISTIOCYTOSIS)
•• It is a systemic disease primarily affecting the reticuloendothelial system.
•• It may involve the central nervous system with a predilection for the
hypothalamus, infundibulum and posterior pituitary.
•• Involvement of the anterior pituitary is far less common.
•• It generally represents extension from an adjacent bony lesion.
•• Patients generally present with diabetes insipidus.
•• Growth hormone deficiency and hyperprolactinaemia may also be present.
•• Histologically, the lesions consist of infiltrates of histiocytes, eosinophils
and lymphocytes.
•• Characteristic Langerhan’s giant cells are present, which express S-100
protein and HLA-DR (CD-1) antigen.
•• Neuroimaging shows a thickened infundibulum which enhances on contrast
and the presence of hypothalamic granulomas.
•• Destructive osseous lesions may be seen in the calvarium.
CAVERNOUS ANGIOMA OF
CAVERNOUS SINUS
•• Cavernous angiomas of the cavernous sinus are rare lesions with an
incidence of 1−3% of all lesions of that area.
•• Their origin may be extracavernous with enlargement into the middle cranial
fossa or primary intracavernous with enlargement into the middle cranial fossa.
•• Growth in these lesions occurs by progressive ectasia of vascular channels,
capillary outgrowth from cavernous spaces into the interstitium, internal
microhaemorrhages causing thrombosis of contiguous blood vessels,
followed by organisation and sclerosis and cyst formation by rupture of
septae between adjacent sinusoids.
•• Subsequent rapid expansion of the cyst may be due to imbibing water
through osmosis.
•• These lesions occur between the second and the fifth decades of life with
the male:female ratio being 1.7:2.8.
•• The gradually expanding lesion may cause cavernous cranial nerves deficit
and sellar hypothalamic involvement may result in endocrinopathies.
•• Pregnancy, steroid administration or even physical exertion may cause
exacerbation of symptoms due to engorgement of the lesion.
•• Spontaneous haemorrhage is rarer in these extradural haemangiomas
compared to their intra-cerebral counterparts.
•• CT scan shows an isodense to hyperdense lesion with dense homogeneous
enhancement on contrast.
•• Bony erosion in the sellar region may be seen.
•• These lesions are angiographically occult due to the small size of the
nutrient vessels, as well as extensive thrombosis within the malformation
so that adequate concentration of the dye for clear definition of the lesion
is not provided.
1161
•• Thus, angiography may be negative or may show displacement of adjacent

normal vessels, a focal capillary blush or venous pooling. This apparent
avascularity is deceptive as the lesion bleeds profusely during surgery.
•• Occasionally, feeding arteries including the meningohypophyseal trunk,
artery of the inferior cavernous sinus, the middle meningeal artery and the
accessory meningeal artery have been identified.
•• MRI may show an isointense to mildly hyperintense lesion on the T1-
weighted image, markedly hyperintense on T2-weighted images, enhancing
brilliantly with contrast administration.
•• The intensity of enhancement may vary.
•• The lesion may have a reticulated core of mixed intensity with a surrounding
rim of decreased intensity on T2-weighted images caused by haemosiderin-
laden macrophages.
•• The lesion may contain foci of haemorrhages with resultant intensity
variations depending upon the age of haemorrhage.
•• Surgical excision may cause extensive haemorrhage.
•• The surgery is facilitated by proximal internal carotid artery control in the
neck or the petrous segment, preparation for extracranial-intracranial
bypass, incising the dura between the III, IV, V cranial nerves, early
devascularisation of the lesion by coagulating its blood supply, developing
a plane of cleavage between the pseudocapsule formed by the inner and
outer layers of the dura, and avoiding piecemeal dissection.
•• The VIth nerve and internal carotid artery, being intracavernous, have to
be skeletonised from the tumour.
•• Frontotemporal craniotomy with orbitozygomatic osteotomy with drilling
of medial sphenoidal wing and anterior clinoids, facilitates the exposure.
•• A course of pre-operative radiation has been recommended to help shrink
the lesion and reduce its vascularity.
MISCELLANEOUS TUMOURS
•• A few very rare tumours which may arise in the sellar-parasellar region
include:
Schwannomas
•• Schwannomas may arise from the cranial nerves of the cavernous sinus,
especially the trigeminal nerve and may secondarily involve the sellar
region.
•• The current histopathological hypothesis for the origin of these lesions include
perivascular or ectopic Schwann cells, lateral nerve plexus within the cav-
ernous sinus, as well as Schwann cells from small nerve twigs of the dura.
•• These tumours may mimic pituitary adenoma clinically, endocrinologically
and radiologically.
•• Intrasellar schwannomas presenting with hypopituitarism, hyperprolacti-
naemia and visual disturbance due to chiasmal compression have been
reported.
Giant Cell Tumours of the Sphenoid

•• These constitute 3−7% of primary bony neoplasms.
•• Involvement of the skull is rare and occurs in less than 1% of cases of giant
cell tumours and occurs in the sphenoid and temporal bones, reflecting the
genesis of these bones through endochondral calcification.
1162
•• CT scan showing an expansile lytic lesion in the body of sphenoid or

temporal bones, with marked contrast enhancement, is characteristic of
this lesion.
•• MRI reveals a low to moderate signal intensity on T1- and T2-weighted
images.
•• Haemorrhage within the tumour may produce high signal intensities on both
the sequences. A “soap bubble” image may be seen on the T2-weighted
image.
•• The histological features include oval, undifferentiated mononuclear cells
with evenly dispersed, large multinucleated giant cells, with closely packed
nuclei in them.
•• Giant cell tumours display aggressive local behaviour.
•• Soft tissue extension may compromise vital neurovascular structures.
•• Dural penetration, cerebral invasion and sarcomatous change may occur.
•• The ideal treatment is wide local excision with a good margin of healthy
tissue.
•• In case of local recurrence, local resection is safer than radiotherapy.
•• However, in many cases, radiotherapy following surgery has achieved
good local control without tumour recurrence or malignant transformation.
Paragangliomas
•• This tumour is very rare in the sellar area where there are no paraganglionic
cells.
•• The cellular origin of these tumours is thought to be from the paraganglionic
tissue rests which persist from early pituitary embryogenesis.
Lipomas
•• Lipomas may present as suprasellar masses.
•• They generally arise from the hypothalamus or tuber cinereum and extend
downwards.
•• Hypothalamic dysfunction and secondary hypopituitarism may occur in
these cases.
Primary Melanoma
•• Only a few cases of primary melanoma of the pituitary gland have been
reported.
•• They may arise from melanin containing cells of the posterior pituitary or
from the meninges overlying the diaphragma sellae.
Angiofibroma
•• It is a benign tumour that tends to bleed and occurs in the nasopharynx of
prepubertal and adolescent males.
•• The lesion occurs commonly in the second decade with the age ranging
7−19 years.
•• The tumour starts in the nasopharynx and pterygopalatine fossa.
•• The rare superior growth is directed towards the sphenoid sinus, cavernous
sinus and sella.
•• Occasionally, the greater wing of the sphenoid may be eroded, exposing
the middle fossa dura.
•• Proptosis and optic nerve atrophy result if the orbital fissures are
encroached upon by the tumour.
1163
•• Nasopharyngeal angiofibroma is usually encapsulated and composed of

vascular tissue and fibrous stroma, with coarse or fine collagen fibres.
•• Vessels are thin-walled, lack elastic fibres and have absent or incomplete
smooth muscle.
•• Stromal cells have plump nuclei and tend to radiate around the vessels.
•• There is an abundance of mast cells in the stroma and a lack of other
inflammatory cells.
•• Localised areas of myxomatous degeneration may be observed in the
stroma.
•• Pre-operative embolisation and radiotherapy may reduce the vascularity
and the size of the lesion.
•• Surgery usually aims at complete excision but exsanguinating haemorrhage
from the tumour may often be encountered during its surgical excision.
Esthesioneuroblastoma
•• This is a neuroblastoma arising from the olfactory epithelium invading the
skull base, cranial vault, orbit, sphenoid sinus and sellar area.
•• On histology, there is a lobulated structure with sheets of cells having poorly
defined cytoplasm and round to oval nuclei in a densely neurofibrillary
background.
•• Sometimes, olfactory rosettes or pseudorosettes may be present.
•• Surgery followed by radio and chemotherapy provides relief but local
recurrences and metastasis are frequent.
Fibrous Dysplasia
•• This consists of proliferative connective tissue, causing thickening of bones.
•• There are three forms:
1. Compact form is a dense thickening of bone, especially of the skull
base, resulting in ground glass appearance. It may cause stenosis
of the optic foramen, superior orbital fissure, shallow orbits with
proptosis, sellar and sphenoid involvement causing hypopituitarism
and expansion of the temporal bone and greater wing of the sphenoid.
2. Lytic form takes the shape of a radiolucent area limited by a thin scle-
rotic line.
3. Pseudo pagetoid form is characterised by a combination of both
sclerotic and radiolucent lesions. The lesion stabilises after the age of
25–30. There is a small risk of malignant transformation.
155
CHAPTER
Craniopharyngioma
SN Bhagwathi  Suresh Sankhla
INTRODUCTION
•• Craniopharyngiomas are the most common intracranial tumours of non-
glial origin in children.
•• These neoplasms arise from cell, rests from the remnants of Rathke’s
pouch and are histologically benign.
PATHOLOGY
•• Craniopharyngiomas are most frequent cystic tumours or have a large
cystic component, although sometimes they can be entirely solid or may
present as a solid rock of calcium.
•• These tumours are located mainly in the suprasellar region, as the site of
origin is usually along the infundibulum at the floor of the third ventricle.
•• As the tumour enlarges, it often extends into the sella inferiorly and elevates
the floor of the third ventricle superiorly.
•• The size of the tumour varies from a centimetre in diameter to large tumours
occupying the anterior and middle fossae.
•• Invasion of the sphenoid bone, nasopharynx, the orbit and the cavernous
sinus has also been reported.
•• Growth of the tumour superiorly into the third ventricle can cause blockage
of one or both foramina of Monro, leading to hydrocephalus.
•• The outer surface of the tumour is greyish pink in appearance. It is often
irregular and adherent to the surrounding structures.
•• A layer of arachnoid separates the tumour from almost all the structures,
except in the region of the tuber cinereum.
•• Calcification in the wall of the cyst is a common feature.
•• The cyst contains chocolate-coloured fluid with shimmering cholesterol
crystals (“machine oil” fluid). Occasionally, the cyst fluid may be lighter in
colour, mildly xanthochromic or even watery.
•• The cholesterol is derived from the epidermal layer lining the cyst.
•• Histochemical investigations reveal such a secretion in a microcyst and
electron microscopy has demonstrated zymogen granules in the epithelial
cells, suggesting a secretory function to these tumours.
•• The immunohistochemical distribution of the subunits of S100 proteins for
these tumours had shown them to be S100 alpha (+ve) and beta (–ve) (like
pituitary adenomas and pinealomas).
•• Histologically, these are epithelial tumours, the cyst being lined by simple
stratified squamous epithelium over a collagenous basement membrane.
The tumour enlarges by desquamation of epithelial debris, formation of cyst
Chapter 155 • Craniopharyngioma
1165
fluid and simple cellular proliferation. The growth of the tumour, therefore,
is generally slow.
•• The blood supply of a craniopharyngioma is the same as that of the dien-
cephalon, as it evolves from the embryological remnants of Rathke’s pouch.
•• Two branches arising on each side from the intracavernous portion of the
internal carotid or the inferior hypophyseal arteries supply the intrasellar
portion of the tumour.
•• The suprasellar portion receives its supply anteriorly from branches coming
off the anterior cerebral and the anterior communicating arteries and later-
ally on either side from branches of the posterior communicating arteries.
Other Epithelial Cysts in the Suprasellar Region

•• Other types of epithelial tumours may occur in the suprasellar region, name-
ly, epidermoid cysts, Rathke’s cleft cysts, arachnoid cysts and germinomas.
•• Epidermoid cysts develop in the region of the infundibulum or tuber
cinereum, from small nests of squamous epithelial cells which border on
the pars tuberalis. They contain keratohyaline material.
•• Rathke’s cleft, separating the anterior (pars distalis) from the posterior
(pars intermedia) part of the pituitary, is lined by cuboidal or columnar
epithelium, which may be ciliated and contains mucus secreting glands.
Cystic transformation of the cleft results in Rathke’s cleft cyst.
•• Arachnoid cysts may be congenital (or primary) or acquired. Congenital
or true cysts may be an outpouching of the membrane of Liliequist, while
acquired ones are usually the result of trauma, haemorrhage or inflamma-
tion. Anatomically, two groups can be identified: suprasellar (developing
above the diaphragma sellae) and intrasellar (within the sellar cavity).
•• Germinomas or ectopic pinealomas located in the infundibular region are
identical to the atypical teratomas of the pineal gland and are morpho-
logically similar to the germ cell tumours of gonadal origin, viz. testicular
seminoma. The suprasellar germinoma is usually situated beneath and
behind the optic chiasm, which it both displaces and infiltrates as it spreads
along the optic nerves and tracts to extend into the infundibulum and hypo-
thalamus. Precocious puberty, diabetes insipidus and other hypothalamic
manifestations are commonly seen and, like other intracranial germinomas,
they may sequestrate or spread to different sites.
INCIDENCE
•• Craniopharyngiomas are one of the most common intracranial tumours
of childhood.
•• A bimodal age distribution is seen for these tumours at presentation, with
the first peak between 5 years and 10 years and the second between 55
years and 60 years.
•• The symptoms and signs depend on the direction of the growth of
the tumour resulting in pressure on optic apparatus anterosuperiorly,
hypothalamus posterosuperiorly, pituitary gland inferiorly and brainstem
posteriorly.
CLINICAL FEATURES
•• The most common triad of presenting symptoms in a child with
craniopharyngioma is:
–– Visual failure due to compression of the optic nerves, chiasm or tracts.
1166
–– Hormonal disturbances, most frequently growth hormone (GH) or

antidiuretic hormone (ADH) deficiencies.
–– Raised intracranial pressure, usually a result of large tumour mass,
obstructive hydrocephalus, or both.
–– The symptoms of hypothalamic disturbances including obesity and
somnolence may be seen in large tumours.
•• Symptoms and signs of raised intracranial pressure predominate in children
and endocrinological deficits in adolescents.
•• Visual symptoms predominate in adults, while the elderly present with
mental disturbances.
Endocrine Manifestations
•• About one-third of the patients are stunted, although somatotrophic function
is found to be deficient in 90−100%.
•• The second most common manifestation is delayed sexual development.
•• Precocious puberty is extremely rare with craniopharyngiomas in contrast
to other suprasellar tumours like hamartomas and germinomas. This is
because craniopharyngiomas extend usually anterosuperiorly, unlike
the other lesions which commonly spread posterosuperiorly into the
hypothalamus.
•• In adults, gonadal failure leads to loss of libido and secondary amenorrhoea
can occur.
•• Obesity may be seen, but the emaciation syndrome common to hypotha-
lamic tumours is extremely rare.
•• Diabetes insipidus is a more common presenting feature of germinomas
and histiocytosis.
•• Hypothyroidism, hypocortisolaemia or panhypopituitarism are very rare.
•• Neurobehavioural disorders are uncommon in children, but are a fairly
common presenting feature in adults and the elderly. These are due to
either subfrontal extension of the tumour or to hydrocephalus and often
appear before other signs of raised intracranial pressure develop. They
usually comprise of intermittent confusion, hypersomnia, dementia, apathy,
severe depression and Korsakoff’s syndrome.
•• In very slow growing tumours, pressure on the cerebral peduncle may cause
hemiparesis or paraparesis; pressure posteriorly on the brainstem may re-
sult in a broad based gait and ataxia, simulating a midline cerebellar tumour.
IMAGING
•• Plain X-rays of the skull continue to be useful in the workup of a patient
suspected to harbour a craniopharyngioma. These are often diagnostic,
especially in children. The characteristic feature is the presence of
irregular, speckled calcification just above the sella turcica. Another type
of calcification, seen less frequently, is the semicircular shell outlining the
wall of a cystic lesion. Other sellar changes include a ballooned sella and
decalcified or eroded clinoids.
•• Computed tomography (CT) is probably the most useful investigation for
evaluating these calcareous tumours.
•• A typical craniopharyngioma would show a cyst with a partially calcified
contrast enhancing capsule.
•• Solid portions containing calcium and isodense areas with some enhance-
ment on contrast may be seen in solid tumours, but more commonly a
mixed picture containing solid and cystic areas of varying degrees is seen.
1167
•• Effacement of the suprasellar cistern is seen frequently and compression

of the third ventricle may be observed in larger suprasellar tumours.
•• Distortion of the interventricular foramina may result in unilateral or bilateral
lateral ventricular dilatation. This is more common in craniopharyngiomas
than in pituitary adenomas.
•• Density of the cysts on the CT scan may vary from that of water to that of the
brain, depending upon the content of cholesterol and other components within it.
•• A cyst containing high protein appears isodense to hyperdense, while
occasionally, keratin may have a lower density than water.
•• Rarely, there may be layering within the cyst, cholesterol lying superiorly
because of its low density. Calcification is seen more frequently in the CT
scan than in plain X-rays.
•• The cystic component in the tumour is more often seen in children than in
adults, as is the enhancement of the tumour on contrast CT.
•• Coronal CT helps in defining the superolateral relationship with the optic
pathways and the hypothalamus; sagittal reconstruction is useful in
confirming the retrochiasmal location of the tumour.
•• Pituitary adenomas, meningiomas, giant aneurysms, optic and hypothalamic
gliomas, arachnoid cysts, tuberculomas, and hamartomas occurring in the
suprasellar region can pose problems in differential diagnosis.
•• The characteristic features of craniopharyngiomas, tumour cyst, calcification
and enhancement on contrast administration are seen in over 75% of cases.
•• Magnetic resonance (MR) imaging of craniopharyngiomas requires both
T1- and T2-weighted images obtained in the sagittal, coronal and axial
planes to determine the extent of the lesion and its relationship to the
surrounding vital structures.
•• The sagittal and coronal images are sensitive for evaluating the chiasm
and its relationship with the tumour, and the signal characteristics depend
upon the contents.
•• The usual cystic lesions, with a predominantly cholesterol content, are
hyperintense on T1- and relatively hypointense on T2-weighted images.
•• The cystic lesions predominantly containing keratin are hypointense on
T2-weighted images, resembling water.
•• The solid lesions are isointense to hypointense on T1- and turn isointense
to hyperintense on T2-weighted images. Occasionally, the tumours are
very heterogeneous, showing a solid-cystic appearance or a fluid level of
cholesterol/keratin.
•• Calcium in the lesion may be visualised as areas of signal dropout.
Enhancement with Gd-DTPA is seen in the non-calcified solid portion of
the tumour.
•• Perifocal oedema along the optic pathways, causing a unique characteristic
‘moustache’ appearance, has been observed infrequently with certain
craniopharyngiomas.
•• Intraventricular craniopahryngiomas are not associated with tumoural
calcification or cyst formation and are isointense on T1, hyperintense in
T2 and enhance homogeneously with contrast.
•• Chiasmal thickening with pot belly expansion and a bilobed shape of an
intraventricular tumour on the MR have been described.
TREATMENT
Aims of Treatment
•• The treatment of craniopharyngioma should be aimed at reversing or
halting progression of symptoms and prevention of tumour recurrence,
1168
while leaving the child’s physical, visual, hormonal and intellectual state
at an acceptable functional level.
•• The modalities of treatment that may be employed are:
a. Surgery, which may include radical removal, partial removal or simple
drainage of the cyst. It may be a staged procedure, especially if total
excision is planned for a large tumour, to try and avoid hypothalamic
damage.
b. Radiotherapy, external beam fractionated radiation or stereotaxic
radiotherapy (SRT) for residual tumours or tumour recurrences.
Pre-operative Evaluation and Management

•• Complete endocrinological evaluation is done to establish a baseline and
to uncover hypopituitarism, especially with respect to growth hormone,
cortisol and thyroid hormones.
•• Corticosteroid replacement is done and diabetes insipidus treated with
DDAVP.
•• Even in the absence of specific complaints, diabetes insipidus should be
excluded by appropriate investigations.
•• As thyroid replacement takes several days to two weeks with oral L-thyroxin,
intravenous therapy may be given if the patient needs immediate surgery.
Surgical Management
Associated Hydrocephalus
•• Although hydrocephalus is often associated with craniopharyngiomas,
especially in children, the tumour can be tackled directly in most cases.
•• However, if there are signs of rapidly rising intracranial pressure, the patient
may require CSF diversion by a ventriculoperitoneal shunt.
•• This is also a useful procedure in children presenting in a moribund
condition or with gross metabolic disturbances, while preparing them for
major surgery.
•• External ventricular drainage can be used as a temporary measure in
moribund patients.
•• It is important to drain both the ventricles separately, in view of obstruction
of the foramina of Monro; this can be achieved by attaching a Y-connector to
the tubing to connect both the ventricles or by inserting two separate shunts.
•• Hydrocephalus is more common in retrochiasmal tumours than in the
prechiasmal variety.
•• Recurrent or residual tumour, aseptic meningitis or CSF rhinorrhoea may
necessitate a shunt insertion post-operatively.
Operative Approaches
•• The important factors that decide the route of approach to a craniophar-
yngioma are the location and extent of the tumour, the configuration of
the visual pathways, and the blood supply to the tumour and the optic
apparatus.
•• Enlargement of the sella and the type of sphenoid sinus are also important
if a trans-sphenoidal approach is being considered.
•• Four locations of craniopharyngiomas are recognised for surgical
management: sellar, prechiasmal; retrochiasmal and intraventricular.
•• The operative approaches for tumours at different locations are summarised
below:
1169
I. Subfrontal
a. Interoptic
b. Opticocarotid
c. Translamina terminalis
d. Combined
II. Pterional
a. Interoptic
b. Opticocarotid
c. Lateral carotid
d. Translamina terminalis
e. Combined
III. Trans-sphenoidal
a. Transnasal
b. Transcranial
IV. Transventricular
a. Transcortical
b. Transcallosal
V. Subtemporal
VI. Cyst aspiration
VII. Intracystic bleomycin
VIII. Combined approaches for giant tumours.
Radical Surgery versus Conservative Surgery and Radiation
•• The optimal treatment of childhood craniopharyngioma remains
controversial.
•• Most neurosurgeons advocate total excision of the tumour, both for its
curative role and in order to avoid the potential side effects of radiation.
•• However, total excision of certain craniopharyngiomas may be extremely
difficult and hazardous.
•• A craniopharyngioma that is small or prechiasmatic in location can be easily
excised completely with relative impunity.
•• When the tumour is large or multicompartmental or retrochiasmatic in
location, total excision is difficult.
•• The main difficulty in removing the tumour radically is due to its adherence
to the optic nerves, chiasm and tracts, pituitary stalk, hypothalamus and
vessels of the circle of Willis.
•• Aggressive surgery is usually associated with high mortality and
increased incidence of hypothalamic, endocrinologic, metabolic and visual
disturbances.
•• Hypothalamic damage and endocrinological disturbances are more
frequently associated with extensive surgery in the suprasellar area.
•• The incidence of hypothyroidism, hypocortisolemic and hypogonadism was
significantly higher in patients with total excision.
•• Most of these patients required endocrine support during surgery and
sustained replacement therapy for many years following surgery.
•• Surgical resection is often advocated to alleviate visual symptoms promptly.
•• Radiotherapy, as an adjuvant to surgery, has been proven to offer good
tumour growth control.
•• The outcome of contemporary management of craniopharyngiomas should
reflect the twin goal of tumour control and enhanced quality of survival.
1170
Radiotherapy
•• Although radiotherapy has proven to be beneficial in the management of
craniopharyngioma, complications from this form of treatment are also
well known.
•• The degree and extent of morbidity associated with radiotherapy was related
to the high dose of radiation (60−70 Gy) and lack of precise localisation of
the target.
•• Increasing attention is given to the effects of high dose radiation therapy
on brains of children.
•• Optic neuropathy and radionecrosis of brain have been noted.
•• One of the long-term hazards of radiation therapy is the induction of a
secondary tumour, following radiation therapy.
•• Tumours following irradiation of craniopharyngiomas, include brainstem
gliomas, supratentorial and infratentorial sarcomas and meningiomas.
•• Modern three dimensional conformal radiation treatment (3D CRT) using
CT and MRI leads to accurate localisation. The dose of radiation also does
not need to increase beyond 5400 Gy.
•• The stereotactic techniques permit precise delivery of highly focal ionising
radiation to the tumour.
•• Either a linear accelerator (LINAC) is used to deliver the radiation dose to
the target or intensity modulated radiation therapy (IMRT) in which conformal
radiation is given to a target, using multiple small beamlets varying radiation
intensity or SRT, (stereotaxically) directed multifractional radiotherapy may
be given.
Complications
•• The common disturbances are in visual functions and in functions of the
hypothalamus and the pituitary, resulting in endocrinological deficiencies
with need for hormonal replacement.
•• Diabetes insipidus or SIADH, psychosocial impairment resulting in mental
dullness, poor educability and poor intellectual performance also occur.
•• The incidence of immediate treatment-related complications is relatively
lower with other modes of treatment including intracavitary chemotherapy,
stereotactic brachytherapy, Linac therapy or radiosurgery (SRS) with
gamma knife or stereotaxic radiotherapy (SRT).
Other Treatment Modalities

•• In the management of craniopharyngioma, there are several goals: tumour
control, combined with preservation of endocrine, visual, and cognitive
functions.
•• The likelihood of achieving these goals is enhanced by a multimodality
approach in which staged excision of tumour, drainage of the cyst,
instillation of radioactive or chemotherapeutic agents into the cyst through
a reservoir or stereotactic radiosurgery (SRS) may be employed.
Cyst Aspiration
•• Stereotactic aspiration of a cystic craniopharyngioma or periodic
percutaneous aspiration of the cyst, using a reservoir/catheter system can
be carried out easily without any significant morbidity. This form of treatment
is simple and effective in certain cases of recurrent cystic tumours.
1171
Intracavitary Bleomycin Injection

•• A fair number of tumours are essentially cystic or have a large cystic
component. These are the lesions that can respond reasonably well to
intracystic instillation of bleomycin.
•• A catheter is placed in the cavity with an Omayya reservoir either
stereotactically or through an open craniotomy. If there is more than one
large cyst, a catheter is placed in each cyst.
•• A contrast cystogram is performed to make sure that there is no leakage
from the cyst. Thereafter 3−5 mg of bleomycin is instilled 2−3 times a week
through the Omayya reservoir.
•• A total of 40−50 mg may be injected.
Intracavitary Irradiation
•• Intracavitary irradiation should be considered as a primary management
strategy in patients with a solitary cystic craniopharyngioma.
•• Stereotactic intracavitary irradiation, using beta emitting colloids is an
effective alternative method to treat cystic craniopharyngiomas.
•• This mode of therapy is less invasive and is associated with low risks of
mortality and morbidity and a high rate of endocrinological, visual and
cognitive preservation.
•• A variety of isotopes for intracavitary radiation have been tried and eliminated
including rhenium, gold and bismuth.
•• Radioactive isotopes, such as 32P, 198Au and 90Y, have been used
successfully for intracavitary irradiation of large cystic craniopharyngiomas.
•• Significant cyst shrinkage occurs in up to 80% of cases with more than 50%
chance of endocrinological preservation and maintenance or improvement
of visual functions.
•• For those patients with multicystic lesions, intracavitary irradiation can be
performed for each cyst separately if they do not communicate.
•• SRS is a highly accurate and precise technique that utilises stereotactically
directed convergent beams of ionising radiation (proton beam or gamma-
knife) to treat a small and distinct volume of tissue with a single dose.
•• The minimum dose prescribed is 9−20 Gy.
•• The multiple beam approach of radiosurgery results in sharp dose fall-off
beyond the target, sparing adjacent normal tissue.
•• This method, however, should be reserved for selected small lesions since
it ablates normal and abnormal tissue within the treatment volume.
•• The parameters are related to the size and location of the target volume.
•• Certain intracranial lesions cannot safely or effectively be treated with SRS,
once the target volume is relatively large or located near the brainstem,
retina and optic pathways or cranial nerves.
Stereotactic Radiotherapy
•• Fractionation is necessary to provide highly focal and precise dose delivery
to larger lesions or lesions located within the vicinity of vital neurovascular
structures, without producing significant morbidity.
•• It includes the use of SRS techniques in combination with routine
fractionation (180−200 cGy/day) or some form of altered fractionation, such
as hyperfractionation (a few large fractions of 400−800 cGy).
1172
•• SRT combines the advantages of conventional fractionation used in

external beam irradiation with the accurate and focal distribution of radiation
as in SRS.
Childhood Craniopharyngiomas
•• In order to compare the two most commonly employed therapeutic
strategies for childhood craniopharyngiomas, one must look at four factors:
(1) recurrence rate; (2) salvageability of the recurrent tumour; (3) quality of
life, and (4) complications.
•• Based on this information, the following recommendations can be made:
–– Radical surgery:
¾¾ Children older than 5 years of age.
¾¾ Tumours less than 3 cm in size.
¾¾ Favourable location—intrasellar, prechiasmatic or pure intraven-
tricular.
–– Limited surgery plus irradiation:
¾¾ Large tumours greater than 3 cm in size.
¾¾ Multicompartmental tumours.
¾¾ Pre-operative hypothalamic disturbances.
1173
Ommaya Reservoir with Intracystic Instillation

•• Essentially cystic tumours
•• Bleomycin
•• Radioactive isotopes—90Y, 32P.
•• Smaller tumours less than 3 cm in size
•• Intrasellar tumours
•• Tumours away from optic pathways.
156
CHAPTER Dermoids and
Epidermoids
•• Tumours due to disordered embryogenesis are a heterogeneous group of

neoplasms of the nervous system of congenital origin.
•• They include dermoids, epidermoids, teratomas, chordomas and
craniopharyngiomas.
•• They are characterised by a slow rate of growth, the growth potential in
some of these being so slow that they are often considered as hamartomas.
•• Due to the slow rate of growth in some, the initial clinical manifestations
may not appear till adulthood.
EPIDERMOIDS
Pathogenesis
•• Congenital epidermoids are believed to arise as a result of cellular
dysfunction during embryogenesis, which leads to an abnormal migration
of ectodermal cells.
•• This epithelium lined ectopic tube may expand into a cyst, either at its inner
or outer end or both and form an epidermoid or a dermoid cyst.
•• Secondary vesicles, like otic and optic vesicles formed during development,
may also have epithelial misplacement, accounting for laterally placed
squamous lined cysts.
•• This theory explains the frequency of association of intraspinal midline
lesions with spinal anomalies, dermal sinus tracts and laterally situated
lesions in the cerebellopontine angle and the orbit.
•• Another mode of pathogenesis is iatrogenic. Intraspinal dermoids and
epidermoids may also form, as a result of inclusion of epidermis, following
repeated lumbar punctures, when done using a needle without the stylet.
Location
•• Intracranially, epidermoids are more common than dermoids.
•• They have an affinity for the subarachnoid cisterns at the base of the brain.
•• The suprasellar and cerebellopontine angle cisterns are the most favoured
sites, whereas the lateral ventricles, optic chiasm, collicular plate, pineal
gland and paratrigeminal area, sphenoid sinus, temporal bone, brainstem,
intradiploic, and lateral orbital wall are less favoured sites.
•• When these are extradural, the most common location is intraosseous in
the diploe of the calvarial bones.
•• Epithelial rests may give rise to a primary congenital epidermoid in the
petrous bone with gradual onset of facial palsy, hearing loss and vestibular
disturbances. The roof of the petrous bone is usually eroded.
Chapter 156 • Dermoids and Epidermoids
1175
•• Intraorbital lesions are usually located superolaterally at the site of fusion

of bones and gradually push the eyeball downwards and medially.
•• Epidermoids do not occur in the vertebrae and are uncommon in the scalp.
•• Over three quarters of all intracranial epidermoids occur in the basal
cisterns.
•• They may be classified as per their location as follows:
A. Extracranial
1. Spinal
2. Orbital.
B. Cranial-extradural
1. Intraosseous (intradiploic)
2. Orbital
3. Paranasal sinuses.
C. Intracranial-intradural
1. Intraventricular
2. Suprasellar—chiasmatic
3. Parasellar—Sylvian fissure
4. Restrosellar—cerebellopontine angle
5. Basilar—posterior fossa
6. Multicompartmental.
Pathology
•• Epidermoid is a well-delineated encapsulated lesion that has a characteristic
“pearly shine” that permits diagnosis merely on inspection.
•• It may be cystic in suprasellar and intraventricular locations, but is usually
solid, especially in the cerebellopontine angle, quadrigeminal cistern and
over the corpus callosum.
•• The solid lesion is characteristically filled with whitish, often cheesy material
rich in cholesterol crystals and a debris of desquamated keratinised
epidermal cells that accumulate centrally and add to the bulk of the growth.
•• These lesions are often large, almost giant sized, insinuating between
fissures and sulci, starting from one compartment and extending into
adjacent ones and becoming multicompartmental.
•• The capsule may be thin at places and nodular at others.
•• It is often adherent to the vascular structures, cranial nerves, and brainstem,
making total excision difficult without damage to these structures.
•• Foci of calcification may be found in the cyst wall.
•• The diagnostic histological finding is a simple stratified squamous epithelial
lining. The epithelial cells rest on an outer layer of collagenous tissue.
•• The outermost layer consists of homogeneous material, for the most part
quite structureless. It is this layer that has the beautiful pearly sheen, so
characteristic of these tumours.
•• Irritation of the surrounding brain may produce fibrillary gliosis and
thickening of the leptomeninges with foreign body giant cells.
•• Daughter cysts may be found within the main mass.
•• The tumour is entirely benign. It can recur after a long time if incompletely
removed, but usually does not turn malignant.
Incidence
•• Epidermoids constitute 0.5−1.8% of all intracranial tumours.
1176
Clinical Features
•• Epidermoid tumours typically present in the fourth or fifth decade of life with
symptoms related to pressure on adjacent structures or intracranial rupture.
•• The clinical picture of intracranial epidermoids varies according to their
location, direction and rate of growth, interference with cerebrospinal fluid
pathways, compression of neural and vascular structures or chemical
meningitis following rupture into the subarachnoid space or ventricle.
•• As epidermoids are soft with a pliable capsule, they grow very slowly and
tend to fill up any available space. They often reach a large size before
becoming symptomatic. For the same reasons, many of these lesions
attain a large size without producing signs of raised intracranial pressure.
•• Lesions are large at presentation and the initial symptoms usually involve
the cranial nerves.
•• Papilloedema is noted in only a small percentage of cases. In the more
laterally placed tumours, clinical symptoms are produced by compression
and deformation of adjacent neural and vascular structures.
•• Intradiploic epidermoids present essentially as painless masses with
characteristic radiological appearances. These occur more commonly in
the frontal and parietal bones and may occasionally be tender.
•• They are usually small, but may be large and accompanied by signs of
raised intracranial pressure and focal neurological deficit.
•• A primary epidermoid occurring in the petrous bone grows slowly, erodes
the bone steadily and produces tinnitus, progressive impairment of hearing
and facial nerve paresis.
•• Orbital epidermoids are usually located in the upper outer quadrant and
push the eyeball downwards and medially.
•• When the epidermoid is located in the frontal region, impairment of memory,
emotional lability, depression and incontinence of urine may occur.
•• When located in the suprasellar-chiasmatic region, they compress the optic
apparatus and produce visual impairment, optic atrophy and bitemporal
haemianopia. There may be associated widening of the optic foramina
with a normal sella turcica and normal pituitary function. Occasionally, the
patient may develop diabetes insipidus.
•• Epidermoids in the parasellar area extend into the Sylvian fissure laterally and
spread to the temporal and frontal lobes.
•• Depending on the direction of extension, the person may suffer from focal,
complex partial or grand-mal type of seizure disorder.
•• Epidermoids in the parapontine and cerebellopontine angle cisterns may
present initially with irritative manifestations, like trigeminal neuralgia,
hemifacial spasm or tinnitus, till they grow sufficiently large to produce
paresis of the trigeminal, facial and auditory nerves.
•• Paresis of the sixth nerve will result in diplopia.
•• Pressure on the cerebellum will result in nystagmus and ataxia and that on
the brainstem in hemiparesis or quadriparesis.
•• In intraventricular epidermoids, headache, dementia, psychiatric problems,
ataxia, hemiparesis and cranial nerve palsies are often seen when
obstruction to the CSF pathways is significant.
•• Pineal region tumours most commonly present with headache, diplopia and
vertigo. Neurological examination may demonstrate papilloedema, impaired
pupillary reaction, ataxia, Parinaud’s syndrome and long-pathways deficit.
•• Leakage of cholestrin and fatty acids into the subarachnoid space may
give rise to chemical meningitis, presenting with headache, irritability, and
neck stiffness.
1177
•• Spinal epidermoids have a predilection for the conus and for the low to mid
dorsal region and are largely intramedullary. They may be associated with
other abnormalities of the spinal cord and bony vertebral column. Being slow
growing lesions they may become apparent in the second decade of life.
They present with backache, progressive paraparesis, sphincter impairment
and sensory dysfunction or may present with recurrent aseptic meningitis.
Radiological Findings
•• Plain X-rays of the skull reveal occasional stippled calcification in a third
ventricular epidermoid or amputation of the apex of the petrous bone in a
cerebellopontine angle lesion.
•• The destructive area may be rounded or may appear scalloped and may
cause expansion of the calvarial bones.
•• In orbital lesions there is an erosion of the upper and outer margins of the
orbit, whereas in the petrous bone possible thinning or destruction of the
tegmen tympani is found.
•• The lesion usually appears as a hypodense mass with an attenuation
value of 22−32 Hounsfield units, although lesions of relatively high density
(80–120 HU) can occur.
•• The varying density is due to low-density lipid and high-density keratin in
the desquamated debris of the tumour.
•• Fat and fluid may also be seen within the tumour or in the ventricle or
subarachnoid space after it ruptures.
•• Foci of calcification may occasionally be seen in the tumour capsule.
•• Intraventricular lesions grow slowly and distend and dilate the ventricular
system, allowing cerebrospinal fluid to flow between and around the tumour,
rather than obstruct it.
•• Fissural epidermoids grow insidiously, tend to fill up and distend the
subarachnoid space and present as irregular shaped masses in the CT scan.
•• Hydrocephalus is only occasionally seen. This is an important differentiating
factor between an epidermoid and other tumours that act as obstructive
space occupying lesions.
•• Epidermoids do not enhance following intravenous contrast administration.
•• ln T1-weighted images, the signal intensity is between the brain
parenchyma and the CSF and in T2-weighted images it exceeds both
brain and CSF signals.
•• The signal intensity of some of the lesions is virtually the same as that of
CSF in short and long T images.
•• The presence of a cerebellopontine angle mass is usually suggested by
displacement of the brainstem.
•• Intravenous gadolinium does not show enhancement of the lesion or its
capsule.
•• In contrast, acquired cholesteatomas of the middle ear contain
predominantly keratinising stratified squamous epithelium and may have
moderate signal intensity in TR/TE images.
•• Intravenous gadolinium may show enhancement in such inflammatory and
neoplastic lesions.
•• Petrous apex epidermoids are well delineated in short TR/TE images due
to the negligible signal from the adjacent bone and CSF. They may have
1178
high intensity signals from cholesterol or other fatty material in short TR/
TE images.
•• Apparent diffusion coefficient (ADC) of epidermoid tumours is lower than
that of chordomas with the accuracy reaching 100%.
Treatment
•• The ideal treatment consists of complete excision of the cyst and its
contents.
•• Surgery is the only effective treatment modality for these lesions and as
radical a resection as possible should be performed in all cases to avoid
tumour recurrence; however, because the cyst capsule can adhere firmly
to vital structures and attempts at its radical removal can be dangerous,
subtotal resection may be a wise option in selected cases.
•• There is no role for radiation or chemotherapy.
•• Endoscope-assisted microsurgical techniques enable safe removal even
when tumour parts are not visible in a straight line. Tumour extensions into
adjacent cranial compartments can be removed with the same approach
without retracting neurovascular structures or enlarging the craniotomy.
Complications
•• While excising the tumour, spilling the contents into the subarachnoid
space should be prevented, as cholesterin and desquamated keratin act
as irritating agents and cause aseptic chemical meningitis.
•• Pre-operative administration of steroids and irrigation of the operative field
with fluids containing steroids is said to help in alleviating the chemical
irritation.
•• Post-operative administration of steroids, similarly, helps in reducing the
risk of chemical meningitis.
•• Lumbar puncture and drainage of contaminated CSF also helps in
alleviating the headache and pyrexia that sometimes occur with chemical
meningitis.
•• Chemical meningitis may end in basal arachnoiditis and communicating
hydrocephalus, requiring ventriculo or theco-peritoneal shunt insertion.
•• Transient paresis of cranial nerves may occur due to their being handled
during surgery.
•• Attempts at excising densely adherent tags of capsule from neural and
vascular structures may result in permanent dysfunction and cause
significant morbidity.
DERMOIDS
Incidence
•• Dermoids develop from congenital ectodermal inclusions as a result of
imperfect embryogenesis.
•• These are usually found at the sites of epithelial fusion lines and have a
tendency to occur in the midline.
•• Their incidence varies from 0.1−0.72% of all intracranial tumours.
•• These occur more commonly in the paediatric age group.
•• Paediatric dermoid cysts are unusual lesions with the mean age at
presentation being 22 months.
•• Dermoid cyst is by far the most common orbital cystic lesion in children.
1179
Location
•• Dermoids can occur in the scalp, the calvarium, the epidural space,
intracranially at various locations and in the spinal canal.
•• Dermoids in the scalp usually occur in the midline over the region of the
anterior fontanelle or laterally as angular dermoids over the outer aspect
of the eye.
•• These are frequently associated with midline fusion defects and in nearly
a fourth of the cases these are connected with the intracranial structures
or the spinal canal by a congenital dermal sinus or a stalk.
•• In the skull, dermoids occur more frequently in the nasal and paranasal
regions and the orbits.
•• These occupy the region of the glabella, bridge of the nose and deep part
of the septum.
•• They may extend into the anterior cranial fossa.
•• Orbital lesions arise superolaterally at the site of embryologic fusion, erode
the orbit and may enter the anterior or middle cranial fossa.
•• Intracranially, these occur essentially in the posterior fossa as midline
dermoids associated with a dermal sinus and often present as a cerebellar
lesion.
•• Dermoid cysts may infrequently occur “primarily” in the temporal fossa.
•• Dermoids may also occur in the suprasellar region where they have to be
differentiated from craniopharyngiomas.
•• They may be intraventricular in location either in the fourth or the third
ventricle.
•• Intraspinal dermoids are more common than epidermoids and are often
associated with dermal sinuses and spinal dysraphism. They may coexist
with dermoids in other organs.
Pathology
•• Dermoid cysts are developmental lesions and not true neoplasms.
•• These occur as rounded or oval, opaque masses that may have a pearly
shine externally with a wall of varying thickness.
•• The wall is composed of dermal epithelium with external collagenous tissue
and contains dermal appendages such as hair follicles, sweat glands, and
adipose tissue.
•• Dermoids contain sebaceous material and hair in addition to keratinised
desquamated debris.
•• The contents are fluid or pultaceous and resemble soft butter.
•• A dermoid may rarely rupture into the subarachnoid space resulting in
severe reactive meningitis which may prove fatal.
•• The most irritant element is cholesterol, which is derived from the
breakdown of keratin.
•• It excites a granulomatous form of meningitis.
Clinical Features
•• Dermoids of the scalp usually occur in the midline and are mostly located
over the region of the anterior fontanelle or the inion.
•• They are globular, soft, and slightly mobile and the overlying skin may
show a skin dimple.
•• They may erode both the tables of the bone and may be adherent to the
underlying sinus.
1180
•• A dermoid in the posterior fossa is usually situated in the midline. It is mostly

intracerebellar, although it may be found just underneath the dura. It may
present with manifestations of raised intracranial pressure and ataxia or
with recurrent bacterial meningitis or as a cerebellar abscess when it is
associated with a dermal sinus.
•• Suprasellar dermoids present with visual impairment and bitemporal
hemianopia and may be associated with diabetes insipidus.
•• Intra third ventricular dermoids present with manifestations of raised
intracranial pressure due to obstructive hydrocephalus.
•• Nasal dermoids may be located over the glabella, the bridge of the nose
or deep in the septum and are usually a consequence of an abnormality
of anterior neural tube closure.
•• Infection may result in cellulitis, abscess, osteomyelitis, and recurrent
meningitis.
•• Dermoids in the fourth ventricle may present with progressive headache,
unsteady gait, balance disturbances, deglutition disorder and diplopia.
•• Spinal dermoids usually present with recurrent attacks of meningitis when
they are associated with a communicating dermal sinus and other stigmata
of spinal dysraphism. These are located mostly over the lower dorsal and
dorsolumbar regions.
•• Compressing the dorsal cord, the conus or the nerve roots, they produce
progressive paraparesis, sensory impairment, and sphincter disturbances.
•• Spinal dermoids may occur at the cranio-cervical junction and may be
associated with a spinal anomaly like Klippel-Feil syndrome.
Radiological Findings
•• Dermoids of the scalp may cause erosion of the bone, often the outer
table of the skull.
•• The margins of the erosion are typically sclerotic.
•• Plain X-ray may, at times, show the opening through which a dermal sinus
traverses or erosion of the bone when a dumb-bell orbital dermoid extends
into the frontal or temporal fossae.
•• Dermoids may, occasionally, contain teeth.
•• CT scan often shows a cystic mass with flakes of calcium which may not
be seen on plain X-ray.
•• There is a large range of attenuation values depending on the nature of
the contents, viz. desquamated debris, sebaceous secretions, hair, and
fatty tissue.
•• The dermoid may appear as a hyperdense mass if it contains oily cystic fluid.
•• Dermoid cysts are typically hypodense on computed tomography, but when
hyperdense may mimic a haemorrhage.
•• It is often associated with a dermal sinus and may show associated
developmental anomalies. Associated hydrocephalus may be seen.
•• In a ruptured dermoid cyst multiple fatty globules are visualised in the
ventricles or subarachnoid space.
•• MR scan shows the above changes more graphically, especially the tract
of the dermal sinus, the relationship of the dermoid cyst to the various
structures in the posterior fossa and its exact location within the spinal cord
or the conus. Often, the associated tethering of the cord may be vividly seen.
•• In case of ruptured dermoid cysts, fat appears strongly hyperintense on
Tl-weighted images.
•• The imaging characteristics of dermoids and lipomas are extremely similar.
1181
Treatment
•• Ideal treatment consists of total excision of the dermoid cyst along with
any associated dermal sinus.
•• Radical excision of intracranial dermoids is usually possible, unless
adhesions have developed following attacks of aseptic or purulent
meningitis.
•• Dermoids do not usually undergo malignant change.
157
CHAPTER
Teratomas
INTRODUCTION
•• A teratoma is a true neoplasm composed of multiple tissues of kinds foreign
to the part in which it arises.
•• It is composed of tissues of adult type and organic pattern derived from all
three germinal layers.
•• When the derivatives of all the three germinal layers are not clearly defined,
the lesion has been called a teratoid.
•• Many of these tumours grow rapidly and may become malignant and
such teratomas almost always display some tissue elements which are
embryologically immature.
•• Teratomas most commonly arise in the ovaries and testes.
•• In relation to the nervous system, the most common site is the
sacrococcygeal region.
•• Within the brain, most of these tumours arise in the midline anywhere from
the optic chiasma to the pineal gland, mostly in the latter situation.
•• The incidence of intraspinal teratomas is approximately five times more
than that of intracranial teratomas.
INCIDENCE
•• Teratomas constitute 3.5% of all paediatric tumours.
•• The brain is considered to be one of the rare sites for teratomas.
•• The intracranial incidence of these tumours varies in different series from
0.2 to 2%, and is somewhat higher in children.
•• Teratomas usually occur in younger age groups and males are affected
more than females.
•• Nearly 50% of the intracranial teratomas are located in the pineal gland. The
other preferential sites are the ventricular system and the posterior fossa.
•• Intracranial teratomas of the newborn have several characteristics different
from the teratoma of the pineal region seen in older children. In the former,
the sex ratio of female to male is about 2:1, while the pineal teratoma is
predominantly reported in males.
PATHOGENESIS
•• Teratomas arise at early stages of embryonic development.
•• For unknown reasons, many do not manifest themselves until several years
after birth, occasionally not until several years into adult life.
Chapter 157 • Teratomas
1183
•• Those occurring in the newborn are a special variety, which grow to an

appreciable extent at a very early period.
•• Differences in the rate of growth seem to account for the various forms in
which these tumours present themselves in infancy.
•• Of the various theories on the pathogenesis of these tumours (the
blastomeric theory, Masson’s twin theory, the parthenogenetic theory),
anomalies of the primitive streak alone appear to be applicable to the
nervous system.
•• Teratomas are assumed to develop, following inclusion within the embryo of
a fragment of the primitive streak in the multipotent stage. This theory lends
support to the role of the neural groove, thus explaining fairly satisfactorily
the appearance of sacrococcygeal spinal, midline supratentorial and
infratentorial teratomas.
PATHOLOGY
•• Macroscopically the striking characteristic of a teratoma is its partly cystic
nature, the cysts usually being multiple and containing whitish fluid from
desquamation of the lining cells.
•• The solid portion of the tumour is firm, greyish-white and discoloured yellow
from previous haemorrhage.
•• Some of the teratomas are sharply demarcated from the adjacent nervous
structures and can readily be dissected away from them.
•• Others, especially the intraspinal group, are blended so closely with the
neural tissue that no plane of cleavage can be identified.
•• An outstanding feature is a tendency to obstruct the CSF pathways.
•• Congenital teratomas manifesting early in life may attain massive propor-
tions, replacing the greater part of the brain.
•• Microscopically, the tumour tissue consists of elements of all the three
germinal layers.
•• Depending upon the different proportions of embryonic and mature tissues,
the tumour may be classified benign or malignant.
•• If the cells are mature and well differentiated then it is labelled benign.
•• As a general rule, the more embryonic the tissue, the more malignant is
the tumour.
•• Typical foci of germinomas may be seen in pineal, suprasellar and other
teratomas.
CLINICAL FEATURES
•• The symptoms and signs are those of any space occupying lesion.
•• There are local effects depending upon the site of tumour and pressure
effects resulting from an increase in the volume of the cranial contents.
•• There are no specific clinical signs which may suggest the pathological
diagnosis pre-operatively, unless an associated congenital anomaly is
present.
•• The presence of a congenital anomaly in a patient with signs and symptoms
of a space-occupying lesion does not establish the diagnosis of a teratoma
or teratoid tumour but makes the chances of finding this lesion somewhat
greater.
•• In infants, the onset is marked by rapidly progressing hydrocephalus with
occasional localising signs, such as gaze palsy, pupillary change and
hemiparesis and lucency on transillumination of the head.
1184
•• Teratomas in infants and the newborn may be classified into three groups
on the basis of clinical and autopsy findings:
1. The infant may be born dead with complete replacement of the brain
tissue above the brainstem by the tumour. The birth of these infants
may be associated with dystocia. The lesion is inoperable because of
replacement of brain tissue.
2. The infant may be born alive but show progressive cranial expansion.
3. The infant may look normal at birth but subsequently develop hydro-
cephalus and focal neurological deficits.
•• In older children and adults, localising signs are infrequent.
•• Endocrinal disturbances, as also Parinaud’s syndrome, may be found, if
the teratoma develops near the pineal region.
•• Suprasellar teratomas cause a characteristic syndrome of diabetes
insipidus, visual disturbances and hypopituitarism.
IMAGING
•• Roentgenograms of the skull show widened sutures, craniofacial
disproportion and calcification of the tumour mass or other organoid
structures like a tooth in the tumour.
•• CT is useful in demonstrating even small tumours, provided they contain
fat or calcium.
•• The CT pattern of a malformative tumour is that of a relatively well defined
extra-axial mass lesion with or without calcification that fills or moderately
expands the pre-existing CSF spaces.
•• While the fat components have a low attenuation value, other components
may show hyperdensity
•• MR findings vary with the tissue component of the teratoma.
•• The characteristic angiographic findings of intracranial teratomas are
deviation of the main cerebral arteries by a large mass of tumour, a fine
vascular network and early venous shunting.
TREATMENT
•• The ideal treatment, wherever possible, is excision.
•• Mature teratomas have a good prognosis if completely excised. This may,
however, not always be possible, in which case a shunting procedure may
be necessary to relieve the hydrocephalus.
•• Aggressive resection seems to be of utmost importance in the treatment
of immature teratomas of the CNS.
•• Ten-year survival for surgical excision alone varies with histological type,
being more than 90% for mature teratomas, less than 70% for immature
teratomas and less than 50% for teratomas with malignant components.
•• Adjuvant chemotherapy and radiotherapy can be deferred if gross total
resection is achieved in low-grade, immature teratomas but adjuvant
therapies may be warranted for high-grade ones.
•• Treatment recommendations are:
–– Mature teratomas: Completely resected and no adjuvant therapy;
Sub-total resection: Adjuvant therapy (cisplatin) followed by second
look surgery, and
–– Immature teratomas: Radiotherapy and chemotherapy both are used
with variable efficacy.
Chapter 157 • Teratomas
1185
•• Chemotherapeutic agents used include carboplatin, etoposide, bleomycin,

ifosfamide, vincristine and dactinomycin.
•• High recurrence rates are encountered with chemotherapy alone even if
beta-hCG/alpha-fetoprotein levels come to normal post-operatively.
•• Teratomas with highly malignant components including embryonic
carcinoma, yolk sac tumour, squamous cell carcinoma, adenocarcinoma
and sarcoma are chemo-resistant.
•• Chemotherapy along with craniospinal irradiation with local booster
radiotherapy is indicated.
•• Second look surgery is indicated in cases where tumour markers are
elevated and suggestive of malignancy.
•• Non-malignant teratoma lesions or teratomas mixed with haemorrhagic
necrosis or inflammatory cells may also benefit from second look surgery.
•• Higher tumour marker levels indicate poorer treatment response and
although useful for monitoring disease status, tumour markers have no
impact on the patient’s final outcome.
158
CHAPTER
Acoustic Schwannomas
Ravi Ramamurthi  Murali Mohan S
INTRODUCTION
•• Intracranial schwannomas can arise from any of the cranial nerves with a
Schwann cell investing layer.
•• A schwannoma arising from the VIII cranial nerve is called acoustic
schwannoma [synonyms—acoustic neurinoma, acoustic neuroma, acoustic
neurofibroma and vestibular schwannoma (VS)].
•• This tumour should ideally be termed as VS as they arise from the Schwann
cells investing the vestibular nerve, but the term acoustic schwannomas is
so firmly entrenched in the literature that its use is continued.
EPIDEMIOLOGY
•• Schwannomas constitute about 8% of all intracranial tumours which present
clinically.
•• The majority of acoustic schwannomas are sporadic and unilateral.
•• Bilateral acoustic schwannomas are hereditary and constitute less than
5% of all schwannomas.
Age and Sex Distribution

•• Acoustic schwannomas are commonest in the fourth to sixth decades.
•• Acoustic schwannomas developing in patients with neurofibromatosis
type-2 (NF-II) tend to present earlier, with a peak incidence around the
third decade.
•• Acoustic schwannomas can occur in children.
•• There is a slight female preponderance with an aggravation of symptoms
during pregnancy.
Tumour Syndromes and Genetic Factors

•• Most of the acoustic schwannomas are unilateral and are sporadic in nature
•• Hereditary acoustic schwannoma occurs in NF-II more frequently than
neurofibromatosis type-1 (NF-I), though the latter is much more common.
•• Unilateral acoustic schwannoma has been reported only in 2–4% of cases
with NF-I. Bilateral acoustic schwannoma is a hallmark of NF-II.
•• Both these conditions have high penetrance and are autosomal dominant.
•• The defective genetic locus has been localised to chromosome 17 in NF-I
and chromosome 22 in NF-II.
•• The NF-II gene is considered to be a tumour suppressor gene.
Chapter 158 • Acoustic Schwannomas
1187
Natural History
•• The growth rates of these tumours are generally slow, usually less than
2 mm per year, however, there are reports of rapid growth rate of about
2.5–4 mm per year.
•• The growth rates in bilateral acoustic schwannomas are on an average
considered to be faster than in unilateral lesions.
•• There are marked differences in the duration of symptoms at the time of
presentation. An important factor determining the future course in these
cases is the initial size of the tumour at presentation.
PATHOLOGICAL ANATOMY
•• Acoustic schwannomas arise most commonly from the vestibular nerves
(80%) with an origin from the cochlear part in only about 5–7%.
•• The inferior vestibular nerve is involved in 70% of patients, the superior
vestibular in 20% and the cochlear nerve in 10% of patients.
•• The origin of the tumour is from the junctional (Obersteiner-Redlich) zone
where the central and peripheral myelin meets. This zone is situated at the
region of the internal auditory meatus (IAM) or within the internal auditory
canal (IAC) in most instances.
•• The tumour grows initially within the canal and thereafter extrudes into the
cerebellopontine angle (CPA).
•• Inside the petrous bone, the tumour may compress the cochlear component
of the nerve or the labyrinthine artery, causing sudden severe hearing loss.
•• Tumour growth into the CPA results in anterior displacement of the facial
and cochlear nerves.
•• The relationship of the tumour to the vestibulocochlear nerve varies:
–– In about 50% the nerve fibres are intimately involved with the tumour
making separation impossible
–– In 40%, though the nerve is in the form of a bundle initially, it becomes
adherent to a part of the tumour capsule making functional preserva-
tion impossible
–– In 10% the uninvolved portion of the nerve maintains anatomical integ-
rity and the nerve is displaced as a separate bundle. Clinically, this last
group of cases present with preserved hearing and this should alert
the surgeon to the possibility of hearing preservation post-operatively.
•• Depending on the direction of growth of the tumour, the facial nerve may
run one of four courses around acoustic schwannomas:
–– The nerve runs anterior to the tumour in about 70% of cases,
–– Superior to it in about 10% of cases
–– Posterior in about 7% of cases
–– Inferior in about 13% of cases.
•• The position of the facial nerve is most constant at the lateral end of the
IAM and it is best to locate the nerve here, rather than more medially, where
displacement may make its position more variable.
•• Since the tumour arises from outside the CSF space, it pushes the lateral
layer of the arachnoid inwards till it comes into contact with the more medial
layer. The double layer, thus formed contains the important vessels and
nerves of the CPA and is an important aid to dissection.
•• There is often a loculation of CSF which presents as an arachnoid cyst
dorsolateral to the tumour.
1188
•• The cerebellar hemisphere is displaced backwards and the brainstem is

compressed and rotated along its long axis with gross displacement and
stretching of the basilar artery and its branches.
•• As the anterior inferior cerebellar artery (AICA) most often passes below
the VII and VIII nerves, it is displaced inferiorly. In large lesions, the AICA
may be seen lying in close relation to the IX and X cranial nerves.
•• The superior cerebellar artery is displaced rostrally and the posterior inferior
cerebellar artery caudally.
•• The veins surrounding the tumour form bridging veins which empty into
the superior petrosal sinus. While small tumours can be removed without
sacrificing these veins, in large tumours it may be necessary to sacrifice
one, if not more, or even the superior petrosal vein, to reach the superior
pole of the tumour.
PATHOLOGY
•• Grossly the tumour is usually firm, rubbery and pale grey in colour with
varying degrees of vascularity and has a well-defined capsule, which may
be covered by displaced and stretched nerve fibres.
•• The cut surface is usually pale grey and firm with a finely whorled or
trabeculated appearance.
•• In large tumours there is, frequently, evidence of cystic degeneration,
haemorrhage, xanthomatous change and occasionally foci of calcification.
These changes give a variegated appearance in colour and consistency
to the large tumours.
•• The blood supply of the tumour is initially derived from the internal auditory
artery, which provides multiple minute ramifications over the surface of
the tumour.
•• As the tumour grows, small branches from the neighbouring cerebellar and
pontine arteries may supply the tumour.
•• On light microscopy, the tumour is composed of spindle cells with elongated
nuclei and fibrillary cystoplasm, arranged in two distinctive patterns termed
Antoni A and Antoni B.
•• Antoni A tissue is compact, with fairly prominent interwoven streams of
elongated bipolar cells. At times, the arrangement of the nuclei and fibres
results in structures simulating the whorls seen in meningiomas.
•• Antoni B is less structured and consists of random collections of cells clustered
around areas of cystic change, necrosis, blood vessels and old haemorrhage.
There is a variable amount of lymphocytic infiltration of this tissue.
•• The Antoni B type of tissue, seen mostly in large tumours, is believed to
be the result of ischaemia.
•• The relative amounts of these two types determine the consistency of the
tumour.
•• Nuclear pleomorphism is common in schwannomas, but these are benign
changes, as malignant transformation almost never occurs.
•• Mitotic figures are rare.
•• Necrosis, when seen, is also more a reflection of a poor blood supply rather
than of rapid growth.
•• The degenerative changes in the tumour tissue include oedema, formation
of micro or macro cysts, xanthomatous alteration, hyalinisation and foci of
calcification.
1189
•• Electron microscopy (EM) reveals the characteristic basement membrane

of the Schwann cells and the presence of wide-spaced collagen.
CLINICAL FEATURES
•• The signs and symptoms of an acoustic schwannoma are those referable
to the VIII nerve itself, as well as those due to involvement of the adjacent
cranial nerves (VII, V, IX and X), the cerebellum and the brainstem.
•• To these may be added the symptoms and signs of raised ICP.
•• Small tumours may exist for a long time producing only VIII nerve symptoms.
•• The most common symptoms of acoustic schwannomas are unilateral
sensorineural hearing loss, unsteadiness, tinnitus, headache, mastoid pain
or otalgia, facial numbness and diplopia.
•• Usually slow growing and presenting insidiously, they can have acute
presentations when there is haemorrhage within the tumour, or due to
rapid expansion of a cyst.
Auditory
•• Though the tumour originates from the vestibular nerve, the commonest
presenting symptom in acoustic schwannomas is unilateral hearing
impairment, which is found in almost all cases.
•• The hearing loss is a high frequency retrocochlear sensorineural type and
is slowly progressive.
•• Being insidious in onset, the impairment of hearing, which commonly
precedes all other symptoms by several years, may pass unnoticed for
a long time.
•• Even though some patients may not complain of unilateral deafness, the
way they turn their normal ear towards the examiner to listen better is a
characteristic sign.
•• Deafness may be tested in the consulting room; speech discrimination by
using whispered words and tone deafness by using tuning forks of varying
frequency (256–1018 Hz). High tone deafness will be apparent from this.
•• Air conduction is tested by placing the tuning fork near the external ear
and bone conduction by placing it on the mastoid process and the frontal
bone (Weber’s test and Rinne’s test). These give an approximate idea of
whether the deafness is of the conduction or sensorineural type.
•• Tinnitus is another common symptom of acoustic schwannomas being
reported as the initial symptom. It may be intermittent or may completely
disappear after some time.
Vestibular
•• Subjective symptoms of vestibular dysfunction are uncommon as the
presenting complaint; though on objective testing 80–96% of patients
may have signs of vestibular dysfunction. This is thought to be due to
suppression of the abnormal impulses by higher centres.
•• The commonest vestibular symptom is a sensation of instability on
movement of the head.
•• Nystagmus may be seen in a number of cases and is usually due to a
vestibular disturbance in the early stages and pressure on the brainstem
in the later stages. This may be spontaneous, positional (when the head
is hyperextended and the head turned to the right or left) or optokinetic.
1190
•• The most common variety is the fine horizontal beats directed away from
the side of the lesion produced due to unilateral labyrinthine dysfunction.
•• Large tumours producing significant brainstem compression manifest as
bidirectional nystagmus with a coarse gaze evoked optokinetic nystagmus
on looking to the ipsilateral side and a high frequency fine small amplitude
vestibular nystagmus on looking to the contralateral side.
•• Spontaneous nystagmus, though bilateral, is usually more marked on
looking to the opposite side. It is not dependent on visual fixation, but on
conjugate deviation of the eyes.
Facial Nerve
•• The facial nerve has been clinically observed to be remarkably resistant to
stretch, and symptoms and signs due to involvement of this nerve appear
late and are minimal, except in very large tumours.
•• A slight lag in blinking of the eyelid on the affected side is an indication of
early facial palsy.
•• Signs of irritation of the facial nerve, like twitching or increased lacrimation
occasionally seen.
•• A minimal facial weakness may be detected by electromyography.
Other Cranial Nerves

•• The trigeminal is the next common nerve to be involved, the nerve
being stretched by the upward growth of the tumour when it reaches an
extracanalicular size of about 3 cm.
•• The common abnormality referable to the fifth nerve is impairment of the
corneal reflex.
•• Subjective numbness and/or paraesthesia in the trigeminal distribution may
be complained of by many patients.
•• Tingling of the tongue may be the first symptom of an acoustic neurinoma
for many weeks.
•• Infrequently, there may be pain which may mimic typical trigeminal
neuralgia.
•• The glossopharyngeal and vagus nerves are involved usually late, and
manifest as palatal paresis, hoarseness of voice and dysphagia.
Cerebellar
•• Symptoms related to cerebellar dysfunction are found in patients with
large tumours.
•• The deficits are commonly gait ataxia and incoordination of the upper limb,
dysarthria being rare.
•• When nystagmus is present, it is usually due to vestibular and brainstem
involvement rather than cerebellar involvement.
•• In the presence of brainstem compression the nystagmus is slow and
prolonged and there may also be a vertical nystagmus.
Brainstem
•• A large tumour can cause compression and later torsion of the brain-
stem with resultant pyramidal weakness and contralateral cranial nerve
deficits.
1191

•• Though the technical capacity now exists to diagnose an acoustic
schwannoma when it is still intracanalicular, a significant number of patients
still present for the first time only after the onset of features of raised ICP.
•• Mental symptoms due to chronic hydrocephalus have been the presenting
feature in some elderly patients with large acoustic tumours.
•• Headache in most of these cases results from increased ICP. Headache
may also occur in the absence of raised ICP due to pressure or traction upon
blood vessels. It may also be caused by pressure on the tentorium, which
is innervated principally by branches of the first division of the trigeminal
nerve. The pain may thus be frontal or retro-orbital in the initial stages.
•• Papilloedema may range in its manifestations from slight to severe.
INVESTIGATIONS
Neuro-Otological Workup
•• Most of these tests can be performed only if the affected ear has usable
hearing.
•• A baseline workup is necessary for later comparison and to document
the deterioration during follow-up or post-operatively. There are several
systems for grading hearing; the modified Gardner-Robertson system is
described in Table 1.
Clinical Testing of the Auditory System
•• Schwabach test:
–– In this test, a tuning fork of 256 Hz or 512 Hz is used and the patient’s
bone conduction is examined. The 512 Hz tuning fork is preferred. The
duration of perception of the tone is noted.
–– The stem of the tuning fork is placed on the patient’s mastoid process
and transferred to the examiner’s, once the former can no longer hear
it.
–– The test may be repeated for the evaluation of air conduction.
•• Rinne test:
–– In this test, the patient’s air and bone conduction are compared.
–– The stem of the tuning fork is first placed firmly on the mastoid process
of the patient while closing the external auditory meatus (EAM). The
patient is asked to indicate when he can no longer hear the sound. The
tuning fork is then immediately transferred to the front of the EAM and
the time up to when the sound is heard is noted.
–– In normal individuals or a positive Rinne test, air conduction is better
than bone conduction, i.e. the patient continues to hear the sound
Table 1: Gardner and Robertson modified hearing classification

Class Description Pure tone audiogram # (dB) Speech discrimination #
I Good–excellent 0–30 70–100%
II Serviceable 31–50 50–59%
III Non-serviceable 51–90 5–49%
IV Poor 91–maximum 1–4%
V None Not testable 0
# if audiogram and speech discrimination score do not qualify in the same class, use the lower class
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when the tuning fork is placed in front of the EAM after he has stopped
hearing it on the mastoid.
–– In a negative Rinne test, bone conduction is better than air conduction,
with the tuning fork heard better over the mastoid process.
–– The Rinne test is negative in conductive deafness.
–– In sensorineural hearing loss, both bone and air conduction are
reduced, but maintain a normal relationship to one another.
•• Weber test:
–– This test is performed by placing the stem of the tuning fork on the
forehead or over the vertex of the skull. In normal individuals the sound
is heard equally in both ears.
–– In conductive deafness, the sound is heard best in the involved ear,
while in sensorineural deafness the sound is best heard in the unin-
volved ear.
Specialised Testing
•• Pure tone audiometry:
–– It differentiates between conductive and sensorineural deafness. In
patients with a conductive deafness, the pure tone bone conduction
has a normal threshold, while pure tone air conduction has elevated
thresholds.
–– In patients with sensorineural hearing loss, both air and bone conduc-
tion thresholds are elevated.
•• Loudness recruitment:
–– In patients with sensorineural deafness it is essential to further char-
acterise the deafness, whether it is cochlear or retrocochlear in origin.
–– A phenomenon of abnormal growth of loudness, termed as loudness
recruitment, serves to differentiate between cochlear and retrococh-
lear lesions as purely VIII nerve lesions are not characterised by this
phenomenon.
–– The alternate binaural loudness balance test (ABLB) and the short
increment sensitivity index (SISI) are tests of recruitment.
•• Alternate binaural loudness balance (ABLB) test:
–– The ABLB compares the loudness of a tone in an impaired ear with the
same or a different tone in the normal ear.
–– In the ear where recruitment is positive, tones of equal intensity will be
judged equally loud in both the impaired and the normal ear, despite
the fact that the threshold for hearing is elevated in the impaired ear.
•• Short increment sensitivity index:
–– The SISI is measured by superimposing 1 db intensity increments on
a continuous tone. The ability to perceive these small increments is
associated with cochlear pathology while with lesions of the VIII nerve
the scores are low.
•• Speech discrimination:
–– It is another phenomenon which is associated with cochlear damage.
–– It is tested by using standardised monosyllables using a live voice or
taped material.
–– Patients with both cochlear and retrocochlear lesions have low speech
discrimination scores, with patients with retrocochlear lesions having
lower scores than those with cochlear lesions.
–– Non-behavioural auditory testing is now being used mainly in two
forms: impedance audiometry and brainstem auditory evoked
response audiometry.
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•• Impedance audiometry:
–– This is an extremely sensitive index of retrocochlear disease. It con-
sists of three separate measurements:
–– Static compliance or measurement of the “stiffness” of the conducting
apparatus of the ear.
–– Tympanometry or measurement of the pressure differentials between
the external auditory canal and the middle ear.
–– Acoustic or stapedial reflex.
•• The measurements of static compliance and tympanometry assess middle
ear disease.
•• The acoustic or stapedial reflex is a sensitive indicator of retrocochlear
pathology.
•• The reflex has an afferent arc in the form of an intense sound signal
delivered to the VIII nerve. This produces a reflex contraction of the
stapedius muscle innervated by the VII nerve.
•• In patients with a cochlear lesion, the gap between the behavioural threshold
and the acoustic reflex threshold is small (less than 55 db). Patients with
retrocochlear lesions show absent or elevated acoustic reflex thresholds.
•• The acoustic reflex decay measures the rate of adaptation of the reflex.
To measure the decay, a sustained tone is presented at 10 db above
the patient’s reflex threshold for a period of 10 seconds. The testing
is conducted at frequencies below 2000 Hz, because normal persons
frequently show reflex decay at higher frequencies. If the reflex amplitude
reduces more than 50% during the 10 second tune period, the results point
towards a retrocochlear lesion.
•• Brainstem auditory evoked response audiometry: It has a 96% detection
rate with an 8% false positive and 4% false negative rate.
Imaging
•• Plain X-rays of the skull with special views to visualise the petrous bones
are still useful as a first step.
•• Enlargement and/or erosion of the porus acousticus and the IAC are
diagnostic of an acoustic schwannoma.
•• Caldwell and Towne’s views are employed routinely in most clinics.
•• Of these, the transorbital projection (Caldwell view) is more useful in
demonstrating the canals.
•• In the Stenver view, the IAM is visualised in a shortened form, whereas
the transorbital view depicts the canal and the meatus in actual form and
size in one single film.
•• A contrast-enhanced computerised tomography (CT) can easily detect a
tumour with an extracanalicular extension of 1–1.5 cm.
•• On the non-contrast CT scan the tumour is seen as well marginated lesions
centred on the IAM.
•• A majority of tumours are isodense. The proportion of hypodensity or mixed
density lesions increases with increasing tumour size.
•• Following contrast injection, almost all tumours show enhancement. Antoni
type B tumours enhance irregularly with contrast while Antoni type A
tumours enhance homogeneously.
•• Cysts are uncommon. These are usually small and often close to the
arachnoidal surface of the tumour.
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•• The CT using bone window settings characteristically demonstrates the

widening of the porus acousticus.
•• On MR, the tumour is usually hypointense in relation to the pons in
T1-weighted images and isointense to mildly hyperintense on proton density
and T2-weighted images.
•• Intracanalicular lesions are recognised on the basis of a differential signal
between the tumour and CSF on T1-weighted images, the tumour being
relatively hyperintense compared to CSF.
•• Focal swelling or obscuration of the VIII nerve may be the earliest sign of
tumour growth on the MR.
•• Use of contrast is also helpful to exclude or demonstrate residual or
recurrent tumour. The study should be done at least 6 weeks after surgery.
•• The differentiation of an acoustic schwannoma from a meningioma is more
easily done with an enhanced MR.
•• The differential diagnosis of a CPA mass is given in Table 2.
•• The pre-operative distinction between a meningioma and an acoustic
schwannoma is important for technical and prognostic reasons.
Table 2: Differential diagnosis of acoustic schwannoma

• Acoustic schwannoma [80–90% of cerebellopontine angle (CPA) lesions]
• Meningioma (5–10% of CPA lesions)
• Ectodermal inclusion tumours
–– Epidermoid (5–7% of CPA lesions)
–– Dermoid
• Metastases
• Neuroma from cranial nerves other than VIII (also see below):
–– Trigeminal neuroma: expands towards Meckel’s cave
–– Facial nerve neuroma
–– Neurinoma of the lowest four cranial nerves (IX, X, XI, XII)
• Arachnoid cyst
• Neurenteric cyst
• Cholesterol granuloma (distinct from epidermoid)
• Aneurysm
• Dolichobasilar ectasia
• Extensions of:
–– Brainstem or cerebellar glioma
–– Pituitary adenoma
–– Craniopharyngioma
–– Chordoma and tumours of skull base
–– Fourth ventricle tumours (ependymoma, medulloblastoma)
–– Choroids plexus papilloma—from 4th ventricle through Foramen of Luschka
–– Glomus jugulare tumour
–– Primary tumours of temporal bone (e.g. sarcoma or carcinoma)
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•• The facial nerve typically is located on the anterior or anterosuperior

surface of an acoustic neuroma. This relationship is lost in the case of a
CPA meningioma. The facial nerve may be displaced in any direction or
may be engulfed by tumour, thus making its preservation more difficult.
•• An important differentiating feature is that an acoustic neuroma is usually
centred over the IAM, whereas CPA meningiomas are usually eccentric.
•• The enhancement after gadolinium administration of a tail of dura
adjacent to the main tumour has been termed the meningeal sign seem
in meningiomas.
•• Rarely, an acoustic neuroma may display a pseudomeningeal sign.
This is a thin, short dural tail present on a single aspect of the tumour,
which is caused by bone marrow adjacent to the porus acousticus. This
pseudomeningeal sign is present on T1-weighted images before and after
gadolinium enhancement, unlike the true meningeal sign that is present
only after the administration of gadolinium.
•• Both acoustic neuroma and CPA meningioma have a heterogeneous
appearance on the T1-weighted MRI. This heterogeneity is due to cystic
degeneration in acoustic neuroma, and to calcifications in CPA meningioma.
•• On T2-weighted scans, the cystic areas will appear hyperintense, whereas
the calcified areas remain hypointense. Thus, a CPA tumour that has
regions of low intensity on T1 and T2-weighted MRI probably is a calcified
meningioma.
MANAGEMENT
•• The options available for the management of VSs include observation,
surgery, stereotactic radiosurgery (SRS) and fractionated radiotherapy.
•• The ideal treatment is total excision of the tumour in a single stage with
preservation of neurological function.
•• Resection is indicated for patients harbouring larger tumours that have
caused major neurological deficits due to brain compression.
•• SRS indicated for small-sized or medium-sized tumours, with twin goals to
preserve neurological function and prevent tumour growth.
•• The long-term outcomes of SRS, particularly gamma knife surgery (GKS),
have proven its role in the primary or adjuvant management of this tumour.
•• Fractionated radiotherapy has been suggested as an alternative in selected
patients with larger tumours for whom microsurgery may not be feasible,
as well as in some patients in whom preservation of cranial nerve function
is being attempted.
•• Before choosing any particular therapy, primary clinical issues such as
avoidance of tumour-related or treatment-related mortality, prevention
of further tumour-induced neurological disability, minimising treatment
risks such as CSF leakage, infections, cardiopulmonary complications,
maintaining regional cranial nerve function (facial, trigeminal, cochlear and
glossopharyngeal/vagal), avoiding hydrocephalus, maintaining quality of
life (QOL) and employment, and reducing cost should be considered and
the surgeon should strive to meet all of these goals.
•• Surgery is indicated for the treatment of small and medium-sized VSs.
Observation
•• There are patients for whom long-term observation may be indicated.
Because surgery carries some risk and these tumours are generally slow
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growing, a conservative policy may be adopted especially in elderly patients

without any serious neurological symptoms.
•• Measurement of the maximal tumour diameter on MRI is a reliable method
for following acoustic neuroma growth.
•• The vast majority of patients older than 65 years with small acoustic
neuromas do not require intervention.
•• The indications for intervention should be based on the evidence of rapid
tumour growth with deterioration of symptoms.
•• A substantial number of acoustic schwannomas are discovered incidentally.
These incidental schwannomas have a more benign nature, and may be
less likely to require intervention.
•• However, conservative management of acoustic schwannomas requires
long-term clinical and radiological follow-up.
•• The irregular behaviour of the tumour underlines the importance of
monitoring with MRI at least once a year.
Surgery
•• There are mainly three operative approaches to the IAM and the acoustic
neuroma.
–– The lateral suboccipital approach (the retrosigmoid transmeatal ap-
proach).
–– The translabyrinthine approach.
–– The middle fossa approach.
•• Other approaches which have been utilised for the removal of acoustic
neuromas include:
–– The retrolabyrinthine approach.
–– The transcanal approach.
–– The suboccipital–translabyrinthine approach.
–– The subtemporal transtentorial approach.
The Middle Fossa Approach
•• This was developed by WF House.
•• It offers several advantages for the removal of small laterally placed
acoustic neuromas:
–– Dissection is mainly extradural and therefore morbidity is less
–– As the lateral end of the IAM is exposed, total removal of the tumour
is assured
–– Early identification of the facial nerve at the lateral end of the IAC and
exposure of the labyrinthine and upper tympanic segments of the
nerve facilities preservation of the facial nerve
–– It enables hearing preservation, especially for tumours arising from the
superior vestibular nerve
–– In a small group of patients with NF-II it helps decompress the IAC.
•• The disadvantages of this approach are:
–– The facial nerve is in the field and the surgeon must work beyond the
nerve to remove the tumour
–– Post-operative unsteadiness is encountered due to partial preservation
of vestibular function
–– Limited access to the posterior fossa, especially if there is bleeding
at surgery.
•• The complications seen with this approach include:
–– Epidural haematoma which may occur early in the post-operative period.
1197
–– Complications as in other procedures, e.g. meningitis, injury to the

temporal lobe, hearing loss and facial nerve paresis.
•• The prerequisites for hearing conservation in the middle fossa approach
include:
–– Speech discrimination score of greater than 50%, with a speech recep-
tion threshold of less than 50 db
–– Presence of an intracanalicular tumour.
The Translabyrinthine Approach
•• The advantages of this approach are:
–– Short distance between the surface and the tumour
–– Absence of significant cerebellar and brainstem retraction
–– Access to the anterior surface of the brainstem
–– Early identification of the facial nerve
–– Ability to repair the facial nerve during the primary procedure itself
–– Easy access to the operative site for the management of post-opera-
tive complications.
•• The disadvantages of the approach are:
–– Total deafness on the operated side
–– Reduced exposure of the tumour
–– Increased incidence of post-operative CSF leaks.
•• Contraindications for this approach are:
–– Middle ear infection
–– A perforation of the tympanic membrane should be ruled out before
surgery
–– In patients with externalised mastoid cavities, obliteration with closure
of the external auditory canal should be carried out before surgery.
•• Complications which are seen in this approach include:
–– Vascular injury: The most important and potentially fatal injury is one
to the AICA. The possibility of damage to the sigmoid sinus and the
jugular bulb during the drilling of bone should be borne in mind
–– Injury to the facial nerve with loss of continuity is not uncommon. Direct
repair or use of an interposition cable graft at the same sitting is the
treatment of choice
–– Haematoma in the operative bed is a serious complication. Evacuation
can be performed at the bedside, if necessary, when this approach is
used.
–– CSF leak is the most common complication with this approach and
may lead to meningitis.
The Retromastoid Suboccipital Approach
•• The advantages of the suboccipital approach include:
–– Good exposure of the tumour
–– Direct visualisation of the major vessels in the cerebellopontine angle
–– Possibility of preserving facial and cochlear nerve function
–– Familiarity among neurosurgeons.
•• The disadvantages of the approach include:
–– Incomplete exposure of the contents of the IAC
–– Risks associated with an intracranial procedure.
The Retrolabyrinthine Approach
•• The concept of the procedure is to allow exposure of the CPA anterior
to the sigmoid sinus, thus reducing the necessity of cerebellar retraction.
1198
•• Though used mainly for sectioning the sensory root of the trigeminal or
the vestibular nerves, it has also been used occasionally for the removal
of small acoustic neuromas in cases where it was desirable to preserve
hearing.
•• While the major advantage of the procedure is the exposure of the CPA
without significant cerebellar retraction and without sacrifice of hearing,
the limitation is the limited exposure available when the mastoid air space
is small.
The Transcanal Approach
•• This approach exposes the IAC through the external auditory canal using
a post-auricular incision.
•• This approach helped the otologic surgeons to detect very small acoustic
neuromas that may otherwise not be identified.
•• The major disadvantages are the very limited operating space, risk of
damage to the facial nerve and the possibility of CSF leak and meningitis.
The Suboccipital Translabyrinthine Approach

•• Trying to overcome the disadvantages of both the suboccipital and the
translabyrinthine approaches, efforts to combine the two were finally
successful by being able to work on both sides of the sigmoid sinus, the
surgeon gets a wider operative field and better control of the anterior and
posterior extents of the exposure.
The Subtemporal Transtentorial Approach
•• It is an intradural subtemporal approach, and sectioning of the tentorium 1
cm behind the petrosal sinus brings the tumour into view.
•• There is no need for cerebellar retraction.
•• However, there is a risk of temporal lobe injury due to retraction and small
tumours which are mainly intracanalicular cannot be reached via this
approach.
•• This approach is also not suitable if the tumour extends more inferiorly
than superiorly.
Endoscopy
•• The adjunctive use of endoscopy offers some advantages including
improved visualisation, more complete tumour removal, and a lowered
risk of CSF leakage.
•• Tumours removed via 1.5 cm “keyhole” retrosigmoid craniotomies.
Post-operative Complications
•• The incidence of post-operative complications depends on numerous
variables including the size of the tumour and the clinical condition of the
patient, the approach used and the experience of the anaesthetic and
surgical teams.
•• The complications seen include the following:
–– Mortality: With the use of microsurgical techniques in acoustic neu-
roma surgery, peri-operative mortality varies between 0% and 3%.
The causes of death vary and are related to the size of the tumour,
thrombosis of the AICA, post-operative haematomas and respiratory
and cardiac problems.
1199
–– Haematoma: Haematoma in the tumour bed, in the immediate

post-operative period, is a devastating complication. Post-operative
deterioration in sensorium can also be caused by a supratentorial sub-
dural haematoma, due to the sudden decompression and rupture of
bridging veins, especially when the ventricles are large pre-operatively.
–– Pneumocephalus: Tension pneumocephalus is a complication which
occurs when the surgery is performed in the sitting position, though it
may rarely occur even after surgery in the lateral position. If the amount
of air, assessed by plain X-rays of the skull or by a CT scan is thought
to be significant it can be evacuated via a frontal twist drill hole through
a water seal.
–– Hydrocephalus may become acutely symptomatic in the post-oper-
ative period, with a presentation that is difficult to differentiate from
intracranial haematomas. If the CT scan confirms this, the problem
may temporarily be managed with a ventriculostomy. If hydrocephalus
persists a CSF diversion procedure may be performed.
–– Cranial neuropathies:
¾¾ A common sequel of total extirpation of an acoustic neuroma is
injury to the facial nerve.
¾¾ The larger the tumour, the less are the chances of saving the nerve.
¾¾ Where anatomical continuity of the nerve is preserved, the patients
are followed up with physiotherapy to watch for improvement in
function.
¾¾ Electroneurography may be helpful in deciding on the possibility of
post-operative recovery of function.
¾¾ Incomplete degeneration is a good predictor of early recovery and
carries a good prognosis.
¾¾ When the facial nerve is cut at surgery, either intentionally or other-
wise, there are several choices for repair.
¾¾ The continuity of the nerve can be restored during surgery by pri-
mary suturing or by gluing the severed ends.
¾¾ If necessary, a cable graft may be used to bridge the gap between
the ends of the nerve.
¾¾ Intra-operative restoration usually results in moderate facial sym-
metry and movement. Typically, the facial appearance is better at
rest.
¾¾ If the proximal stump of the facial nerve is not adequate, proce-
dures to reanimate the facial muscles may be undertaken. These
include peripheral nerve procedures (e.g. cross facial nerve graft-
ing, nerve transfers), dynamic muscle reconstruction procedures
(e.g. local and distant muscle transfers) and static procedures (e.g.
canthoplasty, facial and dermal slings).
¾¾ The nerves used for anastomosis include the hypoglossal nerve,
the spinal accessory nerve, the phrenic nerve and the glos-
sopharyngeal nerve.
¾¾ The trigeminal nerve is usually in contact with even medium-sized
tumours, and is stretched by large masses. Post-operative de-
creased corneal sensation with the risk of developing exposure
keratitis and ulceration, especially with a simultaneous facial pare-
sis. This can be conservatively managed with protection of the eye
with spectacles, moisturising drops or artificial tears during the day
1200
and ointment at night, as long as improvement of facial function

is expected. If no return of facial function is anticipated, a lateral
tarsorrhaphy should be done, especially if the impaired sensation
also persists.
¾¾ Impaired function of the glossopharyngeal and vagus nerves may
be seen after excision of large tumours, with resultant difficulty in
swallowing, nasal regurgitation and risk of aspiration pneumonitis.
The paresis is usually transient and feeding may be done through
a nasogastric tube until recovery.
–– Cerebellar dysfunction: Signs of cerebellar dysfunction are seen in
cases where marked retraction of the cerebellum is necessary when
dealing with large tumours. Severe and prolonged cerebellar dysfunc-
tion may also result from undue traction and contusion of the cerebellar
peduncles.
–– Brainstem: Damage to the pons is the leading cause of mortality in
acoustic neuroma surgery. This can occur due to damage to the AICA,
which can result in varying degrees of brainstem infarction as well as
infarction and swelling of the cerebellum.
–– Infection:
¾¾ CSF leak can occur from the wound, or can be in the form of otor-
rhoea or paradoxical rhinorrhoea.
¾¾ This is the single most common complication, other than VII nerve
dysfunction with the translabyrinthine or suboccipital-transmeatal
approaches.
¾¾ Prevention consists mainly in ensuring a water tight dural closure,
either primarily or with a graft, and of thoroughly occluding any
opened mastoid air cells with bone wax, free fat, muscle, fibrin
glue, etc.
¾¾ Once the leak via the air cells occurs, a lumbar subarachnoid drain
may be placed and CSF drained for 3–4 days to enable the leak to
seal off. If this does not work, the wound has to be reopened and
the site of the leak repacked.
Facial Nerve Preservation
•• House and Brackmann devised a grading system to evaluate facial nerve
function and this is now used universally (Table 3).
•• When considering each operative approach individually, the facial nerve
was preserved most (97.6%) when the middle fossa approach was used.
This could be expected as these tumours were very small and mainly
intracanalicular.
•• The facial nerve was preserved in 72.8% of patients where the suboccipital
approach was used and in 74.9% when the translabyrinthine approach
was used.
•• Anatomical continuity of the nerve, however, does not imply good functional
outcome.
•• The status of facial nerve function should be assessed periodically as
what appears as reasonably good in the immediate post-operative period
may worsen even to a complete paralysis within 48 hours post-operative.
•• The speed of recovery of facial nerve function is variable.
•• It is, therefore, important that patients with a paralysed face have either a
tarsorrhaphy or some other procedure to protect the eye.
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Table 3: Clinical grading of facial nerve function by House and Brackmann

Grade Description Detailed description
1. Normal Normal facial function in all areas
2. Mild dysfunction • Gross: slight weakness noticeable on close in-
spection; may have very slight synkinesis
• At rest: normal symmetry and tone
• Motion:
–– Forehead: slight to moderate movement
–– Eye: complete closure with effort
–– Mouth: slight asymmetry
3. Moderate dysfunction • Gross: obvious but not disfiguring asymmetry;
noticeable but not severe synkinesis
• Motion:
–– Forehead: slight to moderate movement
–– Eye: complete closure with effort
–– Mouth: slightly weak with maximal effort
4. Moderate to severe dysfunction • Gross: obvious weakness and/or asymmetry
• Motion:
–– Forehead: note
–– Eye: incomplete closure
–– Mouth: asymmetry with maximum effort
5. Severe dysfunction • Gross: only barely perceptible motion
• At rest: asymmetry
• Motion:
–– Forehead: none
–– Eye: incomplete closure
6. Total paralysis No movement
•• Facial nerve weakness that is evident immediately after acoustic neuroma

surgery is caused by a number of possible mechanisms.
•• The most common cause of post-operative facial nerve palsy is direct
trauma or nerve stretching during surgery.
•• Both neuropraxia and axonotmesis are reversible phenomena and facial
nerve function should fully return. Very large tumours place the nerve
under greater tension, which increases the likelihood of stretch injury and
may explain the high rate of facial palsy seen in patients with tumours
larger than 4 cm.
•• Another common mechanism of facial nerve injury is compromise of the
vascular supply to the facial nerve. The facial nerve is supplied by three
separate vascular systems:
–– The labyrinthine artery of the AICA
–– The greater superficial petrosal branch of the middle meningeal artery
–– The stylomastoid artery of the external carotid system.
1202
•• Thermal injury can also cause temporary facial nerve palsy or paralysis.
Overly cold irrigation may “stun” the nerve and is avoidable with use of
warmed saline solutions. Thermal injury can be more permanent if the
laser is used for tumour extirpation.
Hearing Preservation
•• An attempt at hearing preservation may result in the compromise of gross
total removal of the tumour and a subsequent increased risk of recurrence
and post-operative morbidity and mortality.
•• However, the most commonly used criteria are a speech reception threshold
of less than 50 db and a speech discrimination score of more than 50%.
•• The idea to preserve hearing in patients with a unilateral acoustic neuroma
is to provide binaural hearing. This enables the individual to perceive
stereophonic sound, allows him or her to localise the sound and to suppress
background noise.
•• Hearing preservation will, therefore, be useful only to those patients in
whom the hearing can be aided with a hearing aid. An aidable ear is one
that has a pure tone audiometry average of at least 70 db and a speech
discrimination score of 70% with a normal dynamic range.
•• The suboccipital approach and the middle cranial fossa approach are used
in hearing preservation surgery.
•• Intra-operative monitoring is extremely useful when hearing preservation
is attempted. Brainstem auditory evoked potential (BAEP) and
electrocochleography, when used together, monitor the entire auditory
system.
•• A syndrome of delayed post-operative hearing loss has been described,
where patients who have initial hearing preservation gradually lose
hearing in the post-operative period. The cause of this deterioration is not
known. It is postulated that the post-operative deterioration may be due
to a combination of the effects of cerebellar retraction, disturbances in the
microcirculation in the vasa nervorum during mechanical manipulation of
the cochlear nerve, or an increased permeability of the endoneural vessels
after mechanical compression trauma.
Radiosurgery
•• Despite major advances in skull base surgery and microsurgical techniques,
surgery for acoustic schwannoma carries a risk of complications.
•• Some are inherent to general anaesthesia and surgery of any type and
include myocardial infarction, pneumonia, pulmonary embolism and
infection.
•• Some are specific to neurosurgery in this area of the brain, and include
hydrocephalus, CSF leak, facial nerve paralysis, facial numbness, hearing
loss, ataxia, dysphagia and major stroke.
•• Radiosurgery provides an outpatient, non-invasive alternative for the
treatment of small acoustic schwannomas.
•• Initially radiosurgery was undertaken in “high-risk” patients including the
elderly, those with severe medical comorbidities and those in whom tumour
recurred after surgery.
•• Radiosurgery is well suited for acoustic neuromas as it is typically well
demarcated from surrounding tissues on neuroimaging studies.
1203
•• The sharp borders of this non-invasive tumour makes it a convenient match

for the characteristically steep dose gradient produced at the boundary of
a radiosurgical target, allowing the radiosurgeon to minimise the radiation
affecting the normal tissue.
•• Excellent spatial resolution on gadolinium-enhanced MR images facilitates
radiosurgical dose planning.
•• Certainly, the role of radiosurgery is limited by its inability to expeditiously
relieve mass effect in patients for whom this is necessary.
•• The radiobiological nature of SRS also requires lower, potentially less
effective doses for higher target volumes to avoid complications. This limits
the use of SRS to the treatment of smaller tumours.
Fractionated Stereotactic Radiotherapy

•• “Fractionated stereotactic radiotherapy” employs administration of multiple-
session treatments by fractionation of radiation dose, in an attempt to
reduce complications, especially hearing loss.
•• The gamma knife technique involved a fixed-frame, multiple-shot, high-
conformality single treatment, whereas the LINAC technique involved
daily conventional fraction treatments involving a relocatable frame, fewer
isocentres, and lower conformality.
•• Long-term outcome studies proving the efficacy of fractionated radiosurgery
is awaited, and at present, only SRS administered as a single shot is
accepted as one of the primary treatment options for lesions smaller than
3 cm. They are also being increasingly used for residual lesions.
CYSTIC VESTIBULAR SCHWANNOMA

•• The incidence of cyst formation in acoustic schwannomas ranges from
4 to 48%.
•• Cystic acoustic schwannomas are believed to be associated with sudden
expansion, shorter symptom duration, atypical initial symptoms (such as
dysgeusia, vertigo, facial pain and unsteadiness) and an increased rate of
pre-operative facial palsy.
•• This type of acoustic schwannoma rarely demonstrates enlargement of the
IAC in neuroimaging findings despite increased tumour size.
•• The observation that the rate of cell proliferation, expressed as the
number of Ki 67–positive nuclei, was lower in cystic than in solid acoustic
schwannomas indicates that the increase in volume is caused by cyst
formation and not by genuine tumour growth.
•• It is known that the cystic portion of acoustic schwannomas is located in
the Antoni type B area, which is softer than the type A area.
•• The cyst formation in acoustic schwannomas is generally regarded as
resulting from degenerative changes. Other pathogeneses, such as
intratumoural haemorrhage, necrosis and secretion could also be involved
in the mechanism of cyst formation.
•• Fluid accumulation due to a direct osmotic effect or the extravasation
of serum proteins from an impaired blood-tumour barrier augments cyst
enlargement.
•• The possibility of haemorrhage in acoustic schwannomas is well known
and even massive intratumoural haemorrhage occurs. Histological features
of haemosiderin-laden macrophages, haemosiderin deposits and thrombotic
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vessels are frequently observed in cystic tumours. The factor that triggers the
haemorrhagic tendency is unknown.
•• Surgical treatment of cystic tumours is favoured over radiosurgery, but
cyst formation is still predictive of a worse surgical outcome compared
with solid tumours.
•• The “wait and scan” policy is not generally recommended, because
the expanding cyst elements cause displacement of the brainstem and
compression of the fourth ventricle, resulting in hydrocephalus.
•• Even though the operation in the case of a cystic tumour may appear to be
easier and faster in terms of the initial debulking than in a solid tumour there
is a higher risk of accidental lesions of the facial nerve, mainly because of
adhesion of the cyst to the surrounding structures.
BILATERAL ACOUSTIC NEUROFIBROMAS

•• Bilateral acoustic neurofibromas are uncommon, when compared to
unilateral neuromas, with the ratio varying from 1:10 to 1:50.
•• While bilateral acoustic neuromas are Schwann cell tumours which cannot
be distinguished histologically from unilateral Schwann cell tumours, at
surgery these tumours present as multilobulated masses engulfing the
facial and the cochlear nerves.
•• Studies with G-6-PD suggest a multicentric origin for these tumours.
•• Though hearing has been preserved in a few cases there is a high risk of
hearing loss and facial paresis after surgery for these tumours.
•• Large tumours showing signs of brainstem compression, hearing loss and
facial paresis should be operated upon.
•• There is a definite role for observation and follow-up in cases where the
tumours are small and the clinical condition is stable.
•• Even intratumoural decompression can result in loss of hearing and facial
function.
•• Occasionally, decompression of the bony IAC and limited tumour decom-
pression with use of intra-operative BAEP may help preserve hearing.
•• Radiosurgery is a useful option in small tumours.
•• With large tumours requiring surgery, the side with the larger tumour
should be operated on first, so that pressure on the brainstem is relieved.
The tumour on the opposite side is removed at a second sitting once the
patient recovers from the first surgery.
•• A major problem exists in the decision regarding when and whether to
operate on the side of the remaining hearing ear when hearing has been
lost on the other side, particularly when the remaining tumour is small
and not immediately incapacitating. Though some authors advocate an
early proactive strategy in order to preserve hearing, classically, only
symptomatic lesions are to be treated.
•• When treatment is advisable, surgery remains the treatment of choice for
tumours and an auditory brainstem implant (ABI) must be considered for
hearing rehabilitation.
159
CHAPTER
Trigeminal Schwannomas
BS Sharma  Ramdurg S  Sarat Chandra P
INTRODUCTION
•• Schwannomas (also known as neuromas, neurilemmomas, neurinomas
and Schwann cell tumours) are benign, slow growing nerve sheath tumours
composed of Schwann cells, which normally produce the insulating myelin
sheath covering peripheral nerves.
•• The tumour cells lie outside of the nerve, thereby causing compression.
•• Intracranial schwannomas arise most commonly from the vestibular nerves
but can involve any of the other cranial nerves.
•• Schwannomas of the trigeminal nerve are uncommon accounting for 0.07–
0.36% of all intracranial tumours and 0.8–8% of intracranial schwannomas.
•• The first successful removal was documented by Frazier in 1918.
SURGICAL ANATOMY
•• The trigeminal nerve emerges from the ventrolateral surface of the pons
and runs anteriorly 1–2 cm through the cerebellopontine cistern to reach
the petrous apex.
•• Vascular structures, such as the petrosal vein and the superior cerebellar
artery lie close to the trigeminal nerve.
•• Over the petrous apex, 7 mm from the medial lip of the internal acoustic
meatus, the Gasserian ganglion is enveloped by a dural deflection forming
Meckel’s cave, lateral to the cavernous sinus and the carotid artery.
•• As it leaves Meckel’s cave, the trigeminal nerve divides into three branches:
(1) Ophthalmic (V1), (2) Maxillary (V2), and (3) Mandibular (V3) branches.
•• These three nerves run under the middle fossa dura mater and leave the
temporal bone through the lateral wall of the cavernous sinus (for V1),
foramen rotundum (for V2), and foramen ovale (for V3).
•• The trigeminal nerve can also be surgically classified into three segments:
(1) Cisternal, from the brainstem to the petrous apex; (2) Intracranial-
extradural, from Meckel’s cave to the foramina, and (3) Extracranial
(V1, V2, and V3).
•• Functionally, the trigeminal nerve has two portions: (1) The “pars compacta”,
which constitutes the triangular portion and comprises the primary afferent
fibres that are responsible for sensations of the face; and (2) The motor
root, which carries the branchiomotor fibres to the muscles of mastication.
•• The motor root runs practically separated from the “pars compacta” but runs
together with the cranial portion of the nerve. At the level of Meckel’s cave,
it is oriented medially and leaves the skull together with the maxillary nerve.
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•• The intracranial-extradural portions of V2 and V3 are surgically identified,

using the foramen spinosum as an anatomical landmark, which is located
in the sphenoid bone and contains the middle meningeal artery.
•• The foramina ovale and rotundum are located 2–5 mm superoanteriorly
and 10–12 mm superomedially to the foramen spinosum, respectively.
SURGICAL PATHOLOGY
•• Tumours arising from the Gasserian ganglion usually compress the
ganglion, which is visualised after tumour removal. The nerve fibres usually
are stretched over the tumour, although a few fibres may course through
the tumour.
•• Microscopically they are composed of Antoni A and Antoni B regions.
•• Antoni A regions are characterised by bipolar cells, which are arranged
in compact interlacing fascicles. The nuclei line up in palisades with
intervening nuclear zones called verocay bodies.
•• A looser arrangement of cells, with poorly arranged vacuolated cells with
pyknotic nuclei may be seen in Antoni B regions.
•• These regions may represent degenerative changes.
•• Cystic changes, hyalinised blood vessels, thrombosis and haemosiderin
deposition may often be seen.
•• Immunohistochemically, these tumours are positive for S-100 protein.
They occasionally are positive for Leu-7 and glial fibrillary acidic protein.
•• Trigeminal schwannomas present most commonly in the third to fifth
decades of life.
•• The tumours affect women slightly more frequently than men.
•• The clinical presentation of trigeminal neurinomas depends on the site of
origin of the tumour and the growth pattern.
•• Jefferson divided these tumours into four groups depending on their
anatomical location:
Type I Posterior fossa (root type)
Type II Combined posterior fossa–middle fossa (dumb-bell type)
Type III Middle fossa (ganglion type), and
Type IV Peripheral (division type)
•• Samii et al. classified tumour extension into four categories based on
radiological findings:
Type A Intracranial tumour predominantly in the middle fossa
Type B Intracranial tumour predominantly in the posterior fossa
Type C Intracranial dumb-bell shaped tumour in the middle and
posterior fossa, and
Type D Extra cranial tumour with intracranial extensions
•• Cranial nerve involvement is the most common presenting symptom.
Trigeminal nerve dysfunction is observed in more than 70% of cases.
•• Facial hypoaesthesia is a much more common symptom, as compared
to pain.
•• Classical trigeminal neuralgia is a rare initial symptom.
•• Tumours arising from the ganglion usually produce constant pain, in
contrast to tumours arising in the root, in which pain is frequently absent.
•• The sensory disturbance may involve either one of the divisions or more
frequently all the three divisions to a variable degree.
Chapter 159 • Trigeminal Schwannomas
1207
•• It is important to differentiate the sensory loss on the face due to root

involvement, which may occur in V nerve schwannomas from that occurring
due to high cervical intramedullary tumours.
•• Usually, Vth nerve hypoaesthesia due to intramedullary pathologies lead
to sensory loss starting from the periphery of the face and extending to
the centre (like the French ‘balaclava helmet’) and is more commonly
associated with dissociated sensory loss.
•• In contrast to this, root involvement specifically involves the separate
divisions (V1/V2/V3) of the face. Wasting of muscles of mastication is
another important sign of V nerve involvement and is likely to be due to a
tumour like schwannoma.
•• Abducens nerve paresis is the next common symptom, closely followed by
involvement of the VIIth–VIIIth nerve complex.
•• Less than 10% of patients have lower cranial nerve involvement.
•• The IIIrd, IVth and VIth nerve can be involved by the tumour. If the tumour
extends to the middle fossa, it may cause exophthalmos.
•• Visual loss can be either due to neuronal compression or raised intracranial
pressure.
•• Large tumours tend to present with features of raised intracranial pressure
with headache, vomiting and failing vision.
•• They may also rarely present with pathological laughter and crying.
Radiological Diagnosis
Plain X-Rays
•• Conventional X-rays demonstrate bony erosion of the petrous apex.
•• The margins are smooth without sclerosis differentiating primary or
secondary bony tumours of the region.
•• Larger tumours with middle fossa extensions may demonstrate erosion of
the sella turcica, clinoid process and widening of the superior orbital fissure.
•• Tumours with a large posterior fossa component cause erosion of the
inferomedial aspect of the petrous bone.
•• Sparing of the internal acoustic meatus differentiates these tumours from
acoustic neuromas.
Computed Tomography Scans
•• The tumours are usually seen as iso- to hyperdense lesions with
homogeneous contrast enhancement.
•• Occasional cystic changes may be seen in the tumour.
Magnetic Resonance Imaging (MRI)
•• These tumours appear hypointense on T1W images and hyperintense on
T2W images with intense contrast enhancement.
•• These tumours may show cystic changes with occasional calcification.
•• The extensions of the tumour can be demonstrated well with a contrast
enhanced MRI scan.
•• Small tumours do not demonstrate any change or abnormality in the
vasculature.
•• Larger tumours, however, may show enlarged feeding vessels which are
usually derived from the precavernous and cavernous segments of the
carotid artery.
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•• Displacement of the precavernous ICA is the most commonly seen

abnormality and it may be anterior and inferior displacement. However,
superior and posterior displacement may also be seen.
•• Tumours with a larger posterior fossa component may displace the posterior
cerebral arteries medially and superiorly, while the anterior inferior cerebral
arteries may be pushed downwards with stretching of the basilar artery.
SURGICAL TECHNIQUES
•• The location and size of the tumour dictates the most appropriate approach.
•• They are usually easily separable from the cavernous sinus and the carotid
artery, which facilitates their radical removal.
•• Often, the tumour does not completely destroy the trigeminal nerve and
can be separated from its fascicles, while preserving neurological function.
•• Complete removal of the tumour should be the aim but not at the cost of
neurological function.
•• In elderly or medically unfit patients and with tumours with firm adherence
to the brainstem, cranial nerves or blood vessels, sub-total tumour excision
may still be the optimal treatment.
•• Most of the tumours with a large middle fossa component may be accessed
via the middle fossa approach.
•• The medial part of the petrous may be drilled (Kawase approach) and the
posterior fossa tumour may be now delivered through the enlarged opening.
•• Rarely, a sub-temporal trans-zygomatic or an orbitozygomatic approach
will be required.
•• However, giant tumours are an exception as they may invade the entire
nerve and even the brainstem. Caution must be exercised when reaching
the anterior and the superior part of the tumour, where it may infiltrate the
cavernous sinus densely and brisk bleeding may occur.
•• The following approaches are commonly employed for trigeminal neuromas.
1. Middle Fossa Approach:
– Large tumours can be approached intradurally by opening the
Sylvian fissure and exposing the optic nerve, the internal carotid
artery and the third cranial nerve.
– The lateral wall of cavernous sinus is exposed via a temporopolar
approach and the tumour is removed. The trigeminal fibres are
preserved as much as possible.
– The petrous apex is drilled and the petroclinoid ligament is cut to
expose the posterior fossa portion, allowing complete excision of
the remaining tumour.
2. Retrosigmoid Approach:
– This approach is used for patients with a large posterior fossa
extension and smaller middle fossa component.
– The asterion is exposed to determine the junction of the transverse
and sigmoid sinuses.
– A craniotomy, 4 cm in diameter, is performed with the superior and
anterior margins bordering the transverse and sigmoid sinuses,
respectively.
– All opened mastoid cells are sealed with bone wax to help prevent
CSF leaks.
Chapter 159 • Trigeminal Schwannomas
1209
3. Presigmoid Approach:
– Two burr holes are placed anteriorly and two are placed posteriorly
at the intersection of the transverse and sigmoid sinuses.
– The temporal and retromastoid dura mater is exposed through a
craniotomy.
– Mastoidectomy is performed with preservation of the labyrinth and
the facial nerve canal.
– The superior petrosal sinus is then ligated and transected.
– The tumour is identified and the VIIth and VIIIth cranial nerves are
usually displaced inferiorly.
– The tumour within the cavernous sinus is removed after opening its
lateral wall.
POST-OPERATIVE COURSE
•• Transient cranial nerve deficits are common in the early post-operative
period.
•• Abnormalities of trigeminal nerve, either new, or worsening of existing
deficits may be seen, which may be permanent. This may be in the form
of sensory loss or weakness of muscles of mastication.
•• Prevention of corneal opacity may require an early tarsorraphy.
ROLE OF RADIOSURGERY
•• Smaller tumours or residual tumours may be subjected to stereotactic
radiosurgery.
•• Gamma knife therapy using a Leksell Gamma knife with a tumour margin
dose of 12–13 Gy.
•• The mean radiological follow-up was 15.7 months (range 6–37 months)
and there was a tumour growth control rate of 85.75%.
160
CHAPTER
Jugular Foramen Lesions
Siddhartha Ghosh
INTRODUCTION
•• Jugular foramen (JF) lesions, once thought to be one of the most surgically
unapproachable ones, are now becoming safely manageable with
reasonable morbidity and mortality rates.
•• The highly complex nature of the jugular foramen and the morphological
organisation of its surrounding neurovascular structures, coupled with the
plethora of pathological conditions in this region, still pose a major challenge
to the neurosurgeon.
•• The jugular foramen is located at the posterolateral skull base with its long
axis obliquely directed in the posterolateral to anteromedial direction. It is
formed by the petrous temporal bone anterolaterally and by the jugular
process of the condylar part of the occipital bone posteromedially.
•• It is configured around the sigmoid sinus and the inferior petrosal sinus.
•• On the intracranial side, the jugular foramen is inferior to the porus acoustics
and superolateral to the intracranial orifice of the hypoglossal canal.
•• On the extracranial side it is located just behind the carotid canal separated
by the carotid ridge, lateral to the anterior half of the occipital condyle,
anteromedial to the stylomastoid foramen and posteromedial to the styloid
process.
•• The jugular foramen is traditionally divided into a large posterolateral
compartment (pars venosa) and a smaller anteromedial compartment
(pars nervosa).
•• Katsuta, et al. divided the jugular foramen into three compartments: two
venous compartments and one neural intrajugular compartment in between.
•• The venous compartments include a large posterolateral sigmoid part and
a small anteromedial petrosal part.
•• At the junction of these two compartments there are two bony prominences
(intrajugular processes), arising from the temporal and occipital bones,
joined by a fibrous or less commonly osseous bridge forming the intrajugular
septum.
•• The relationships between the lower cranial nerves (IX−XII) and the major
vessels [internal carotid artery (ICA), internal jugular vein (IJV), external
carotid artery (ECA) and branches of vertebral artery (VA)], are extremely
complex at the level of the JF and in the upper neck.
Chapter 160 • Jugular Foramen Lesions
1211
PATHOLOGY
•• Owing to the presence of osseous, muscular, neural, vascular, dural and
connective tissue elements in the jugular foramen region, a variety of lesions
arising from these elements are encountered in this region and some are
more common than others.
•• Table 1 lists the lesions involving the jugular foramen region.
•• They are broadly classified into intrinsic and extrinsic or neoplastic and
non-neoplastic.
•• Since the choice of the surgical approach is dependent on the site of
origin, size and extent of the lesion, attempts were made to classify these
lesions into various types or classes, for example, Fisch’s and Glasscock
and Jacobson’s classification for glomus jugular tumours and Keye’s and
Franklin’s classification for schwannoma.
•• The classification proposed by Bertalanffy and Ulrich is applicable to any
type of lesion, which is as follows:
Type I: Small lesions confined to the jugular foramen.
Table 1: Pathological lesions around the jugular foramen

Neoplastic Non-neoplastic
Common
Paraganglioma Internal jugular vein thrombosis
Schwannoma Large jugular bulb (pseudomass)
(included because of radiological importance)
Meningioma
Metastasis (haematogenous,
nasopharyngeal, carcinoma)
Uncommon
Exophytic brainstem glioma Aneurysm
Chondroma Osteomyelitis
Chondroblastoma Malignant external otitis
Chondrosarcoma Cholesterol granuloma
Chondromyxoid fibroma Amyloidoma
Osteoblastoma
Plasmacytoma
Chordoma
Haemangiopericytoma
Haemangioblastoma
Choroid plexus papilloma
Cavernoma
Rhabdomyosarcoma
Carcinoma of tympanic cavity
Neurenteric cyst
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Type II: Intrinsic lesions of lower brainstem located in the vicinity of the
jugular foramen.
Type III: Lesions of the jugular foramen with predominant intradural
extension located above the level of foramen magnum.
Type IV: Lesions of the jugular foramen with intradural extension beyond
the level of foramen magnum into the spinal canal.
Type V: Lesions of the jugular foramen with intradural and extradural
extension into the petrous bone.
Type VI: Lesions of the jugular foramen with predominant extradural
extension.
CLINICAL MANIFESTATIONS
•• The clinical presentation of jugular foramen lesions is dependent on the
size, extent and pathology of the tumour.
•• Typically, they produce the jugular foramen syndrome (Vernet’s syndrome)
and depending on their extension produce other related syndromes
(Table 2).
•• Patients with IX, X, and XI cranial nerves dysfunction may present with
dysphagia, dysarthria, hoarseness of voice, dysphonia, nasal regurgitation,
ipsilateral trapezius, and sternomastoid muscle weakness and atrophy,
depressed gag reflex, palatal droop on the affected side with ipsilateral
vocal cord paralysis and loss of taste on the posterior 1/3rd of the tongue,
paresis of the soft palate, uvula, pharynx and larynx.
•• The anterior extension encasing the cavernous sinus and internal carotid
artery may produce Horner’s syndrome and III, IV, V, and VI nerve palsy.
•• Intracranial extension can produce posterior fossa symptoms, such as
nystagmus, ataxia, hemiparesis and increased intracranial pressure.
•• Extracranial extension along the internal jugular vein can produce a visible
mass in the oropharynx or a palpable mass in the neck.
Table 2: The jugular foramen and related syndromes

Syndrome Cranial nerves Site of involvement
Vernet’s syndrome IX, X XI Lesions in jugular foramen
Collet-Sicard syndrome IX, X, XI, XII Lesions in retroparotid space
Vallaret’s syndrome IX, X, XI, XII Retropharyngeal extension
Sympathetic chain
Schmidt’s syndrome Occasionally VII Intradural extension
Avellis syndrome X, XI Intradural extension,
XI (accessory to X) Occasionally inferior margin of JF
Jackson’s syndrome X, XI, XII Intracranial extension before the
nerves leave the skull base
Tapia syndrome X, XII, occasionally Lesions high in the neck
Cerebellopontine angle XI, sympathetic chain Extension into CP angle
Syndrome VII, VIII, V
Garcin’s hemibase All cranial nerves on one Infiltrative nasopharyngeal
syndrome side (often incomplete) carcinoma
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•• Intraluminal growth can block venous drainage and occlude the sigmoid
sinus and, if present bilaterally, increased intracranial pressure can occur.
•• Intracranial extension superiorly can produce the cerebellopontine angle
syndrome (deafness, tinnitus, VII nerve palsy) and those extending still
laterally can produce bloody otorrhoea, a visible mass through the tympanic
membrane and a bruit may be heard over the mastoid.
NEUROIMAGING
•• Plain and contrast CT scan of the brain with 1.5 mm cuts, bone window
algorithm and coronal cuts help to reveal normal bony variations and the
pathological bony involvement at the site of the jugular foramen and extension
into the nearby osseous structures, and also the type of involvement, either
expansile (compressive) or invasive (destructive) enlargement. The presence
of obstructive hydrocephalus is also visualised.
•• MRI images are extremely useful in delineating the exact location, origin,
size, limits, margins, vascularity and extent of the lesion, degree of
involvement of the important neurovascular structures and also to some
extent the pathological diagnosis.
•• For the pathological diagnosis a dynamic, high dose Gd-study with creation
of time intensity curves is found to be particularly useful.
•• With this technique, glomus jugulare tumours can be differentiated from
schwannomas, meningiomas and metastases.
•• MRI venography is highly predictive in differentiating pseudomas (large
and high lying jugular bulb) from the pathological lesions.
•• Octreotide scintigraphy, if available, is helpful in the diagnosis of multifocal
paragangliomas since these tumours more than 1.5 cm in size take up the
radioisotope.
•• Finally bilateral cerebral angiography with cross-compression or balloon
occlusion test will demonstrate enlarged feeding arteries, degree of
vascularity, dominance and pathology of sigmoid sinus, jugular bulb and
internal carotid artery. If the tumour is highly vascular, then a preoperative
super-selective endovascular embolisation can also be undertaken to assist
its safe surgical removal.
SURGICAL APPROACHES
•• The surgical approaches used for JF lesions, although not always directed
primarily to the jugular foramen, include the suboccipital retrosigmoid,
presigmoid and trans-sigmoid, retrolabyrinthine and translabyrinthine,
transcochlear and subcochlear, trans-supra and juxtacondylar, far lateral
suboccipital, lateral skull base, infratemporal fossa and middle cranial
fossa approaches.
•• These approaches can broadly be grouped into posterior, lateral, anterior,
superior and inferior approaches and further subdivided into limited,
extended and combined approaches.
•• In general, the limited approaches are useful for small lesions and extended
and combined approaches for the larger lesions.
•• The latter two approaches are not suitable when used alone for JF lesions
but definitely require to be combined with other approaches to deal with
inferior, anterosuperior and medial extensions of the JF lesions.
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Major Groups
Posterior (through Suboccipital retrosigmoid
posterior cranial fossa) transcondylar, supracondylar approaches
Lateral (through mastoid) Lateral skull base, juxtacondylar approaches
Anterior Preauricular subtemporal infratemporal
Superior Middle fossa approaches
Inferior Neck dissection
Lateral Approaches
•• The classification is shown in Table 3.
•• These are the most commonly used access routes for jugular foramen
lesions having large extracranial extensions.
•• The exposure can be widened anteriorly by sacrificing the external auditory
canal and middle ear structures or medially by drilling away the otic capsule
(translabyrinthine) or cochlea (transcochlear).
•• When combined with upper neck dissection, it provides a satisfactory
exposure of the JF, mastoid air cells, tympanic cavity and extracranial
structures.
•• The removal of the styloid process with transposition of VII nerve facilitates
wide opening of the extracranial orifice or JF and provides access to the
lower part of the petrous portion of the ICA.
Table 3: Classification of lateral approaches

Juxtacondylar
LATERAL APPROACHES
Lateral skull base
Approaches conserving otic Approaches sacrificing otic capsule

capsule (extra-labyrinthine) 1. Translabyrinthine
2. Transcochlear
– Original
– Transotic
– Modified types A–D
1. Passing above otic capsule
(supralabyrinthine):
a. Middle cranial fossa
b. Extended middle cranial fossa
c. Middle fossa transpetrous
2. Passing behind the otic capsule (retrolabyrinthine):
a. Retrosigmoid
b. Retrolabyrinthine
c. Retrolabyrinthine transtentorial
3. Passing anterior to otic capsule (prelabyrinthine):
a. Infratemporal fossa Types B and C (Fisch’s)
b. Preauricular subtemporal—infratemporal
4. Passing inferior to otic capsule (infralabyrinthine):
a. Approaches to jugular foramen—infratemporal fossa Type A (Fisch’s)
- petro-occipital trans-sigmoid (POTS)
b. Extreme lateral approach
1215
•• Still wider exposure of extracranial tumour is achieved by removing the

transverse process of the atlas or dislocating or resecting the mandibular
condyle.
•• However, these approaches cannot be used for the removal of large intra-
dural extensions, which require a combination of the posterior approaches.
•• These are the most suitable approaches for predominantly intradural lesions
and for lesions extending down to the foramen magnum and medially to
the lower and midclivus.
•• The retrosigmoid approach provides access to the cerebellopontine angle
and the intracranial orifice of the JF.
•• The posterior and posterolateral margin of the JF is approached by
removing a part of the jugular process of the occipital bone behind the JF
and the portion of the mastoid just behind the mastoid segment of the VII
nerve and the stylomastoid foramen.
Anterior Approaches
•• They use the pathway anterior to the external auditory canal and through
the tympanic bone, exposed by removal or displacement of the glenoid
fossa and temporomandibular joint.
•• The subtemporal-infratemporal fossa approach alone can access the
anterior part of the JF after reflecting the petrous portion of the ICA
anteriorly.
•• Further drilling exposes the midline and upper clivus anteriorly.
•• However, more commonly, this approach has to be combined with lateral
approaches to access the anterior extension of the pathology. These
combined procedures are designated by Fisch as infratemporal fossa Type
B and C approaches.
Posterior Approaches
•• Suboccipital retrosigmoid
•• Suboccipital transcondylar
•• Suboccipital supracondylar.
Suboccipital Retrosigmoid Approach
•• The main indications are Type A schwannomas of lower cranial nerves,
epidermoid cyst and acoustic neurinoma extending down into the jugular
foramen.
•• It is technically simple, familiar and associated with few complications and
can be easily combined with other skull base procedures to gain further
exposure.
•• But, it has limited applicability in that, only the intradural portion of the
tumour can be removed and does not allow removal of either intrajugular
pathology or extracranial extensions.
Suboccipital Transcondylar Approach
•• This approach is an extended modification of the retrosigmoid approach
providing more extended lateral and inferior exposure.
•• This is not synonymous with the far lateral approach for the foramen
magnum (FM) lesions, which requires the resection of only the medial
one-third of the occipital condyle.
•• The indications are intrinsic lesions of the lower brainstem up to the
pontomedullary junction, tumours located anterior or anterolaterally to
1216
the lower brainstem, extradural pathology from the lower clivus, occipital
condyle, anterolateral rim of the foramen magnum and jugular process of
the occipital bone and aneurysms of the vertebrobasilar complex.
•• There is a potential risk of injury to the vertebral artery (VA), and the lower
cranial nerves and a risk of craniocervical instability, if the atlanto-occipital
joint is opened.
Supracondylar Approach
•• This is a limited variation of the transcondylar approach and is indicated
for small lesions confined to the hypoglossal canal and to the medial rim
of jugular foramen.
•• The advantage of this approach is the low morbidity and the disadvantage
is that radical excision is not possible and is adequate only for biopsy and
for small intradural lesions confined to the hypoglossal canal.
Juxtacondylar Approach
•• The prime indication is for extradural tumours confined to the jugular
foramen like lower cranial nerve schwannoma, meningioma, etc.
•• It provides a wide exposure of the posterolateral aspect of the jugular
foramen without extensive petrous bone drilling and hence preserves
hearing and VII nerve functions.
•• There is no risk of CSF leak because the dura is usually not opened.
•• It can be combined with a supracondylar exposure, which is mainly indicated
for intradural pathology or with infratemporal fossa approach Type A.
•• But this is a limited exposure of the JF with the potential risk of venous
bleeding around the VA within the foramen transversarium of the atlas.
Petro-occipital Trans-sigmoid (POTS) Approach
•• It is one of the lateral infralabyrinthine skull base approaches primarily
targeting the jugular foramen.
•• It is primarily indicated for jugular foramen lesions especially lower cranial
nerve schwannomas with intracranial extensions, meningioma of the
jugular bulb and some cases of glomus jugulare tumours with predominant
posterior extension.
•• It is also indicated in small petroclival meningiomas lying anterior to the
internal auditory canal (IAC) with preserved hearing.
•• The advantages of this approach are that the middle ear and VII nerve
functions are preserved and it can be combined with the transtentorial
approach for tumours with supratentorial extension or with the translabyrin-
thine approach for tumours involving the IAC in the absence of preoperative
serviceable hearing (and if hearing is preserved then the posterior and
inferior wall of IAC is drilled away without sacrificing the labyrinth) or with
the extreme lateral approach for tumours extending downwards to involve
the CV junction ventral to the brainstem.
•• The disadvantages are that it only provides limited control of the ICA
(dorsal and lateral aspects) and hence extensive involvement of the IAC is
a contraindication for the POTS approach for which either modified trans
cochlear or infratemporal fossa Type A approach is indicated.
•• Injury to the lower cranial nerves and CSF leak are the potential
complications.
•• Also this is not useful in highly vascular and invasive glomus jugulare
tumours for which the infratemporal fossa Type A approach is preferable.
1217
Infratemporal Fossa Approach Type A

•• It is one of the most important combined approaches to jugular foramen
lesions, belonging to the lateral group of approaches.
•• Indications: Jugular foramen lesions, especially large glomus jugulare
tumours, some lower cranial nerve neurinomas and meningiomas and
lesions of infralabyrinthine and apical portion of the petrous temporal bone,
like cholesteatoma, chordoma of lower clivus and carcinomas invading
these regions and extensive facial nerve neurinomas.
•• Advantage: It offers wide exposure anterior to the JF and to the
infratemporal fossa up to the petrous apex.
•• Disadvantage: Apart from hearing loss, facial paralysis and numbness and
malocclusion, this is not suitable for large intracranial tumour extension and
for the large tumours reaching the foramen lacerum or cavernous sinuses.
For this infratemporal fossa, Type B or C (anterior) approaches has to be
combined with this Type A (lateral) approach.
Modifications of Type A Approach
•• The Type B infratemporal fossa approach is mainly designed for extradural
petrous apex and midclival tumours, with preservation of the inner ear
function.
•• It is used in association with the Type A infratemporal fossa approach for
extensive glomus tumours involving the petrous and the midclivus.
•• This involves reflection of the zygomatic arch inferiorly and division of the
middle meningeal artery and mandibular branch of V nerve. This gives
exposure up to the foramen lacerum, petrous apex and clivus.
•• The Type C approach involves an orbitozygomatic reflection, sectioning
of some branches of the facial nerve in the parotid area, resection of the
pterygoid process and sectioning of V3 nerve. This gives wider exposure
to the carotid artery in the cavernous sinus.
Modified Transcochlear Approach
•• One of the lateral skull base approaches provides better visualisation
of the ventral brainstem and vertebrobasilar junction by removing the
petrous apex and clivus and excellent control of the vertical and horizontal
segments of the ICA.
•• It is classified into Types A−D.
•• Type A is the basic approach which, but by itself, provides only limited
access to tumours extending into the jugular bulb and down to the foramen
magnum.
•• It is indicated for extradural lesions involving the petrous apex with VII nerve
and inner ear compromised (e.g. petrous bone cholesteatoma, extensive
VII nerve neurinoma, recurrent VIII nerve neurinoma), intradural recurrent
VIII neurinomas, large petroclival meningiomas and for transdural lesions
invading the petrous bone like residual glomus tumour, chordoma, etc.
POST-OPERATIVE COMPLICATIONS
•• Many of the complications are related to the size, vascularity and extent
of the tumour, choice of the surgical approach, skill of the surgeon and the
preoperative condition of the patient.
•• Some complications (e.g. infarct) that are related to pre-operative
endovascular embolisation can also occur in the post-operative period.
1218
•• In preventing post-operative CSF leak, which is the most frequent

complication, a lumbar drain is preferred to intraventricular drain since the
latter is fraught with the risk of intraventricular haemorrhage, which may
prove fatal.
•• In smaller lesions the post-operative morbidity is minimal and the chance
for long-term improvement is excellent.
•• Another important point is that if lower cranial nerve dysfunction is already
present pre-operatively, the patients will usually be compensated for this
deficit and so an aggressive surgical strategy can be undertaken without
producing any increase in their pre-operative deficit.
161
CHAPTER Other Intracranial
Schwannomas
INTRODUCTION
•• Schwannomas are benign, slow-growing, encapsulated tumours, which
arise from the proliferation of Schwann cells.
•• They constitute about 8% of all brain tumours.
•• Since Schwann cells myelinate all the cranial nerves with the exception of
I and II cranial nerves, schwannomas can potentially originate from any of
the remaining cranial nerves.
•• Cranial nerve schwannomas account for 60% of all the schwannomas.
•• Along the course of the nerve root, the site of origin of these tumours is
at or distal to the Obersteiner-Reidlich zone where the transition between
central and peripheral myelin occurs.
•• The zone of transition is usually within several millimetres of the origin of
the nerve from the brainstem.
•• Schwannomas have a predilection for the sensory cranial nerves.
•• Involvement of motor cranial nerves is commonly associated with
neurofibromatosis.
•• Vestibular schwannomas, with an annual incidence of 1/100,000 of the
general population, comprise 80–90% of all intracranial schwannomas.
•• The non-vestibular schwannomas most commonly involve the V nerve
(40%), followed by the facial (23%) and the lower cranial nerves (LCNs)
(20%).
FACIAL NERVE SCHWANNOMAS

•• Facial nerve schwannomas (FNSs) make up only about 1.9% of all
intracranial neuromas.
•• Although the facial nerve is predominantly motor, association of FNSs with
neurofibromatosis is rare.
•• The FNSs may arise from any segment of the nerve, from the
cerebellopontine angle (CPA) to the extracranial extent of the nerve.
•• Lipkin have classified FNSs according to the site of origin along the VII
nerve into labyrinthine, tympanic, geniculate and vertical segment lesions.
•• The geniculate ganglion and the adjoining labyrinthine segment of the nerve
is considered to be the most common site of origin for facial schwannomas.
•• Large FNSs arising from the geniculate ganglion can present as middle
cranial fossa masses with erosion of the anterior surface of the petrous
bone.
•• Extension along the course of the greater superficial petrosal nerve (GSPN)
may also be seen.
1220
•• These tumours usually occur in the fourth decade, and incidence in both
sexes is similar.
•• The presenting features of FNSs vary according to the facial nerve segment
from which they arise.
•• Slowly progressive facial paresis and hearing deficits are the most common
symptoms of FNSs.
•• Hearing loss may either be conductive or sensorineural depending upon
the location of the tumour.
•• A proximally arising tumour may compromise the vestibulocochlear nerve
while the middle ear cavity may be involved by distally originating FNS.
•• Occasionally, hemifacial spasms evolving into progressive facial weakness
may also be seen with FNS extending within the internal auditory canal
(IAC).
•• Extension of tumour into the middle cranial fossa and early involvement of
the facial nerve by a relatively small sized tumour often provide a clue to
the facial nerve origin of a schwannoma.
•• The diagnosis should be entertained in patients with progressive facial
paresis or worsening of weakness following an incomplete Bell’s palsy.
•• Otorrhoea and ear canal fullness is observed in tumours arising from the
mastoid/vertical segment of the facial nerve.
Diagnosis
•• FNSs appear as round, well-delineated masses in the CPA, IAC or facial
nerve canal.
•• They can extend to the middle cranial fossa, middle ear, the stylomastoid
foramen or parotid gland.
•• Computerised tomography (CT) scan shows an enhancing soft-tissue
density mass. With use of bony algorithm, CT demonstrates a benign type
of expansile, lytic change or remodelling of the bone. Aggressive bony
destruction is not seen.
•• On magnetic resonance imaging (MRI), FNS is mildly hypointense to
isointense on T1-weighted images; is heterogeneously hyperintense on
T2-weighted images and enhances following administration of gadolinium.
•• Heterogeneity or cystic change may also be seen in large FNSs.
•• The FNSs in the CPA or in the IAC may be clinically and radiologically
indistinguishable from acoustic schwannomas, however, eccentricity of
tumour mass to the axis of the IAC may be a diagnostic clue.
Management
•• The timing of intervention in FNS is debatable.
•• Those in favour of early intervention argue that the risk to hearing is less
and chances of preservation of facial nerve function/reconstruction of the
facial nerve is better in patients with mild paresis.
•• Proponents of the “wait and watch” policy, emphasise the slow growing
nature of these tumours with potentially prolonged preservation of facial
nerve function, which has to be weighed against the risk of deterioration
following surgery.
•• Generally, incidentally detected and small sized tumours with mild facial
paresis are managed expectantly.
Chapter 161 • Other Intracranial Schwannomas
1221
•• Microsurgical excision with repair of the facial nerve has traditionally been
recommended as the treatment of choice in symptomatic patients.
•• The main concern is facial nerve palsy following surgical excision of the
schwannoma.
•• End-to-end anastomosis with interposition cable graft and facial-hypoglossal
anastomosis have been used for partial restoration of facial nerve function.
•• However, improvement beyond House-Brackmann grade III has rarely
been seen after postoperative facial palsy.
•• The experience with radiosurgery for FNSs is limited, in part, because of
the rarity of these tumours.
Surgical Approach
•• The approach to these tumours is determined by the location of the tumour.
•• Schwannomas projecting predominantly into the CPA are approached by
the retrosigmoid suboccipital route.
•• Tumours based in the middle fossa are exposed and resected extradurally
via the subtemporal middle fossa approach.
•• Anterior petrosectomy (Kawase’s) may be added to the middle fossa
approach for tumours extending into the posterior fossa.
•• Transpetrous approaches (retrolabyrinthine, translabyrinthine, transcoch-
lear) can be used in patients with complete loss of hearing and tumour
extension into the IAC and middle ear.
•• The transpetrous approach may facilitate anastomotic facial nerve
reconstruction by identification of the proximal end of the facial nerve at
the IAC and the uninvolved mastoid segment.
•• Sural nerve interposition graft is used.
•• Large tumours with extensive middle fossa and posterior fossa extension
often require staged resection by the subtemporal and retrosigmoid routes.
LOWER CRANIAL NERVE SCHWANNOMAS

•• The LCN schwannomas constitute about 2.9–4% of all intracranial
neuromas.
•• They include schwannomas arising from the glossopharyngeal, vagus, and
accessory and hypoglossal nerves.
•• The IX, X and XI cranial nerves arise from the post-olivary sulcus of the
anterior brainstem, traverse the jugular foramen and emerge extracranially
in close relation to the internal jugular vein and the internal carotid artery.
•• The hypoglossal nerve originates by a series of rootlets in the pre-olivary
sulcus anterior to the IX, X and XI nerve rootlets and exits the posterior
skull base through the hypoglossal canal.
•• The schwannomas may arise from the intracisternal, intraforaminal or the
extracranial segment of these cranial nerves.
•• Intracranially, these tumours mainly present as jugular foramen masses.
•• In most cases, the nerve of origin cannot be determined but in cases where
the nerve of origin was recognisable, IX nerve origin was the most common
followed by the X and XI nerve origin.
•• The site of origin of these tumours along the pars nervosa has been
postulated to manifest distinct patterns of tumour growth.
•• On the basis of this, jugular foramen schwannomas have been classified
(Table 1) by Kaye et al with modifications by Pellet et al. and Samii et al.
1222
Table 1: Classification of jugular fossa schwannomas

Class Growth pattern Postulated site Clinical presentation
of origin
A Primary intracranial tumour Proximal, Audiovestibular symptoms
with small extension into the intracisternal pars and ataxia akin to vestibular
bone nervosa schwannoma. Lower cranial
nerve involvement uncommon
B Primary tumour in the jugular Intraforaminal Lower cranial nerve paresis
foramen with or without
intracranial extension
C Primary extracranial tumour Distal pars nervosa Jugular foramen syndrome—
with extension into the hoarseness of voice, diminished
jugular foramen or into the gag and atrophic weakness of
posterior fossa shoulder
D Dumb-bell shaped tumour Can have features of all the three
with intracranial and above. Extracranial extension
extracranial extension may be palpable as neck mass
in parapharyngeal space
•• Overall features of raised intracranial pressure, hearing loss, tinnitus,

ataxia and LCN dysfunction are the most common manifestations of jugular
foramen schwannoma.
•• Other presentations include facial nerve dysfunction (facial paresis,
hemifacial spasm, loss of taste sensation), ear canal masses and neck lumps.
Diagnosis
•• The CT and MRI appearances of jugular schwannomas are similar to those
of other schwannomas, varying with the proportion of cellular and cystic
components of the tumour.
•• Jugular schwannomas are isodense or hypodense on CT because of their
rich lipid content.
•• Bone algorithm CT shows smooth and sharply-marginated jugular foramen
enlargement.
•• Selective enlargement of the pars nervosa can be suggestive of
glossopharyngeal schwannomas.
•• In MRI, jugular schwannomas appear as well-circumscribed masses
with low-signal intensity on T1-weighted and high-signal intensity on T2-
weighted magnetic resonance images.
•• Following administration of gadolinium, dense enhancement with or without
intratumoural cysts is seen.
•• No intratumoural flow-voids are seen.
•• Differential diagnosis of jugular fossa masses includes glomus jugulare
and jugular fossa meningioma.
•• Glomus jugulare produces irregular erosion of the margin of the jugular
foramen with decalcification or destruction of the surrounding bone.
•• Additionally, glomus jugulare are angiographically highly vascular, with an
intense contrast stain and readily apparent vascular pedicle(s) and have
intratumoral flow-voids on T2-weighted MRI.
•• On the other hand, LCN schwannomas symmetrically expand the jugular
foramen with smooth, sharply outlined and sclerotic margin of the eroded
adjacent bone, do not appear very vascular at conventional angiography
and have no intratumoural flow-voids.
Chapter 161 • Other Intracranial Schwannomas
1223
•• Primary jugular foramen meningioma is characterised by a permeatal–

sclerotic appearance of the bone margins of the jugular foramen, the
presence of dural tails and an absence of flow-voids.
Management
•• Presently, microsurgical resection and radiosurgery are the available
options for the management of these patients.
•• Observation is reserved for patients who are extremely poor surgical risks.
•• Due to limited availability and high cost of radiosurgical apparatus,
stereotactic radiotherapy has also been tried in patients with non-acoustic
schwannomas.
Surgical Approach
•• The choice of surgical approach is determined by the size, location of the
lesion and preoperative hearing status.
•• Type A tumours:
–– Since these tumours are primarily limited to the intracranial compart-
ment with little erosion of the bone, they can safely be excised with the
classical retrosigmoid approach.
•• Type B to D tumours:
–– The complete extirpation of these tumours is difficult.
–– A cervical transmastoid approach is generally recommended for these
tumours.
–– The LCNs are identified in the neck and followed-up to the skull base.
–– For type B tumours, an infralabyrinthine approach is recommended to
preserve hearing function in patients with preserved hearing.
–– A translabyrinthine–transcochlear approach is chosen in patients with
complete loss of hearing.
–– Type C tumours are best approached through an infratemporal
approach (Type A) described by Fisch, which enables direct access
to the jugular foramen and the neck and provides good control of the
adjoining vasculature.
–– The Type D tumours represent a special case. For a single-stage
resection, an extreme lateral transcondylar approach is combined
with suboccipital craniotomy. Alternatively, a staged suboccipital cra-
niotomy followed by an infratemporal approach can be undertaken.
•• Schwannomas do not infiltrate the cranial nerves or the jugular bulb and
safe radical excision of these tumours is possible with acceptable morbidity.
•• The postoperative morbidities generally seen are facial nerve dysfunction,
transient worsening of LCN function and CSF leak.
•• Radiosurgery and stereotactic radiotherapy are the treatment options for
small LCN schwannomas with intact cranial nerves though microsurgical
complete excision is possible in general and is potentially curative.
SCHWANNOMAS OF THE OCULAR

MOTOR NERVES
•• Schwannomas of the oculomotor, trochlear and abducens nerve are rarely
encountered in the absence of neurofibromatosis.
•• The oculomotor and the trochlear nerves are more frequently involved.
•• Celli et al. have classified these tumours into cisternal, cisternal-cavernous
and cavernous according to their location in the course of these cranial
nerves.
1224
•• Trochlear nerve schwannomas are almost always intracisternal in location
and originate from the precavernous segment of the nerve.
•• From the ambient cistern they may extend medially into the pre-pontine
cistern or superiorly above the tentorium.
•• Trochlear nerve paresis in association with these tumours is encountered
in a minority with symptoms attributable chiefly to brainstem compression.
•• Frequently, the clinical syndrome constitutes ipsilateral cerebellar ataxia,
hemiparesis and sensory disturbances in association with an extra-axial
tumour at the tentorial notch.
•• Oculomotor and abducens nerve schwannomas can arise from both the
cisternal and cavernous segments of the nerves.
•• The most common manifestation of III nerve tumours is oculomotor paresis.
•• The VI cranial nerve schwannomas manifest chiefly with VI nerve paresis,
but tumours arising proximally within the cistern may have a more malignant
course as the tumour growth causes obstructive hydrocephalus.
•• The nerve of origin is difficult to distinguish in intracavernous schwannomas,
and the much more common trigeminal nerve tumour must be strongly
considered in the differential diagnosis.
Diagnosis
•• On CT, schwannomas generally are of lower density than brain parenchyma
and show moderate enhancement.
•• The MRI appearances of schwannomas are variable but generally of
well-circumscribed lesions, isointense or slightly hypointense to brain
parenchyma on T1-weighted images and isointense or heterogeneously
hyperintense on T2-weighted images.
•• The heterogeneity tends to increase with increasing tumour size and
may be the result of regions of different histology (hypercellular Antoni A
tissue appearing isointense and hypocellular Antoni B tissue appearing
hyperintense) or cystic change.
•• Regions of hypointensity on T2-weighted image may be seen corresponding
to areas of calcification, haemorrhage or hyalinised stroma.
•• Contrast enhancement is intense but may be inhomogenous.
Management
•• The surgical morbidity of cavernous sinus exploration for extirpation of
intracavernous schwannomas is substantial. Moreover, surgical excision
is associated with permanent loss of function of the affected nerve.
•• Hence, stereotactic radiosurgery is generally recommended for
intracavernous ocular motor schwannomas.
•• Trochlear nerve schwannomas are amenable to surgical resection owing
to their cisternal location.
•• The subtemporal approach with division of the tentorium is suitable for the
resection of the majority of these tumours.
•• Anterior petrosectomy may be supplemented to this approach for larger
tumours with significant extension below the tentorium.
•• Postoperative loss of IV nerve function is generally well tolerated.
•• Cisternal oculomotor schwannomas should be considered for surgical
decompression only in the presence of mass effect from large tumours.
•• Oculomotor palsy resulting from total excision of these lesions is disabling.
•• Either a pterional or subtemporal, transtentorial transpetrosal corridor can
be used depending upon the configuration of the tumour.
162
CHAPTER
Phakomatoses
INTRODUCTION
•• Phakomatoses is a term coined by Van der Hoeve, in 1920, to describe a
group of hereditary neurological disorders that have cutaneous and ocular
stigmata.
•• They were initially divided into:
–– Neurofibromatosis (NF)
–– Tuberose sclerosis (TS)
–– Von Hippel-Lindau disease (VHL)
–– Neurocutaneous angiomatosis.
•• All the phakomatoses do not manifest ocular and cutaneous findings; VHL
shows no skin markers and the neurocutaneous angiomatoses show no
ocular lesions.
•• The genetic abnormality in many of these disorders has not yet been
identified and the fact that stigmata of more than one of these syndromes
have been seen in the same patient could indicate that they are all due to
an abnormality in a small group of genes.
NEUROFIBROMATOSIS
•• This is the most common of the phakomatoses, with a reported incidence
of one in 3,000 births.
•• It is an autosomal dominant disease with high penetrance but variable
expression.
•• This syndrome has been variously classified in the literature but consensus
is for two types designated NF-1 and NF-2, which account for over 95%
of all cases.
•• Other cases of NF represent either poorly expressed or variant types.
Neurofibromatosis-1
•• Neurofibromatosis-1 (NF-1), previously termed “von Recklinghausen
neurofibromatosis” or “peripheral neurofibromatosis”, was first described
by von Recklinghausen.
•• The genetic abnormality is thought to be in chromosome 17 and is of
extremely variable expression, with members of the same family showing
marked differences in clinical features.
•• Individuals with NF-1 present with abnormalities of both astrocytes and
neurons that result from reduced or absent expression of the NF type 1
(NF-1) gene product neurofibromin.
1226
•• Impaired neurofibromin function in these nervous system cells contributes

to the development of astrocytomas, learning disabilities and radiographic
abnormalities of the brain.
•• Neurofibromin is expressed in many different tissues and it is now known
that one role of neurofibromin is as a GTPase activating protein, very likely
in the same pathway of signal transduction as ras.
•• A diagnosis of NF-1 is made if the patient fulfils any two of the following
criteria:
1. Two or more neurofibromas of any type or one plexiform neurofibroma.
2. Six or more café-au-lait skin macules visible in room light, each
5 mm or more in size in prepubertal patients or 15 mm or more in post-
pubertal patients.
3. Two or more Lisch nodules.
4. Optic glioma.
5. Axillary or inguinal freckling.
6. Characteristic osseous lesions such as sphenoid dysplasia or thinning
of long bones’ cortices, with or without pseudoarthrosis.
7. A first degree relative (parent, sibling or offspring) with NF-1 by the
above criteria.
•• Not all the patients of NF-1 fulfil the criteria given above. These patients
must be presumed to have the NF-1 gene but with poor gene expression.
•• Cutaneous neurofibromas are characteristic of NF-1.
•• These Schwann cell tumours occur on the distal cutaneous nerve endings.
•• They are most numerous in the thoracoabdominal region, the presence of
neurofibromas on the nipple or areola of the breast suggests an association
with pigmentation and/or hormones.
•• They do not pose any serious problem to the patient except cosmetic, or
rarely pain or itching. Operative removal of the lesion is done for painful or
irritant lesions or for cosmetic purposes.
•• Plexiform neurofibromas may form along the course of any nerve.
•• •Lisch nodules are pigmented hamartomas of the iris.
•• Though spinal neurofibromas occur mostly on the dorsal nerve root, the
ventral roots may also be involved. These are often multiple and are most
common in the cervical and lumbar regions.
•• Surgery is necessary if cord compression develops.
•• Optic nerve gliomas occur in about 5–10% of patients with NF-1. The
tumours behave like hamartomas and the treatment is as for these tumours
occurring in the general population.
•• Macrocephaly, learning disorders, sphenoid wing dysplasias, pseudo-
arthrosis, phaeochromocytoma and kyphoscoliosis are the other lesions
which may be seen in NF-1.
Neurofibromatosis-2
•• Neurofibromatosis-2 (NF-2) was previously called “central NF” or “bilateral
acoustic NF”.
•• It is an autosomal dominant disease, with the genetic abnormality on
chromosome 22, though the method of gene expression is not clear.
•• The criteria for the diagnosis of NF-2 are:
–– Radiological evidence of bilateral acoustic neuromas
–– A first degree relative with NF-2 and either
¾¾ A unilateral acoustic neuroma, or
Chapter 162 • Phakomatoses
1227
¾¾ Two of the following: Neurofibroma, Schwannoma, Meningioma,

Glioma, Juvenile posterior subcapsular cataract
•• Patients with NF-2 present with bilateral acoustic neuromas, which are in
the majority symmetrical and present with symptoms during adolescence
and early adulthood.
•• A diagnosis of NF-2 should be suspected in any patient below 30 years of
age, who has an acoustic neuroma, in a patient with multiple meningiomas
and in patients with Schwann cell tumours and minimal stigmata of NF-1.
•• Patients with NF-2 are liable to have other tumours, including multiple
Schwann cell tumours on peripheral nerves, spinal roots and cranial nerves,
cranial and spinal astrocytomas and meningiomas.
•• Surgery is offered for the larger tumours first, while small tumours without
any major pressure effects are kept under observation.
•• Treatment of these patients is aimed at maintaining brainstem and spinal
cord function.
TUBEROSE SCLEROSIS
•• The first recognisable report of TS was that of von Recklinghausen, in 1862.
•• The clinical syndrome of seizures and mental defect with pathological
lesions in the brain was postulated by Bourneville, who also coined the term
“tuberose sclerosis”, sometimes also known as adenoma sebaceum and
also recognised its frequent association with renal and cardiac tumours.
•• TS is an autosomal dominant disorder with a variable penetrance.
•• The gene responsible is thought to be on chromosome 9.
•• The incidence is about one in 10,000 births and again the extent of
expression is very variable.
•• The clinical diagnosis of TS can be made by Vogt’s triad of seizures, mental
deficit and adenoma sebaceum.
•• Skin Manifestations:
–– Ash leaf spots and other depigmented macules are best seen under a
Wood’s lamp. They are seen mostly on the trunk, arms and legs
–– Adenoma sebaceum is an angiofibroma. It is a progressive lesion
which develops after birth and which shows rapid growth around
puberty. It has a characteristic distribution, over the cheeks, nose and
chin, sparing the upper lip. It is often confused for acne vulgaris.
–– Shagreen or shark-skin patches are dermal fibromas which usually
develop after 10 years of age. They occur mostly in the lumbosacral
region. They are not pathognomonic of TS and may occur in isolation
–– Ungual fibromas or Koenen’s tumours are angiofibromas which occur
in the lateral nail groove, along the proximal nail-fold or under the nail.
They are more common in the toes than in the fingers.
•• Nervous System Manifestations:
–– Patients with TS present clinically with seizures and mental retarda-
tion.
–– The seizures are mostly tonic-clonic or infantile myoclonic, though
partial-motor and complex partial seizures are also seen.
–– The degree of mental retardation in these patients varies and regres-
sion has been noticed in older patients.
1228
–– They may be due to either uncontrolled seizures or to the development

of a brain tumour.
–– Cortical plaques (or tubers) and subependymal glial nodules are devel-
opmental lesions which do not enlarge once brain growth has stopped.
–– Cortical tubers are hamartomas containing glial and neuronal cell
populations.
–– There is no evidence of malignant transformation in these lesions.
–– Degenerative changes take place with gliosis and umbilication of the
cortex at the site of the tubers, leaving normal brain in between.
–– Subependymal nodules are scattered along the entire wall of the
lateral and third ventricles. They are mainly glial hamartomas and
contain prominent calcium deposits.
–– Subependymal “giant cell astrocytomas” occur in about 10% of pa-
tients with TS. They probably arise from the germinal cell matrix which
explains their vascularity.
–– Lesions are also seen in other organs, such as the retina, heart, kidney
and lungs.
–– The CT and magnetic resonance imaging (MRI) scan of the brain is
characteristic in patients with TS. Subependymal periventricular calci-
fication is the most frequent and characteristic finding.
–– The tendency for these lesions to protrude into the lateral ventricle
(“candle guttering” was seen on ventriculography), distinguishes them
from other calcified lesions seen in cytomegalovirus infection, cysticer-
cosis and toxoplasmosis.
–– The calcifications are mostly just lateral to the foramen of Munro and
in the body of the lateral ventricle, though rarely, they may occur in the
wall of the third and fourth ventricles.
–– Multiple hypodense intracerebral lesions are seen especially in the
frontal, parietal and occipital lobes. These represent areas of defec-
tive myelination and heterotopic hamartomatous tissue, which occur
particularly at the junction of grey and white matter.
–– In MRI scans cortical tubers were more frequently demonstrated on
spin-echo images obtained with a long repetition time (TR).
–– Because the signal abnormality is located predominantly in the
subcortical portion of the tubers, the terms “gyral core” and “sulcal
island” have been used to describe the patterns noted on MRI.
–– Treatment involves controlling seizures with antiepileptic drugs and
special education for the mentally handicapped.
–– The brain tumours can be excised with a good prognosis.
–– The life expectancy of these patients is decreased, the causes of
death being cardiac failure, brain tumours, status epilepticus and renal
failure.
VON HIPPEL-LINDAU DISEASE

•• The VHL disease or complex is an autosomal dominant disorder
with variable expression, characterised by either more than one
haemangioblastoma within the neuraxis associated with at least one
visceral manifestation.
•• No cutaneous stigmata are seen in patients with VHL complex.
•• The typical lesion in the neuraxis is a cerebellar haemangioblastoma, which
at autopsy is found in at least 60% of patients with the disease.
Chapter 162 • Phakomatoses
1229
•• Haemangioblastomas may also be found in the brainstem, spinal cord and

in the supratentorial compartment.
•• The lesions may be solid or cystic. They are commonly multiple, with the
tumours appearing metachronously.
•• Retinal angiomas are seen in over 50% of patients with the VHL complex.
•• The lesions are seen mostly in the peripheral parts of the retina, though
they have also been recorded at the macula and the optic disc.
•• They are usually seen in both the eyes.
•• With time, they are covered with exudates which surround the lesion, the
feeding artery and the draining vein.
•• Retinal oedema, haemorrhage, retinal detachment, gliosis and secondary
glaucoma may cause loss of vision. Photocoagulation is the treatment of
choice for the ocular lesions.
•• Angiomas may also be found in other organs, such as the liver, spleen,
kidneys, lungs, the skeletal system, epididymis and the adrenal cortex.
•• However, the most common and dangerous tumours are pheochromocytoma
and renal cell carcinoma, which cause death in a significant proportion of
the VHL patients.
•• The investigation of a patient with suspected VHL complex must include
examination of the fundi with a record of the visual acuity and fields,
abdominal ultrasound or CT with special focus on the kidneys, pancreas
and adrenals, urinary metanephrine screening and haematocrit and blood
counts, besides CT scan of the brain and upper cervical cord.
NEUROCUTANEOUS ANGIOMATOSIS
•• These are a group of genetic disorders, which have an abnormality of blood
vessels of the skin and nervous system as their only common feature.
•• Each syndrome has other systemic angiomata as well as haematopoietic
and immunologic deficiencies.
Ataxia Telangiectasia
•• It is an autosomal recessive disorder with progressive ataxia, cutaneous
telangiectasias and immunological abnormalities.
•• Prognosis is poor, with death usually occurring in the second decade due
to infection or neoplasia like lymphomas or leukaemias.
Sturge-Weber Syndrome
•• It is defined by the association of a facial capillary malformation (port-wine
stain), with a vascular malformation of the eye, and/or vascular malformation
of the brain (leptomeningeal angioma).
•• They may be caused by a somatic mutation occurring sporadically, rather
than an inherited disorder.
•• The characteristic skin lesion is a unilateral facial angioma (port-wine stain)
in one or two dermatomes of the trigeminal nerve.
•• There is an ipsilateral parieto-occipital leptomeningeal venous angiomatosis
with underlying cortical atrophy.
•• Calcification of the second and third cortical layers of this region appears
as the characteristic “rail-road” calcification on plain X-rays.
•• Patients present with seizures or with hemiparesis. Subarachnoid
haemorrhage is rare.
1230
•• Early onset of seizures and poor response to medical treatment, bilateral

cerebral involvement and unilateral severe lesions indicate poor prognosis.
•• Uncommonly, glaucoma secondary to retinal angiomatosis may cause
loss of vision.
•• Laser therapy is the optimal approach for treating port-wine stains but
whether it is effective for patients with facial dermatomal port-wine stains
and Sturge-Weber syndrome is undetermined. Laser treatment produced
unsatisfactory outcomes in patients with facial dermatomal port-wine stains.
Klippel-Trenaunay-Weber Syndrome
•• The cutaneous angioma is unilateral on the trunk, involving one or more
dermatomes, with a haemangioma of the spinal cord at the same level.
•• The lesions are unilateral and may be associated with osseous and
muscular hypertrophy of the involved areas.
•• The lesion is seen as a spinal variant of the Sturge-Weber syndrome.
Osler-Weber-Rendu Syndrome or
Hereditary Haemorrhagic Telangiectasia
•• Osler-Weber-Rendu (OWR) syndrome is a rare autosomal dominant
disease with angiomas of the skin, mucosal surfaces and nervous system
and usually presents with haemorrhage.
•• It is a genetic disorder caused by an abnormality in either the endoglin
gene on chromosome 9, or the activin receptor-like kinase 1 gene on
chromosome 12. Both of these genes are involved in blood vessel
formation.
•• A mutation in either of these genes will result in similar OWR symptoms
and those who have the disorder generally only have an abnormality in
one of the genes.
•• Majority of the symptoms are the result of haemorrhage due to abnormal
formation of capillaries.
•• Arteriovenous malformations (AVMs) may occur on the surface of the skin
or in the lungs, brain, liver, stomach or gastrointestinal tract.
•• Brain AVMs may be treated by surgery, embolisation, or stereotactic
radiosurgery.
Fabry’s Disease
•• Fabry’s disease results from the accumulation of ceramide trihexoside in
the media and endothelium of small blood vessels due to a deficiency of
alpha-galactosidase.
•• It is an X-linked recessive disorder, characterised by telangiectasias of the
lower half of the body.
•• Skin lesions apart, renal function may be impaired with resultant
hypertension and myocardial infarction.
•• More severe forms have a diffuse involvement of vessels of the peripheral
nerves and of the CNS, leading to neuropathies and strokes.
163
CHAPTER
Convexity Meningiomas
Vasudevan MC
INTRODUCTION
•• Meningiomas are classified as convexity (cranial vault) or basal based on
their dural attachment.
•• Convexity meningiomas are those tumours whose attachment is confined
to the convexity of the brain and do not involve the dura of the skull base,
the venous sinuses or the falx.
•• Convexity meningiomas are the most frequently encountered meningiomas,
followed by meningiomas of the sphenoid ridge and cerebellopontine angle.
INCIDENCE
•• Intracranial meningiomas account for 20% of brain tumours of which
15−25% are convexity meningiomas.
•• These convexity lesions are the most common meningiomas.
•• The factors that may predispose to meningioma formation are female sex,
previous ionising radiation and neurofibromatosis.
•• Meningiomas may be associated with Werner’s syndrome, and these are
seen to occur two times more frequently in men and are associated with
extracranial tumours like sarcomas and thyroid carcinoma.
•• The incidence of cranial vault or convexity lesions is increasing due to
routine imaging, which has become a part of contemporary health care.
•• Almost one-third of these tumours are now discovered as incidental findings
on CT or MRI.
LOCATION
•• Cushing and Eisenhardt subclassified convexity meningiomas as pre-
coronal, coronal, postcoronal, paracentral, parietal, occipital and temporal
types.
•• A meningioma which involves more than one location is classified according
to the site of the main attachment.
•• Anterior meningiomas are those which lie at or in front of the coronal suture
and include meningiomas of the pterion.
•• Median meningiomas are those astride the Rolandic fissure.
•• Posterior meningiomas are those which involve the posterior parietal and
occipital regions.
•• Temporal meningiomas are those which develop in the temporal region
and pterion and grow posteromedially and project on the temporal side of
the Sylvian fissure.
1232
CLINICAL FEATURES
•• Like any other slow growing intracranial lesion, convexity meningiomas have
a long clinical history.
•• Incidental asymptomatic meningiomas are increasingly seen on routine
imaging of the neuraxis.
•• The clinical features are in accordance with the site of the lesion.
•• Patients often have a long history of headache, mental deterioration,
visual disturbances, focal neurological deficit, seizures and signs of raised
•• Some of the convexity meningiomas are diagnosed solely from the
presence of skull or scalp swelling, due to an often associated hyperostosis
and rarely due to osteolysis and tumour involving the calvarium and scalp.
•• The growth of meningiomas may increase during pregnancy, due to the
presence of receptors for progesterone hormone in the tumour and they
may become symptomatic during pregnancy and present as eclampsia.
ANTERIOR CONVEXITY MENINGIOMAS

•• These tumours produce symptoms and signs of frontal lobe dysfunction,
mainly mental deterioration.
•• These are often overlooked and attributed to the ageing process, as they
occur mostly in elderly patients.
•• These tumours attain a large size before showing signs of increased
intracranial pressure or papilloedema.
•• Rarely, subtle signs of pyramidal involvement are the only signs and these
may be difficult to pickup.
MEDIAN CONVEXITY MENINGIOMAS

•• Sensory and motor signs and symptoms are characteristic of convexity
meningiomas in this location.
•• When the dominant hemisphere is involved, speech disturbances are
common.
•• Cushing had noted that Jacksonian type of seizures starting from the face
or hand, preceded by motor or sensory aura, may occur.
POSTERIOR CONVEXITY MENINGIOMAS

•• They often present with signs of increased intracranial pressure, sensory
motor symptoms or, characteristically, visual field defects (homonymous
hemianopia).
TEMPORAL CONVEXITY MENINGIOMAS

•• These often present with seizures, contralateral motor deficit and visual
field defects (due to involvement of visual fibres along the temporal horn).
•• Speech disturbances are common when the dominant hemisphere is
involved.
•• Rarely, when large, they may compress the ipsilateral cerebral peduncle,
leading to contralateral motor disturbances.
•• In some cases, compression of the contralateral cerebral peduncle against
the tentorial edge may result in ipsilateral hemiparesis.
Chapter 163 • Convexity Meningiomas
1233
IMAGING
X-rays
•• X-rays of the skull can show hyperostosis or osteolysis, with expansion
of the calvarial bone and prominence of vascular channels, signifying the
presence of a meningioma.
•• Calcified lesions and those with specky calcification are easily made out.
•• Plain X-ray of the skull as an initial investigation gives information regarding
calcification of the lesion or erosion of the skull associated with convexity
meningiomas.
Computed Tomography
•• The CT scan may show hyperostosis of adjacent bone and prominent
vascular channels.
•• These lesions are generally isodense with brain on non-contrast scan, have
smooth contours and are in close proximity to the dura.
•• They may be partially or, rarely, fully calcified.
•• In few cases they can have atypical radiology with necrosis, cystic
degeneration, haemorrhage, indistinct margins, severe brain oedema,
multiple nubbins of the tumour which deeply invade the brain and have
heterogeneous enhancement. These findings indicate a malignant
transformation or an atypical meningioma.

•• Magnetic resonance imaging gives much better soft tissue delineation.
•• On T1-weighed images, they are isointense or hypointense to grey matter
and on proton density and T2-weighted images, they are isointense or
hyperintense.
•• These tumours compress the adjacent brain and they can extend along and
infiltrate Virchow-Robin spaces and can have an infiltrating morphology.
•• Gadolinium is a paramagnetic contrast agent and causes these lesions to
enhance brilliantly.
•• MRI scores over CT in demonstrating the “dural tail” and invasion of the
venous sinuses, thereby eliminating the need for angiography.
Electroencephalogram
•• Electroencephalogram to locate the site of a meningioma is of historical
value only but may be useful in monitoring the epileptogenicity of the
affected cortical area for medical therapy.
Angiography
•• Angiography is done when imaging suggests a highly vascular lesion and
one which may require preoperative embolisation.
•• The external carotid injection shows a “sunburst” pattern and internal carotid
injection shows the arterial and pial blood supply.
•• Preoperative embolisation is generally not necessary in cases of convexity
meningiomas, as the majority of the supply is from meningeal vessels which
are cut off in the early stages of surgery.
1234
•• The differential diagnosis includes fibrous dysplasia, tuberculoma,
sarcomas, lymphomas, non-Hodgkins MALT lymphoma, plasmacytomas,
carcinomas, dural based secondaries, Rosai Dorfman’s disease,
melanocytoma and cavernous haemangioma.
SURGICAL MANAGEMENT
•• Generally surgery is recommended in patients diagnosed with a convexity
meningioma greater than 1.5−2 cm except in the elderly and frail.
Preoperative Protocol
•• In the presence of raised ICP and seizures, pre-operative adequate dosage
of steroids, furosemide (lasix) and anticonvulsants is essential.
•• If needed, peroperatively, 20% mannitol (1 g/kg body wt) may be given in
the early phase of surgery.
•• Being generally a vascular tumour adequate supply of blood should be
available. There could be sever blood loss even while turning the bone
flap and exposing the tumour.
Scalp Incision
•• The neuroimaging, including the multiplanar MRI and the CT scan, which
is better in showing the relationship of the lesion to bony landmarks like the
coronal suture, are studied before marking the appropriate scalp incision.
•• It is also prudent to look for signs of hyperostosis, osteolysis and prominent
scalp vessels.
•• The scalp incision should be large and care must be taken in cases where
resurgery is undertaken.
•• Normally, a U-shaped incision is sufficient.
•• Surface anatomy scanning (SAS) with the help of MRI imaging may
precisely localise the tumour and also give information regarding the
surrounding venous anatomy.
•• Intraoperative image guidance is useful in precise location of the craniotomy.
•• Navigation also helps to provide visualisation of the relationship of the
tumour to the veins.
•• Current surgical strategy is to use neuronavigation, making possible a
targeted linear incision and a small craniotomy, followed by resection and
taking a 5 mm dural margin around the tumour.
•• The scalp incision and the craniotomy flap should be wider than the lesion
itself.
•• A free bone flap is preferable as it provides an early disruption of the
external carotid blood supply.
•• One needs to preserve the pericranial tissue which may be used later as
a graft to replace the dural defect.
•• The elevated bone flap needs to be inspected for any tumour invasion and,
if found, this needs to be removed in toto.
Postoperative Care and Complications

•• The patient needs constant monitoring of the level of consciousness, blood
pressure, pulse rate and oxygenation and coagulation profile.
•• The fluid balance is to be maintained.
Chapter 163 • Convexity Meningiomas
1235
•• The central line is left in place, of which one line is connected to a CVP
monitor.
•• The patient is nursed in the 30 degree head-up position.
•• Anticonvulsants need to be continued.
•• Steroids are continued in high doses during the first 3 post-operative days
and gradually tapered (4 mg of dexamethasone IV 8 hourly). Apart from
this, furosemide 40 mg per day is given.
•• Occasionally, intermittent mannitol is given if the patient deteriorates due to
cerebral oedema.Controlled ventilation may be resorted to in this situation.
During this period, electrolytes and blood gases are monitored and need
to be repeated at least 8 hourly.
•• Other complications include meningitis, CSF leak, chest infection and stress
induced gastric bleed.
PROGNOSIS
•• The prognosis for convexity meningiomas is very good, as total excision
is possible.
•• There is no doubt that the single most important prognostic factor is
completeness of surgical removal of the meningioma and its surrounding
involved dura.
•• Simpsons’s grading can be used to prognosticate recurrence.
RECURRENCE
•• Factors contributing to the recurrence of tumour include the type of removal
and pathological nature of the tumour.
•• The biological characteristics that are implicated in recurrence are the male
sex, lack of calcification, high MIB-1 index, loss of chromosome 1p and
vascular endothelial growth factor expression.
•• Increased MIB-1 labelling index which is an immunohistochemical measure
of Ki-67 antigen expression has been associated with meningioma
recurrence and is useful in planning adjuvant therapy.
•• The term recurrence should be reserved for cases for type I or type II
excision of Simpson’s grading.
•• Some authors have suggested the necessity of an additional margin of 2
cm around the tumour (Simpson grade 0).
•• For growth of tumour after sub-total excision (Type III), the term regrowth
should be used.
•• Atypical or anaplastic tumours carry an increased risk of recurrence.
•• Histopathological findings of increased mitosis, focal necrosis, features of
atypia or frank malignancy, directly correlate with the rate of recurrence.
•• The grading system to diagnose atypical meningiomas proposed by
Mahmood et al. is the most appropriate and includes the criteria:
–– Increase in mitotic rate
–– High cellularity
–– Sheeting of tumour cells with loss of typical histological pattern
–– Prominent nucleoli
–– Focal necrosis and
–– Tumour invasion into bone or cortex.
•• Radiation is resorted to for malignant lesions, and occasionally following
subtotal resection.
1236
•• In small meningiomas, where primary surgical excision is not possible

due to medical and anaesthetic problems, stereotactic radiosurgery may
be an option.
•• The role of chemotherapy is debatable.
•• On histopathology, expression of androgen and progesterone receptors in
primary human meningiomas may allow hormonal manipulation of lesions.
•• The use of antiprogesterone (RU480) to control tumour recurrence has not
been clearly established.
•• It is better to have a periodic CT scan once in 2 or 3 years to detect early
recurrence.
•• About 85% of patients with recurrence can undergo one or more additional
operations, usually with good and long-lasting results.
164
CHAPTER Parasagittal and
Falx Meningiomas
Vasudevan MC
•• Cushing, in 1922, suggested the term ‘parasagittal’ for meningiomas along

the superior sagittal sinus (SSS).
•• These tumours arise from the arachnoid villi of the SSS and often involve
the adjacent convexity dura and falx.
•• Nearly 50% invade the sinus, 50% get secondary attachment to the falx
and 25% are bilateral.
•• Hyperostosis of the adjacent skull is associated with 25% of these tumours
and is a valuable pointer to their diagnosis.
•• Falcine meningioma arises from the falx cerebri or inferior sagittal sinus
and may rarely invade the SSS. It is usually completely concealed by the
overlying cerebral cortex and does not cause bony changes.
•• About 50% of the tumours grow through the falx to become bilateral.
•• Falx meningiomas are about five to seven times less common than
parasagittal meningiomas (PSMs).
•• The distribution of parasagittal and falx meningiomas along the longitudinal
axis is about 20%, 50% and 30% in the anterior, middle and posterior-third,
respectively.
CLINICAL FEATURES
•• Tumours in the middle-third, from the coronal suture to the lamboid suture,
classically present with contralateral focal motor or sensory epilepsy
followed by progressive weakness of the contralateral lower limb. These
tumours are detected at an early stage because of focal epilepsy.
•• Bilateral tumours may, occasionally, give rise to bilateral disturbances
and, rarely, paraplegia that may be wrongly attributed to spinal pathology.
•• Anterior-third meningiomas, located between the crista galli and the coronal
suture, have a more insidious onset and often attain a large size before
diagnosis.
•• Headache is the predominant symptom and may be present for years
followed by gradually progressive impairment of memory, intelligence and
personality changes.
•• Generalised epilepsy is a presenting symptom in 25–30% of patients.
•• Ataxia, tremor and ipsilateral facial pain may, occasionally, accompany
a large meningioma and thus may be misdiagnosed as a posterior fossa
tumour.
•• Tumours in the posterior-third between the lambdoid suture and the
torcular herophili may present with features of raised intracranial pressure
1238
alone. The only characteristic sign, a homonymous field defect, either

quadrantanopic or hemianopic, may not be noticed by the patient.
IMAGING
•• The CT scan best reveals the chronic effects of slowly growing mass lesions
on bone remodelling.
•• Calcification in the tumour (seen in 25%) and hyperostosis of overlying
skull may be seen.
•• MR imaging findings include a tumour, which is dural-based and isointense
with grey matter, demonstrates prominent and homogenous enhancement,
frequent cerebrospinal fluid/vascular cleft(s) and often an enhancing dural
tail.
•• Meningiomas may have an atypical appearance on MR images, mimicking
metastases or malignant gliomas.
•• In particular, these meningiomas may have a significant amount of
peritumoural oedema due to venous compression.
•• Angiography, the most preferred diagnostic procedure in the pre-CT era,
may still be helpful in revealing the vascularity of the tumour, its blood
supply and its relationship to the venous sinuses.
•• Contrast-enhanced magnetic resonance venography (CE-MRV) provides
additional and more reliable information concerning venous infiltration and
the presence of collateral anastomoses compared with phase contrast
(PC) sequences.
•• There has also been interest in the use of MR spectroscopy to assist in the
diagnosis of meningiomas. Creatinine containing peaks in meningioma are
20% that of comparable levels in normal brain.
•• Differential diagnosis include dural metastasis, primary dural lymphoma,
solitary fibrous tumours, gliosarcomas, leiomyosarcomas, hemangioperi-
cytomas, melanocytomas, plasmacytomas, inflammatory pseudotumours,
en-plaque meningiomas, neurosarcoidosis, plasma cell granulomas and
Rosai–Dorfman disease.
TREATMENT
•• Many studies confirm the tenet that most meningiomas grow very slowly and
that a decision not to operate is justified in selected asymptomatic patients.
•• As the growth rate is unpredictable in any individual, repeated brain imaging
is mandatory to monitor an incidental asymptomatic meningioma.
•• The treatment of meningiomas is dependent on both patient related factors
(age, performance status, medical comorbidities) and treatment-related
factors (reasons for symptoms, goals of surgery and resectability, which is
judged by the location and bilaterality of the tumour, patency of SSS and
displacement of the cortical veins).
•• In patients who are considered surgical candidates (surgically accessible
symptomatic meningiomas), the goal of therapy is total excision.
•• However, a small tumour, without focal deficit, especially in the elderly
can be kept under serial observation or may be subjected for primary
radiosurgery.
•• For anterior-third tumours, the patient is positioned supine and a bicoronal
incision is employed.
•• In mid-third tumours, the patient is in a semilateral position and in posterior-
third lesions, it is the three quarter prone position.
Chapter 164 • Parasagittal and Falx Meningiomas
1239
•• In falcine tumours, care is taken not to sacrifice cortical veins draining into
the SSS while exposing the tumour posterior to the coronal suture.
•• Very large tumours may be operated upon in two stages, the feeders on
either side of the falx being removed at each stage.
PROGNOSIS
•• Rate of recurrence of parasagittal and falx meningioma significantly
increases in cases of nonradical resection of tumour.
•• The extent of resection of meningiomas in this region is closely related to
tumour recurrence.
•• Hence, if total resection is aimed at, then sinus repair and reconstruction
is required.
•• However, if a conservative and less aggressive approach is adopted, then
the patient has to be informed regarding the prognosis and may be given
the option of adjuvant radiosurgery.
165
CHAPTER Olfactory Groove
Meningioma
ANATOMY
•• Olfactory groove meningiomas may arise from the anterior cranial fossa
near the crista galli, from near the cribriform plate of the ethmoid bone or the
planum sphenoidale and account for 8−13% of all intracranial meningiomas.
•• The tumour may be symmetric around the midline or extend predominantly
to one side.
•• The principle blood supply of the tumour is from the ethmoidal, meningeal
and ophthalmic arteries through the base of the skull along the midline.
In large tumours, the anterior cerebral arteries may be involved with the
tumour capsule.
•• The frontopolar and small branches of the anterior cerebral arteries may be
adherent to the superior and posterior part of the tumour capsule.
•• In large tumours, the olfactory nerve is usually adherent and splayed out on
the tumour, while the optic nerves and chiasm may be pushed downwards
and posteriorly.
CLINICAL FEATURES
•• These are usually slow-growing tumours. These tumours can be silent
for a long time.
•• Due to the ability of the brain tissue to adapt to slow compression and the
absence of focal eloquent cortical regions in the adjacent brain tissue, these
tumours can grow to large size before the patient becomes symptomatic.
•• Unlike meningiomas at other locations, there was no female predominance.
•• The most common initial symptom was long standing headache and the
other presenting symptoms were epilepsy and visual dysfunction.
•• Although anosmia occurs in 85−90% of cases, it is rarely the initial or
presenting symptom.
•• As these tumours grow in size, symptoms of pressure on the frontal lobe
may be apparent.
•• Mental symptoms often lead the patient to seek treatment from a
psychiatrist.
•• While inferior tumours may cause excitement or restlessness, pressure
over the convexity of the frontal lobe may lead to indifference and apathy.
•• The more anterior tumours cause a central scotoma and papilloedema.
•• Growing posteriorly, these tumours press on the optic nerve and chiasma,
leading to unilateral blindness or bitemporal haemianopia with optic atrophy.
•• With the rise in intracranial pressure, there may be papilloedema in the
opposite eye and a Foster Kennedy syndrome may be seen.
Chapter 165 • Olfactory Groove Meningioma
1241
•• Further extension posteriorly puts pressure on the hypothalamus and

pituitary gland. By this time, the ICP rises to cause obvious features of
raised ICP.
•• Rarely, by eroding through the orbital roof or the cribiform plate, the tumour
may cause proptosis.
RADIOLOGY
•• On CT scan the lesion is a well circumscribed, rounded, isodense to slightly
hyperdense mass, with dense uniform enhancement after intravenous
contrast.
•• The density is partly due to the cellularity and to the presence of calcified
psammoma bodies. Calcification may also be seen and is easily detected
by CT.
•• There may be increased thickness of the bone due to hyperostosis at the
site of dural attachment. Occasionally, bone destruction may be present
due to invasion by the tumour.
•• With MRI, the configuration of the tumour in all directions, the anatomical
extent and the relationship of the anterior cerebral arteries and optic nerves
can be clearly defined.
•• On T1-weighted images, the lesion is usually relatively isointense with grey
matter but may have variable signal intensity.
•• With contrast, they enhance intensely uniformly and often are seen to have
a ‘dural tail’, probably due to dural reaction.
•• In angioblastic meningiomas, the lesion will show flow voids within them
due to rapid flow of the blood in the veins.
•• Although angiography is not mandatory, when performed, it provides useful
information in large tumours, regarding the blood supply and location of
the anterior cerebral arteries and their major branches.
•• The anterior cerebral arteries are pushed backwards and upwards and a
frontal arterial branch is generally stretched over or involved in the tumour
capsule.
•• In large tumours, the anterior cerebral artery and its branches may be
involved within the tumour capsule. Care is necessary to avoid injury to
these vessels during surgery.
SURGICAL MANAGEMENT
•• Surgical treatment should aim at total excision which is generally possible
even in large tumours.
•• A bicoronal skin incision is preferred. This will depend upon the precise
extent of the tumour.
•• In large tumours that extend equally on both sides of the midline, a bilateral
bone flap is preferred. This approach is associated with minimal amount
of retraction on the frontal lobes, gives adequate access to all sides of the
tumour, allowing the surgeon to decompress the tumour while working along
the skull base to cut off the blood supply early during surgery.
•• The anterior end of the sagittal sinus may be ligated and the falx cerebri
detached from its inferior attachment when indicated.
•• Variety of surgical approaches, such as bifrontal craniotomy, a unilateral
subfrontal approach, pterional approach, a fronto-orbital craniotomy and a
subcranial approach have been recommended for OGM resection.
•• An approach tailored to the tumour’s size, location and extension and
combined with modern microsurgical cranial base techniques has been
1242
advocated as it allows full OGM removal with minimal permanent morbidity,

excellent neurological outcome and very low recurrence rates.
•• The endoscopic endonasal technique represents a possible alternative
approach for suitably selected cases and could be expected to minimise
neuropsychiatric sequelae.
•• Despite apparent gross total resection, OGMs have a high rate of late
recurrence (average, 23%).
•• The cranial base and paranasal sinuses are sites of predilection for
recurrence of OGMs.
•• Recurrence is the result of a direct extension, attributable to incomplete
resection of involved bone and regrowth at the edge of a previous surgical
field.
•• Extensive resection of all suspicious underlying bone is a complement to
radical removal of these lesions.
•• Reconstruction of the floor with a vascularised pericranial flap to prevent
cerebrospinal fluid leakage, is crucial.
Complications
•• Following complications can be encountered during surgical removal of
olfactory groove and suprasellar meningiomas, as the surgical approaches
are more or less the same. They are:
1. Cerebrospinal fluid leak and infection: Once the frontal sinus has
been breached, removal of the sinus mucosa, followed by a meticulous
repair with muscle and a vascularised pedunculated pericranium is
mandatory.
2. Vascular injury: Injury to the anterior cerebral arteries can result in
postoperative ACA territory infarct.
3. Postoperative seizures: Seizures occurring in the early post-
operative period.
4. Visual loss: Visual deterioration in the postoperative period is usually
the result of surgery, due to rough manipulation of the optic nerve and
chiasm or injury to the chiasmal blood supply.
SUPRASELLAR MENINGIOMA
INTRODUCTION
•• These were defined as tumours arising from the presellar area around the
tuberculum sellae and growing upwards between the two optic nerves. They
are also referred to as tumours of the tuberculum sellae.
•• They comprise 5−10% of all intracranial meningiomas.
ANATOMY
•• Most of meningiomas arising from the tuberculum sellae, planum sphenoi-
dale, diaphragma sellae and/or anterior clinoid process are grouped under
suprasellar meningiomas.
•• Based on the direction of growth of the tumour, the optic nerves are elevated
and laterally displayed when the lesion occupies a subchiasmal position.
•• Lesions arising from the diaphragma sellae grow retrochiasmally and
manifest with ocular paresis and endocrine dysfunction.
1243
•• The blood supply to these tumours is predominantly from the posterior

ethmoidal arteries and, to some extent, from the smaller branches of the
anterior cerebral arteries. This is the area of vital arterial perforators.
CLINICAL FEATURES
•• The mean age of occurrence is the fourth decade, with a female predomi-
nance in a ratio of 3:1.
•• As these tumours arise in close proximity to the optic chiasma, displacing it
posteriorly and superiorly and stretching it, visual symptoms are early and
common, leading to earlier detection than olfactory groove meningiomas.
•• Around 90−99% of the patients complain of either monocular (55%) or
binocular (45%) visual loss.
•• The other common symptoms are headache, epilepsy and mental changes.
•• The presence of bitemporal hemianopic field defects in the presence
of a normal sized sella, should suggest the possibility of a suprasellar
meningioma.
•• The size of these meningiomas is a major factor that determines a patient’s
outcome.
•• Cushing classified these tumours into four stages according to their size:
(1) initial stage; (2) pre-symptomatic; (3) favourable for surgery and (4)
late, or essentially inoperable.
•• Anosmia is rarely a presenting in these meningiomas.
RADIOLOGY
•• Plain X-rays may show a thickening in the region of the tuberculum sellae
or erosion of the dorsum sellae, planum sphenoidale or clinoids.
•• Rarely, calcification in the region may simulate a craniopharyngioma.
•• The CT scan typically shows an isodense or slightly hyperdense, rounded,
mildly lobulated, densely enhancing mass in the suprasellar area.
•• There can be bony hyperostosis at the site of dural attachment to the bone.
This may be associated with expansion of the underlying sphenoid sinus,
a finding that can be recognised on CT scan and X-ray skull.
•• MRI with MRA gives additional information about encasement and
displacement of vessels and also a more precise extent of the lesion.
•• In spite of the great advances in CT and MRI, it may not always be possible
to differentiate a meningioma from a pituitary macroadenoma by imaging
alone.
•• Taylor, et al. have proposed a combination of three features in a
meningioma that may differentiate it from a pituitary tumour in a gadolinium
enhanced MR. These are:
–– Bright homogeneous enhancement with gadolinium as opposed to
heterogeneous relatively poor enhancement in a pituitary tumour
–– A suprasellar rather than a sellar epicentre of the tumour and
–– Tapered extension of an intracranial tumour base, described as the
‘dural tail’ which represents a hypervascular non-neoplastic process,
not the meningioma.
•• Such a differentiation is worthwhile as the surgical approaches to these
lesions are different.
•• Angiography, in addition to showing a vascular tumour in the suprasellar
area, may show displacement of the ICA inferiorly (closure of the siphon),
posteriorly and laterally and elevation of the A1 segment of the ACA and
proximal part of the A2.
1244
•• Narrowing or irregularity of the ICA suggests encasement of the artery by

the tumour.
SURGICAL MANAGEMENT
•• Surgery for tuberculum sellae meningiomas presents a special challenge
because of their proximity to arteries of the anterior circulation, anterior
visual pathways and the hypothalamus.
•• The tumour is usually approached by a right frontotemporal craniotomy
through a lateral subfrontal microsurgical exposure just in front of the lesser
wing of the sphenoid.
•• The tumour is approached from the left side, if the tumour arises from the
left anterior clinoid or if the bulk is greater on that side.
•• Occasionally, the tumour grows into the optic canal, necessitating its
deroofing for complete extirpation.
•• Also a basal approach, supraorbital-pterional may be used to minimise
brain retraction and shorten the dissection distance.
•• The best chance of total excision is at the initial operation.
•• Elective partial excision of the tumour followed by a second-stage attempt
for total extirpation is usually not successful.
•• Tuberculum sellae meningiomas are microsurgically removed using three
different surgical approaches:
–– The bifrontal approach
–– Pterional/frontotemporal approach and
–– The frontolateral approach.
•• Considering the operative morbidity and mortality, the frontolateral and
pterional approach provided remarkable improvement, compared with the
bifrontal approach.
•• These approaches allowed quick access to the tumour and were minimally
invasive with less brain exposure, with high rates of total tumour removal.
Other Surgical Approaches

•• Direct endonasal trans-sphenoidal approach for removal of suprasellar
meningiomas.
•• Ultrasound was used to help define tumour location before dural opening.
•• The surgical dural and bony defects were repaired in all patients with
abdominal fat, titanium mesh and 2−3 days of cerebrospinal fluid lumbar
drainage.
•• The anterior skull base defect was reconstructed with a pedicled mucosa
flap from nasal septum (Hadad-Bassagasteguy flap).
•• The endonasal approach with the operating microscope appears to be an
effective minimally invasive method for removing relatively small midline
tuberculum sellae meningiomas.
•• Intraoperative ultrasound, the micro-Doppler probe and angled endoscopes
are useful adjuncts for safely and completely removing such tumours.
•• Exclusive endoscopic endonasal approaches have also been described
for the removal of tuberculum sellae meningiomas.
•• More recently, the sublabial trans-sphenoidal approach has been used to
remove such tumours.
1245
ADJUVANT THERAPIES
•• Meningiomas, which invade intracranial bone structures and the adjacent
areas, are frequently unresectable because of their aggressive and
recalcitrant growth behaviour.
•• Also, surgically inaccessible meningiomas may not be removed completely.
They have a high recurrence rate and in approximately 10% of these
tumours there is an increased risk of malignancy.
•• Significant morbidity and mortality rates associated with recurrent
meningiomas demand non-surgical approaches.
•• There is currently no effective chemotherapy for meningiomas and adjuvant
hormonal treatment has not proven beneficial.
•• The topoisomerase I inhibitor irinotecan (CPT-11) was much more
effective against the malignant meningioma cell line than against primary
meningioma cultures.
•• The anticancer drug hydroxyurea has been tested for its potential use in the
treatment of meningiomas. A significant arrest of meningioma cell growth in
the S phase of the cell cycle was revealed on DNA flow cytometry.
•• Fractionated stereotactic conformal radiosurgery (SCRT) is a feasible
high precision irradiation technique for residual and recurrent skull base
meningiomas, including both small and larger tumours with excellent early
tumour control and low toxicity.
•• Longer follow-up is necessary to demonstrate sustained tumour control
and low morbidity of such a high precision localised method of fractionated
irradiation.
•• Intensity modulated radiotherapy (IMRT) in the treatment of central nervous
system meningiomas is feasible and safe, offering highly conformal
irradiation for complex-shaped skull-base tumours, while sparing adjacent
critical structures.
166
CHAPTER Sphenoidal Wing
Meningiomas
Trimurti D Nadkarni
INTRODUCTION
•• Meningiomas account for 14−18% of all intracranial neoplasms.
•• Meningiomas arising from the sphenoid ridge constitute approximately
14−20% of all meningiomas.
•• The complexity of these tumours is due to the involvement of the anterior
circulation, anterior visual pathways and oculomotor nerve.
•• The rate of recurrence for medial sphenoid wing meningiomas after surgery
is reported as one of the highest for intracranial meningiomas.
•• Two main types of tumours have been described according to their
presentation: globoid tumours with a nodular shape and en plaque tumour.
•• The nodular type is an encapsulated tumour of variable size that displaces
or encases intracranial arteries or cranial nerves (CNs). This tumour has a
dural site of implantation through which it receives its blood supply.
•• In meningioma en plaque, the tumour cells fill the haversian canals
spreading into the adjacent bones that include the pterion, orbital wall,
malar bone, zygomatic, temporal and middle cranial fossa. The tumour
produces a hyperostotic reaction of these structures causing exophthalmos
and temporal bowing. In addition, an intracranial meningiomatous plaque
is always present.
•• Cushing and Eisenhardt have classified these tumours based on their site
of origin along the sphenoid wing as inner third, middle third and outer
third tumours.
•• Inner third tumours have been subdivided into sphenocavernous tumours
[(arising from the external wall of the cavernous sinus (CS)] and clinoidal
tumours (arising from the clinoid process).
•• Middle third tumours or alar tumours and the outer third or sphenotemporal
or pterional tumours present with symptoms due to compression of adjacent
structures.
Inner Third Sphenoid Wing Meningiomas
•• Clinoidal meningiomas produce a progressive diminution of vision beginning
with ipsilateral nasal hemianopsia.
•• As the tumour grows, a superior temporal field defect occurs and eventually
the eye becomes blind.
•• Foster Kennedy syndrome, ipsilateral primary optic atrophy associated with
contralateral papilloedema, may result.
Chapter 166 • Sphenoidal Wing Meningiomas
1247
•• In sphenocavernous tumours, abducens palsy is the first presentation.

•• As symptoms evolve, total ophthalmoplegia is associated with hypoesthesia
in the ophthalmic division of the trigeminal nerve.
•• Exophthalmos may result due to venous compression at the orbital apex.
Middle Third or Alar Meningiomas

•• These tumours present with features of raised intracranial pressure.
•• Headache and papilloedema are followed by anosmia, contralateral
homonymous hemianopsia, personality changes, visual or olfactory
hallucinations, contralateral facial palsy and hemiparesis.
•• Seizures may occur.
External Third or Pterional Meningiomas

•• The en plaque variant presents with proptosis or chronic palpebral oedema.
•• Skull deformities, loss of visual acuity leading to blindness, diplopia,
epiphora, photophobia and seizures may occur.
•• Globoid pterional meningiomas present with hemicranial headaches,
seizures, contralateral hemiparesis and increased intracranial pressure.
•• The tumour behaves either as a temporal or a frontal mass.
•• Signs of orbital involvement may also be present.
NEURORADIOLOGY
•• Focal hyperostosis, sclerosis, erosion at the site of tumour attachment,
widening of vascular grooves, superior orbital fissure and narrowing of
optic canal are all demonstrated on bone algorithms and three-dimensional
CT reconstruction.
•• CT scans clearly demonstrate the bone involvement, the orbit and extension
of the tumour plaque.
•• In addition, tumour calcification and peritumoural oedema are observed.
•• Magnetic resonance (MR) scans clearly show the intracranial extensions
of the mass.
•• Meningiomas enhance uniformly after gadolinium injection.
•• The extent of the meningiomatous plaque and thickened adjacent dura
(dural tail sign) are clearly defined.
•• The arterial relationship of the tumour is noted as flow voids.
•• The ICA may be encased and may be narrowed or occluded.
•• MR angiography can be done simultaneously to demonstrate the anterior
circulation in relation to the tumour.
•• ICA encasement was more commonly seen in tumours that involved the CS.
TREATMENT
•• Radical excision of the tumour is the primary treatment for meningiomas
and is the principle surgical goal.
•• Inner third meningiomas present problems different from those of the outer
third of the sphenoid ridge.
•• Sphenocavernous meningiomas arising from the outer wall of the CS,
involving the oculomotor or trigeminal nerve, involve the CS and encase
the ICA. In such cases total resection of the tumour is impossible.
•• Similarly, an en plaque pterional meningiomas presenting with proptosis,
frontotemporal involvement and palpebral oedema, tumour infiltrating
1248
into the dura, periorbital tissues, CS and zygomatic fossa, are difficult to
operate upon.
•• Cerebral angiography is now used to embolise tumour feeders to permit
tumour resection without excessive blood loss.
Surgical Treatment
Pterional Meningiomas
•• A frontotemporal craniotomy is performed through an incision within the
hairline. This permits a wide orbital exposure and provides for a pericranial
graft, if necessary.
•• The hyperostotic thickened bone is excised, decompressing the superior
orbital fissure and optic canal, along with a wide frontal craniotomy.
•• The thickened dura, intracranial tumour and orbital extension are excised.
•• The middle cerebral artery, carotid artery and optic nerve are preserved.
•• The pericranial graft is used to close the resected dura.
•• Bone reconstruction is done with methyl methacrylate, split calvarial or rib
graft if required.
Inner and Middle Third Meningiomas
•• Clinoidal tumours have a dural attachment on the upper surface of the
anterior clinoid process, whereas sphenocavernous tumours are attached
to the sphenocavernous angle.
•• A frontotemporal craniotomy is performed.
•• The lesser wing of the sphenoid is nibbled to the superior orbital fissure, to
allow exposure of the tumour with minimal brain retraction.
•• The Sylvian fissure is widely opened and the MCA and its branches are
identified in relation to the capsule of the tumour.
•• The supraclinoid ICA, MCA and its branches need meticulous dissection
to avoid vascular injury.
•• Simpson Grade I excision of a clinoidal meningioma is possible.
•• For sphenocavernous tumours, extracavernous extirpation with coagulation
of dural attachment is advised (Simpson Grade II).
•• In tumours with CS invasion, the CS is opened through its superior wall,
the optic canal is opened and tumour is excised.
•• CSF leak and infection are carefully avoided by using pericranial graft
and fibrin glue.
Surgical Complications
•• The most common surgical complication is post-operative subcutaneous
cerebrospinal fluid collection and hydrocephalus.
•• Post-operative infarction of the middle cerebral artery territory can occur.
•• The other complications seen were haemorrhage, brain oedema and
meningitis.
Results
•• Meningiomas of the skull base are associated with the highest rate of
tumour recurrence, related to their wide dural attachment, invasion of the
CS, invasion of the underlying bone and extension of the tumour through the
foramina and fissures of the skull base into the orbit and zygomatic fossa.
•• Radiotherapy appears to halt the growth of the tumour.
Chapter 166 • Sphenoidal Wing Meningiomas
1249
GAMMA KNIFE SURGERY FOR

MENINGIOMAS OF THE SPHENOIDAL WING
•• Radiotherapy for meningiomas has been used in recurrent or partially
resected tumours, especially when performed to avoid neurological
morbidity.
•• As the sphenoid bone forms the lateral and posterior walls of the orbit, these
tumours involve the periorbital structures. The tumour displaces rather than
invades the orbital contents.
•• Tumour growth has been effectively controlled with a dose of 9 Gy, tolerable
to the optic pathway and nerves within the CS.
•• The dose limit for the optic nerve is 8 Gy, 15 Gy for the third, fourth and
sixth CNs and 13 Gy for the fifth CN.
•• The tumour responds within 4−20 months.
•• Growth arrest and reduction in tumour volume is achieved in 90% of cases.
MEDIAL SPHENOID WING OR

CLINOIDAL MENINGIOMAS
•• Clinoidal meningiomas are formidable tumours to resect when their size
is large and when they involve the optic nerve, ICA and its branches and
the oculomotor nerve.
•• Goel et al. have classified tumours based upon the extent of visual
impairment, size of tumour and the tumour relationship with the internal
carotid artery.
•• The grading system is used to plan the operative strategy, anticipating
the extent of resectability and possible difficulties in dissecting the carotid
artery and optic nerve during the operation.
•• Al-Mefty has identified three distinct groups of clinoidal meningiomas on
the basis of the site of tumour origin and the presence/absence of the
arachnoidal plane between the tumour and the ICA.
•• Group 1 tumours are those encasing and directly attaching to the ICA
adventitia, without a definable arachnoidal plane between the tumour and
ICA. Total resection is not possible in these cases.
•• Group 2 consists of tumours with a separate arachnoidal plane between
the tumour and the ICA that facilitates total removal.
•• Group 3 tumours are actually optic nerve sheath or optic foramen
meningiomas and not truly clinoidal tumours.
•• Unilateral visual loss is the most common clinical presentation of these
tumours.
•• The visual impairment occasionally involves the contralateral eye.
•• The deterioration is in both visual acuity as well as fields.
•• The other presentations include headaches, diplopia, seizures, facial pain,
proptosis and ptosis.
•• The skull base surgical technique involves the following steps:
–– Frontotemporal craniotomy
–– Sphenoid ridge drilling
–– Limited posterior orbitotomy
–– Posterolateral orbital wall removal (or osseous decompression of the
superior orbital fissure)
–– Optic canal unroofing
–– Extradural complete anterior clinoidectomy and
–– Optic nerve sheath opening.
1250
•• The intracranial tumour is excised.

•• If the CS involvement is extensive and the tumour is fibrous, surgery is
stopped after confirmation of the following:
–– Gross-total resection of the intradural extracavernous portion of the
tumour and removal of any accessible tumour-involved dura.
–– Decompression of the optic nerve.
–– Decompression of the oculomotor nerve.
•• In conclusion, total resection of clinoidal meningiomas is feasible with an
excellent visual outcome, keeping the surgery related morbidity low, by the
use of skull base technique.
•• Tumours without involvement of the CS have better resection, less
recurrence and neurological improvement.
•• The CS tumours are best managed with adjuvant radiosurgery.
167
CHAPTER
Tentorial Meningiomas
Vijendra Kumar Jain  Sanjay Behari  Pramod Giri
INTRODUCTION
•• Tentorial meningiomas (TM) are relatively uncommon lesions accounting
for 2−9% of all intracranial meningiomas and 30% of posterior fossa
meningiomas (Fig. 1).
RELEVANT MICROSURGICAL ANATOMY

Tentorium
•• The tentorium separates the cerebellum from the temporal and occipital
lobes and contains an opening in the centre, known as the incisura,
connecting the supratentorial and infratentorial compartments.
•• The apex of the tent shaped tentorium is formed by the posterior edge of
the incisura.
•• From the apex, the tentorium slopes downwards up to its bony attachments
to the temporal, occipital and sphenoidal bones.
•• It has three borders, namely, anterior (attached to the petrous ridge and
enclosing the superior petrosal sinus) and lateral and posterior (attached to
the temporal and occipital bones at the groove of the transverse sinus and
internal occipital protuberance) enclosing the transverse sinus and torcula.
Fig. 1: Schematic diagram showing various locations of tentorial meningiomas

(TM). 1: Medial tentorial edge; 2: Lateral tentorial edge; 3: Attached margin of
tentorial leaf; 4: Falcotentorial; 5: Torcular
1252
•• The free edge of the tentorium is attached anteriorly to the petrous apex
and anterior and posterior clinoid processes.
•• Between these three structures lies the oculomotor trigone through which
the IIIrd and IVth cranial nerves enter the cavernous sinus.
•• From the anterior part of the free edge of the tentorium, the dura mater
slopes steeply downwards to form the lateral wall of the cavernous sinus
and the base of the middle cranial fossa.
•• In the posterior part of the tentorium, the falx cerebri fuses with the dorsal
surface of the tentorium in the midline behind the apex and encloses the
straight sinus in the falcotentorial junction.
•• The tentorial incisura is triangular, its anterior edge is based on the dorsum
sellae and its apex is dorsal to the midbrain, just posterior to the pineal gland.
•• Its width varies from 26 mm to 35 mm and the anteroposterior diameter
from 46 mm to 75 mm.
Dural Venous Sinuses

•• From the torcula, at the level of the internal occipital protuberance, the
transverse sinus extends laterally and continues as the sigmoid sinus.
•• The occipital sinus extends inferiorly in the midline of the posterior fossa
dura and the superior sagittal sinus joins the torcula from the superior
aspect.
•• The straight sinus continues within the leaves of the tentorium in the midline
and joins the confluence of the transverse sinuses.
•• The superior petrosal sinus runs along the superior petrosal ridge from the
cavernous sinus to the transverse-sigmoid junction.
•• The temporal anastomotic vein of Labbe courses back on the surface
of the temporal lobe from the superficial middle cerebral vein to join the
transverse-sigmoid sinus junction.
Blood Supply of the Tentorium

•• The anterior and medial portions of the tentorium are supplied by branches
of the meningohypophyseal trunk namely: the artery of Bernasconi and
Cassinari (the basal tentorial artery) and the artery of the inferior cavernous
sinus (the marginal tentorial artery). These are branches of the cavernous
carotid artery.
•• The posterior tentorial margin and apex are supplied by branches from
the posterior cerebral and superior cerebellar arteries, as well as from the
meningeal branches of the external carotid and vertebral arteries.
CLASSIFICATION
•• TM may have supratentorial, infratentorial or combined supra and
infratentorial growth (perforating meningiomas).
•• The true dural attachment is often not reliably defined, because the tumour
may extend to the tentorium after originating from the dura of the petrous
bone, clivus, anterior clinoid, falx, and transverse and sigmoid sinuses.
•• Mallis has divided TMs into: (a) parasellar; (b) petroclival tentorial angle;
(c) tentorial apex; (d) tentorial leaf and (e) torcular.
•• Bassiouni et al. have modified Yasargil’s classification of TM as: T1-2:
medial; T3-8: falcotentorial; T4: paramedian; T5: peritorcular; T6-7: lateral
and falx cerebelli.
Chapter 167 • Tentorial Meningiomas
1253
•• Bret, et al. distinguish the various subtypes of TM according to their

relationships to the free edge (inner ring) and to the peripheral tentorium
(outer ring).
SIGNS AND SYMPTOMS

•• The majority of patients are women (approximately 60%) who present in
the fourth and fifth decades.
•• The most common presentations of TM include headache, seizures,
raised intracranial pressure, papilloedema, bilateral sixth nerve palsy and
cognitive disturbances.
•• Tumours with extension under the occipital lobe may produce homonymous
hemianopia, while those with posterior fossa involvement may present
with cerebellar and long tract signs, multiple cranial nerve palsies and
hydrocephalus.
•• TMs involving the tentorial incisura may present as fourth nerve palsy
and brainstem compression syndrome, while tumours extending up to the
posterior third ventricular region may present rarely as Parinaud’s syndrome
•• Those with cerebellopontine angle extension may also present with
Vth, VIIth, VIIIth, IXth and Xth cranial nerve involvement with cerebellar
signs and those extending into the anterior clinoid, cavernous sinus and
suprasellar region may produce IIIrd, IVth, Vth and VIth nerve palsies and
•• Other reported presentations include impaired mentation, trigeminal
neuralgia, hemifacial spasm, gelastic seizures, pituitary and hypothalamic
disturbances and predominant contralateral signs due to brainstem
distortion.
•• Syringomyelia may be associated with TMs, perhaps due to tumour induced
tonsillar herniation.
INVESTIGATIONS
•• Multiplanar CT and MR imaging with contrast (with CT or MR angiography)
give an accurate localisation, supra and infratentorial extension, site of dural
attachment, involvement and patency of dural venous sinuses and deep
venous system, infiltration along the skull base, involvement of adjacent
vasculature and relation of the tumour to the brainstem and cranial nerves.
•• MR imaging with contrast may often show an extensive dural tail sign.
Angiography with Tumour Embolisation

•• The blood supply to TM as well as the involvement of the dural venous
sinuses and their dominance may be defined on the basis of arterial and
venous phase angiography, respectively.
•• The displacement of vessels indicating attachment of the tumour to the
tentorium may be seen.
•• In case of encasement of major blood vessels by the TM, a balloon
occlusion test may be performed to evaluate the capacity of the contralateral
circulation to support the circulation on the side of the TM, in the event that
the latter circulation is compromised during surgery.
•• Superselective catheterisation of the meningeal supply to the TM and pre-
operative embolisation permits surgical resection with minimal blood loss.
1254
•• Embolisation is especially helpful when the major arterial supply is from the
external carotid artery by its meningohypophyseal trunk or by the posterior
middle meningeal or ascending pharyngeal arteries.
•• It is recommended that surgical resection be performed within 1−10 days
of the pre-operative embolisation to allow for maximum vessel thrombosis
without recanalisation.
SURGICAL APPROACHES
•• The primary goal of surgery is to remove the TM along with its dural
attachment and also the involved bone in the case of bony invasion.
•• The selection of the approach (Table 1) and decision of radical excision
entirely depend on the location of the lesion.
•• Although the ideal goal is total tumour resection, it should not be achieved
at any cost and all attempts should be made to preserve the brainstem,
cranial nerves and vascular structures.
•• Intra-operative monitoring may be performed by recording brainstem
evoked potentials, somatosensory evoked potentials and facial nerve
electromyographic evaluations.
•• The tumour, medial or lateral is usually approached through a combined
supratentorial-infratentorial exposure, unless the tumour is on one side of
the tentorium with only a minimal extension into the other compartment.
PRIMARY TENTORIAL MENINGIOMAS

Tentorial Free Edge Meningiomas
•• Anterior supratentorial lesions in this location may be approached by the
subtemporal or trans-sylvian frontotemporal route or a combination of both
the approaches.
•• With these approaches, one can visualise the superior surface of the
tentorium, the anterolateral surfaces of the midbrain and pons, the posterior
cerebral, posterior communicating and superior cerebellar arteries and the
IIIrd and IVth cranial nerves.
•• When the tumour extends along the cerebellopontine angle in the posterior
fossa, compressing the brainstem and cranial nerves and reaching up to
Table 1: Location of tumours and their surgical approaches

Tumour location Surgical approach
T1−T2 (medial) Infratentorial Supracerebellar infratentorial
T3−T8 (falcotentorial) Supratentorial Suboccipital retrosigmoid
T4 (paramedian) Supra-infratentorial Subtemporal
Supratentorial Infra-supratentorial presigmoid
T5 (peritorcular) Supra-infratentorial Bioccipital interhemispheric
Infratentorial Occipital transtentorial
Supra-infratentorial Bioccipital/suboccipital
T6−T7 (lateral) Infratentorial Supracerebellar infratentorial
Supratentorial Bioccipital/suboccipital
Falx cerebelli Infratentorial Suboccipital retrosigmoid
Supracerebellar infratentorial
Subtemporal
Supracerebellar infratentorial
1255
the free edge of the tentorium from the inferior aspect, the retromastiod
approach should be considered.
•• A combination of the subtemporal and retromastoid approach may also be
used in case the tumour extends in both the supratentorial and infratentorial
regions, as well as anteromedially to involve the cranial nerves and
brainstem.
•• When the TM lies along the lateral incisural space, preservation of the
basal vein of Rosenthal, posterior cerebral and posterolateral choroidal
arteries, IIIrd and IVth nerves, lateral aspect of the mesencephalon and
medial aspect of the temporal lobe is required.
Tentorial Leaf and Lateral and Posterior Tentorial

Attached Margin Meningiomas
•• An occipital/parieto-occipital craniotomy or infratentorial supracerebellar
approach or a combination of both (on either side of transverse sinus) may
be adopted, depending on whether the tumour is mainly supratentorial,
infratentorial or both respectively.
•• The transverse sinus may only be resected when angiogram shows the
sinus on that side to be occluded by the tumour and when there is a clear
demonstration of a patent contralateral one.
•• Bleeding, air embolism from the sinus or visual field defects from occipital
lobe handling are the major causes of morbidity.
Falcotentorial Meningiomas
•• These may be approached by an occipital, interhemispheric, transtentorial
approach utilising a bilateral or ipsilateral occipital craniotomy.
•• The supratentorial transtentorial approach may also be used for tumours
which have an infratentorial extension.
•• With lesions that are predominantly infratentorial, the infratentorial
supracerebellar approach may be used.
•• If located at the posterior part of the tentorial incisura, an occipital
interhemispheric transtentorial route may be used to access it from the
superior aspect, especially when the tumour is small.
•• In large infratentorial-falcotentorial tumours, the occipital interhemispheric
route may be combined with suboccipital craniectomy and supracerebellar
infratentorial approach.
•• A unilateral approach may cause homonymous hemianopia, while bilateral
occipital lobe retraction may result in cortical blindness due to contusion
and ischaemia of the calcarine gyrus.
Torcular Meningioma
•• The torcula consists of the confluence of five sinuses including two
transverse, one straight, one superior sagittal and one occipital sinus.
•• The surgical approach depends on tumour growth into one or more of the
four quadrants—right, left, supra and infra tentorial.
•• Patients with a unilateral lesion with both supratentorial and infratentorial
extensions may often be approached by a unilateral occipital or suboccipital
exposure but the approach may be augmented by a craniotomy both above
and below the tentorium and by cutting the tentorium and the falx.
1256
•• Venous infarction secondary to compromise of the venous sinus and

cortical blindness due to retraction damage of the occipital lobes are the
major hazards.
Complex Tentorial Meningioma

Parasellar and Cavernous Meningioma
•• These may involve the cavernous sinus, the carotid, anterior cerebral,
middle cerebral, posterior communicating, anterior choroidal and superior
cerebellar arteries and the IIIrd, IVth, Vth and VIth nerves.
•• They may be approached by a pterional craniotomy and trans-sylvian
approach and/or subtemporal approach or a combination of both the
approaches.
•• The need for pre-operative extracranial-intracranial bypass, may be
evaluated in case one expects to sacrifice the carotid artery during excision
of the tumour.
Cerebellopontine Angle Meningioma
•• These may be approached by a retromastoid craniectomy.
•• The cerebellopontine angle may be involved with tumours extending from
the tentorium to the petrous dura/clival dura.
Petroclival Meningioma
•• The approaches that may be used include combined subtemporal and
retromastoid approach with extra exposure provided by dividing the
transverse sinus and superior petrosal sinus distal to the insertion of the
vein of Labbé.
•• A large tumour in this location may also be approached by combining the
presigmoid and retrosigmoid approach and dividing the tentorium parallel
to the superior petrosal sinus towards the incisura.
Pineal Meningioma
•• These arise from the velum interpositum and may be approached using
either an infratentorial supra-cerebellar approach or via an occipital
transtentorial approach.
Basal Approches to Tentorial Meningiomas
•• In the excision of predominantly posterior fossa TMs, those meningiomas
situated posterior to the internal auditory meatus may be accessed easily
using a retrosigmoid approach.
•• However, for TMs that are premeatal, tentorial edge and petroclival,
the surgeon has to traverse the cerebellopontine angle cistern and its
neurovascular structures before reaching the tumour in the retrosigmoid
approach.
•• Medially situated TMs may be accessed using variations of skull base
approaches. These include presigmoid supra-infratentorial approach,
presigmoid and retrosigmoid translabyrinthine approach, subtemporal
presigmoid approach and transpetrosal approach.
•• Total surgical resection along with the adjacent dura and involved bone
may be difficult to achieve in a TM, where the tumour is adherent to the
brainstem, cranial nerves and venous sinuses.
1257
•• Since recurrence of the tumour following incomplete resection is always a

possibility, alternative management strategies may be used.
•• These are radiotherapy, stereotactic radiosurgery, chemotherapy and
steroid receptor antagonists.
•• Radiosurgery is a viable option for TM, due to their lack of brain invasion,
tendency to become symptomatic when relatively small, ability to be defined
by high resolution imaging and due to their basal blood supply that can be
included in the radiosurgical volume.
•• The efficacy of radiosurgery in the treatment of meningiomas is reflected
by a tumour control rate of almost 96−98%.
•• Radiosurgery is a valuable option for patients with small tumours (less
than 30 mm), those with minimal or no neurological deficits, but with a
documented increase in tumour size, those with small residual tumours
following microsurgical resection, elderly or medically unfit patients and
those who are unwilling to undergo surgery.
•• The maximum tumour dose varies from 24 Gy to 40 Gy; the dose received
by the brainstem has to be kept at or below 16 Gy.
•• Tumour control rate of 98% has been reported during a mean follow-up
of 3 years.
168
CHAPTER Posterior Fossa
Meningiomas
Amitabha Chanda  Abhijit Guha
EPIDEMIOLOGY
•• Meningiomas comprise about 20% of all primary intracranial neoplasms.
•• Of all meningiomas, 10−15% are in the posterior fossa.
•• Children show an increased incidence of posterior fossa meningiomas
(PFM) in comparison to adults.
•• The ratio of male to female incidences ranged from 1:1.4 to 1:2.8.
•• The incidence of meningiomas increases with age.
•• There is a predisposition of meningioma in Type II neurofibromatosis,
multiple meningioma syndrome and post-radiation to skull.
AETIOPATHOGENESIS INCLUDING
MOLECULAR BIOLOGY
•• Papovavirus antigen has been identified in human meningioma by
immunocytochemical techniques.
•• Many reports have shown that meningiomas have occurred following low
levels of radiation.
•• The latency of occurrence of meningioma is longer following low dose
radiation than that for meningiomas following high dose radiation. The
latency range is from 24 to 36 years.
•• In these radiation-induced meningiomas there is a higher incidence of
atypical meningiomas with more aggressive biological features.
•• It is well known that meningiomas occur with higher frequency in patients
with neurofibromatosis Type II (NF-2). With this knowledge, extensive
cytogenetic examination demonstrated that monosomy of chromosome 22
(or more specifically deletion of the 22q12 locus) was the most common
chromosomal abnormality seen in meningiomas.
•• A loss of NF-2 or other tumour suppressive genes along with activation
of proto-oncogenes are thought to cause meningiomas to arise. That the
product of the NF-2 tumour suppressor gene, merlin, is important in genesis
of meningiomas was supported by the fact that overexpression of merlin
significantly inhibited proliferation of meningioma cells.
•• Meningiomas, which occur more frequently in females, especially those
occurring in the spine, grow more rapidly during the luteal phase of the
menstrual cycle and during pregnancy.
•• This epidemiological observation has led to a search for the importance
of sex hormones and their receptors in the pathogenesis of meningioma.
Chapter 168 • Posterior Fossa Meningiomas
1259
•• The oestrogen receptors were found in about 30% of the tumours in a recent
study and most of them were the Type II subtype, which have lower affinity
and specificity for oestrogen than Type I have.
•• The other receptors found were progesterone receptors (50−100%),
androgen receptors (almost same frequency as that of progesterone
receptor), somatostatin receptors (almost 100%), growth hormone receptor
mRNA and dopamine receptors.
CLASSIFICATION
•• The classification of these tumours by Sekhar, et al. which is a modification
of the classification by Castellano and Ruggiero is based on dural
attachment (Table 1).
•• Type I includes meningiomas arising from the cerebellar convexity dura,
the lateral tentorium, transverse sinus, sigmoid sinus and the straight sinus.
These meningiomas have a propensity to invade the major venous sinuses.
Torcular meningiomas are also included in this type.
•• Meningiomas arising from the posterior face of the petrous bone dura,
lateral to the trigeminal nerve are Type II meningiomas. These can also
be classified as cerebellopontine angle meningiomas and can in turn be
divided into pre-meatal and post-meatal types.
•• Meningiomas arising from the dura mater around the jugular foramen with
or without extracranial extension, are Type III meningiomas.
•• Type IV or petroclival meningiomas arise from the petrous apex, medial
petrous ridge medial to the trigeminal nerve, upper two thirds of the clivus
with or without extension to the cavernous sinus and/or Meckel’s cave.
•• Meningiomas arising from the foramen magnum region, lower third of the
clivus and C1, C2 regions are Type V meningiomas.
•• Intracanalicular tumours (tumours in the internal auditory canal) or very
large posterior fossa cranial base meningiomas, which cannot be fitted
into any particular group. These are Type VI PFMs.
•• Five per cent of all intraventricular meningiomas arise in the fourth ventricle.
•• PFM without dural attachment were classified by Abraham and Chandy
into three types: (1) Meningiomas originating from the choroid plexus of
the fourth ventricle and developing solely within the fourth ventricle; (2)
Meningiomas originating in the inferior tela choroidea, developing partly
in the cerebellar hemisphere and vermis and (3) Meningiomas within the
cisterna magna without any attachment to the dura mater.
Table 1: Classification of posterior fossa meningioma

Type I Cerebellar convexity and lateral tentorial
Type II Pre-meatal
– Lateral petrous ridge and
– Cerebellopontine angle
Type III Post-meatal
– Jugular foramen
Type IV Petroclival
Type V Foramen magnum
Type VI Unclassified
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PATHOLOGY
•• Meningiomas arise from the arachnoid cap cells. This origin was supported
by the fact that the arachnoid cap cells parallel in frequency the sites of
meningioma formation.
•• Macroscopically, these tumours appear well encapsulated and lobulated
with a fine leash of vessels on the surface.
•• More vascular meningiomas are characterised by a reddish meaty
appearance.
•• Most of the tumours tend to be globular but other shapes according to the
location may also be seen.
•• There are several histopathological classification schemes for meningiomas.
•• However, the most popular one is the classification by Russell and
Rubenstein, who classified meningioma into meningotheliomatous
(syncitial), fibrous, transitional and angioblastic types. Fatty degeneration,
haemorrhage, calcification and cyst formation may occur.
•• However, in this system there is always a controversy whether an
angioblastic meningioma is the same as haemangiopericytoma.
•• The World Health Organization (WHO) classification is simpler and
distinguishes three grades of meningioma which is useful for prognosis
(Table 2).
•• The grading is mostly dependent on the proliferating potential of the tumour.
Proliferative activity is usually determined by a labelling index (LI).
•• The LI distinguishes Grade I meningiomas (LI: 0.02−0.9%) from “atypical”
meningiomas (LI: 1.5−2.0%) and “anaplastic” meningiomas (LI: 9−13%)
and predicts the chance of recurrence.
•• Several histopathological features are also associated with recurrence
and aggressive behaviour. They are haemosiderin deposition, loss of
architectural pattern, growth in sheets, prominent nucleoli, mitotic figures,
necrosis, nuclear pleomorphism, frank invasion of brain by meningioma
cells and overall atypical or malignant tumour grade.
Table 2: WHO classification of meningoepithelial tumours

I. Benign meningioma
i. Meningothelial (syncitial)
ii. Transitional
iii. Fibrous
iv. Psammomatous
v. Angiomatous
vi. Microcystic
vii. Secretory
viii. Clear cell
ix. Chordoid
x. Lymphoplasmacyte-rich
xi. Metaplastic variants (xanthomatous, myxoid, osseous, cartilaginous, etc.)
II. Atypical meningioma
III. Anaplastic (malignant) meningioma
i. Variants of benign meningioma
ii. Papillary
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CLINICAL FEATURES
Type I
•• Type I PFMs usually present with raised intracranial pressure and progressive
cerebellar signs (ataxia, dysmetria, nystagmus, etc.).
•• When the supratentorial component of a tentorial meningioma is large, there
may be visual field defects.
Type II
•• Type II PFMs commonly present with cranial nerve deficits and/or cerebellar
signs and symptoms.
•• Facial pain and/or numbness, facial weakness, hearing loss and ataxia are
the usual presenting features.
•• CPA meningiomas tend to involve the trigeminal and facial nerves earlier than
auditory and vestibular impairment, compared to vestibular schwannomas.
•• These Type II PFMs tend to involve the lower cranial nerves more than
vestibular schwannomas.
Type III
•• Type III PFMs usually present with lower cranial nerve symptoms like
dysphagia, hoarseness of voice, nasal regurgitation, etc.
•• Additionally, they may also present with a neck mass, when there is
significant extracranial extension into the neck.
•• Several syndromes are associated with meningiomas of this group
depending on the combination of cranial nerve involvement (e.g. Vernet’s
syndrome—Cranial nerves IXth, Xth, XIth; Collet’s syndrome—Cranial
nerves IXth, Xth, XIth, XIIth).
Type IV or the Petroclival Meningiomas

•• They most commonly present with trigeminal nerve involvement like facial
numbness and/or pain.
•• Facial nerve involvement and hearing impairment are not uncommon.
•• The lower cranial nerves and ocular motor nerves (most commonly
abducens) are involved in approximately one-third of patients.
Type V
•• Type V meningiomas arise in the foramen magnum region and commonly
present with suboccipital and neck pain (usually in C2 dermatome),
ipsilateral upper limb paraesthesia, cold dysaesthesia, contralateral
dissociated sensory loss, limb weakness starting in the upper limbs and
wasting of small muscles of the hands.
•• Lhermitte’s phenomenon in the absence of other evidence of multiple
sclerosis or cervical spondylosis may also be present.
•• Patients may also demonstrate “piano-playing fingers”, which means when
they close their eyes and hold their arms outstretched, they will have slow
athetosis-like movements of their arms, hands and particularly fingers.
Type VI or the Unclassified Posterior Fossa Meningiomas

•• They may be asymptomatic and the symptoms depend upon the location
and size of the tumour.
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•• For example, an intracanalicular meningioma will have hearing loss as the

presenting feature, while very large PFMs can have multiple cranial nerve
palsies, cerebellar involvement, sensory and motor dysfunctions.
•• Fourth ventricular meningiomas usually present with features of increased
intracranial pressure due to hydrocephalus, truncal ataxia, nystagmus,
down beat nystagmus, etc.
DIAGNOSTIC RADIOLOGY
•• A typical meningioma on non-enhanced CT scan is isodense to slightly
hyperdense to brain with homogeneous density.
•• Calcification may be seen in 15−20% of cases and may be punctate, rim-
like, chunky or nodular.
•• Dense calcifications may be confused with haemorrhage but can be
differentiated by density numbers.
•• Variable degree of oedema, evidenced as low density on CT scan, may
be found, but is usually mild or absent in PFMs.
•• Bone changes may be hyperostotic or destructive. There is usually intense,
homogeneous enhancement on contrast administration.
•• Typically, there is sharp demarcation and a broad base against bone or
free dural margins.
•• Areas of hyperdensity, hypodensity and non-uniform enhancement may be
seen, which may represent haemorrhage, cystic degeneration or necrosis.
Often, aggressive meningiomas are characterised by indistinct or irregular
margins.
•• Magnetic resonance imaging (MRI) scan is usually the radiological
investigation of choice.
•• On the T1 image most of these tumours are isointense to grey matter.
•• On the T2 image approximately half of the tumours appear isointense to
grey matter and less than half are hyperintense to grey matter.
•• Features like vascular distortion and/or encasement, tumour vascularity
and marginating characteristics are much better appreciated on MRI scans
than on the CT scan.
•• Displacement of blood vessels, presence of CSF spaces between the
tumour and the brain parenchyma and inward displacement of grey-white
junction are the typical marginating characteristics.
•• As the intensity in the T2 image depends on water content of the tumour,
a hyperintense tumour on the T2 image usually means a softer tumour.
•• The aetiology of oedema in the adjacent brain parenchyma is controversial.
•• There are many hypotheses like venous obstruction, invasion of
parenchyma, pial invasion and secretion of oedemogenic factors.
•• The most likely aetiology is pial invasion in conjunction with release of
oedema promoting factors such as vascular endothelial growth factor (VEGF).
•• It has been shown that the peritumoral “oedema” implicates difficulty in
microsurgical dissection of the tumour from the brain parenchyma, worse
surgical results and increased chance of recurrence.
•• On administration of gadolinium contrast, most meningiomas enhance
intensely and homogeneously.
•• Contrast MRI is the most sensitive test and the investigation of choice to
detect meningioma.
•• Contrast enhancement of the dura mater extending away from the margin
of the lesion is the “dural tail” and a characteristic sign to differentiate from
other tumours.
1263
•• Although once considered almost pathognomonic for meningioma, it may

also be rarely seen in other tumours like acoustic neuromas, superficial
intra-axial malignancies or dural-based metastasis.
•• The role of angiography in management of meningiomas has changed in the
modern era, due to the advent of CT and MRI scans. Visualisation of the pial
blood supply, in the arterial phase of the angiogram, has been shown to
predict difficulty in extrapial dissection.
•• Magnetic resonance spectroscopy (MRS) is still evolving as a diagnostic
tool for meningioma. Although both hydrogen (proton) and phosphorous-
based in vivo MRS have been reported, proton based MRS is used clinically
more often.
•• In normal hydrogen-based MR, the spectrum for brain tissue displays well-
defined peaks at 3.2 ppm for choline, 3.0 ppm for phosphocreatine/creatine
(PCr/Cr), 2.0 ppm for N-acetyl aspartate (NAA) and a less well-defined
peak for lactate at 1.3 ppm.
•• In meningiomas, there is a marked increase in choline signal and a marked
drop in both NAA and PCr/Cr peaks. The reduction of NAA is explained by
the fact that NAA is confined to neurons.
•• Increase in choline signal implies an elevated concentration of mobile
membrane components, which is expected in any tumour.
•• Magnetic resonance spectroscopy can be useful in differentiating many
slow growing tumours from meningioma and for grading of tumour
aggressiveness.
DIAGNOSTIC CHALLENGES
•• Some CPA meningiomas may be difficult to differentiate from vestibular
schwannomas, which are much more common.
•• Certain diagnostic useful points include:
–– Relationship of the tumour to the internal auditory canal and meatus
(usually vestibular schwannomas are centred over the internal auditory
meatus, whereas meningiomas are eccentric);
–– Presence of dural tail in meningiomas, although dural tail has been
reported with vestibular schwannomas also
–– Hearing preservation is much more likely in larger CPA meningiomas
than in a large vestibular schwannoma and
–– Extension into the internal auditory canal suggests, but is in no way
pathognomonic, of vestibular schwannomas.
•• Another diagnostic challenge is differentiation between a jugular foramen
meningioma and a glomus jugulare tumour. Computed tomographic scan
shows bony destruction, sclerosis or hyperostosis in meningioma, whereas
in glomus jugulare tumour the smooth regular contour of the eroded bone is
characteristic. Salt and pepper appearance and serpentine flow voids in MRI
and angiograms with early venous drainage are characteristics of glomus
tumour. Angiogram shows longer lasting tumour blush in meningiomas.
•• A third diagnostic challenge is distinction between a fourth ventricular
meningioma and other fourth ventricular tumours like ependymoma,
medulloblastoma or choroid plexus papilloma.
TREATMENT
•• Observation, radiation treatment and surgical resection are the main
treatment options.
1264
•• Several factors affect the ease of surgical removal including location, size,
consistency, vascular and neural encasement or involvement, prior surgery
or radiation treatment.
•• The necessity for resection of not only the tumour but also the involved
dura mater and bone are appreciated.
•• Although a number of adjuvant therapies have come up, the only validated
form of adjuvant therapy is radiation therapy, of which, gamma knife
radiosurgery is a promising one.
•• Observation in a small asymptomatic meningioma or in an elderly or
medically sick patient remains a valid option.
SURGICAL TREATMENT
Factors in the decision to operate include:
•• Tumour is causing symptoms.
•• Tumour is growing as evidenced by serial imaging.
•• Operation can relieve symptoms or at least stop progression of symptoms
•• Even though asymptomatic the patient is in imminent danger of
decompensation, as in a tumour with significant brainstem compression
or tonsillar herniation.
•• Tissue diagnosis when diagnosis is in doubt especially when there is a
confusion whether the lesion could be a dural based metastasis; and
•• Acceptable risks versus natural history of the tumour and patient
characteristics.
General Principles
•• Embolisation prior to surgery may reduce the tumour vascularity and
decrease tumour bleeding during surgery.
•• The optimum time between embolisation and operation is controversial.
•• When non-absorbable particles are used, it is prudent to wait for 7−10
days, allowing time for necrosis of the tumour. If absorbable particles are
used, it is advisable to operate within 48 hours of embolisation, i.e. before
recanalisation occurs.
•• Positioning of the patient should account for: (1) Accessibility to the tumour;
(2) Unimpeded venous drainage; (3) Maximum benefit of gravity (so that
the brain falls away by gravity and not by retraction); and (4) Position is
safe for the patient and comfortable for the surgeon.
Surgical Approaches Used by Tumour Location

Type I Posterior Fossa Meningiomas
•• The status of the lateral sinus is of prime importance in these meningiomas,
especially the lateral tentorial meningiomas.
•• If the lateral sinus is completely occluded, the sinus can be transected
along with the tumour.
•• In a partially occluded sinus the status of the contralateral sinus is important
before one can contemplate excision to achieve total removal.
•• For tentorial meningiomas with both supratentorial and infratentorial com-
ponents, a combined occipital-suboccipital craniotomy is helpful. For this,
somatosensory evoked potential (SSEP) should be monitored. Moreover,
if possible, visual evoked potential (VEP) should also be monitored.
•• For cerebellar convexity meningioma, the surgical approach is suboccipital
craniotomy. Depending on the location, the approach can be midline
suboccipital or lateral suboccipital.
1265
•• For midline suboccipital craniotomy, the patient is positioned prone and for
lateral suboccipital craniotomy the patient is operated upon in the lateral
position with side of the approach uppermost.
•• For tentorial meningiomas with both the supratentorial and infratentorial
components, the patient is placed in the three-quarter prone position with
the side of approach lowermost.
Type II Posterior Fossa Meningiomas
•• For post-meatal type of CPA meningiomas usually a standard retrosigmoid
approach allows sufficient exposure.
•• Brainstem auditory evoked potentials (BSAEP) and SSEP should be
monitored in all cases in addition to facial nerve monitoring.
•• Depending on the extent of lesion, trigeminal, glossopharyngeal, vagus,
accessory and hypoglossal nerves should also be monitored.
•• In smaller pre-meatal tumours, with a posteriorly placed sigmoid sinus
and significant anterior brainstem compression, the pre-sigmoid approach
is usually done to have an unobstructed and more lateral view, without
undue cerebellar retraction. A retrolabyrinthine type of pre-sigmoid petrosal
approach is sufficient in these cases and does not compromise hearing.
•• In contrast, tumours reaching the supratentorial compartment, especially
the Meckel’s cave, may be resected by adding a supratentorial craniotomy
or by the retrosigmoid intradural suprameatal approach (RISA).
•• The extended middle cranial fossa approach provides excellent access and
exposure to tumours in the anterior cerebellopontine angle and petroclival
junction.
Type III Posterior Fossa Meningiomas
•• These lesions are best approached by a posterior fossa infratemporal,
transjugular or infralabyrinthine approach, which are basically similar with
very minor variations.
•• Monitoring of the lower cranial nerves, BSAEP and SSEP is necessary.
•• The petro-occipital transigmoid (POTS) approach used for primary jugular
foramen meningiomas.
Type IV Posterior Fossa Meningiomas
•• For this group of meningiomas, a more lateral approach is needed than
for CPA meningiomas, in order to have adequate visualisation without
significant cerebellar retraction.
•• A petrosal approach is usually the ideal choice.
•• For lesions in the upper petroclival region or lesions lying completely above
the trigeminal nerve and reaching above the dorsum sellae, a frontotemporal
craniotomy with orbitozygomatic osteotomy is recommended.
•• If the tumour is not reaching above the dorsum sellae, a petrosal or partial
labyrinthectomy petrous apicoectomy (PLPA) approach is preferred.
•• The management of small petroclival meningiomas is still controversial, with
clinical observation, radiosurgery and surgical removal being the options for
treatment.
Type V Posterior Fossa Meningiomas
•• The approach depends on the precise location of the lesion.
•• For posteriorly located lesions, it is approached by midline suboccipital
craniotomy with resection of the posterior arch of atlas and laminae of axis
depending on the size of the lesion.
1266
•• A posterior suboccipital approach was utilised with lateral extension of the

bone opening, according to the localisation of the tumour which was ventral,
ventrolateral, dorsal and dorsolateral.
•• For tumours in the anterior or anterolateral aspect of the foramen magnum,
the extreme lateral transcondylar approach is recommended.
Type VI Posterior Fossa Meningiomas
•• The surgical approach depends on the location of the tumour.
•• Fourth ventricular meningiomas are approached via a standard midline
suboccipital approach.
•• Purely intracanalicular meningiomas can be resected either by the
retrosigmoid transmeatal approach or middle fossa approach.
RADIATION TREATMENT
•• The usual forms of radiation used are fractionated external beam radiation
and stereotactic radiosurgery.
Fractionated External Beam Radiation

•• A few retrospective well-conducted studies showed its effectiveness using
a higher dose of 45 to 60 Gy.
•• This was shown to be effective both for recurrence and after subtotal
resection.
•• However, caution must be exercised, as scattering of radiation can induce
complications, especially when dealing with lesions close to the brainstem.
•• Other complications include radionecrosis and secondary neoplasms.
•• Stereotactic radiosurgery is being used in increasing frequency and includes
proton beam, gamma knife radiosurgery (GKRS) and linear accelerators
(LINAC or X-knife).
•• A major advantage of gamma knife is the possibility of using a larger
number of isocentres.
•• However, risk of gamma knife or other forms of radiosurgery for meningioma
exists. This includes injury to encased cranial nerves, which tolerate
radiation poorly.
•• A potential long-term risk of either gamma knife or X-knife radiosurgery is
the risk of secondary neoplasms including malignant tumours.
•• The risk of complication is uncertain but linked to the degree of scatter
radiation and length of patient survival.
OTHER TREATMENTS
•• Apart from surgery and radiation treatment very little data is available on
the efficacy of chemotherapy, although several agents have been tried.
•• A combination of 5-fluorouracil, folinic acid and levamisole might be effective
in some forms of meningiomas.
•• A modest improvement in survival is seen in patients treated with a combination
of cyclophosphamide, adriamycin and vincristine for malignant meningioma.
•• Hormonal agents, like tamoxifen and mifepristone (RU-486), have been
tried without encouraging results.
•• Recombinant interferon α-2b has been used for a small number of patients
with aggressive meningiomas and it is apparently more effective than the
traditional chemotherapeutic agents.
169
CHAPTER Petroclival
Meningiomas
Trimurti D Nadkarni
INTRODUCTION
•• Meningiomas account for 14−18% of all primary intracranial tumours.
•• Approximately 10% of these occur in the posterior fossa.
•• Amongst the infratentorial meningiomas, 3−10% are clival and petroclival.
•• Radiosurgery has a definite role in the control of small tumour remnants,
as well as small unoperated tumours.
CLINICAL FEATURES
•• These tumours are predominantly seen in women in the fourth and fifth
decades of life.
•• The most common neurological deficits include cranial nerve deficits, ataxia
and hemiparesis or monoparesis.
•• The clinical syndrome is of insidious onset, often mimicking other
pathological processes; in elderly patients, the presenting symptoms are
often attributed to vertebrobasilar insufficiency.
•• The cranial nerve deficits include facial hypoaesthesia or anaesthesia with
or without dysaesthesia, dysconjugate gaze, decreased hearing, facial
paresis and decreased gag reflex.
•• Headache, gait ataxia, facial dysaesthesia, vertigo and deafness are the
more frequent presenting symptoms with the trigeminal nerve as the single
structure most often involved from onset.
•• Later symptoms include gait ataxia, diplopia, swallowing difficulty and
somatomotor deficits.
•• The typical sign of a petroclival meningioma is a relatively fair preservation
of hearing, in contrast to severe trigeminal involvement and impairment of
the cranial nerves below VIII, with accompanying cerebellar signs.
NEURORADIOLOGICAL EVALUATION
•• A contrast computed tomographic (CT) scan with bone algorithm in axial
and coronal views and a magnetic resonance imaging (MRI) scan are
performed to evaluate the relationship between the meningioma and the
cranial base and its bony involvement.
•• Fine cuts through the temporal bone define temporal bone anatomy and
the degree of pneumatisation, which facilitates the surgical exposure when
a transpetrosal approach is planned.
•• The most important information to know before surgery includes the site and
extension of dural attachment, tumour size, consistency, vascularity, bone
1268
involvement, tumour-brainstem interface, the position and encasement of

arteries and extensions of the tumour specifically to the cavernous sinus.
•• The presence of oedema on T2-weighted MR scans indicates a disruption
of the blood-brain barrier and invasion or adherence of the tumour to the
brainstem surface.
•• Pial invasion of the tumour is indicated by the loss of the arachnoid plane
on T1-weighted images and to the presence of blood supply to the tumour
from the vertebrobasilar complex in the arterial phase of angiography.
•• Patients may undergo cerebral angiography to study the vascular supply of
the tumour and to plan the endovascular and surgical procedure.
•• The tumour is principally fed by the meningohypophyseal trunk of the
ICA, the posterior branch of the middle meningeal artery, the meningeal
branch of the vertebral artery, the clivus artery originating from the carotid
siphon, the petrosal branches of the meningeal arteries and the ascending
pharyngeal branches of the external carotid artery.
•• Pre-operative embolisation should be performed through the main feeding
vessels, which makes the surgical procedure easier.
•• Encasement and narrowing of the main vascular channels may be noted.
Venous anatomy should be studied, especially if ligature of a dural sinus
is planned during the surgery. Temporal lobe venous anatomy is studied
if the presigmoid petrosal approach is planned.
OPERATIVE DETAILS
•• The primary goal of surgery is to define and protect cranial nerves and
vascular structures, as the tumour is progressively dissected free and
debulked.
•• Facial nerve stimulation with electromyography and brainstem auditory
evoked potentials may be used.
•• The selected approach should allow access to the vascular base during
the initial stages of resection.
•• The extent of surgical resection may be gross total, sub-total (more than
90% tumour volume resection) or partial (less than 90% tumour volume
resection).
•• This assessment is done on the basis of post-operative MR scan done at
3 months after surgery.
•• Simpson Grades I and II resection include complete excision of the tumour,
including dura and bone and reliable excision of the dural attachment
including coagulation.
•• The preferred approach for resection of petroclival meningiomas is
controversial.
•• Some surgeons prefer the retrosigmoid approach in the sitting position,
arguing for simplicity of approach and others prefer the petrosal approaches.
•• The transpetrosal partial labyrinthectomy petrous apicoectomy approach
or the orbitozygomatic frontotemporal approach takes a much longer time
to perform than the retrosigmoid approach.
•• The transpetrosal approach permits a direct view of the tumour, whilst in
the retrosigmoid approach the cranial nerve traction is extensive.
•• Transzygomatic approach may be used when the tumour involves the
upper clivus.
•• Tumours involving the lower and mid-clivus are approached by a presigmoid
approach, occasionally with division of a non-dominant sinus.
•• Skull base reconstruction is essential in all approaches to avoid CSF leaks.
Chapter 169 • Petroclival Meningiomas
1269
Surgical Approaches
•• Combined petrosal
–– Transpetrosal partial labyrinthectomy petrous apicoectomy
–– Transpetrosal total petrosectomy
–– Transpetrosal translabyrinthine.
•• Frontotemporal orbitozygomatic osteotomy (with transcavernous or
pericavernous dissection).
•• Retrosigmoid (with or without combined transcondylar exposure).
•• Middle fossa (preauricular sub-temporal with anterior petrosectomy).
Adjunctive Procedures
•• Arterial bypass with saphenous vein graft after excision of encased ICA and
sigmoid sinus division are the adjunctive procedures that may be required.
Tumour Characteristics
•• Surgical strategy is guided by the tumour characteristics is size, location,
extension etc.
•• The term petroclival implies an involvement of the petrous apex and upper
two-thirds of the clivus.
•• Tumours may be classified on the basis of size as small (< 1 cm), medium
(1−2.4 cm), large (2.5−4 cm) and giant (> 4 cm).
•• These tumours extend from the petroclival region to the cavernous sinus,
sphenoid, middle fossa, tentorium, Meckel’s cave, cerebellopontine angle,
jugular foramen and foramen magnum.
•• Adherent tumours are firmly attached to the pia, epineurium or vascular
adventitia and cannot be dissected free or can be separated using sharp
dissection.
•• Fibrous tumours are described as hard or rubbery requiring resection with
scissors and knife for most of the tumour removal.
•• Engulfing tumours are those that encircle neurovascular structures with an
identifiable intervening plane.
•• Adherent and fibrous tumours are often tethered to the brainstem and
cranial nerves. Dissection of these tumours may lead to excessive
manipulation of these vital neural structures resulting in morbidity.
•• Tumour remnants are best left attached to neurovascular structures rather
than risk direct injury.
•• Factors that limit extent of resection include hypervasularity, tumour
adhesion to neurovascular structures, tumour engulfment of neurovascular
structures and firm tumour consistency.
Post-operative Radiotherapy
•• Residual tumours may be subjected to radiosurgery or radiotherapy.
•• Stereotactic radiosurgery affords excellent tumour control with low morbidity
of cavernous sinus remnants, rather than the high risk of cranial neuropathy
associated with a cavernous sinus exploration.
Surgical Complications
•• New onset/progressive cranial nerve palsies
•• Long tract deficits
•• Brain infarction/cerebral oedema
•• Aspiration pneumonia
1270
•• Hydrocephalus
•• Cerebrospinal fluid leak
•• Brainstem haematoma
•• Cerebellar haematoma
•• Infection
•• Stupor and coma
•• Sinus thrombosis.
Long-term Disabilities
•• These include diplopia, hearing loss, facial numbness, imbalance, trigeminal
neuralgia, diminution of vision, xerophthalmia, facial weakness, limb
weakness, lower cranial nerve dysfunction and speech difficulties.
CONCLUSION
•• The ultimate goal of surgical treatment is a complete resection which is,
however, not always possible due to the consistency of the tumour, multi-
compartment involvement, adherence to the brainstem or encasement of
vertebrobasilar branches.
•• The excellent quality of life if the tumour is radically resected warrants
aggressive but judicious tumour resection with or without radiosurgical
treatment of tumour remnants.
170
CHAPTER Foramen Magnum
Meningiomas
Shrivastava RK  Chandranath Sen
INTRODUCTION
•• While meningiomas at the foramen magnum are the most common
tumour at this location, they are still very rare lesions when compared to
all intracranial tumours, and account for only 0.3–3.2% of all meningiomas
and between 4% and 15% of all posterior fossa meningiomas altogether.
•• The foramen magnum is a skull base foramen that is composed of the
occipital bone.
•• The occipital bone surrounds the foramen magnum and is composed of
two parts: the posterior squamosal and the narrower anterior part (basal
extension of the clivus).
•• The anterolateral walls are formed by the occipital condyles.
•• The contents of the foramen magnum consist of the caudal medulla, cranial
nerve XI (entering the skull), vertebral artery (VA), and the anterior and
posterior spinal arteries.
•• The XI cranial nerve is the only cranial nerve that passes through the
foramen magnum.
•• Its spinal component arises as a series of rootlets midway between the
ventral and dorsal rootlets of the upper cervical cord.
•• The transition between medulla and spinal cord is arbitrarily set to be at the
upper limit of the dorsal and ventral rootlets forming the first cervical nerve.
•• The rootlets of the XII cranial nerve exit the anterior medulla and pass
behind the VA to reach the hypoglossal canal just above and anterior to
the occipital condyles.
•• The specific orientation of the VA at this location and its course through the
transverse foramina and through the intracranial dura is what corresponds
to the landmarks to the surgical approaches to this region.
•• The VA enters the dura inferior to the lateral edge of the foramen magnum
through a tunnel approximately 5 mm in length.
•• The posterior inferior cerebellar artery usually has an intradural origin, but
may arise below the level of the foramen magnum.
•• Most tumours found at the foramen magnum are located anterolaterally,
however, most approaches to these lesions have historically been strictly
posterior.
•• The anatomical area of the anterior foramen magnum is comprised of
brainstem structures, cranial nerves and blood vessels all in a tight geo-
metric arrangement.
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•• The three general approaches to the anterior foramen magnum are:

1. Posterior/posterolateral suboccipital
2. Transoral
3. Extreme lateral transcondylar.
•• The choice of surgical approach is determined by the unique pathological
anatomy and each case is evaluated independently.
•• Most authors have adopted the Simpson scale as applied to meningiomas
to involve three categories:
–– Gross-total resection, including excision of the dural attachment and
drilling of adjacent bone (Simpson I and II)
–– Near-total resection, in which a few millimetres of insulated and cauter-
ised tumour were left on the vertebral artery (VA) or other vital structure
if the arachnoid plane could not be established (Simpson grade III)
–– Subtotal removal of more than 50% of the tumour (Simpson grade IV).
•• The general surgical determinants are:
–– Tumour location with respect to the foramen magnum
–– Anterior-posterior relationship of the tumour with respect to the caudal
medulla/spinal cord
–– Rostral-caudal extent
–– Laterality
–– Encasement/involvement of the VA.
•• The surgical corridor involves the space between the lateral margin of the
cervicomedullary junction and the medial aspect of the occipital condyle.
•• Corridor is defined as “narrow” if it provides a diameter of access to the
tumour of less than 1 cm; “adequate” if it is greater than 1 cm but less than
2 cm; and “large” if greater than 2 cm.
TUMOURS AT THE FORAMEN MAGNUM

•• Tumours at the foramen magnum are characteristically difficult to diagnose
clinically.
•• The wide spectrum of presenting signs and symptoms, combined with
their often insidious onset have been known to mimic many common
neurological diseases, such as cervical spondylosis, multiple sclerosis,
and other degenerating diseases.
•• The differential diagnosis of extra-axial foramen magnum tumours include:
–– Meningiomas are the most common
–– Chordomas
–– Neurilemmomas
–– Epidermoids
–– Chondroma
–– Chondrosarcomas
–– Metastatic lesions.
GENERAL PERI-OPERATIVE CLINICAL EVALUATION

AND NEUROPHYSIOLOGICAL MONITORING
•• The critical location of these tumours to vital neurological and vascular
structures necessitates a more detailed cranial nerve study.
•• Ophthalmological, audiometric, and electromyographic studies can be
supplemented to the pre-operative assessment of the patient’s baseline
functions.
Chapter 170 • Foramen Magnum Meningiomas
1273
•• Cranial nerves IX through XII are especially important, and a detailed

swallowing study and otolaryngological study of the vocal cords and the
larynx are also useful as a pre-operative baseline.
•• Careful assessment of the patient’s ability to protect the airway is man-
datory, and early tracheostomy may be advisable to avoid aspiration
pneumonitis.
•• The importance of preserving lower cranial nerve function is crucial during
the intra-operative procedure.
•• Intra-operative neurophysiological monitoring is used to prevent injury to
the cranial nerves.
•• Somatosensory evoked potentials and brainstem auditory evoked potentials
are monitored bilaterally.
•• Electromyographic monitoring of the vagal, accessory and hypoglossal
nerves are done on the ipsilateral side (or bilaterally if necessary).
•• The vagal nerve can be monitored with an electromyography electrode-
endotracheal tube or by laryngeal surface electrode that is placed after
intubation.
•• The accessory and hypoglossal nerves are monitored directly with
electrodes placed on the ipsilateral trapezius and the inferior aspect of the
tongue, respectively.
SURGICAL APPROACHES
THE POSTERIOR/POSTEROLATERAL
SUBOCCIPITAL APPROACH
•• The posterior suboccipital approach and its modifications (posterolateral)
have been the traditional approach for lesions of the foramen magnum
for many years.
•• The approach typically consists of a suboccipital craniectomy and partial
to complete laminectomy of C1/C2 depending on the size of the tumour.
•• The prone, three-quarter prone (“park bench”) or semi-sitting (“slouch”)
may be utilised depending upon the surgeon’s preference.
•• The vertical incision is used for lesions situated in the upper spinal canal
and posterolaterally at or above the foramen magnum.
•• The hockey-stick incision is selected if the lesion extends anterior
or anterolateral to the brainstem towards the jugular foramen or the
cerebellopontine angle (CPA).
•• This incision allows for removal of the full posterior rim of the foramen
magnum, the posterior elements of the atlas and axis and in addition,
a unilateral suboccipital craniectomy of sufficient size to expose the
anterolateral surface of the brainstem and the nerves in the CPA.
•• The actual amount of the suboccipital craniectomy and cervical laminectomy
varies depending upon the rostral/caudal extent of the tumour.
•• For anteriorly located tumours in this approach, the spinal cord is often
displaced dorsally and rotated away from the side on which the bulk of the
tumour mass is located.
•• The ventral cervical rootlets are usually displaced dorsally by these tumours.
•• Early identification of these rootlets is crucial as they must be separated
from the dorsal rootlets and dentate ligaments, as well as the spinal rootlets
of the XI cranial nerve that can often be draped directly over the tumour.
1274
•• During the tumour removal it is also important not to injure the radicular
vessels running with the upper cervical roots, since they supply blood to
the spinal cord.
•• An important landmark in the posterior approach to anteriorly placed
tumours is the most rostral dentate ligament that lies at the level of the
foramen magnum and more importantly indicates the point at which the
VA pierces the dura.
•• The upper 2–3 dentate ligaments may be sectioned with caution to reduce
traction on the spinal cord and to allow for gentle rotation of the cord to
facilitate tumour removal.
•• The advantage of the posterior suboccipital approach to anteriorly based
tumours is the familiarity that most neurosurgeons feel with the anatomy
and the technique, as this approach is employed for many lesions of the
posterior fossa.
•• A laminectomy and its extension into the pedicle may be sufficient to allow
removal of ventral tumours when the tumour is not attached by a broad base
and there is little adhesion between it and the anterior surface of the cord.
•• The disadvantages of this technique are, however, the inability to safely
reach the anterior midline or contralateral component of the tumour.
•• In those cases in which the tumour extends laterally into the jugular
foramen, the sigmoid sinus is sectioned between the vertical and horizontal
portions. This technique requires exposure of the VA within its periosteal
sheath from C2 to the intradural component.
•• The exposure of the VA by this method allows for superior and lateral
retraction of the VA, or medial displacement of the VA, requiring resection
of the transverse foramen of C1 and giving access to the tumour lateral
to the VA.
•• Other modifications to the posterior approach have included a partial
condylar resection, or condylar drilling to improve anterior exposure.
TRANSORAL/TRANSPHARYNGEAL APPROACH
•• The direct anterior approaches consist of the transcervical or transoral
which involve removal of the vertebral bodies to expose the intradural
portion of the tumour.
•• These approaches are most suitable for anterior extradural lesions, where
direct midline exposure is the most relevant.
•• The transoral route does provide for the most direct route to the clivus and
the ventral foramen magnum, but it does have many limitations.
•• The patient can be positioned one of three ways:
–– Supine with slight neck extension
–– Modified lateral
–– Semi-sitting (“slouching”).
•• The surgical technique generally involves early identification of the anterior
tubercle of C1 and a vertical midline incision on the posterior wall of the
pharynx.
•• The anterior arch of C1 is exposed, and the fascia-muscle layers are
retracted laterally approximately 20 mm on either side.
•• The VA is 33 mm from the midline at C1, and the hypoglossal foramen is
7.5 mm above the arch of C1 and 18 mm from the midline. The jugular
foramen is 26 mm from the midline.
Chapter 170 • Foramen Magnum Meningiomas
1275
•• The superoinferior extent of the exposure can be enlarged by the addition

of maxillectomy above and mandibulotomy and glossotomy below.
•• The lateral exposure is the limiting factor, as it is not safe to expose greater than
1 cm to either side of the midline. The lateral limitations are due to the
pterygoid plates, the occipital condyles and the hypoglossal canals.
•• The closure in the transoral approach is especially crucial due to the issue
of cerebrospinal fluid (CSF) leakage, fistula and post-operative infection
because of the potentially contaminated avenue of exposure.
•• The dura is the main determinant of the complexity of the closure, as a
good dural closure is the best protection from post-operative meningitis.
•• A multi-layered closure using fibrin glue plus abdominal fat and/or muscle
is often employed with post-operative CSF diversion with either a spinal
drain or a lumboperitoneal shunt.
•• The specific issue of airway management is the most important issue in
the post-operative period, and the nasotracheal tube is often kept in place
until pharyngeal swelling has reduced (facilitated by hydrocortisone cream
applied locally).
THE EXTREME LATERAL TRANSCONDYLAR

APPROACH (ELTA)
•• The extreme lateral approach provides excellent exposure of the anterior
foramen magnum and allows for proximal control of the VA.
•• The ELTA is suitable for both intradural and extradural lesions, allows
control of the VA, permits dissection of the brainstem-tumour interface
tangentially along this plane, and avoids traversing contaminated spaces.
•• The approach has gained wide acceptance because it avoids entering the
contaminated oral cavity, provides early visualisation of the VA and creates
wider surgical exposure.
•• The MRV/MRA imaging provides information regarding the regional
vascular anatomy, including the patency and dominance of the vertebral
arteries and dural sinuses.
•• The surgical approach of ELTA essentially involves six steps:
1. C-1 hemilaminectomy and suboccipital craniectomy (small, extend-
ing 3 cm posterior to the sigmoid sinus) with unroofing of the sigmoid
sinus.
2. Partial resection of the occipital condyle (up to the hypoglossal canal).
3. Removal of the jugular tubercle.
4. Mastoidectomy (limited to the labyrinth and the Fallopian canal) and
retraction of the sigmoid sinus.
5. Resection of the lateral mass of C1 with mobilisation of the VA (in the
suboccipital triangle).
6. Resection of the remaining portion of the occipital condyle.
•• To maximise exposure, suboccipital craniectomy, a lower mastoidectomy to
skeletonise the lower part of the sigmoid sinus and a partial C1 laminectomy
are necessary.
•• The dura must be completely opened around the VA entry area before
mobilising this vessel to work anterior to the artery during tumour resection.
•• The dorsal ramus of C2 that runs posterior to the VA between C1 and C2
can serve as a guide to the artery as a landmark.
•• When the jugular bulb is occluded (as is more often the case in an extradural
tumour), the sigmoid sinus and the internal jugular vein are ligated above
1276
and below the bulb and the bulb is opened directly to remove tumour from
the IX, X and XI cranial nerves.
•• For extradural tumours, the occipital condyle resection extends more
anterior to excise the entire condyle.
•• If the tumour extends into the lower clivus, one can resect it by working
through the petrous bone and the inferior occipital area.
•• Tumours that extend medially and superiorly can be resected with a
combined subtemporal infratemporal approach.
•• Resection of the C1 intradural rootlets and the upper dentate ligaments will
facilitate tumour exposure to better resection.
•• The dural closure in ETLA can be difficult, and a combination of dural graft
and fibrin sealant is often used with the possible addition of local muscle/fat.
•• A spinal drain is often used as a CSF diversion to facilitate wound closure.
•• If more than a partial resection of the occipital condyle is performed,
stabilisation may be needed.
•• This occipital-cervical fusion and instrumentation can be performed at the
same sitting or as a different stage.
•• Complications in this approach are psuedo-meningocoele, CSF leakage,
lower cranial nerve injury (especially IX, X and XI) and craniocervical
instability.
EXTENDED ENDOSCOPIC ENDONASAL

APPROACHES TO SKULL BASE
•• The standard transnasal endoscopic procedures have been recently
expanded to remove lesions involving the skull base.
•• These approaches to caudally located midline anterior skull base and
cervicomedullary lesions are feasible and hold great potential for decreased
morbidity.
•• The midline skull base is an anatomical area extending from the anterior
limit of the anterior cranial fossa down to the anterior border of the foramen
magnum. Resection of lesions involving this area requires a variety of
innovative skull base approaches.
•• These include anterior, anterolateral and posterolateral routes, performed
either alone or in combination.
RADIOSURGERY
•• If contraindications to surgery exist or if the patient elects not to undergo
surgical resection, then radiotherapy should be considered.
•• Because of the vital and critical anatomy within the foramen magnum and
the size of most tumours (less than 3 cm in maximum dimension), focused
gamma knife surgery is recommended rather than standard conformal
radiotherapy.
•• In patients with small residual tumours who are under observation, if the
tumour grows, then gamma knife surgery is recommended.
171
CHAPTER Intraventricular
Meningiomas
Harjinder S Bhatoe  Prakash Singh  Vibha Dutta
INTRODUCTION
•• Intraventricular meningiomas, together with deep Sylvian meningiomas,
constitute the entity of “meningiomas without dural attachment.”
•• The cerebral ventricles are unusual sites for occurrence of tumours of the
central nervous system.
•• These intraventricular meningiomas, which are rare tumours, account for
0.5−5% of all intracranial meningiomas.
ORIGIN
•• Meningiomas arise from arachnoid cap cells, which are specialised cells
in arachnoid granulations.
•• Intra-ventricular meningiomas too arise from arachnoid cells, found within
the choroid plexus.
•• The presence of arachnoid cell nests in the normal choroid plexus stroma
has been illustrated in the literature and a thorough examination of the
choroid plexus will reveal a small or large collection of these cells.
•• The choroid plexus develops initially from an invagination of mesenchyme in
the thin roof area of the mylencephalon, during the 6th week of intrauterine
life.
•• In the 7–9 week human embryo, the telencephalic choroid plexus has
started to develop a loose mesenchymal stroma, covered by a layer of
cells derived from ependyma.
•• Arachnoid tissue is carried with the choroid plexus, as the ventricular
system invaginates and by 20–40 weeks of intrauterine life, the central
stroma of the choroid plexus contains meningocytes, connective tissue
and blood vessels.
•• Meningothelial inclusion bodies are normally found in the arachnoid and
choroidal tela and meningiomas arise from this mesenchymal stroma of
the choroid plexus.
•• For some unexplained reasons, meningiomas of the lateral ventricles occur
more frequently in the left than in the right one (up to 60% of all lateral
ventricular meningiomas).
•• Since the choroid plexus is more bulky in the lateral ventricles, the incidence
of lateral ventricular meningiomas is higher, as compared to those in the
third or fourth ventricle.
•• In the lateral ventricles, the tumour originates from the choroid plexus in
the region between the posterior portion of the body of the lateral ventricle
1278
and the entrance to the inferior horn. This origin explains the predominant
location of the tumour in the trigone.
•• Tumour restricted to the frontal horn is extremely rare.
•• Meningiomas are rare in the third and fourth ventricle.
•• Fourth ventricular meningiomas arise from the inferior tela, when they
are partly intracerebellar, and from choroid plexus, when they are true
intraventricular tumours.
PATHOLOGY AND CLINICAL COURSE

•• The ventricles of the brain provide space for tumour expansion, and till
the CSF pathways are mechanically occluded, manifestations are mild
and non-specific.
•• Regardless of their location, most of the clinical symptoms are due to raised
•• Lesions grow into the ventricular cavity till they produce obstructive
hydrocephalus.
•• Visual field deficits may be seen in 25% of patients.
•• Cerebellar signs may be seen in fourth ventricular tumours and hypo-
thalamic features with or without endocrinopathy may be seen in third
ventricular tumours.
•• Manifestations of neurofibromatosis type 2 (NF2) syndrome may be evident
on clinical and neurological evaluation.
•• The rarity of intraventricular meningiomas, in contrast to those with dural
attachment, may also be due to yet unknown factors.
•• Multiple meningiomas arising from the dura are regarded as due to inherent
multicentricity of the dural foci, possibly influenced by hormonal factors.
•• Meningiomas of the third ventricle, occurring primarily in young children,
have a tendency to grow into both lateral ventricles as a trifoliate tumour.
HISTOPATHOLOGY
•• Intraventricular meningiomas can be of any of the histopathological types
of the tumour, as per the WHO classification of meningiomas.
•• These are predominantly either fibrous, fibroblastic or psammomatous.
•• The structure of psammoma bodies in the choroid plexus is very similar
to that in meningiomas.
•• In general, meningiomas are diagnosed by morphological features alone.
•• The expression of oestrogen receptor is low in these tumours, and two-
thirds of these patients are positive for progesterone receptors.
IMAGING
•• Lateral ventricular meningiomas are seen most commonly in the trigone
or atrium of the ventricle.
•• Third ventricular meningiomas are seen in the anterior third ventricle, while
fourth ventricular meningiomas can appear partially intracerebellar (when
they arise from the inferior tela) and as tumours surrounded by CSF when
they arise from the choroid plexus.
•• Intraventricular meningiomas may occasionally be densely calcified so as
to be visible on plain skull radiograph.
•• The tumour is generally lobulated and appears isointense on T1-weighted
and T2-weighted images.
Chapter 171 • Intraventricular Meningiomas
1279
•• Calcification, nodular or punctate, is seen as an area of signal loss.

•• The tumour enhances uniformly after intravenous gadolinium.
•• The presence of other lesions, like optic nerve sheath tumour and vestibular
schwannoma, indicate underlying NF2 syndrome.
•• Computed tomography supplements MRI by showing calcification.
•• Digital subtraction angiography can be utilised for assessment of the
vascularity and location of the principal feeder.
•• Lateral ventricular tumours occurring in the body are fed by the lateral
posterior choroidal vessels, while those in the temporal horn receive their
blood supply from the anterior choroidal artery.
•• Tumours in the atrium are supplied by both anterior and posterior choroidal
arteries.
•• Third ventricular tumours are supplied by the medial posterior choroidal
vessels, while fourth ventricular tumours derive their blood supply from
choroidal branches of the posterior inferior cerebellar artery (PICA).
SURGICAL MANAGEMENT
•• Meningiomas are solid, discrete lesions that can be totally excised.
•• Surgical management has to be individualised for each patient, depending
upon the tumour location and its vascularity, involved ventricle and the
presence of other tumours (as in NF2).
•• The strategy should be to reach the blood supply with minimum neural
section/retraction, coagulation of the tumour prior to incision, internal
decompression and occluding of the feeding vessel(s).
•• Since the surgical approach invariably means entry through neural tissue,
neurological morbidity due to the approach has to be borne in mind.
Lateral Ventricular Tumours

•• The proximity of the optic radiation, left sided preponderance with potential
for speech and cognitive deficits, the “C” shape of the lateral ventricle and
aiming for early control of the vascular pedicle have led to a plethora of
surgical approaches for meningiomas of the lateral ventricle.
•• These approaches may be through the cerebral convexity (temporal,
parieto-temporal, parieto-occipital), involving occipital lobectomy, or through
the corpus callosum.
•• Most of these approaches described lead to iatrogenic morbidity in the
form of visual field deficit, disconnection syndrome or speech and cognitive
deficits.
•• The parieto-occipital approach follows a cranio-caudal orientation parallel to
the optic radiation over the cerebral convexity, and is least likely to damage
the optic radiation. Moreover, this is often the thinnest region overlying the
trigone and the tumour.
Third Ventricular Tumour

•• A small third ventricular tumour can be approached by the transcortical
transforaminal approach, while large tumours may require transcallosal
exposure.
•• There should be no traction on the tumour, so as to avoid hypothalamic
injury.
1280
•• Large tumours lend themselves poorly to excision due to morbidity

associated with neuroendocrine, hypothalamic dysfunction and deep
venous system injury associated with surgery of large third ventricular
tumours.
Fourth Ventricular Tumour

•• These tumours are exposed by suboccipital craniectomy and splitting of
the vermis.
•• There can be severe brainstem distortion and the PICA can be seen draped
over the tumour.
•• The dura is closed primarily or by duroplasty utilising pericranium or
temporalis fascia.
Results
Lateral Ventricular Tumours
•• Recovery is smooth in majority of the patients after tumour excision.
•• However, a left-sided approach can result in cognitive deficits and speech
disturbances that usually resolve within 2−4 weeks.
•• Motor deficits can result in infiltrating tumours, when an attempt is made
to separate them from the ventricular wall.
•• Intraventricular haemorrhage can occur from choroidal vessels.
•• Transient or persistent post-operative homonymous hemianopia may be
seen.
Third Ventricular Tumours
•• Excision of third ventricular meningiomas carries a higher morbidity, due
to neuroendocrine, osmotic and hypothalamic disturbances.
•• The floor of the third ventricle has to be respected during surgery to avoid
these complications.
Fourth Ventricular Tumours
•• Meticulous care of the fourth ventricular floor and PICA avoids potential
post-operative respiratory dysrhythmias and oropharyngeal paralysis due
to injury to the floor of the fourth ventricle.
172
CHAPTER
Haemangioblastomas
Ravi Ramamurthi
•• Haemangioblastoma is a histologically benign tumour and has also been

referred to as haemangioma, capillary haemangioendothelioma, Lindau’s
cyst, Lindau’s tumour and angioreticuloma.
•• These tumours may occur independently or may be part of Lindau’s disease
or von Hippel-Lindau complex (VHL).
GENETICS
•• Haemangioblastomas may occur sporadically or as a part of VHL complex.
•• VHL complex is a familial disorder which has an autosomal dominant
inheritance with variable penetrance and can be passed on by affected
and unaffected members.
•• This belongs to a group of disorders known as phakomatoses or
neurocutaneous syndromes.
•• VHL complex is characterised by single or multiple haemangioblastomas
in the neuraxis associated with one or more of the following visceral
manifestations: Haemangioblastoma of the retina (von Hippel’s tumour),
renal carcinoma, renal cysts, pancreatic cysts, cysts and angiomas of the
liver, epididymal cysts and adenomata and phaeochromocytoma.
•• Q-PCR is the method of choice for fast (within 3.5 hours), accurate and
sensitive screening in routine DNA diagnosis of VHL disease.
•• Renal cancer constitutes one of the main causes of death.
•• The VHL gene, situated at 3p25−26, is a tumour suppressor gene, which
plays a major role in regulation of VEGF transcription and expression.
•• The germ cell mutation can be identified in 70% of patients.
•• Somatic mutations of the VHL gene are also responsible for sporadic clear
cell carcinomas.
•• The von Hippel-Lindau (VHL) disease product is thought to down-regulate
transcription, by antagonising elongin-enhanced transcriptional elongation.
•• Germline VHL gene mutations predispose to the development of retinal,
cerebellar and spinal haemangioblastomas, renal cell carcinoma and
phaeochromocytoma.
INCIDENCE
•• Haemangioblastomas constitute 1.5–2.5% of intracranial tumours and
7–12% of posterior fossa tumours.
•• There is a complex relationship between CNS haemangioblastoma, retinal
haemangioblastoma and Lindau’s disease. About 20% of patients with CNS
haemangioblastoma have VHL complex.
1282
•• Fifty per cent of patients with VHL complex have CNS haemangioblastoma.
•• The most common age at which they present are the third and fourth
decades and there is a slight male preponderance.
•• The age of onset of symptoms in VHL complex is earlier than in the
sporadic variety.
•• Supratentorial haemangioblastomas are rare, forming 2–8% of all such
tumours.
•• Haemangioblastomas may occur concurrently with other tumours like
meningioma, acoustic neurinoma or AV malformations.
PATHOLOGY
Macroscopic Features
•• Haemangioblastomas occur most commonly in the cerebellar hemisphere.
•• They may also occur in the vermis, brainstem, supratentorial compartment
and in the spinal cord.
•• In familial cases, the tumours tend to be multiple.
•• Seventy per cent of haemangioblastomas in the cerebellum and about 20%
in the brainstem and supratentorial location are cystic.
•• Haemangioblastomas are pinkish or yellow and usually above the pial
surface.
•• Dilated vessels may be seen on the cerebellar cortical surface.
•• They do not have a true capsule, but are well circumscribed from the
surrounding tissue.
•• The cyst fluid is xanthochromic and the protein content may be up to 5 g/dl.
•• The cyst wall is smooth and made up of glial cells and compressed
cerebellar tissue.
•• The solid portion is seen as a nubbin of varying sizes; the smallest may be
even 2 mm and may be missed at surgery.
•• The cut surface of the solid tumour is red in colour due to vascularity.
•• Cavernous spaces and cysts may be seen and some areas may appear
yellow from lipid deposition. Occasionally, the tumour may be totally solid
as often happens in midline vermian lesions.
•• The tumour consists of a mesh of vascular spaces lined by plump
endothelial cells.
•• The vascular spaces are separated by numerous polygonal cells called
interstitial or stromal cells.
•• The capillary channels are surrounded by reticulin fibres which are
demonstrated by reticulin stains.
•• Pericytes, which lie just outside the periendothelial basement membrane
and are themselves surrounded completely by a basement membrane, are
best seen on electron microscopy.
•• The presence of histological variants of haemangioblastoma is well
established.
•• Clinical factors associated with histological subtypes, that is, of the cellular
and reticular variant of haemangioblastoma.
•• Astrocytomas are rarely found in von Hippel-Lindau disease and they may
contain genetic changes common to both haemangioblastomas and some
astrocytomas.
Chapter 172 • Haemangioblastomas
1283
•• Malignant spread, distant metastases and subarachnoid seeding are very

rare.
•• Recurrence and extensive spread are excellently demonstrated by MRI.
•• Histology of the cyst wall is consistent with reactive gliosis.
•• CNS peritumoral cyst formation is initiated by increased tumour vascular
permeability, increased interstitial pressure in the tumour and plasma
extravasation with convective distribution into the surrounding tissue.
•• When the delivery of plasma from the tumour exceeds the capacity of
the surrounding tissue to absorb the extravasated fluid, oedema (with its
associated increased interstitial pressure) and subsequent cyst formation
occurs.
SYMPTOMS AND SIGNS

•• The most common initial symptoms are headache and other symptoms of
raised intracranial pressure.
–– Vertigo and diplopia may occur.
¾¾ Papilloedema occurs in a majority of patients.
•• Depending on the location in the posterior fossa, there may be cerebellar
or brainstem signs or both.
•• Ataxia of gait, upper limb incoordination and nystagmus occur in about
60% of patients.
•• If the tumour is located in the brainstem, cranial nerve and long tract signs
may be present.
•• Other presenting symptoms reported are adult cerebellar mutism and
intractable hiccoughs.
•• About 25% may have mental changes which may be caused by
hydrocephalus.
•• Rarely, they may present as subarachnoid or parenchymal haemorrhage.
•• The overall incidence of haemorrhage in patients with haemangioblastoma
is low. An important indicator for the probability of haemorrhage is tumour
size, as spontaneous or post-operative haemorrhage occurred exclusively
in extraordinarily large tumours.
•• Supratentorial lesions may mimic the clinical presentation of meningiomas.
•• Paralysis of upward gaze may occur if the tumour is located in the roof of
the fourth ventricle.
•• Vascular engorgement of cerebellar haemangioblastomas during
pregnancy may cause patients to become symptomatic.
INVESTIGATIONS
•• The best screening test for haemangioblastomas is computed tomography
in the axial and coronal planes.
•• The solid lesions generally appear isodense with the cerebellar tissue on
plain scans, but enhance intensely with contrast injection.
•• There is either homogenous enhancement or a mottled appearance, due
to the presence of intratumoural cysts.
•• The cystic lesion is seen as a sharply defined low density with attenuation
values of CSF or slightly higher if the protein content is high.
•• A mural nodule will enhance intensely with contrast, but the cyst wall does
not. A small mural nodule may be missed on CT scanning.
•• Vertebral angiography is very useful, especially in patients with evidence
of VHL complex, who have a cerebellar cyst with the mural nodule not
visible on the CT.
1284
•• The following vascular patterns have been observed: (i) A vascular mural
nodule within an avascular cyst; (ii) A doughnut ring of abnormal vessels
surrounding an avascular space representing an intra-tumoural cyst;
(iii) A large solid vascular mass and (iv) Multiple small widely separated
vascular nodules.
•• MRI is the most sensitive investigation for haemangioblastomas, especially
those with small mural nodules and the ones near the base of the skull or
the tentorium.
•• The cyst does not appear as hypointense as CSF on T1-weighted images
and they may exceed the CSF signal on T2-weighted images.
•• On T1 and proton density weighted images, mural nodules stand out well
against the darker background of cyst fluid.
•• With T2 images, the nodule may become less apparent, since their signal
rises along with that of cyst fluid. Highly vascular lesions will remain low
on T2 images and will be clearly visible.
•• Prominent feeding arteries and draining veins are characterised by flow
void.
•• If larger vessels are present in the tumour, a ‘salt and pepper’ appearance
may be seen.
•• Solid tumours and mural nodules enhance brightly and homogenously
after Gd-DTPA injection.
•• Gd-DTPA enhancement is useful to detect multiple tumours, assure
complete removal and detect possible recurrence.
•• The apparent diffusion coefficients are increased in haemangioblastomas.
•• These findings may indicate rich vascular spaces of the haemangioblastomas.
•• Diffusion-weighted imaging may be useful for distinguishing haemangio-
blastomas from other enhancing cerebellar tumours.
•• Erythrocythaemia occurs in 9–49% of patients.
•• After removal of the tumour, the polycythaemia regresses and may reappear
with either recurrence of the tumour or tumour occurring in another area.
TREATMENT AND RESULTS

•• Surgery with total excision of the tumour leads to good results.
•• Surgical outcome for patients with CNS haemangioblastomas is favourable,
however, management of haemangioblastomas is more difficult and
prolonged for patients with VHL syndrome, as these patients present at
younger ages and are at risk for development of new lesions, often multiple,
and require lifelong follow-up.
•• Surgery for posterior fossa haemangioblastomas is done through an
appropriate craniectomy either midline, paramedian or retromastoid.
•• The sitting, semi-sitting, prone or semiprone position is used, depending
on the surgeon’s preference.
•• Two types of brainstem haemangioblastomas (BSHs) can be identified.
–– Patients with cystic BSH lesions could have an excellent outcome
after surgery.
–– Patients with giant or large solid BSHs remain a challenge to neuro-
surgeons.
•• A combined strategy of pre-operative embolisation, mild hypothermia with or
without hypotension, microsurgical technique and intensive peri-operative
management are mandatory for removal of these tumours with acceptable
morbidity and mortality.
Chapter 172 • Haemangioblastomas
1285
•• Solid haemangioblastomas can be difficult to treat surgically because

of their hypervascularity and requirement for circumferential dissection.
They can be safely resected utilising wide transtemporal posterolateral
skull-base exposures.
•• A complete excision of the lesion has been achieved by means of
endoscopy without any violation of the subarachnoidal space.
•• The need for pre-operative CSF diversion in patients with hydrocephalus
depends on the surgeon’s preference and is debatable.
•• Recurrence after total removal is rare.
•• If there is evidence for recurrence of the tumour, it will most likely be a
tumour arising at a different site.
•• Radiation therapy in high doses may retard the growth of the tumour and
reduce its size and vascularity. It is only palliative and should be used
only in large solid tumours involving the brainstem which are inoperable.
•• Radiosurgery often lends itself particularly well to these discrete lesions
allowing highly focused treatment.
•• For patients with multiple and metachronous cerebellar haemangioblastomas
as part of the von Hippel-Lindau syndrome, the data support a policy of
conventionally fractionated external beam radiotherapy to the whole
cerebellum of 50–55 Gy followed, after a period of time, by radiosurgery
for persisting lesions.
•• The long-term prognosis is good in cystic and in non-familial tumours.
•• The prognosis for tumours involving the brainstem is not very good, as the
operative mortality and morbidity are high.
•• In VHL complex, the prognosis depends on multiplicity of tumours and
occurrence of carcinoma in the kidney.
173
CHAPTER Primary Central Nervous
System Lymphomas
Sanjay Behari  Punita Lal  Samir Kalra  Manoj Jain
INTRODUCTION
•• Primary central nervous system lymphomas (PCNSLs) are the non-
Hodgkin’s lymphomas (NHL) arising in and within the central nervous
system (CNS).
•• These are extranodal malignant lymphomas arising within the CNS in the
absence of obvious lymphoma outside the nervous system at the time of
diagnosis.
•• They are usually found in the brain parenchyma but may occur in the eyes,
leptomeninges or rarely the spinal cord.
•• CNS lymphomas were first described by Bailey in 1929 as “perithelial
sarcoma”, since the tumours appeared to be reticuloendothelial in origin
and perivascular in location.
•• They have also been classified as reticulum cell sarcoma, microglioma or
perivascular sarcoma in an effort to describe the cell of origin.
•• An analysis revealed that PCNSLs were non-Hodgkin’s lymphomas of B
cell lineage with only 1−3% having a T cell phenotype.
•• In the past two decades, their incidence has risen significantly in both
immunocompromised and non-immunocompromised individuals.
•• The disease has certain unique features. It is usually restricted to,
yet disseminated within the CNS. Its radiological appearance, steroid
responsiveness and the relative roles of surgery, chemotherapy and
radiotherapy have distinctive features that make the management of this
disease quite different from all other CNS tumours.
•• The source of the cell responsible for the development of PCNSLs is not
known since the CNS lacks lymphatics and lymph nodes. Under normal
circumstances, lymphocytes do move in and out of the CNS and may be
the primary source of PCNSLs. However, it is the T cell lymphocytes that
move through the CNS and B cells are usually not found there and yet
PCNSLs are predominantly B cell tumours.
•• It has also been postulated that PCNSLs arise as metastasis from an occult
systemic lymphoma. However, this is unlikely since PCNSLs are almost
never associated with systemic NHL at diagnosis or autopsy.
•• CNS spread of lymphoma usually occurs in patients with advanced
systemic disease, a state never found in PCNSLs; and CNS metastasis
from a peripheral NHL is usually leptomeningeal or spinal epidural and
very rarely parenchymal.
•• If a lymphoma at an extra CNS site is found coexisting with the lesion in
the brain then, by definition, the brain lesion is no longer considered as a
PCNL but a lesion that has metastasised to the CNS.
Chapter 173 • Primary Central Nervous System Lymphomas
1287
•• Systemic lymphomas and leukaemias involve the CNS in approximately

5−35% of patients and their lesions are often confined to the leptomeninges
and cranial or spinal nerve roots.
•• Another hypothesis postulates that since CNS is an immunologically
privileged organ, lymphoma cells that arise elsewhere in the body migrate
into and preferentially reside in the CNS. The normal immune system in
the rest of the body would destroy these tumour cells.
•• PCNSLs accounts for approximately 3% of all brain neoplasms and less
than 1−4% of all non-Hodgkin’s lymphomas. This has been associated with
an overall increase in the other systemic non-Hodgkin’s lymphomas (NHL)
as well as a higher prevalence of AIDS related PCNSLs.
•• PCNSLs may often be associated with other immunodeficiency states both
congenital (e.g. hereditary immune deficiency, Wiskott-Aldrich syndrome,
immunoglobulin A deficiency, hyperimmunoglobulin M syndrome or severe
combined immune deficiency) and acquired (e.g. organ transplantation
recipients or chronic pharmacologic immune suppression).
•• The Ebstein-Barr virus (EBV) is an important cause in the genesis of
PCNSLs in immunocompromised patients. Human herpes virus 8 (HHV-8)
DNA has also been identified in PCNSLs in patients with or without AIDS.
•• The other risk factors for PCNSLs include myasthenia gravis, vasculitis,
autoimmune disease, rheumatoid arthritis, systemic lupus erythematosis,
sarcoidosis and Sjogren’s syndrome.
•• PCNSLs may occur in all age groups.
•• Its peak incidence is in the sixth and seventh decades (mean approximately
58−60 years) in immunocompetent patients, but it occurs in a much younger
age group (mean approximately 37−43 years) in immunocompromised
patients.
•• Among the immunocompetent individuals, there is a 3:2 male-to-female
ratio, but in the AIDS population, more than 90% of patients are men.
CLINICAL FEATURES
•• PCNSLs generally grow more rapidly than gliomas and may have a history
of progression of only a few weeks to months.
•• Most PCNSLs present with pressure symptoms caused by the mass lesion.
•• Focal neurological deficits occur in nearly half of the patients depending
upon tumour location.
•• Behavioural and personality changes are also common presenting
symptoms.
•• PCNSLs often have a deep periventricular location and, therefore, seizures
are less common.
•• Diencephalon infiltration may cause hypothalamic syndromes including
diabetes insipidus or the syndrome of inappropriate antidiuretic hormone
secretion; altered sexual behaviour and eating disorders.
•• Posterior fossa lesions may cause cerebellar syndromes and hydrocephalus.
•• Brainstem lesions may produce long tract signs, internuclear ophthalmo-
plegia, vertigo and diplopia.
•• Spinal cord lymphomas are rare and cause transverse myelopathies.
•• The thoracic cord is usually involved, but lumbar infiltration with nerve root
involvement may also occur.
•• The leptomeningeal involvement is usually close to the site of the
parenchymal lesions in the CNS and is usually asymptomatic. However,
in an advanced stage, signs of meningism may occur.
1288
•• Neurolymphomatosis is the painful or painless selective invasion of either

cranial or peripheral nerves or the plexus they form.
•• Sensory symptoms are common and include burning paraesthesias,
allodynia, vibratory/position sense deficit or numbness.
•• Cranial or peripheral nerve motor deficits, such as Bell’s palsy, facial pain
or limb weakness, are less common.
•• PCNSLs widely infiltrate the brain parenchyma. An autopsy usually shows
microscopic disease even in areas that were appearing normal on magnetic
resonance imaging (MRI).
•• Multifocality is seen in nearly 40% of immunocompetent patients and in
almost 100% of immunocompromised patients.
•• Most lesions are periventricular, allowing tumour cells to gain easy
access into the cerebrospinal fluid (CSF). At least 40% of patients have
demonstrable CSF seedling on examination or on MRI. The CSF spread
of the disease is, however, often asymptomatic.
•• Ocular lymphoma involving either of the layers of the eye is a fairly common
manifestation of PCNSL.This may cause visual deterioration, floaters in the
eye fields, uveitis or retinitis. Indirect fundoscopy with slit lamp examination
may be required to detect the ocular lymphoma. An orbital lymphoma, on
the other hand, is usually associated with metastatic NHL.
PATHOLOGY
•• About 60% of PCNSLs involve the supratentorial space, especially the
cerebral hemispheres (52%) [frontal (15%), temporal (8%), parietal (7%),
occipital (3%), basal ganglia/periventricular region (10%) and corpus
callosum (5%)].
•• In the posterior fossa it occurs in the cerebellum and the brainstem.
•• The spinal cord is involved in 0.6−1% patients.
•• Approximately 25−50% of lesions are multiple.
•• Secondary meningeal spread is seen in 30−40% of PCNSLs, while
leptomeningeal lymphoma may account for up to 8% of these tumours.
•• On the other hand, secondary CNS malignant lymphomas usually occur
in the dura and leptomeniges but parenchymal lesions may also occur.
•• Systemic dissemination occurs late in the course of the disease in 7−8%
of cases, often in the lymph nodes in the abdomen and retroperitoneum.
•• On gross examination, PCNSLs occur as single or multiple masses in the
cerebral hemispheres.
•• Commonly, they are deep seated and adjacent to the ventricular system.
•• The tumours can be firm, friable, granular, centrally necrotic, focally
haemorrhagic, grey, tan, yellow or virtually indistinguishable from the
adjacent neuropil.
•• Some tumours appear well-demarcated, like a metastastic lesion. When
diffuse borders and architectural effacement are present, the lesions
resemble gliomas.
•• Macroscopically, meningeal lymphoma mimics a meningioma or meningitis.
•• On microscopic examination, a PCNSL diffusely infiltrates the brain
parenchyma in an angiocentric pattern forming collars of tumour cells within
concentric perivascular reticulin deposits.
•• Virtually, all PCNSLs show a diffusely infiltrating pattern.
•• When tumours become confluent, geographic necrosis may be seen with
perivascular islands of viable tumour cells surrounded by large regions of
coagulative necrosis.
1289
•• A focally prominent astrocytic and microglial response, large macrophages

and reactive lymphocytic infiltrates are common. On higher magnification,
PCNSLs show lymphoid cells with a variable appearance.
•• Approximately 98% of PCNSLs are B-cell lymphomas with the
immunohistochemical expression of pan-B markers, such as CD20 and
CD79a, usually with IgM-κ production.
•• T-cell lymphomas constitute about 2% of PCNSLs and have mainly been
seen in immunocompetent patients. They occur as solitary or multiple
intraparenchymal masses, often having more frequent posterior fossa
localisation, particularly in the cerebellum and with a propensity to arise
in the leptomeninges.
•• Hodgkin’s disease is rare in the CNS and is most often seen in the setting
of Grade III or IV systemic disease but primary CNS presentations have
been described.
•• Lesions are typically dural based but firm and well demarcated parenchymal
tumours do occur.
•• The diagnosis of Hodgkin’s disease rests upon the identification of
Reed-Sternberg cells or their variants in the background of appropriate
non-neoplastic haematopoetic cells (lymphocytes, plasma cells, histiocyte
and eosinophils).
DIAGNOSTIC TESTS
Imaging Radiology
•• On non-contrast CT scans, these lesions are often hyperdense. They
enhance brilliantly on contrast administration.
•• The tumours are typically hypointense on T1-weighted images. On T2-
weighted MR images, these lesions may be isointense to hyperintense
due to their hypercellularity. Dense, homogeneous enhancement occurs
on gadolinium administration. Only rarely are the lesions non-enhancing.
•• The oedema is usually less than that seen in a malignant glioma of similar size.
•• There may be multifocality in nearly 50% of tumours, especially in
immunocompromised patients. Calcification is not a feature of these lesions.
•• They characteristically occur in the deep white matter of the centrum
semiovale of the cerebral hemispheres and often have a periventricular
location.
•• There may be a subependymal spread or along the corpus callosum or
they may occur as diffusely infiltrative lesions without a primary mass.
•• In immunocompromised patients, they may show ring enhancement with
significant oedema and a hyperintense signal on T2-weighted images
reflecting the higher incidence of necrosis seen on pathological examination
in this group.
•• Spontaneous haemorrhage may also occur.
•• PCNSLs lesions (as all other malignant lesions) show restriction in proton
diffusion producing a hyperintense appearance on diffusion weighted
images.
•• MR spectroscopy reveals decreased N-acetylaspartate peak and an
increased ratio of choline to creatine (> 3:1).
•• PCNSLs in immunocompromised individuals mimic infections and MRI may
not be able to differentiate between the two.
•• SPECT using Thallium-201 (a potassium analogue that only enters the
region of disrupted blood-brain barrier proportional to the activity of the
1290
sodium-potassium adenosine triphosphatase pump) or PET scans (using

fluorodeoxyglucose) are usually effective in differentiating lymphoma from
toxoplasmosis in immunocompromised patients since a PCNSL lesion
shows a greater hypermetabolic state than is seen in infection.

•• The CSF cytology (consisting of reactive or malignant lymphocytes) may
be positive in nearly 35−40% of the cases and may obviate the need
for a brain biopsy.
•• Immunohistochemistry may often demonstrate the monoclonal population
of malignant cells.
•• The protein concentration may be mildly elevated in 85% of patients
(≤ 150 mg/dL).
•• The glucose concentration is usually normal.
•• However, low glucose concentrations with an increase in levels of tumour
markers like β2-microglobulin, lactic dehydrogenase and β-glucuronidase
may suggest a leptomeningeal invasion.
•• In large supratentorial or posterior fossa lesions, performing a lumbar
puncture may precipitate transtentorial or tonsillar herniation respectively
or even both.
Vitreous Fluid Examination

•• Vitrectomy may also establish the diagnosis particularly in patients with
isolated ocular lymphoma.
•• Identification of interleukin 10 levels in the vitreous fluid and the immu-
nophenotyping of vitreous cells may be done.
Systemic Evaluation
•• Staging for patients with PCNSLs includes CSF cytology, slit lamp
examination of the eyes, CT scan of chest, abdomen and pelvis, bone
marrow biopsy and serological testing for HIV.
•• Since PCNSLs are frequently seen in AIDS patients, systemic evaluation
for AIDS is recommended for these patients.
•• In the immunodeficient patient, detection of Epstein Barr virus DNA by
polymerase chain reaction of the CSF is a reliable indicator of PCNSLs.
•• The radiographical appearance of PCNSLs may resemble toxoplasmosis
and therefore, most patients with AIDS and a cerebral mass lesion are
initially treated with antitoxoplasmosis therapy.
•• An early brain biopsy should be considered in patients who have negative
toxoplasma titres and those who continue to deteriorate during the first
week of antitoxoplasma therapy.
•• Toxoplasmosis and other CNS infections, like tuberculosis, may also
coexist with PCNSLs mass lesions. However, there is an increased risk of
CNS haemorrhage during brain biopsy of immunocompromised patients,
when compared to the procedure performed in immunocompetent patients.
RESPONSE TO CORTICOSTEROIDS
•• PCNSLs are corticosteroid responsive and may induce lysis of tumour cells.
•• If the diagnosis of PCNSLs is suspected, then steroids should be avoided
(unless impending herniation due to severe raised intracranial pressure
1291
makes their use necessary) until a definitive diagnosis has been established
since the biopsy may only yield reactive T cells after steroid administration.
•• Astrocytomas, metastasis and multiple sclerosis plaques also respond
to steroid therapy and so, steroid responsiveness of the lesion is not
diagnostic of PCNSLs.
•• If corticosteroids have been administered and the biopsy has proven to be
inconclusive in a patient suspected to be having a PCNSL, the drug should
be withdrawn and a re-biopsy of the lesion attempted.
•• The patient should be kept under constant observation during the period
of withdrawal of the corticosteroids because, occasionally, the tumour may
enlarge rapidly.
MANAGEMENT AND THERAPY

•• All PCNSLs are treated in the same manner regardless of the sub-type
or the cell of origin, since the response to treatment and prognosis is not
related to the pathological sub-type.
•• Using the clinical staging criteria for systemic lymphomas, PCNSLs
correspond to stage IE (Ann Arbor staging system), that is, disease confined
to a single extra-nodal site.
•• Systemic stage IE disease has a 100% complete response rate and at least
a 70% 10-year survival rate with focal radiotherapy (RT).
•• Despite the high responsiveness, the median survival with RT alone for
PCNSLs is 12−18 months with a 3−4% 5-year survival rate.
•• The median survival, however, increases to 41–44.4 months with a
combined modality treatment.
Immunocompetent Individuals
Corticosteroids
•• PCNSLs respond dramatically to steroids.
•• At least 90% of patients improve clinically and 40% of patients have
significant shrinkage or disappearance of tumour masses (as evident on
MRI) after steroids.
•• This is due to a direct cytotoxic effect of the steroids; biopsy after steroid
administration often yields normal, necrotic or non-diagnostic tissue.
•• The patients often become clinically asymptomatic after steroid administra-
tion for a short period of time. This may be due to regression in the mass
or stabilisation of the blood-brain barrier without any detectable change in
the tumour size.
•• However, the steroid-induced remission is short-lived. Thus, steroids
are generally used only for the first few weeks of treatment, often for
symptomatic management of raised intracranial pressure and for prevention
of oedema during radiotherapy.
Surgery
•• Surgery is performed for these tumours to obtain a histological diagnosis.
•• Tumour decompression has no therapeutic advantage. This is because of
its multifocal and infiltrative nature.
•• The mean survival of these patients after surgical resection is 3−5 months.
Therefore, stereotactic biopsy is the diagnostic method of choice.
•• Excision of large lesions situated in deep periventricular locations is often
associated with a high morbidity and, therefore, should not be attempted
1292
once a diagnosis of PCNSLs has been established by a minimally invasive

technique.
•• If a frozen section of a small surgical specimen reveals a PCNL, no
further resection of the tumour is performed and the patient is treated with
radiotherapy and chemotherapy.
Radiotherapy
•• Conventionally whole brain radiotherapy (WBRT) given under the cover of
steroids is an effective modality for the treatment of PCNSLs.
•• Although a complete response may be obtained, the median survival with
radiotherapy (RT) alone has been between 12 and 18 months with only a
3−4% five-year survival rate.
•• The dose-response relationship derived from retrospective data suggests
that a dose of 40−50 Gy improved survival, when compared to smaller
radiation doses.
•• The Radiation Therapy Oncology Group (RTOG) conducted a prospective
study of PCNSL patients treated with 40 Gy WBRT plus a 20 Gy boost to the
involved area, to assess whether dose intensification improved outcome.
The median survival was approximately 12 months.
•• The problem with whole brain radiation is that of delayed development of
cognitive and intellectual deterioration.
Chemotherapy
•• In systemic lymphomas, drug combinations are more effective than a single
agent chemotherapy (ChT).
•• ChT must be administered before RT if its efficacy is to be assessed since
PCNSLs usually respond very well to RT and the lesions often disappear.
•• Preradiation ChT reduces the enhanced neurotoxicity of adding ChT to RT.
•• In PCNSLs, the blood-brain barrier needs to be overcome and the disease
is widespread.
•• Use of agents in high doses to enable them to penetrate the blood-brain
barrier, the use of intrathecal therapy to deliver drug to the leptomeningeal
tumour and the use of osmotic agents to disrupt the blood-brain barrier are
methods for an efficacious drug delivery in PCNSLs.
Commonly Used Drugs to Treat PCNSL

•• Methotrexate (MTX)I is the drug of choice for the initial treatment of
PCNSLs.
•• It inhibits dihydrofolate reductase, an essential coenzyme for folate
reduction.
•• Reduced folate is an essential coenzyme in the synthesis of purine and
thymidine.
•• This drug is poorly lipid soluble and, therefore, blood-brain barrier
penetrance is poor.
•• High dose MTX greater than 1 g/m2 penetrates into the brain and CSF but
therapeutic levels are only established in CSF at levels greater than 3 g/m2.
•• An Ommaya reservoir may deliver MTX into the CSF and achieve a
sustained therapeutic level for 48 hours.
•• MTX administration prior to RT may be protective against neurotoxicity. It
is also nephrotoxic in high doses and should not be given if the creatinine
clearance is below 60 mL/min. Intrathecal MTX may still be given when
renal clearance is impaired.
1293
•• Vincristine, Doxorubicin and Bleomycin are effective but do not cross the
blood-brain barrier.
•• Procarbazine and Nitrosoureas (e.g. CCNU, lomustine) are lipophilic agents
that cross the blood-brain barrier.
•• Cytarabine (ara-C) is a pyrimidine analogue that inhibits DNA synthesis by
competitively inhibiting DNA polymerase with resultant inhibition of DNA
chain elongation and template function. It may cross the blood-brain barrier
and is also useful for ocular and leptomeningeal lymphomas. It may cause
dementia and reversible cerebellar ataxia.
Systemic Lymphoma Protocols

•• The drugs used for treatment of systemic lymphomas, like CHOP
(cyclophosphamide, doxorubicin, vincristine and prednisone), CHOD
(dexamethasone instead of prednisone) or MACOP-B (methotrexate,
doxorubicin, cyclophospamide, vincristine, prednisone and bleomycin),
for 3−4 cycles, followed by cranial irradiation may show a median survival
between 8.5 and 14 months.
•• The poor results may be due to the inability of the non-lipophilic drugs to
cross the blood-brain barrier.
•• The development of leucoencephalopathy and drug resistance may also
play a role in treatment failure.
Methotrexate Based Protocols

•• The recent protocol recommended is to use high dose (3.5 g/m2) systemic
MTX together with intrathecal MTX (12 g per dose) administered via an
Ommaya reservoir followed by cranial irradiation (4500 cGy) and high
dose ara-C (3 g/m2).
•• A higher median survival of approximately 42 months was seen.
•• Dementia and ataxia were seen in patients older than 50 years but not in
those less than that age.
•• Among the newer therapies, rituximab, an anti-CD20 antibody that has an
excellent activity against systemic follicular and diffuse large cell lymphoma
may be used in PCNSLs, as an adjunct to MTX, as approximately 90% of
PCNSLs express CD20 antigen.
•• In patients with immunocompromise, RT remains the primary treatment
of PCNSLs.
•• Patients with CD4 counts greater than or equal to 200/mm3, a good
performance status and no active co-morbid conditions may respond to
additional ChT (often 3 cycles of PCV).
174
CHAPTER Intracranial Melanomas
and Other Tumours
Bhawani S Sharma  Sumit Sinha
INTRODUCTION
•• Primary melanomas rarely affect the central nervous system.
•• Intracranial melanomas develop from the proliferation of melanocytic
elements normally present in the leptomeninges, which can assume
neoplastic potential.
•• Melanin containing cells can develop melanoblastic activity, ranging
between histologically benign and malignant patterns.
•• These neoplasms are largely confined to the subarachnoid space with
perivascular extension into brain parenchyma, depending on anaplastic
features and the invasive potential of different clones.
•• The pigmented tumours of the CNS can be classified into:
1. Primary pigmented lesions: Neoplasms derived from leptomenin-
geal melanocytes are uncommon lesions that present in localised or
diffuse forms. Localised lesions present sporadically as meningeal
masses and range from well-differentiated melanocytomas to malig-
nant, potentially disseminating melanomas.
2. Metastasis: The CNS is commonly affected by metastasis from a
cutaneous melanoma. Among all the primary cancers, cutaneous
melanomas have the highest propensity to metastasise to the brain. It
is the third most common cause of metastatic brain tumours.
3. Primary CNS tumours with melanotic elements:
– Meningiomas
– Medulloblastomas
– Astrocytoma
– Acoustic neuromas
– Pituitary tumours
– Choroid plexus papillomas.
PRIMARY PIGMENTED LESIONS

Localised Melanocytic Neoplasms—Benign
Melanocytomas and Malignant Melanomas
•• The term ‘meningeal melanocytoma’ was first proposed for ‘pigmented
meningioma’.
•• The presence of polar cytoplasmic processes, few zonula adherens and
premelanosomes and melanosomes in the cells, suggests a tumour that
has some of the histological characteristics of meningioma.
Chapter 174 • Intracranial Melanomas and Other Tumours
1295
•• Their epidemiological characteristics, natural history and response to

treatment remain poorly understood.
•• Melanocytes are derived from the neural crest during early embryonic
development and are widely distributed throughout the normal
leptomeninges.
•• Melanocytes occur in the highest concentration ventrolateral to the medulla
oblongata, which accounts for the propensity of these lesions to occur in
the cerebellopontine angle.
•• The highest concentration of melanocytes in the spinal leptomeninges is
found in the upper cervical levels, but spinal meningeal melanocytomas
are not confined to the cervical region and have been described as far as
the thoracolumbar junction.
•• Both intracranial and intraspinal meningeal melanocytomas frequently arise
in proximity to the cranial and spinal nerves, as they exit the brainstem
and spinal cord.
•• Meningeal melanocytomas are more common in females, with a female
to male ratio of 2.2:1.
•• The mean age at presentation is in the early fifth decade.
•• The onset of symptoms is insidious over a period of several months to years.
•• Intracranial meningeal melanocytomas usually present with signs and
symptoms of an expanding mass in the posterior fossa, sometimes
compounded by obstructive hydrocephalus and cerebellar dysfunction.
•• The tumour may grow to a significant size and the patient may present with
single or multiple cranial nerve palsies.
•• Intracranial meningeal melanocytomas are rare lesions and the differential
diagnosis includes pigmented meningiomas, melanotic schwannomas and
primary or secondary malignant melanoma.
•• The pre-operative diagnosis in meningeal melanocytomas is usually
meningioma, because both the tumours have a long duration of symptoms,
appearance of a dural-based extra-axial large mass, features of tight cellular
nests or whorls with similar imaging features.
•• The dark colour of the tumour seen at surgery and the presence of melanin
in the tumour cells at frozen section suggest a diagnosis of melanocytoma.
•• Electron microscopy is required to rule out meningioma, which shows many
intermingling cell processes, not lined by the external lamina but joined
by well-developed desmosomes, unlike the ultrastructure of meningeal
melanocytes where the cell processes are surrounded by a single profile
of external lamina.
•• On CT scan, they appear as well circumscribed, dural based iso- to
high-density masses that enhance homogeneously on contrast, similar
to meningiomas.
•• The degree of melanisation strongly influences the CT pattern. There is
usually sparing of the internal auditory canal and lack of haemorrhage.
•• The MR imaging appearance of these rare tumours is not uniform and
depends on the degree of melanisation, with more melanin causing greater
shortening of T1 and T2 relaxation times.
1296
•• Thus, MR imaging of intracranial meningeal melanocytomas is not a very

reliable or specific technique for the diagnosis of this rare tumour.
•• On MR examination, they are isointense to hyperintense on T1-weighted
images and isointense to hypointense on T2-weighted images with intense
homogeneous contrast enhancement.
Histopathology
•• On gross examination, these tumours are dark brown or black, heavily
pigmented, and well-demarcated lesions that are firmly attached to the
underlying leptomeninges.
•• Microscopically, the low-grade lesions have architectural and cytological
features different from the high-grade aggressive tumours.
•• The most specific feature of melanocytoma is the presence of melanocytes
in tight nests with heavily pigmented cells at their periphery.
•• At high magnification, low-grade lesions reveal remarkably uniform oval
or bean shaped nuclei with small regular, eosinophilic nucleoli, and the
mitotic indices are low.
•• The clinically aggressive melanomas differ from low-grade lesions in that
they are highly cellular tumours with high nuclear to cytoplasmic ratio,
increased mitotic activity, nuclear atypia which are more basophilic in
nature.
•• Immunohistochemistry reveals a positive reaction to vimentin antibodies,
S-100 protein and antimelanoma antibody (HMB-45) with absent response
to epithelial markers—EMA, NSE, GFAP and cytokeratin. Vimentin is rarely
present in malignant melanoma; while meningioma cells lack the presence
of HMB-45 and S-100 protein.
Management
•• The extent of surgical resection is the most important determinant of
outcome and support the view that long-term patient survival is enhanced
by complete tumour resection.
•• The role of radiotherapy in the management of these tumours is
controversial, however, it is worth considering for those patients with
symptomatic residual, progressive or recurrent tumours not amenable for
further resection.
Prognosis
•• Meningeal melanocytomas have a much better prognosis as compared to
their malignant counterparts.
•• These patients have a relatively good prognosis, with most of the patients
surviving at least several years after the diagnosis.
•• However, these tumours do locally recur.
•• Despite various treatments including surgery and radiotherapy, there is a
71% recurrence rate at 5 years.
Diffuse Melanocytic Neoplasms

Neurocutaneous Melanosis
•• Neurocutaneous melanosis (NCM) is a rare congenital syndrome.
•• The criterion for the diagnosis of this syndrome are: (1) one or more
congenital giant hairy nevi, multiple pigmented nevi or marked generalised
brown cutaneous pigmentation that is unduly large (more than 20 cm);
(2) there is no malignant melanoma transformation of the involved skin
Chapter 174 • Intracranial Melanomas and Other Tumours
1297
area; (3) diffuse thickening and brownish black melanin pigmentation of

CNS pia mater, with no evidence of primary malignant melanoma in any
organ other than the CNS.
•• Extensive surgical biopsy is essential to establish a correct diagnosis.
•• NCM is considered a phakomatosis because it is thought to arise from
congenital dysplasia of the neuroectodermal melanocytic precursor.
•• The disease affects both the sexes equally and occurs more frequently
in whites.
•• The neurological symptoms usually appear within the first two years of life.
•• The cutaneous lesions of NCM are congenital melanocytic nevi.
•• Malignancy can occur at any age, but it occurs mostly during the first
decade of life.
•• The clinical features are usually the result of raised intracranial pressure,
manifesting as vomiting, seizures, headache, increased head circumference
and photophobia.
•• Raised intracranial pressure is due to the presence of an abnormal mass
of melanotic cells in the meninges or the presence of hydrocephalus.
•• The patient may develop ataxia with inability to walk, and show psychiatric
symptoms with disease progression.
•• NCM must be differentiated from melanotic neuroectodermal tumour
(MNET) of the cranium of infancy and from melanotic nerve sheath tumour.
•• MNET is a benign pigmented tumour arising from the neural crest cells
and mostly occurs at the anterior fontanelle. They have an excellent
prognosis following an early, complete excision. Radiotherapy is reserved
for incompletely resected lesions.
•• Melanotic nerve sheath tumours are slow growing benign plexiform melanin
containing neurofibromas found in young adults, which do not metastasise.
Secondary Malignant Melanoma
•• Melanoma has the highest tendency to metastasise to the brain among
all the primary cancers.
•• It is the third most common cause of cerebral metastasis after breast and
lung.
•• Malignant melanomas commonly metastasise to lung and liver; however,
the reported incidence of cerebral metastasis in patients with melanoma
ranges from 6 to 43% in clinical series and 12 to 74% in autopsy series.
•• Most of them are solitary but multiple metastases are not uncommon.
•• Seventy-five per cent of the patients with malignant melanoma with
metastatic disease have intracranial involvement with the frontal and
parietal lobes being the most common sites.
•• There is also a high incidence of extracerebral metastasis at the time of
diagnosis of cerebral involvement.
•• The time interval from the diagnosis of the primary lesion to cerebral
metastasis varies from 6 to 60 months.
•• The clinical features depend on the site of cerebral involvement.
•• Cerebral metastases carry the worst prognosis of all the visceral metastasis
in patients with melanoma and are the cause of death in more than 50%
of patients dying of malignant melanoma.
•• Malignant melanomas have a characteristic appearance on CT and MRI
and are classified according to their size into less than 1 cm, 1–4 cm and
more than 4 cm.
1298
•• They are usually seen at the grey-white junction of the cerebrum and are
slightly hyperdense with moderate contrast enhancement.
•• Most of these lesions show moderate perilesional oedema and occasionally
show a leptomeningeal spread.
•• On MRI, T1 and T2 shortening is seen due to the presence of melanin.
•• The poor prognostic factors are the presence of more than one cerebral
metastasis and disease in multiple sites, including the brain.
•• Surgical treatment has also been indicated for the treatment of cerebral
metastasis from melanoma.
Indications
•• Single brain metastasis accessible to safe and complete resection without
any other visceral metastasis.
•• Multiple brain metastasis with symptomatic or life threatening brain lesion
accessible to safe and complete resection and no other visceral metastasis.
•• Single brain metastasis accessible to safe and complete resection and one
other visceral metastasis accessible to complete resection or responding
to systemic therapy.
•• Multiple brain metastasis all accessible to safe and complete resection
and one other visceral metastasis accessible to complete resection or
responding to systemic therapy.
•• Single symptomatic or life threatening brain metastasis accessible to safe
and complete resection and one other untreatable visceral metastasis.
•• Multiple brain metastasis with a symptomatic or life threatening brain lesion
accessible to safe and complete resection and one other untreatable visceral
metastasis.
Contraindications
•• Brain metastasis not accessible to safe and complete resection.
•• More than one visceral metastasis in addition to the brain lesion.
•• Radiological or pathological evidence of leptomeningeal spread of tumour.
•• Surgical procedure likely to be life threatening.
–– Malignant melanoma is relatively radioresistant.
–– Over the past decade, stereotactic radiosurgery has been found to
provide control of cerebral metastasis from melanoma.
175
CHAPTER Benign Intracranial
Tension
Nigel Peter Symss  Ravi Ramamurthi
INTRODUCTION
•• The term benign intracranial hypertension (BIH) refers to a condition of
increased intracranial pressure (ICP) in which the ventricles are not dilated
and the cerebrospinal fluid (CSF) is normal.
•• The patients present with symptoms and signs of increased ICP usually
without any focal neurological deficit.
•• Thorough investigations fail to reveal a space occupying lesion or any other
specific cause for the raised ICP.
PATHOPHYSIOLOGY
•• The factors that may contribute to BIH are cerebral oedema, reduced CSF
resorption, increased CSF production, increased cerebral blood volume
and increased venous pressure.
•• The basic pathology is either an excess of accumulation of CSF in the
intracranial subarachnoid space or an increase in the bulk of the brain
parenchyma.
•• In either case, the ventricles do not dilate and the biochemistry of the CSF
remains normal.
•• Thus, two main groups may be recognised, those with obstruction to the
exit of the CSF from the cranial cavity and those without.
•• Absorption of CSF may be interfered with when there is thrombosis of the
dural sinuses or the cerebral veins or an obstruction in the arachnoid villi.
This may be caused by head injury, intracranial infections or thrombotic
lesions.
•• In these cases, the back pressure builds up initially in the subarachnoid
space and then gets communicated to the ventricular system. Hence,
although the ventricular pressure rises, the ventricles do not dilate.
•• The subarachnoid space often contains an excess of CSF. This group falls
under the definition of communicating hydrocephalus and not BIH.
•• CSF is thought to flow continuously from the site of production in the
ventricles into interconnected spaces, i.e. cisterns and subarachnoid
spaces (SASs).
•• Computed cisternography, with a contrast agent in three patients with
idiopathic intracranial hypertension and asymmetric papilloedema,
demonstrated a lack of contrast-loaded CSF in the SAS of the optic
nerve, despite it being present in the intracranial SAS, thus suggesting
compartmentalisation of the SAS of the optic nerve.
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•• A convective transependymal flow of water with increased outflow

resistance resulted in interstitial brain oedema and intracellular brain water
accumulation.
•• CSF outflow resistance has been confirmed by lumbar steady state infusion
tests and by radioisotope cisternography.
•• BIH is rarely seen in very young children or in old people. In elderly patients
the ventricles may show minimal enlargement.
•• It is possible that the resistance to ventricular dilatation in the presence of
decreased CSF absorption may be related to the volume and the state of
maturity of the brain.
INFANTILE PRESENTATION OF
BENIGN INTRACRANIAL HYPERTENSION
•• These infants present with an enlarging head and a full fontanelle.
•• The cranial sutures show separation.
•• Apart from these, the infants do not show any abnormality and the mile-
stones are normal.
•• CT shows mild enlargement of the ventricles with enlarged SASs.
•• The prognosis is good as the disease is self-limiting.
AETIOLOGY
•• Many conditions and agents lead to the development of BIH.
•• Hypervitaminosis, hypoparathyroidism, prolonged steroid therapy, chronic
adrenal insufficiency, severe anaemia and pregnancy may cause BIH.
•• Hypervitaminosis is known to produce hydrocephalus.
•• The use of oral contraceptives and the consequent water and sodium
retention may cause BIH.
•• BIH may also follow antibiotic therapy with tetracycline, ampicillin,
amphotericin B, minocycline and/or ciprofloxacin.
•• The aetiology of BIH also includes administration of eltroxin or growth
hormone, danazol or of chemicals like cytosine arabinoside and benzene
hexachloride (Lindane) (Table 1).
•• Higher levels of weight gain and BMI are associated with greater risk of BIH.
•• Even non-obese patients (BMI < 30) are at greater risk for BIH in the setting
of moderate weight gain.
•• Vision-specific and overall health-related quality of life (HRQOL) is affected
to a greater extent in BIH than in other neuro-ophthalmological disorders.
•• Increased incidence of this condition in middle aged, obese, females and its
association with pregnancy, menarche and menstrual dysfunction suggest
a possible endocrinal aetiology.
•• A defect in endogenous corticotrophin metabolism or of its release has been
implicated as a cause of BIH. Patients with BIH did not show a response
to metyrapone. The test became normal when clinical remission occurred.
CLINICAL DESCRIPTION
•• The condition is characteristically described in middle aged females who
are usually obese. However, it affects all ages and both sexes.
•• The signs and symptoms are those of increased ICP with headache,
vomiting and papilloedema.
Chapter 175 • Benign Intracranial Tension
1301
Table 1: Conditions associated with benign intracranial hypertension

Drugs
Tetracycline
Oral contraceptives
Nitrofurantoin
Sulphamethoxazole
Systemic steroid withdrawal
Dietary conditions
Hypervitaminosis
Hypovitaminosis
Obesity
Systemic illnesses
Anaemia
Hypertension
Pregnancy
Heart failure with venous hypertension
Congenital heart disease
Renal disease
Multiple sclerosis
Systemic lupus erythematosus
Thrombocytopaenic purpura
Addison’s disease
Sarcoidosis
Reye’s syndrome
Familial Mediterranean fever
Chronic respiratory insufficiency
•• Headache in BIH can be excruciating in some patients. It is usually pulsatile

and the increasing intensity during sleep may waken the patient.
•• Pain along the trigeminal or occipital nerve root distribution and retrocular
pain often occur in BIH, unlike in other headaches.
•• There are no localising neurological signs.
•• Diplopia, vertigo, tinnitus and ataxia, and various cranial nerve palsies
can be seen.
•• Pituitary deficiency and empty sella syndrome may occur in BIH.
•• There may be a history of ear infection in some cases.
•• It is essential to exclude an intracranial lesion before diagnosing BIH.
•• Imaging studies show a normal or narrowed ventricular system.
•• Visual evoked potentials are useful in determining the state of visual function
and in following up patients.
•• Optical coherence tomography (OCT) shows increased peripapillary retinal
nerve fibre layer (RNFL) and macular thickness in PTC and may be a useful
clinical tool for diagnosis in children.
1302
•• Acquired choroidal folds and optic nerve subarachnoid space enlarge-

ment may be signs of BIH and their appearance depend on the level of
ICP. They can be identified by OCT, fluorescein angiography and ocular
fundus photography.
•• Nevertheless, the diagnosis should be confirmed by lumbar puncture.
CT AND MR STUDIES
•• The diagnosis of BIH is one of exclusion and based on a series of diagnostic
negatives.
•• CT and MR help to exclude other possible causes of raised ICP.
•• The scans are normal before and after contrast enhancement.
•• In some patients, the subarachnoid space or the perioptic CSF space may
be widened and there may be an empty sella.
•• MR is more sensitive to exclude an intracranial lesion and to show sinus
or venous thrombosis.
•• Flattening of the posterior aspect of the globe on cross-sectional imaging
and if present, strongly suggest the diagnosis of BIH.
•• In addition, evaluation of extra-luminal and intra-luminal narrowing of the
transverse and sigmoid dural sinuses, with contrast-enhanced MRV using
a simple grading system, provides a highly sensitive and specific test.
•• Vaphiades et al. analysed cranial and orbital MRI scans and found six
neuroimaging signs to predict elevated ICP in these patients: flattening
of the posterior sclera; optic nerve enhancement; perioptic subarachnoid
space distension; optic nerve vertical tortuosity; empty sella and intraocular
protrusion.
•• The venous phase during angiography may reveal a block in a major venous
sinus in an occasional case.
•• Isotope cisternography may show abnormality of CSF absorption through
the arachnoid villi in some cases, while in many it may be normal.
•• Pulsatile tinnitus, hearing loss and a feeling of fullness in the ear may be
complained of by some patients.
•• Brainstem auditory evoked response may show bilateral prolongation of
peak latencies, which return to normal after treatment.
•• CSF pressure measurements are high and the composition of the CSF
is normal.
•• In tropical countries, one should exclude cysticercosis, which may simulate
BIH. The CT scan and MR are both diagnostic in cysticercosis; MR is more
sensitive and may show the cysts even when the CT scan is negative.
•• Mild residual arachnoiditis following tuberculous meningitis usually causes
hydrocephalus, but rarely may mimic the clinical picture of BIH.
•• Toxic and lead encephalopathies may simulate BIH.
•• Pseudopapilloedema with headaches can be differentiated from BIH by
careful ophthalmological examination, including fluorescein angiography
and delineation of the blind spot.
•• Bilateral disc drusen is an important differential diagnosis of PTC.
TREATMENT
•• The aim of treatment is to relieve headaches and specially to prevent loss
of vision.
Chapter 175 • Benign Intracranial Tension
1303
•• Conservative therapy is useful in most cases, but surgery is necessary

when vision is threatened. Hence, a careful watch is necessary to detect
deterioration in acuity of vision or in the visual fields.
•• Visual evoked potentials and repeated quantitative perimetry are helpful
in assessing the progress and in helping to decide on surgical treatment.
•• Any detectable cause for BIH, e.g. hypervitaminosis, antibiotics or anaemia,
requires suitable corrective measures.
•• In other cases it is necessary to reduce the ICP. This may be done for a
few days by intravenous mannitol or diuretics like furosemide.
•• Dexamethasone, 12 mg a day, is administered for a few days in resistant cases.
•• When the response is satisfactory, this may be followed by oral glycerol
for some weeks.
•• Topiramate seems to be effective in the treatment of BIH, weight reduction
and the reduction of CSF formation being the possible mechanism of action.
•• In many cases, it will be necessary to do frequent lumbar punctures to
lower the ICP.
•• Barbiturate augmented hypothermia has been used to reduce ICP.
•• In cases where the pressure is very high, the patient is ill or the vision is
threatened, surgical therapy is indicated.
•• Lumboperitoneal shunt is favoured by many surgeons, but has drawbacks
like backache and persistent root pains.
•• Cisternal shunting has been found useful.
•• Recent reports have shown promising short-term to medium-term results
in patients with refractory idiopathic intracranial hypertension (BIH), treated
using the stereotactic ventriculoperitoneal shunting (SVPS) technique.
•• Before appropriate shunts were available, subtemporal decompression has
been used successfully on many patients and is still preferred by some
surgeons to avoid problems associated with shunts.
•• Recently, endoluminal venous sinus stenting has been proposed as an
effective and safe alternative treatment. It was performed under intravenous
heparin administration and anti-platelet therapy was administered for 3
months post-treatment.
OPTIC NERVE SHEATH DECOMPRESSION

•• Patients with BIH and progressive visual impairment have been shown to
benefit from optic nerve sheath decompression.
•• It is desirable to perform the operation as soon as it is obvious that medical
therapy is not effective in preventing progressive visual deterioration.
•• This operation is also known to provide relief from intractable headache.
•• Demonstration of retrobulbar optic nerve sheath enlargement by CT or
orbital echography is essential before making a decision to operate.
•• A variety of surgical approaches have been described for optic nerve
sheath decompression.
•• However, the medial approach of Galbraith and Sullivan remains the most
frequently employed technique.
•• The procedure is safe, with few complications.
•• Endoscopic endonasal optic nerve fenestration is a safe, minimally invasive and
extremely effective procedure with good success rate and minimal morbidity.
•• Bariatric surgery and weight loss has been advocated for obese patients
with BIH and stable visual symptoms to avoid shunt placement or optic
nerve sheath fenestration.
176
CHAPTER Tumours of the
Cranial Vault
Narayanan R  Ravi Ramamurthi
INTRODUCTION
•• The skull bones are affected by lesions similar to those seen in the other bony
structures such as benign or malignant neoplasms or metastatic deposits,
congenital dysplasias, metabolic disorders and haemopoietic diseases.
•• Lesions that are primarily intracranial may involve the skull secondarily, and
similarly, tumours arising in the skull bones can spread inside, producing
raised intracranial pressure and focal neurological deficits.
•• Malignant conditions from the paranasal sinuses, nasopharynx and orbit
may spread to the base of skull and produce cranial nerve palsies.
•• The vault of the skull is made up of membrane bones, whereas the base
is of cartilaginous origin. This influences the type of pathological lesions
that may develop in different parts of the skull.
•• The deeper periosteum of the skull bones (the endosteum) is firmly
incorporated with the dura mater.
•• The dura forms an effective barrier against the intracranial spread of
lesions of the skull.
•• Dural lesions, however, often invade the inner table of the skull.
Classification
Tumours of the skull can be primary or secondary.
A. Primary tumours:
1. Benign 2. Malignant
• Osteoma • Chondrosarcoma
• Haemangioma • Osteogenic sarcoma
• Giant cell tumour • Fibrosarcoma
• Dermoid • Carcinoma of the temporal bone
• Epidermoid • Fibrous histiocytoma
• Chondroma • Chordoma
• Lipoma • Reticulum cell sarcoma
• Aneurysmal bone cyst • Angiosarcoma
• Ossifying fibroma • Malignant sweat gland tumour
• Cavernous haemangioma • Orbital rhabdomyosarcomas
• Myxomas • Bone penetrating Marjolin’s ulcer of
• Benign osteoblastoma scalp
• Ewing’s sarcoma
Chapter 176 • Tumours of the Cranial Vault
1305
B. Secondary tumours:
1. Contiguous spread 2. Haematogenous
• Meningioma • Secondary metastases
• Glomus jugulare tumour • Lymphoma
• Nasopharyngeal tumours • Leukaemic deposits
• Carcinoma of the
paranasal air sinuses
• Sinonasal melanoma
• Nasal basal cell carcinoma
C. Conditions simulating skull tumours:
• Osteomyelitis • Sarcoidosis
• Cephalhaematoma • Paget’s disease
• Leptomeningeal cyst • Fibrous dysplasia
• Vascular disorders • Hyperparathyroidism
• Vascular impression • Mucocoele
• Sinus pericranii • Neuroectodermal dysplasia
• Histiocytosis X • Haemolytic anaemias
• Pacchionian granulations • Petrous apex cholesterol
• Hyperostosis frontalis interna granuloma
DIAGNOSTIC EVALUATION
•• The common presenting symptoms are swelling, deformity, disfigurement
and local pain.
•• Many skull tumours are detected incidentally on radiographical examination
done for other reasons.
•• The usual diagnostic procedures include plain films of the skull, computer-
ised tomography, magnetic resonance imaging and cerebral angiography.
•• Radionuclide bone scanning is occasionally done to detect metastases in
bones from other primary malignancies.
Plain Skull Films

•• Routine views and tangential or edge-to-edge views are taken to detect the
location, extent and the degree of involvement of the tables and diploe, and
also to know whether the lesion is sclerotic, lytic or mixed.
•• When both the tables are involved, the lesions appear more lucent (punched
out).
•• Examination of the margins of the radiographic abnormality gives valuable
information.
•• Sharply defined and sclerotic edges indicate that the process is a slowly
expanding one, permitting enough time for the adjacent bone to react by
condensation and thus, the process is more likely to be benign.
•• Irregular, poorly defined margins suggest a more aggressive process, either
malignant or inflammatory.
Computed Tomography
•• Computed tomography (CT) provides more accurate information regarding
the extent of involvement of the skull bones as well as the soft tissues, both
within and outside the skull.
1306

•• Signal intensity in magnetic resonance (MR) depends primarily on the
concentration of mobile protons (hydrogen nuclei) in the tissue being imaged.
•• As compact cortical bone lacks in unbound protons, the inner and outer
tables of the skull appear as a signal void in the MR image.
•• The diploe has abundant fat and hence images well, so also the pathological
lesions arising in the diploe.
•• Lesions at the base of the skull are better imaged by MR than CT, as the
latter produces bone artefacts.
•• Neoplasms have greater water content and hence are imaged with sharp
contrast from the surrounding structures.
•• Assessment of possible intracranial extension when the CT and MR are not
clear and the mapping out of the vascular supply of the neoplasm, before
surgery, are some of the indications.
•• Selective external and internal carotid studies are useful.
MANAGEMENT
•• In principle, the treatment of neoplasms of the skull is similar to that of
bone tumours elsewhere.
•• The close proximity of the brain and other vital structures necessitates
certain modifications in the therapy.
•• Surgery, radiotherapy and chemotherapy are the modalities of treatment
available and are often used in combination.
Operative Treatment
•• This depends on the suspected nature of the lesion, its location, single
or multiple and whether neurological deficits are already present or are
likely to result.
•• A suspicious skull lesion, in the absence of any other demonstrable primary
process, calls for a biopsy to determine the line of therapy. A needle biopsy
may be adequate in some cases.
•• In hard non-penetrable lesions, an open biopsy is done through an incision
made at the circumference of the lesion, taking an adequate amount of
tissue.
•• Primary tumours of the skull are excised completely whenever possible.
This is especially important if the lesion produces neurological symptoms,
causes cosmetic deformity or becomes infected.
•• Cranioplasty may be done at the same sitting or at a later date.
Radiation Therapy
•• When deciding on radiation therapy, careful planning is necessary, taking
into consideration the radiation sensitivities of adjacent normal structures
such as the brain and eyes.
•• Multiple small fractionated doses per day spread out over a longer time, give
a greater tumour killing response with less damage to normal structures.
•• Generally, the required dose is 55 Gray (Gy) or 5,500 rads in 30 fractions
over 6 weeks utilising megavoltage photon radiation.
•• Higher energy photon or electron beam therapy is the ideal treatment and
can be tailored to the tumour volume by computerised techniques.
1307
•• Adjuvant therapies, like the use of hyperthermia and hypoxic cell sensitisers,
are being tried.
•• Palliative radiation to reduce the size of the mass may be advised, depending
on the expected survival time and the probability of late adverse reactions.
Chemotherapy
•• Chemotherapy alone is useful in a few conditions like Hodgkin’s disease,
acute childhood lymphocytic leukaemia and testicular carcinoma.
PRIMARY TUMOURS OF THE SKULL

Benign Tumours
Osteoma
•• Osteomas are the most common of the benign neoplasms of the skull and
facial bones.
•• Usually solitary lesions are seen in the frontal region.
•• They arise from membranous bone and proliferate into dense cortical bone
or spongy cancellous bone.
•• They commonly occur in the frontal sinus and in the mastoid air cells.
•• These slow growing tumours form an outward excrescence which is hard
and painless and are usually noted while combing the hair.
•• A compact osteoma may become hard like ivory.
•• The attachment to the skull may be narrow or broad.
•• Rarely, an osteoma may extend intracranially and cause seizures.
•• In plain X-rays, an osteoma is seen as a solid homogeneous bony shadow.
There are no increased vascular channels.
•• Tangential projections reveal the base and the absence of involvement of
the diploe and inner table. When the inner table is involved, differentiation
from a meningioma becomes necessary.
•• CT gives the precise diagnosis.
•• Multiple osteomas of the calvaria and mandible with soft tissue tumours
of the skin and colonic polyposis form the triad of Gardner’s syndrome.
•• Microscopically, the tumour is a nucleus of osteoid tissue in a background
of osteoblastic connective tissue and is completely enclosed by reactive
bone. Histological differentiation from fibrous dysplasia is difficult; but the
presence of smooth, homogeneous and sharply defined sclerotic nodules
is unusual in fibrous dysplasia.
•• Osteomas are surgically curable.
•• The indications for removal are rapid growth, pain, obstruction to sinus
outlets and noticeable deformity.
•• Small osteomas of the outer table may be resected easily without
destruction of the inner table.
•• A large lesion needs removal of the entire bone as a flap and the defect
is closed by cranioplasty.
Haemangiomas
•• Haemangiomas constitute about 7% of all skull tumours.
•• About two-thirds of haemangiomas of bone occur in the skull or the
vertebral column.
•• They arise from the vascular elements of the diploe, mainly in the vault of the
skull and to a lesser extent in the roof of the orbit or petrous temporal bone.
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•• They are slow growing and may reach a large size. They are painless and
the presence of a swelling is the chief complaint.
•• The swelling is hard, but may be soft at some places. The skull is involved
by erosion and the margins are imperceptible. Dilated veins may be present.
•• In haemangiomas of the orbit, proptosis, blindness or extraocular palsies
may be seen. Haemangioma of the petrous bone may present with deafness
and cranial nerve palsies.
•• The plain X-rays show a swelling with a typical honeycombed or sunburst
appearance. The diploe is enlarged and both tables of the skull bulge, outer
more than the inner. Rarely, intracranial extension is seen. The trabeculae
are seen vertically oriented. The edges are well defined and a thin margin
of bony condensation may be evident.
•• CT images with ‘bone window’ show the hypodense matrix with discrete,
thickened, sclerotic and widely separated trabeculae. Despite the vascular
nature of the lesion, contrast enhancement is an exception rather than
the rule.
•• Carotid angiography shows enlargement of the external carotid artery
branches.
•• Treatment is usually by en bloc excision or wide curettage.
•• Radiotherapy is advisable in situations where excision is not feasible.
•• Doses up to 30 Gy (3,000 rads), in 3 weeks, may be required.
Giant Cell Tumours (Osteoclastoma)
•• Giant cell tumours arise from the cartilaginous bone in the sphenoid,
mastoid or occipital areas.
•• They are extremely rare in the bones of the vault, as osteoclasts are usually
not present in membrane bones.
•• Their pathogenesis is unknown, although trauma and haemorrhage may
precede their occurrence.
•• Osteoclastoma of the skull presents as a painless bony swelling and
radiographs show evidence of rarefaction or destruction of bone.
•• Excision is the treatment of choice; but it is often incomplete and needs
supplementary radiotherapy to ensure freedom from recurrence.
•• Occasionally, malignant changes have been reported after surgery and
radiotherapy.
•• Considering the aggressive nature and potential malignancy of these
lesions, careful long-term clinical and imaging follow-up is recommended.
Chondroma
•• These arise mainly in the cartilaginous bones of the base of the skull.
•• They commonly occur between the ages of 20 and 40 years.
•• The common sites are the paranasal sinuses and the sphenoethmoidal
and spheno-occipital synchondroses.
•• Depending on the site of origin, they may extend into the sellar or parasellar
region, producing visual and ocular nerve palsies or endocrine dysfunction.
•• The posterior lesions may compress the brainstem and involve the lower
cranial nerves.
•• Radiographically, a chondroma appears as a lytic lesion at the base of the
skull with fairly sharp margins.
•• Areas of stippled calcification may be seen in more than 60%.
•• CT reveals well marginated bone destruction and an associated homogene-
ous, isodense and lobulated soft tissue mass with interspersed calcification.
Contrast enhancement is infrequent and when present is minimal.
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•• Differentiation from metastasis is based on the sharpness of the bony

margin and the presence of calcification. Other lesions to be differentiated
are chordoma and meningioma.
•• Rapid growth indicates a malignant change.
•• Histologically, malignancy is deduced by the presence of atypical cartilage
cell nuclei in the actively growing peripheral portions of the neoplasm.
•• The treatment of a chondroma is total removal wherever possible.
•• Most often, only partial removal is possible, especially at the skull base.
Other Benign Tumours
•• Calvarial lipomas: They are rare. They present as painless, benign and
slowly progressive lesions, often an incidental finding. These lesions appear
hyperintense on both T1- and T2-weighted images. On CT scan, evidence
of mixed bony destruction and proliferation are reported. Gross and
histological features are like lipomas elsewhere. They are cured by excision.
•• Cavernous haemangioma of the skull: Despite their low incidence,
cavernous haemangiomas must be included in the differential diagnosis of
slow-growing osteolytic lesions located in the skull. The elective treatment
of these tumours includes a complete resection by craniectomy, with safe
bony margins. A large cranial cavernous haemangioma can be treated using
embolisation and craniotomy with preservation of the outer cranial table.
•• Aneurysmal bone cyst:
–– It is a multiloculated expanding cystic tumour with a rich vascular
network in the walls.
–– The encircling inner and outer tables are eroded to form thin bony
shells.
–– Some cysts show a central core of haemangioma and repeated haem-
orrhage may be the cause of the cystic expansion of the skull tables.
–– These lesions may either become symptomatic or enlarge during
pregnancy.
–– On CT, the contents of the cyst may be of high or low density, depend-
ing on the protein content of the fluid.
–– The superficial temporal and middle meningeal arteries supply the
tumour and this is made out well on selective external carotid angi-
ography.
•• Ossifying fibromas or benign osteoblastoma: It is a rare tumour and has
been described as a giant osteoid osteoma. It is a solitary vascular tumour,
predominantly osteolytic in character, with varying degrees of calcification
and new bone formation. Treatment is by local excision.
•• Osteoblastomas:
–– They are occasionally seen in the base of the skull, but rarely in the
vault.
–– Most frequently, they occur in the midline in the clivus.
–– Depending on the site of origin, they produce signs of pressure on the
optic nerves, the pituitary, the hypothalamus, the brainstem and the
other cranial nerves.
–– Radiologically, islands of erosion with normal bone in between are
seen in the region of the clivus and sella.
–– A suitable skull base approach enables excision of as much of the le-
sion as possible to ensure decompression of neural structures and the
pituitary gland. Radiotherapy can be given post-operatively.
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•• Myxomas:
–– They are rare benign tumours arising from mesenchymal tissues
throughout the body.
–– Involvement of the skull base with intracranial extension has been
reported but is extremely rare.
–– It requires surgical excision.
–– Despite radical surgery, the tumour may recur requiring re-surgery.
–– The differential diagnosis frequently includes chondrosarcomas, chordo-
ma, metastatic tumours of the skull, haemangiopericytoma, meningioma
and other neoplasms of the dura and skull base in this location.
Malignant Tumours
Chondrosarcoma and Osteogenic Sarcomas
•• They are the two primary malignant tumours of the skull and both are rare.
•• Chondrosarcomas form 0.1% of all intracranial tumours and 6% of skull
base lesions.
•• Chondrosarcoma is a tumour of adult life, usually occurring as a malignant
transformation in a benign chondroma.
•• The common site is the base of the skull, in or around the sella, the
cerebellopontine angle or the frontoethmoidal air sinuses.
•• They grow for a long time and produce pain, deformity and cranial nerve
palsies in the advanced stages.
•• Roentgenograms show destruction of bone with irregular poorly defined
margins.
•• In more than 50% of cases, stippled calcification is seen, a fact used to
differentiate these lesions from metastatic carcinoma, lymphoma and
myeloma.
•• CT demonstrates an irregular destructive process with a soft tissue mass
that is homogeneous and hyperdense.
•• Areas of calcification are seen within the mass in more than 60% of cases.
•• On contrast infusion, irregular and heterogeneous enhancement of
moderate intensity is noted within the tumour.
•• They are locally invasive and tend to recur.
•• Radical resection with supplemental radiation therapy is the treatment of
choice.
•• The five-year survival rate is usually in the range of 60−70%. Systemic
chemotherapy is ineffective.
Osteogenic Sarcoma
•• This rare tumour occurs usually in the vault and accounts for about 2% of
all primary osteogenic sarcomas.
•• It usually occurs in young adults, between the ages of 15 and 25 years.
•• A second modest peak occurs in older patients secondary to advanced
Paget’s disease of the skull.
•• Osteogenic sarcomas grow rapidly and hence the history is quite brief.
•• Pain and local swelling are the common symptoms.
•• Early metastases to the lungs and other bones usually occur.
•• On the plain radiographs they appear as a large lytic area with poorly
defined margins. Radiating bony spicules, in the form of sun rays, may be
seen in some cases at the edge of the tumour. The calvarium is thickened
at the advancing edge of the tumour due to subperiosteal extensions.
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•• CT shows irregular and prominent new bone formation within a large

heterogeneous extradural mass showing irregular contrast enhancement.
These tumours are extremely vascular and are sometimes referred to as
bony aneurysms.
•• Histological features are extremely variable with foci of new bone formation,
necrosis, haemorrhage, telangiectasia and a frank sarcomatous stroma.
•• Radiographically, there is rapidly progressive lysis within the thickened
and irregularly dense bone.
•• The usual treatment is complete excision followed by high doses of
irradiation of 60–70 Gy (6,000–7,000 rads) post-operatively.
•• Adjuvant chemotherapy with methotrexate and leucovorin in high dose is
administered.
Fibrosarcoma
•• Fibrosarcoma may arise from the periosteum of the skull or from the dura.
•• It presents as a rapidly growing painful tumour.
•• In the early stages, X-rays show only a thinning of the outer table by an
overlying soft tissue mass.
•• In the later stages, there are large areas of complete destruction of both
tables. The margins are irregular.
•• The differential diagnosis is from other lytic tumours.
•• Carcinomas are usually smaller and multiple.
•• Osteogenic sarcoma without new bone formation at the periphery may
cause difficulty in diagnosis on plain X-rays.
•• Microscopic examination of a fibrosarcoma shows only a sarcomatous
stroma without any new bone formation.
•• Fibrosarcomas are treated by radical resection, followed by high doses
of post-operative radiation; 60–70 Gy (6,000–7,000 rads) in 6–7 weeks.
•• Chemotherapy has not been found to be advantageous. A five-year survival
rate of 3% has been reported.
Ameloblastic Fibrosarcoma
•• It is a malignant odontogenic tumour that rarely affects the skull base and
surrounding regions.
•• This is due to a malignant transformation of a benign ameloblastic fibroma.
•• The ameloblastic fibrosarcoma can extend from the site of origin to the orbit,
anterior or middle cranial fossa, infratemporal fossa or to the cavernous
sinus.
•• Progressive proptosis with complete monocular vision loss was the
presenting symptom.
•• Multidisciplinary skull base approach, resection of all tumour except that
in the cavernous sinus is recommended.
Malignant Fibrous Histiocytoma
•• This is a pleomorphic sarcoma arising in the deep soft tissue of the
extremities.
•• It has also been found to arise from the bones and rarely from the skull.
•• The frontal, temporal and occipital bones were seen to be involved.
•• Metastases occur in the mediastinum, thoracic vertebrae and lungs.
•• CT shows a large mass of low density with patchy enhancement, extending
on the inner and the outer surfaces of the cranial bone with patchy
enhancement.
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•• MR shows a bulky tumour with mottled enhancement with contrast.

•• Sometimes, local scalp tenderness and a skull defect in the plain film in
the corresponding area may be present for several months, before the
tumour becomes obvious.
•• The gross appearance and conventional histological examination do not
show any specific features.
•• There is a highly cellular pleomorphic picture consisting of spindle shaped
cells of fibroblastic and histiocytic origin arranged in a spongiform pattern.
•• The exact diagnosis can be made only by immunohistochemical methods
to demonstrate intracytoplasmic granules, with staining of alpha-1
antichymotrypsin and alpha-1 antitrypsin.
Ewing’s Sarcoma
•• It is rarely seen as a primary lesion in the skull.
•• The most common site for primary Ewing’s sarcoma of the cranium is the
temporal bone followed by the frontal, parietal and occipital bones.
•• The patient usually complains of intermittent pain, more at night.
•• The swelling appears later and may fluctuate in size, with increasing pain
during periods of enlargement.
•• Anaemia, leucocytosis and fever are common.
•• The lesions are often multicentric in origin involving the tibia, ribs and
vertebrae.
•• Metastasis may occur in the liver.
•• On plain X-rays, the lesion appears as an irregular area of bone destruction
with poorly defined margins and an overlying soft tissue mass.
•• A minor periosteal reaction may be present.
•• CT and MR help to delineate the extent of bony involvement and the soft
tissue mass, both extracranial and intracranial and will also demonstrate
a diploic lesion.
•• The venous phase of carotid angiography demonstrates depression of the
superior sagittal sinus.
•• The lesion is composed of compact strikingly uniform cells with indistinct
borders and large prominent nuclei.
•• Differentiating this tumour from reticulum cell sarcoma and from
neuroblastoma with skeletal metastases is difficult, but is very important
to assess the prognosis.
•• Diagnosis can be confirmed by either immunohistochemistry or chromo-
somal abnormalities.
•• Chromosomal abnormalities (translocation 11;22) can be detected by
karyotyping and RT PCR.
•• Ewing’s sarcoma is initially quite radiosensitive, so that radiation therapy
with systemic chemotherapy is the treatment of choice.
•• Recurrences are common and the prognosis is not good with any kind of
treatment.
Other Malignant Tumours
•• Reticulum cell sarcoma is a rare tumour of the skull.
•• It appears as a lytic lesion and the diagnosis is made on histology.
•• En bloc excision followed by radiotherapy has produced clinical cures.
•• Angiosarcoma is occasionally seen in the skull as a soft, painful, rapidly
enlarging tumour which may invade the adjacent scalp and dura.
•• It is seen as a poorly demarcated osteolytic lesion in plain X-rays.
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•• Distant metastases are common.

•• Microscopically, it consists of highly vascular channels, marked anaplasia
and moderate mitotic activity.
•• Wide en bloc excision followed by radiotherapy is recommended.
TUMOURS INVOLVING THE SKULL BY

DIRECT EXTENSION
•• Meningiomas may produce varying degrees of incidental bony changes in
the overlying skull and may also invade the skull bone itself.
•• The tumour may extend into the diploe and sometimes break through the
outer table to form a subcutaneous palpable tumour.
•• Such bony involvement may occur in the vault, the cribriform plate, the
sphenoidal ridge or in the planum sphenoidale.
•• While convexity meningiomas are large tumours, the dural involvement in
basal lesions is often en plaque.
•• The bone involved by meningiomas can be highly vascular with tortuous
arteries and large venous channels.
•• The bony changes caused by basal lesions may resemble those of fibrous
dysplasia.
•• The latter is usually bilateral, occurs at a younger age and angiography
does not show enlarged external carotid artery branches.
•• Sometimes, meningiomas may fail to produce a blastic response and may
destroy the bone, giving an appearance very much like a metastasis in the
plain skiagrams.
•• Bone infiltrated by meningiomas is highly vascular.
•• Cranioplasty may be needed if the involved skull bone is excised.
•• Sometimes, meningiomas remain completely intradiploic, expanding the
two tables resulting in a doughnut like lesion in the plain skiagram.
•• Total excision with repair of the bone defect gives good results.
•• Recurrent craniofacial meningiomas can usually be managed by using a
lateral cranial base approach.
•• A radical resection may prevent further recurrence with an acceptable
quality of life.
Nasopharyngeal Tumours
•• Benign tumours invading the base of skull are commonly angiofibroma and
squamous cell papilloma.
•• These tumours usually become symptomatic long before they invade the
base of skull.
•• When skull involvement is minimal, they can be removed through the
nasopharynx.
•• If there is marked intracranial extension, a combined approach will be
necessary to ensure complete excision.
•• The incidence of nasopharyngeal carcinomas is low, being about 0.01%
of all cancers.
•• They are either epidermoid carcinomas or lymphoepitheliomas.
•• The tumour originates from the nasopharyngeal epithelium and invades
the base of the skull through the foramina and also metastasises to the
regional lymph nodes.
•• Usually they are detected late, after intracranial extension has occurred.
•• Almost all the cranial nerves may get involved.
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•• Hard lymph node enlargement high in the neck may be the first symptom.
•• Quite late in the disease, dysphagia, nasal obstruction and epistaxis may
occur.
•• The diagnosis is made by local inspection and palpation of the nasopharynx
and from evidence of erosion of the base of the skull in plain X-ray films.
•• CT reveals the bony erosion and the soft tissue mass both intracranially
and extracranially and the displacement of neural structures.
•• SPECT is superior to CT in detecting early bone involvement by showing
markedly increased focal radiotracer uptake in regions of bone involvement.
•• Differentiation from other similar lesions, e.g. chemodectoma or chondro-
sarcoma, is difficult and a biopsy is necessary.
•• Nasopharyngeal carcinoma is primarily managed by radiation therapy with
curative doses of 60–70 Gy (6,000–7,000 rads) delivered over a period
of 6−7 weeks.
•• Intensity modulated radiotherapy is being increasingly used in recent days
along with chemotherapy for treating nasopharyngeal carcinoma.
•• Better prognosis is seen in younger patients and those without lymph node
metastasis at presentation.
Haematogenous Metastasis
•• The usual primary sites for skull metastases are the breast, the lungs, the
prostate, the thyroid and the kidneys.
•• The skull metastases are osteoblastic when the primary is in the prostate,
breast or gastrointestinal tract or osteolytic when they arise from carci-
noma of the lung, uterus, thyroid, pancreas and kidney or from malignant
melanoma.
•• Since the close attachment of the dura mater to the cranial bones, malignant
deposits in the skull may invade the dura.
•• Osteolytic metastases to the skull are typically seen in plain X-ray films as
multiple radiolucent areas with poorly defined margins.
•• The size and degree of radiolucency is variable and it is estimated that
more than 50% demineralisation must occur before a lesion could become
radiographically evident.
•• The larger lesions are quite typical in appearance, but lesions less than
5 mm and confined to the diploe are very much like multiple myeloma.
•• Osteomyelitis of the skull may also have a similar radiographic appearance,
but bone destruction appears later in the disease and clinical manifestations
of severe pain, a soft tender swelling and constitutional symptoms occur
earlier.
•• Osteoblastic metastases appear radiographically as multiple, poorly
marginated areas of slightly increased density.
•• On CT, the bone shows slight thickening. In some cases, mixed lucent
and sclerotic areas appear, e.g. metastases from carcinoma of the breast.
•• Although metastases can affect any part of the skull, they are found to be
common in the vault.
•• In the base, the common sites are the dorsum sellae and the clivus, where
the radiographical appearance may be mistaken for demineralisation due
to chronic raised intracranial pressure.
•• Biopsy of the skull lesions may be needed to establish a diagnosis.
•• A complete excision of the lesion can be done and the treatment correlated
with that of the primary disease.
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•• Local palliative radiation may be useful to relieve pain and symptoms of

nerve compression at the base of the skull.
Lymphoma
•• Involvement of bone is a common late feature in disseminated lymphomas
and occurs in 10–15% in Hodgkin’s and 7–25% in non-Hodgkin’s lymphoma.
•• Skull radiography shows areas of osteolysis and it is not uncommon to find
an admixture of sclerotic areas also.
•• CT shows the lesions at the stage of diploic permeation and also delineates
extradural and scalp extension.
•• The more aggressive lymphosarcoma and reticulum cell sarcoma rarely
involve the skull.
•• Treatment consists of local radiotherapy 30–40 Gy (3,000–4,000 rads) over
3–4 weeks, with chemotherapy for wide spread disease.
Leucaemia
•• Leukaemia in childhood manifests with skeletal pain, anaemia and fever.
•• Calvarial lesions are uncommon and, when they occur, they appear as
ill-defined areas of rarefaction with peripheral new bone formation similar
to a neuroblastoma.
•• Low dosage radiation may give rise to symptomatic resolution.
•• Chemotherapy of the systemic disease produces a more effective
remission.
Myeloma
•• Multiple myeloma is the most common primary malignancy of the skeletal
system.
•• It affects males more commonly and occurs between the ages of 40–60
years.
•• The skull is a common site for these lesions.
•• Pain, weight loss, palpable tumours, anaemia, hypercalcaemia, hyperglob-
ulinaemia and Bence Jones proteinuria are the usual features.
•• Biopsy of the lesion or bone marrow biopsy will usually clinch the diagnosis.
•• Skull radiography usually shows multiple punched out areas of bone
destruction of different sizes and density.
•• In more than 80% of cases the solitary type lesion eventually becomes
multiple.
•• Solitary plasmacytomas are treated with radiotherapy in curative doses of
50 Gy spread over 5 weeks.
•• Multiple myeloma is treated with chemotherapy, melphalan and prednisone
being the most commonly used drugs.
•• Frequently, skull involvement is treated palliatively with radiation doses of
30 Gy in 2 weeks.
Neuroblastoma
•• It is a common tumour of childhood.
•• Skull metastases often precede detection of the primary adrenal tumour.
•• Typically, the child presents with periorbital ecchymosis and an associated
abdominal mass.
•• Diffuse nodular lucencies are seen in radiographs.
•• The lesions are highly vascular and they lift up the periosteum, thus
producing radial bone speculation extending into the soft tissues.
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•• Although the dura often resists the spread of the lesion, spontaneous
intratumoural haemorrhage may rupture through the dura into the brain
parenchyma.
•• CT is useful in detecting the gross thickening of the skull, the extent
of the intracranial mass and also complications like haemorrhage and
compression of dural venous sinuses.
•• Spontaneous resolution of a neuroblastoma into more benign forms has
been known to occur occasionally, as the patient matures; but involvement
of the skull suggests a poor prognosis.
•• Local irradiation and systemic chemotherapy are the treatment of choice.
CONDITIONS SIMULATING
SKULL NEOPLASMS
Osteomyelitis
•• Radiological changes appear long after the onset of clinical signs and
symptoms.
•• In the plain films, multiple nodular areas of lucencies appear in the outer
table or diploe.
•• CT demonstrates these early lesions clearly.
•• In young children, the sutures usually limit the process, but in adults
contiguous spread to adjacent bones is common.
•• In course of time, the nodular lucencies condense into a large defect and
visible and palpable oedema of the scalp (Pott’s puffy tumour) occurs.
•• Inward spread leads to an extradural empyema or granuloma.
•• CT shows this as a biconvex extradural hyperdense mass with marked
peripheral contrast enhancement. Poorly defined sclerosis occurs at the
edges of the bone. Practically no subperiosteal new bone formation occurs.
The radiological appearance may remain stable or endosteal regeneration
may continue to occur in healed osteomyelitis.
•• Tuberculosis, syphilis and other low grade chronic infections appear on
radiographs as irregular, poorly defined areas of sclerosis.
Traumatic Conditions
Cephal Haematoma
•• In the newborn, it results from birth injury due to forceps delivery and is
commonly seen in the parietal bone and is limited by the sutures.
•• Initially, the X-rays show a soft tissue shadow overlying the bone.
•• About a week later, calcific edges are seen arising from the sutural areas
and these gradually project into the soft tissues of the scalp, resulting in a
shell-like calcification completely bridging the mass.
•• Simultaneously, there is gradual resorption of the inner table with
progressive remodelling.
•• A review of previous skull radiographs and clinical history should aid in the
differential diagnosis.
Leptomeningeal Cyst (Growing Fracture of the Skull)
•• A linear fracture of the skull in infants may be associated with a laceration
of the dura and the brain pulsations may herniate a pouch of arachnoid,
which may enlarge and widen the fracture and form a cystic collection
under the scalp.
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•• Varying degrees of pressure atrophy of the brain occurs, resulting in a

subdural cystic collection.
•• The plain films show an area of lucency in the skull with scalloped margins
and a soft tissue shadow outside the skull.
•• CT shows the intracranial porencephalic cyst and atrophic changes resulting
in focal dilation of the ventricle towards the defect.
•• Occasionally, these cysts cause expansion between the tables of the skull
bone, producing an intraosseous leptomeningeal cyst.
Vascular Diseases
Vascular Impressions in the Skull
•• Normal vascular structures and vascular tumours of the scalp, dura and
brain produce impressions on the skull and may simulate the radiographic
appearances of skull tumours.
•• Pacchionian granulations produce focal thinning of the inner table with
slightly lobulated margins.
•• Venous lakes are wider and they invade the inner table with sloping
margins.
•• The arachnoid granulations occasionally involve the outer table also. They
are commonly seen in the parietal parasagittal regions and in the occipital
squama and occasionally, more laterally.
Sinus Pericranii
•• It is a congenital defect involving the skull, containing abnormal emissary
veins which connect an intracranial venous sinus, commonly the superior
sagittal sinus in the frontal region with a cluster of veins or a venous
angioma in the extracranial space.
•• A cluster of smooth sharply marginated circular defects in the midline of
the frontal region, seen in plain skiagrams, should suggest the diagnosis.
Histiocytosis X
•• This disease complex comprises of Hand-Schuller-Christian syndrome
which has associated diabetes insipidus, Letterer-Siwe disease and
eosinophilic granuloma.
•• The first two occur in young children as multiple recurrent areas of skull
involvement.
•• Eosinophilic granuloma occurs as a solitary non-recurring lesion in older
children and young adults.
•• Co-existence of psoriatic arthritis and eosinophilic granuloma has been
observed and an autoimmune mechanism is thought to be an aetiological
factor.
•• Eosinophilic granuloma is manifested by local tenderness and pain.
•• Skull radiographs show an irregular area of rarefaction without any
sclerosis.
•• Tangential views of the skull and the CT scan show the edges of the lesion
to be bevelled, due to differential involvement of the outer and inner tables.
Sclerosis is, however, seen at the time of healing of the lesion.
•• The solitary lucent lesion may be difficult to differentiate from myeloma
or a metastatic deposit. Hence, it is important to establish a diagnosis by
complete excision and histopathological examination.
•• Radiation therapy in small doses, 10 Gy (1,000 rads) over 1 week is curative.
1318
•• The multiple recurrent type of lesion seen in younger children often involves
the frontal bone and spreads extensively, showing clear cut but irregular
edges described as “map like” or “geographic skull”.
•• Soft tissue masses may become palpable, when the outer table gets
perforated.
•• Orbital involvement produces proptosis. The facial bones and paranasal
sinuses eventually get involved.
•• Other parts of the skeleton are involved simultaneously.
•• Following diagnostic biopsy, systemic chemotherapy with prednisone,
vincristine and cyclophosphamide is usually given.
•• Local radiation is given as for palliation.
Sarcoidosis
•• This is another condition which destroys multiple areas of bone.
•• Skull involvement is rare and is seen as multiple punched out areas of
bone rarefaction.
•• The growth of such lesions is very slow and may remain unchanged for
several years.
Osteitis Deformans (Paget’s Disease)
•• The aetiology is still not known.
•• The patients are usually of middle age, men being more frequently affected
than women.
•• The disease is multicentric, affecting the pelvis, the femora, the vertebral
column and more commonly the skull.
•• It starts as a diffuse mottled thickening of bone in the frontal or occipital area
or as irregular patches or lysis which give the appearance of a geographical
skull when viewed on radiographs.
•• After some months or years, patchy sclerosis develops, gradually
progressing to produce gross thickening of the skull.
•• The new bone is soft and the involvement of the base of skull leads to
basilar invagination.
•• The skull loses its three tabled architecture in the late stages.
•• Differential diagnosis includes fibrous dysplasia of mixed type, mixed blastic
and lytic metastases and healing stage of hyperparathyroidism.
•• Widespread involvement of the vault and the base, gross thickening and
distortion of the normal bony architecture and the much older age of the
patients help in differentiation.
•• Pain and asymmetric enlargement of the skull and deafness and blindness
due to foraminal involvement may occur.
•• Involvement of the axial skeleton may produce an ape-like appearance.
•• When there is widespread bony involvement, the level of serum alkaline
phosphatase is considerably raised.
•• Except for neural decompression, this condition usually does not need
treatment.
•• Osteogenic sarcoma may occur as an infrequent sequel.
Fibrous Dysplasia
•• It is a benign disorder of bone commonly seen from childhood to the third
decade.
•• Normal bone is replaced by fibrous connective tissue with varying degrees
of osseous metaplasia.
1319
•• The skull alone may be involved, but usually other parts of the skeleton
are also affected.
•• The radiographic pattern may be cystic, sclerotic or mixed.
•• The cystic type mainly affects the cranial vault.
•• It is seen in plain films or CT as a focal homogeneous widening of the diploic
layer with gross thinning of the outer table and relatively less involvement
of the inner table.
•• The margins of the lesion are ill defined and gradually taper into the
surrounding skull.
•• The sclerotic variety involves the skull base and facial bones, causing
diffuse bilateral thickening of the floor of the anterior and middle cranial
fossae.
•• Despite gross involvement of the bones of the base of skull, neural
structures are rarely compressed.
•• The optic nerve may be compressed when the optic foramen is involved.
•• When unilateral, the bone thickening may be difficult to differentiate from
the hyperostosis due to a meningioma.
•• The mixed type is least common and it involves the vault of the skull more
often. The diploe is widened and the outer table is thinned. There are
patches of lucent and dense areas as in Paget’s disease, but they are
more sharply defined and well localised.
•• Histologically, fibrous dysplasia appears as multiple areas of fibrous tissue
contained within islands of bone with evidence of both blastic and clastic
activity.
•• Usually, no treatment is advised except in the case of orbital compression
or neural involvement.
•• If active enlargement or local inflammation occurs, excision and cranioplasty
is advised.
Hyperparathyroidism
•• This metabolic abnormality of calcium and phosphorus is characterised
by elevated blood calcium and lowered blood phosphorus, and there is
increased loss of both ions from the body.
•• Bony changes generally occur.
•• In the skull, wide areas of granular osteoporosis occur.
•• These may coalesce to form large areas of lysis forming “Brown Tumours”
(osteitis fibrosa cystica).
•• During the healing process, patchy areas of sclerosis occur superimposed
on the diffuse granular osteoporosis.
Mucocoele
•• This condition occurs in any one of the paranasal air sinuses, frontal,
frontoethmoidal or sphenoidal sinuses in that order.
•• As a result of obstruction to the outflow tract, the mucoid secretions collect
in the sinus cavity and gradually enlarge, thinning out the walls of the sinus.
•• In the case of the frontal sinus, a small osteoma at the frontonasal duct
may be the obstructing agent. The anterior wall bulges out forming a visible
swelling on the forehead.
•• The posterior wall may also bulge and compress the dura. Sometimes the
mucocoele may burst through the dura.
•• Ethmoidal sinus mucocoele may occur alone or in conjunction with frontal
sinus mucocoele. It produces proptosis.
1320
•• Mucocoeles of the sphenoidal sinus are rare and they erode into the sella
and parasellar regions, the optic foramen and the superior orbital fissure.
•• In certain instances, with spontaneous drainage, regression of the
mucocoele and later recurrence of the swelling may occur. When infected,
it may form a pyocoele.
•• Plain skiagram shows enlargement and opacification of the sinus and a
soft tissue swelling.
•• A sphenoidal lesion may erode the optic foramen and enlarge the superior
orbital fissure.
•• The floor of the sella may bulge upwards and appear eroded.
•• The location and extent of the lesion are seen well on the CT.
•• The cystic contents, however, appear denser than the usual cysts in the
cranium, due to the high protein content of the fluid.
•• Treatment consists of complete excision of the mucocoele, along with all
the sinus lining and obliteration of the cavity.
•• Where the skull defect is large, it is better to close it with autogenous
bone graft than with acrylic material, as the mucocoele is often potentially
infected. Even if it is not infected, care must be taken not to spill the contents
into the subarachnoid space as this may result in chemical meningitis.
•• Mucocoeles of the sphenoid sinus are treated through the transnasal route.
Neuroectodermal Dysplasias
•• Skull bone involvement in neurofibromatosis is common and may manifest
as a deficiency in the orbital wall due to the local erosive effect of an
overlying tumour, or as a sharply marginated round or oval defect in the
lesser wing of the sphenoid or in the region of the lambdoid suture due to
bone dysplasia.
•• The lesions may rarely mimic skull neoplasms and a CT scan clearly shows
the margins of the lesion and the absence of a soft tissue mass.
•• Osteosclerotic nodules may be seen on plain films in cases of tuberose
sclerosis.
•• These may be mistaken for the peripherally located calcified glial nodules
which are so typical of this disease. CT clearly defines the location and
nature of the process.
Haemolytic Anaemias
•• In infants with severe anaemia, the cranial diploe provide a major source
of red blood cell production.
•• The abnormalities are marked in thalassaemia or Cooley’s Mediterranean
anaemia.
•• The disease is endemic in many parts of the country.
•• The diploe widens with resultant atrophy of the outer table. The trabeculae
of the diploe assume a radial striated pattern and are seen perpendicular
to the inner table which remains intact.
•• The occipital bone inferior to the internal occipital protuberance is spared,
as marrow is absent at this site.
•• The tremendous enlargement of the marrow prevents pneumatisation of
the air sinuses.
•• Similar changes have been observed in chronic iron deficiency anaemia
and in infants with congenital cyanotic heart disease.
1321
Hyperostosis Frontalis Interna

•• This is an idiopathic benign condition seen in the skiagrams of middle aged
and elderly women.
•• There is diffuse hypertrophy of the inner table, commonly seen in the frontal
bone, but sparing the midline.
•• It is not of any clinical significance. When it occurs on one side, the differ-
entiation from meningeal hyperostosis of the inner table becomes difficult.
Petrous Apex Cholesterol Granuloma
•• Cholesterol granuloma produces symptoms of trigeminal, facial and
abducens nerve palsy and may not affect the auditory nerve.
•• CT shows a non-enhancing, smooth-walled, expansile isodense lesion at
the petrous apex with bilaterally well pneumatised mastoids.
•• Asymptomatic patients can be observed till the condition becomes
symptomatic.
•• Those with good hearing can be treated by the infralabyrinthine approach.
•• The infratemporal fossa approach is advocated in patients with extensive
disease and internal carotid artery involvement.
•• Complete removal is indicated in selected cases where placement of a
drainage tube is not feasible.
Section XII: Skull Base Surgery
177
CHAPTER
Clival Chordomas
Chandranath Sen
INTRODUCTION
•• Chordomas are rare primary malignant bone tumours that arise in the
axial skeleton.
•• They are believed to originate from remnants of embryologic notochordal
cell rests and thus manifest epithelial as well as mesenchymal features.
•• Although chordomas are found throughout the axial skeleton, they are
much more frequent at either end.
•• It has been reported that 25−39% of chordomas arise in the clivus.
•• The incidence of chordomas in the clival location is 1/2,000,000 per year.
•• They are slightly more prevalent in males and can be found at any age,
but the mean age incidence is 40 years.
•• These tumours are generally slow growing but are locally aggressive and
hence the clinical course of a patient is typically punctuated by multiple
local recurrences.
•• Metastases are uncommon. Local recurrence is usually the cause of the
patient’s death.
PATHOLOGICAL FEATURES
•• These tumours are characterised by a lobular growth pattern of tumour
cells that are arranged in clusters, chords and strands.
•• The cells are large and contain abundant eosinophilic cytoplasm.
•• Many of them contain large clear vacuoles and hence the name,
“physaliferous”.
•• The nuclei may vary from small and hyperchromatic to large and vesicular.
•• They are usually surrounded by a myxoid matrix.
•• Three variants have been described on the basis of histology: conventional
chordoma, chondroid chordoma and dedifferentiated chordoma.
•• Chondroid chordomas contain conventional chordomas surrounded by
neoplastic hyaline cartilage occupying up to 75% of the tumour area.
•• The dedifferentiated tumours have tumour cells arranged in irregular
nests in a collagenous fibrous stroma and resemble a poorly differentiated
carcinoma.
•• Immunohistochemistry is essential in confirming a diagnosis of chordoma.
•• They stain positively for cytokeratin, epithelial membrane antigen, S-100
protein and vimentin.
Chapter 177 • Clival Chordomas
1323
CLINICAL FEATURES
•• The clinical features depend on the anatomical location of the lesion.
•• Clival chordomas are classified as upper, middle, lower or craniovertebral
junction and the symptoms and signs depend on the spread of the lesion.
•• They have also been classified as basisphenoidal and basioccipital,
depending on whether they arise above or below the spheno-occipital
synchondrosis.
•• Diplopia due to abducens paralysis is the most common symptom.
•• The other clinical features that may be present are visual loss, pituitary
endocrinopathy, chiasmal syndrome, cavernous sinus syndrome,
nasopharyngeal mass, multiple cranial nerve involvement, brainstem
signs, cerebellopontine angle involvement, hydrocephalus and lower
cranial nerve palsies.
IMAGING FEATURES
•• On the MRI scans, they usually appear as lobulated masses manifesting
low signal intensity on T1-weighted images and high signal intensity on
T2-weighted images. They do enhance after administration of gadolinium,
but this occurs to a variable degree.
•• They can vary greatly in size and distribution.
•• They often extend intracranially as well as extracranially into adjacent
anatomical areas and also, sometimes, intradurally.
•• On CT images, they appear isointense on the non-contrast studies.
•• There is irregular bone destruction at its site of origin, which may be in the
midline of the clivus or eccentrically located.
•• The tumour may also show areas of calcification.
•• Differentiating chordomas from chondrosarcomas is often difficult due to the
identical imaging appearance. Chondrosarcomas usually arise eccentrically
at the petroclival synchondrosis.
PRINCIPLES OF SURGICAL MANAGEMENT

•• Radical surgical excision is the primary treatment of choice.
•• The tumour is often located in close proximity to many critical neurovascular
structures and at a considerable depth from the surface.
•• The tumours often reach a relatively large size by the time they are
diagnosed and thus have a propensity to involve many contiguous
anatomical areas such as the cavernous sinuses, retropharyngeal space,
the occipital condyle and its articulation with C1.
•• There may be substantial intradural extension with variable degrees of
brainstem compression.
•• The internal carotid arteries and the vertebrobasilar system are often
intimately involved by the tumour.
•• Not a single surgical approach provides access to all the regions of the
skull base. Thus, a variety of surgical approaches have been described.
•• The surgical approaches to this area are broadly divided into anterior
midline and lateral approaches (Table 1).
•• Anterior midline approaches:
–– Extended subfrontal
–– Trans-sphenoidal
Section XII • Skull Base Surgery
1324
Table 1: Surgical approaches

Approach Areas exposed
Anterior midline approaches Trans-sphenoidal Sphenoid sinus, upper clivus
Transoral Lower clivus, foramen
magnum, C1, C2
Le Fort maxillotomy Middle clivus with lateral
extensions
Mandibulotomy and Lower clivus, foramen
glossotomy magnum and upper three
vertebrae
Extended subfrontal Sphenoid sinus, middle and
(transnasal) lower clivus
Endoscopic endonasal Entire midline clivus from
sella and upper clivus, down
to foramen magnum
Lateral approaches Frontotemporal, Upper clivus, parasellar
orbitozygomatic
(anterior transpetrosal)
Presigmoid transpetrosal Midclivus
(retrolabyrinthine or
translabyrinthine)
Subtemporal and preauricular
infratemporal
Extreme lateral transcondylar Lower clivus, jugular
foramen, C1, C2
–– Endonasal endoscopic with image guidance

–– Transfacial
–– Transoral
–– Transmandibular circumglossal retropharyngeal.
•• Lateral approaches:
–– Frontotemporal with orbitozygomatic osteotomy
–– Preauricular subtemporal and infratemporal
–– Presigmoid combined supratentorial and infratentorial
–– Extreme lateral transcondylar.
•• Each approach has its advantages and disadvantages.
•• Each approach often permits access to a very specific area and thus
requires detailed planning based on the imaging studies and the clinical
status of the patient.
•• The surgical procedure usually involves three components: (1) surgical
approach; (2) tumour resection and (3) reconstruction of the skull base.
•• Each of these components has to be carefully planned and executed to
ensure a successful outcome.
•• Since these operations are complex and involve access through facial,
pharyngeal and temporal bone structures, close collaboration with an
otolaryngologist is very helpful.
Chapter 177 • Clival Chordomas
1325
Reconstruction of the Skull Base and

Potential Complications
•• Reconstruction is also aimed at the function and appearance of the patient.
•• It is, therefore, extremely important to devote special attention and effort
in reconstruction and closure of the wound.
•• After removal of these tumours, there is often communication into the
pneumatic sinuses at the skull base, nasopharynx, the temporal bone, etc.
•• There may also be a substantial dural defect that will need to be covered.
•• The facial skeleton may have been disassembled for the approach.
•• All these factors predispose to the development of cerebrospinal fluid
fistulae and post-operative infections.
•• If there is a dural defect, it should either be closed primarily or a dural graft
should be used. Watertight closure is often not possible and, therefore, soft
tissue layers are a helpful adjunct.
•• This is in the form of free-fat graft or rotation flaps such as the pericranial
flap, the temporalis muscle flap and the temporo-parietal fascial flap.
•• Free-fat graft is preferred to free-muscle graft, since it is easily visible in
the post-operative imaging studies.
•• If the reconstruction is performed in a systematic manner, future recurrence
of the tumour can be detected more readily in the subsequent MRI studies.
•• Bony reconstruction of the clivus or the central skull base is not necessary,
provided a secure layered soft-tissue reconstruction has been performed.
•• Loss of bone around the orbit will need to be reconstructed in order to
prevent enophthalmos.
•• Loss of bone from the external surface should be reconstructed to restore
the contour and appearance of the patient.
•• Usually, commercially available titanium mesh and plating systems are
excellent for this purpose.
•• Cerebrospinal fluid diversion by a lumbar spinal drain or an external
ventriculostomy is often used during the early post-operative phase.
RADIATION TREATMENT
•• Radiation has been regularly used for the management of chordomas.
•• Higher doses, more than 70 Gy are needed to control the tumour.
•• The optic nerves, chiasm, the brainstem and the pituitary gland represent
limitations to such doses when the tumour is in proximity to these structures.
•• Although megavoltage fractionated photon radiation, as well as stereotactic
radiosurgery have been used for the treatment of these tumours, the largest
body of data exists for proton beam therapy.
•• The “Bragg Peak” effect allows a high dose to be delivered to the precise
target site with no exit dose, making it an attractive modality for treatment
of chordomas.
•• Proton-beam irradiation seems to add to the length of survival of the
chordoma patient.
•• Its benefit is clearly seen in patients with residual tumour, but its effect on
patients with no obvious residual tumour is not definite.
•• The volume and distribution of the tumour are critical for the dose planning,
as well as efficacy of the treatment.
•• The proton radiation data are quite encouraging with an excellent effect
on tumour control.
178 Transfacial Transmaxillary
Approaches to Anterior
CHAPTER
Skull Base
Sojan Ipe • Bobby Jose
INTRODUCTION
•• The term transfacial approach is used to describe any procedure that
mobilises the midface skeleton, through a facial skin incision irrespective
of the extent of midface disassembly employed.
•• The nasal bone, maxilla and zygoma may be mobilised alone or in
combination unilaterally or bilaterally and either as an osteoplastic flap or
as free bone fragments.
•• The surgical disarticulation of the craniofacial skeleton can be used to gain
access to otherwise inaccessible sites in the skull base.
•• These approaches allow access to the anterior and middle cranial fossa,
cavernous sinus, clivus, craniovertebral junction, upper cervical vertebrae
up to the level of C4, infratemporal and pterygopalatine fossa, nasopharynx,
paranasal sinuses and the orbit.
INDICATIONS
•• The basic principles of anterior skull base surgery are as follows:
–– Identify the epicentre of the mass.
–– Take the shortest route from the skin to the target lesion.
–– Bypass the vital structures essential for satisfactory functional
outcome.
–– Use pre-existing spaces in the face and the skull bones.
–– Plan reconstruction depending upon the approach.
–– Reconstruct aesthetically with best cosmetic end result.
–– Maintain compartmentalisation—segregate neurocranium and
viscerocranium.
–– Evaluation of tumour biology and appropriate pre-treatment to
downgrade the tumour.
•• The transfacial transmaxillary approach is useful for a variety of lesions
from the paranasal sinuses to the clivus.
•• It can be extended with mandible splitting procedures, to reach up to the
upper cervical spine.
•• This approach is ideal for lesions arising from the paranasal sinuses with
or without intracranial extension, anterior skull base lesions, extradural
lesions of the upper and middle third of the clivus such as clival chordoma
and chondrosarcoma.
•• Other potential lesions that can be treated with this approach are fibrous
dysplasia, inverting papilloma, osteoma and ossifying fibroma.
Chapter 178 • Transfacial Transmaxillary Approaches to Anterior Skull Base
1327
•• It can also be used for the removal of small to moderately sized nasopharyn-
geal lesions, such as juvenile angiofibromas, with limited lateral extension,
esthesioneuroblastoma (olfactory neuroblastoma), adenocarcinoma and
adenoid cystic carcinoma.
•• Purely intradural lesions, such as basal meningiomas, are also approached
by combining this with transcranial approaches for the ease of repair of the
dural defect and thus to avoid potential complications.
•• The transmaxillary approach has the advantage of being an extradural
anterior inferior midline approach with a relatively low risk of injury to the
cranial nerves and the major blood vessels.
•• The advantages of the transfacial approaches are the following:
–– Facial anatomy has developed from embryonic fusion of nasofrontal,
maxillary and mandibular processes.
–– Normally the fusion takes place in the midline or in the paramedian
region, thus logically presenting the optimal lines of separation of
facial units for surgical approaches and facilitating the least traumatic
displacement.
–– The primary blood supply to the facial units is through the external
carotid system which also has a lateral to medial direction of flow, thus
ensuring viability of displaced surgical units.
–– The midface contains multiple hollow anatomical spaces (oronasal
cavity, nasopharynx and paranasal sinuses) that facilitate the ease of
surgical access to the central skull base.
–– Displacement of facial units for approach to the central skull base of-
fers much greater tolerance to the post-operative surgical swelling, as
opposed to similar displacement of the contents of the neurocranium.
–– Re-establishment of the normal anatomy, following repositioning of
the reconstructive phase of surgery, leads to good functional as well
as aesthetic results.
•• The disadvantages of transfacial approaches are the following:
–– Contamination of the surgical wound with oropharyngeal bacterial flora.
–– The need for facial incisions with subsequent scar formation.
–– Emotional consideration of the patient related to surgical facial disas-
sembly.
–– The potential need for supplementary airway management like post-
operative endotracheal intubation, temporary tracheotomy, etc.
SURGICAL ANATOMY
•• The cranium is sub-divided into the cranial vault and the cranial base which
consists of the floor of the cranial cavity intracranially and the inferior surface
of the skull extracranially and the facial skeleton which includes the orbital
cavities, the nasal fossae and the jaws.
•• The base of the cranial cavity is divided into three distinct fossae—the
anterior, middle and posterior.
•• The floor of the anterior cranial fossa is at a higher level than the others.
The anterior cranial fossa occupies less than the anterior one-third of base
of the skull.
PRE-OPERATIVE EVALUATION
•• The patient is evaluated with high resolution CT scan and MRI to define
the anatomical extent of the lesion.
1328
•• Angiography may be done in selected cases.

•• Some cases may benefit with pre-operative embolisation.
•• Adjuvant pre-operative chemotherapy and\or radiotherapy may be planned
in some cases to down size the tumour.
•• The decision on the approach is based on the anatomical site and the
extent of the lesion, experience and familiarity of the surgeon, and the
age and overall prognosis of the patient and the presumptive biological
characteristics of the lesion.
•• The dental hygiene of the patient should be evaluated and any infection
should be treated to avoid post-operative complications.
•• A dental splint is fabricated to reproduce normal occlusion after surgery,
depending on the type of osteotomy planned.
•• Culture of the nasal and throat flora should be obtained pre-operatively.
•• Appropriate antibiotics should be started with the induction of anaesthesia,
to be continued post-operatively.
ANAESTHESIA
•• The airway is maintained either with orotracheal intubation or with tracheotomy.
•• Arterial and central venous pressure lines and a precordial stethoscope to
detect venous air embolism are desirable.
•• Hypotensive anaesthesia is not mandatory.
•• A spinal drain may be used if dural breach is expected.
Classification of Transfacial
Transmaxillary Approaches
•• Medial
–– Medial maxillectomy
–– Medial mini-facial translocation.
•• Lateral
–– Total maxillectomy
–– Standard facial translocation
–– Extended osteoplastic maxillotomy.
•• Combined (Medial and Lateral)
–– Medial extended facial translocation (Le Fort I)
–– Medial and inferior extended facial translocation.
•• Bilateral
–– Bilateral facial translocation
–– Extended transfacial subcranial
–– Facial degloving
–– Transmaxillary approaches of Beals and Joganic.
Medial
Medial Maxillectomy
•• The technique requires excision of the medial maxillary sinus wall and
turbinates, ethmoids and lamina papyracea, lacrimal bone and the orbital
wall medial to the infraorbital nerve.
•• This procedure is an extension of the lateral rhinotomy approach made in
the side of the nose for surgical exposure.
•• Medial maxillectomy is indicated for benign and malignant neoplasms
limited to the nasal walls, medial wall of the maxillary sinus and adjacent
ethmoid sinus.
1329
•• When a component of the neoplasm extends intracranially, the medial

maxillectomy can be combined with a frontal craniotomy to allow en bloc
craniofacial resection of the lesion.
•• A number of modifications of medial maxillectomy are possible including
the medial orbital rim, in combination with frontal sinusotomy for lesions of
the ethmoid roof extending to involve the anterior cranial base.
•• Medial maxillectomy approach gives better physical quality of life index
(PQLI) after surgery, early feeding with good dental occlusion and early
mobilisation and rehabilitation of the patient.
•• It minimises intracranial complications that would occur with combined
transcranial approaches such as brain retraction related contusions
of the frontal lobes, intracranial haematomas, dural tears, CSF leak,
pneumocephalus and meningitis.
Medial Mini-facial Translocation
•• This approach is designed to reach the medial orbit, sphenoid and ethmoid
sinus and inferior clivus.
•• The port of entry is through the displaced ipsilateral nasal bone and the
nasal process of the maxilla with attached medial canthal ligament, lacrimal
duct and skin.
•• The skin incision is made along the lateral aspect of the nose and the
inferior aspect of the eyebrow with a triangular design at the level of the
medial canthal ligament.
•• The lateral extent of the osteotomy is just medial to the infraorbital nerve.
The entire unit can be displaced laterally for surgical exposure.
Lateral
Total Maxillectomy
•• Classical total maxillectomy procedures are described in plastic surgery,
which gives clear cut details of this procedure which becomes part of the
extended procedures described by others.
•• The classical Weber-Ferguson-Longmire skin incision and the soft tissue
dissection involved in exposing the anterior surface of the maxilla have to
be followed.
Standard Facial Translocation
•• With this technique of translocation, good exposure of the anterolateral skull
base is achieved, especially when the infratemporal fossa is involved as well.
•• The ipsilateral facial skin including the lower eyelid is displaced laterally
and inferiorly with the underlying maxilla, with or without the hard palate.
•• The nasal incision may extend inferiorly to include an upper lip split.
•• The superior incision continues from the nose to the inferior fornix of the
lower eyelid through the lateral canthus horizontally to the preauricular area.
•• Osteotomies correlate to Le Fort I-II or the mid-palatal lines when the entire
maxilla is being displaced.
Extended Osteoplastic Maxillotomy
•• The basis of osteoplastic maxillotomy is the pedicled osteoplastic unit,
comprised of vascularised bone, muscle, skin and mucosa, whose design
can be tailored to the desired skull base exposure.
•• This technique provides wide, direct exposure of the lateral and/or central
skull base.
1330
•• It is indicated for benign or malignant lesions that involve two or more

of the following anatomic areas: pterygopalatine fossa; sphenoid sinus;
nasopharynx; infratemporal fossa; cavernous sinus and/or floor of the
middle fossa and clivus.
•• The maxillofacial skeleton is exposed via a Weber-Ferguson incision.
•• Osteotomies in the maxilla and zygoma disengage the maxilla from the
facial skeleton.
•• The maxilla is mobilised on the skin and the soft tissues of the ipsilat-
eral cheek, thereby maintaining its blood supply. Due to this osteoplastic
technique, the untoward effects of adjuvant radiation therapy and/or chemo-
therapy are minimal.
•• By varying the position of the facial osteotomies, this approach is very
flexible.
•• Medial positioning of the anterior osteotomy of the maxilla determines the
extent of exposure of the nasopharynx and the positioning of the lateral
osteotomy determines the extent of exposure of the infratemporal fossa.
•• Pterional or temporal craniotomy can be combined to gain access to the
corresponding cranial cavity.
•• Miniplate fixation of the maxilla and the zygoma re-establishes the contour
of the facial skeleton functionally and cosmetically.
Combined (Medial and Lateral)

Medial Extended Facial Translocation (Le Fort I)
•• This approach incorporates the standard translocation unit of Janecka plus
the nose and the medial one-half of the opposite face up to the infraorbital
nerve.
•• It can be rotated at the Le Fort I level or include the ipsilateral palate and
upper lip split.
•• The skin incisions are similar to the standard technique, except that the
paranasal incision is made on the contralateral side.
•• The surgical exposure involves the ipsilateral infratemporal fossa and
central and paracentral skull base bilaterally.
•• The entire clivus, optic nerves, precavernous internal carotid arteries and
nasopharynx are accessible.
•• Reconstruction is with the temporalis muscle flap.
Medial and Inferior Extended Facial Translocation
•• This exposure is the same as the medial extended facial translocation with
an inferior extension by a mandibular split.
•• The lower lip incision is performed in a zigzag fashion to conform to the
tension lines of the skin.
•• Mandibular osteotomy is performed just medial to the mental foramen.
•• Prior to osteotomy, it is wise to select an appropriate miniplate for eventual
fixation, contour it to the mandible and create drill holes. This assists in
post-operative re-establishment of normal occlusion. This inferior extension
adds a significant inferior cranial as well as upper cervical surgical access.
Bilateral
Bilateral Facial Translocation
•• This approach combines complete right and left standard facial translocation
units of Janecka with or without palatal split.
1331
•• The exposure incorporates both infratemporal fossae and the central and
the entire paracentral skull base.
•• Both distal cervical internal carotid arteries and the clivus are in view.
•• The palatal split permits a reach to the level of C2-3 and an added
mandibular split adds a vertical reach to C3-4.
•• The surgical defect is repaired with a single temporalis flap.
Extended Transfacial Subcranial Approach
•• The extended subcranial approach to the anterior skull base, which is
an extended exposure of the anterior, middle and posterior planes of the
anterior fossa.
•• The other advantage of this method is that only minimum retraction of the
frontal lobes is required.
•• The type A would include the anterior frontal sinus wall along with the
nasal bones.
•• The type B osteotomy involves taking off the posterior frontal sinus wall
just anterior to the crista galli. Before doing this, however, a radical
ethmoidectomy is performed.
•• In the type B osteotomy, after both orbits have been dissected, the
anterior ethmoidal arteries ligated, and radical ethmoidectomies have been
performed bilaterally, the whole fronto-naso-orbital segment is taken out
and this will include the posterior frontal sinus wall as well.
Facial Degloving
•• This is performed to prevent surgical incision on the face.
•• First, a midface degloving procedure is done and then the regular
osteotomies as per requirements are done for excision of the lesion.
•• For the degloving procedure, the medial palpebral ligament is first dissected
and wired after making a small incision near the medial angle of both eyes.
These wires are tied under the nasal skin at the end of the surgery.
•• The elevation is extended as high as the infraorbital rim and the glabella
as per the requirement. Then the necessary nasomaxillary and Le Fort I
osteotomies, as required, are performed.
Transmaxillary Approaches of Beals and Joganic
•• The system is based on selecting the most appropriate angle and exposure
to the anatomic site of the tumour.
•• Six levels of exposures are described.
•• The upper three approaches are transfrontal approaches incorporating a
supraorbital bar, either alone or with nasal and medial orbital walls; and
further extended by including the lateral orbital walls.
•• The lower three levels of approaches provide exposure to the midline skull
base through the maxilla.
•• The transnasomaxillary approach (level IV) achieves a wide exposure of
the entire central skull base but requires a Weber-Ferguson incision and
a Le Fort II osteotomy.
•• Level V transmaxillary approach requires a midfacial degloving and a Le
Fort I osteotomy. It is mainly indicated for extradural lesions of the upper
two-thirds of the clivus.
•• Level VI is a transpalatal approach.
•• Level IV: Transnasomaxillary approach:
–– This approach can be used for nasopharyngeal lesions or for large
clival lesions that extend in any direction.
1332
–– This technique requires a modified Weber-Ferguson incision, which

extends across the radix and along the subciliary margin of the op-
posite lower lid.
–– The nasomaxillary area is exposed and a Le Fort II osteotomy is
performed.
–– The osteotomy skirts along the infraorbital foramen anteriorly and
along the nasolacrimal canal at the medial aspect of the inferior orbital
rim.
–– The fragment is split at the nasal process of the maxilla on one side
and the palate is split at the midline.
–– The nasal complex remains on any one side of the fragment, depend-
ing on the best angle for exposure of the tumour and is retracted with it.
•• Level V: Transmaxillary approach:
–– This exposure is ideally suited for moderately sized nasopharyngeal
lesions as well as for clival lesions with superior or inferior extensions.
–– An intraoral approach using an upper buccal sulcus incision is used as
for midface degloving.
–– Le Fort I osteotomy is performed along with a midline split and each
half is retracted.
–– After tumour resection, reassembly is done using an interdental splint.
•• Level VI: Transpalatal approach:
–– This approach gives access to the lower clival region.
–– A midline incision is made from one side of the uvula towards the
incisive foramen.
–– A separate incision is made in the upper labial sulcus and the floor
of the nasal mucosa is lifted from the palatal surface and then the
osteotomies are performed.
COMPLICATIONS
•• Complications fall in three main categories: (1) bleeding; (2) infection and
(3) wound healing and can be quite hazardous.
•• Venous bleeding is often encountered, which can be quite bothersome and
may be controlled with bone wax or with gelfoam.
•• Inadvertent injury to the vertebral or the carotid artery may be fatal and
repair should be attempted after application of temporary clips.
•• Infection is often due to the presence of non-vascularised tissue or post-
surgical dead space or due to inadequate dural repair leading to CSF leak
and meningitis.
•• Wound healing problems are more common in patients who had previous
surgery or radiotherapy.
•• Attention to certain details, such as the assurance of the displaced tissue
viability, judicial use of electrocautery, detailed and thorough knowledge
of the vascular anatomy along with judicious use of vascularised flaps,
lessens the potential for complications.
179
CHAPTER Approaches to the
Lateral Skull Base
Atul Goel • Muzumdar D
IDEAL APPROACH
•• The ideal approach has the following features:
–– The working distance between the surgeon and the tumour should
possibly be the minimum.
–– The direction of the approach selected should therefore be such that
the tumour is closest to the surface.
–– Temporal bone drilling could be done on some occasions only to re-
duce the operating distance.
–– The approach should be quick to perform.
–– The approach should be least difficult. Manoeuvres, like exposure and
mobilisation of the petrous carotid artery, unroofing and mobilisation
of the sigmoid sinus, transposition of the facial nerve, are difficult and
potentially dangerous and time consuming procedures and should be
avoided as much as possible.
–– The exposure should be low which could avoid retraction of brain.
–– The exposure should be wide enough such that the entire lesion can
be excised in one single operative field.
–– The exposure should provide access to the base of the tumour so that
in cases of meningiomas, the tumour could be devascularised early in
the operation.
–– The exposure should be such that the tumour and the normal sur-
rounding structures are exposed in the same field so that dissection is
possible under vision.
–– As far as possible, an approach through a potentially infective field
should be avoided.
–– Reconstruction should be easy, safe and with a vascularised pedicle
graft.
•• The following important characters of the tumour determine the nature of
approach:
1. Size of the tumour, its relationship to arteries and nerves, and to
the adjacent bone: The larger the size of tumour, the more difficult is
the surgery and consequently the outcome can be affected.
2. Nature of the tumour:
– In most cases the arterial displacements, as a result of growth of
the tumour, differentiate meningiomas from other tumours.
1334
– A trigeminal neurinoma displaces the intracavernous carotid medi-

ally, while chordomas and chondrosarcomas displace the internal
carotid artery at the petrous apex anteriorly.
– Soft tumours, like the chordomas and pituitary tumours, displace
the artery but only rarely narrow its lumen.
– Such and other characters help in histologically classifying the
tumours and thus assist in deciding the route of approach and the
extent of resectability and for prognosticating the ultimate outcome.
3. Consistency of the tumour:
– Long-standing symptoms and symptomatic involvement of adja-
cent nerves suggest the presence of a firm tumour.
– Signal characters on T1- and T2-weighted MR images help in diag-
nosing the nature of the tumour.
– These characteristics determine to a considerable extent the ease
of surgical resection and the extent of exposure that may be neces-
sary to resect the lesion.
– The consistency of the tumour and its vascularity are important
variables on which the course of surgery depends.
– Narrowing of the encased vessels suggests the firm nature of the
tumour. Resection of such tumours could be a formidable surgical
problem.
4. Vascularity of the lesion: Vascularity of the lesion can be observed
on angiography. Multiple punctate spots in the tumour on MRI also
suggest high vascularity. More vascular the lesion, the larger is the
exposure that is necessary.
5. Presence of arachnoidal plane of dissection around the tumour:
It can be determined on MRI scanning. Such information can critically
be important. The presence of arachnoidal lakes around the tumour
should be carefully analysed.
6. Patient related factors like age, presence of other major illnesses:
It can also guide towards the extent of the surgery that would be neces-
sary.
Bone Work
•• Drilling of the petrous bone to obtain basal and wider exposure is frequently
necessary. However, such a procedure should be done only when it is
absolutely necessary.
•• The drilling should be minimal and only at sites where it is necessary to
expand the exposure.
•• In more difficult lesions, extensive temporal bone drilling may be required.
SURGICAL APPROACHES TO
LATERAL SKULL BASE
Anterior Subtemporal Approaches
•• Anterior subtemporal approach is indicated when a majority of the tumour
is in the middle fossa in the region of the cavernous sinus.
•• Basal extension of the anterior subtemporal approach is frequently
necessary to avoid retraction of the temporal pole.
Chapter 179 • Approaches to the Lateral Skull Base
1335
Transtemporal Approaches
•• The petrous part of the temporal bone has been ‘exploited’ to enhance
the exposure of deep seated lesions which were difficult to excise by the
conventional neurosurgical approaches.
•• Transpetrous approaches not only provide better exposure of the tumour
in the cerebellopontine angle and petroclival regions, but also expose the
intrapetrous extensions of the tumour and cranial nerves in healthy areas,
so that their function can be better preserved.
•• Most of the lesions situated in the petroclival region can be approached
and safely resected by conventional neurosurgical operations, like the
subtemporal and retrosigmoid, or combined subtemporal and retrosigmoid
approaches.
•• However, some tumours are hidden behind bony protuberances and in the
angle of the petrous bone and the clivus for which various ‘transpetrosal’
approaches have been adopted.
•• Spetzler, et al. summarised ‘neurosurgical’ approaches through the
temporal bone into three groups:
Group 1: Approach preserving hearing.
Group 2: Approach where hearing is sacrificed.
Group 3: Approach that involves transposition of the facial nerve.
Approaches Preserving Hearing

•• The petrous apex and the mastoid bone are two major areas deprived of
neural or vascular structures.
•• The presigmoid-retrolabyrinthine-transmastoid approach has been used
to approach petroclival lesions.
•• Superior projection of the jugular bulb (high jugular bulb) can also limit the
exposure obtained by the transmastoid (or translabyrinthine) approach.
•• Posterior mobilisation of the sigmoid sinus can be used to enhance the
exposure.
•• The presigmoid transmastoid exposure is combined with the subtemporal
exposure for widening the exposure.
•• Kawase described a triangle (named after him) in the petrous apex lateral
to the root of the trigeminal and medial to the internal auditory meatus.
This part of the petrous bone can be drilled in a middle fossa approach
providing a crucial window to lesions located in the region of the mid clivus.
The exposure can be enhanced underneath the Gasserian ganglion. The
cochlea is the lateral limit, while the horizontal segment of the petrous
carotid artery is the medial limit. The exposure can be increased by the
anterior displacement of the carotid artery or by drilling the cochlea.
Approaches Involving Sacrifice of Hearing

•• The presigmoid translabyrinthine approach is an anterior extension of the
presigmoid retrolabyrinthine approach.
•• The approach involves removal of the semicircular canals, thus enhancing
the exposure.
•• The facial nerve comes in the way during this approach while exposing
petroclival region tumours.
•• The transcochlear approach is the anterior extension of the translabyrinthine
approach.
1336
Approaches Involving
Mobilisation of the Facial Nerve
•• Elaborate transpetrous approaches have been described for petroclival
lesions some of which involve mobilisation of the facial nerve.
•• Approaches involving extensive resection of the petrous bone with or
without translocation of the facial nerve include transcochlear and total
petrosectomy approaches.
•• A total petrosectomy approach has been described. The approach involves
unroofing of the entire facial nerve and its posterior mobilisation. The
petrous carotid artery is displaced anteriorly.
•• The unroofing of the entire petrous segment of the facial nerve is a time
consuming procedure and involves a high possibility of jeopardising facial
nerve function.
•• The transcochlear approach can be modified and segments of the facial
nerve can be mobilised.
Extended Middle Fossa Approach

•• This approach relatively quick, safe for the facial nerve and results in an
extensive manoeuvrable exposure.
•• It involves unroofing and depression of the external ear canal, removal
of the glenoid cavity of the temporomandibular joint, exenteration of the
middle ear ossicles, posterior mobilisation of the labyrinthine and tympanic
segments of the facial nerve and drilling of the petrous bone from an entirely
lateral perspective.
•• An extensive and low exposure of the petroclival region, posterior aspect
of the cavernous sinus, upper and mid clivus and the cerebellopontine
angle is obtained.
•• The anterior surface of the brainstem up to the pontomedullary junction is
exposed with minimal or no retraction of the temporal lobe.
•• The vein of Labbe and the sigmoid sinus drainage are unhampered. Anterior
and posterior extension of the exposure is possible.
•• Only a limited mastoidectomy and labyrinthectomy, necessary to facilitate
exposure and mobilisation of the facial nerve, is required. The dome of the
jugular bulb sets the inferior limit of the exposure. Hearing is sacrificed.
Basal Extension of Lateral

Subtemporal Craniotomy
•• The temporal line (supramastoid ridge) forms the inferior limit while the
zygomatic arch is the anterior limit of a conventional neurosurgical basal
craniotomy.
•• Zygomatic osteotomy, inferior displacement of the temporalis muscle and
resection of the floor of the middle fossa have been employed to improve
the basal exposure.
•• Partial unroofing of the external ear canal has also been recommended for
enhancing the inferior angle of vision.
•• Resection of the root of the zygomatic arch, including the glenoid fossa,
roof of the external ear and superior third of the mastoid process, was
seen to improve the basal exposure for lateral subtemporal middle fossa
approaches.
•• The enhanced exposure helps in reducing the extent of brain retraction and
improves the working space for manipulation of the instruments.
1337
Middle Fossa Sub-Gasserian

Ganglion Approach
•• Most of the lateral procedures described for resection of clival chordomas
involve relatively complex and extensive skull basal dissection, exposure
and mobilisation of the carotid artery, facial nerve, sigmoid sinus and
temporomandibular joint.
•• A modified lateral subtemporal, transpetrous apex and sub-Gasserian
ganglion approach is suitable for clival chordomas.
•• The approach selection is based on the typical anatomic relationship of
chordomas in terms of site of origin, pattern of growth, bone destruction
and neural and vascular displacements.
•• The approach is suitable for dealing with tumour anterior and lateral to the
brainstem, clival part of the tumour and its sub-cavernous sinus extensions.
The carotid artery is under control.
•• The approach has the advantage of being simple and relatively quick and
its familiarity to general neurosurgeons.
•• The tumour can be excised radically and extension of the anterior, posterior
and inferior exposure is possible.
Infratemporal Fossa Interdural Approach

•• A small craniectomy in the infratemporal fossa incorporating the foramen
ovale can be used to resect even large trigeminal neurinomas with
extensions from the posterior cranial fossa into Meckel’s cave and the
lateral wall of the cavernous sinus.
•• The approach appears to be ideal for selected cases of trigeminal
neurinomas.
Presigmoid Approach
•• Presigmoid approaches are advocated to provide an anterior line of vision
to the cerebellopontine angle or clival tumours. The working distance
between the surgeon and the tumour can be minimised by this approach.
•• However, there are the following disadvantages of the approach:
–– The working space between the anterior surface of the sigmoid sinus
and the external ear canal is small. The space can be extended by
posterior mobilisation of the sigmoid sinus, but complete unroofing and
mobilisation of the sigmoid sinus is not always an easy procedure and
can sometimes lead to tears in the sinus with its attendant problems.
–– The line of vision to the tumour in the presigmoid transmastoid ap-
proach can severely be limited by the posterior semicircular canal.
Partial labyrinthectomy can help in improving the exposure. Although
some authors report preservation of hearing after partial labyrinthec-
tomy, such results are difficult to achieve.
–– The line of vision by a selective presigmoid approach is in the inferior
and posterior direction of the cerebellopontine angle.
Retrosigmoid Approach
•• In some situations, a selective retrosigmoid approach may be appropriate.
•• Lateral extensions into the cerebellopontine angle and inferior extensions
of the lesions along the clivus are indications for such an approach.
1338
Transcondylar Transclival Approach

•• An anterior approach is rarely needed for lesions located in the pontomed-
ullary region.
•• An approach which involves unroofing of the jugular bulb followed by either
its superior mobilisation or packing, drilling off of the condyle and continuing
the drilling to resect part of the clivus provides a considerably anterior view
to lesions anterior to the lower brainstem.
Supracondylar Infrajugular Bulb Keyhole

Approach to Anterior Medullary Lesions
•• Lesions located anterior to the brainstem in the lower clival and foramen
magnum region pose a formidable surgical challenge.
•• Various lateral approaches have been suggested to widely expose anterior
medullary lesions.
•• An alternative approach is suggested, which involves resection of the
subsigmoid and retrosigmoid sinus, lateral occipital squamous bone,
lateral border of the foramen magnum and a small area of bone between
the jugular bulb and the condyle.
•• Exposure, manipulation or mobilisation of the extradural vertebral artery
is avoided.
•• Condylar resection is not necessary.
•• The exposure is relatively quick and significantly anterior.
SELECTION OF APPROACHES
Petroclival Meningiomas
•• There are various approaches described to deal with lesions present in
this location.
•• The issues in the decision regarding the approach should include consid-
erations for the approach, which could be performed in the shortest time,
is least difficult and safest for the patient.
•• The exposure must be wide and it must also provide with avenues for
dealing with disasters like major arterial tears, and for reconstruction of
nerves and arteries whenever necessary.
•• A secure basal reconstruction is vital to prevent CSF leakage.
•• Petroclival meningiomas are described as those which arise from the dura
in the region medial to the entry of the trigeminal root into Meckel’s cave.
•• Frequently, these and other lesions situated in this region involve the cav-
ernous sinus and extend down to the mid-clivus, encasing and/or displacing
critical arteries and perforators.
•• Meningiomas in proximity to the clivus are amongst the most difficult
surgical problems. The difficulty in resection of these lesions stems from
the following facts:
–– These benign lesions are frequently of large size at the time of pres-
entation.
–– Patients present with relatively subtle neurological symptoms and
signs. Thus delaying the diagnosis.
–– Tumours may encase vital major arteries and perforators, sacrifice
of which could result in permanent neurological deficit or even death.
–– Alternative methods of treatment, like radiosurgery, chemotherapy,
photodynamic therapy, etc. are of no proven value in the management
of these cases.
1339
•• A variety of transpetrous and middle fossa approaches have recently been

described and successfully employed for surgical resection of petroclival
meningiomas.
•• The selection of a surgical approach for petroclival meningiomas will
depend on a large number of variables. The nature of tumour extensions,
its relationship with the petrous bone, clivus, tentorium and cavernous
sinus and the adjoining critical neural and vascular structures, generally
determine the surgical approach.
•• The posterior fossa approach is far easier, safer and quicker and the
exposure of the tumour is wider, as compared to the transpetrous or basal
subtemporal approaches. It avoids any major arterial or venous or venous
sinus handling, manipulation or sectioning, petrous bone drilling and
temporal lobe retraction related problems.
Trigeminal Schwannomas
•• On the basis of the presenting clinical features and characteristic
radiological signs, a diagnosis of a trigeminal schwannoma could be made
in a majority of cases.
•• Due to the location in the depth, close proximity to vital neural and vascular
structures; the ideal surgical approach should be the shortest and most
direct, it must be wide and low, avoiding the need for prolonged and
excessive brain retraction.
•• For small tumours in the middle fossa and those having a relatively small
extension into the posterior fossa, an infratemporal fossa interdural
approach as described by us was found safe, quick and provided adequate
exposure.
•• In larger tumours located in the middle fossa, a basal lateral subtemporal
exposure is suitable.
•• Extradural exposure for relatively smaller tumours and intradural exposure
for larger tumours is appropriate.
Foramen Magnum Meningiomas

•• Meningiomas in the region of the foramen magnum are relatively rare.
•• A large proportion of foramen magnum meningiomas are located anterior
to the brainstem and have a close relationship to vital neural, vascular and
bone structures.
•• The clinical course is slowly progressive, leading to dysaesthesia,
asymmetric motor weakness, gait ataxia and relatively less commonly,
lower cranial nerve affection.
•• Misdiagnosis due to uncommon symptoms, leading to wrong decisions and
inappropriate treatment has frequently been observed with these lesions.
•• MRI has provided a significant advancement in the diagnosis. It clearly
delineates the exact tumour size, location, site of dural attachment and
relationship to vascular and neural structures, and provides an opportunity
to assess its consistency and vascularity.
•• Anterior transoral, anterolateral transcervical, extreme lateral, far lateral
and lateral approaches have been advocated.
•• The meningiomas located in the region ‘anterior’ to the brainstem in the
region of the foramen magnum are only rarely strictly anterior. Despite
their varied sizes, most of these tumours point laterally on one side of the
midline and the brainstem is displaced or twisted posterolaterally rather
than posteriorly.
1340
Clival Chordoma
•• Most of the lateral procedures, described for resection of clival chordomas,
involve relatively complex and extensive skull basal dissection, exposure
and mobilisation of the carotid artery, facial nerve, sigmoid sinus and
temporomandibular joint.
•• A modified lateral subtemporal, transpetrous apex and sub-Gasserian
ganglion approach is suitable for clival chordomas.
•• The approach selection is based on the typical anatomic relationship of
chordomas in terms of site of origin, pattern of growth, bone destruction
and neural and vascular displacements.
•• The approach is suitable for dealing with tumour anterior and lateral to the
brainstem, clival part of the tumour and its sub-cavernous sinus extensions.
•• The carotid artery is under control. The approach has the advantage of being
simple and relatively quick and its familiarity to general neurosurgeons. The
tumour is excised radically and extension of the anterior, posterior and
inferior exposure is possible.
180
CHAPTER
Transpharyngeal
Approach to the
AH Menezes
•• The transoral approach to the ventral craniocervical border is the most direct
route for decompression of irreducible extradural pathology.
•• These procedures encompass the transoropharyngeal, the transpalatal
and the median mandibulotomy with glossotomy.
INTRODUCTION
•• The relevant diagnostic imaging for abnormalities of the craniocervical
junction consists of plain radiographs of the region which should include
the skull and cervical spine.
•• Dynamic studies with the flexed and extended position are made to assess
the stability and the need for possible reduction.
•• The cervical spine radiographs should include the mandible so that the
relationship of the craniovertebral border to the hard palate can be judged,
including its accessibility.
•• In patients with normal anatomy, the configuration of the clivus is normal
(almost vertical). Thus, with the transoral approach, elevation of the soft
palate suffices to provide anterior exposure of the craniocervical junction.
•• On the other hand, in patients with congenital abnormalities associated with
hypoplasia of the clivus, this now tend to become horizontal. It appears as
though the upper cervical spine has “ascended”. Consequently, the soft
and the hard palate must be sectioned.
•• Magnetic resonance imaging (MRI) is the mainstay of the neurodiagnostic
armamentarium.
•• The T1- and T2-weighted mid-sagittal MRI should be done in both the
flexed and extended positions.
•• This modality provides information about the neural structures, as well as
their relationship to the bony abnormality and vascularity.
•• Magnetic resonance angiography should be performed when neurological
dysfunction cannot be fully explained.
•• In that circumstance, it is done with the head in the rotated, flexed and
extended positions, to identify vascular occlusions that can appear when
the patient changes position.
•• Computed tomography (CT) of the craniocervical junction is an integral part
of this author’s assessment of the bony pathology. Conventional CT (2D
CT) is further augmented by 3-dimensional CT reconstructions.
•• This modality shows the location of the occipital condyles, the lateral atlantal
masses and the axis body, as well as the lateral masses.
1342
•• The odontoid process is visualised and, in congenital abnormalities, it is

very frequent that the odontoid process is actually smaller than in normal
adults, because of segmentation abnormalities.
ASSESSMENT OF NUTRITIONAL STATUS

•• This issue is particularly important in patients who have had difficulty
with swallowing and failure to thrive. It is also important in patients with
rheumatoid arthritis, atlantoaxial dislocation, tuberculosis and rheumatoid
arthritis, vertical migration of the odontoid process that compresses the
brainstem.
•• Thus, pre-operative nutritional support is mandatory before operative
intervention. Failure to do so results in wound dehiscence and non-fusion.
Dental Hygiene
•• Dental hygiene is addressed to remove causes of bacterial contamination
such as pyorrhoea, gingivitis or dental caries.
•• This author has custom-built dental guards made so as to provide protection
of the upper and lower dentition during surgery.
Assessment of Co-morbidities
•• Abnormalities of the lower cranial nerves can cause brainstem dysfunction.
•• It then becomes necessary to perform pulmonary function studies and to
assess for sleep apnoea.
•• Significant loss of glossopharyngeal, vagal and hypoglossal nerve function
mandates a tracheostomy before proceeding with surgery. Likewise, the
cardiac status assessment is crucial.
Oropharyngeal Cultures
•• Oropharyngeal cultures are obtained 3–4 days before surgical intervention.
•• The cultures must be from the oral cavity as well as from the nasal passages.
•• As a precaution, Nystatin rinses and Peridex gargles are performed three
times a day before the procedure.
DECISION TREE FOR

TREATMENT OF CRANIOCERVICAL
JUNCTION ABNORMALITIES
•• Bony abnormalities of the craniocervical junction can be divided into those
that are reducible and the irreducible categories (Flow chart 1).
•• Stabilisation is the primary treatment for reducible craniovertebral junction
lesions.
•• Surgical decompression of the ventral cervicomedullary junction is
necessary, when irreducible pathology is encountered.
•• This decompression must be made in the direction in which encroachment
has occurred.
•• Thus, the transoral-transpalatopharyngeal route is utilised when a lesion is
ventrally situated. The other possible approaches to the craniovertebral bor-
der are the lateral extrapharyngeal and the maxillary dropdown procedures.
•• In lateral compressions, a lateral or posterolateral approach is utilised.
•• When dorsal compression is seen, a posterior approach is made.
Chapter 180 • Transpharyngeal Approach to the Craniovertebral Junction
1343
Flow chart 1: Types of craniovertebral abnormalities
•• If instability exists following any of the situations, it is mandated that the

posterior fixation be made.
•• Thus, the factors that guide the surgical approaches to lesions of the
craniovertebral junction are: (1) the reducibility of the lesion; (2) the direction
of the encroachment and (3) the type of lesion.
•• The main indication for the transoral-transpalatopharyngeal approach to
the ventral cervicomedullary junction is extradural pathology and, rarely,
intradural tumours.
PRE-OPERATIVE CERVICAL TRACTION

•• Skeletal traction is applied with an MRI compatible halo device, so as to
assess the reducibility of the bony lesions.
•• This is usually instituted 3–4 days prior to the operative procedure.
•• Should the lesion be reducible, a dorsal fixation is all that is necessary.
•• On the other hand, if it is irreducible, both the ventral and the dorsal
procedures are carried out under the same anaesthetic.
•• In other situations, where one knows that a grossly irreducible lesion is
going to be present, the crown halo traction is placed only after the induction
of general anaesthesia to stabilise the craniovertebral junction.
•• A median glossotomy allows caudal exposure to the vertebral body of C4.
•• The lateral extent of this exposure is between the condylar canals of the
hypoglossal nerve (18 mm to either side of the midline), the Eustachian
tubes and the vertebral artery before it enters the intradural space.
•• When a tumour, such as chordoma, has created the dissection, the expo-
sure may extend as far laterally as the medial aspect of the jugular foramen.
•• The ability to open the mouth and the space between the incisor teeth
must be at least 3 cm. Achieving this opening is facilitated by the use of
paralysing agents during the general anaesthesia.
SPECIAL CIRCUMSTANCES
Transpalatal Route
•• This is used routinely to treat congenital abnormalities where the clivus is
foreshortened and seems to be more horizontally oriented than vertical.
•• Removal of 1 cm of the posterior hard palate in the sagittal plane and
about 8 mm to either side of the midline exposes a sufficient amount of
nasopharynx and clivus.
1344
•• The posterior edge of the vomer is exposed.

•• The soft palate should then be closed in a layered fashion at the end of
the procedure.
Median Glossotomy Combined with

Transoral-Transpalatopharyngeal Approach
•• This procedure provides a wide caudal exposure down to the vertebral
body of C4.
•• If combined with mandibular split, the exposure is significant along the
ventral and rostral caudal dimensions. The cosmetic outcome is excellent.
Intradural Extension for Tumour and

Repair of Cerebrospinal Fluid Leak
•• An intradural lesion at the upper cervical spine, craniocervical border
or behind the clivus necessitates pre-operative recognition of the dural
extension and placement of a lumbar subarachnoid drain prior to the
commencement of the operation.
•• The dural turgidity may be reduced by draining cerebrospinal fluid during
the procedure.
•• Once the intradural operation is complete, it is essential to bring the dural
leaves together as much as possible. This is done with 4-0 polyglycolic
sutures.
•• It is then covered with an external oblique aponeurosis graft which is sutured
to the dura. This prevents migration of the graft. Fibrin glue is now used
over this. This is then backed with fat obtained from the anterior abdominal
wall after which the posterior pharyngeal closure is made in the earlier
described layered fashion.
•• CSF tension is reduced by drainage from the lumbar subarachnoid space
during and after the operative procedure.
•• The endotracheal tube is maintained in place for post-operative
convalescence until the swelling in the oral cavity has receded. This usually
stays for 3–4 days in the non-rheumatoid patient and may be longer in
patients with advanced rheumatoid arthritis.
•• It is important to maintain caloric intake of 2,500 calories by the 3rd or
4th day.
•• The post-operative management comprises of ventilator and respiratory
care and nutrition, antibiotic regimen, pain management and immobilisation.
•• The halo ring that was utilised intra-operatively for traction and stabilisation
is left in place if it is to be connected to a halo vest later.
•• It is preferable to have the feeding tube in a transpyloric location. Enteral
feedings are instituted in a graduated manner at the end of 24 hours.
•• A clear liquid oral intake is initiated by the fifth post-operative day and
converted to a full liquid diet by the 10th day. By this time, the patient’s
caloric intake has been 2,500−3,000 calories per day.
•• A soft diet is started at the end of the 15th day.
•• Post-operative immobilisation is accomplished in a soft collar until a final
decision is made to either use a halo vest or an occipitocervical brace.
Chapter 180 • Transpharyngeal Approach to the Craniovertebral Junction
1345
Table 1: Peri-operative complications of transoropharyngeal surgery at

the craniovertebral junction; prevention and management
Complication Prevention/Management
Unnecessary ventral Pre-operative reduction, if possible
procedure
Too small an oral aperture Distance between incisors must be >25 mm
May improve with administration of IV paralysing agents. May
need mandible and/or tongue split or another approach
Damage to Eustachian Limit lateral exposure to 2 cm from midline
tubes and hypoglossal
nerves
Inability to reach clivus for Divide soft palate and possibly hard palate. Intra-operative
resection due to platybasia fluoroscopy
Lost—cannot reach distal Fluoroscopy. Novice may use “frameless stereotaxy”. Start
dens or epidural masses resection of dens from rostral end
Persistent bleeding at Bleeding from circular sinus needs fibrillar collagen/oxidised
clivus cellulose. Else clip both leaves of dura. Pannus and arterial
bleeding must be coagulated
Intra-arachnoid lodgment. Pre-operative lumbar drain. Attempt dural closure. Fascia + fat +
CSF leakage plasma glue. CSF drainage. 1 week antibiotics
Table 2: Delayed complications of transoropharyngeal surgery at the

craniocervical junction; prevention and management
Complication Prevention/Management
Severe tongue swelling IV Dexamethasone; intermittent release of tongue depressor.
Retain dental guards in children
Meningitis CSF exam. Lumbar drainage. No oral intake. Antibiotics. Close CSF leak
Palatal dehiscence Inadequate closure. Must be reclosed
Pharyngeal dehiscence <1 week–reclosure
>1 week–hyperalimentation, antibiotics
Neurological worsening Check alignment → traction Reassess ?meningitis,
?abscess,?retained lesion. Vascular compromise ? MRI and MRA
Retropharyngeal abscess Check for osteomyelitis and meningitis. Extrapharyngeal drainage
Delayed pharyngeal Secondary infection. Exclude osteomyelitis and vertebral artery
bleeding erosion and false aneurysm MRI, CT and angiography necessary!
Velopalatine Usually appears 4–6 months post-operative pharyngeal retraining/
incompetence prosthesis
Retropharyngeal fat injection. May need pharyngeal flap
Persistent hoarseness Appears 4–6 weeks after surgery. Needs visualisation of vocal
of voice cords. Likely granulomas on cords. Needs vocal cord rest and
proton pump inhibitors
PREVENTION AND MANAGEMENT OF

COMPLICATIONS
•• The prevention of peri-operative complications as well as delayed adverse
events is described in Tables 1 and 2, respectively.
181
CHAPTER
Reconstruction of the
Skull Convexity and Base
Atul Goel • Muzumdar D
•• There are various inherent problems involved in skull base reconstruction,
especially the proximity of the skull base to potentially infective spaces like
the paranasal sinuses, nasal, oral and pharyngeal pathways, external ear
canal and other such spaces.
•• After the required surgery, it is important to seal off the cranial cavity from
these spaces to avoid ascending infections.
•• The basal dura is relatively thin, friable and densely stuck to the bone.
Approximation of the edges and watertight suturing often may not be
possible, especially in areas of vessel and nerve transit.
•• Opening up of the paranasal air sinuses, middle ear cavity and Eustachian
tube, can subject the patient to risks of cerebrospinal fluid fistula.
•• Frequently, there are large dead spaces that need to be filled in after basal
bone, soft tissue and tumour resection.
•• Sometimes, persistent post-surgical or traumatic cerebrospinal fluid fistula
can pose a formidable surgical challenge and super-added infection can
be a life threatening condition.
Reconstruction of Bone Defects
•• Reconstruction of bone defects following skull base surgery is a
controversial subject.
•• All bone defects do not require reconstruction.
•• The size of the defect, extent of resection of the associated structures,
history of previous operative procedures, endovascular and radiation
treatment are important variables that determine the appropriate
reconstructive procedure.
•• The site and volume of tumour extirpation are also important determinants
in the method of reconstruction.
•• Various methods of reconstruction of basal bone have been described.
•• Reconstruction of bone defects in the cranial base should preferably be
done with the help of bone.
•• In sterile fields, free small or large bone pieces can be used for this purpose.
•• Ribs, iliac crest and scapular grafts have been used successfully.
•• Acrylic and metal plates can also be used.
•• Autogenous tissue such as fascia lata or allografts can be used for some
tumours, which require excision of the overlying dura.
Chapter 181 • Reconstruction of the Skull Convexity and Base
1347
•• Fat grafts have been used to obliterate small defects. These grafts are
devoid of vascular supply upon transplantation.
•• Necrosis is also a potential problem if the mass of the graft exceeds the
ability for vascularisation.
•• In potentially infective fields, which are more frequently encountered after
a skull base operation, use of a bone flap based on a vascularised pedicle
is recommended.
•• Larger defects over the tegmen tympani and orbital roof should preferably
be replaced with bone, as the dura in these regions is relatively thin and the
region is devoid of large basal cerebrospinal fluid cisterns and consequently
initially the brain pulsations can be transmitted and later the brain can
herniate into these spaces.
Flaps
Vascularised Osteomyoplastic Flap
•• The vascularised bone flaps remain viable and are characterised by
normal evolution, while free bone grafts show typical signs of necrosis
and resorption.
•• Such vascularised bone flaps based on a muscle pedicle have been used in
cosmetic facial surgery and mandibular, maxillary and palatal reconstruction
and mastoid cavity obliteration.
•• The temporalis muscle, being in close proximity to the skull base and also
the ease with which it could be rotated in various directions, can be used
effectively for such an osteomyoplastic flap for skull base reconstruction.
•• The temporalis muscle has an extensive blood supply to the calvarium
through multiple perforators.
•• Elevation of the bone flap with wide attachment to the muscle pedicle results
in a well-vascularised flap.
•• A vascularised bone flap can also be based on muscles of the nape of
the neck.
•• Judicious use of split cranial grafts can fill-up the resulting defects in the
skull.
•• Osteomyoplastic flaps can be used for reconstruction of middle fossa and
petrous bone defects with relative ease.
•• The fascial layers covering the temporalis muscle can be used to seal the
defects in the basal dura while the muscle and bone occupy the area of
bone defect.
Pericranium Based Bone Flaps
•• Pericranial and galeal flaps have been described for reconstruction of
anterior cranial base and craniofacial deformities.
•• The pericranium comprises of an outer layer of loose areolar tissue and
an inner layer of osteoblasts and contains an extensive vascular network.
•• The pericranium derives blood supply anteriorly from the supratrochlear
and supraorbital arteries and laterally from the superficial temporal arteries.
•• Pericranial layer pedicled flaps can be based on either of these vessels,
and accordingly rotated anteriorly or laterally.
•• The pericranium can sustain the calvarial flap by means of multiple small,
vertical perforators.
•• Bone flaps of the calvarium can be either of full thickness or only of the
outer table.
1348
•• The bone piece can be pedicled on a large base of pericranium and can
additionally be nourished by the galeal flaps.
•• Whenever necessary, the bone flap can be turned upside down so that the
bone surface is not directly exposed to the paranasal sinuses. The flap can
even be sandwiched between the pericranial layers.
•• In cases with extensive defects, an extended subgaleal fascia-pericranial
temporalis flap can be first placed in the region of the defect over which the
described bone flap can be placed. Reconstruction can thus be with multiple
layers of vascularised tissue.
Long Vascular Pedicle Composite Cranial Flap
•• The flap described is a split or full thickness cranial bone flap based on
the pericranial layer, which receives its vascular nourishment from the
temporalis muscle and its overlying fascial layers.
•• The outer table of the skull bone is split preserving the overlying pericranium.
•• A part of the temporalis muscle (and fascial layers) along with the
pericranium is elevated and rotated as required.
•• The superficial fascial layer over the temporalis muscle is a part of the
pericranial aponeurosis, whilst the deep temporal fascial layer completely
invests the superficial aspect of the temporalis muscle.
•• The temporalis muscle and its fascial envelope and the pericranium receive
their blood supply from the anterior, middle and posterior deep temporal
and superficial temporal arteries.
•• Subperiosteal elevation of the temporalis muscle along with the fascial
layers preserves the integrity of all the major vascular supply.
•• The advantages of such a flap include harvesting of grafts of adequate
size, ease of access within the same operative field, and no or minimal
post-operative morbidity and discomfort for the patient.
Use of Bone Dust and Debris
•• With the use of modern craniotomes for making burr holes, a large amount
of bone dust can be obtained.
•• The bone dust can be flattened and placed in the form of a sheet over the
site of defect.
•• Small bone chips and bone debris, which is generally available during a
craniotomy, can be placed interspersed in the bone dust.
•• This forms a template over which new bone and fibrous tissue is laid and
a firm, strong and resistant barrier is formed.
Reconstruction of Skull Base with Free Bone Flap
•• Whenever possible, bone defects should be filled up with a vascularised
pedicle bone flap.
•• However, such a vascularised bone flap is sometimes not available and in
this situation a free bone flap may be required.
•• A free bone flap should not directly be exposed to the paranasal sinuses
or mucosal surfaces. Whenever such a free bone flap is placed in the skull
base, it should be as small in size as possible and care should be taken
that it is covered on both sides with vascularised and viable soft tissue.
•• Such a ‘sandwich’ free bone flap can be placed between muscle and
fascial-pericranial layers.
•• Post-operative collection of haematoma around the bone flap should also
be avoided and whenever necessary external drains can be placed.
•• Tenting scalp stitches can be used whenever possible and indicated.
1349
Suturing of Bone Pieces

•• Small bone pieces usually obtained after zygomatic and orbital osteotomy
should be sutured preferably with thin wires, unbraided silk or nylon stitches.
•• The use of miniplates, screws and an excessive volume of metal can be
avoided.
•• Rotation of a vascularised pedicle muscle, pericranial or fascia flap or free
fat graft or muscle can be performed to occupy the area of bone defect
and empty spaces.
Subgaleal Preservation of Bone Flaps
•• Various techniques of preservation of bone flaps have been described both
inside and outside the body.
•• The flaps have been more frequently and successfully stored in the
subcutaneous plane of the abdominal wall or in the thigh.
•• External storage methods include deep freezing, autoclaving it while
replacing, storing after radiation treatment and using antibiotic solutions.
•• An alternative method of preservation of the skull bone flap in the subgaleal
space adjacent to the site of operation is exposed widely, using blunt
dissection was found to be effective.
Use of Synthetic Material in Skull Base Reconstruction
•• Synthetic material is rarely required and advocated to reconstruct basal bone.
•• Issues of biocompatibility, corrosion characteristics and metallurgic
properties of the implant, its hardness and malleability and suitability of the
host area to adjust to the foreign intrusion and various other factors have
to be adequately analysed prior to selection of such material.
•• Various substances including acrylic casts, plastics, glassionomer cement,
silicone bars, prolene mesh and stainless steel have been used.
•• Recently there has been a renewed interest in titanium miniplates, screws
and wires.
•• These are more commonly advocated for reconstruction of cosmetically
sensitive areas such as the orbital rim, zygomatic arch and facial contour
defects.
Reconstruction of Dural and

Soft Tissue Defects
Fat and Free Muscle as a Packing Material
•• Small or large pieces of fat have been effectively used for this purpose.
•• The fat globules get vascularised early from the surrounding tissues.
•• Whenever free muscle is being used as packing material, it should be
ground into small pieces, so that these pieces can get vascularised from
the surrounding tissues.
•• If large pieces of muscle are placed, it gets vascularised from the periphery
and the central portions of the tissue can get necrosed. Such necrosed
tissue can get absorbed or even pose a problem of infection.
•• Free tissue should never be placed over free tissue, as this procedure can
lead to ischaemic necrosis of the tissue most distant from the vascularised
structures.
Lyophilised Dura, Gelfoam® and Fascia Lata
•• These dural substitutes have been used extensively and successfully for
basal reconstruction. However, whenever possible, live and vascularised
pedicle fascial material should be used to obtain a compact closure.
1350
Use of Pericranial and Galeal Flaps

•• Pericranial and galeal flaps have extensively been used for reconstruction
of basal defects.
•• Their use is more effectively possible for reconstruction of bone and dural
defects in the anterior cranial base.
Use of Rotation of Muscle Flap
Extended Vascularised Temporalis Muscle-Fascia Flap
•• The deep layer of the temporalis fascia is everted partially over the
temporalis muscle, preserving its vascularity.
•• A composite flap, comprising of temporalis muscle and its fascia attached
along its superior border, is rotated for reconstruction of post-operative
defects in the middle cranial fossa floor and mastoidectomy cavities.
•• Partial eversion of the temporalis fascia over the muscle increases the
length of the flap, while retaining its vascular pedicle.
•• The long length vascularised pedicle flap can be used to cover defects,
may be folded for bulk and may be used to carry blood supply to poorly
vascularised recipient sites.
•• The deep layer of the temporalis fascia is nourished by multiple small
branches, which traverse through the muscle.
•• Similar flaps using the thinner superficial layer of temporalis fascia have
been used in craniofacial reconstruction, filling up post-traumatic defects
in the anterior cranial fossa and for facial reanimation.
Extended Subgaleal Fascia-Pericranial Temporalis Flap
•• A long pericranial flap can be used to line an anterior skull base defect.
•• The temporalis muscle is rotated along the pericranial flap and forms the
vascular pedicle of the flap.
•• Subgaleal fascia is preserved to enhance the vascularity of this long flap.
•• Subgaleal fascia, known previously as ‘loose areolar tissue layer’ of the
scalp and believed to be a relatively avascular zone has now been shown
to have its independent and extensive blood supply entering into it at the
base of the cranial vault circumferentially.
•• It is a thin but well-defined trilaminar fibrous structure and discretely
separable layer.
•• The blood supply to the subgaleal fascia is also enhanced by the vascular
connections with the branches of the deep temporal arteries which supply
the temporalis muscle and its fascial coverings.
•• While elevating the pericranial flap, some of the subgaleal fascia is almost
always included.
•• The described flaps can be used to reconstruct cranial defects, where there
is poor local nourishment and in potentially infective fields.
•• Relative ease of harvesting and the ability to alter the arc of rotation of this
flap can be effectively used.
Temporalis Muscle and Temporoparietal Fascia
•• The temporalis muscle has been used for head and neck reconstruction
and is a suitable muscle for lateral and anterior defects.
•• The vascular supply to the temporalis muscle is from the internal maxillary
artery.
•• It can be used for defects in the infratemporal fossa, anterolateral skull base,
orbit and maxillary regions. It is limited by its inability to reach the midline.
1351
•• It can be split longitudinally or rotated by subperiosteal dissection and

fracturing of the coronoid process.
•• Maintaining its muscular attachment to its insertion should preserve the
venous drainage of the flap.
Myocutaneous Flaps
•• The pectoralis, latissimus and trapezius muscle can be used to raise a
myocutaneous flap based on their vascular pedicles.
•• The pectoralis and the latissimus muscle flap have a limitation that they
can deliver only a limited volume of tissue above the zygomatic arch and
infraorbital rim.
•• The trapezius flap is a versatile flap fed by the descending branch of the
transverse cervical artery.
•• The vertical part of the muscle is raised since the transverse part is required
to maintain shoulder shrugging. The paravertebral perforators, which
additionally supply the vertical part of the muscle, should be ligated whilst
harvesting the flap.
•• The flap is bulky and has a considerable length. Hence, it is the flap of
choice for coverage over the posterior temporal fossa and the lateral and
posterior skull base. It can reach up to the vertex without any difficulty.
Free Tissue Transfer/Free Flaps
•• Free transfer of tissue or flaps is indicated in patients who have large
geometrically complex defects of soft tissue, bone or dura following
craniofacial resection, extended transtemporal bone surgery or excision
of recurrent tumours.
•• Usually they require a large volume of tissue for reconstruction.
•• The site of defect, patient positioning for harvesting, donor morbidity,
recipient vasculature and the need for an adequate pedicle length are
factors to be considered.
•• Moderate to large defects can be reconstructed using the rectus muscle
or the latissimus muscle myocutaneous flap.
•• The rectus muscle free flap is a natural choice.
Multilayer Reconstruction of Middle Fossa Base
•• Frequently there are large spaces that need to be filled after basal bone,
soft tissue and tumour resection.
•• Such spaces can be a site for haematoma or CSF loculation.
•• In most cases of middle fossa defects, a simpler method of reconstruction
may suffice.
•• The multilayered reconstruction could be performed as a radical measure,
in situations where problems of CSF fistula or those related to herniation of
the brain matter are anticipated or where earlier attempts at reconstruction
have failed.
Anterior Cranial Base Reconstruction
•• Repair recommended in a large medial dead space, a large lateral orbital
removal, thereby avoiding enophthalmos and pulsation of the eyeball,
resection of the orbitofrontal rim, supraorbital margins and the frontal area
for cosmetic reasons.
•• Autogenous bone is recommended for closure of air-filled cavities of the
face that have widely been opened and are predisposed to contamination.
•• Iliac graft or split calvarial grafts have been used.
1352
•• Bone-dust harvested from the partial thickness burr holes behind the
posterior margin of the bifrontal free flap can also be used.
•• A cortical graft should be placed between the nasion and the clivus beneath
the horizontal portion of the sellar floor, to close the ethmoidosphenoidal
area.
•• If the clivus has been removed, the graft should be placed between the
floor of the sella and anterior margin of the foramen magnum or anterior
arch of the atlas.
•• Bone-dust should be packed intracranially to provide a tight closure.
Multilayer Reconstruction of the Anterior Cranial Fossa Floor
•• Multiple combinations of flaps can be used to cover anterior cranial basal
defects.
•• The flaps could comprise only of soft tissues or may include a bone piece.
•• A bicoronal incision is made and scalp flaps are reflected both anteriorly
and posteriorly in the subgaleal plane.
•• Harvesting a long pericranial flap, based on the temporalis muscle and its
fascial cover from both sides and rotating them over the anterior cranial
fossa defect, can result in a multilayer closure.
•• The long length of the flaps can be useful in placing the flaps loosely or
even double-breasting it over the defect.
•• For adequate reconstruction a vascularised pericranial based bone flap
can be used.
•• The split or full thickness bone flap can also be pedicled on a laterally
based pericranial flap.
Use of Outer Layer of Dura as a Pedicled Flap
•• Cranial dura is formed by two layers: (1) the outer endosteal layer and (2)
the inner meningeal layer.
•• These layers are well defined and ‘separable’ by manual dissection,
particularly in younger individuals.
•• Multiple small and medium sized arteries supply the dura circumferentially.
•• The meningeal blood vessels are largely located in the endosteal layer.
When preserved intact, the outer endosteal layer can be rotated and used
to cover defects in the proximity.
•• The principle advantage of using such material is that it may be used as a
vascularised pedicle flap or a free graft.
•• Local availability and ease of rotation of this flap are the other advantages.
•• Despite the limitations in using this flap, due to technical difficulties in
separating the layers, it can be useful only in an occasional patient.
182
CHAPTER
Orbital Tumours
Aadil S Chagla
INTRODUCTION
•• Orbital tumours are uncommon.
•• They have a wide histological variety.
•• Benign tumours are far more common in children.
•• They pose difficult surgical challenge despite advances.
•• Safe access to the orbit is via the cranium.
•• Orbital tumours arise from several locations within the orbit and have
varied aetiologies.
•• Each of these locations is associated with its own symptomatology,
epidemiology, management problems and prognostic factors.
CLINICAL FEATURES OF ORBITAL TUMOURS

•• Orbital tumours produce symptoms and signs by compression, infiltration
and/or infarction of the orbital structures.
•• Often, they act as mass lesions producing only proptosis.
•• Occasionally, they may produce limitation of eye movements.
•• They may also produce neuro-ophthalmological symptoms and signs
through their effect on:
–– The optic nerve.
–– The ocular motor nerves.
–– The orbital branches of the ophthalmic division of the trigeminal nerve.
–– The nerve supply to the iris sphincter and dilator muscles.
Proptosis
•• Most orbital tumours produce some degree of proptosis.
•• Optic sheath meningiomas may take up little room in the orbit and may
produce minimal proptosis but present early with visual complaints.
•• On the other hand, vascular tumours, which are soft in consistency and
can become quite large, produce significant proptosis.
•• Tumours located within the extraocular muscle cone, e.g. haemangioma,
optic nerve glioma, meningioma, are more likely to produce axial proptosis
(the eye is pushed directly forwards), while tumours outside the muscle
cone, e.g. dermoid cyst, neurinoma, lacrimal gland tumour, tend to push
the eye out or in a direction opposite to that of the lesion.
•• Proptosis can also be caused by lesions outside the orbit, e.g. cavernous
sinus, when the venous flow is impaired. Pulsatile proptosis may occur
in vascular lesions or when the roof of the orbit or the sphenoid bone is
deficient.
1354
Optic Neuropathy
•• Vision is generally impaired with tumours involving the optic nerve namely
optic sheath meningiomas and optic nerve gliomas.
•• Benign tumours of the orbit, such as neurofibromas and haemangiomas
tend to produce visual deficits only when they are of large size and have
been symptomatic and have been present for a while.
•• Malignant lesions often produce visual deficits. Visual field involvement
may be subtle, i.e. enlargement of the blind spot and slight peripheral
field constriction. The optic disc will show swelling and would appear
similar to unilateral “papilloedema” from increased intracranial pressure
(ICP).
•• A second form of presentation of orbital tumours is that of unilateral transient
visual loss. This may occur only in certain positions of gaze and immediately
clears when the direction of gaze is changed. Either direct pressure on the
optic nerve or interruption of the blood supply is the explanation for this
phenomenon.
•• Chronic compression of the intraorbital portion of the optic nerve will
produce:
–– Progressive loss of vision.
–– Optic disc swelling that may lead to optic atrophy.
–– The appearance of optociliary venous shunts. This is often seen in
spheno-orbital meningiomas but may also occur in cases with optic
nerve gliomas.
Ocular Motor Nerve Paresis

•• The three ocular motor nerves enter the orbit through the superior orbital
fissure (SOF). Each of these nerves may be involved resulting in varying
degrees of diplopia.
•• Tumours that are located at the orbital apex may involve the ocular motor
nerves early, before they are large enough to produce proptosis.
•• The ophthalmoparesis that is produced by orbital tumours is indistinguishable
from that produced by intracranial lesions.
•• Ophthalmoplegias are most common in malignant tumours of the orbit,
metastatic carcinomas or lymphomas, although optic nerve gliomas,
neurinomas, haemangiomas and lymphangiomas can also produce it.
•• To differentiate diplopia due to oculomotor nerve paresis and muscle
involvement due to mechanical restriction of ocular movement can be
gauged by the following:
–– Intraocular pressure increases substantially when the patient attempts
to look in the direction of gaze limitation. The intraocular pressure
measurements are performed using a pneumatic tonometer.
–– Forced duction (or traction) testing can also be used to detect
mechanical limitation of motion.
Pain
•• Tumours that involve the orbit are generally not painful.
•• Neoplasms causing pain are likely to be malignant.
•• Inflammation causes severe pain and one can confidently predict
neural infiltration at the orbital apex and cavernous sinus, when there is
ophthalmoplegia and pain together.
Chapter 182 • Orbital Tumours
1355
Pupillary Abnormalities
•• It is theoretically possible that patients with an orbital tumour could develop
either a Horner’s syndrome from damage to the oculosympathetic pathway
that supplies the iris dilator muscle or a tonic pupil from damage to the
ciliary ganglion or short ciliary nerves that supply the iris sphincter muscle.
•• Such abnormalities do not occur in isolation and if they are present, they
are usually masked by the oculomotor nerve palsy.
Chemosis and Bruit

•• Chemosis is often seen in tumours that cause obliteration of the venous
outflow of the orbit.
•• It is generally seen in inflammatory or malignant tumours and also seen in
carotico-cavernous fistulae (CCF), due to the back pressure in the veins
secondary to the arteriovenous shunt.
•• Bruit is sometimes audible on auscultation which should be routinely
carried out in all patients with proptosis and suspected arteriovenous
malformations (AVMs).
•• A bruit that disappears on carotid compression is characteristic of CCF.
•• Opto-ciliary shunts and retro-ocular striae may be seen on fundus
examination.
INVESTIGATIONS
Plain X-ray
•• Plain X-ray films are important to detect:
–– Bony erosions: Bony erosions are seen on the superolateral margins
of the orbit. Erosions may occur at this site which suggests a lacrimal
gland neoplasm.
–– Sclerosis: Sclerosis of the bones may suggest an intraorbital men-
ingioma or metastatic disease. But when sclerosis is associated with
an expanded bony contour, the diagnosis of fibrous dysplasia must be
entertained.
–– Calcification: Osteomas of the paranasal air sinus are extremely
dense which is diagnostic on plain X-ray.
•• Plain radiographs also demonstrate enlargement and changes in the bony wall.
•• The optic canal may be widened in optic nerve gliomas and sometimes the
posterior lateral wall is deficient in neurofibromatosis.

•• Axial scans along with coronal images help in localisation of tumours,
show the bony changes, calcification and various enhancing patterns of
different tumours.
High Resolution Magnetic Resonance Imaging Scan

•• Magnetic Resonance Imaging (MRI) is the investigation of choice for
orbital tumours.
•• Gadolinium enhanced MRI also shows the varied enhancing patterns of
orbital tumours.
•• The location of the tumour in the orbit in the extraconal, in the intraorbital
but outside the periorbita, inside the periorbita but extraconal and intraconal
is easily delineated.
1356
•• Infiltration of various intraorbital structures in malignant and inflammatory

conditions is also seen.
•• Non-tumourous conditions, such as Grave’s disease and inflammatory
myositis, are also picked up.
Angiography
•• Angiography is sometimes required when tumours are suspected to have
increased vascularity in cases of:
–– Meningiomas
–– Haemangiopericytomas
–– Retro-orbital pial or dural arteriovenous malformations (AVMs)
–– Carotid cavernous fistula
•• Angiography is sometimes coupled with embolisation techniques to prevent
excessive blood loss during surgery. This angiographic technique is rarely
used today. It is still a good tool to diagnose and treat intraorbital varix and
other developmental vascular lesions.
Ultrasonography
•• Ultrasound is particularly useful in evaluating intraocular lesions by
ophthalmologists and in diseases involving the anterior portion of the
retrobulbar space.
•• At times, intra-operative ultrasound may be required to locate small
tumours.
MANAGEMENT OF ORBITAL TUMOURS

Principles in the Treatment of Orbital Tumours
•• The essence is to achieve safe “total” excision of benign tumours.
•• “En bloc” excision in malignant tumours.
•• Use “safe” orbital spaces to access the tumour.
•• Attack the tumour from the base of the cone.
•• Avoid bipolar coagulation.
•• Gentle handling of the intraorbital structures.
•• No fat to be sacrificed.
•• Reconstruction of the walls of the orbit.
Various Areas in the Orbit may be
Approached in the Following Manner
•• Extracranial approaches are generally reserved for tumours that involve
the anterior two-thirds of the orbit.
•• Medially placed lesions may be tackled by transethmoidal, anteromedial
orbitotomies, whereas lateral lesions may be tackled by an anterolateral
orbitotomy.
•• The subfrontal approach is generally used to tackle superiorly placed
tumours or tumours medial to the optic nerve.
•• The frontolateral approaches provide greater access into the orbit and are
used for tumours that are superolateral in the orbit and may encroach into
the orbital apex or SOF.
•• The fronto-temporo-zygomatic approaches are used to access tumours
superiorly and laterally placed in the orbit, extending into the intracranial
region involving the SOF, IOF, orbital apex and inferior orbit as well.
1357
Table 1: Choice of operative approach for orbital tumours
Subfrontal approach with superior Superiorly and medially placed moderate and
orbitotomy small-sized tumours
Intraconal tumours medial to optic nerve
Fronto-orbito-zygomatic craniotomy Superiorly and medially placed large size tumours

All tumours with involvement of the apex
Fronto-orbito-zygomatico-temporal All tumours with middle fossa extension

craniotomy All tumours with infratemporal extension
Lateral orbitotomy Laterally placed extraconal tumours

Intraconal tumours lateral or inferior to the optic
nerve
Surgical Approaches (Table 1)

•• Lateral orbitotomy
•• Subfrontal approach
•• Fronto-orbito-zygomatic craniotomy
•• Fronto-temporal-orbito-zygomatic craniotomy.
DIFFERENT ORBITAL TUMOURS

Neurofibroma
•• Neurofibromas of the orbit are common tumours which occur in the latter
half of the second decade to the fourth decade of life.
•• Multiple neurofibromas occur in the younger age group and may also have
a diffuse or plexiform appearance and may be a part of Neurofibromatosis
Type I.
•• The tumour is seen in both sexes with a slight pre-prominence in the
female sex.
•• These tumours have an excellent plane of cleavage and are distinct from
the surrounding orbital tissue.
•• Unless the tumour is totally excised, there is always a possibility of
recurrence and at times the recurrence may be cystic.
•• These tumours often arise from sensory twigs of the ophthalmic division
within the orbit.
•• These tumours are intraconal and often can be tackled using the
microlateral orbitotomy.
•• The plexiform variety of tumours are more diffuse and spread extraconal
and at times outside the orbit as well, making it difficult to excise the tumour
completely.
Meningioma
•• There are three types of meningiomas that involve the orbit:
–– Optic sheath meningioma.
–– Tumours arising from the arachnoid cap cells involving the periorbita
or the dura around the orbital fissure or optic canal.
–– Meningiomatosis that involves the dura extensively in and around the
orbit.
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•• Optic sheath meningiomas comprise about 5–7% of primary orbital

tumours.
–– They occur around the latter half of the third and fourth decades of life.
–– Optic sheath meningiomas are either: within the optic nerve sheath,
encircling the optic nerve, within as well as outside of the optic sheath,
causing an exophytic growth adjacent to the optic nerve, purely
exophytic growth of tumour outside the optic nerve sheath.
–– Although these tumours are benign and generally are meningothelial,
transitional or fibromatous in their histological types, they produce
profound visual loss, as these tumours are firm and they may encircle
the optic nerve.
–– In addition to the above symptoms, impaired movement of the globe,
disc swelling or optic atrophy with shunt vessels and an afferent
papillary defect may occur.
–– There are some tumours that have exophytic extensions and are
favourable for surgery.
–– However, most of them are difficult to excise completely.
–– When the vision is well preserved it may be best to follow these tu-
mours as some of them have long indolent courses.
–– Radiotherapy proponents have claimed excellent results in control of
these tumours.
•• Orbital meningiomas not arising from the optic sheath pose less surgical
challenges in terms of compromised visual function.
–– It is safer, therefore, to leave a small cuff of tumour at the orbital apex,
if there is no compromise of oculomotor nerve function pre-operatively.
–– These tumours are firm to hard and have indolent courses and can be
closely observed.
–– The unpredictable and relatively slow growth rate of a meningioma al-
lows the surgeon to practice sub-total removal and decompression, in
order to preserve vision and oculomotor function.
•• Meningiomas with a more diffuse dural involvement are most common
in women and may be associated with spread of the tumour intradurally
to involve the planum sphenoidale, tuberculum sella and the sellar region.
–– These tumours need to be excised early so that they may not cause
compromise of vision on the opposite side as well.
–– The surgical approach often entails a wide fronto-temporal-zygomatic
craniotomy.
–– The bone flap also comprises of the roof of the orbit taken as one piece.
–– The exophytic variety may produce proptosis with relatively less visual
deterioration.
–– When the tumour is within the optic sheath, even small tumours pro-
duce dense visual impairment.
–– Early disc swelling is recognised.
–– If the vision is completely lost at the time of presentation, radical
excision of the tumour is feasible and the aim is to prevent intradural
spread of tumour and to correct the proptosis.
–– If the patient’s eye movements are intact, using microsurgical
techniques it is possible to preserve the same after surgery.
–– Total excision of these tumours is difficult; in order to preserve oculo-
motor function it may be advisable to leave a cuff of tumour at the apex
of the cone, so as to prevent handling of the nerves and muscles, as
they crowd together at the orbital apex.
1359
Cavernous Haemangioma
•• These are among the common benign tumours involving the orbit in adults.
•• They are often intraconal; however, some of them may have extraconal
extensions as well.
•• They present with painless proptosis with remarkably well preserved vision
and normal eye movements, in spite of their huge size.
•• They occur from the second to the fourth decades of life and have a female
pre-ponderance.
•• These tumours are well encapsulated.
•• They have variable consistency and although they bleed at surgery, the
bleeding is never difficult to control.
•• They have a typical bluish hue, due to the stagnant blood filled cavernous
spaces. At times, they may also show micro calcification.
•• These tumours have the best prognosis following surgery and are often
tackled by microlateral orbitotomy.
Lymphangioma
•• These tumours are similar to haemangiomas; however, they are far more
extensive and infiltrative and often involve the intraconal and extraconal
spaces simultaneously.
•• Total eradication of this tumour is difficult.
•• If micro-neurosurgical principles are adhered to and no aggressive surgical
options are undertaken, remarkable clinical results can be achieved.
•• These tumours pursue a relatively benign course.
Optic Nerve Glioma

•• Optic nerve gliomas arise from the anterior visual pathway and may involve
the optic nerve, chiasm or tract.
•• They generally manifest in the latter half of the first decade or second
decade of life.
•• They are often associated with neurofibromatosis.
•• Most of these tumours have an indolent course; however, there are some
tumours that are aggressive in nature.
•• Tumours that are associated with neurofibromatosis have a more indolent
course. They are common with neurofibromatosis type I (NF 1).
•• Tumours involving the optic nerve present with blindness and proptosis.
•• The typical imaging finding shows enlargement of the optic foramina.
•• These tumours progress and grow intracranially and can involve the chiasm.
•• The general principle of management is close observation and regular
follow-up.
•• Tumours that demonstrate progression are excised when the vision is
completely compromised.
•• It is important to cut the optic nerve beyond the tumour to prevent the spread
of the tumour into the chiasm.
•• Tumours that involve the chiasm are generally biopsied and given
radiotherapy.
•• The surgical approach for these tumours would often entail a frontotemporal
craniotomy coupled with a subfrontal approach to the orbit.
•• The histology of these tumours shows a predominantly fibrillar pattern with
microcystic changes sometimes. Rosenthal fibres are commonly seen.
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•• As the tumour enlarges, reactive proliferation of the meninges occurs,

contributing to the increased size of the tumour.
Lacrimal Gland Tumours

•• Lacrimal gland tumours make-up 35% of lesions involving the lacrimal
gland and the rest being inflammatory lesions.
•• The most common tumour is the benign mixed tumour which accounts for
approximately 50–60%.
•• The malignant mixed tumours account for 5–10%, adenoid cystic
carcinomas for 20–30% and other carcinomas for about 5–10%.
•• Microlateral orbitotomies may suffice for benign tumours, however, “en
bloc” resection of malignant tumours is required.
Fibrous Dysplasia
•• These are not actually tumours; however, these are lesions of childhood
and adolescence which can cause significant deformity of the orbit, frontal,
zygomatic, ethmoid or sphenoid bones.
•• The fibrous dysplasias are generally of two varieties:
1. The mono-osteotic variety where only one bone is involved.
2. The polyosteotic where many bones in the orbit are involved.
•• They produce unsightly proptosis and distortion of the face.
•• When the optic nerve is compressed in its canal surgery becomes
mandatory.
•• Surgical removal of the roof of the canal and the optic struts provide relief
from compression.
Dermoid and Epidermoid Cysts

•• Dermoids are the most frequent developmental cysts.
•• They are found usually in the latter half of the first decade or first half of
the second decade.
•• However, as they are slow growing and innocuous in their presentation,
they can be encountered in late adult age.
•• They are usually located at the lateral canthus and are almost always
extraconal and extraperiosteal in location.
•• These tumours may sometimes cause scalloping of the bone due to
prolonged and slow growth and may produce radiolucent bone defects
with well corticated margins on X-ray or CT scans.
•• They usually are painless, generally produce cosmetic disfigurement of the
face and cause little or hardly any displacement of the globe.
•• They can be completely excised by various approaches; a lateral orbitotomy
would suffice in most cases.
Osteoma
•• These are commonly found in the frontal or ethmoid sinuses.
•• They are hard lesions which displace the globe laterally and produce a
bulge superior to the medial canthus.
•• These are usually present in the second decade of life.
•• They may also have intracranial extensions.
•• Depending on the location and the extent, transcranial or extracranial
approaches may be used.
•• It is important to excise the entire osteoma or else recurrences are known.
1361
Mucocoele
•• This is a cystic collection of obstructed mucous lined by the mucous
membrane, arising either from the frontal or from ethmoidal air sinus and,
occasionally, from a pneumatised roof of the orbit.
•• The blockage may be secondary to chronic inflammation, scarring due to
trauma or surgery and at times polyps or bony tumours.
•• The radiology shows “ballooning” of the sinus walls, producing a
characteristic “eggshell” appearance.
•• Patients can present with proptosis, pain, visual discomfort, headache and,
at times, a palpable mass.
•• Often a transcranial approach would provide a better cosmetic result,
however, direct eyebrow incision with excision of the mucocoele by using
an anterior approach may also be used.
Metastatic Tumours
•• Neuroblastoma and Ewing’s tumours are common in childhood and may
metastasise to the orbit.
•• These malignant tumours of the orbit have a short history with ecchymosis,
pain and swelling.
•• The most common malignant tumour of the orbit in an adult is a metastatic
tumour and common primary sites are testicular tumours, breast, lung and
some skin tumours.
•• When malignant tumours are suspected, a fine needle aspiration biopsy is
preferred so that the treatment protocol may be planned.
•• As far as possible “En Bloc” resection must be performed whenever surgery
is indicated.
Vascular Lesions
•• CCF: The fistula causes increased venous pressure in the veins of the orbit,
particularly the superior ophthalmic vein. This leads to increased orbital
volume and produces proptosis.
•• At times, muscle thickening is also seen due to the increased venous
pressure.
•• All these features are reversible on treatment of CCF.
Venous Varix
•• It is a congenital condition where a venous pouch is present in the orbit and
any increase in venous pressure produces exophthalmos.
•• Valsalva manoeuvre, dependency of the head and straining tend to fill the
venous pouch and produce the characteristic symptoms.
•• Today, such lesions are treated by the neurointerventional team.
Arteriovenous Malformations
•• AVMs may be located within the orbit and are diagnosed a bruit audible
over the eye and verified by characteristic scan and angiogram findings.
Intraorbital Ophthalmic Artery Aneurysms

•• These are extremely rare.
•• More commonly, the aneurysms from the cavernous and clinoidal segments
of the internal carotid artery encroach upon the orbit and orbital structures.
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Pseudotumours
•• They represent a heterogeneous group.
•• Inflammatory pseudotumours of the orbit are far more frequent than specific
granulomas, such as tubercular or cysticercus.
•• At times, they have extensive spread of disease with involvement of the
paranasal air sinuses.
•• They have the following characteristics: There is a dense tissue reaction
due to mobilisation of chronic inflammatory cells, vascular proliferation
and hyperplasia of connective tissue forming an indurated orbital mass,
which often surrounds the optic nerve and also incorporates one or more
extraocular muscles.
•• There is absence of any aetiologic agent and, at times, histological
verification may be required to rule out:
–– Specific granulomas
–– Hodgkin’s lymphoma
–– Lupus erythematosus among other diseases
•• Ultrasound provides a characteristic image.
•• Besides the MRI and CT findings the per-operative gross features are also
quite pathognomonic.
•• The treatment of choice is dexamethasone which is given over a period
of 3–6 weeks in tapering doses. Surgery is generally limited to a biopsy.
Section XIII: Stereotaxy
183
CHAPTER
Stereotaxy:
General Principles
Ravi Ramamurthi • Vikram M
•• The development of stereotaxic surgery has given this capacity to the

surgeon to operate in the depth of the brain, without undue mortality or
morbidity.
•• It has led to advancement in knowledge about the functioning of the deep
areas of the human brain and has helped to provide relief from diverse types
of neurological disabilities, apart from the diagnosis of deep-seated lesions.
•• The idea of using internal landmarks in the centre of the brain increased the
accuracy of the placement of the electrode. The nearer these landmarks
are to the target aimed at, the greater is the accuracy.
•• Most of the measurements in stereotaxic terminology refer to the line
connecting the anterior and posterior commissures in the midline and these
calculations ensure anatomical accuracy of the placement.
•• When the technique is used for other indications with other targets to be
reached, the landmarks will naturally vary, e.g. tip of the temporal horn for
amygdalotomy, anterior horns of the lateral ventricle for cingulotomy and
the fourth ventricle for dentatectomy.
•• The modern techniques that are being used in stereotaxic surgery ensure
a safe degree of accuracy for therapeutic purposes.
•• One limiting factor in achieving such extreme accuracy is the variation seen
in different human brains.
•• This difference is not only seen between the sexes but also in different
individuals belonging to the same ethnic group.
•• An important achievement of stereotaxic surgery, in the early years, has
been the treatment of involuntary movements, chiefly Parkinsonism.
Deliberate placement of a lesion initially in the globus pallidus and later in
the thalamus led to marked amelioration of symptoms in patients suffering
from Parkinson’s disease.
•• The success attending this procedure encouraged further advancement
in the science of stereotaxic surgery and the scope of such surgery has
been widened to include other involuntary movements like dystonia,
hemiballismus and choreoathetosis.
•• The other condition for which the technique has been utilised with success
is the relief of intractable pain.
•• Further progress has included surgery for epilepsy and for some well
defined psychotic conditions.
•• The stereotactic technique can also be used in many other situations, e.g.
clipping a deep aneurysm, introducing radioactive seeds into a pituitary
adenoma or pineal tumours, biopsy of deep seated tumours, removal of deep
lying foreign bodies, draining of cysts and haematomas and for radiosurgery.
Section XIII • Stereotaxy
1364
•• Thus, stereotaxic surgery has increased our ability to give relief to patients,
simultaneously providing a tool for neurophysiological investigations on the
structures in the depth of the brain.
PRINCIPLES AND TECHNIQUES

•• All the instruments use internal landmarks as guides from which one can
determine the exact location of the target.
•• During the past three decades, many stereotactic instruments, which are
CT compatible, have been introduced. These instruments, while accurate
enough for biopsy, do not provide enough accuracy to locate physiological
targets in the depths of the brain.
•• Special CT images are needed or the CT scan has to be done with positive
contrast ventriculography, to provide clear delineation of the internal
landmarks.
•• MR compatible machines provide accurate visualisation of the needed
landmarks in the centre of the brain. When such machines are not available,
stereotaxic surgery can still be done accurately with air or non-ionic water-
soluble contrast X-ray studies.
•• Air may be introduced into the ventricles through a lumbar puncture
(pneumoencephalography) or through a burr hole (ventriculography).
•• In the sagittal and the horizontal planes of reference, the line joining the
anterior and posterior commissures is used as the guide.
•• In the coronal plane, the site of the target is calculated with reference to
the midline of the brain, as determined by the centre of the third ventricle
demonstrated in the AP view.
•• The position of the anterior and posterior commissures and the midline
of the brain, which are the common landmarks used, are determined by
contrast studies.
•• In the CT and MR guided machines, once the target is defined, the
calculations are made by the computer.
•• Using the average or the model brain chart and calculating for X-ray
magnification, the x, y and z co-ordinates are determined to fix the target
accurately and also to determine the angle of inclination for introducing
the electrode.
•• There are two types of stereotactic apparatuses that are commonly used; in
one type (Spiegel and Wycis) horizontal or linear co-ordinates are used and
in the other polar co-ordinates are used (Leksell, Talairach, Riechert, Sugita
and the Brown Todd-Wells apparatus, Cosman-Roberts-Wells apparatus).
•• In the linear type, the measurement of the target is taken in three planes
and then the electrode is introduced in one of the three planes. Adjustment
is possible for the needle (electrode) only in the three planes. It is not
possible to incline the needle (electrode), as calculations for angle are not
included. Hence, to reach different targets, the burr hole has to be made
at different sites.
•• In the apparatus that utilises polar co-ordinates, the needle (electrode) can
be tilted to the required angle to reach the target. Thus, through one burr
hole, different structures can be reached.
STIMULATION AND DEPTH RECORDING

•• The stimulation is performed at the tip of radiofrequency lesioning
electrodes.
Chapter 183 • Stereotaxy: General Principles
1365
•• Stimulation is performed at low current levels (less than 1 mA) and low
frequency (2–5 Hz) and the current is increased until an effect is seen.
•• The current is then reduced to sub-threshold levels and the frequency
increased until a response is seen.
•• Monopolar stimulation results in greater current spread than bipolar
stimulation; the optimal probe is a 1.1 mm bipolar concentric electrode
with 0.5 mm pole separation.
•• Recording of evoked potentials from the nuclei during stimulation of the
target is another way of identifying and delimiting the target.
•• It is also possible to record the electrical discharges from these deep areas
of the brain and the information utilised for locating the various nuclei. Such
depth recording is especially useful in surgery for epilepsy.
•• Microelectrodes may be used to record the response from single cells or
from a small group of cells to peripheral stimuli (evoked responses).
METHODS OF MAKING THE LESION

Temporary Lesions
•• Before making a permanent lesion, a temporary lesion may be made to
enable one to know whether the correct target has been reached and
whether benefit will accrue from placing the lesion in the particular area.
•• Temporary lesions can be made by heating the electrode tip to about 40°C
for about 20–30 seconds to a level when function would be interrupted.
•• If the placement is satisfactory, then the electrode is heated to coagulation
levels.
•• Similarly, when using cold as the lesion-making agent, the cryoprobe can
be cooled to about 0°C for 30 seconds to make a temporary lesion, which
may later be made permanent by cooling to minus 80°C.
Chemical Lesions
•• Chemicals have been used for many years to produce lesions during
stereotaxic procedures.
•• Alcohol or a mixture of alcohol with myodil or cellulose or bees wax has
commonly been used.
•• The danger of these chemicals seeping along the various tissue planes
is always present.
•• One can also not be absolutely sure about the shape of the lesion and its
direction of spread.
Electrolytic Lesions
•• By using a diathermy current and coagulating the tissues, precise
radiofrequency lesions can be made in the various deep nuclei.
•• With the help of a thermocouple fixed to the tip of the electrode, the
temperature at the tip may be increased to the desired level (62.5°C for 2
minutes) so that a constant lesion could be made.
•• Radio-frequency lesion-makers are available and help to create a
predictable lesion.
•• The optimum size of the lesion is 100–150 mm.
Cold Lesions (Cryogenic Lesions)

•• By using vacuum-insulated probes conducting liquid nitrogen gas, the tip
of the probe may be cooled to minus 80°C.
1366
•• After the accuracy of the probe placement has been confirmed by a

temporary lesion, by cooling the tip of the probe to 0°C, the temperature
of the tip is brought down to minus 80°C and kept down at that level for
3 minutes.
•• This usually produces a frozen lesion about 8 mm in diameter.
•• The size of the lesion depends on the temperature of the tip and the duration
of cooling and can be accurately monitored.
•• The tip of the probe is warmed to 20°C before being withdrawn. The temporary
post-operative disturbances are minimal when cold lesions are used.
Mechanical Lesions
•• Mechanical lesion-makers are useful, as one can be sure of the exact
extent of the lesion.
•• Small wire leucotomes have been used successfully.
•• When the needle is in the correct position, the wire is protruded to the
required extent (2−4 mm). The leucotome is turned around 45 degrees on
each side. The wire is now withdrawn into the leucotome, the direction of
the leucotome rotated to 90 degrees and the process is repeated.
Radiosurgery
•• Lesions can be made by using radioactive substances like radioactive
gold or yttrium.
•• It is also possible to make the lesion by using high-energy proton beams.
•• The use of the proton beam obviates the need for a burr hole.
•• The high speed accelerator is so adjusted that the concentration of the
protons would be at the target area whose co-ordinates are calculated in
the usual manner.
POST-OPERATIVE STUDY OF THE

SITE OF THE LESION
•• After the permanent lesion is made, to mark the site of the lesion, a small
stainless steel ball or an MR compatible radio-opaque marker is introduced
through a cannula and pushed into the area of the lesion.
•• By studying the position of the marker on the X-rays, it is possible to chart
accurately the site of the lesion on anatomical maps of the brain.
ASPIRATION OF CYSTS AND HAEMATOMAS

•• Using stereotactic localisation, a number of cysts, neoplastic and non-
neoplastic, may be biopsied for diagnosis and then drain them to relieve
compression on the brain.
•• A stereotactically guided Archimedes screw-type device has been
advocated to evacuate organised deep brain haematomas, as well
endoscopes may be used to irrigate and evacuate haematomas.
•• Catheter reservoirs may be implanted into the haematoma, followed with
streptokinase or tissue plasminogen activator injections to lyse the clot
with periodic aspiration.
STEREOTACTIC CRANIOTOMY
•• Image-guided stereotaxis can be used to guide the surgeon to deep-seated
or small tumours that need to be resected.
1367
•• Vascular lesions, such as cavernous malformations and small arteriovenous

malformations, can be localised and removed as well.
•• Use of an arc-centred system, such as the Cosman-Roberts-Wells system,
allows the surgeon to tailor the incision and bone flap appropriate for the
lesion, as the pointing device can be rotated out of the field while the
craniotomy is performed.
•• After the dura is opened, the probe can be used to guide or create a
corridor to the lesion.
•• Tumour-brain interfaces can be detected more easily by correlating the
intra-operative position with the stereotactic co-ordinates.
CHRONIC IMPLANTATION
•• Instead of making an acute lesion, fine electrodes can be left in the
desired target in the brain (chronic electrodes) and periodic stimulation
and recording may be done. As indicated, small incremental lesions could
be made.
•• Such chronic implanted electrodes have to be made of special alloy or
stainless steel to diminish tissue reaction.
•• Similarly, a chemode can be inserted into a desired area and chemical
agents may be delivered to focal areas in the depth of the brain for the relief
of seizures, pain, abnormal movements or behaviour disorders.
STEREOTACTIC ANGIOGRAPHY
•• There are several applications for stereotactic angiography: vessels to
be avoided during biopsy or implantation procedures can be visualised,
localisation of arteriovenous malformations for radiosurgery or open
procedures can be done and specific cortical gyri and sulci can be identified
by the positions of cortical arteries and veins.
•• The angiogram is performed with the patient in the stereotactic head frame
in the lateral and anteroposterior projections.
•• The referencing system consists of nine points on a radiolucent plate that
fits on the four sides surrounding the patient’s head.
•• Each film contains 18 points that are related by the degree of separation
between them and the divergence of the X-ray beams.
•• Structures located between the two plates can be described in stereotactic
space after the appropriate computer programme transformations.
TECHNIQUE USING THE LEKSELL’S

APPARATUS
•• The Leksell’s apparatus has a square frame with opaque markings that
help in calculating the co-ordinates.
•• On this, a semicircular frame with an electrode carrier is fitted, so that the
electrode may be introduced into the target from any angle.
•• This is one of the simplest and most accurate stereotactic apparatuses and
the technique is easily learnt.
•• The apparatus can be modified suitably for further sophisticated use.
COSMAN-ROBERTS-WELLS SYSTEM
•• The head ring, localiser ring and phantom frame of the Cosman-Roberts-
Wells system are identical to those of the Brown-Roberts-Wells system.
1368
•• The difference rests in the design of the arc guidance frame.

•• An arc-centred frame similar to those of the Todd-Wells and Leksell
systems is used.
•• The four angles of movement and the need for separate entry point
calculation are avoided.
•• Anteroposterior, lateral and vertical co-ordinates are accounted for in the
arc, placing the lesion in the centre of the sphere with a fixed radius.
•• The simplicity, flexibility and accuracy of the Cosman-Roberts-Wells frame
have made it the preferred stereotactic system.
PHANTOM INSTRUMENTS
•• Some stereotactic instruments, like Riechert’s and Sugita, use the principle
of phantom apparatus; the calculations and the adjustments are all made
in the phantom set-up from which they are directly transferred to the frame
on the patient’s head.
STEREOTACTIC EXTERNAL BEAM

RADIATION THERAPY
General Concepts
•• Ideal radiation therapy would subject the lesion to very high levels of ionising
radiation sparing all normal tissue.
•• This ideal can be approximated with the use of interstitial brachytherapy
or external beam radiation (teletherapy).
•• With the advent of computed tomography-guided stereotaxis, radiation may
be targeted and focused onto a lesion within the brain at a much higher
dose than is possible with conventional radiotherapy.
•• The Leksell’s Gamma knife uses fixed cobalt-60 sources that emit gamma
rays (photons) to a focal point 403 mm away. A collimator helmet with
various diameters is used to alter the volume of radiation emitted. The
stereotactic device allows accurate targeting from imaging and places the
target at the focal point of the converging gamma rays.
•• The second system that uses photons as an energy source is a modification
of the standard linear accelerator (Linac). Secondary collimators are fitted
to the head of the machine, which rotates with intersecting arcs to produce
a high concentration of radiation at the isocentre. A stereotactic frame is
used to place the target at the isocentre.
•• The last method uses collimated beams of charged heavy particles, such
as protons (hydrogen ions) or helium ions. Charged particles have several
properties that make them ideal for radiotherapy. They penetrate through
matter with a low initial dose, followed by a very high dose at the end of the
range of the beam (the Bragg peak), which is well defined for each particle.
•• Stereotactic radiosurgery has found its greatest application in the treatment
of small, deep-seated arteriovenous malformations, small benign tumours
of the cerebellopontine angle and metastatic disease.
•• Obliteration of arteriovenous malformations after radiosurgery is due to
radiation-induced vascular injury, resulting in the thrombosis of vessels
and ultimately of the nidus. This effect is delayed, often not seen for as
long as 2 years.
1369
•• Although surgical resection is still the mainstay of therapy for acoustic

neuromas, stereotactic radiosurgery is gaining popularity, especially in
elderly patients with medical illnesses that preclude surgery. Growth arrest
of the tumour is seen in most cases, but long-term follow-up is lacking.
•• Tumour shrinkage from radiosurgery usually is minimal, although central
necrosis may be seen.
FRAMELESS STEREOTAXY
•• With the introduction of computers, frameless stereotactic systems have
been developed.
•• These are based on the co-registration of an instrument or a pointer relative
to the patient’s anatomy, as demonstrated by CT or MRI scans.
•• The use of ultrasonography, light emitting diodes, or video “machine vision”
to localise hand held pointers or instruments in stereotactic space has made
them more user friendly.
SPINAL STEREOTAXIC SURGERY

•• The principles of cranial stereotaxic surgery can be extended to the spinal
cord, thus facilitating the placing of accurate small lesions in the various
tracts.
•• As cordotomy after laminectomy carries a fair amount of risk for debilitated
patients, the technique of percutaneous cordotomy was developed. Spinal
stereotaxic surgery is a further step.
•• A special stereotaxic frame suitable for spinal surgery was devised by
Hitchcock.
•• The midline is found in relation to the AP view of the frame, using co-
ordinates based on either the odontoid process or the third and fourth
ventricle.
•• By suitable adjustments of the frame, the spinal target in the lateral view can
be related to the radio-opaque markings on the horizontal and vertical bars.
•• The vertical and horizontal bars are then re-arranged, so they lie within
the plane of the target, at the desired laterality from the midline and at the
required depth below the frame.
•• An electrode carrier fitted with a Vernier scale is attached to the vertical
bars, thus permitting the movement of the electrode tip by 0.1 mm distances.
•• This technique can be used for various types of tractotomy in the medulla
and for cordotomy in the upper cervical cord.
184
CHAPTER
Stereotaxy:
Brain Tumours
Murali Mohan S • Ravi Ramamurthi
INTRODUCTION
•• The fundamentals of stereotactic surgery lie in the understanding of the
brain as a three-dimensional structure and the application of the Cartesian
co-ordinate system to define a specific region of interest.
•• Any geometric volume can be divided by three imaginary intersecting
spatial planes, orthogonal to each other, based on the Cartesian co-
ordinate system.
•• The brain is considered as a geometric volume and can thus be defined in
the horizontal, frontal and sagittal planes.
•• With reference to the centre point of intersection of these orthogonal planes,
any point within the brain can further be defined by precise numerical values
termed as co-ordinates.
•• Classically, stereotactic surgery is performed using a stereotactic frame, the
popular frames are the Leksell, Brown-Roberts-Wells, Patil and Cosman-
Roberts-Wells frame.
•• The basic principle of nearly all current stereotactic equipment is firm fixation
of the stereotactic apparatus to the patient’s skull vault with metal pins.
•• Once the head frame is attached under local anaesthesia, the patient is
shifted to obtain magnetic resonance (MR) or computed tomography (CT)
images with the reference frame in place.
•• The patient is then returned to the operation theatre, where the procedure
is performed.
•• Frame-based fiducials and target points are entered into a computer that
calculates the entry points and trajectory.
•• In the frameless stereotactic technique, the surgeon can navigate through
the spine and cranium with image guidance. The spatial accuracy of
frameless stereotaxy has been further enhanced with the introduction
of intra-operative MR imaging (MRI) that provides real-time images to
document the residual lesion and to assess brain shift during surgery as
the operation proceeds.
•• Stereotactic techniques, though commonly used in functional neurosurgery,
have been widely utilised for brain tumour surgeries mainly biopsy and
aspiration of critically located masses or combined with craniotomy for
excision of lesions.
STEREOTACTIC BIOPSY
•• Stereotactic biopsies are generally performed for the following intracranial
masses:
–– Suspected malignant intraparenchymal tumours in eloquent areas
Chapter 184 • Stereotaxy: Brain Tumours
1371
–– Deep-seated lesions
–– Multiple lesions
–– Patients reluctant for open surgery.
–– Stereotactic biopsies are avoided in the following conditions:
–– Extra-axial lesions
–– Superficial (grey-white junction) lesions
–– Suspected vascular malformations/vascular lesions.
•• Currently the use of biopsy sampling is reserved for a specific subset of
patients, particularly those with the following lesions:
–– A focal, enhancing, peripontine mass in the midbrain, medulla or
peduncle
–– A posteriorly exophytic tumour protruding into the fourth ventricle
–– A tumour exhibiting an uncharacteristic MRI pattern and is probably
non-glial
–– Focal, enhancing (especially ring-enhancing) lesions (to identify pa-
tients with benign non-neoplastic lesions)
–– Clinical or neuroimaging evidence of disease progression in tectal
masses.
Results
•• The non-specific diagnostic biopsies could be classified into two categories:
1. Negative biopsy in which the tissue obtained failed to indicate the
nature of the lesion.
2. Inconclusive biopsy in which a representative tissue was obtained, but
the definitive diagnosis could not be made.
•• Although experience of the pathologist is the most important factor in the
diagnostic yield, the small size of the samples is the major disadvantage
of stereotactic biopsy.
•• The presence of massive necrosis and the absence of a diagnostic
histological component in the small biopsies are causes of the discordance.
•• Stereotactic biopsy has also been shown to have a high specificity.
•• The diagnostic yield in CT-guided stereotactic biopsy of gliomas is highest
at the enhancing margin.
STEREOTACTIC ASPIRATION
•• Primary and metastatic brain tumours often have associated cystic
components.
•• Conventionally, the presence of a single, large and cystic brain tumour has
been regarded as an indication for surgery.
•• However, if the lesion is deep within the brain or located adjacent to
eloquent areas, surgical procedures may result in severe neurologic deficits.
•• In addition, surgical procedures are not effective or safe for patients in poor
general condition or those with multiple lesions.
•• Stereotactic cyst aspiration with or without Ommaya reservoir insertion is
a safe and effective alternative procedure in these patients.
•• Possible complications include haemorrhage, focal neurosurgical deficits,
seizures and infection.
STEREOTACTIC BRACHYTHERAPY
•• Stereotactic brachytherapy, the temporary or permanent implantation of
radioisotopes into brain tumours, is one method of overcoming the limitation
of conventional teletherapy.
1372
•• Another advantage is that this mode of therapy can also be employed in

recurrent tumours, which already have received the maximum tolerated
dose of EBRT.
•• For solid tumours, iodine-125 or Iridium-192 sources are most commonly
used.
•• The most often used dose rate is of the order of 40–60 rads/hour.
•• The goals of intracavitary radiotherapy are reduction of the cyst and long-
term control of the tumour, in many respects similar to the goals of EBRT.
•• Iodine-125 interstitial irradiation has been used for gliomas, pinealomas,
brainstem tumours, recurrent meningiomas, solid craniopharyngiomas
and metastases.
•• One of the negative aspects of intracavitary radiotherapy is the difficulty in
accessing the radioisotopes and the complexity of the process for instillation
of such materials into the cyst.
STEREOTACTIC CRANIOTOMY
•• The stereotactic system can be effectively combined with conventional
neurosurgical craniotomies for treating smaller lesions located in deeper
or eloquent areas and helps in reducing morbidity.
•• Stereotactic and computer-assisted techniques have revolutionised the
diagnosis and treatment of many brain disorders, enabling the surgeon to
adopt the least traumatic approach.
•• Frame-based systems are designed to mechanically constrain
instrumentation to a direct path to tumour tissue.
•• Stereotactic craniotomy is most useful for small, deep-seated lesions where
reliance on surface anatomic landmarks can be misleading.
•• Normally for this procedure seven targets are chosen—lesion centre, lateral
edge, medial edge, posterior edge, anterior edge—these five are calculated
from the same axial slice, and the superior edge and inferior edge—these
are calculated from slices showing the upper and lower limits of the lesion.
•• The calculation of multiple target co-ordinates enables a more accurate
planning of the craniotomy as well as aiding in volumetric excision. The
initial procedure is similar to stereotactic biopsy.
•• The posterior, anterior, superior and inferior edges of the lesion are marked
out on the skin using the sterile pointer—this procedure outlines the lesion.
•• Generally the centre target is used to plan the trajectory.
STEREOTACTIC ENDOSCOPY
•• Cerebral endoscopy has been used to approach an intracerebral tumour for
visualisation, irrigation, tumour cyst wall puncture, aspiration and biopsy.
•• Planning the entry point and trajectory is often the most crucial aspect of
the surgical procedure; this step can be guided by stereotaxy.
•• An entry site must be selected that provides a direct, linear route to the
cyst to accomplish two distinct goals:
1. One is to minimise any torque on the cortical or intraventricular neural
tissue.
2. The second is to allow direct, inline access to the distal edge of the cyst
wall; the edge abutting the CSF-containing cistern into which the cyst
will be fenestrated.
•• The application of stereotactic techniques to endoscopy enhances both
precision and safety.
Chapter 184 • Stereotaxy: Brain Tumours
1373
•• Stereotactic endoscopy has the advantage of control over depth penetration

and precise trajectory to deep-seated lesions under direct vision.
•• In colloid cysts stereotactic aspiration may at times be unsuccessful due to
the viscosity of the intracystic colloid and the displacement of the cyst away
from the aspiration needle. The CT/MR-guided stereotactic endoscopic
technique gives the opportunity to fenestrate the cyst wall under direct
visual control.
185 Movements: Anatomy
CHAPTER
Involuntary
and
Pathophysiology
Srinivasan AV
INTRODUCTION
•• Extrapyramidal disorders lead to a category of neurologic illnesses now
more often referred to as movement disorders.
•• Such a disturbance may cause excessive movements—Huntington’s
disease (HD) or a poverty of movements—Parkinson’s disease (PD), or a
disturbance of tone, posture or other manifestations.
•• These ganglia consist of the caudate nucleus (CN), putamen, globus
pallidum, claustrum and amygdaloid nuclear complex. In addition, the
related structures, i.e. substantia nigra (SN), subthalamic nucleus (STN)
and red nucleus (RN) are also included.
•• The CN and putamen are functionally related as also the SN and globus
pallidum.
•• The caudate, putamen and pallidum are known as corpus striatum.
•• The caudate and putamen are together called neostriatum and the
phylogenetically older globus pallidus (GP) or pallidum is designated
paleostriatum.
•• Striatum refers to the neostriatum. The putamen and GP are commonly
spoken of as one unit using the term lentiform nucleus or lenticular nucleus
with the putamen lateral to the GP, which lies like a wedge between the
internal and external capsules.
•• The putamen develops from the telecephalon while the pallidum develops
from the diencephalon.
•• The caudate and putamen are identical histologically. They contain few
large and many small neurons with the small cells predominating in the
ratio of 20:1. The dendrites may be spiny or aspiny.
•• The most common cell type in the striatum is small and spiny and contains
GABAergic neurons along with either substance P (SP) or enkephalin
(ENK).
•• The small spiny neurons are the primary source of striatal efferents. The
small aspiny neurons are cholinergic.
•• The microstructure of the striatum consists of a matrix and striosomes.
In the CN the matrix contains cholinergic neurons while the striosomes
primarily contain SP neurons (D1 dopamine receptors) and ENK neurons
(D2 dopamine receptors).
•• The GP is medial to the putamen and separated by the external medullary
lamina. Internally, the GP is divided by the internal medullary lamina into
a lateral part [globus pallidus externa (GPe)] and a medial part [globus
pallidus interna (GPi)].
Chapter 185 • Involuntary Movements: Anatomy and Pathophysiology
1375
•• Neurons throughout the GP use primarily gamma-aminobutyric acid (GABA)

as a neurotransmitter and less use ACh.
•• The SN consists of the substantia nigra compacta (SNc) which contains
large melanin containing dopaminergic neurons and substantia nigra
reticulata (SNr) which contains large, multipolar, non-pigmented GABAergic
neurons similar to those in the GPi.
•• The SNr is closely related functionally to GPi.
•• Other important structures involved in the extrapyramidal motor control
system include the thalamus, RN, the brainstem reticular formation, the
inferior olivary nucleus in the medulla, zona incerta, the pedunculopontine
nucleus (PPN), and the grey matter of the quadrigeminal plate.
MAJOR BASAL GANGLIA PATHWAYS

Connections of the Basal Ganglia
•• The BG is part of a complex network of neuronal circuits organised in
parallel to integrate activity from different cortical regions.
Striatal Afferents
•• Striatum forms the main input zone of the BG.
•• Corticostriate fibres: The major inputs to CN are from the entire ipsilateral
neocortex which is arranged somatotopically. The head of the CN receives
afferents from the frontal lobe, the body from the parietal and occipital lobes
and the tail from the temporal lobe.
•• The putamen (mainly medium spiny neurons) receives projections from
areas 4 and 6, the parietal lobe and perirolandic motor areas.
•• Thalamostriate fibres: The striatum receives afferents from the dorsomedial
and ventral anterior nucleus of the thalamus.
•• Nigrostriate fibres: The SNc sends fibres to the striatum which release
dopamine at their terminals and are inhibitory in function.
•• Brainstem striatal fibres: Brainstem raphe nuclei from the locus ceruleus
also send ascending fibres to the striatum.
Striatal Efferents
•• The primary efferent fibres project to the GPi. They have GABA as their
neurotransmitter. The CN also sends fibres to the putamen and to the
thalamus.
•• Striatonigral fibres: Fibres pass from the CN and putamen to the SN. Some
of the fibres use GABA or ACh as the neurotransmitter while others use SP.
Pallidal Afferent
•• Striatopallidal fibres: The principle afferents to GP are from the CN and
putamen. They have GABA as their neurotransmitter.
•• There are also afferents from STN, thalamus, SNc and from areas 6 and 4.
Pallidal Efferent
•• The pallidal efferents are the principal outflow of the BG. They are:
–– Fasciculus lenticularis
–– Ansa lenticularis
–– Pallidotegmental fibres which arise from GPi
–– Pallidosubthalamic fibres which arise from GPe.
1376
•• Both the ansa lenticularis and fasciculus lenticularis have the same origin,
the GPi, the same destination, the thalamus; the difference is that the
fasciculus penetrates through and the ansa curves around the internal
capsule.
Subthalamic Nucleus
•• The connection to STN is the only pallidal efferent to arise from GPE, all
others arise from GPi.
•• The STN sends back fibres to GPe and to GPi through the subthalamic
fasciculus.
Substantia Nigra
•• Afferents: This includes: Striatonigral fibres: SNr receives fibres from the
striatum, Gp and STN
•• Efferents: This includes: Nigrostriatal fibres, Nigrothalamic fibres,
Nigrotectal fibres: It connects SN with the ipsilateral superior colliculus and
is concerned with the control of eye movements. There are also connections
between SN and PPN and reticular formation.
FUNCTIONAL ORGANISATION OF THE BASAL

GANGLIA AND OTHER PATHWAYS
•• Afferent projections to the striatum arise from all areas of the cerebral
cortex, the intralaminar nuclei of the thalamus, mesencephalic SN, and
from the locus ceruleus and raphe nuclei. There is also a projection from
the cerebral cortex to the STN.
•• The major efferent projections are from the GPi and SNr to the thalamus
and brainstem nuclei such as PPN.
•• The GPi and SNr project to ventral anterior and ventrolateral thalamic nuclei.
•• The GPi also projects to the centromedian thalamic nuclei and the SNr
projects to the mediodorsal thalamic nuclei and superior colliculus.
•• The ventral anterior and ventrolateral thalamic nuclei then project to the
motor and premotor cortex.
•• The BG have dense internuclear connections. Five parallel and separate
closed circuits through the BG have been proposed. These are the motor,
oculomotor, dorsolateral prefrontal, lateral orbitofrontal and limbic loops.
•• It is now generally agreed that these loops form three major divisions—
sensorimotor, associative, and limbic, that are related to motor, cognitive
and emotional functions, respectively.
•• The functions of the sensorimotor striatum are subserved mainly by the
putamen, which derives its afferent cortical inputs from both motor cortices.
•• Sensorimotor pathways are somatotopically organised and the pathway
ultimately terminates in the premotor and primary motor cortices and the
supplementary motor area.
•• Cognitive functions are managed by the associative striatum. In this
pathway, the dorsal CN receives afferent input from the homolateral frontal,
parietal, temporal and occipital cortices.
•• Projections from this pathway ultimately terminate in the prefrontal cortex.
•• The limbic striatum subserves emotional and motivational functions. Its
input derives from the cingulate, temporal, and orbitofrontal cortices, the
hippocampus, and the amygdala. It comprises mainly the ventral striatum
with ultimate projections to the anterior cingulate and medial orbitofrontal
cortices.
Chapter 185 • Involuntary Movements: Anatomy and Pathophysiology
1377
•• Within each BG circuit lies an additional level of complexity. Each circuit

contains two pathways by which striatal activity is translated into pallidal
output.
•• These two pathways are named the direct and indirect pathways, depending
on whether striatal outflow connects directly with the GPi or first traverses
the GPe and STN.
•• The direct and indirect pathways have opposite effects on outflow neurons
of the GPi and SNr.
•• Direct pathway:
–– In the motor direct pathway, excitatory neurons from the cerebral
cortex synapse on putaminal neurons, which in turn send inhibitory
projections to the GPi and its homologue, the SNr.
–– The GPi/SNr sends an inhibitory outflow to the thalamus.
–– Activity in the direct pathway disinhibits the thalamus, facilitating the
excitatory thalamocortical pathway and enhancing activity in its target,
the motor cortices.
–– Thus, the direct pathway constitutes part of an excitatory cortical-
cortical circuit that functions to maintain ongoing motor activity.
•• Indirect pathway:
–– In the indirect pathway, excitatory axons from the cerebral cortex syn-
apse on putaminal neurons. These neurons send inhibitory projections
to the GPe.
–– The GPe sends an inhibitory projection to the STN.
–– The net effect of these projections is disinhibition of the STN.
–– The STN in turn has an excitatory projection to the GPi. Activity in the
indirect pathway thus excites the GPi/SNr, which in turn inhibits the
thalamocortical pathway.
•• Thus, the net effect of increased activity in the indirect pathway is cortical
inhibition.
•• The striatum also receives a robust afferent input from the SNc. This
projection, from the SNc, an important modifier of striatal activity, facilitates
activity in the direct pathway and inhibits activity in the indirect pathway,
thus promoting cortical excitation through both pathways.
•• In addition to these pathways there are other closed loop circuits, which
seem designed to modulate and regulate the excitability of the BG
themselves. Several circuits may be recognised which are as follows:
–– The centromedian/parafascicular (CM-Pf) thalamic nuclei striatum GPi
CM-Pf circuit, which is probably a positive feedback loop leading to
increased neuronal activity.
–– The CM-Pf STN GPi CM-Pf circuit, which is probably a negative loop
leading to reduced neuronal activity.
–– The STN GPe STN circuit, which is an excitatory-inhibitory loop with
“autostabilising” characteristics.
–– The STN-GPe/GPi dual projection, which is an “open” but inter-
connected loop by which the STN might induce excitation and
inhibition of the same GPi neurons within less than 5 ms.
•• The primary motor cortex (area 4) STN GPi motor thalamus area 4 loop,
which is perfectly suited to provide inhibitory feedback signalling to the
cortex and probably very relevant for the termination of movement.
•• Disorders of the BG result in prominent motor dysfunction, though not
generally in frank weakness.
1378
•• The absence of direct primary or secondary sensory input and the lack of
a major descending pathway below the level of the brainstem suggest that
the BG moderates rather than controls movement.
•• In Parkinson disease(PD) death of neurons in the SNc decreases activity
in the direct pathway and increases activity in the indirect pathway.
•• These changes cause an increased rate of firing of subthalamic and GPi
neurons with excessive inhibition of thalamocortical pathways and produce
the behavioural manifestations of bradykinesia in PD.
•• On the other hand, selective loss of indirect pathway neurons, as in HD,
interferes with suppression of involuntary movements.
•• Direct electrophysiological recordings of the STN and GP during stereotactic
functional neurosurgical procedures confirm that the GPi and STN are
overly active in patients with PD.
186
CHAPTER Stereotaxy for
Parkinson’s Disease
Dilip Panicker • Paresh K Doshi
•• Meyers carried out the first direct operation on the basal ganglia in an
attempt to treat Parkinsonian tremors.
•• He performed sequential excision, under local anaesthesia, to examine its
effect on Parkinson’s disease. Excisions included:
–– The caudate head.
–– The caudate head and the anterior limb of the internal capsule.
–– The caudate head, the oral half of the putamen and the anterior limb
of the internal capsule.
–– The caudate head, oral half of the putamen and the oral pole of the
globus pallidus (GPi), with section of the anterior limb of the internal
capsule.
–– Section of the ansa lenticularis (ansotomy) either alone or in
combination with the above procedures.
PHYSIOLOGICAL BASIS OF THE TARGET

•• It is hypothesised that in Parkinson’s disease there is increased activity
of the internal globus pallidus (GPi) and the subthalamic nucleus (STN),
resulting in akinesia and bradykinesia.
•• In a simplified manner, this circuit can be understood through the following
diagram (Fig. 1).
•• The projections from the cortex to the striatum (caudate nucleus and
putamen) are excitatory.
•• The striatal projection neurons can be divided into two groups.
•• D1 receptor linked neurons projecting to the GPi are inhibitory.
•• They regulate the inhibitory output of GPi to the thalamus via the ansa
lenticularis projections.
•• The thalamocortical projections are in turn Flow chart 1: Basal
excitatory in nature. ganglia physiology
•• Any increased inhibition of the thalamus by
GPi can lead to decrease in this excitatory
thalamocortical output, resulting in slowness
and poverty of movements seen in Parkinson’s
disease.
•• The indirect pathway constitutes inhibitory
projections from the striatum to the external
globus pallidus (GPe).
•• The GPe neurons in turn inhibit STN. They use
D2 receptors, which are inhibited by dopamine.
1380
•• In Parkinson’s disease, lack of dopamine decreases this inhibition of STN,

which becomes hyperactive and in turn excites the GPi causing increased
thalamic inhibition, leading to decreased excitation of the thalamocortical
pathway.
•• Thus, lesions involving GPi, STN and ansa lenticularis would be expected
to release the motor system from the functional consequences of over
inhibition of the basal ganglia.
SELECTION OF PATIENTS
•• Patients with advanced Parkinson’s disease should be considered for the
surgical option.
•• The common guidelines that are followed are based on the Core
Assessment Program for Neurosurgical Interventions and Transplantation
in Parkinson’s disease (CAPSIT-PD).
•• The most important selection criteria are the diagnosis of Parkinson’s
disease.
•• There are many diseases that may mimic Parkinson’s disease in the initial
stage, which need to be carefully excluded.
•• One of the ways to ensure this is not to consider surgery for patients with
less than 5 years of disease duration.
•• The second criterion is responsiveness to Levodopa. Patients should
show a minimum 33% improvement in their off period motor scores after
Levodopa.
•• The patients should have the ability to tolerate “awake” surgery as certain
patients, especially older patients, may get confused during surgery.
•• One more aspect about patient selection is the expectations from surgery.
The patient and their family members should be adequately counselled
about the surgical outcome.
PRE-OPERATIVE WORK-UP
•• All patients are evaluated by a neurologist or a movement disorder specialist
for the confirmation of the diagnosis of Parkinson’s disease.
•• CAPSIT-PD guidelines of pre-operative evaluation based on the clinical
experience of Deep Brain Stimulation (DBS).
•• Unified Parkinson’s Disease Rating Scale (UPDRS) evaluation in 12 hours
“off” medication conditions and post-Levodopa challenge (one and a half
times the usual Levodopa dose) is performed. Video recordings are also
performed in both these stages.
PALLIDOTOMY/PALLIDAL STIMULATION
•• Laitinen used the posteroventral GPi as the surgical target for pallidotomy.
•• This target was typically located 17.23 mm lateral to the midcomissural
plane, 3.6 mm ventral and 2.3 mm anterior to the midcommissural point.
•• The target is identified on an inversion recovery MRI sequence in the
coronal plane.
•• Typically it is just above the optic tract and lateral to the internal capsule.
•• A lesion is made by replacing the MER electrode with a 2 mm x 2 mm
exposed tip electrode.
•• The lesion is started 6 mm above the target and three lesions of 70°C for
60 seconds are made.
•• The electrode is advanced 2 mm after each lesion.
Chapter 186 • Stereotaxy for Parkinson’s Disease
1381
•• In case of pallidal stimulation, a deep brain stimulation (DBS) electrode

(Medtronic 3389-40), having four contact points of 1.5 mm width spaced
at 0.5 mm interval, is used to replace the MER electrode.
Complications
•• Adverse reactions are minor and well tolerated, but there is a risk of serious
adverse reactions.
•• The complications included fatigue and sleepiness, worsening of memory,
depression, aphonia, dysarthria, scotoma, hemiparesis and delayed
stroke.
Discussion
•• Pallidotomy was a highly popular target for Parkinson’s disease surgery
from 1990 to 1997.
•• One of the most dramatic effects of the surgery was to eliminate L dopa
induced dyskinesias and off period pain associated with Parkinson’s
disease.
•• The improvement in axial symptoms, gait and postural stability is less
noticeable.
•• There is a transient improvement in ipsilateral rigidity; however, this has
been known to decrease over time.
•• There is no reduction in medications following Pallidotomy, in fact in some
patients the requirements for medicines increase over time as the disease
progresses.
•• Another major benefit of pallidotomy is the complete relief of off phase
pain and dystonia.
•• GPi stimulation for Parkinson’s disease is not so widely practiced.
SUBTHALAMIC NUCLEUS
STIMULATION/LESION
•• Presently, STN DBS is the most commonly practiced Parkinson’s disease
surgery.
Surgical Procedure
•• MRI and CT scan used for anatomical localisation of STN.
•• Frame Link (Neuronavigation software, Medtronic) protocol and
independent targeting methods to localise STN.
•• MRI is obtained 1–4 days prior to surgery.
•• The first sequence is an inversion recovery, sagittal acquisition, with slice
thickness of 2 mm.
•• The anterior commissure (AC) and posterior commissure are identified and
their distance measured.
•• The next sequence is T2-weighted coronal MRI, oriented perpendicular to
the AC:PC plane (independent method).
•• STN is identified as a hypointense structure dorsomedial to the substantia
nigra (SNr). This is best seen on a slice passing through the anterior one-
third of the red nucleus.
•• On the day of surgery, a stereotactic CT scan is obtained.
•• Based on the co-ordinates the STN target is selected to be 2 mm behind
the midcommissural point, 4 mm inferior to AC:PC plane and the laterality is
guided by the measurements obtained from the MRI (independent method).
1382
•• The images are imported on the Frame Link workstation.

•• The desired target is chosen and the appropriate trajectory is planned, so
as to avoid the ventricles and cortical blood vessels.
•• The usual trajectory is close to the coronal suture and 3.4 cm lateral to
the midline.
•• The target is explored with the help of 4−5 microelectrode trajectories.
•• Recording done 5 mm proximal to the target and extend it up to 5 mm or
more distal to the target.
•• STN neurons are easily distinguished from cells of the overlying zona
incerta and the underlying substantia nigra.
•• The trajectory yielding the strongest signal for at least 3−4 mm is selected
for stimulation.
•• Stimulation is performed at 130 Hz, 60 µsec and up to 2 mA.
•• Following effective stimulation there is a loss of rigidity, which is usually
assessed at the wrist joint.
•• There is abolition of tremors and improvement in bradykinesia.
•• In the majority of cases, stimulation also produces dyskinesias on the
contralateral side.
•• Induction of dyskinesias during surgery generally predicted a good
antikinetic effect of chronic STN stimulation.
•• Stimulation related side effects may indicate the electrode position relative
to STN.
•• STN is close to the corticobulbospinal tract laterally, the sensory tract
fibres posteriorly, the third nerve fibres medially and the red nucleus
posteromedially.
•• Stimulation response related to any of these structures, without motor
improvement, indicates that the stimulating electrode is in an inappropriate
position and necessitates exploration of another trajectory.
•• Once finalised the trajectory, motor stimulation at 2 Hz, 60 µsec is
performed, increasing the current up to 7 mA, to look for muscle
fasciculation and dysarthria.
•• On finalising the trajectory, the DBS lead (Medtronic 3389-40) is implanted,
with the contact 1 positioned at the point of best stimulation response.
•• This is performed under fluoroscopic guidance. In case of STN lesioning,
two lesions are made with the help of a 1 mm x 0.75 mm exposed tip
electrode at the station of the best STN response.
•• Following the procedure, the patient is taken for a check CT scan to rule
out intracranial haemorrhage.
•• On the next day, if the patient is not confused, the implantable pulse
generator (Kinetra 7428, Medtronic) (IPG) is inserted in the left
infraclavicular region under general anaesthesia.
•• Programming of the IPG is commenced from day 3 or 4.
•• Each electrode contact is tested for maximal improvement and side effect
threshold.
•• The contact (usually 1 or 2) that has the largest therapeutic window is
selected for permanent programming.
•• Medicines are reduced slowly as the current thresholds are increased.
•• By the time of discharge, most of the patients are on stable programming
parameters and a 30−40% reduction in their medicines.
Chapter 186 • Stereotaxy for Parkinson’s Disease
1383
Discussion
•• Psychiatric problems, including depression or mania, have been reported
by several groups in patients treated with stimulation of the STN.
•• These complications may be related to pre-existing psychiatric illness,
surgery related stress, changes in medication, alterations in social life that
are associated with improvements in motor function and the mismatch
between the final outcome of treatment and the patient’s expectations.
•• Changes in the limbic circuit may also contribute to psychiatric problems.
•• Although stimulation of the STN requires very close follow-up of the patient
by a clinician experienced with this approach, once a good balance is
achieved between the amount of stimulation and dopaminergic treatment,
therapeutic adjustments are infrequent, as shown by the stable treatment
settings and the low incidence of complications beyond the first post-
operative year.
•• However, over time there is deterioration in akinesia, axial symptoms and
cognitive problems that is consistent with the progression of the underlying
disease. This deterioration may be more marked in elderly patients.
•• Those patients who already have disabling motor signs that are resistant
to Levodopa, or who have cognitive deterioration, are not good candidates
for this treatment.
Future Therapies
•• The pedunculopontine (PPN) nucleus is a new target being explored for
“on” phase gait and postural symptoms.
•• Early results have shown that the PPN nucleus might help to improve
these symptoms, besides simultaneous stimulation of the PPN and STN
may offer greater benefit.
•• Given the cognitive changes following STN stimulation, some centres are
contemplating revisiting GPi stimulation for Parkinson’s disease.
•• Research on stem cell therapy is actively progressing and early results
of mesenchymal stem cells implantation in animal models of Parkinson’s
disease have shown encouraging results.
187
CHAPTER Surgery for
Movement Disorders
Paresh K Doshi • Animesh Upadhyay
•• Movement disorders can be classified according to the predominant motor

manifestations (Table 1).
TREMORS
•• Tremor is an unintentional (involuntary), rhythmical alternating movement
that may affect the muscles of any part of the body.
•• Tremor is caused by the rapid alternating contraction and relaxation of
muscles (Table 2).
•• The thalamus is involved in the genesis of various types of tremors.
•• It functions as a relay nucleus in the cortico-basal ganglia-thalamocortical
loop in Parkinsonian tremor, the premotor cortex and cerebellar thalamic
connections in cerebellar types of tremors, and the premotor cortex and
connections with the triangle of Mollaret in essential tremor and brainstem
tremor, or Holmes tremor.
•• Although part of the motor thalamus [ventralis oralis posterior (Vop) and
ventralis intermedius] is considered as the target of choice for tremor relief
by stereotactic neurosurgery recently, tremor suppression in PD was also
demonstrated after surgery of the globus pallidus and subthalamic nucleus
(STN).
Table 1: Clinical classification of movement disorders

Akinetic—rigid form
Parkinsonism: Parkinson’s disease; Parkinsonian syndromes
Stiff man syndrome
Hyperkinetic forms
Chorea syndromes
Dystonias
Myoclonus
Ballism
Tics
Atactic movement disorders
Cerebellar ataxias
Spinocerebellar degeneration
Chapter 187 • Surgery for Movement Disorders
1385
Table 2: Tremor classification and treatment

Tremors classification
Parkinson’s disease
Essential tremor
Post-traumatic and Post-hemiplegic tremors
Tremors from multiple sclerosis
STN is the target of choice for PD tremor
Vim nucleus of thalamus is the target of choice for other tremors
Thalamotomy for unilateral cases/thalamic stimulation for unilateral or bilateral cases
Bilateral thalamotomy has high morbidity
More than 90% success rate in relieving tremors by either procedure
Major morbidity is less than 5%
•• The most common types of tremor amenable to stereotactic neurosurgery

are Parkinson disease(PD) tremor, essential tremor, tremors due to multiple
sclerosis (MS), stroke and post-traumatic tremor.
•• The Vim nucleus of the thalamus, as defined by Hassler, is the currently
preferred target for tremor suppression.
•• Thalamotomy or thalamic stimulation can be offered for unilateral tremor.
However, bilateral thalamotomy carries a significant risk of morbidity of
speech and cognition and hence is not currently practiced.
•• The results of thalamotomy and thalamic stimulation are dependent on the
type of tremor aetiology.
Parkinsonian Tremor
•• Unilateral thalamotomy results in a permanent significant improvement of
Parkinsonian tremor in approximately 80% of the patients.
•• Permanent morbidity is 4−47% and mortality is below 1%.
•• Pallidal and STN stimulation may give both striking and lasting suppression
of Parkinsonian tremor.
•• Permanent adverse events are less frequent and less severe with these
targets after bilateral stimulation as compared to the thalamic target.
•• Another advantage of this procedure is simultaneous reduction in rigidity
and dyskinesia with improvement in bradykinesia.
•• These procedures have replaced thalamic surgery in patients with advanced
PD even with severe tremor.
•• STN is the target of choice for advanced PD, including patients with severe
tremors.
Essential Tremor
•• Essential tremor is also known as familial tremor as it runs in families.
•• It is characterised by tremors on action or posturing.
•• There are no tremors at rest.
•• Usually, they remain under control for long years up to 10−15 years.
•• When the tremors become severe, the patient can be considered for
1386
•• The number of patients referred for surgery is rather small as compared

to PD.
•• Vim nucleus of the thalamus is the preferred target by most workers.
Post-traumatic and Post-hemiplegic Tremor

•• These tremors are mainly postural and action tremors.
•• They are more violent in nature as compared to the essential or
Parkinsonian tremors.
•• They manifest following recovery from the original cerebral insult and can
be of considerable disability to the patient.
•• Pharmacotherapy is generally not effective.
•• The surgical target for their treatment is once again the Vim nucleus.
Multiple Sclerosis Tremors

•• Of the various disabilities from MS, tremors also form one important
component.
•• The tremors are coarse and have a large amplitude proximal component.
•• They are also associated with neck tremors or dysarthria.
•• These tremors are very difficult to control, especially the proximal
component.
•• Besides, they also have very low side effect thresholds precluding use of
higher stimulation parameters.
The Vim Target

•• The Vim nucleus is the common site for lesioning and DBS target is used
for the treatment of tremors.
•• In the somatotopic organisation of the Vim nucleus the face area lies
medially, followed by the upper extremity laterally and the lower extremity
is the most lateraly situated close to the internal capsule.
•• The Vim nucleus of the thalamus has neurons that fire in synchronous
bursts with the tremor frequency and are called tremor cells (TCs).
•• The DBS target for tremor control is the electrophysiologically defined Vim.
•• This electrophysiologically defined motor thalamus (Vim) has TCs and
kinesthetic cells, and it lies immediately anterior to the cutaneous receptive
cells, which lie in the sensory thalamus.
•• The somatosensory relay nucleus ventralis caudalis (VC) of the thalamus
lies immediately posterior to Vim.
•• The VC has specific neurons that respond to tactile stimulation in small,
receptive fields.
•• The Vop nucleus lies immediately anterior to the Vim. The internal capsule
lies lateral to the Vim.
•• The Vop receives afferents from pallidal neurons and the Vim receives
afferents from the cerebellar neurons (cerebellothalamic fibres).
DYSTONIA
•• Dystonia is defined as an involuntary movement disorder characterised
by repetitive, patterned or sustained muscle contractions causing twisting
movements or abnormal postures.
•• Dystonia is classified as primary or secondary.
1387
•• Primary dystonia is the classical familial dystonia described by Oppenheim.

It is also known as dystonia musculorum deformans (DMD).
•• Primary idiopathic dystonia refers to dystonia with no discernible aetiological
factor responsible for its onset.
•• DMD is a disease of young people, with most cases commencing in
childhood (Age: 0−12 years), although some do not appear till the age of
10 years; adult onset is rare.
•• Patients with primary idiopathic dystonia have normal imaging findings,
cerebrospinal fluid composition and laboratory test examinations.
•• Secondary dystonia occurs due to a variety of disorders ranging from
hereditary neurological syndromes, like Wilson’s disease and Huntington’s
disease, to perinatal cerebral injury causing cerebral palsy or later on in life
secondary to head trauma, brainstem lesions or brain tumours.
•• Tardive dyskinesia is another subset of dystonia that results from super-
sensitivity of the post-synaptic dopamine striatal receptors due to long-term
administration of dopamine receptor blocking agents such as neuroleptics.
•• The most common drugs implicated are metoclopramide, olanzapine and
risperidone.
•• Risperidone appears to have fewer dystonic effects, only clozapine
has been shown to have a lower risk of tardive dyskinesia than older
antipsychotics. These are commonly used to treat psychiatric conditions.
•• Another form of dystonia that is amenable to surgical treatment is a focal
dystonia known as Writer’s cramp. This is a task specific dystonia. Patients
develop abnormal posturing during performance of a particular task like
writing, playing a musical instrument, drawing, etc. whereas they are
completely normal during rest and with other activities.
•• Dystonia can also be classified according to the affected body part. In focal
dystonia, a single region of the body is affected, such as in blepharospasm
(eyes), cervical dystonia/torticollis (neck) and spasmodic dysphonia or
laryngeal dystonia.
•• In segmental dystonia, two or more adjacent body parts are affected, such
as cranial-cervical dystonia, or brachial dystonia.
•• Generalised dystonia refers to dystonia involving most body parts.
•• Currently accepted clinical rating scales for dystonia include physicians
global dystonia rating scale (PGDS), The Burke-Fahn-Marsden (BFM)
scale, and the unified dystonia rating scale (UDRS).
•• Primary, generalised dystonia of DYT-1-positive or non-DYT-1 types, as
well as patients with idiopathic cervical dystonia can obtain the best motor
benefits with bilateral GPi DBS.
•• Patients with juvenile-onset idiopathic dystonia whose age of onset is older
than 5 years and who do not have multiple orthopaedic deformities also
have a good response to surgery.
•• Appendicular symptoms (e.g. those affecting the limbs) appear to respond
better than axial symptoms.
•• With regard to focal dystonia, ideal surgical candidates are those with
cervical dystonia.
•• The results of DBS for secondary dystonia are inconsistent.
•• In general, DBS for secondary dystonia is less effective than for primary
generalised dystonia, particularly in those patients with an identifiable
structural brain abnormality.
•• The only exception is tardive dystonia, which respond well to surgery.
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Indications for Surgical Treatment of Dystonia

•• Surgery does not alter the progress of dystonia or the underlying
•• Thus, not withstanding how successful the surgery is, the eventual outcome
is determined by the subsequent disease progress and the underlying
neurological deficit.
•• Selection of suitable candidates for dystonia surgery is extremely crucial.
•• Patients with primary generalised dystonia, also those who are DYT1 gene
positive, are the best surgical candidates.
•• Primary dystonia of sporadic variety also benefits from surgery.
•• Secondary dystonia, especially hemi-dystonia, which has been stabilised,
can be offered a surgical option.
•• Patients whose progress has halted and have been stable for the last 6
months or more could also be offered surgical treatment.
•• Severe pain from dystonia also forms one of the indications for surgical
intervention.
•• It is important to exclude the primary dystonias that are responsive to
medical treatment with trihexyphenidyl hydrochloride or levodopa.
Surgical Options in Dystonia

•• The GPi is currently the most common target for treating dystonia although,
earlier, the thalamus (Voa, ventrolateral) and subthalamus have been used.
•• The GPi DBS target is the posteroventrolateral GPi, which is the
predominant motor territory of the nucleus.
•• The Gpi is well-visualised on MRI (inversion recovery and T2 sequences)
to define the surgical target and identify the internal capsule and the optic
tracts.
•• The globus pallidus is divided into two anatomic segments: (1) internal
(GPi) and (2) external (GPe).
•• Although these segments are separated by the medial medullary lamina,
the pallidal neurons from each segment are similar and, for the most part,
morphologically indistinguishable.
•• The GPi is bound laterally and dorsally by the GPe.
•• Medially the GPi is bound by the internal capsule.
•• Ventrally it is close to the optic tracts.
•• The therapeutic sensorimotor territory of the GPi is ventral and posterior,
and the somatotopy places the face and arm posterior and ventral, and
the leg central and more dorsal.
•• Pallidal stimulation is a better alternative to pallidotomy. This has the
advantage of being completely reversible and chances of cognitive deficits
are much less.
•• Bilateral pallidotomy does carry a risk of cognitive impairment and hence
in bilateral cases only pallidal stimulation should be performed.
•• However, pallidotomy is a useful adjunct for treating focal and unilateral
dystonias.
Results
•• Results of pallidotomy or pallidal stimulation are both comparable.
•• However, pallidal stimulation offers an added advantage of post-operative
titration.
1389
•• The current requirements for the stimulation are considerably high and
hence, it affects the battery life used for the pulse generator. However,
with the currently available batteries they would require to be replaced
within 3 years or less, if used for stimulation of the pallidum for dystonia.
•• It may take months for the full effect of pallidal stimulation to develop.
•• Mild improvement in “mobile” dystonia is often seen within the first few hours
after the initial programming of the stimulators and is a good predictor for
continuing improvement.
•• There are several case reports about dramatic improvement of generalised
dystonia after bilateral pallidotomy.
•• The most striking effect was the clear benefit of axial dystonia without side
effects, such as hypophonia, known to be associated with bilateral pallidal
lesioning in PD.
•• For secondary generalised dystonia, reported results are highly variable,
ranging from no benefit at all to significant improvement in some cases.
•• DBS offers a therapeutically viable option for patients with severe, primary
dystonia and also for a small subset of patients with secondary dystonia.
•• The key to favourable responses after DBS in patients with dystonia is
proper patient selection.
•• Patients who are refractory to all conservative measures, including
medication trials (anticholinergics, baclofen, benzodiazepines or other
muscle relaxants) and botulinum toxin injections are potential candidates.
COMPLICATIONS
•• Complications of pallidotomy and thalamotomy are uncommon. Both
procedures are designed to create defined lesions in deeply seated and
critically located brain nuclei.
•• Haemorrhage is the primary concern in both procedures. Since, the
electrode is small and no tissue is removed during such procedures, the
haemorrhage rate is low.
•• The second common complication is infection.
•• Minor infection presenting as inflammation can be conservatively managed
with antibiotics; however, if there is an implant, any evidence of discharge
or pus formation warrants removal of the implant.
•• If the infection is at the pacemaker site, the pacemaker and the connecting
extension needs to be removed.
•• If it is at the burr hole site the intracranial electrodes have to be removed.
Pallidotomy Complications
•• Neurologic deficits may be produced by the lesion itself.
•• The most common neurologic deficits after pallidotomy include visual field
deficit, hemiparesis and dysarthria. Such symptoms are usually temporary.
•• The close approximation of the globus pallidus interna to the internal
capsule and optic tract are the basis for these deficits.
•• Radiofrequency lesion generation causes focal tissue necrosis surrounded
by a zone of oedema. This peripheral oedema may cause transient deficits.
•• The mainstays of complication avoidance for pallidotomy surgery are
appropriate patient selection and target planning, the use of test lesions
and visual evoked potential monitoring, physiologic evaluation, careful
intra-operative neurologic examinations and judicious lesion generation.
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Thalamotomy Complications
•• Common complications following thalamic surgery include dysarthria and
pyramidal and cognitive deficits.
•• Bilateral thalamotomies have the highest risk of these complications
followed by unilateral lesioning and then stimulation procedures.
•• Bilateral thalamotomies are rather contraindicated in present day functional
neurosurgery.
•• Bilateral stimulation was more effective than unilateral stimulation in
alleviating axial tremors; however, as for bilateral thalamotomies, the rate
of neurological complications was higher in patients who underwent bilateral
stimulation. Disequilibrium was more common during bilateral stimulation.
•• Complications, particularly intracerebral haemorrhages, were more common
among patients with thalamotomies. Likewise, cognitive deterioration and
hemiparesis can occur.
188
CHAPTER Gamma Knife
Radiosurgery
Manish Singh Sharma • BS Sharma
•• It is a platform used to deliver highly focused beams of gamma radiation

onto an immobilised intracranial target within a frame, using the principles
of stereotaxy.
MEDICAL PHYSICS
•• The Leksell Gamma Knife™ (LGK) contains 201 cobalt-60 sources of
approximately 30 curies (1.11 TBq) each, placed in a heavily shielded
assembly.
•• A combination of helmets with pores (collimators) focuses the gamma
rays into the centre of a circular array where the patient’s head is placed.
•• Gamma rays are ionising rays in that they have the capability to generate
secondary electrons, by removing outer shell electrons from atoms, thus
creating a positive ion.
•• Co-60 is produced in nuclear reactors by adding a neutron to the naturally
occurring isotope Co-59.
•• The advantage of Co-60 is its relatively high radioactivity for a small volume
(specific activity), ruggedness, reliability and output stability.
•• The disadvantages are that the radiation is always ‘on’ unlike Linear
Accelerators (LINAC), the half-life is relatively short and the sources need
to be reloaded.
•• There are two basic principles in radiosurgery:
–– Conformity: This implies that the isodose at which the radiation is
prescribed (prescription isodose) should hug the margin of the tumour
target as closely as possible. Conformity is achieved in GK by using
multiple isocentres (“shots”), changing the position of the isocentres,
adjusting the beam diameter (by using 4, 8, 14 and 18 mm collimators),
adjusting the weight of the beams (which determines the time spent by
the patient within the gantry) and finally by beam blocking (by plugging
specific pores with the collimator helmet).
–– Selectivity: This implies precise targeting of the lesion with a rapid
dose fall-off, thus avoiding radiation damage to adjacent normal tissue.
This is influenced by the size of the collimator, the beam penumbra
(distance between the 80% and 20% isodose lines), mechanical stabil-
ity of the treating machine and the number of radiation fields. Multiple
shots with small sized collimators is likely to improve the selectivity of
a given radiation dose plan.
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Dose-Volume Histogram
•• These measurements can be used to compare and contrast multiple dose
plans by indicating the radiation doses received by a specific volume of
target tissue at a particular isodose.
•• Most users target 90–100% of the lesion at the 50% isodose line.
RADIOBIOLOGY
•• GKS is better classified as a form of stereotactic radiosurgery (SRS), which
has been defined as the precise destruction of a chosen target containing
healthy and/or pathological cells, without significant concomitant or late
radiation damage to adjacent tissues.
•• SRS involves the delivery of high dose single fractions of radiation,
as opposed to multiple smaller doses (fractionation) in stereotactic
radiotherapy (SRT), which is used to treat larger volumes.
•• SRS is by necessity highly accurate and the system has an inherently steep
dose fall-off (selectivity), which enables the precise and focused delivery
of a single fraction of high dose radiation.
•• GKS has been performed mostly for benign tumours. As these patients
generally have normal survival and rarely require salvage surgery, little
tissue is available to study its in vivo effects.
•• GKS in AVMs seems to cause a proliferative vasculopathy and endothelial
cell injury, leading to vessel wall thickening, hyalinisation and luminal
closure.
•• Activated myofibroblasts too may add to the obliteration of AVMs.
•• In the standard recommended doses, GKS does not seem to affect normal
brain vessels, not even tiny perforators. Perhaps it is only abnormal angio-
genesis that may be selectively affected by high dose single fraction GKS.
•• Gamma radiation changes may be characterised as:
–– Acute: This entails sharply demarcated parenchymal coagulative
necrosis with apoptosis and an acute inflammatory reaction. Blood
vessels show endothelial destruction and fibrinoid changes in the walls.
–– Subacute: In this stage, macrophages replace polymorphonuclear
cells. Granulation tissue and reactive gliosis sets in as does prolifera-
tive vasculopathy with luminal narrowing.
–– Chronic: Necrosis is replaced by scar tissue, lymphocytic infiltrates,
hyaline change and calcification. Sub-endothelial cell proliferation
is seen in vessel walls with hyalinisation and subtotal/total luminal
obliteration.
DOSE SELECTION
•• The dose to be administered depends on the actual or anticipated
histopathology based on the imaging, the proximity and radiation safety
tolerance limits of adjoining normal structures and the anticipated lifespan
of the patient.
•• It is useful to consult risk prediction curves, especially in AVMs, to balance
the therapeutic advantage of dose escalation versus the risk of developing
an adverse radiation reaction.
•• GKS uses marginal doses between 12 and 25 Gy for the most benign and
malignant tumours prescribed at the 50% isodose. Maximum doses up to
90 Gy have been used to treat trigeminal neuralgia (TGN).
Chapter 188 • Gamma Knife Radiosurgery
1393
Table 1: Commonly recommended dose prescriptions

Diagnosis Prescription dose (Gy) at the 50% isodose
AVM 20−25 Gy
AVF 20−25 Gy
Acoustic Neuroma 12−14 Gy
Meningioma 12−14 Gy
Pituitary adenoma 12 Gy
Functional pituitary 25−35 Gy
Craniopharyngioma 12−14 Gy
Neurofibroma 12−14 Gy
Metastasis 20−25 Gy
Glomus jugulare 16−25 Gy
Malignant glioma 20−25 Gy
Haemangioblastoma 20−25 Gy
Trigeminal neuralgia 70−90 Gy
Cavernoma 14−20 Gy
Table 2: Radiation tolerance limits

Critical structure Radiation tolerance limit (Gy)
Brainstem 12 Gy
Visual pathways 8−10 Gy
Cranial nerves 8−12 Gy
Eye lens < 1.5 Gy
•• The following tables indicate standard prescription doses to the margin

of the lesion and the radiation safety tolerance limit of crucial adjoining
structures (Tables 1 and 2).
PROCEDURE
Basic Principles
•• Prior to beginning GKRS, the patient’s head is immobilised in a frame
which has posts and screws which provide secure skeletal fixation and
rigid immobilisation.
•• The frame also houses a marker box with columns for copper sulphate
solution which can be picked up on axial MRI images as round fiducials
in each cut.
•• These fiducials are used to define the images in proprietary software and
transpose CT/MRI co-ordinates into Cartesian co-ordinates, based on the
gradations present on the Leksell frame.
•• Combined with the rate of radiation available for that day as per the half-life
and days since installation of the Cobalt source, the software calculates the
time duration for which radiation therapy will be given at each isocentre.
1394
•• The software also gives the isocentre (x, y and z) co-ordinates for each
shot and the patient’s head and frame are positioned in such a manner, as
to place the tumour in the centre of a secondary collimator with a pore size
varying between 4, 8, 14 and 18 mm, which further focuses the gamma
rays onto the exact centre of the target for the particular shot.
Specific Steps
•• Frame fixation.
•• Imaging:
–– MRI with contrast is best used for evaluating brain tumours. Routine
T1- and T2-weighted (T1WI and T2WI) sequences are run in thin 2 mm
contiguous sections, either in the axial and/or coronal planes through
the region of interest.
–– Fat saturation may be added for base of skull lesions and in post-op-
erative patients with pituitary adenomas with nasal packing performed
at the time of surgery.
–– T2WI may be of superior benefit in treating patients with AVMs.
–– Heavily T2-weighted images are of benefit (CISS) in visualising the
trigeminal nerve for the treatment of neuralgic pain.
–– CT scans can be acquired at 1 mm intervals and thus may halve the
error of image acquisition.
–– Angiograms are performed with simultaneous vertebral and carotid
injections and images acquired in the anteroposterior and lateral pro-
jections in the capillary phase.
•• Cross-Registration:
–– MRI and/or CT images are then defined by the software after feeding
them into the computer by scanning, through a PACS/Ethernet system
or via a CD/DVD.
–– Fiducials are recognised as is orientation and images are accepted
only after the error is within permissible limits.
–– The software generates its own coronal and sagittal reconstructions
based on the axial imaging.
–– The shape of the skull is also generated based on manual depth read-
ings, provided by a bubble placed on the patient’s frame.
•• Planning:
–– Images are viewed on a convenient workspace on the computer and
the target is defined using a marker function.
–– Adjoining vital structures such as the optic pathway and the brainstem
too are delineated (segmented).
–– Multiple isocentres are then placed to encompass at least 90% of the
tumour with minimal spillage onto normal structures.
–– The dose is finally prescribed in consultation with the radiation oncolo-
gist based on proximity to adjoining vital structures and the actual or
anticipated histopathology.
•• Manual/Automatic Positioning:
–– The older GKS platforms use mandatory manual changing of secondary
collimators and the patient’s head position while partial and complete ro-
boticisation is a feature of the 4C and Perfexion™ systems, respectively.
–– This is as crucial as planning because the sub-millimetric accuracy of
the software can easily be negated by a manual error in reading the
Vernier caliper scale used to fix the frame in the x, y and z axes.
Chapter 188 • Gamma Knife Radiosurgery
1395
ADVANTAGES OF
GAMMA KNIFE RADIOSURGERY
•• Gamma Knife is superior to conventional surgery in that it has the accuracy
of a knife, especially when conventional surgery may be risky or lesions
may be considered inoperable.
•• is extremely precise as it is guided by thin slice stereotactic MRI and CT
scans.
•• The mechanical precision of the unit has been estimated at between
0.25 mm and 0.3 mm.
•• It is safe as the radiation fall off is steep and the exposure of normal brain
is minimised.
Current Uses
•• GKS is used in a variety of benign lesions such as pituitary adenomas,
acoustic neuromas, meningiomas, schwannomas, haemangioblastomas,
chordomas, glomus jugulare (GJ), posterior third ventricular tumours, pilo-
cytic astrocytomas, gangliogliomas and craniopharyngiomas.
•• Malignant lesions, such as haemangiopericytomas, malignant gliomas,
endolymphatic sac tumours and metastases, may also benefit because of
the excellent local control that may be provided by GKS.
•• AVM therapy has possibly been the most significantly revolutionised by
the introduction of GKS. Three-year obliteration rates may approach 90%
with minimal side effects.
•• AVMs remain the primary indication for GKS followed by schwannomas.
•• Standard limitations for administering GKS are:
–– Tumour diameter exceeding 3 cm.
–– Tumour volume greater than 19 cc.
•• These limits are only indicative and depend largely on the proximity of
critical neural structures such as the optic pathways and the brainstem.
Functional Disorders
Trigeminal Neuralgia (TGN)
•• TGN was one of the first indications for GKS. However, microvascular
decompression provides more effective pain control over longer periods of time.
•• GKS should be reserved for patients who are not optimal surgical
candidates and have TGN refractory to medical treatment.
•• It is the procedure of choice for patients with TGN secondary to multiple
sclerosis.
Movement Disorders and Epilepsy Surgery
•• Although SRS is the only non-invasive form of treatment for functional
disorders, these contribute only a small percentage of treated patients.
•• The drawbacks in using GKS is that only anatomical targeting is possible,
this is an ablative procedure and very high doses (up to 150 Gy) are utilised,
making shielding of adjacent neural structures impossible.
•• A promising new application of GKS is the delivery of a high-dose of 160
Gy to the pituitary stalk, using an 8 mm or two 4 mm collimators in patients
with intractable pain related to bone metastasis.
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COMPLICATIONS AND SIDE EFFECTS

•• Acute complications like post Gamma Knief headache.
•• Radiation myelitis:
–– Cyst formation
–– Hydrocephalus
–– Second malignancy.
PLATFORMS DELIVERING
Leksell Gamma Knife™
•• The Leksell Gamma Knife™ (Elekta instruments AB, Stockholm, Sweden)
has patented most of the widely used GKS platforms using either 201
(models B and C) or 180 (Perfexion) Co-60 radiation sources.
•• Most available research in GKS emanates from this technology. These
platforms remain some of the most expensive single pieces of medical
equipment that a hospital could invest in.
Rotating Gamma System

•• A more recent entrant in this field is a rotating gamma system (RGS)
developed by OUR International Inc. Shenzen, China.
•• This uses 30 Co-60 sources contained in a revolving hemispherical shell with
six groups of five collimator holes, which provide varying radiation beams.
•• The advantages lie in that helmets need not be changed manually and the
chances of collisions are low.
LINAC Based Radiosurgery

•• Great interest has recently been focused on the Cyberknife® (Accuray Inc.
Sunnyvale, California, USA) which utilises a 6 MeV linear accelerator (LINAC)
attached to a robotic manipulator which is mobile in six different axes.
•• The robot guides the LINAC which aims the beam at the target.
•• Unlike GKS, a rigid stereotactic frame is not used, target localisation is
achieved by a mask or by fiducials.
•• Two orthogonal X-ray cameras and an optical tracking system are used to
track the patient’s movements.
•• An integrated X-ray image processing system then compares the actual
real time images with those acquired previously and stored in a database
to determine the shift. This information is then conveyed to the robot which
makes the necessary corrections before radiation delivery.
•• The accuracy of this system is 0.7 mm.
•• CT is the primary modality of imaging.
•• Treatment is often over multiple days and can be fractionated.
•• The advantage lies in that this system can be used to target extracranial
targets too.
Charged Particle Radiosurgery

•• Proton beam radiation using either the Bragg-peak to make these charged
particles stop within the target or the plateau-beam to deposit particle
energy remains, theoretically, the most attractive option of delivering
intracranial radiation, as spillage is minimal due to a sharp dose fall-off as
the charged particle rapidly loses energy.
189
CHAPTER
Psychosurgery
Ramamurthi B • V Balasubramaniam
• Ravi Ramamurthi • Santosh Mohan Rao K
•• The WHO defines psychosurgery as; “the selective surgical removal or

destruction of nerve pathways for the purpose of influencing behaviour”.
•• Another definition of psychosurgery is as follows: “Any surgical procedure
that attempts to alter, through manipulation of neural tissue a thought or
thought process that is associated with a psychiatric disorder categorised
in DSM-IV and that is not caused by any known structural lesion”.
•• Surgical procedures on the brain to control restless or aggressive behaviour
have been included under the term sedative neurosurgery.
LIMBIC SYSTEM ANATOMY—NEWER

PERSPECTIVES
•• The earliest concept of networking was provided by Professor Niewenhuys
in 1936 when he considered the Limbic System (LS) to be comprised of
five concentric C-shaped circuits which were as follows:
–– Stria medullaris thalami, habenular nuclei and habenulointerpedun-
cular tract.
–– Amygdalae and stria terminalis.
–– Fimbriae and fornix.
–– Hippocampus with extension over the corpus callosum and the septal
nuclei.
–– Parahippocampal gyrus and cingulum.
•• Another classification is the division of the limbic system into limbic areas
comprising the amygdala, parahippocampal gyrus, hippocampus, septum,
hypothalamus, limbic thalamus, insula and paralimbic areas comprising the
anterior temporal pole and the orbitofrontal cortex.
•• Papez suggested a circuit for human emotion which was as follows:
Cingulate gyrus → Hippocampus → Fornix → Mammillary bodies
(Hypothalamus) → Anterior thalamic nuclei → Cingulate gyrus.
•• Goldenberg in suggested three limbic sub-circuits:
–– Medial limbic circuit: This is the classical Papez circuit.
–– Basolateral circuit: Orbitofrontal cortex and anterior temporal cortex →
amygdala → magnocellular DM nucleus of thalamus (fronto-thalamic
fibres).
–– Defence reaction circuit: Comprising the hypothalamus, stria terminalis
and amygdala.
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Concept of Thalamocortical Dysrhythmias

•• These are a group of disorders characterised by localised and protracted
low frequency spontaneous recurrent activity of the thalamocortical system
and this underlies certain chronic psychotic, affective and anxiety disorders,
including obsessive compulsive disorders (OCD).
•• The re-establishment of normal oscillation could be achieved with
anteromedial pallidal and centrolateral thalamic lesions.
•• The features of thalamocortical dysrhythmias (TCD) are as follows:
–– Hyperpolarisation through disfacilitation and/or over-inhibition of tha-
lamic relay and/or reticular cells by the disease source.
–– Psychosis is therefore attributed to corticothalamic disfacilitation and a
striatal anomaly providing thalamic over-inhibition. Chronic dysfunction
of the cognitive network triggers neurotic disorders.
•• Hyperpolarised state is due to a source of calcium T channel de-inactivation,
causing production of low threshold Ca2+ spike (LTS) bursts by thalamic
or reticular neurons.
•• The targets selected by researchers of TCD are:
–– Centrolateral nucleus of the thalamus
–– Anteromedial paralimbic thalamic nucleus
•• The above targets employed in patients with psychotic hallucinations/
delusions, OCD, major depression, BPD, anxiety states and impulse control
disorders (ICDs) and had good results.
Amygdala
Structure of the Amygdala
•• Broadly speaking, the amygdala can be divided into the basolateral (which
is non-olfactory) and corticomedial (which is olfactory) parts.
•• The basolateral part is further divided into a basal and a lateral nucleus;
similarly the corticomedial is divided into a medial and a cortical part. The
main sub-divisions have different afferent and efferent connections.
Connections of the Amygdala
•• The connections of the amygdala are to the temporal lobe, the
hypothalamus, the thalamus and the frontal lobe. All these connections
are predominantly unidirectional circuits.
•• The important fasciculi of the amygdala are as follows:
–– Amygdalo-temporal connections.
–– The Amygdalo-hypothalamic pathways
–– The Amygdalo-thalamic bundle
–– The uncinate fasciculus
–– The olfactory connections of the amygdale: They are practically con-
fined to the corticomedial group of nuclei. The olfactory tract divides
into three bands:
1. The intermediate fibres end in the anterior perforated substance,
which is encircled by the lateral and medial bands.
2. The medial tract passes deep to the cortex and ends in the region
of the subcallosal gyrus.
3. The lateral goes to the corticomedial group.
Chapter 189 • Psychosurgery
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Nucleus Accumbens
•• The nucleus accumbens is an enigma that has long been thought to be one
of the main crossroads between the limbic (hippocampus and amygdala)
and the motor systems, the focal point of an expression of motivational and
emotional processes into motor behaviour.
•• The shell of the nucleus accumbens is in reality a transition zone between
the amygdala and the striatum.
•• The ventral tegmental area (VTA) has a modulatory effect on this limbic-
motor interface.
•• Derangements of this meso-limbic dopamine system at the level of the
nucleus accumbens has been implicated in specific aspects of drug
addiction, schizophrenia and other affective disorders.
HYPOTHALAMUS
•• Two important fibre tracts course through the hypothalamus:
1. The median forebrain bundle connecting the various areas of the limbic
system and the mesencephalon.
2. The fornix, an efferent pathway from the hippocampus to the mamillary
body, consisting of many fibres to the hypothalamic nuclei.
•• The afferent connections of the hypothalamus are:
–– The amygdala-hypothalamic pathways that have already been de-
scribed
–– Fronto-hypothalamic fibres and
–– Fibres from the ventral anterior nucleus of the thalamus to the hypo-
thalamus.
•• The efferent connections are many, the more prominent one being
the dorsal longitudinal fasciculus of Schultz. This runs from the medial
hypothalamic zone up to beyond the mesencephalic tegmentum.
Physiology
•• For the purposes of behavioural physiology, the hypothalamus can be
divided into two zones: the medial-ergotrophic and the lateral-trophotrophic
zone.
•• Most of the amygdaloid connections end in the medially situated ergotrophic
zone. Stimulation of this zone (particularly near the periforniceal nucleus)
produces sham rage.
•• If one compares the behavioural brain to the motor system, one can
distinguish an upper level and a lower level.
•• The upper level is represented by the amygdaloid nucleus and its
connections with the limbic system and the thalamus. The amygdala acts
as the higher centre by receiving inputs from various regions and levels,
like the viscera, the endocrine organs and from the hippocampus.
•• The lower level is represented by the hypothalamus and the periaqueductal
grey, which are the common efferent pathways for all behavioural impulses
akin to the final common pathway in the anterior horn cells for motor
phenomena.
•• The internal medullary lamina helps to reinforce the amygdalo-hypothalamic
influences and can be considered as a reinforcing centre like the cerebellum
in the motor system, if one might extend the analogy.
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CLASSIFICATION OF
PSYCHIATRIC DISORDERS
•• Most mental disorders are categorised into mild, moderate, severe, in partial
remission, in full remission and as past history of mental illness.
•• There are five axes in DSM-IV TR namely:
–– Axis I: That comprises clinical disorders and other conditions that may
be a focus of clinical attention
–– Axis II: Personality disorders, mental retardation
–– Axis III: General medical conditions
–– Axis IV: Psychosocial and environmental problems
–– Axis V: Global assessment of function
•• Personality disorders are classified into three clusters:
–– Cluster A: Which comprises paranoid, schizoid and schizotypal dis-
orders.
–– Cluster B: Under which come antisocial, borderline, histrionic and
narcissistic personality disorders.
–– Cluster C: Which includes avoidant, dependent, obsessive disorders
and personality disorders not otherwise specified.
Obsessive Compulsive Disorder (OCD)

•• It afflicts about 2–3% of the general population.
•• It starts in childhood/adolescence and is characterised by recurrent
thoughts, images, feelings or behaviours that persist after the patient’s
attempts to eliminate them and which are accompanied by marked and
often overwhelming anxiety.
•• The mainstay of treatment is selective serotonin re-uptake inhibitors (SSRIs)
with clomipramine as a 2nd line drug.
•• The main side effects of these medications are weight gain, sexual
dysfunction and sedation.
•• Tardive dyskinesias and dystonias can also occur.
•• Ten per cent of all cases of OCD are refractory to all medical/behaviour
therapies.
•• It is in this subgroup of patients that psychosurgery has a role to play.
Neuropathologic Circuitry
•• In OCD, the circuitry involved is the cortico-striato-thalamocortical circuitry
(CSTC).
•• The orbitofrontal cortex, anterior cingulated cortex and the caudate nucleus
are central to the pathogenesis of OCD.
•• The relative imbalance favouring the direct versus the indirect paths within
this circuitry, leads to overactivity, i.e. amplification within the orbitofrontal
cortex and the anterior cingulated cortex including the caudate nucleus
and thalamus resonant with failed striato-thalamic inhibition, i.e. filtration
within this same circuitry.
•• Intractable OCD which comprises 10% of all OCD cases is defined as:
–– Failure of treatment despite maximum doses of 5 or more than 5 SSRI
for 10 weeks with augmented doses of buspirone hydrochloride and
lithium carbonate.
–– Yale-Brown obsessive compulsive score more than 20.
–– Global assessment of function score (GAF) less than 50.
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Depression
•• Major Depression (MD) is characterised by apathy, anhedonia, appetite and
weight disturbances, sleep disruptions, psychomotor abnormalities, fatigue,
guilt, suicidal ideas and behaviour, delirium, hallucinations and catatonia.
•• It affects 2.6–5.5% of males and 6–11.8% of females.
•• The circuitry involved in major depression is as follows:
–– Dorsal component: Anterior, dorsal and lateral prefrontal cortex, dorsal
anterior cingulated cortex, parietal cortex and pre-motor cortex (Cogni-
tive circuit).
–– Ventral component: Paralimbic cortex, subgenual anterior cingulated
cortex, orbitofrontal cortex, anterior insular cortex (Affective circuit).
–– The hypothalamic-pituitary-adrenal pathways are also associated with
behaviour.
•• Major depression, therefore, is due to hypoactivity of the dorsal circuit and
hyperactivity of the ventral circuit.
IMAGING IN PSYCHIATRY
•• MRI, fMRI, SPECT and PET are the main modalities of imaging in
neuropsychiatry.
•• MRI is able to detect subtle volumetric abnormalities in the striatum in
OCD.
•• Decreased caudate nucleus volume is also reported in OCD.
•• MRS showed a decrease in striatal NAA but normal NAA in the lenticulum
in OCD.
•• fMRI in post-traumatic stress shows stimulation of the anterior cingulate
cortex and other anterior paralimbic regions.
•• In symptomatic OCD, there is recruitment of the caudate nucleus and the
anterolateral orbitofrontal cortex.
•• Increased activity in the orbitofrontal cortex suggests a better treatment
response to behaviour therapy versus pharmacotherapy (and also predicts
the usefulness of SSRI therapy) in OCD.
•• The SPECT studies in OCD are as follows: There is increased perfusion
in the anterior cingulate gyrus, left basal nuclei and orbitofrontal cortex.
A decrease in rCBF in the above structures results in symptomatic
improvement.
•• MRI studies in depression are done by cortical parcellation methods.
•• In depression, decreased volume of the subgenual cortex and the
orbitofrontal cortex are noted.

•• There are no universal guidelines for surgery of these disorders.
•• The criteria are as follows:
–– The patient must fulfil the DSM IV or WHO criteria for OCD/major af-
fective criteria/anxiety.
–– The duration of the illness must be 5 or more than 5 years duration and
has been documented to be refractory to all therapy available.
–– The disease must be shown to cause substantial suffering and signifi-
cant impairment to the patient’s psychosocial functions.
–– Prognosis without relief of symptoms is shown to be very poor.
–– The patients and the family must be willing to participate in pre-
operative evaluation and long-term post-operative rehabilitation.
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–– The referring physician must demonstrate a commitment to pre-

operative and long-term post-operative care of the patient.
•• The contraindications are as follows:
–– Age less than 18 years or more than 65 years.
–– Concurrent complicating DSM IV-Axis I disorders (organic brain syn-
dromes/substance abuse).
–– Complicating Axis II cluster A or B disorders (personality disorders).
–– Complicating Axis III disorders (brain tumour, atrophy).
–– Medical conditions which would increase the risk of surgical/imaging
complications.
PROCEDURES USED IN MODERN

PSYCHOSURGERY
•• Modern psychosurgery has seven standard procedures in its armamentarium
to help combat mental illness. (Deep brain stimulation has been approved
by the FDA for obsessive compulsive disorder, depression, major epilepsy
and Parkinson’s disease).
•• They are:
–– Cingulotomy
–– Subcaudate tractotomy
–– Anterior capsulotomy
–– Limbic leucotomy
–– Amygdalotomy
–– Hypothalamotomy
–– Thalamotomy.
Cingulotomy
•• The goal of cingulotomy is to cut the anterior supracallosal fibres of the
cingulate gyrus and interrupt a major component in the medial limbic circuit.
•• Indications for Cingulotomy:
–– Unipolar disorder
–– Depressive component of bipolar disorder
–– OCD
–– Generalised anxiety disorder
–– Chronic pain syndrome
–– Drug addiction.
•• It has been advocated even for aggressive behaviour.
•• It was found that after cingulumotomy for painful conditions, it was possible
to withdraw the pain killing drugs without serious side effects.
Anatomical Considerations
•• The cingulum bundle runs anteroposteriorly in the cingulate gyrus, forms
an essential part of the Papez circuit and is a major integrating force in
the limbic system.
•• It contains fibres that run from the frontal lobes to the hippocampus and
also has connections to the anterior and dorsomedial nuclei of the thalamus
and the hypothalamus.
•• As the hypothalamic connections are the pathways through which the
autonomic disturbances are mediated, the lesion must be made at the
point where these fibres join the cingulum (i.e. in the plane of the foramen
of Monro).
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Subcaudate Tractotomy
•• The aim of the procedure is to lesion the substantia innominata of Reichert
in the area inferior to the caudate nucleus head, whereby white matter tracts
between the orbitofrontal cortex and the subcortical structures (thalamus,
hypothalamus, amygdala) are interrupted.
•• This disrupts the basolateral circuit and cortico-striato-thalamic pathways.
•• In this area, the diagonal band of Broca, anterior commissure and medial
forebrain bundle traverse with cholinergic inputs from the entorhinal cortex,
pyriform cortex and hypothalamus.
•• Secondary degeneration of the dorsomedial nucleus of the thalamus
occurs.
•• The connections in this area generate endocrine, autonomic and somato-
motor responses to emotional and motivational states, leading to increasing
primary sensory stimuli.
•• Indications:
–– Major depression (most common indication).
–– Chronic pain.
–– OCD (2nd most common indication).
–– Anxiety.
–– Bipolar disorder.
•• The target co-ordinates for stereotactic tractotomy using an MRI based
system are as follows: Three lesions are made of about 8 mm diameter
each bilaterally in the same coronal plane, 15 mm anterior to the base of
the anterior clinoid process.
–– 1st lesion: 6 mm lateral to the midline and 10 mm superior to the floor
of the anterior cranial fossa.
–– 2nd lesion: 6 mm lateral to the midline and 15 mm superior to the floor
of the anterior cranial fossa.
–– 3rd lesion: 14 mm lateral to midline and 10 mm superior to the anterior
fossa.
•• The complications are: Headache, confusion, transient disinhibition and
somnolence for about a week.
Anterior Capsulotomy
•• The rationale behind anterior capsulotomy is as follows: By lesioning the
anterior limb of the internal capsule, anterior capsulotomy interrupts the
connections between the orbitofrontal cortex and the midline thalamic
nuclei, thus disrupting part of the basolateral limbic circuit and cortico-
striato-thalamic pathways.
•• Electrical stimulation of the anterior limb of the internal capsule results in
a generalised sense of well-being with decreased anxiety and tension.
•• Extrapyramidal responses, like tremors in the contralateral limbs, also
occur.
•• Disruption of the pathological CSTC circuitry at the level of the orbitofrontal
cortex-caudate nucleus/reciprocal orbitofrontal corticothalamic connections
underlies the therapeutic effects of anterior capsulotomy.
•• The target co-ordinates for anterior capsulotomy are as follows: The target
height is 20 mm that spans the anterior limb of the internal capsule bilaterally.
•• Radiofrequency probes are used for lesioning at 80–85°C for 45 secs.
•• The inferior target is 2–4 cm lateral to the anterior tip of the lateral ventricle
and the superior target is 1 cm superior to the inferior target site.
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•• The target used by Lars Leksell for his capsulotomy was as follows: Anterior
1/3rd of the anterior limb of the internal capsule, 5 cm behind the frontal
horn tip and 20 mm lateral to the midline at the intercommissural plane.
•• The technique used routinely involved the use of thermocoagulation and
was also called thermocapsulotomy, in contrast to Leksell’s Gamma Knife
capsulotomy.
•• Transient deterioration in mental status was seen more in the patients
undergoing capsulotomy, compared with those who underwent
cingulumotomy.
•• Other rare but longer lasting complications include haematomas, nocturnal
incontinence, mild frontal syndrome, aggressiveness, memory deficits and
weight gain.
•• “Slovenliness” has been described after capsulotomy.
•• Gamma Knife capsulotomy results are as good as conventional stereotactic
capsulotomy.
Limbic Leucotomy
•• This procedure combines anterior cingulumotomy and subcaudate
tractotomy, although the lesions for subcaudate tractotomy are more
anteriorly placed.
•• Long-term side effects, although rare, are transient like headache,
confusion, lethargy, sphincter disturbances and perseveration.
Dorsomedian Thalamotomy
•• The aim and effectiveness of leucotomy lies in the division of the fronto-
thalamic and hypothalamic connections.
Amygdalotomy
Aetiology of Behaviour Disturbance
•• A disturbance of the delicate balance between various neuronal circuits
in the hypothalamo-limbic system results in abnormal behaviour patterns.
While such disturbances may occur temporarily from injury, drugs, toxins,
etc. more lasting trouble results from epileptic disorders and encephalitis.
•• Post-epileptic behavioural disorders may occur in a patient who has a long
history of tonic-clonic seizures.
•• Post-encephalitic behavioural disorders may follow immediately or some
months after an attack of encephalitis.
•• The other aetiological factors include trauma, meningitis, vascular disorders
and schizophrenia. In these cases the behaviour disorder occurs without
epilepsy.
Selection of Cases
•• Surgery is indicated when adequate drugs or psychiatric therapy have not
helped, even after a prolonged trial.
•• When all conservative measures have failed, surgery is advised.
•• Once surgical therapy has been decided upon, it is better to do it early
to give relief to the patients as well as to the long-suffering parents and
family members.
Selection of Targets
•• Amygdalotomy or hypothalamotomy is effective in aggressive, violent
behaviour, in low rage threshold and self-mutilation.
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•• Restlessness or hyperkinesis sans violence is difficult to treat. In these

cases thalamolaminotomy combined with amygdalotomy gives better
results than either of these procedures alone.
•• In amygdalotomy, the lesion usually involves the entire nucleus, although
the part directly concerned with behaviour is the basolateral part.
Unilateral or Bilateral Operations
•• Unilateral amygdalotomy or hypothalamotomy may be done if the
behavioural disturbances are of moderate severity but most cases require
bilateral amygdalotomy or hypothalamotomy.
•• Operations for behavioural (or emotional) disorders have generally to be
done on both sides, since there is no laterality demonstrable in emotion
or behaviour.
•• One condition in which a strictly unilateral procedure (either amygdalotomy
or hypothalamotomy) gives good relief is the behaviour disorder associated
with infantile hemiplegia. These patients, who were once candidates
for hemispherectomy, are considerably benefited by unilateral sedative
neurosurgery.
One-stage or Two-stages
•• Bilateral amygdalotomy may be done in two successive stages.
•• Bilateral one-stage amygdalotomy can be done safely and is not
accompanied by extra deficits attributable solely to the bilaterality of the
procedure.
•• Bilateral hypothalamotomy is done only in successive stages.
Amygdala First or Hypothalamus First
•• The amygdala is considered to be the ‘higher’ centre.
•• Bilateral amygdalotomy is a one stage operation, whereas hypothalamotomy
has to be done in two stages.
•• Eliminating the amygdala is perhaps more logical, as in many cases of
behaviour disorders there is likely to be a defect in the amygdala.
•• In patients in whom bilateral amygdalotomy does not succeed,
hypothalamotomy is performed.
•• Hypothalamotomy done after amygdalotomy has been termed secondary
hypothalamotomy and in such cases, unilateral lesions in the hypothalamus
are usually effective.
•• In severely retarded violent children, it is preferable to perform
hypothalamotomy as the first procedure (primary hypothalamotomy).
•• The following are the types of abnormal behaviour patterns amenable to
amygdalotomy and hypothalamotomy:
–– Hyperkinesis (restlessness and wandering tendency)
–– Destructive and violent tendencies:
–– Pyromania
–– Self-destruction.
OUTCOME MEASUREMENTS IN
PSYCHOSURGERY
•• There are several disease specific scores such as Yale-Brown Obsessive
Compulsive score (Y-BOCS) for OCD, Hamilton depression rating (HA-
DRS) and the Beck depression inventory (BDI) for depression and the
Hamilton Anxiety Rating Scale (HA-ARS) for anxiety.
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•• Other tests used in neuropsychological evaluation of the patient are—the

Wechsler Adult Intelligence score and its Korean modification (WAIS and
K-WAIS), Hopkin’s Verbal Language Test (HVLT), Rry-Osterrieth complex
figure test, Wisconsin Card Sorting Test, Stroop test, tests of verbal imaging,
Mini Mental State Examination (Folstein’s and the Korean versions), etc.
•• The pre-operative and post-operative assessment of behavioural disorders
is based on clinical impression in most cases. The results may be graded
under the following five categories:
1. There is no need for drugs. The patient is able to mingle easily with
others.
2. Very much docile and given only to occasional outbursts.
3. Manageable when given drugs, although not leading a useful life.
4. Transient improvement followed by relapse.
5. No change.
NEWER MODALITIES OF TREATMENT IN

PSYCHOSURGERY
Vagal Nerve Stimulation (VNS)
•• The vagal nerve nucleus (nucleus of the tractus solitarius) projects to the
limbic system, higher cortex, parabrachial nuclei and the locus coeruleus
which in turn project to the thalamus, amygdala, hypothalamus, insula and
orbitofrontal cortex.
•• VNS acts in two ways: It increases NTS GABA which in turn is responsible
for the anti-seizure activity. VNS also increases 5-HIAA, HVA and DA which
is responsible for the mood stabilising action of VNS.
•• Another interesting feature is that VNS seems to be effective only in the
long-term and this has been proven by blood oxygen level dependent MRI
(BOLD-MRI).
•• There have been several other applications for pulsed electrical signals.
These include: movement disorders, eating disorders (obesity), anxiety,
dementia, Alzheimer’s disease, chronic pain, migraine, cardiac arrest,
post-traumatic stress and bilateral diaphragmatic VNS for morbid obesity.
•• The battery life of a VNS unit is about 8–10 years.
•• Another very important feature of VNS is that whole body MRI is
contradicted in patients with VNS.
Transcranial Magnetic Stimulation (TMS)

•• Transcranial Magnetic Stimulation (TMS) is a non-invasive method of
cortical stimulation by creating a powerful transient magnetic field.
•• The principle behind TMS involves the use of a powerful handheld magnet
to create a time varying magnetic field, so that a localised pulsed magnetic
field over the head surface depolarises underlying superficial neurons.
•• High intensity current is rapidly turned on and off in an electromagnetic coil
through discharge of capacitors.
•• This generates brief but very powerful magnetic fields, which is different
from the ‘magnetic fields used in alternative therapy’.
•• TMS acts solely through production of electric currents in the cortex.
•• Repetitive and rhythmic TMS is called rTMS. If the frequency is more than
1 Hz, it is known as fast rTMS with current frequencies up to 25–30 Hz.
•• Increasing the frequency in TMS increases the seizure risk.
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•• The frequency of TMS is slow, compared with that of DBS (where

stimulation frequencies progress up to 150 Hz).
•• An important parameter to be defined in TMS is that of the motor threshold.
Motor threshold is defined as the minimal amount of electricity needed
to produce movement in the contralateral thumb, when the coil is placed
optimally over the primary motor cortex. This can be determined either by
an observer or by EMG.
•• Paired pulsed TMS has immediate effect within seconds. It comprises of
applying two TMS pulses to the same region with varying interpulse intervals
and intensities. This can be used to assess the stimulatory and inhibitory
systems of the brain at rest in individuals with different disorders.
•• Speech arrest can easily be accomplished by TMS and is due to a “virtual
lesion” in the speech centre.
•• The TMS safety table is calculated using a surrogate end point—for seizure;
it is the spread of TMS induced motor evoked potential (MEP) beyond
the target area of stimulation. This is applicable only to the motor cortex.
•• A past history of seizures puts one at an increased risk of seizures during
TMS.
•• TMS has been found to increase dopamine levels in the pre-frontal cortex.
It provides insights into the methods of drug action, e.g. lamotrigine was
found to augment the effects of TMS in the limbic region.
•• TMS has been found to be beneficial in the treatment of drug resistant
depression.
•• TMS is being evaluated as a therapy for writer’s cramp, Tourette’s syndrome
and OCD.
•• Schizophrenia with hallucinations and anxiety disorders may also be
amenable to TMS, although some reports suggest that prolonged TMS
aggravates the auditory symptoms of schizophrenia.
190
CHAPTER Neural Transplantation
and Stem Cell
PN Tandon
DEFINITIONS
Stem Cells
•• Stem are cells able to reproduce themselves throughout the life span of
the animal and are able to give rise to differentiated cells.
•• They have the ability to divide for indefinite periods in culture and give rise
to specialised cells.
Embryonal Stem Cells

•• Cells derived from embryo—pre-implantation or post-implantation—prior
to their differentiation into specific cell types.
Totipotent Cells
•• Cells which have the potential to differentiate into derivatives of all three
embryonic germ layers, i.e. ectoderm, mesoderm and endoderm. In
addition, they can also specialise into extraembryonic membranes and
tissues.
Pluripotent Cells
•• Cells which can give rise to different types of cells representing derivatives
of two different germ layers, e.g. skin (ectoderm) and muscle (mesoderm).
Neural Stem Cells

•• Cells which can generate neural tissue, either both neurons and glia
(astrocytes, oligodendrocytes) or one of them.
•• The term is also used for stem cells derived from embryonic or adult nervous
system, which normally differentiate into nervous tissue.
•• These cells remain undifferentiated for long periods of time while retaining
the potential to differentiate into nervous tissue.
Progenitor Cells
•• Cells with a more restricted potential than a stem cell and are generally
destined to give rise to a specific cell type.
•• Stem cells could deliver bioactive proteins or peptides to modify or
biomodulate the disease process.
•• At the opposite end of the spectrum, stem cells could generate exact
neuronal or glial cells lost in disease affected systems.
Chapter 190 • Neural Transplantation and Stem Cell
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•• Stem cells from different sources have unique attributes that will
differentially affect their suitability for use in therapeutic strategies.
SOURCES OF STEM CELLS

•• Human embryonic stem cells (hESCs), derived from the blastocyst inner
cell mass of excess embryos generated by in vitro fertilisation, can provide
an unlimited source of cells for transplantation and can be directed into
neural precursors which can generate neurons, oligodendrocytes and glia
both in culture and in vivo.
•• The ease with which hESCs can be expanded in culture as normal diploid
cells is a significant advantage over foetal and adult stem cells that require
immortalisation via mutation or proto-oncogene introduction, to escape
eventual senescence.
•• Cultured hESC grow very efficiently and maintain pluripotency, but the
potential risk of developing malignant transformation cannot be ruled out
in the current stage of knowledge.
•• Foetal neural stem cells harvested from the postmortem human foetal brain
maintain a normal karyotype for a significant number of passages in culture
and can produce a large number of neurons and astrocytes.
Adult Neural Stem Cells

•• It has been claimed that adult neural stem cells can be harvested from
brain tissue, postmortem or through biopsy and expanded in culture both
in rodents and humans.
•• These cells exhibit genetic stability over many passages and differentiate
into neurons, astrocytes and oligodendrocytes, under suitable culture
conditions.
Non-neural Adult Stem Cells

•• Bone-marrow derived stem cells (BHMSC) could develop into liver cells,
muscle, bone and neural tissue.
•• Recently there has been great excitement about the possibility of generating
neural progenitor cells from such diverse sources as mesenchymal cells
derived from skin, bone marrow, adipose tissue, foetal umbilical cord.
•• Recently, evidence has been presented that stem cells identified in organs
other than the haematopoietic system (HSC) and skin thought to be
responsible for the generation of mature differentiation cells of one organ,
such as HSC, may have the ability to differentiate across lineage and
contribute to tissues other than haematopoietic cells, including neuronal
tissue. Such apparent lineage switch has been termed stem cell plasticity.
Induced Pluripotent Stem Cells

•• The methods to re-program adult human cells from skin to a pluripotent
state, using genetic engineering techniques are called induced pluripotent
stem cells (iPS). These were found to be similar to human embryonic stem
(ES) cells in morphology, proliferation, surface antigens, gene expression,
epigenetic status of pluripotent cell-specific genes and telomerase activity.
•• Furthermore, these cells could differentiate into cell types of the three germ
layers. This technique could help generate patient and disease specific
cells, which cannot be generated from ES cells.
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•• Neuroepithelial cells produced from human ES cells using different

methods may appear similar in morphology and expression of certain
neural precursor markers.
•• Inspite of a large number of trials in laboratory animal models of various
diseases of the CNS and several clinical trials on patients with spinal cord
injury, stroke, parkinson’s disease etc, it is prudent to state that currently
there are no proven benefits established for stem cell therapy. However,
its potentials, following further research, should not be underestimated.
OTHER USES OF STEM CELLS

•• Human ES cell-generated neural cells provide a tool for screening
pharmaceuticals that may have therapeutic values in neurological disorders,
as also for toxicity screening and possibly drug discovery.
•• The availability of human ES cells with natural diseases, via somatic
nuclear transfer or through genetic alterations in laboratories, will provide
not only disease-specific neural cells for drug screening but also a tool
to unveil some fundamental pathological processes underlying individual
neurological disorders.
Section XIV: Pain
191
CHAPTER Pain: Anatomy and
Physiology
Ravi Ramamurthi • Santosh Mohan Rao K
DEFINITIONS OF PAIN
Anatomical and Physiological Considerations
•• The human sensory nervous system carries information from the external
and internal environment to the brain which is responsible for the ultimate
perception and appreciation of pain.
•• Particular areas of the CNS are especially involved in different facets of
sensation like appreciation, memories of sensations and their emotional
significance.
Peripheral Receptors
•• There are a variety of sensory receptors, usually known after the names
of those who initially described them, namely, Meissner, Ruffini, Merkel,
Krause, Pacini, Golgi, Mazzoni, etc.
•• The occurrence of hyperalgia at the site of the noxious stimuli and the
surrounding area has been attributed to the production of pain producing
chemicals from the injured tissue.
•• Tissue damage releases H+, K+, 5-HT, histamine, prostaglandins, bradykinin,
and substance-P and these cause pain.
•• Calcitonin gene related peptide (CGRP), vasoactive intestinal peptide (VIP)
and somatostatin are also released by C-fibre stimulation.
•• Prostaglandins potentiate the role of inflammation and pain and enhance the
effects of other inflammatory substances.
•• Corticosteroids, by blocking the formation of arachidonic acid (precursor
of prostaglandin) from membrane phospholipids, reduce pain and the
inflammatory response.
•• Aspirin and indomethacin relieve pain by inhibiting cyto-oxygenase, an
essential enzyme in the cycle of production of prostaglandins.
•• Substance P, present in the peripheral terminals of unmyelinated fibres,
has a role in the initiation of pain.
•• Capsaicin is used in the study of secondary hyperalgesia. It selectively
activates nociceptors and causes a large zone of hyperalgesia when
topically applied. Capsaicin hyperalgesia closely resembles thermal injury/
laceration.
•• There are four peripheral mechanisms of pain generation and transmission:
1. Tissue receptors
2. Generated potentials (voltage and ligand gated channels)
3. Membrane receptors (NMDA, AMPA, GABA, etc.)
4. Signal modulators (NMDA agonists, etc.).
Section XIV • Pain
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Sensory Nerve Fibres

•• Thirty per cent of autonomic nervous system (ANS) fibres in the ventral root
are unmyelinated. These ventral root fibres take two pathways: they either
turn back and enter via the dorsal root (DR) and the dorsal root ganglion
(DRG) or they continue through the ventral root and traverse the grey matter
and terminate in the superficial layers of the dorsal horn.
•• The sensory nerve fibres travel proximally in the peripheral nerves towards
the spinal cord, form the first relay in the bipolar cells of the dorsal root
ganglia and they enter the spinal cord in the posterior roots.
•• The cells in the dorsal root ganglia are of two types: large A cells and
small B cells.
•• The A cells give rise to large myelinated axons and the B cells to small (A
delta) myelinated axons and non-myelinated axons (C fibres).
•• The pain impulses travel in the small myelinated fibres (A delta) and in
non-myelinated fibres (C fibres).
•• Conduction in A delta and C fibres is blocked early during the injection of
local anaesthetics, whereas the bigger fibres get blocked early in ischaemia.
•• The conduction along A delta fibres leads to discrete localisation of the
pain, whereas C fibre stimulation leads to a diffuse and longer lasting
uncomfortable sensation resembling pain.
•• Sensory perception on the skin surface is not compartmental. There are
overlapping areas supplied by adjacent sensory nerves.
•• After surgical section of a single posterior root, the analgesic effects are
negligible.
Nociceptors
•• Pain sensitive fibres are called nociceptors.
•• There are two types of pain receptors namely, unimodal nociceptor
subserving only one sensation and polymodal nociceptor subserving
chemical, mechanical and thermal nociception.
•• A delta and C fibres comprise the various nociceptors.
Visceral Pain
•• Pain sensation from the viscera is generally more diffuse. This is due to the
high proportion of small C fibres in the visceral nerves and the existence
of extensive ramifications between the nerves.
•• In addition, afferent impulses from a given visceral area enter the central
nervous system via many DRs.
•• The visceral afferent fibres run in the autonomic nerves but are not a part of
the autonomic nervous system. This explains the value of sympathectomy
in some types of visceral pain and pain of vascular origin.
•• The convergence theory wherein somatic and visceral afferents converge
on the same spinothalamic neurons and the facilitation theory wherein
collateral connections for visceral afferents to dorsal horn neurons receiving
pain impulses from somatic stimulation facilitate pain have both been used
to explain referred pain which occurs in association with visceral pain.
ORGANISATION OF THE SPINAL CORD

•• The spinal grey matter has been organised into 10 laminae.
•• These were initially studied in the cat by Rexed.
Chapter 191 • Pain: Anatomy and Physiology
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•• Lamina I:
–– The grey matter is situated at the margin of the dorsal horn.
–– There is a marginal plexus which constitutes a horizontal group of
fibres.
–– Larger elements of this lamina constitute the marginal cells of Wal-
deyer which respond to mechanical or thermal nociceptive information
released secondary to tissue destruction and contributes elements to
the contralateral spinothalamic tract.
•• Lamina II (Substantia Gelatinosa of Rolando):
–– This exists throughout the spinal cord with a narrow outer zone and a
broader inner zone.
–– Afferents to the SGR come from the tract of Lissauer, posterior column
and adjacent parts of the lateral funiculus of the spinal cord.
–– Nociceptive special neuronal soma is in lamina I and in the outer
Lamina II. Innocuous mechanical stimuli are transmitted in the inner
zone of lamina II.
–– The SGR neurons project to Lissauer’s tract and fasciculus proprius.
–– Lamina II primarily serves to influence the neurons in the deeper lami-
nae and has a modulatory function.
–– Laminae I and II have a high concentration of substance P which is
synthesised in the DRG and then transported into the terminals of the
DR fibres.
–– Substance P stimulates nociceptive impulse transmission.
–– Both these regions have high concentration of opiate receptors. After
dorsal root rhizotomy, there is a significant decrease in the number of
opiate receptors in the de-afferenated spinal segments.
•• Laminae III-V:
–– The grey matter of laminae III and IV comprise the principal sensory
nucleus/nucleus proprius.
–– These are vertically oriented with larger neurons and dendrites which
arborise dorsally into laminae I and II.
–– Afferent input consists of myelinated axons.
–– The laminae are mostly comprised of interneurons and receive low
threshold mechanoreceptor input.
–– There are 2 types of projection neurons here namely, dorsal columns
and spinocerebellar tract.
–– Lamina IV has the thickest layer of large neurons external to lamina II.
–– Lamina V is a broad zone across the neck of the dorsal horn.
–– The output depends on the degree of convergence of large and small
fibre input—low threshold, wide dynamic range (WDR) or nociceptive
specialised neurons.
–– Hyperalgesia is primarily due to unmasking of low threshold inputs to
nociceptive neurons.
•• Laminae VI and VII:
–– Lamina VI is across the base of the dorsal horn and in the cervical and
lumbar region.
–– It has group I muscle afferents to the medial lamina VI terminating in
the lateral zone.
–– Lamina VII (zona intermedia) is situated between the anterior and
posterior horns.
–– The size and the boundaries of the laminae vary according to the level
of the spinal cord. They have well defined cell groups, including the
dorsal nucleus of Clarke (nucleus thoracicus).
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–– Lamina VII also serves as the origin for the uncrossed dorsal spi-
nocerebellar tract and intermediolateral and intermediomedial nuclei
and tract.
•• Laminae VIII-X:
–– These occupy the ventral horn of the grey matter. They also contribute
to the gamma efferents to the muscle spindle.
–– Lamina X is around the central canal and processes nociceptive input
from visceral afferents and spinothalamic projection neurons.
A brief synopsis of the above is as follows:
•• Lamina I-VI: Dorsal grey, Lamina II-SGR, III and IV-nucleus proprius,
V-formatio reticularis, VI-limb enlargements (brachial and lumbar), VII-
nucleus thoracicus, intermediomedial and intermediolateral columns
which include the inhibitory interneurons of Renshaw, VIII-base of ventral
column, IX-somata of motor neurons (alpha and gamma), VIII-X: Dorsal
grey, X-spinal grey commissures.
PAIN PATHWAYS IN THE SPINAL CORD

Dorsolateral Tract of Lissauer
•• The tract of Lissauer (TL) is situated dorsolateral to the dorsal horn.
•• This tract is situated laterally and caps the dorsal horn.
•• It has A-delta and C-fibres and is concerned with nociception.
•• Fibres from the lateral division of the dorsal root bifurcate into ascending
and descending branches that give off a number of collaterals.
•• These terminate in the SGR with interneuronal synapses.
Spinothalamic Tract
•• The spinothalamic tract (STT), spinoreticular tract (SRT) and
spinomesencephalic tract (SMT) together constitute the spinal lemniscus
and may be considered to be a single path.
•• The origin is from laminae I and V-X.
•• The fibres from laminae I-V go to the ventralis posterior nucleus of
the thalamus and those from laminae VI-IX project to the ventralis
posteromedial nucleus.
•• In the brainstem, as it is nearing the thalamus, the spinothalamic tract
divides into:
–– A large lateral neospinothalamic tract, which terminates in the
ventroposterior lateral nucleus along with the quintothalamic tract
(trigeminothalamic) fibres and
–– A small medial portion which terminates in the most rostral part of the
ascending reticular activating system (ARAS) and in the central nuclei
of the thalamus (the so-called non-specific thalamus).
•• In the cervical cord, the disposition of the tract is as follows: sacral, lumbar,
thoracic, cervical from outside inwards. At different levels of the spinal cord,
the depth of the incision required to interrupt the spinothalamic fibres during
an anterolateral cordotomy must vary to obtain optimal effect.
Spinoreticular Tract
•• This is triggered by arousal and is influenced by emotional and affective
aspects of pain and somatic autonomic reflexes.
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•• The fibres originate from lamina VII and VIII and are in the anterolateral
quadrant of the cord.
•• It projects ipsilaterally and contralaterally but mostly to the contralateral
side in the lumbar region.
•• It terminates bilaterally in the medullary reticular formation, the nucleus
subceruleus and the raphe magnus nucleus.
•• From here, fibres proceed to the medial thalamic nuclei.
Spinomesencephalic Tract
•• It is similar to the spinoreticular tract.
•• The fibres originate from laminae I and V.
•• These fibres are 1–5 µm in thickness and conduct at 7m/s.
•• Sixty per cent to seventy five per cent project to the contralateral brainstem,
where these fibres diverge from those of the STT and SRT and turn
dorsomedially into the midbrain.
•• Most of the fibres terminate in the mesencephalic reticular formation (RF),
periaqueductal grey and rostrally in the medial and ventrobasal thalamus.
•• These fibres serve a discriminative function and also have a role in
autonomic reflexes.
Spino-Cervical Tract
•• This originates in laminae III and V and subserves non-noxious tactile
stimuli.
•• It lies in the ipsilateral dorsal funiculus and extends up to the lateral cervical
nucleus; a small group of cells in the upper cervical cord lying lateral to
the dorsal horn.
•• Fibres from the spino-cervical tract (SCT) project to the contralateral
thalamus. It is an inconsistent pathway in humans and has a yet unclear
role in nociception.
Dorsolateral Posterior Synaptic Pathway

•• Laminae III and IV of the dorsal horn give rise to dorsolateral posterior
synaptic pathway (DLPSP).
•• This carries noxious and non-noxious stimuli. Less than 10% respond to
noxious input.
•• Somatotopic arrangement exists in this pathway. This tract plays a role in
pain modulation.
Propriospinal Multisynaptic Ascending System

•• Propriospinal Multisynaptic Ascending System (PMAS) originates in the deep
dorsal column in lamina X, with input from nociceptors and midline structures.
•• It projects to the brainstem reticular formation and medial and intra-laminar
thalamic nuclei.
•• Selective ablation of this path is considered to be effective in the treatment
of bilateral visceral pain, without the potential problems associated with
commissural (extralemniscal) myelotomy.
Dorsal Root Entry Zone

•• The dorsal root entry zone (DREZ) is an entity including the 1 mm central
part of the dorsal rootlet, the posterior medial part of the tract of Lissauer
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and the most dorsal layers (I-V) of the dorsal root where afferents synapse
with cells of the spino-reticulo-thalamic pathway.
•• Each DR divides into 4–10 rootlets according to metameres and is 0.25–1.5
cm in diameter, according to the cord level.
•• Each rootlet is a functional entity, i.e. a miniature root.
•• In each dorsal rootlet and in its corresponding DREZ, there is a spatial
segregation of afferent fibres according to their size and destination. The
fine fibres re-group in the lateral region of the DREZ.
•• The tract of Lissauer (TL) is situated dorsolateral to the dorsal horn.
•• When large lemniscal afferents in the peripheral nerve/dorsal root are
stimulated, there is a decrease in the inhibitory control of the dorsal horn
which can cause excessive firing of the dorsal horn neurons. This is the
origin of de-afferenation pain.
•• Micro-DREZotomy (MDT) involves preferential destruction of the
nociceptive fibres in the lateral bundle of the dorsal rootlets, as well as the
excitatory medial part of the LT.
•• Descending control of dorsal horn cells is well known.
•• Stimulation of the periaqueductal grey or the nucleus raphe magnus results
in prolonged analgesia.
Trigeminal Nerve and its Nuclei

•• A special reference is made here to the trigeminal system as it subserves
the pain of the face and as tic douloureux is so commonly seen in clinical
practice.
•• There are two patterns of trigeminal somatotopic organisation within the
descending trigeminal tract and the nucleus caudalis.
•• The first is that of concentric rings with the middle part of the face being
subserved by the trigeminal nucleus in the rostral medulla. The caudal
end of the face is subserved by the spinal nucleus at the caudal end of
the medulla.
•• The second pattern is that arranged along the three divisions of the
trigeminal nerve V1,V2,V3.
The Thalamus
•• The spinothalamic tract enters the posterior part of the ventral lateral
nucleus (VpL).
•• The pain fibres from the face travel as a separate bundle called the
quintothalamic tract and terminate in the posteroventromedial (VpM)
nucleus of the thalamus.
•• Other fibres carrying pain sensation enter the interlaminar nucleus and
many of them terminate in the centromedian and parafascicular nucleus,
which comprise the nucleus parafascicularis (the paleosensory system).
•• The dorsomedian nucleus of the thalamus, through its connections with the
VA nucleus and the limbic system, plays a part in the emotional reaction
to pain. The thalamus has been divided into:
–– Medial paleothalamus which comprises the medial and intralaminar
nuclei. It has no somatotopy. The role of these nuclei in pain processing
is primarily related to the emotional and motor reaction associated with
aversive behaviour, rather than discriminative sensory function.
–– Neothalamus which receives fibres from laminae VI-VIII of the dorsal
horn through multiple ascending systems and the brainstem RF.
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The neothalamus comprises the VpL and VpM nuclei and has a high
degree of somatotopic organisation. VpL receives the neoSTT via the
medial lemniscus and the VpM receives the spinal-trigeminal system
via the ventral tegmental tract (VTT).
Summary of the Neurophysiology of the Thalamus
•• The thalamic lesion sites for pain relief have been classified as follows:
–– Thalamic nuclei of the limbic system and their radiation
–– Hypothalamus
–– Thalamic nuclei of the frontal association system and their radiation
–– Spino-thalamic relay nuclei for the medial lemniscus and the spino-
quintothalamic tract and their radiations
–– Intralaminar nuclei.
NEUROPHARMACOLOGY OF PAIN
•• An understanding of the neurochemical mechanisms involved in sensory
conduction and pain helps to understand the basis of pharmacological
therapy.
•• Substance P is an important neurotransmitter concerned with transmission
of nociceptive stimuli.
•• Substance P also contributes to the inflammatory response and nerve
sensitisation.
•• Recent studies have shown calcitonin gene related polypeptide (CGRP) to
co-exist with substance P in the primary afferent neurons.
•• Its role may be neuromodulation rather than neurotransmission.
•• Other substances are serotonin and norepinephrine which mainly act as
neurotransmitters of the descending pathways from the nucleus raphe
magnus and locus ceruleus, respectively.
•• The other important modulators are endogenous opiates which are
present in the substantia gelatinosa, lamina V, nucleus raphe magnus and
periaqueductal grey (PAG).
•• Peptides like substance P, VIP, somatostatin, cholecystokinin and
angiotensin are present in the dorsal horn.
•• Opiate receptors are found in laminae I and II of the dorsal horn, the
medial raphe nucleus, the periaqueductal grey, the locus ceruleus and
the hypothalamus.
•• The endogenous analgesic system: This consists of the periaqueductal
grey (PAG), nucleus raphe magnus (NRM), parabrachial region, midbrain
medullary RF, dorsal raphe nucleus, cuneiform nucleus, medial reticular
formation, nucleus of trigeminal spinal tract and SGR; the first four being
the most important. The pathway on receiving painful stimuli stimulates the
release of endorphins which serve as pain modulators. Low intensity electric
stimulation of the raphe nuclei cause analgesia mediated by norepinephrine
and serotonin (5-HT). Analgesic action of the system of endogenous opioids
is blocked by the depletion of 5-HT levels and NE.
Pain Models
The Gate Control Theory of Pain
•• One of the functions attributed to the interneurons is that of a gate control
system modulating the afferent input (Gate control theory of Melzack and
Wall).
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•• The theory was first stated in 1965 by Wall and Melzack and was then
re-stated by Wall in 1978 and 1983 to embrace the criticism about the role
of the SGR, extent of pre-synaptic inhibition in nociceptive afferents in
the dorsal horn and the known fact of stimulus specificity of nerve fibres.
•• Simply stated the theory runs thus—information about the presence of
injury is transmitted to the CNS by peripheral nerves.
•• Cutaneous small diameter fibres (A delta and C fibres) respond only
to injury, while others with lower thresholds increase their discharge
frequency if stimuli reach noxious thresholds.
•• Cells in the spinal cord/trigeminal nucleus which are excited by these
injury signals are also facilitated or inhibited by other nerve fibres which
carry information about innocuous events.
•• A descending control system originating in the brain modulates the
excitability of cells which transmit information about the injury.
•• The brain receives by way of the gate control system, injury signals,
descending signals and other types of afferents.
• • This theory of gating, although modified later, is generally still
applicable to many levels of the nervous system.
• • The interneurons have an inhibitory effect on the afferent fibre
terminals.
• • This inhibition is increased by activity in the large diameter fibres and
decreased by activity in the small diameter fibres.
• • The balance of activity between the two sets of fibres influences the
interneurons, to control the afferent input into the central nervous
system.
• • The descending pathways from the cortex and the brainstem also
exert an inhibitory influence on the gate control system. Thus, the
role of the interneurons is to help in the convergence, interaction and
control of afferent influences.
•• The technical details of the gate control theory are as follows (Fig. 1):
–– Ongoing activity preceding a state is caused by tonic, slowly adapting
fibres that tend to keep the gate open.
–– Peripheral stimulation activates both small and large fibres. Discharge
of large fibres will initially cause the tract cells (T cells) to fire by the
Fig. 1: Sensory gate control circuit (Melzack and Wall)

1419
direct route and then partly close the gate in Lamina II. This facilitates
pre-synaptic inhibition.
–– Balance between large and small fibre activation will determine the
state of the gate. If the stimulus is prolonged, large fibres will adapt
which will result in a relative increase in small fibre activity and cause
the gate to open. The gate functions and there is an increase in T
cell activity. However, if large fibre activity is increased by a proper
stimulus (vibration) the gate will then close and the T cell activity will
decrease.
Neuromatrix Theory of Pain
•• Neuromatrix theory of pain states that the body-self neuromatrix comprises
a widely distributed neural network that includes somatosensory, limbic and
thalamic cortical components.
•• There are 3 parallel networks which account for the dimensions of pain
experience namely, S-sensory discriminative, A-affective motivational and
E-evaluative-cognitive.
•• The synaptic architecture of the neuromatrix is determined by genetic and
sensory influences.
•• Multiple inputs that act on the neuromatrix programs and contribute to
output neurosystems include:
–– Sensory inputs from the somatic receptors
–– Visual and other sensory inputs that influence cognitive interpretation
of the situation
–– Phasic and tonic cognitive and emotional inputs from other brain areas
–– Intrinsic neural inhibitory modulation inherent in all brain function
–– Activity of the body’s stress regulation systems including cytological
as well as endocrine, autonomic, immunologic and opioid systems.
CHRONIC PAIN SYNDROMES

•• The onset and continuance of chronic pain appears to arise from the intrinsic
complexity of the peripheral sensory and pain conducting systems, the
peripheral nerves, the dorsal root ganglion, the dorsal horn, the ascending
tracts and the higher brain centres.
•• In chronic pain syndromes (CPS), the complaints are usually stated in
affected terms like—excruciating, throbbing, stabbing, etc. and have no
dermatomal pattern.
Pain in Peripheral Nerve Lesions

•• In peripheral nerve injuries, long-lasting discharges occur in the small
sensory fibres and not in the large sensory or motor fibres.
•• It was suggested that cross connections between sensory and motor fibres
in an injured nerve (ephaptic transmission) leads to perpetuation of pain
as seen in causalgia.
•• The persisting pain has been attributed to the possible formation of small
injury neuromas inside the nerve, where the axonal sprouts are sensitive
to physical and chemical stimulation.
•• Spontaneous and evoked afferent activity has been noted from the affected
area.
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•• Adrenergic receptors have been shown to develop on the axonal sprouts

at the site of the injury. While catecholamines increase the afferent activity,
local anaesthetics abolish these.
•• Neurotrophins, Protein Kinase-C, 5-HT and NO are involved in neuropathic
pain.
•• During regeneration after nerve injury, recovery is only partial even after
carefully performed surgery. The patients often suffer from paraesthesiae
in the affected part, and also spontaneous pain, allodynia and hyperpathia.
These abnormal sensory phenomena arise from many factors. The
possibilities are:
1. Conduction in sensitive fibres that have not yet made a receptor con-
nection in the periphery
2. Death of DRG cells affecting the larger cells more than the smaller
cells and increasing small fibre input into the cord
3. Functional connection between fibres serving high threshold and low
threshold receptors and
4. Impaired inhibition in the spinal cord.
•• Root pain:
–– Root pains are referred to discrete areas, can be intense and usually
there is no sensory loss.
–– Pressure on the posterior nerve roots often causes changes in the
DRG, because of its close proximity to the affected area and cell death
can occur in the DRG.
–– Prolonged pressure causes demyelination in the nerve roots leading to
ectopic discharges and mechanosensibility.
–– In long standing cases, the radiating pain may disappear leaving an
area of sensory loss with hyperaesthesia or hyperalgesia.
•• Post-herpetic neuralgia is a painful syndrome characterised by anaesthesia,
paraesthesia, hyperpathia and allodynia in the affected area.
•• The virus of herpes zoster causes damage to the peripheral nerve, the
DRG, the dorsal root and the dorsal columns.
Cerebral Areas for Pain Perception

•• Fibres from the posteroventral nucleus of the thalamus proceed to the
sensorimotor cortex. Although the majority ends in the post-Rolandic
sensory area, many of them can be traced to the motor strip also.
•• The sensory cortex is concerned with the primary appreciation of sensation.
•• Lesions in this area which include the parietal lobe may cause spontaneous
hemibody pain and dysaesthesia which may be indistinguishable from
thalamic pain except for its paroxysmal nature, resembling an epileptic
discharge.
•• Its pathogenesis is dependent on complex paleothalamic interrelationships.
•• The other complex routes for pain assessment are to the limbic system, to
the temporal lobes (for memory storage and comparison) and to the frontal
lobes (for final assessment and judgement) and back to the limbic system,
viz. the claustrum, the amygdala and the orbital cortex (for emotional
colouring).
•• The connections to the limbic system are important as they are involved
in the motivational and affective determinants of pain.
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Mechanisms of Central Pain

•• Selective destruction of neo-spinothalamic tract.
•• Irritation of the sensory pathways.
•• Irritation of sympathetic pathways.
•• Hypothalamic disturbances.
•• Loss of nociceptive inhibitory influences.
•• Activation of secondary pathways.
•• Activation of non-specific pathways related to the paleospinothalamic
system.
•• Abnormal findings of de-afferenation.
•• Hyperactivity in de-afferenated reticulo-thalamic pathway.
Physiological Classification of Pain

•• Stimulation of peripheral nociceptors (e.g. Carcinomatous deposits in the
long bones).
•• Direct stimulation of nerve trunks, plexi and roots (e.g. Carcinoma in the
L-S plexus).
•• Impulses related to neural injury (neuropathic pain/sciatica).
•• Central re-organisation of pain (allodynia, hyperpathia, peripheral
neuropathy, sympathetically mediated pain).
•• A special type of pain is “mirror pain” seen post-cordotomy, occasionally
due to unmasking of cord pathways subserving pain.
Mechanisms of Chronic Pain

1. Nociceptive:
a. Somatic
b. Visceral.
2. Neuropathic:
a. Deafferentation
b. Peripheral.
3. Sympathetic:
4. Psychogenic:
a. Without a coexisting organic lesion
b. With an organic lesion.
CHRONIC REGIONAL PAIN SYNDROME

•• Chronic regional pain syndrome (CRPS) was first described by Paget in
1862.
•• There are three types:
1. Chronic regional pain syndrome (Type I) (Reflex sympathetic
dystrophy):
The features are as follows:
• The syndrome develops after an initial noxious event.
• Spontaneous pain/allodynia/hyperalgesia not limited to the territory of
a single peripheral nerve and is disproportionate to the exciting event.
• There is evidence of oedema/shiny skin and abnormal blood flow
with abnormal sudomotor activity in the region of the inciting event.
• Exclusion of any condition that would account for the above dys-
function.
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2. Chronic regional pain syndrome type II (Causalgia):

• This develops after a nerve injury.
• Spontaneous pain/allodynia/hyperalgesia occurs and is not neces-
sarily limited to the territory of the injured nerve.
• There is evidence of oedema/shiny skin and abnormal blood flow
with abnormal sudomotor activity in the region of the inciting event.
• Exclusion of any condition that would account for the above dys-
function.
• There are three stages in causalgia:
– Pain/oedema and wasting
– Cold skin with trophic changes
– Atrophy.
3. Chronic regional pain syndrome type III: Not otherwise specified.
Pathophysiology of Chronic
Regional Pain Syndrome
•• There are several theories of CRPS:
–– Pain in CRPS is relieved by local anaesthetic sympathetic blockade/
sympatholytic procedure like the regional application of guanethidine/
IV phentolamine.
–– Pain may re-initiate/exacerbate by the application of an alpha adreno-
ceptor agonist, either iontophoretically or by injection of a limb with
pain and hyperalgesia.
–– Guanethidine elicits pain when injected IV in the affected extremities.
Represents a response to NE released from the post-ganglionic tissue.
–– Coupling of sympathetic afferents and efferents results in abnormal
afferent impulses generated by the sympathetic nervous system. This
explains why reflex sympathetic dystrophy (RSD) is abolished by
sympathetic block.
Diagnostic Criteria for Chronic

Regional Pain Syndrome
Clinical Signs and Symptoms
•• Burning pain
•• Hyperpathia/allodynia
•• Temperature or colour changes
•• Oedema
•• Hair changes/nail changes.
Lab Results
•• Thermometry/thermography
•• Bone radiography
•• Three phase bone scan
•• Quantitative sweat test
•• Response to sympathetic blockade.
Interpretation
•• More than 6 points present—probable RSD
•• 3–5 points present—possible RSD
•• Less than 3 points present—unlikely to be RSD.
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Scores
•• 7–definitive RSD
•• 4–6-probable RSD
•• 2–3-possible RSD
•• 0-not RSD.
Clinical Correlates in Pain

•• The symptomatology of pain is easily remembered by the mnemonic
“PQRST” wherein P, Q, R, S and T stand for palliative/provocative factors,
quality of pain (burning, shooting or stabbing), radiation of pain, spatial
distribution and temporal aspect, respectively.
•• The definitions of certain terms used in pain vocabulary are as follows:
Allodynia: Increased sensibility to pain, pain in response to a stimulus
which is not normally painful.
Alloaesthesia: Perception of a sensory stimulus at a site other than where it
was delivered. Kinetic alloaesthesia is feeling something other than at the site
of stimulation.
Analgesia (alganaesthesia): Abnormal sensitivity to pain.
Anaesthesia: Absence of all sensations.
Dysaesthesia: Unpleasant/painfully abnormal perverted sensation—
spontaneously or caused by normally non-painful stimuli, e.g. burning
response to touch, other accompanying paraesthesiae.
Hypalgesia: Decrease in pain sensibility.
Hyperalgesia: Increase in pain sensibility or pain in response to a stimulus
not normally painful.
Paraesthesiae: Abnormal spontaneous sensations experienced in the
absence of specific stimulation (feelings of hot, cold, numbness, burning,
itching, etc.).
Grading of Pain
•• Unidimensional scales (Verbal rating scale): This rates pain as none,
mild, moderate, severe.
•• Visual analogue scale (VAS): Continuous/intermittent pain. This is a 10 cm
unmarked line where the pain is graded from:—no pain to worst pain (Fig. 2).
•• Colour red analogue: This includes a pictographic representation of the
patient’s emotional state of mind in relation to the pain.
•• Berman, Tagg, et al. (1996) put forth a system of pain grading to
standardise quantification of pain:
–– Severe: Continuous disturbance of daily life or of work or study/sleep.
(i.e. VAS 9–10).
Fig. 2: Visual analogue scale for pain

1424
–– Significant: The patient is able to sleep but he cannot work/study/

engage in hobbies due to pain (VAS 7–8).
–– Moderate: The patient is able to work; sometimes severe pain which
results in the patient taking time off (VAS 4–7).
–– Mild: Patient aware of pain but can pursue a normal life (VAS 0–3).
Biostimulation
•• Laser biostimulation is based on the fact that light stimulates pain at low
frequency and inhibits pain at high frequencies.
•• Magnetic biostimulation is based on the principle that a magnetic field
through ions would generate heat (Hall effect) and this heat would then
generate an action potential (Lorentz force). The WHO has recently
approved the use of 2 Tesla magnets for this purpose.
•• Other forms of treatment such as chiropractice (mobilisation and manipulation)
of painful joints and aroma therapy have also been used in the treatment of
chronic pain.
192
CHAPTER
Management of Pain
Nigel Peter Symss
DRUGS
Non-narcotic Analgesic Drugs
Acetaminophen (Official Generic Name: Paracetamol)
•• It is an antipyretic analgesic with no effect on the platelet function or
inflammatory cascade.
•• It acts centrally, inhibiting prostaglandin function.
•• Due to its lack of significant inhibition of peripheral cyclo-oxygenase
(COX), it does not promote bleeding, thus making it safe to use in the
peri-operative period.
•• Taken within the prescribed dose range, it is safe.
•• The main safety concern is dose-related hepatic toxicity.
•• Overdose is treated with N-acetylcystine.
Salicylates
•• Aspirin is an antipyretic, anti-inflammatory, analgesic agent.
•• It is quite effective and its action may be central, blocking prostaglandin
synthesis.
•• It is the prototypical non-steroidal anti-inflammatory drug (NSAID), being
a non-selective COX inhibitor at usual analgesic doses, although it may
somewhat selectively inhibit COX-1 at doses typically used to reduce
platelet aggregation therapeutically.
•• It is used in a dosage of 500−1000 mg/q 4−6 hourly, with a maximum daily
dose of less than 4,000 mg.
•• Gastrointestinal side effects are common.
•• It predisposes to haemorrhage even in low doses; while gastrointestinal
bleed is common, intracranial haemorrhage is well documented.
Non-steroidal Anti-inflammatory Drugs
•• These types of non-opioid analgesics are frequently used as first-line
analgesics.
•• They lack significant abuse potential and do not induce the development
of analgesic tolerance.
•• These drugs act by inhibiting the biosynthesis of prostaglandins at
various stages, through inhibition of the COX enzymes, thus reducing the
inflammatory process.
•• There are two similar, but distinct, isoforms of COX identified: (1) COX-1
and (2) COX-2.
1426
•• Several drugs are now available that selectively, more accurately and
preferentially inhibit COX-2, which is responsible for inflammatory
processes and pain relief.
•• They too have side effects on the gastrointestinal system.
•• The commonly used drugs are indomethacin (25−50 mg/q 8 hourly),
diclofenac (50 mg/q 6 hourly), ibuprofen (200−400 mg/q 4−6 hourly) and
naproxen (250 mg/q 6 hourly).
•• The COX-2 selective non-steroidal anti-inflammatory drugs are etodolac,
meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib.
Phenothiazines
•• Phenothiazines block dopamine and epinephrine postsynaptically and have
a strong atropine like action.
•• Commonly used phenothiazines are chlorpromazine 50 mg/q 8 hourly,
thioridazine 50 mg/q 8 hourly and fluphenazine 2 mg/q 12 hourly.
•• Combinations of tricyclic drugs, which are mood elevators, with
phenothiazines have been found to be useful in the management of post-
herpetic neuralgia and intractable cancer pain.
Phenytoin
•• Phenytoin has a direct effect on both axonal conduction and synaptic
transmission.
•• It is found useful in many pain syndromes such as trigeminal neuralgia, post-
herpetic neuralgia, glossopharyngeal neuralgia and diabetic neuropathy.
Carbamazepine
•• It may act at the level of central synapses.
•• It is found effective in treating patients with trigeminal neuralgia and some
forms of neuropathic pain.
•• It is effective at serum levels between 8 mmg/mL and 12 mmg/mL.
•• The dosages of these drugs have to be individualised for effective response.
Oxcarbazepine
•• Oxcarbazepine is the 10-keto analogue of carbamazepine, but has a distinct
pharmacokinetic profile.
•• In contrast to the oxidative metabolism of carbamazepine, oxcarbazepine
is rapidly reduced to its active metabolite, 10,11-dihydro-10-hydroxy-
carbamazepine.
•• Direct comparison of oxcarbazepine and carbamazepine has shown no
difference in efficacy between these two agents in terms of reducing
seizure frequency in patients with partial epilepsy with or without secondary
generalisation, or with tonic-clonic seizures.
•• Limited data indicate that oxcarbazepine may be a useful alternative to
carbamazepine in the management of trigeminal neuralgia.
Gabapentin
•• Gabapentin resembles gamma-aminobutyric acid (GABA), and was initially
marketed as an adjunctive anticonvulsant.
•• However, it was found to be an effective analgesic for conditions where
neuropathic pain was a significant contributor, such as post-herpetic
neuralgia.
•• Its advantages are that it is not metabolised, so there is no concern
regarding accumulation of active metabolites.
Chapter 192 • Management of Pain
1427
•• Gabapentin is not a GABA agonist, nor is it metabolised into GABA.

•• It is cleared renally, and needs to be used cautiously in the presence of
renal dysfunction.
•• Gabapentin absorption is mediated by a saturable transporter system
located in the upper gastrointestinal tract, indicating a short window of
absorption.
•• It has a dose dependent oral bioavailability. A dose of 400 mg is
approximately 25% less bioavailable than of a dose of 100 mg. Above
800 mg per dose, there is little additional absorption of gabapentin. The
recommended maximum daily dose is approximately 3,600 mg.
Benzodiazepines
•• They increase both pre- and post-synaptic inhibition.
•• The effect appears to be caused by facilitation of the inhibitory
neurotransmitter GABA.
•• Clonazepam is effective in the management of chronic neuropathic pain
and in patients with nerve or plexus injury.
•• The commonly used benzodiazepines are diazepam, alprazolam,
chlordiazepoxide and flurazepam.
Tricyclic Antidepressants
•• They probably act by facilitation of monoamine transmission by inhibition
of serotonin and norepinephrine reuptake at the synapse.
•• They may also potentiate the descending analgesic pathways.
•• They are effective in neuropathic pain, especially post-herpetic neuralgia
and diabetic neuropathy.
•• They also inhibit the encephalin hydrolyzing activity, thus increasing the
level of encephalin in the CNS.
•• The commonly used tricyclic antidepressants are amitriptyline (75−300
mg/day), imipramine (150−300 mg/day) and doxepin (150−300 mg/day).
Pregabalin
•• Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-
gated calcium channels in the central nervous system that exhibits potent
anticonvulsant, analgesic and anxiolytic activity in a range of animal models.
•• Pregabalin has been advocated for the treatment of neuropathic pain
associated with diabetic peripheral neuropathy and post-herpetic neuralgia.
•• Most patients with chronic lumbosacral radiculopathy have also been found
to respond well to pregabalin therapy.
•• Pregabalin is rapidly absorbed following oral administration, with peak
plasma concentrations occurring between 0.7 hour and 1.3 hours.
•• Pregabalin oral bioavailability is approximately 90% and is independent of
dose and frequency of administration.
•• Food reduces the rate of pregabalin absorption, resulting in lower and
delayed maximum plasma concentrations. However, the extent of drug
absorption is unaffected, suggesting that pregabalin may be administered
without regard to meals.
•• Pregabalin elimination half-life is approximately 6 hours and steady state
is achieved within 1−2 days of repeated administration.
•• Pregabalin is eliminated renally; thereby renal function affects its
pharmacokinetics. It is not subject to hepatic metabolism and does not
induce or inhibit liver enzymes such as the cytochrome P450 system.
•• An effective starting dose of 150 mg/day is advocated in clinical practice.
1428
Narcotics
•• Narcotics should be reserved only for the management of chronic pain
due to cancer.
•• Patients usually develop tolerance and may require increasingly higher
doses.
•• If a narcotic is used for non-malignant pain it should be for short periods
only.
•• Morphine, codeine and thebaine are naturally occurring opioids isolated
from opium poppy.
•• Fentanyl, meperidine and methadone are synthetic opioids.
•• Oxycodone, hydromorphone and hydrocodone are semisynthetic opioids
made by chemically modifying thebaine.
Opioids in Cancer Pain

•• About 70% of patients with advanced cancer experience moderate to severe
pain, necessitating the use of opioid medication for pain relief.
•• Opioids are the main stay in the treatment of moderate to severe cancer
pain of all causes.
•• The WHO advocates the following three step approaches:
–– Step 1 for mild pain involves 24 hours coverage with acetaminophen
or NSAID medication.
–– When these medications fail to provide adequate analgesia or when
pain is moderate at onset, a “weak” opioid, such as codeine or oxyco-
done, is appropriate (step 2).
–– A strong opioid (step 3) is indicated for the patient in whom relief of
pain is inadequate with step 1 or 2 or when the pain is severe at onset.
Some of the common drugs used in step 3 are morphine, hydromor-
phine, levorphanol tartrate, methadone hydrochloride and fentanyl.
•• To begin with, the oral route is preferred because of the ease of
administration and good oral bioavailability of most opioids.
•• Orally administrated morphine sulfate immediate release (MSIR) is
generally considered the first-line drug in severe cancer pain.
•• Treatment generally begins with a low dose.
•• Mean starting doses of MSIR are 10−30 mg 4 hourly throughout the day
and night.
•• “As needed” dosing is inappropriate and should be avoided and a constant
plasma level required for good analgesia is achieved by ‘round the clock’
administration.
•• There is no “standard” opioid dose and therapy should be highly
individualised and dose titrated until analgesia is achieved or side effects
are unmanageable.
•• Adverse effects of opioids include sedation, nausea, constipation,
respiratory depression or myoclonus.
•• Most opioid side effects are manageable. Constipation, to which tolerance
rarely develops, is avoided by the use of stool softeners or bowel stimulation.
•• Tolerance to respiratory depression develops rapidly. Severe respiratory
depression may necessitate mechanical ventilation and the use of the
opioid antagonist naloxone hydrochloride. Tolerance also develops to
opioid induced sedation but, if it is incomplete, a trial of a stimulant like
methylphenidate hydrochloride or dextroamphetamine 5 mg bd may be
used.
1429
•• Nausea during opioid administration may be produced by different

mechanisms. Nausea due to direct stimulation of the chemoreceptor trigger
zone of the medulla occurs constantly is unrelated to food intake and is
best relieved by a phenothiazine.
•• Nausea which is worse after eating is due to reduced gastric motility and
decreased gastric secretions and this responds to metaclopromide.
•• Nausea due to sensitisation of the vestibular apparatus occurs with changes
in the position of the head, and responds to treatment with scopolamine
or meclizine.
•• Myoclonus, especially common with meperidine occurs during sleep and
responds to clonazepam or change of opioid. Thus, most opioid side
effects are manageable either by waiting for tolerance to develop or by
symptomatic treatment.
•• Parenteral administration of opioids by intravenous or subcutaneous
administration has the advantage of rapid pain relief, ease of adjustment
of dosage, constant plasma levels and fewer side effects and is also useful
in patients with gastrointestinal dysfunction.
•• Continuous infusion by long-term central venous catheter or by portable
ambulatory infusion pumps which are presently available is suitable for
some patients. Patient controlled analgesia has also proved to be useful
in selected patients with cancer related pain.
Spinal Delivery of Opioids
•• Injection of morphine or fentanyl in the spinal epidural or subarachnoid
space, when parenteral administration fails, provides intense analgesia
with lesser side effects. The injection can be as a bolus or continuous
infusion with a pump system.
•• For long-term spinal analgesia access to the epidural or intrathecal space
by an indwelling catheter system is possible, but appropriate test doses
of an opioid should be administered to ensure that the patient’s pain will
respond to spinal analgesia without excessive or intolerable side effects.
Anaesthetic Measures
•• The use of reversible nerve blocks or lysis of neural tissue by appropriate
agents is efficacious both in the diagnosis and management of certain
painful states.
•• Reversible nerve blocks result in temporary interruption of nociceptive
transmission and can be achieved by percutaneous injection of a local
anaesthetic, which results in temporary abolition of pain.
•• More permanent nerve blocks can be achieved by destruction of neural
tissue, by the use of chemicals such as alcohol or phenol or by physical
methods such as heat or cold.
•• Chemical neurolysis can also be achieved by intraspinal delivery of the
analgesic agent (epidural, subdural or subarachnoid).
Peripheral Nerve Block

•• This can be achieved by using phenol or alcohol.
•• The nerve to be blocked has to be confirmed first by using a local
anaesthetic agent.
•• An RF lesion can also be used to destroy the nerve. This is commonly used
for intercostal block and trigeminal neuralgia.
1430
•• Autonomic nerve blocks are also used to relieve visceral or causalgia pain.
The commonly used targets are the paravertebral sympathetic chain, the
coeliac plexus and the stellate ganglion.
•• The relief of pain following sympathetic blockade may be because of
‘cross talk’ between sympathetic efferents and unmyelinated afferents,
the sympathetic efferents interacting with cutaneous afferents to produce
contacts between sensory efferents and tiny cutaneous afferents within
the skin, or excessive sympathetic outflow resulting in change in vascular
permeability and an elevation in extracellular substances that produce pain.
Spinal Neurolysis (Subarachnoid,

Subdural and Epidural)
•• Subarachnoid neurolysis is one of the most common methods used.
•• The duration of pain relief is directly related to the amount of nerve fibre
destruction.
•• The major drawback of this procedure is the risk of destruction of other
structures coming in contact with the neurolytic agent. There is gradual
regeneration of pain fibres following chemical neurolysis. Hence the pain
will recur after varying periods.
•• The agents commonly used are phenol (5−8%) in glycerine (0.5−1 mL),
absolute alcohol (1−2 mL) and chlorocresol (parachlorometacresol (1 in
50) in glycerine (0.5−1 mL). The drugs should be given slowly.
•• Phenol and chlorocresol are gradually released from glycerine, limiting
their spread.
•• Phenol and chlorocresol in glycerine are hyperbaric solutions while absolute
alcohol is hypobaric.
•• Injection of cold or hypertonic saline into the subarachnoid space helps to
relieve pain in many cases. The effect on the roots is more due to the ions
than to the low temperature of the fluid.
•• The main complication with these procedures is the risk of injury to other
nerves resulting in motor weakness and sphincter disturbances.
•• Epidural neurolysis has the advantage of less risk of spread intracranially
and less chance of motor and sphincter disturbances.
•• Subdural neurolysis is not an easy procedure and is used in intractable
neck and shoulder pain.
SURGICAL PROCEDURES
•• On the basis of the sites of operative intervention, they can be classified as:
1. The peripheral and cranial nerves: Peripheral neurectomy.
2. The posterior roots:
a. Section (Rhizotomy) in:
i. The spinal canal
ii. The middle cranial fossa
iii. The posterior cranial fossa.
b. Intrathecal injections for blocking the posterior roots, chemical
rhizotomy using phenol, alcohol, glycerol or cold saline.
3. The sympathetic chain: sympathectomy.
4. The spinal cord:
a. Dorsal root entry zone (DREZ) lesions
b. Spinothalamic tractotomy, open or percutaneous
c. Commissural myelotomy.
1431
5. The medulla:
a. Medullary spinothalamic tractotomy
b. Trigeminal tractotomy.
6. The mesencephalon: mesencephalic spinothalamic tractotomy.
7. The thalamus: Stereotaxic thalamotomy (chemical, thermal, cryogenic
or gamma rays): Posteroventrolateral nucleus, centrum median, dor-
somedian, pulvinar.
8. The hypothalamus: Posterior median hypothalamotomy.
9. The sensory cortex: Ablation of the sensory cortex.
10. The frontal lobes:
a. Prefrontal leucotomy or lobotomy
b. Cingulumotomy
c. Basifrontal tractotomy
d. Fornix section.
11. Pituitary ablation.
12. Non-destructive procedures:
a. Transcutaneous nerve stimulation (TNS)
b. Acupuncture
c. Dorsal column stimulation (DCS)
d. Periaqueductal grey stimulation
e. Thalamic stimulation
f. Spinal and intraventricular morphine.
Peripheral Neurectomy
•• The common indications for peripheral neurectomy are supraorbital or
infraorbital neuralgias, inferior alveolar neuralgia, and painful stump
neuromas.
•• The other indications are meralgia paraesthetica, malignant invasion of the
chest wall, selected cases of post-herpetic neuralgia, causalgia, painful
arthritis and phantom limb.
•• Radiofrequency or cryogenic techniques can be used to make lesions.
•• The procedure is also useful in some cases of peripheral vascular disease
of the lower limbs with incapacitating rest pain, where the cutaneous nerves
can be divided with benefit.
•• As the peripheral nerves tend to regenerate after simple division, a section
of the nerve is removed during surgery.
•• Although neurectomy is useful in many instances, there is always a risk of
development of neuropathic pain.
•• As some peripheral nerves contain both motor and sensory fibres, division
can cause sensory loss, weakness and atrophy.
Posterior Root
Section (Rhizotomy)
•• Posterior root section or posterior rhizotomy implies section of the posterior
root of a peripheral or cranial nerve for relief of pain.
•• In the spinal canal, the section is made between the cord and the posterior
root ganglion.
•• It is a useful operation which can be selectively done to cover a number of
dermatomes without any involvement of the motor fibres.
•• Considering sensory overlapping in continuous dermatomes it is necessary
to cut at least two posterior roots above and below the area of pain.
1432
•• The sensory supply of muscles and bones (myotomes and sclerotomes)

does not conform to the overlying cutaneous sensory arrangement in
all parts of the body. Hence, in disease involving bones and muscles,
rhizotomy, to be useful, must include the concerned roots, also in addition
to those supplying the dermatome.
•• In cases of thoracic pain due to tumour infiltration of the chest wall or pleura
or other causes, posterior rhizotomy is helpful.
•• In some cases of post-herpetic neuralgia, as also thoracic radiculopathy,
pain may be relieved by such an operation.
•• Sensory rhizotomy is also useful in patients with chronic pain in the lower
extremity resulting from repeated disc surgery.
•• The posterior roots can be sectioned intradurally after laminectomy.
•• In the thoracic region an interlaminar approach may be adopted.
•• In cases of malignant disease of the head and neck, pain can be relieved
by section of the upper cervical and lower cranial nerve roots.
•• Rhizotomy is also useful in occipital neuralgia and in coccydynia where
bilateral sacrococcygeal root section helps.
•• The drawback of rhizotomy is the possible development of deafferentation
pain syndrome in some cases. Rhizotomy is also not useful for benign
peripheral neuropathic pain.
Selective Rhizotomy (Rhiziditomy)
•• Selective destruction of rootlets which carry the small afferent fibres.
•• These are grouped on the ventrolateral part of the posterior root before
they re-enter the cord.
•• The technique has been found useful in the treatment of malignant lesions
involving the brachial and pelvic plexuses.
Percutaneous Radiofrequency Rhizotomy
•• Interruption of nerve root function by the percutaneous route using
radiofrequency current is now preferred over the previous techniques
mentioned; this has proved to be effective and safe and has been performed
for relief of pain as well as of flexor spasms.
Dorsal Root Entry Zone Lesions
•• The procedure is based on the concept that deafferentiation in the root
or peripheral nerve lesions leads to loss of control and inhibition in the
neurons of the dorsal horn and a DREZ lesion helps to restore the balance.
•• The lesion probably involves Lissauer’s tract and the deeper layers of the
dorsal horn.
•• DREZ lesions have been found useful for pain following brachial plexus
avulsions, phantom pain, painful paraplegia and some cases of post-
herpetic neuralgia.
Chemical Rhizotomy
•• It is done using phenol, alcohol, glycerol or cold saline.
•• Percutaneous transovale trigeminal rhizotomy by injecting glycerol into
the retrogasserian cistern of Meckel’s cave is a useful treatment modality
for tic douloureux.
•• The major advantage of glycerol rhizotomy is significant reduction in
post-operative facial deafferentation and its sequelae when compared
to differential thermal rhizotomy performed by graded radio-frequency-
induced lesions.
1433
Sympathectomy for Visceral Pain

•• The fibres carrying pain sensation from the viscera and blood vessels
travel along the sympathetic system and interruption of the system at the
appropriate level gives relief from specific types of visceral pain.
•• Paravertebral injection of procaine may relieve intractable visceral pain for
short periods; this may be followed by surgical section of the sympathetic
chain for more lasting effects.
•• Resection of the upper four thoracic ganglia relieves precordial pain of
cardiac origin.
•• Alcohol block of the coeliac plexus helps to control pancreatic pain.
•• Resection of the splanchnic nerves and the lower thoracic sympathetic
ganglia relieves upper abdominal visceral pain and if, along with these,
the lumbar sympathetic ganglia are also resected, pain from the kidneys
is abolished.
•• Presacral neurectomy has been found to be of benefit in severe
dysmenorrhoea, as well as in pain due to lesions of the urinary bladder
and other pelvic viscera.
•• Sympathetic denervation of limbs relieves vascular pain and the pain of
phantom limb in some cases. Sympathectomy is the treatment of choice
for cases of causalgia.
•• Unilateral thoracoscopic sympathectomy induces adequate and lasting
relief of pain caused by benign as well as malignant diseases originating
from the pancreatic region, chronic pain from upper gastrointestinal tract
diseases and portal vein thrombosis.
•• The sympathetic chain and splanchnic branches are divided from level IV
to X-XI, with all patients reporting substantial relief of pain post-operatively.
Operations on the Spinal Cord

•• Cordotomy is one of the treatment choices in pain caused by malignancies
localised unilaterally to the extremities as well as the thorax and the
abdomen.
•• Spinothalamic Tractotomy-Anterolateral Cordotomy: In anterolateral
cordotomy the pain carrying fibres in the anterolateral quadrant of the cord
are divided. The level of choice for this operation is the upper thoracic (the
2nd thoracic level) and the upper cervical region (between the first and
the second cervical segments). Open cordotomy is seldom performed
nowadays although it was a popular procedure four decades ago.
•• Percutaneous Cervical Cordotomy:
–– This approach is safer, as it leads one directly to the anterolateral part
of the cord and the incidence of respiratory complications are minimal.
–– PCC remains a valuable treatment option in patients with treatment-
resistant cancer pain and still deserves a place in the treatment
of terminal cancer patients with severe unilateral neuropathic or
intractable pain.
–– CT-guided percutaneous cordotomy is an option in specially selected
cases with malignancy with intractable pain. The target of computed
tomography (CT)-guided percutaneous cordotomy is the lateral
spinothalamic tract located in the anterolateral region of the spinal cord
at the C1–C2 level
–– Despite the drawbacks of the level of analgesia falling after a few
weeks and of the possibility of limb, bladder or respiratory weakness,
1434
the procedure of cordotomy (thoracic or cervical) continues to be a

useful procedure, giving benefit to the majority of patients operated
upon, specially to those suffering from pain due to malignancy.
–– Cordotomy is not effective in deafferentation syndrome.
–– Complications: While unilateral cordotomy spares bladder function,
bilateral cordotomy most often results in its involvement. Impairment of
respiratory function may occur after bilateral cervical cordotomy due to
interference with the motor fibres to the diaphragm that lie between the
anterior horn and the cervical fibres of the spinothalamic tract.
•• Commissural Myelotomy:
–– Commissural myelotomy (CM) was introduced to overcome some of
the limitations of bilateral cordotomies in the treatment of bilateral pain
syndromes.
–– CM disrupts pain-conducting fibres as well as a polysynaptic pain pathway
that runs through the centre of the spinal cord.
–– The thin fibres which enter the spinal cord through the zone of Rolando
and cross over to the opposite side may be severed at the site of crossing
by splitting the cord in the midline. This results in bilateral relief of pain at
the segmental level corresponding to the site of incision.
–– The operation has been used for relief of pain in the upper abdomen and
pelvis and also for pain in the upper limbs, chest and neck.
–– The most common side effect is transient diffuse dysaesthesia which
improves over days or weeks. The procedure may also produce sphincter
or motor dysfunction.
Medullary and Mesencephalic Tractotomy

•• Patients complaining of severe pain in the head, face, neck and shoulders
due to malignancy cannot be helped even by high cervical cordotomy. In
such cases, the spinothalamic tract may be divided in the medulla or the
midbrain.
•• Mesencephalic tractotomy is most effective for nociceptive cancer pain,
and the aim is to interrupt the lateral spinothalamic and spinoreticular
tracts at the level of the superior or inferior colliculus while preserving the
medial lemniscus.
Thalamus: Stereotaxic Thalamotomy

•• Currently, ablative stereotactic procedures for relief of chronic pain have
limited application except in a few patients, because of the low rate of
success achieved, relatively short duration of pain relief and associated
complications.
•• The advent of newer non-destructive techniques such as electrical
stimulation of deep brain structures, chronic intraspinal and intraventricular
administration of opiates with lower chances of complications and the
reversible nature of the effect have further reduced the need for ablative
stereotactic procedures.
•• Lesions can be made in the thalamus for the relief of intractable pain, but
the results may not always be good or constant.
•• Heat, cold (cryo) or chemical lesions may be produced stereotactically at
predetermined foci.
•• The area of maximum pain response is determined by stimulation studies
using a bipolar probe of 1 mm diameter. Pain relief was reported with no
demonstrable sensory deficit.
1435
•• The lesions were made in the termination of the quintothalamic tract which
is most medially situated.
•• The operation seems to work in pain due to malignancies and not in other
types of facial pain.
•• Lesions in the dorsomedian nucleus interfere with pain appreciation and
not with pain perception and act more like a selective leucotomy.
•• Medial thalamotomy is one of the first stereotactic operations to have been
used for neurogenic pain, and has a low complication rate with no risk of
the development of iatrogenic neurogenic pain.
•• Medial thalamotomy with the Gamma Knife produces thalamic lesions
which are reliable in size, shape and location with a low complication rate
and offers a minimally invasive, cost effective treatment for certain selected
patients with chronic intractable pain.
Hypothalamotomy
•• Implantation of chronic electrodes in various parts of the brain in intractable
pain. Stimulation studies are conducted later on to determine the best site
for the lesion which is by thermocoagulation.
Sensory Cortex Ablation

•• It has been observed during stimulation experiments on the human sensory
cortex that pain occurring in a ‘phantom limb’ could be explained by a
cortical sensory projection from the missing limb.
•• In this type of painful condition, the sensory cortex is subpially ablated
under local anaesthesia.
•• The precise area of ablation is determined by electrical stimulation during
surgery.
•• It is disappointing that after initial success from such operations the end
results are temporary.
Frontal Lobes
•• Frontal lobotomy or prefrontal leucotomy can be performed to give relief to
patients suffering from intractable pain when other measures have failed.
•• The frontal lobe fibres which are severed in such an operation have no
relation to pain pathways; still the operation proves effective on many
occasions, as the patient is relieved from the psychic apprehension of pain.
•• Fibres project from the dorsomedian nucleus of the thalamus to areas 9,
10, 11 and 12 of the anterior portion of the frontal cortex as well as to areas
13 and 14 of the supraorbital cortex, while fibres from the anterior nucleus
run to area 24 in the cingulate gyrus.
•• Interruption of these fibres or the corresponding cortical areas suppresses
awareness of suffering and the reactive expression of pain. These
operations do not raise the sensory threshold for pain.
•• Operations on the frontal lobe have been performed for relief of pain chiefly
on patients in the terminal stages of malignancy.
•• These operations carried with them definite risks of psychological
disturbance and were performed only on those patients with a short life
expectancy.
•• Specific and limited operations on the frontal lobe can now be performed
by dividing only the fibres in the inferior quadrant of the frontal lobe, those
1436
arising from the orbital cortex (subcaudate tractotomy). This may be done
either as an open operation or by the stereotactic technique.
•• Personality disturbances are minimal after these operations. Operations
on the frontal lobe should be performed only when other methods have not
given relief and when the life expectancy is very short.
Cingulumotomy
•• Stereotactic coagulation of the rostral part of the cingulum bundle gives
relief from chronic pain.
•• The operation is based on the knowledge that the cingulum consists of
multisynaptic pathways connecting the medial frontal cortex, the anterior
thalamic nuclei and the rostral midline and intralaminar nuclei with the
hippocampal formation.
•• In painful conditions, this system becomes overactive and hypersensitive
so that the emotional status of the patient becomes dominant in his reaction
to an evaluation of the pain.
•• The operation is simple and does not leave behind an apathetic person
or any obvious psychological defect associated with frontal leucotomy.
•• Patient selection for cingulumotomy must be based on assessment of the
cause of pain and the overall personality of the patient.
Hypophysectomy
•• Hypophysectomy has been efficacious in reliably relieving pain due to
secondaries from carcinoma of the breast and the prostate.
•• Endocrine manipulative measures, such as oopherectomy and adrenalectomy
were found to have a beneficial effect in advanced carcinoma of the breast
with metastasis, by tumour regression and pain relief.
•• The addition of hypophysectomy to the armamentarium of the surgeon
dealing with advanced carcinoma of the breast and prostate was possible,
following the popularisation of the trans-sphenoidal microsurgical approach
which reduced the morbidity and mortality of the transcranial approach.
•• Hypophysectomy can be performed by various means such as stereotactic
radiofrequency or cryogenic destruction, chemical destruction by use of
absolute alcohol through the transnasal trans-sphenoidal route or the
trans-sphenoidal microsurgical approach.
•• Hypophysectomy by stereo radiosurgery, radiofrequency coagulation or
by chemical agents carries the least risk.
•• The most reliable complete destruction of the pituitary gland is achieved
by direct surgical exposure (trans-sphenoidal), but involves slightly more
morbidity than the percutaneous stereotactic methods.
•• The mechanism of pain relief is not clear and an endocrine effect
(endorphin) and a neurogenic mechanism have been postulated.
•• Currently, hypophysectomy is considered a useful procedure for relieving
terminal disseminated cancer pain when other less invasive measures
have failed.
Intracranial Neurostimulation for Pain Control

•• Currently, there are two kinds of intracranial neurostimulation, which are
commonly used to control pain:
–– Motor cortex stimulation (MCS)
–– Deep brain stimulation (DBS).
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•• These have proven effective for treating a number of neuropathic and

nociceptive pain states not responsive to other therapies.
•• Intracranial neurostimulation for pain relief is most frequently delivered
by stimulating the motor cortex, the sensory thalamus (ST), or the
periaqueductal and periventricular grey matter.
•• The increasing use of intracranial neurostimulation for the treatment of
chronic pain, especially for pain not responsive to other neuromodulation
techniques, reflects the efficacy and relative safety of these intracranial
procedures.
•• Motor Cortex Stimulation for Neuropathic Pain Syndromes:
–– MCS has emerged as a promising technique for the management of
pain in patients with difficult neuropathic and central pain conditions.
–– Although MCS has proven most successful for patients with trigeminal
neuropathic/deafferentation pain and central post-stroke pain, other
conditions are now emerging as potential targets for this therapy.
•• Deep Brain Stimulation:
–– DBS may be employed for a number of nociceptive and neuropathic
pain states, including cluster headaches, chronic low back pain, failed
back surgery syndrome, peripheral neuropathic pain, facial deafferen-
tation pain and pain secondary to brachial plexus avulsion.
–– Stimulation sites included the periventricular/periaqueductal grey mat-
ter (PVG/PAG), internal capsule (IC) and ST.
Afferent Stimulation for Abolition of Pain

•• Transcutaneous Electrical Nerve Stimulation (TENS):
–– The skin and peripheral nerves could be electrically stimulated to
obtain relief of pain
–– The principle on which it is based is the fact that when the larger di-
ameter myelinated afferent cutaneous fibres or their extensions into
the dorsal column are stimulated, there is a diminution in the activity in
the dorsal horns induced by stimulation of the smaller or unmyelinated
fibres. This is based on the gate control theory of pain proposed by
Melzack and Wall.
–– Acupuncture techniques are generally based on the above principle.
The stimulation is of high frequency and low intensity just sufficient to
cause tingling.
–– Endorphin levels in the CSF show an increase during TENS.
–– The indications for TENS are many and include a wide variety of noci-
ceptive, deafferentation and neuropathic pains.
–– TENS has been useful in both acute and chronic painful states.
–– It has been used in acute painful states of post-operative pain or pain
due to musculoskeletal injury.
–– In chronic pain of various causes as the failed back, sympathetic
dystrophies and post-herpetic neuralgia, it has been found useful in
relieving pain.
–– It has no use in the treatment of central pain as in the deafferent state.
–– This procedure has the advantage of being non-invasive and can be
used for long-term stimulation at home by the patient.
–– The efficacy of TENS tends to decrease over time and many patients
show a decline in response after 1 year of use. There is no significant
morbidity due to the procedure.
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–– Pigmentation and skin hypervascularity may occur in areas of chronic

stimulation.
•• Dorsal Column Stimulation:
–– Chronic intractable pain can also be relieved by intermittent stimulation
of the dorsal column.
–– Direct implantation carries with it the risk of morbidity like transient
paresis of the leg, CSF leak, root pains and delayed intraspinal
haemorrhage. There is also the problem of long-term tolerance of the
tissues to the implant.
–– The best results have been obtained using multipolar electrodes, with
epidural placement above the level of the pain segments.
–– When the pain is localised and stimulation induced paraesthesias
completely overlap the pain segments, the results are better.
–– The main indications for DCS are pain due to the failed back
syndrome, post-amputation pain, incomplete plexus lesions, peripheral
nerve lesions, sympathetic reflex dystrophy and rest pain in peripheral
vascular disease.
–– It is contraindicated in pain due to complete transverse lesions of the
cord, cancer pain, deafferentation pain due to spinal root avulsion and
post-herpetic neuralgia.
•• Focal Brain Stimulation:
–– Relief of chronic pain may also be achieved by precise focal electrical
stimulation of brain centres.
–– Stimulation of the periaqueductal grey has been reported with 50%
good results.
–– Thalamic stimulation of the ventrobasal nuclei has also been tried and
found effective in deafferentation pain and anaesthesia dolorosa. The
mechanism of pain relief by stimulation of VPM and VPL is thought
to be due to activation of an inhibitory system independent of the
endogeneous opioid system.
–– The surgical procedure involves placement of flexible platinum
electrodes into the appropriate target area using CT/MR guided
stereotaxy or positive contrast ventriculography.
–– Physiological parameters, especially the response to electrical
stimulation help in accurate placement of the electrodes.
–– The lead wires are brought out of the scalp and temporary electrical stimu-
lation is done for about a week to determine the efficacy of stimulation.
–– If pain relief is good, then the electrodes are internalised for permanent
placement and are connected to a programmable battery powered
pulse generator.
CHRONIC PAIN SYNDROMES

Deafferentation Pain Syndromes
•• Pain is commonly due to tissue injury, but can also result from damage to
peripheral or central somatosensory pathways. Neuropathic pain which
follows damage to peripheral or central somatosensory pathways is
termed deafferentation pain. This chronic pain may then be referred to the
deafferented regions of the body surface.
•• Neuropathic pain is defined as the pain which arises as a result of damage to
the somatosensory pathways that transmit pain. Neuropathic pain after trauma
tends to be delayed in onset, severe in intensity and resistant to treatment.
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•• Pain following brachial plexus avulsion, phantom limb pain, amputation

stump pain and pain occurring after neurosurgical ablative procedures are
examples of deafferentation pain and may be due to changes in central
somatosensory pathways, as in the dorsal horn.
Clinical Syndromes of Deafferentation Pain

•• The clinical syndromes of pain following deafferentation include pain
associated with both peripheral and CNS damage.
•• Peripheral nerve and root:
–– Some common examples of painful peripheral neuropathy include
those due to diabetes, chronic alcoholism, amyloidosis and neuro-
toxins.
–– Pain is due to deafferentation of the dorsal horn.
–– Herpes zoster afflicts the roots to cause neuropathic pain with
deafferentation of the cord segments.
–– Trigeminal and other cephalic neuralgias and arachnoiditis are other
examples of deafferentation pain due to root involvement.
•• Spinal Cord: Traumatic cord injury interrupts the central connections of
nociceptive neurons in the spinal cord. Demyelination, necrotizing myelitis,
spinal cord injury, syringomyelia, spinal cord AVMs and tumours are other
causes of deafferentation pain due to cord involvement.
•• Brainstem: Common examples of pain due to deafferentation of the
brainstem are those due to vascular occlusions, surgical procedures or
demyelination.
•• Thalamus: The thalamic syndrome of Dejerine and Roussy is usually due
to vascular injury (ischaemia or haemorrhage) to the ventroposterolateral
(VPL) and ventroposteromedial (VPM) nuclei of the thalamus and it is
characterised by persistent, spontaneous burning pain.
•• Cortex: Large subcortical parietal lesions interrupting the thalamocortical
sensory pathways may produce pain similar to thalamic pain.
Treatment
•• The treatment of deafferentation pain is difficult, and the pain is intractable.
•• Anticonvulsants, like phenytoin, carbamazepine, clonazepam and valproic
acid, have been reported to be effective in relieving pain due to diabetic
neuropathy, post-herpetic neuralgia, phantom limb pain and trigeminal
neuralgia. Anticonvulsants may inhibit abnormal spontaneous activity of
other damaged neurons.
•• Steroids and NSAIDs may be useful, especially as adjunctive drugs.
•• Opiates are of limited efficacy in the management of deafferentation pain.
•• TENS may be useful in some patients with brachial plexus avulsions,
post-herpetic neuralgia (PHC), phantom limb pain and spinal cord injury.
•• Generally, ablative neurosurgical procedures do not result in lasting relief
in deafferentation pain. However, DREZ lesions have been shown to be
effective in pain relief in conditions like brachial plexus avulsion, phantom
limb pain, post-herpetic neuralgia (PHN), etc.
Phantom Limb and Stump Pain

•• Stump pain is the pain in the residual limb after amputation, and phantom
limb pain is a referred pain in the absent amputated limb.
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•• Long-term control of these pain syndromes is difficult and up to 80% of

amputees are known to experience significant stump or phantom limb pain.
•• The underlying mechanisms of pain are poorly understood, and the most
commonly used treatment regimens are ineffective at one year follow-up.
Acute Pain Following Amputation

•• Most patients undergoing amputation experience acute stump pain as a
result of surgery and nearly all amputees experience phantom limb feelings
after amputation.
•• Stump pain is usually severe immediately after amputation and subsides
with healing.
•• Persistent post-operative pain or worsening pain may indicate an
inadequate blood supply interfering with proper healing or may be due to
post-operative infection.
•• The optimal treatment of acute post-amputation phantom pain includes
patience, stress control and relaxation training.
Mechanisms of Pain in Chronic Stump and

Phantom Limb Pain
•• Phantom limb pain has previously been ascribed to psychological
mechanisms, peripheral nerve and CNS transmission mechanisms or
centrally generated reverberating circuits.
•• The following are some of the mechanisms underlying specific pain patterns
seen in phantom limb pain.
•• Blood Flow:
–– Decreased blood flow in the stump has been described to be
associated with persistent burning, throbbing and tingling phantom
limb and stump pain.
–– An increase in peripheral blood flow to the stump can result in
decreased pain.
–– A further proof of a vascular related mechanism for burning phantom
limb pain is the short-term effectiveness of sympathetic blocks and
sympathectomy that increases blood flow to the limb.
•• Voluntary Muscle Spasm: In some amputees, cramp like pain is present
when the residual limb muscles are in spasm and is relieved when they
are relaxed. Such pain may respond to biofeedback training to reduce
muscle tension.
•• Psychological Factors: Current evidence does not establish a relationship
between the occurrence of phantom limb pain and psychological factors,
but intensity may be affected by stress and exhaustion.
Treatment
•• Complete evaluation of such patients includes correlation of pain with diet,
weather, physical/mental stress and the use of prostheses.
•• Residual limb pain is to be treated before tackling phantom limb pain.
•• The prosthesis should be evaluated for its fitness and its effect on gait.
•• If trigger points are present and pain is reproduced by them local nerve
blockade may be of use.
•• When phantom limb pain is of a burning quality and related to decrease
in stump temperature, it is probably due to decreased blood flow in the
residual limb and may respond to biofeedback, peripheral vasodilators or
sympathetic blocks.
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•• A cramp like pain associated with spasm would be optimally treatment by

muscle tension biofeedback and muscle relaxants.
•• When pain is neither burning nor cramp like it is more difficult to treat, but
short-term treatment may be effective with TENS, active motion exercises,
ultrasound at the stump, steroids and sedatives/hypnotics.
•• Neurosurgical ablative procedures with the exception of DREZ lesions may
not result in long-term effective pain relief.
POST-HERPETIC NEURALGIA
•• Post-herpetic neuralgia (PHN) is a common cause of severe intractable
neuropathic pain.
•• PHN is a consequence of herpes zoster which is caused by reactivation
of varicella zoster virus contracted in childhood. The virus initially causes
varicella and remains dormant for many years in the trigeminal, the
geniculate or the dorsal root ganglia and re-erupts in the elderly or in
immunocompromised states.
•• The resulting segmental haemorrhagic inflammatory reaction of the skin and
mucous membrane is very painful before, during or after the appearance
of the rash.
•• This pain subsides with healing, but if it persists for more than 1 month it
is said to be PHN.
•• PHN occurs in 9−14.3% of patients with herpes zoster. Of these, a third
continue to have pain at 3 months and in another third it lasts for more
than one year.
•• Both the severity and incidence of PHN are directly related to the age of
the patient being worse in the elderly.
•• The sex incidence is equal and PHN has a predilection for the thoracic
dermatomes, especially T5 and T6, and the ophthalmic division of the
trigeminal nerve.
•• Pain in PHN may be both steady and paroxysmal and is described by
patients as burning or gnawing for the constant pain and sharp or shooting
for the paroxysmal component.
•• The pathologic changes are characterised by haemorrhagic inflammation
involving the dorsal root ganglion, peripheral nerve, roots, leptomeninges
•• Both central and peripheral mechanisms may be involved in PHN;
innocuous sensory stimuli from the periphery may cause hyperaesthesia,
dysaesthesia and allodynia. Failure of peripheral deafferentation surgery
and the limited success of DREZ lesions point to a central mechanism.
•• The bulk of evidence supports the use of moderate doses of steroids, such
as prednisolone 60 mg/day at the onset of HZ, in non-immunosuppressed
patients with tapering of the dose over two weeks.
•• Some of the other measures reported successful in reducing the incidence
of PHN are sympathetic blockade, amantadine, levodopa and benserazide
and intramuscular alpha-interferon.
•• Medical Treatment:
–– Antidepressants and neuroleptics.
–– Anticonvulsants: Carbamazepine, phenytoin and valproic acid have
been shown to be of limited use in PHN.
–– Tropical capsaicin: Capsaicin (8-methyl N-vanilyl 1–6 non-enamide)
selectively stimulates and then blocks unmyelinated sensory afferents
1442
from the skin and mucous membranes. Capsaicin is thought to act by

depleting substance P. It should be used 4−5 times a day for at least 4
weeks. Burning after application may be a significant problem, but may
respond to lidocaine ointment and analgesics.
–– Other therapies: Repeated nerve blocks, ethyl chloride spray,
sympathetic blocks, chlorprothixene and epidural injection of methyl
prednisolone have all been claimed to be effective.
•• Surgical Treatment:
–– Stereotactic trigeminal tractotomy was found to be effective for
ophthalmic PHN.
–– DREZ lesions give good long-term results for pain in the region of
spinal nerve roots.
PAIN SYNDROMES WITH CANCER

•• Pain syndromes due to cancer can be due to various causes and can be
broadly considered in three major categories.
•• The first and the most important category is pain associated with direct
tumour infiltration of the dura, cranial nerves, spinal cord and peripheral
nerves or compression of these structures by tumour in contiguous tissues,
e.g. epidural spinal cord compression and brachial plexopathy.
•• The second category includes pain syndromes associated with cancer
therapy including surgery, chemotherapy and radiation. Post-chemotherapy
pain syndromes include peripheral neuropathy, steroid pseudorheumatism,
aseptic necrosis of bone, headache and mononeuropathy. Post-surgical
pain syndrome is observed post-mastectomy, post-radical neck dissection,
post-thoractomy and following amputation. Post-radiation pain may be
due to radiation fibrosis of the brachial or lumbosacral plexus, radiation
myelopathy or acute herpetic and post-herpetic neuralgia.
•• The third category of pain syndromes in cancer are not related to either
cancer or its therapy (e.g. lumbar disc disease, epidural abscess,
osteoporosis). It is, therefore, important to categorise the cause of pain in
cancer patients for their optimal management.
193
CHAPTER
Trigeminal Neuralgia
INCIDENCE
•• The incidence rate of trigeminal neuralgia was reported to be 4.3 per
100,000 in the Rochester population based study.
•• The right side is more often involved than the left, in the ratio of 3:2.
•• The disease is rarely bilateral (about 5% of cases), but the incidence of
bilateral neuralgia in patients with multiple sclerosis is 18%.
•• Women have been reported to be more affected in most series from the
West, while in Indian series men are more affected.
•• The maxillary (V2) division is the most common single division to be
involved and nearly a third of patients have the pain in the maxillary (V2)
and mandibular (V3) divisions, simultaneously.
•• There is over-representation of ophthalmic (V1) division and holotrigeminal
neuralgia in the microvascular decompression (MVD) series, due to
selection bias. The mandibular (V3) division is similarly over-represented
in many series of percutaneous ablative procedures.
•• The age at onset is generally in the sixth decade.
•• The occurrence of trigeminal neuralgic pain in children should prompt a
thorough search for another cause such as abscess or tumour.
CLINICAL FEATURES
•• Tic douloureux is diagnosed solely on the basis of patient’s history.
•• The characteristic feature is the sudden stabbing (described as lancinating
or lightening or electric shock like) pain in the distribution of one or more
divisions (or branches thereof) of the trigeminal nerve, generally on one side.
•• Each pain episode is stereotyped and it occurs as a brief spell lasting a
few seconds or a minute.
•• The onset of each spell is sudden and the intensity severe.
•• The pain can occur spontaneously or may be triggered by light touch over
the nasolabial fold, upper lip or tooth (‘trigger zones’).
•• Talking, smiling, eating (chewing or swallowing), contact with cold breeze or
water on the face, brushing the teeth or shaving are common daily events
that precipitate pain and become impossible tasks.
•• Often the patient can give the history only by writing since speaking may
precipitate the pain.
•• The unshaved, halitotic and cachectic appearance signals unremitting
prolonged spells of pain.
•• The pain commonly starts in the teeth or gums and patients have usually
had several teeth extracted before coming to the neurosurgeon.
1444
•• Some patients rub the face vigorously during the attack while most others
guard their face from the slightest of contact.
•• Patients learn to avoid cold drinks and fear the winter.
•• There might be a sudden wince of the facial muscles in response to the
pain and this characteristic gives the name tic douloureux.
•• True hemifacial spasm is also seen along with trigeminal neuralgic pain
and this is described as tic convulsive. A single dolichoectatic vessel may
be found compressing both the trigeminal and facial root entry zone in
such cases.
•• The pain may be confined to one branch of a division. The supraorbital/
nasociliary (from V1), infraorbital/zygomaticotemporal (from V2) and inferior
alveolar/auriculotemporal (from V3) branches may be exclusively involved.
•• The pain episodes are well known to spontaneously remit and patients may
even be able to stop medication.
•• The pain may cease for several months only to return with renewed vigour,
increasing in severity and frequency with each episode.
•• In due course, the attacks might cease and then start in a different division
and rarely on the opposite side.
•• Recently an attempt has been made to separate the above described
‘classical’ trigeminal neuralgia (TN 1) from the ‘atypical’ trigeminal neuralgia
(TN 2).
•• In the latter syndrome the pain is aching, throbbing or burning for more than
50% of the time and there is constant background pain but strictly confined
to the anatomical distribution of the trigeminal divisions.
•• TN 2 might represent progression of idiopathic TN 1 or it might indicate
a secondary cause, such as tumour. This entity of ‘atypical’ trigeminal
neuralgia is not to be confused with atypical facial pain syndrome. ‘Atypical’
trigeminal neuralgia has also been treated with MVD and multiple vascular
conflicts are the rule.
•• Clinical examination is remarkable for the absence of physical signs.
•• A slight sensory loss over the area of pain may be disclosed by careful
examination during the attack and is in itself not against the diagnosis of
primary or idiopathic trigeminal neuralgia.
•• Absent corneal reflex behoves a search for a cerebellopontine angle mass
in a patient presenting with trigeminal neuralgia.
•• Profound sensory loss may be due to a past ablative procedure but must
lead one to suspect a secondary cause.
•• Arterial hypertension, especially systolic hypertension, is seen more often
than in age-matched controls.
•• Good control of blood pressure alone may reduce the severity and
frequency of trigeminal neuralgia.
PATHOLOGY
•• Trigeminal neuralgia has been classified into primary (idiopathic) and
secondary varieties. The primary variety is far more common.
•• In the secondary variety, there is a tumour, vascular malformation or cyst
causing compression, stretch or distortion of the trigeminal nerve.
•• Epidermoid tumour in the cerebellopontine angle must be suspected in
young patients and vestibular schwannoma in adults.
•• Trigeminal neuralgia can be a false localising sign of raised intracranial
pressure.
Chapter 193 • Trigeminal Neuralgia
1445
Table 1: Causes of secondary trigeminal neuralgia

Lesions causing secondary trigeminal neuralgia
Vestibular schwannoma
Epidermoid tumour
Meningioma
Petrous osteoma
Abscess
Tuberculoma
Cysticercosis
Chiari malformation
Cavernoma of V nerve
Aneurysm
Arteriovenous malformation
•• The list of lesions causing secondary trigeminal neuralgia is summarised

in Table 1.
•• The pathology in the idiopathic variety was not detectable prior to surgery
until the advent of modern MR imaging.
•• It is proposed that with age, the arteries become tortuous, elongated
and rigid. This, coupled with the sagging of the brain, tends to bring the
trigeminal nerve into position of contact or compression by the vessels.
•• Jannetta reported that the compression is on the rostral and anterior portion
of the nerve when the pain is in the V2 or V2–3 distribution. The vascular
contact is on the caudal aspect of the root entry zone in V1 neuralgia. This
correlates well with the known anatomical fact of the inverted distribution
of the fibres in the trigeminal root entry zone (caudal ones representing
the V1 division).
•• The degree of compression may be variable. The compression might be
anywhere from the pontine attachment of the root up to the Meckel’s cave.
This was believed to be because of the variable length of the Obersteiner-
Redlich zone, i.e. the junction of the central (oligodendroglial) and peripheral
(Schwann cell) myelin in the trigeminal root.
•• In an ultrastructural study of trigeminal root entry zone biopsies obtained
during MVD, axonopathy and axonal loss, demyelination, dysmyelination,
residual myelin debris and the presence of excess collagen, including
condensed collagen masses were found.
PATHOGENESIS
•• Gardner postulated that ‘short-circuiting’ between the demyelinated axons
in the trigeminal root results in ‘cross talk’ (ephaptic transmission) leading
to the paroxysms of pain.
•• The abnormal peripheral discharge has been shown by microneurographic
recording during the course of radiofrequency gangliolysis.
•• Since remyelination cannot explain the immediate recovery after MVD,
reversal of a conduction block caused by the compression has been
invoked.
•• Impaired trigeminal nociceptive processing has been described in patients
of trigeminal neuralgia, who have concomitant chronic facial pain. This has
1446
been proved by nociceptive blink reflex (nBR) testing and by recording pain
related evoked potentials (PREP).
•• Central mechanisms in the pontine nuclei or tracts may also play a part in
the genesis of trigeminal neuralgia. Multiple sclerosis is the best example.
IMAGING
•• Trigeminal neuralgia remains a clinical diagnosis.
•• CT scans are routinely done prior to definitive therapy for trigeminal
neuralgia to exclude a secondary cause such as a tumour. The mass lesion
might be on the contralateral side.
•• CT might show dolichoectasia of the vertebrobasilar arteries and this can
be confirmed by CT angiography.
•• Although dolichoectatic vertebrobasilar arteries may be present, the
compression on the root may often be due to a superior cerebellar artery
loop, rather than the dolichoectatic vessel.
•• MR imaging can demonstrate the neurovascular conflict and help select
patients for and to plan the surgery.
•• Several MR techniques are available for imaging the artery and the nerve
simultaneously.
•• These include 3-D constructive interference in steady state (3-D CISS) and
3-D fast inflow with steady-state precession (3-D-FISP).
•• MR angiography with multiplanar reconstruction helps detail the anatomy
of the arterial compression, while the veins are shown in 3-D CISS imaging
only.
•• Recently balanced fast-field echo (BFFE) imaging with 3-D TOF MRA and
gadolinium enhanced 3-D specific gravity (SPGR) imaging have been
combined to accurately predict the neurovascular conflict.
TREATMENT
Medical Therapy
•• Carbamazepine is the sheet anchor drug in managing trigeminal neuralgia.
•• The efficacy of carbamazepine has been proved in at least six placebo-
controlled randomised trials.
•• The response is specific enough to use it as a ‘therapeutic diagnostic test’.
•• The dose that gives relief may be as little as 100 mg bid in some patients,
while others get relief only with 1600 mg per day.
•• It is ideal to keep the dose strength at a low level (200–300 mg) and increase
the frequency (say 4–5 times a day). This gives sustained pain relief and
helps minimise the peak dose ataxia, drowsiness and visual blurring.
•• The patient must be told to take the drug before eating, washing, brushing
or shaving.
•• Skin rash and depression of blood counts are the most frequent reasons
to switch over to another agent.
•• The drug of choice to those intolerant of carbamazepine should be
oxcarbazepine.
•• The pain generally escapes control with carbamazepine over some months
or years.
•• Drug additions at this stage improve the pain.
•• The additional drug could be lamotrigine or baclofen.
•• Gabapentin has been used alone or in combination with trigger point block
with a local anaesthetic.
1447
•• One study suggests that sumatriptan administered subcutaneously controls

intractable trigeminal neuralgia.
•• Recently, injection of botulinum toxin in the face has been advocated for
intractable trigeminal neuralgia, but this drug has been claimed to work for
migraine, tension, headache and post-herpetic neuralgia too.
Surgical Procedures
•• The ideal surgical procedure for trigeminal neuralgia should have a 100%
initial success rate with no recurrence of pain on long-term follow-up.
•• It should not leave the face numb and there should be no dysaesthesia or
anaesthesia dolorosa.
•• It should not be associated with mortality or morbidity due to involvement
of the neighbouring cranial nerves, brainstem and cerebellum.
•• It should be suitable for all ages and should come at an affordable cost.
•• It should also address the aetiology as is known now.
Peripheral Procedures
•• These consist of trigeminal branch blocks with local anaesthetic, followed
by alcohol injection or branch avulsion.
•• Sensory loss is invariable.
•• The pain invariably comes back within a few months in case of alcohol/
glycerol block and within a year or two in case of branch avulsion.
•• The recurrence is due to quicker regeneration following lesion in the more
peripheral sites of the trigeminal nerve, as compared to lesions made in
the retrogasserian roots.
•• Such peripheral procedures may need to be considered only in the very
old and infirm patient with neuralgia restricted to one branch of a trigeminal
division.
Percutaneous Retrogasserian
Glycerol Rhizolysis
•• Glycerol, which can be harmlessly ingested by humans, is neurotoxic when
injected into the nerve or around it.
•• Percutaneous retrogasserian glycerol rhizolysis (PRGR) offers a low-cost,
low-risk method of treating trigeminal neuralgia that can be easily repeated
in case of recurrence.
•• Results of Percutaneous Retrogasserian Glycerol Rhizolysis:
–– The initial complications include headache, transient cardiac dysrhyth-
mia, hypertension, seizure, temporal lobe haematoma, other cranial
nerve palsies due to spread of glycerol, oral herpes and aseptic/bacte-
rial meningitis.
–– The factors, which predict success of PRGR, are patients without any
constant facial pain, patients with immediate facial pain during glycerol
injection and patients with new trigeminal deficits after PRGR.
Percutaneous Radiofrequency
Thermocoagulation (PRFTC)
•• This procedure depends on the differential sensitivity of nerve fibres to
heat damage.
•• The myelinated touch fibres are more heat resistant than the unmyelinated
pain fibres.
1448
•• Therefore, controlled heating using radiofrequency energy ablates the pain

carrying fibres, while theoretically leaving the other sensations largely intact.
•• The technique enables proper localisation in the ‘stimulation mode’ and
temperature monitoring in the ‘lesion mode’.
•• When the electrode is properly placed, the impedance should be 150–350 Ω.
•• The impedance is higher if the electrode is in non-neural tissue.
•• Next, stimulation of the retrogasserian root is done with 100 mV square
wave current at 50 Hz and 1 msec duration. This should produce a tingling
paraesthesia in the distribution of the desired root.
•• The stimulation current strength and frequency are increased in steps until
the patient reports the paraesthesiae.
•• If more than 0.5 V is needed or if there is a motor response, the electrode
tip must be repositioned.
•• The usual limit thermocoagulation is 60°C for 60–90 seconds. If the
threshold for stimulation is high, a higher temperature setting is needed
for lesioning. The end point is hypoalgesia (tested with a pin on the face)
and not hypoaesthesia. This can of course be tested only when the patient
awakens enough from the anaesthesia.
•• If adequate numbing has not been achieved, additional lesions can be
made in 5°C increments up to 80°C.
Percutaneous Trigeminal
Balloon Compression (PTBC)
•• In the procedure a 14G needle is passed percutaneously up to the foramen
ovale but not into it.
•• A balloon catheter is pushed for 1 cm beyond the needle tip and is inflated
to 0.5 cc for about 1−10 minutes.
•• The balloon inflates to a pear shape and this can be seen under image
intensifier screening, as the inflation is done with iohexol.
•• The shorter balloon inflation time is associated with lower rates of initial pain
relief, lesser facial dysaesthesia and a higher recurrence risk.
•• Higher inflation pressures are associated with greater incidence of transient
bradycardia, severe hypertension or hypotension during the procedure.
•• The incidence of trigeminal motor weakness is the highest with PTBC as
compared to PRGR or PRFTC.
Microvascular Decompression (MVD)

•• Table 2 summarises the indications and contraindications for MVD.
•• Microvascular decompression surgery can be accomplished in a minimally
invasive manner.
•• Dolichoectatic vessels are no longer a contraindication for MVD.
•• On exploration, a non-dolichoectatic vessel or vein may be found to be
the cause of the trigeminal root entry zone compression, rather than the
dolichoectatic vessel per se.
•• Even if the dolichoectatic vessel were found directly distorting the root, it
can be effectively encircled.
•• The recurrence rate was higher when muscle was used as the interposing
substance.
•• Muscle was replaced by polytetrafluoroethylene (PTFE-Teflon®) pledgets.
•• The pledget must be placed in contact with the vessel, rather than in close
contact to the nerve.
1449
Table 2: Indications and contraindications for MVD

Indications for MVD
Failure of medical therapy
–– Lack of initial response
–– Escape of control with medication over time
–– Unacceptable side effects of medication
Patient fit for anaesthesia
V1 division pain (singly or in combination)
MR demonstrable compression/distortion by vessel
As a primary procedure for fit patients, especially the young
As a secondary procedure when pain recurs after a previous ablative procedure
Tic convulsive-associated need for facial MVD
Patient choice (those who are averse to facial sensory loss)
Contraindications for MVD
High anaesthetic risk, medical risk
Anaesthesia dolorosa from a previous ablative procedure
Pain on the side of the only good hearing ear
Very elderly patient
•• Transient brainstem signal intensity change on MRI after MVD has been
noted.
•• The mortality for trigeminal MVD is mainly due to cerebellar injury and
brainstem infarction.
Radiosurgery
•• The latest (and the most expensive) method of treating trigeminal neuralgia
is to ablate the retrogasserian cisternal part of the trigeminal nerve with
gamma knife radiosurgery.
•• Linear accelerator based radiosurgery seems to be nearly as effective.
•• The lower radiation dose (70 Gy) with a single 4 mm isocentre results in
less sensory dysaesthesia.
•• Radiosurgery has also been used in patients with multiple sclerosis but
they fare poorer than the idiopathic variety.
194
CHAPTER
Glossopharyngeal and
Other Cranial Neuralgia
Ravi Ramamurthi • Goutham Cugati
•• Glossopharyngeal neuralgia is described as a paroxysmal painful condition

confined to the somatosensory distribution of the IX nerve (ear, tonsillar
region, larynx, posterior one-third of tongue and nasopharynx) and triggered
off by swallowing, coughing, laughing, speaking and yawning.
•• The pain is described classically as lancinating and may last from a few
seconds to several minutes.
•• It can also cause an unpleasant sensation in these areas, palatal
myoclonus, syncope and cardiac arrest.
•• As is usual with paroxysmal painful syndromes, it is characterised by
periods of exacerbation and remission. The period of remissions may vary
from a few months to several years.
•• A very small percentage of patients with glossopharyngeal neuralgia
occasionally become hypotensive, bradycardic, lose consciousness and
have seizures associated with a paraoxysm of pain. This syndrome, called
vago-glossopharyngeal syncope, is due to enhanced vagal outflow.
CAUSES
•• Glossopharyngeal neuralgia is thought to be caused by irritation of the
IX cranial nerve and most of the time the source of irritation is not found.
•• Some of the known causes producing this type of pain are:
–– Vascular loop pressing over the cisternal portion of the IX nerve
–– Benign and malignant lesions of the skull base
–– Local infections and tumours in the throat and mouth
–– Eagle’s syndrome
–– Infarction (Lateral medullary)
–– Multiple sclerosis.
•• In Eagle’s syndrome, an elongated styloid process or an ossified stylohyoid
ligament results in the compression of the glossopharyngeal nerve. This has
been described mostly as an acquired condition after trauma or a surgical
procedure in the throat like tonsillectomy.
EPIDEMIOLOGY
•• A comparison of epidemiological and clinical features of trigeminal neuralgia
and glossopharyngeal neuralgia has revealed that the overall age and sex
adjusted annual incidence rates were significantly higher for trigeminal
neuralgia than for glossopharyngeal neuralgia.
•• Glossopharyngeal neuralgia is milder than trigeminal neuralgia, as indicated
by the number of episodes, duration and characteristics of pain.
Chapter 194 • Glossopharyngeal and Other Cranial Neuralgia
1451
•• The right side is affected more often and bilateral involvement is less
common in trigeminal neuralgia, as compared to glossopharyngeal
neuralgia.
EXAMINATION
•• The patient suffering from glossopharyngeal neuralgia may not have any
•• If a lesion in the skull base is the cause for the neuralgia, there may be
multiple cranial nerve deficits, depending on the extent of the lesion.
•• An enlarged styloid process may be palpable in the tonsillar fossa as in
Eagle’s syndrome.
•• Digital palpation of the styloid process often reproduces pain or a foreign-
body sensation.
•• A thorough ENT evaluation is required if local pathology is suspected.
DIAGNOSIS
•• X-ray lateral views of the skull base and cervical spine may show an
enlarged styloid process ipsilateral to the side of pain which helps to
diagnose Eagle’s syndrome.
•• ECG is mandatory for all patients and especially those having syncopal
attacks.
•• ECG monitoring, done during swallowing induced syncope (loop monitoring),
shows cardiac asystole which is characteristic of glossopharyngeal
neuralgia.
•• MRI is an important investigation to rule out a tumour, one of the common
causes of symptomatic glossopharyngeal neuralgia.
•• Gadolinium enhanced images will pick up even small lesions and, in larger
lesions, it clearly delineates the extent of the tumour.
•• 3D constructive interference in steady state (CISS) and 3D fast imaging
with steady-state free precession (FISP) MR angiography, may be useful
for evaluating neurovascular contact of the nerve root exit zone of the
glossopharyngeal nerve, which is located in the supraolivary fossette.
•• The posterior inferior cerebellar artery (PICA) is the most common offender
followed by the vertebral artery, the anterior inferior cerebellar artery (AICA)
and other vessels or combinations of vessels.
•• Balloon occlusion test using double microcatheter technique helps to
identify the vessel responsible for glossopharyngeal neuralgia.
•• Once the microcatheter is in the desired vessel, the balloon is inflated to
block the vessel which will make the pain disappear, while deflation of the
balloon reproduces the pain. This test is repeated several times and the
same pattern seen consistently confirms vascular compression as the
aetiology. This way, patient selection for MVD can be done.
•• This procedure may lead to complications like thromboembolism, balloon
migration, premature deflation and others.
TREATMENT
Medical Management
•• The medical management of this condition is similar to that of trigeminal
neuralgia and the medications used include carbamazepine, oxcarbazepine,
gabapentin, pregabalin, phenytoin and several other newer antiepileptics.
1452
•• Antidepressants like amytriptyline have also been used in treating this

condition.
•• Neuropathic pain is generally not controlled by opioids. However, usefulness
of opioids in glossopharyngeal neuralgia and its possible mechanism has
been described. Opioids control neuropathic pain by their effects on cortical
brain regions and the thalamus, the descending antinociceptive pathway
(via actions on the periaqueductal grey matter) and by modulating pain
transmission in the spinal dorsal horn.
Surgical Management
Microvascular Decompression
•• Surgery should be advised when medical management fails to control
the pain.
•• This can be microvascular decompression in the posterior fossa or section
of the glossopharyngeal roots in the neck or in the posterior fossa.
•• The supraolivary fossette, which is the most medial portion of the
cerebello-ponto-medullary angle, is close to the root entry zone of the
glossopharyngeal nerve and is the vulnerable location for neurovascular
decompression surgery.
•• In patients with cardiac syncope, peri-operative placement of a temporary
pacemaker is advocated.
Nerve Root Section
•• Glossopharyngeal nerve root section in the posterior fossa gives good
results.
•• The glossopharyngeal nerve emerges out of the skull along with the vagus
nerve roots through the jugular foramen.
•• The glossopharyngeal roots are rostral and are identified from the vagal
roots by a dural partition, which separates the fibres at their exit from the
skull. This makes it easy to pick up and divide the glossopharyngeal roots.
•• Transcranial endoscopic approach for glossopharyngeal neurotomy has
also been tried with good outcome.
•• Recently, there has been a report of keyhole microsurgery with good
outcome.
•• Gamma knife radiosurgery has been used for intractable pain with the target
being the distal part of the nerve and the maximum dosage being 75 Gy.
•• More studies are awaited to determine the optimal radiation dose and target
of GKS for achieving long-term pain relief.
•• Resection of the elongated styloid process or the ossified stylohyoid
ligament will provide relief of pain in Eagle’s syndrome. A lateral
transcutaneous approach and resection is required.
•• Percutaneous rhizotomy of the glossopharyngeal nerve in the jugular
foramen should be undertaken only by surgeons trained in this technique.
•• The surgeon and patient have to be aware of the unavoidable sensorimotor
deficits of the IX and X nerves.
Other Ablative Procedures
•• Tractonucleotomies at the medullary level should be reserved essentially
for pain of malignant origin.
•• Microwave ablation of the glossopharyngeal nerve has been tried.
1453
Complications
•• Post-operative complications of surgical treatment of glossopharyngeal
neuralgia are:
–– Sensory and motor deficits of IX and X nerves
–– Vocal cord paralysis
–– Cerebellar or/and brainstem infarction
–– Hypertensive crisis
–– CSF leak and pseudomeningocoele
–– Intra-operative mortality.
GENICULATE NEURALGIA
•• Geniculate neuralgia, also known as nervus intermedius neuralgia, is
characterised by pain deep in the ear radiating to the pinna.
•• The pain is lancinating and, unlike other typical neuralgic pains, an episode
may last for an hour or so.
•• It is due to abnormalities of the somatosensory branch of the VII cranial
nerve (nervus intermedius of Wrisburg) and the geniculate ganglion.
•• Patients may also complain of excessive salivation, bitter taste, tinnitus and
vertigo during the pain attacks which might reflect the central connections
of the nervus intermedius.
•• The pathology in this condition is presumed to be similar to any other
neurovascular compression syndrome, where a vascular loop causes
compression over the root exit zone of the nervus intermedius.
•• Geniculate neuralgia can also be seen in Ramsay Hunt syndrome which is
caused by varicella zoster virus. Rash with facial paralysis are the additional
features seen in patients with Ramsay Hunt syndrome.
•• Geniculate neuralgia may respond to carbamezapine.
•• Operative treatment consists of MVD or section of the nervus intermedius
or the geniculate ganglion.
•• A combined posterior fossa-middle fossa approach for adequate exploration
and/or section of the V, IX and X cranial nerves, as well as the geniculate
ganglion and nervus intermedius.
•• Gamma knife surgery is an alternative
PERSISTENT IDIOPATHIC FACIAL PAIN

•• Persistent idiopathic facial pain (PIFP) refers to pain in the trigeminal nerve
distribution that does not fit into the classical description of other cranial
neuralgias.
•• Previously termed as atypical facial pain there is no obvious cause and the
pathophysiology is unknown.
•• The International Headache Society defines PIFP as follows:
–– Pain in the face
–– Pain confined at onset to a limited area on one side of the face, which
is poorly localised
–– Pain present throughout or for most of the day and daily
–– No sensory loss or other physical signs
–– No abnormalities in laboratory or imaging studies.
•• This entity predominantly affects adults with no sex predilection.
•• Neurological examination is essentially normal.
1454
•• PIFP is a diagnosis of exclusion. Hence, the more common causes of

facial pain need to be excluded with all available facilities before coming
to the diagnosis of PIFP.
•• Contrast MRI is the investigation of choice.
•• Treating this condition is difficult and is less effective than for other facial pain
syndromes. Medications used include anticonvulsants, antidepressants,
topical anaesthetic agents and narcotics. Multimodality approach with
involvement of a psychiatrist and pain therapist is appropriate.
TOLOSA-HUNT SYNDROME
(PAINFUL OPHTHALMOPLEGIA)
•• This syndrome is a non-specific inflammatory process in the region of the
cavernous sinus/superior orbital fissure.
•• It is characterised by periorbital or hemicranial pain, ipsilateral ocular
nerve palsies, oculosympathetic paralysis and sensory impairment in the
trigeminal nerve distribution (mainly ophthalmic and occasionally maxillary
division).
•• Occasionally, there may be additional cranial nerves palsies (II, V2, VII)
ipsilateral to the ophthalmoplegia.
•• Having a relapsing and remitting course, it responds promptly to systemic
corticosteroid therapy.
•• This syndrome affects patients of any age group and there is no sex
predilection.
•• Orbital pain usually lasts for 2 weeks.
•• All the three nerves supplying the external ocular muscles can be involved
in various combinations.
•• There have been reports of involvement of the optic nerve which might
favour pathology around the orbital apex.
•• The differential diagnosis of this condition is trauma, neoplasm or aneurysm
in the region of the cavernous sinus/superior orbital fissure.
•• Contrast enhanced MRI is the investigation of choice. Coronal views may
show abnormal soft tissue with contrast enhancement in the region of the
cavernous sinus, the intensity of which is similar to an inflammatory process.
•• High resolution CT can demonstrate the same, but is less sensitive.
•• The findings on the MRI may be confused for a cavernous sinus
meningioma, lymphoma or sarcoidosis. Hence, post-steroid therapy MRI
showing decrease in the size of the lesion is considered diagnostic.
•• Cerebral angiogram may show segmental narrowing of the intracavernous
carotid artery, which also resolves with corticosteroid administration.
•• Biopsy of the lesion is done as a last resort.
•• Corticosteroids have been used effectively for treating this condition. They
dramatically decrease the periorbital pain and also shorten the natural
course of the disease.
•• Tolosa Hunt syndrome is a diagnosis of exclusion where all the probable
causes of a parasellar lesion causing painful ophthalmoplegia are ruled out.
OCCIPITAL NEURALGIA
•• Occipital neuralgia is caused by irritation of the greater occipital nerve,
the causes being entrapment of the nerve in the trapezius muscle due to
post-operative scarring or injury to the nerve.
1455
•• Patients may have unilateral or bilateral throbbing pain over the occipital
region.
•• Since the greater occipital nerve receives branches from the superior
cervical sympathetic ganglion, the trigeminal ganglion, acoustic and
vestibular nerves, it may produce additional symptoms of vomiting, nausea,
vertigo and photophobia.
•• Pressure on the greater occipital nerve will produce a positive Tinnel’s sign.
•• Potentially dangerous conditions, like craniovertebral junction pathologies
which may produce similar symptoms, have to be ruled out before coming
to the diagnosis of occipital neuralgia.
•• Nerve block will often relieve the patient of the neuralgic pain. In patients
with persistent pain, nerve decompression or sectioning of the nerve stem,
which causes loss of sensation in the occipital region, may be required.
COSTEN’S SYNDROME
•• Costen’s syndrome is temporomandibular joint dysfunction characterised
by aching pain felt in front of the ear which is aggravated by chewing.
•• It is due to malalignment of the TM joint or rarely to rheumatoid arthritis.
READER’S SYNDROME
•• Reader’s syndrome also called the paratrigeminal syndrome is character-
ised by pain around the eye associated with a sympathetic paresis (ptosis
and small pupil) and is usually associated with granulomatous lesions or
nasopharyngeal carcinoma involving the middle fossa.
•• Some patients have a combination of the features of trigeminal neuralgia
and ciliary neuralgia.
•• The pain occurs in paroxysms and is accompanied by redness and watering
of the eyes.
•• Simultaneously, there are trigger zones in the forehead and around the
eye that initiate the paroxysm.
•• A combination of carbamezapine and ergot therapy has been found
effective.
195
CHAPTER Microvascular
Decompression
Ravi Ramamurthi  Manish Singh
•• The proximity of the blood vessels to the nerves in the cerebellopontine

angle makes the cranial nerves vulnerable to compression by the blood
vessels.
•• This compression is a major cause of trigeminal neuralgia (V), hemifacial
spasm (VII) and glossopharyngeal neuralgia (IX).
•• It may also cause vertigo (VIII), tinnitus (VIII), hypertension (X) and
spasmodic torticollis (XI).
PATHOPHYSIOLOGY
•• It has been proposed that a number of cranial nerve dysfunction syndromes
are caused by vascular cross compression of the root entry zone (REZ) of
the appropriate cranial nerve.
•• This may be a direct reflection of the ageing process which leads to: (a)
arteriosclerotic degeneration of the arteries resulting in their elongation and
(b) in hindbrain sag (descent) which causes abnormal contacts between
the blood vessels and the lower cranial nerves.
•• Elongation of these arteries by sagging of the brainstem may cause
abnormal neurovascular contacts.
•• The arteries in the posterior fossa arise anteriorly and travel posterolaterally
around the brainstem and have a relatively long course.
•• The relation between the neural structures and the veins, both intrinsic and
bridging veins, may also be altered.
•• The abnormal neurovascular contact may cause hyper or hypoactivity,
depending on the site of contact and the rapidity with which this contact
occurs.
•• In general, hyperactivity results when there is a gradually progressive
compression at the point on the nerve where peripheral myelin (Schwann
cell) changes to central myelin (oligodendroglia). This area is at the root
entry zone (REZ) of the V and VII nerves and in the VIII nerve is located
peripherally, near the internal auditory meatus.
•• It had been assumed that vascular contact at the REZ was solely
responsible for the dysfunction.
TRIGEMINAL NEURALGIA
Selection of Patients
•• The indications for MVD are failed medical therapy using carbamazepine,
phenytoin or both, or when the patient has adverse reactions to medication.
Chapter 195 • Microvascular Decompression
1457
•• Fitness for anaesthesia and major surgery is vital in older patients and the
usually accepted cut off point is 65–70 years of age. Older patients may
also be operated upon, if found fit.
Investigations
•• Plain skull X-rays are done to see the configuration of the skull, especially
the posterior fossa and are useful in planning the craniectomy.
•• The size and aeration of the mastoid air cells are noted, as also the
configuration of the auditory meatus and the petrous temporal bone.
•• CT scans and MRI are done to rule out extra-axial tumours, plaques
of multiple sclerosis, ecstatic arteries and possible arteriovenous
malformations.
•• Three-dimensional time-of-flight magnetic resonance angiography (3D-TOF
MRA) is useful in demonstrating cranial nerve compression, as well as in
excluding other aetiologies.
•• A boundary imaging of fusion three dimensional (3D) magnetic resonance
(MR) cisternogram/angiogram has been used for virtual assessment of the
spatial relationship of the neurovascular compression at the REZ.
•• Pre-operative imaging of the neurovascular structures can be performed
using constructive interference in the steady state magnetic resonance
(CISS MR) imaging, which consists of 2D images.
•• Electrophysiological tests are useful in pre-operative assessment and
in post-operative follow-up and include otovestibular testing, BAER and
trigeminal evoked potentials.
Anatomy of the Trigeminal Nerve in the

Cerebellopontine Angle
•• The root entry zone (REZ) of the trigeminal nerve is the first one centimetre
of the nerve after it has entered from the pons.
•• In its intradural course, the nerve enters from the lateral part of the pons
just inferomedial to the ala of the cerebellum and runs obliquely upwards,
towards the petrous apex and enters Meckel’s cave, leaving the posterior
fossa beneath the tentorial attachment.
•• The angle of entry of the trigeminal nerve into the pons is acute and in some
cases the portion near the pons may be parallel to the pons.
•• The number of fascicles is variable, as is the diameter of the nerve.
About a hundred fascicles, which form the dorsal root and emerge from
Meckel’s cave, coalesce about half to one centimetre from the pons into
a gelatinous mass and this mass is surrounded by piamater and is called
the portio major.
•• About 20% of the sensory fascicles do not enter the “fibrous cone” and are
separate from the portio major. They enter the pons between the portio
major and the motor fibres. These fibres carry a considerable part of light
touch and proprioception and, therefore, complete section of the portio
major gives good results without much loss of touch and proprioception.
•• The motor part arises as a large number of fascicles, which join together
2 or 3 mm from the pons to form two distinct structures surrounded by pia
mater. The motor part courses medial to the sensory root, crosses under
the Gasserion ganglion and exits through the foramen ovale.
1458
Surgical Procedure
•• The positions for surgery that may be used are lateral, park bench, supine
with head rotated, and sitting.
•• A vertical retromastoid incision is made about half to one centimetre medial
to the mastoid notch.
•• The incision is 5−7 cm long and one-third of this should be superior to the
nuchal line.
•• The incision is carried down to the bone and craniectomy (2.5 cm x 2.5
cm) is done, exposing the transverse sinus superiorly and the sigmoid
sinus laterally.
•• It is essential to expose the junction of the transverse and the sigmoid
sinuses.
•• The dura may be opened in any convenient fashion, but it is essential to
expose the junction between the superior and the lateral surfaces of the
cerebellum.
•• The superior petrosal vein is identified and, if absolutely necessary, it is
coagulated and divided, if it prevents access to the entire length of the
trigeminal nerve.
•• The ala of the cerebellum is retracted and the trigeminal nerve comes
into view.
•• The arachnoid over the nerve is dissected using sharp dissection and the
whole nerve is exposed.
•• The IV nerve lies above and parallel to the V nerve.
•• In lower division TN, the offending vessel is usually the superior cerebellar
artery compressing the nerve superiorly or anteriorly and in upper division
TN, the anterior inferior cerebellar artery is often the offending artery. The
whole complex of arterial loops is gently elevated from the nerve.
•• Various substances, like Gelfoam®, muscle or plastic prosthesis-like Ivalon
and shredded Teflon felt, have been interposed between the offending
vessels and the nerve.
•• The cross compression may be due to an arterial loop, a vein or a
combination of both. Other causes are tumours, AVM and aneurysm.
Results
•• Any cranial nerve dysfunction that may occur postoperatively is usually
temporary, except in the case of the VIII nerve where there is usually
permanent hearing loss.
•• Cerebellar dysfunction due to infarction or haemorrhage may occur in a
small percentage of patients.
•• Rare complications, like polytetrafluoroethylene-induced granuloma,
brainstem cyst and brainstem infarction, have been reported.
HEMIFACIAL SPASM
•• HFS is more common in women than in men and more on the left side
than the right side.
•• Two types of HFS have to be differentiated, typical and atypical.
•• Typical HFS, seen in 90% of patients, begins in the orbicularis oculi muscle
and spreads caudally to involve the rest of the face.
•• Atypical HFS, affecting 10% of patients, starts in the buccal muscles and
spreads upwards.
•• This differentiation is of surgical importance as, in typical HFS, the offending
vessel is on the anterior caudal side of the nerve or on the pons over the
1459
intrapontine part of the facial nerve. In atypical HFS the vessel compresses
the rostral posterior aspect of the nerve and may be located between the
facial and the auditory nerves or above the auditory nerve.
Selection of Patients
•• MVD for HFS is a cosmetic operation and should be undertaken only if it
seriously affects the patient’s social or professional life. Patients who are
fit for surgery are selected, age being no bar.
Anatomy of the Facial Nerve in the

Cerebellopontine Angle
•• The facial nerve may be compressed either in its intrapontine or
extrapontine course in the cerebellopontine angle.
•• The junction zone between central and peripheral myelin is close to the
exit of the nerve from the pons.
•• The nerve runs superficially in the pons in a caudorostral direction starting
at the pontomedullary junction.
•• On exiting from the pons, it runs laterally in the cerebellopontine angle
to enter the internal auditory meatus along with the VIII nerve and the
nervous intermedius.
Surgical Technique
•• The anaesthesia and positioning are the same as for TN.
•• The pons is then visualised as well as the choroid plexus at the lateral exit
foramen of the IV ventricle.
•• The VII nerve is thus approached from a caudal direction in typical HFS.
•• The view of the VII nerve may be obstructed by the offending vessel, either
single or multiple arteries or a vein.
•• The dissection must be carried out all around the nerve to make sure that
a second compressing vessel is not missed.
•• The technique and the materials used are the same as in TN.
•• BAER and direct monitoring of VIII nerve function during this operation
have been found useful in preventing injury to the VIII nerve.
•• Facial muscle EMG is also useful to make sure that the compression has
been relieved.
Results
•• In the majority of patients the compression is by an artery.
•• The offending arteries may be the AICA, PICA, vertebral or an ecstatic
basilar artery.
•• Good results are obtained with caudal compression by AICA or PICA; howev-
er, the results were not as good in patients with compression by the vertebral
artery or when the offending vessel was between the VII and VIII nerves.
•• The most common and permanent damage is ipsilateral hearing loss.
•• Transient facial weakness may also occur and in a few patients this may
be permanent.
ESSENTIAL HYPERTENSION
•• Experimentally, hypertension may be produced by electrical stimulation
of the cortex, bilateral lesions of the anterior hypothalamus and bilateral
lesions of the nucleus tractus solitarius (NTS).
1460
•• The cell mass, the pars commisuralis, probably forms the primary medullary
centre for the baroreceptor reflex.
•• The rostral ventrolateral medulla (RVL) is a critical area for auto-regulation
and control of arterial blood pressure.
•• At the rostral end of the inferior olivary nucleus and within the RVL,
adrenergic neurons are present which contain the adrenaline synthesising
enzyme phenylethanolamine N-methyl transferace (PNMT).
•• These neurons are innervated by projections from the nucleus tractus
solitarius (NTS).
•• The NTS receives input from arterial baroreceptors, chemoreceptors and
other cardiovascular afferent fibres.
•• Cardiovascular baroreceptor impulses from the carotid sinus travel in the
X nerve and those from the aortic arch in the IX nerve.
•• The left X nerve also carries afferent signals from mechanoreceptors in
the wall of the left atrium.
•• The RVL projects to the intermediolateral and intermediate columns of
the spinal cord via fibres travelling through the principal tegmental tract.
•• This tract is the source of tonic and reflex drive to preganglionic neurons
of the intermediolateral columns of the spinal cord.
•• Lesioning the RVL leads to reduction in blood pressure and stimulation to
an increase, indicating that RVL medulla carries sympathetic fibres.
•• A major portion of the afferent impulses from the myocardial receptors of
the left ventricle and atrium are conducted by cardiac c-fibres of the left
vagus nerve to the NTS.
•• Mechanical damage to these nerve fibres by vascular compression may
partially block conduction in these fibres resulting in partial deafferentation
of the NTS.
•• MVD is indicated for essential hypertension in a select group of patients.
•• It is reserved for those with intractable, poorly controlled essential
hypertension, while on at least three different antihypertensive medications
or who have three failed attempts with different medical regimens.
GLOSSOPHARYNGEAL NEURALGIA
•• Glossopharyngeal neuralgia is uncommon.
•• It is characterised by intermittent lancinating pain in the posterior part of
the tongue and the pharynx.
•• Often it radiates to the inner part of the ear.
•• Medically refractory neuralgia has to be treated by surgery.
•• Classically, the IX nerve and the upper rootlets of the X nerve are cut in
the posterior fossa through a retromastoid approach.
•• The immediate relief from MVD is seen.
•• The complications are permanent hoarseness of voice and mild dysphagia
and, rarely, facial palsy.
•• When there is associated hypertension, the MVD results in reduction in
blood pressure.
•• MVD is a safe and effective procedure in the management of glossopharyn-
geal neuralgia.
ENDOSCOPE IN MICROVASCULAR
DECOMPRESSION
•• Recently, endoscopes have been used for treating neurovascular
compression.
1461
•• Supplementing an endoscope to the microscopic procedure has

demonstrated improved localisation of neurovascular conflicts and has
improved the efficacy of surgery.
•• The endoscope has superior visualisation and also minimises the risks of
brain retraction.
•• Initially, the endoscope was being used to supplement the microscope.
Later on, many have reported fully endoscopic vascular decompression
surgeries.
RADIOSURGERY VERSUS MICROVASCULAR

DECOMPRESSION
•• Gamma knife radiosurgery has been used to treat neurov ascular
compression but the results are delayed and are not satisfactory, with
complete pain relief in less than half.
•• Radiosurgery is more likely to be the final treatment for recurrent TN
regardless of the initial treatment.
•• MVD is an operation that has come to stay and is recognised as the surgery
of choice in TN, HFS, glossopharyngeal neuralgia and in some selected
cases of vertigo, tinnitus, hypertension and spasmodic torticollis.
•• The mortality and morbidity of this procedure is low and decreases further
with increasing experience of the surgeon.
Section XV: Epilepsy
196
CHAPTER
Epilepsy: Overview
Dinesh Nayak S  Radhakrishnan K
DEFINITIONS
•• Epilepsy is defined as a group of neurological conditions characterised by
recurrent unprovoked epileptic seizures.
•• Epilepsy is not a specific disease or even a single syndrome, but is a broad
category of symptom complexes arising from a number of disordered brain
functions that may themselves be secondary to a variety of pathological
processes.
•• A syndrome is defined as a clustering of symptoms and signs consistently
occurring together and not fortuitously.
•• Active epilepsy is defined as having had at least one seizure in the
previous 2 years.
•• Chronic epilepsy is defined as epilepsy being active 5 years after onset.
•• Terminal remission means a seizure-free period of 5 years or more, lasting
to the time of most recent follow-up.
MAGNITUDE OF THE PROBLEM

•• The prevalence rate of active epilepsy from the developed world is around
5 per 1,000 population (0.5%).
•• Around 20−30% of patients with epilepsy continue to suffer recurrent
seizures, despite optimal antiepileptic drug (AED) therapy.
•• This has an adverse impact on education, marriage, employment and
quality of life.
•• The ICMR monograph [Epilepsy in India edited by PN Tandon (1989)]
provides detailed information on this aspect.
•• Patients with medically refractory epilepsy need to be identified early in
the course of the disease and referred to a comprehensive epilepsy care
program for detailed diagnostic evaluation, to determine candidacy for
surgical or other modes of treatment, before their quality of life is irreparably
adversely affected.
BASIC MECHANISMS OF EPILEPTOGENESIS

•• Epileptogenesis is the result of abnormal firing of a group of neurons
sufficient to produce epileptiform activity that can be recorded as
electroencephalographic (EEG) seizure activity with or without clinical
findings.
•• Such activity may be restricted to a small population of neurons, as in
focal epilepsies or may involve large areas of the brain simultaneously as
in generalised epilepsies.
Chapter 196 • Epilepsy: Overview
1463
•• There is alteration in the balance between excitatory and inhibitory

mechanisms.
•• Epileptogenesis may either be due to increased excitation or reduced
inhibition or a combination of both.
•• The three main elements in the expression of epileptogenesis are:
1. The capability of membranes of pacemaker cells to develop intrinsic
burst discharges
2. Reduction of gamma aminobutyric acid (GABA) inhibition and
3. Enhancement of synaptic excitation.
•• Synchronisation of cellular activity and its spread to involve a significant
number of neurons is required to produce EEG and clinical seizure activity,
as well as in the generation of cellular paroxysmal depolarisation shifts.
•• Neurons get depolarised by entry of extracellular sodium (Na+) into the cell
to set-up the action potential, called the sodium action potential.
•• Similarly, calcium (Ca2+) influx also produces the calcium action potential.
•• Repolarisation takes place when potassium re-enters the cell.
•• Any factor that affects the balance of depolarisation or repolarisation can
affect cellular excitability.
•• Therefore, agents that block potassium channels (tetraethyl ammonium and
barium) prolong the action potential and therefore are proepileptogenic.
•• Blockers of Na+ and Ca2+ (e.g. phenytoin, valproic acid, ethosuximide and
lamotrigine) inhibit action potentials and are used in the pharmacotherapy
of epilepsy.
•• A number of neurotransmitters and their receptors mediate excitation and
inhibition in the central nervous system.
•• The amino acid glutamate is an excitatory neurotransmitter and mediates
synaptic excitation.
•• The post-synaptic excitation induced by glutamate largely depends on
stimulation of receptors.
•• Based on their physiological and pharmacological properties, glutamate
receptors are organised into two classes: ionotropic and metabotropic.
•• The ionotropic receptors are further sub-divided into two classes: those
that respond to α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid
(AMPA) or kainic acid (KA) and those that respond to N-methyl-D-aspartate
(NMDA).
•• The metabotropic glutamate receptors (mGluRs) are second messenger-
coupled receptors and play a role in neuronal plasticity and epilepsy.
•• The inhibitory system is mainly based on the neurotransmitter Gama
aminobutyric acid (GABA).
•• The GABA receptors are divided into two subtypes: GABAA and GABAB.
•• Activation of GABAA receptors opens a chloride channel and results in
hyperpolarisation and, therefore, inhibition.
•• GABAB receptor is a G protein-coupled receptor that can open potassium
channels or close calcium channels. This results in prolonged hyperpolari-
sation and therefore leads to post-synaptic inhibition.
•• Other receptors that have been implicated in epileptogenesis are acetyl-
choline receptors and adenosine receptors.
•• One of the most important prerequisites in the development of an epileptic
seizure is the manner in which excitatory neuronal populations synchronise.
•• Usually, recurrent synaptic excitation is balanced by recurrent inhibition.
•• Blockade of inhibition results in paroxysmal depolarisation shifts.
Section XV • Epilepsy
1464
•• When recurrent inhibition is affected in various pathological conditions, there

is multi-synaptic excitatory-induced synchronisation of neurons leading to
the generation of after discharges.
•• The glial network is protective in nature and glial cells take up glutamate.
Failure of these mechanisms can result in secondary generalisation of a
focal seizure.
CLASSIFICATION OF SEIZURES AND EPILEPSIES

•• Seizures are broadly classified into partial and generalised seizures.
•• Partial seizures indicate initial activation of a group of neurons limited to one
part of the cerebral hemisphere, as evident clinically and electrographically.
•• Depending on whether consciousness is preserved or not, partial seizures
are further classified into simple partial (consciousness preserved) and
complex partial (consciousness impaired).
•• A simple partial seizure may evolve into complex partial and then
secondarily generalised seizures.
•• The manifestations of simple and complex partial seizures may be motor,
sensory, autonomic and psychic.
•• Generalised seizures are those in which the first clinical changes indicate
initial involvement of both hemispheres. Consciousness may be impaired
and this may be the initial manifestation.
•• Motor manifestations are bilateral, and the ictal EEG changes are bilateral.
•• The generalised seizures include absences, myoclonic, tonic, atonic, clonic
and tonic-clonic.
•• Epilepsy syndrome classification is a more useful concept for the prognosis
and treatment than seizure classification, because it includes elements
other than seizure symptomatology and EEG.
•• The 1989 International League Against Epilepsy (ILAE) classification is
based primarily on the definition of electroclinical syndromes.
•• They are broadly divided into localisation-related epilepsies (in which
seizure semiology or findings at investigation disclose a localised origin of
the seizures) and generalised epilepsies (seizures in which the first clinical
changes indicate initial involvement of both hemispheres and initial ictal
EEG changes are bilateral).
•• Localisation-related and generalised epilepsies are further divided into
idiopathic, symptomatic and cryptogenic.
•• Idiopathic means “arising spontaneously from” and imply normal intelligence
and neurological examination. Many of the idiopathic syndromes may be
genetic disorders.
•• Symptomatic means there is an obvious underlying cause for the epileptic
syndrome.
•• Syndromes with excellent prognosis consist of the benign epilepsy
syndromes of childhood such as benign Rolandic epilepsy and benign
occipital lobe epilepsy.
GENETICS OF EPILEPSIES
•• The first step is to obtain a detailed family history.
•• On the other hand, spontaneous gene mutations are well known to occur
and in such cases no positive family history will be present.
•• A single genetic defect may result in several phenotypes, while a single
phenotype can be a result of several genetic mutations.
1465
•• Patterns of inheritance follow two broad groups: (1) Simple Mendelian

[autosomal dominant (AD), autosomal recessive (AR) and X-linked] and (2)
complex (non-Mendelian). Mendelian disorders are relatively rare, cluster
in families and have a high rate of penetrance (expression), so that if one
carries the gene, the disorder is likely to manifest. This makes it easier to
trace the abnormal gene.
•• Approximately 10 genes have been identified for the idiopathic generalised
epilepsies within the last 15 years, all of them simple Mendelian disorders
with AD transmission. These genes involve either an ion channel (sodium
and potassium) or a neurotransmitter receptor (acetylcholine and GABA).
•• Autosomal recessive disorders are associated with multiple cerebral
abnormalities as well.
NATURAL HISTORY OF EPILEPSIES

Determinants of Natural History of Epilepsies
•• There are certain well established predictive factors for the development
of pharmacoresistant epilepsy. These include onset of epilepsy in infancy,
organic brain damage (mental retardation and neurological signs), seizure
type (tonic, atonic and myoclonic seizures), multiple seizures, high seizure
frequency, long duration of uncontrolled seizures, failure of past AED
treatments and an abnormal EEG.
•• Most of these factors are especially relevant to prognosticate the outcome
of epilepsy in children.
Refractory Epilepsies
•• Despite the fact that the majority of patients with epilepsy remit, about
20–30% of patients continue to suffer recurrent seizures despite appropriate
AED therapy.
•• These unfortunate patients are a challenge to the treating team.
•• Fortunately, about 25% of these patients are candidates for epilepsy
surgery. When selected appropriately, surgical treatment results in a cure
in the majority of patients.
•• The definition of refractory epilepsy is essentially an individual one.
•• A rough rule would be a patient who suffers two or more disabling seizures
per month and who has failed trials of two appropriate AED monotherapy
trials and one polytherapy trial over a period of 2 years.
•• Patient’s expectation, degree of disability, AED toxicity, employment
and education, and obtaining driving license are some of the factors that
ultimately influence the decision for surgery.
•• The natural history studies have shown that most patients who are destined
to achieve seizure control will do so within the first 2 years of onset of
epilepsy.
Mechanisms of Pharmacoresistance
•• Resistance to AEDs can be explained by two putative neurobiological
mechanisms: (1) removal of AEDs from the epileptogenic tissue through
excessive expression of multidrug transporters and (2) reduced drug-target
sensitivity in epileptogenic brain tissue.
•• Overexpression of certain genes, like MDR 1 and MDR associated protein
1 (MRP1) in the epileptogenic tissue, can result in pharmacoresistance.
1466
•• Therefore, pharmacoresistance may develop even before the first seizure

or may develop many years after the onset of epilepsy.
•• Pharmacoresistance may reverse in some patients.
DIFFERENTIAL DIAGNOSIS OF EPILEPSIES

•• Epileptic seizures are paroxysmal in nature, with varying manifestations
ranging from brief absences to the most bizarre motor phenomena as seen
in some patients with frontal lobe epilepsy.
•• A variety of paroxysmal phenomena, which are non-epileptic, can mimic
epileptic seizures.
•• These can be sub-divided into physiologic and psychogenic non-epileptic
events.
•• Physiological non-epileptic events include syncope, paroxysmal movement
disorders, transient ischaemic cerebrovascular phenomena, non-epileptic
myoclonus and sleep disorders.
•• Psychogenic non-epileptic events include somatoform disorders,
dissociative disorders, anxiety disorders and malingering.
•• A very careful history and appropriate investigations will usually help in
differentiating between true epilepsy and non-epileptic events, although in
some instances, the distinction can be extremely difficult.
•• It is important to recognise that around 20% of patients with chronic epilepsy
referred to a video-EEG unit proved to be non-epileptic attacks.
•• Meticulous history and judicious use of investigations will help clarify the
existence of the two seizure types.
INVESTIGATION OF EPILEPSIES
Electroencephalography
•• The first electroencephalogram in humans was performed by Hans Berger
in 1928.
•• Since that time, EEG has played a central role in the diagnosis and
management of epilepsy.
•• The EEG represents summated synchronised post-synaptic potentials,
which may be excitatory or inhibitory.
•• These excitatory and inhibitory post-synaptic potentials (EPSP and IPSP)
are generated from apical dendrites of neurons in the superficial cortex.
•• The electrical fields generated from deep sources do not normally get
recorded over the scalp, unless the more superficial cortical neurons get
activated.
•• The EEG is the only test that provides information about epileptogenesis.
•• The diagnostic sensitivity of a single awake EEG with photic stimulation
and hyperventilation is about 50% in adults with epilepsy.
•• The diagnostic specificity of the EEG depends on the proper interpretation
of the EEG.
•• Misinterpretation of normal variants and artefacts can lead to a wrong
diagnosis of epilepsy and unnecessary AED therapy.
•• It is also important to understand that a normal EEG does not exclude
epilepsy.
•• Specific interictal EEG abnormalities can be found in a small number of
epilepsy syndromes. These include hypsarrhythmia in West syndrome,
centrotemporal spikes in Benign Rolandic Epilepsy of childhood, and slow
spikes in Lennox-Gastaut Syndrome.
1467
Video-EEG Telemetry
•• Video-telemetry or video-EEG is the simultaneous and synchronous
recording of clinical events on video, along with EEG. It has several
advantages over the routine EEG recording.
•• Prolonged Video-EEG monitoring provides the opportunity to study interictal
and ictal paroxysmal electrographic and clinical events synchronously,
thereby permitting electroclinical correlation.
•• Video-EEG is used to confirm seizure disorder, classify seizure type(s),
distinguish epileptic seizure from non-epileptic seizure, assess seizure
frequency, study precipitating factors and most importantly, to localise the
ictal onset zone in patients who are evaluated for focal resective epilepsy
surgery.
•• Interictal epileptiform abnormalities in the form of spike-waves and sharp
waves can be focal, multi-focal or generalised.
•• The distribution of these discharges helps in localising the lobe of origin.
•• In mesial temporal lobe epilepsy (MTLE), which is the most common
surgically remediable epilepsy syndrome, the epileptiform discharges
are maximal at the anterior temporal electrodes, whereas in neocortical
temporal lobe epilepsy, the spikes are maximal at the mid-and/or posterior
temporal locations. The spikes in mesial frontal epilepsy are usually seen
over the midline vertex region. Generalised spike discharges can also occur
and indicate secondary bilateral synchrony.
•• One of most important aspects of video-EEG monitoring is the recording
of clinical seizures. The semiology of seizures would help classify
seizure types into generalised, complex partial seizures of temporal or
extratemporal (frontal, parietal and occipital) type or simple partial seizures.
•• Ictal electrographic rhythms differ from interictal discharges and consist of
low voltage beta activity, rhythmic medium amplitude theta or alpha activity,
rhythmic delta activity and runs of spikes or sharp waves.
•• Ictal onset can be focal or diffuse.
•• In temporal lobe seizures, the rhythm is typically a focal rhythmic 5–7 Hz
theta activity over the temporal region, which remains lateralised for several
seconds before spreading to other regions.
•• Frontal lobe seizures are typically hypermotor and the ictal rhythm may be
obscured by myogenic and movement artefacts.
•• Post-ictal changes can be in the form of slowing or attenuation of the
background activity and can be focal, hemispheric or generalised. Focal
post-ictal change is of lateralising value.
•• The video-EEG is expensive, labour-intensive and time consuming to
analyse. If used judiciously, the test is cost-effective and can result in a
change in management of the patient.
Neuroimaging
•• Prior to the advent of modern neuroimaging techniques, plain X-rays skull,
pneumoencephalogram or ventriculogram, cerebral angiograms provided
valuable information regarding the underlying pathology responsible for
the epileptic seizures. However, now, by and large these are of little value.
•• The modalities include computed tomography (CT scan), magnetic
resonance imaging (MRI), positron emission tomography (PET), interictal
and ictal single photon emission computed tomography (SPECT), MR
spectroscopy (MRS), T2 relaxometry and functional MRI (fMRI).
1468
•• The main goals of neuroimaging in persons with epilepsy, as laid out by

the commission on neuroimaging of the ILAE, are:
–– Delineation of structural and functional abnormalities in the suspected
epileptic zone.
–– Prediction of the nature of structural pathology.
–– Detection of abnormalities distant from the putative epileptogenic re-
gion (diffuse or dual pathology).
–– Identification of eloquent brain regions, such as language, memory
and sensorimotor areas, and the relation of these regions to the epi-
leptogenic lesion.
•• The CT scan detects only gross structural lesions including any pathological
calcification. A negative CT scan does not exclude subtle epileptogenic
lesions. The current role of CT in epilepsy is mainly in an emergency
situation and in a patient presenting with recent seizures in an area known
to be endemic for cysticercosis.
•• The MRI is currently the best investigation to define both normal and
abnormal brain structures.
•• The most common structural pathology detected on MRI in patients with
focal epilepsy is mesial temporal sclerosis (MTS). Other lesions include
malformation of cortical development, vascular lesions and low-grade
neoplasms, and focal atrophic lesion.
•• Not all patients with epilepsy need neuroimaging.
•• Patients with primary generalised epileptic syndromes, such as childhood
and juvenile absence epilepsies, juvenile myoclonic epilepsy and idiopathic
benign localisation related childhood epileptic syndromes do not need
neuroimaging.
•• On the other hand, patients with refractory focal epilepsy must be
investigated with MRI.
•• The PET scan is usually done in the interictal state and measures the
metabolic rate of the tissue. Epileptogenic tissue will usually be seen as
hypometabolic.
•• The SPECT is usually done by injecting a radiotracer within a few seconds
of a seizure onset. The seizure focus will show hyperperfusion, whereas
interictal SPECT will show reduced perfusion.
•• By co-registration of interictal and ictal SPECT on the MRI (SISCOM), the
seizure focus can be mapped with great accuracy.
•• The fMRI is used to map out eloquent cortical regions using the
blood oxygenation level dependent (BOLD) technique. Changes in
oxyhaemoglobin levels during activation of the cortex results in a change
in MRI signal. Language, sensorimotor and visual areas can be mapped
out. This technique is now being routinely used in the evaluation of patients
with intractable extratemporal epilepsy with epileptogenic zones close to
eloquent areas.
Invasive Video-EEG Monitoring

•• When there is discordance between various non-invasive tests, like
scalp EEG, video-EEG, MRI and functional imaging findings or in cases
of focal cortical dysplasia where the epileptogenic focus is usually more
widespread than the MRI abnormality, invasive monitoring is required to
exactly delineate the epileptogenic focus.
1469
•• This is achieved by means of implanting multicontact subdural grid or strip

electrodes or stereotactically implanted intracerebral depth electrodes.
•• It is very important to generate a hypothesis regarding the probable
epileptogenic focus/foci, before deciding on the type of electrodes and the
extent of coverage. This will avoid the danger of inadequate or inappropriate
sampling of the brain, resulting in a false negative study.
•• Invasive monitoring carries a risk of infection, haemorrhage, weakness
or even death.
NEUROPATHOLOGY OF EPILEPSIES
•• The six common neuropathological substrates of chronic epilepsies in
adults are:
1. Hippocampal sclerosis
2. Malformations of cortical development
3. Traumatic lesions and changes secondary to chronic epilepsy
4. Tumours and hamartomas
5. Infective (tuberculosis, cysticercosis, encephalitis) disorders and
inflammatory lesions (Rasmussen’s encephalitis) and
6. Sturge Weber syndrome and angiomas.
•• Hippocampal sclerosis is the most common pathologically confirmed lesion
in chronic temporal lobe epilepsy.
•• In the last decade, advances in MRI techniques have made it possible to
accurately diagnose MTS pre-operatively.
•• Typically, there is marked loss of pyramidal neurons in the CA1 region,
followed by less severe loss in the CA3 and CA4 sectors, followed by hilar
and granule cells, whereas the neurons in the CA2 region are typically
resistant to damage.
•• Malformations of cortical development have long been recognised as an
underlying cause of epilepsy in a proportion of adults with early or late
onset disease, as well as in the paediatric age group.
•• The basic problem is a disturbance in the migration of neurons from the
periventricular germinal mantle to the cortical mantle along the radially
oriented glial fibres.
•• The type of insult, its severity and time of occurrence, influence the extent,
location and type of malformation, which in turn affects the degree of
clinical disability.
•• Malformations can be divided into focal and diffuse abnormalities; focal mal-
formations include focal cortical dysplasia, cerebral microdysgenesis, grey
matter heterotopia, polymicrogyria, pachygyria or agyria and schizencephaly.
•• Diffuse malformations include hemimegalencephaly, microdysgenesis, grey
matter heterotopia and lissencephaly.
•• The two most common tumours which cause chronic epilepsy are
dysembryoplastic neuroepithelial tumour (DNET) and ganglioglioma. Other
tumours include low-grade astrocytomas, oligodendroglioma, pleomorphic
xanthoastrocytoma and subependymal giant cell astrocytoma.
•• Rasmussen’s encephalitis is a rare disorder that presents in childhood or
adulthood as epilepsia partialis continua and progressive hemiparesis. The
disease progresses through various stages.
•• The neuropathology is one of chronic polio-encephalitis, which is typically
unilateral and characterised by neuronophagia and perivascular cuffs of
lymphocytes.
1470
Emerging and Alternative Treatment for Epilepsy

•• Treatment options are limited for patients with pharmacoresistant epilepsies
who are not candidates for resective surgery.
•• In the recent years, however, two well studied options have emerged: (1)
vagus nerve stimulation and (2) ketogenic diet.
Vagus Nerve Stimulation
•• The device consists of a battery-powered pulse generator (CyberonicsTM)
which is implanted subcutaneously in the anterior chest wall below the
clavicle, lead wires which are attached to the vagus nerve (the left vagus
nerve is used for stimulation since the right vagus has strong cardiac
innervation) and a hand-held magnetic wand which can activate or
deactivate the pulse generator.
•• The stimulation is carried out intermittently once every 2−5 minutes (off
time) for a period of 30 seconds (on time) at a current intensity of 0.25 mA,
which is gradually ramped up to a maximum of 3.5 mA.
•• Meticulous follow-up is required to adjust the duty cycle and to ensure
proper functioning of the device. Optimal stimulation parameters are
achieved usually within 3–4 months.
•• The hand held magnet can be used to abort a seizure, either by the patient
when he/she experiences an aura or by a family member/caretaker as soon
as a seizure develops.
•• The mechanism of action of VNS is still not clear.
•• The vagus nerve has extensive afferent connections in the brainstem,
forebrain and hypothalamus.
•• The adverse effects of VNS consist of hoarseness of voice, cough and
breathlessness. Over time, these symptoms tend to subside.
•• The battery life of newer devices is approximately 7 years.
Ketogenic Diet
•• The ketogenic diet has a long history and antedates the use of AEDs.
•• While on this diet, lower doses of AEDs are required, thereby reducing the
potential for AED-related side effects.
•• The diet is very high in fat and low in carbohydrate and protein at a ratio
of 3:1.
•• The diet is monitored by measuring urinary ketones, which must be 4+ to
ensure that the diet is sufficiently ketogenic.
•• The exact mechanism of action is not known. It appears that its effects on
the brain are multiple, with overall changes in brain phosphorylation state
and altered gene expression.
•• Many studies have shown that ketogenic diet is effective in medically
refractory epilepsy in children.
•• Adverse effects include acidosis, anorexia, dehydration, diarrhoea and
symptomatic hypoglycaemia, renal stones, etc.
197
CHAPTER
Epilepsy:
Medical Management
Ashalatha  Radhakrishnan K
INTRODUCTION
•• The steps in the management of a patient with epilepsy are summarised
in Table 1.
•• Health care delivery in developing regions is largely governed by the three
As: availability, acceptability and affordability.
•• The introduction of seven new AEDs (e.g. clobazam, gabapentin,
lamotrigine, topiramate, oxcarbazepine, levetiracetam and zonisamide)
in India over the last 10 years, in addition to better availability of already
existing standard AEDs (Table 2), have provided physicians and their
patients with new treatment options, but has in several ways complicated
the management of epilepsy.
•• New AEDs are expensive and are beyond the reach of the majority of the
patients with epilepsy in developing countries.
Table 1: Steps in epilepsy management

Correct diagnosis
Epilepsy education
Treatment with appropriate AEDs
Psychosocial support
Early detection of medical refractoriness
Table 2: Commonly used AEDs currently available in India

Standard AEDs New AEDs
Phenobarbitone Clobazam
Phenytoin Gabapentin
Carbamazepine Lamotrigine
Sodium valproate Topiramate
Clonazepam Oxcarbazepine
Levetiracetam
Pregabalin
Zonisamide
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NEWLY DIAGNOSED EPILEPSY

•• The goal of AED therapy is to make the patient completely seizure-free
without causing undesirable side effects and thereby achieve improved
quality of life.
•• Most epileptologists now agree that monotherapy is the appropriate choice
in newly diagnosed epilepsy.
•• The advantages of monotherapy are listed in Table 3.
•• Nearly 75% of patients with newly diagnosed epilepsy achieve one-year
seizure freedom with a single appropriate AED.
•• Various factors, such as seizure type, the epilepsy syndrome, age and
gender of the patient, side effect profile of the AED and economic factors,
influence the choice of AED for a newly diagnosed patient with epilepsy.
•• Valproate is the drug of choice in patients with absence epilepsy and
juvenile myoclonic epilepsy.Carbamazepine is contraindicated in these
groups of patients.
•• If the patient can afford it, valproate is preferred in patients with all types of
primary generalised epilepsies, although phenobarbitone, phenytoin and
carbamazepine are also effective and can safely be used in some of them.
•• Lamotrigine either alone or, if necessary, in combination with valproate is
a good choice in these groups of patients.
•• In partial epilepsies, since there is little difference in the efficacy of different
AEDs, availability and affordability govern the choice.
•• Phenytoin and carbamazepine may worsen absence and myoclonic
seizures. Drug-induced drowsiness caused by clonazepam and clobazam
can exacerbate absence seizures.
•• Sedative drugs, like barbiturates and benzodiazepines, are better avoided in
children as they can produce subtle cognitive and behavioural disturbances
and in adults with occupations involving driving and operating dangerous
machines.
•• Phenytoin can cause coarsening of the face and hirsutism, which may be
unacceptable to women.
•• Coexistent medical problems, like porphyria, hepatic or renal diseases, will
also influence the selection of AEDs.
•• Teratogenic effects of AEDs is an important consideration in women of
child bearing age and supplementation of 5 mg of folic acid is routinely
recommended with all AED prescriptions for this group of patients.
SEIZURE RECURRENCE ON MONOTHERAPY

•• Common diagnostic errors are failure to consider non-epileptic events and
missing the history of myoclonic jerks in syndromes like juvenile myoclonic
epilepsy.
Table 3: Potential advantages of AED monotherapy

Fewer adverse effects
Improved compliance
No drug interaction
Improved seizure control
Less expensive
Less risk of teratogenicity
Chapter 197 • Epilepsy: Medical Management
1473
•• One of the most important reasons for failure of AED therapy is poor
patient compliance.
•• A significant factor that may lead to non-compliance is insufficient education
regarding medication regimen, treatment with multiple drugs, multiple
dosing and apprehension about adverse effects of AED.
•• Some patients may not achieve seizure control until their serum drug levels
are higher than the conventional therapeutic range. It may be advisable
to increase the dose of the AED up to maximum tolerated doses in such
patients, rather than adhering to serum AED levels.
•• Patients who do not improve with appropriate monotherapy should be
switched on to an alternate AED. A second drug is added slowly and, after
reaching the optimal dosage, the first drug is gradually withdrawn.
•• If seizures are completely controlled with duotherapy, consideration should
be given to withdrawing the first AED in order to minimise the adverse
effects and cost of therapy.
CONTROLLED ON POLYTHERAPY
•• The advent of several new AEDs has widened the scope of medical
treatment.
•• Given the lower side effect profile of the newer AEDs, there may be a
role of polytherapy in certain clinical instances, particularly when a patient
develops refractory epilepsy.
•• The term ‘rational polytherapy’ refers to combining AEDs with different,
presumably synergistic mechanisms of action. An example would be com-
bining a sodium channel-blocking agent (such as phenytoin, carbamazepine
or topiramate) with a GABA enhancing agent (benzodiazepines, valproate
or tiagabine).
•• Patients, whose seizures are controlled on polytherapy, should be
re-evaluated periodically to determine the need for multiple AEDs.
•• Withdrawing AEDs in patients on polytherapy can result in complex drug
interactions. For example, discontinuing enzyme-inducing AEDs, such as
phenytoin or phenobarbitone, may increase the plasma levels of other
AEDs.
•• Conversely, stopping valproate in a patient on therapy with valproate and
lamotrigine could result in sub-optimal lamotrigine levels. An increase in
seizures in such a situation could be managed by increasing the dose of
lamotrigine rather than by re-introducing valproate.
SPECIAL CLINICAL SITUATIONS

•• Carbamazepine is a well-documented pro-arrhythmic drug and should be
avoided in patients with cardiac disease.
•• Valproate is generally contraindicated in the setting of hepatic failure
because of direct hepatotoxicity and risks of fulminant hepatic failure.
•• An increased incidence of valproate-induced pancreatitis has been
described in patients with renal failure.
•• Carbamazepine and oxcarbazepine have the least potential for toxicity in
renal failure.
•• Gabapentin is the drug of choice for seizure control in patients with
porphyria.
•• The risk of foetal malformations increases with high dose of valproate and
with polytherapy.
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•• There is no drug of choice for the treatment of epilepsy in the elderly.

•• AED therapy has to be tailored to the individual patient, weighing potential
adverse effects against the benefits. Monotherapy in a low dosage is to be
initiated and titration should be graded until the desired benefit is attained.
LONG-ACTING ANTIEPILEPTIC DRUG

FORMULATIONS
•• The major advantages of extended release AED preparations are: (a)
more stable serum levels with fewer fluctuations, thereby minimising the
chance of peak dose related side effects and breakthrough seizures related
to low serum AED levels and (b) improved compliance resulting in better
seizure control.
•• Several long-acting formulations of carbamazepine and valproate, which
can be administered in once or twice daily doses, are currently available.
ROLE OF SERUM ANTIEPILEPTIC

DRUG LEVEL MONITORING
•• Since the goal of pharmacotherapy of epilepsy is to make the patient
seizure-free without side effects, measuring the serum level of AEDs has
a sound basis in clinical practice.
•• Because of its long half-life, saturation kinetics of its metabolism and narrow
therapeutic index, phenytoin makes the soundest case for therapeutic drug
level monitoring.
•• The serum level monitoring is less dependable for carbamazepine, since its
serum level shows considerable variation between patients and is markedly
influenced by the presence of other enzyme-inducing AEDs.
•• Sodium valproate has a wide therapeutic range of serum levels and has
very little clinical application.
•• The therapeutic serum levels of new AEDs have not been defined.
•• Carbamazepine markedly induces its own metabolism (autoinduction),
which is usually completed within 20−30 days of its initiation. Therefore,
for both phenytoin and carbamazepine, serum AED assay should wait for
at least one month of being on a constant dosage of these drugs.
A PRACTICAL GUIDE FOR ANTIEPILEPTIC

DRUG WITHDRAWAL
•• The decision to withdraw or continue the AED centres on the risk or relapse
and the consequence of seizure recurrence.
•• The social consequences of relapse are smaller in children and women,
as driving privileges and employment are not a concern, while adverse
influence of AEDs on cognitive performance and pregnancy, respectively,
are concerns.
•• Although no data is available on the optimal rate of AED withdrawal, a slow
withdrawal extending not less than 2 months is recommended.
•• In patients taking more than one AED, withdrawal will have to be done of
one drug after the other. Sedative medications, such as phenobarbitone,
primidone, clobazam and clonazepam are usually withdrawn more slowly.
198
CHAPTER
Surgery for Epilepsy:
General Principles
Bhaskara Rao Malla  Jayanti Mani
INTRODUCTION
Definitions
•• An epileptic seizure is a transient occurrence of signs and/or symptoms, due
to an abnormal and excessive or synchronous neuronal activity in the brain.
•• Epilepsy is a chronic condition of the brain characterised by an enduring
propensity to generate recurrent unprovoked seizures and by the neurobio-
logical, cognitive, psychological and social consequences of this condition.
•• Epilepsy surgery is the resection or functional manipulation of part of the
brain with the aim of alleviating seizures, improving the cognitive function
and the quality of life.
SURGICALLY REMEDIABLE LESIONAL

EPILEPSY SYNDROMES
Surgically remediable syndromes (Table 1) are epileptic disorders for which:
•• The pathophysiology is understood.
•• The natural history is reasonably well known to be medically refractory or
even progressive, once the major first-line antiepileptic drugs fail.
Table 1: Surgically remediable lesional epilepsy syndromes

Mesial temporal lobe epilepsy:
Temporal lobe epilepsy associated with hippocampal atrophy/sclerosis
Disorders of cortical development:
Glioneuronal hamartoma
Focal cortical dysplasias
Benign neoplasms:
Ganglioglioma
Dysembryoplastic neuroepithelial tumour
Low-grade astrocytoma
Oligodendroglioma
Other focal lesions:
Vascular malformations
Atrophic scars
Rasmussen’s encephalitis
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Table 2: Indications for pre-surgical evaluation

Persistent seizures despite appropriate pharmacological treatment (usually at least two drugs as
monotherapy and one combination as polytherapy appropriate to seizure type, at adequate doses,
with adequate compliance)
Impairment of quality of life due to ongoing seizures
Memory deficit, attention deficit, injuries, accidents due to ongoing seizures
Severe adverse reactions of antiepileptic medications
Contraindications for epilepsy surgery
Minor seizures that do not impair quality of life
Primary generalised epilepsies
Non-epileptic seizures
Progressive medical or neurological disorder
Active interictal psychosis or behavioural problems
•• Pre-surgical evaluation can be accomplished and

•• Surgery offers an excellent chance that disabling seizures will completely
be eliminated or markedly reduced.
Candidates for Pre-surgical Evaluation

•• As a general rule, patients with refractory epilepsy continuing to exhibit one
or more disabling seizures per month for a period of two years or more,
despite supervised therapeutic trials (six months each) twice with a single
antiepileptic drug and once with a combination of two antiepileptic drugs,
are candidates for detailed evaluation in a comprehensive epilepsy care
program (Table 2).
•• Many epilepsy syndromes are well characterised and have defined
prognoses, simplifying the selection process; thus, idiopathic partial and
generalised epilepsies are not amenable for surgery, whereas surgery
might be considered the treatment of choice for some specific surgically
remediable syndromes discussed above.
•• Absolute contraindications to epilepsy surgery include primary generalised
seizures, underlying degenerative or metabolic disorders or supervening
medical illness and psychogenic seizures.
•• Relative contraindications to surgery include medication noncompliance,
interictal psychosis, mental retardation and severely dysfunctional family
dynamics.
•• Unresponsiveness to antiepileptic drugs should not be due to inappropriate
AED choice or wrong AED combinations, poor drug compliance, social or
psychological factors.
PRE-SURGICAL EVALUATION
Objectives of Pre-surgical Evaluation
•• It aims to accomplish the following:
a. Establish the epileptic nature of the paroxysmal events.
b. Identify a discrete structural abnormality, either directly with neuroim-
aging techniques or inferentially because of an associated functional
deficit.
c. Provide evidence of localised abnormal neuronal excitability of that
actual or presumed structural lesion and
Chapter 198 • Surgery for Epilepsy: General Principles
1477
d. Establish lack of vital function (e.g. speech and movement) in the sus-
pect region.
Pre-surgical Evaluation
•• The principle of epilepsy surgery is to identify and resect or disconnect a
single identifiable epileptogenic focus without risk of neurological deficit.
•• The rate of success of epilepsy surgery depends upon the accurate locali-
sation of the epileptogenic zone, which is defined as the area necessary
and sufficient for initiating seizures and whose removal or disconnection
is necessary for abolition of seizures.
•• The standard pre-surgical evaluation includes non-invasive tests consisting
of high resolution brain MR imaging, scalp video-EEG telemetry and
neuropsychological assessment.
•• Concordance of data obtained from these tests may be adequate to
perform surgery with good results, as in the classical mesial temporal
epilepsy syndrome.
•• For patients with epileptogenic lesions located at or near the primary
motor, sensory, or language cortex, several non-invasive tools of functional
mapping have been developed. These include magnetoencephalography
(MEG), positron emission tomography (PET), and, more recently, functional
MRI.
NEUROIMAGING
•• MRI can detect almost 100% of structural lesions that are associated
with epilepsy and can almost always detect the mesial temporal sclerosis
associated with mesial TLE.
•• The advent of high resolution MR imaging and multiplanar analysis have
significantly improved the ability to visualise malformations of cortical
development in patients with epilepsy.
•• Abnormalities of the gyral and sulcal pattern have been studied with various
techniques, including curvilinear reformatting and volumetric analysis in
patients with focal cortical dysplasia.
•• Ictal SPECT is particularly useful in non-lesional extratemporal epilepsies,
often revealing discrete neocortical regions of activation, not appreciated
by video-EEG monitoring or MRI.
•• Interictal metabolic PET imaging has been extensively utilised in pre-surgical
evaluation of refractory seizures to correlate with ictal electrophysiologic
and structural magnetic resonance findings.
•• Regardless of the presence of structural abnormalities, functional imaging
by PET or SPECT provides complementary information.
Non-invasive Electroencephalography
•• The purpose of video, EEG telemetry is to record habitual seizures, identify
the seizure type and syndrome and obtain information about the electrical
localisation of the seizure onset.
•• It is also useful to rule out the possibility of non-epileptic events.
•• The duration of recording is individualised and varies from 24 hours to 7
days, based on the number of seizures to be captured and the baseline
seizure frequency in the patient.
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•• The semiology of the clinical seizures provides evidence for the

symptomatogenic zone, while the localisation of the scalp ictal-EEG
represents the ictal onset zone.
•• In the classical lesional mesial temporal epilepsy syndromes, the ictal scalp-
EEG patterns are usually typical and adequate for surgical decision making.
•• The interictal EEG represents the irritative zone and provides equally
valuable and often localising information about the epileptogenic zone
during scalp video telemetry.
Neuropsychological Assessment
•• Neuropsychological assessment is included as a part of the standard pre-
surgical evaluation. Neuropsychological assessment is the best single
means of quantifying the cognitive abilities and psychosocial status of a
person.
•• The pattern of cognitive strengths and weaknesses provide evidence for
the area of cerebral dysfunction, also referred to as the functional deficit
zone, which may overlap with the epileptogenic zone.
•• In addition, the neuropsychological evaluation also plays a unique role in
assessing the potential risk to cognitive function after surgery.
•• In the context of temporal lobe surgery, this involves quantification of verbal
and visual memory scores prior to surgery.
•• Frontal lobe epilepsy patients perform worse on measures of speed/
attention, motor sequencing and concept formation.
Intracarotid Amobarbital (Wada) Test

•• The intracarotid amobarbital (Wada) test is used to temporarily anaes-
thetise each hemisphere in turn by intracarotid injection of amobarbital
or methohexital, in order to determine the language and memory abilities
supported by the non-anaesthetised hemisphere..
•• While language assessment during the Wada test is simple and straight
forward, interpretation of memory deficit is complex and requires a carefully
designed protocol.
•• Recently, a non-invasive method, like the functional MRI, is gradually
replacing the Wada test for the lateralisation of language and memory,
due to ease of use and reproducibility.
Functional Magnetic Resonance Imaging

•• Functional magnetic resonance imaging (fMRI) is an exciting new technique
that provides maps of human cortical function.
•• Motor cortex and vision can adequately be displayed using this
methodology.
•• The value of fMRI in language and memory localisation is being assessed,
but requires excellent patient co-operation.
•• Both functional MRI and magnetoencephalography (MEG) can now be
used preoperatively to create functional brain maps that can be linked to
several of the available frameless stereotaxy workstations.
Invasive Electroencephalography
•• Intracranial recording of EEG is indicated in the setting of uncontrolled
epilepsy considered for resective surgical treatment when:
1479
–– There is likely to be a single region of seizure onset

–– Localisation of this region is insufficiently precise or impossible, based
on the combination of non-invasive EEG and tests of focal functional
deficit and structural abnormalities and
–– The available information from non-invasive evaluation in an individual
patient allows a hypothesis about the suspected region of seizure
onset to be further investigated.
•• To further define the ictal onset area, several classes of invasive elec-
trodes have been introduced. These consist of electrodes of intermediate
invasiveness, such as epidural pegs, electrodes introduced through the
foramen ovale and more invasive electrodes, such as depth, subdural
grid, and strip electrodes.
•• Foramen ovale electrodes provide a definite advantage over both scalp
EEG and sphenoidal electrodes.
•• In patients with suspected TLE, foramen ovale electrodes like depth
electrodes reliably pick up epileptiform activity generated in or involving
the hippocampal formation.
•• Depth electrodes are inserted with stereotactic MR or CT guidance, such
that the trajectory, termination point and location of each contact can be
accurately predetermined.
•• Cortical grids may be useful to stimulate and localise certain essential
cortical regions, such as language and sensorimotor areas, when awake
craniotomies are not possible such as in children.
•• Grids are particularly useful when both seizure onset zone and cortical
function have to be mapped.
•• With intracranial EEG, the decision to offer surgery rests primarily on the
ictal EEG, a measure of the brain’s excitability.
•• If seizure onset is well localised, surgery is recommended. If it is poorly
localised, or multifocal seizure onsets are detected, then resective surgery
is not advised.
Cortical Stimulation Mapping

•• When the lesion or the epileptogenic zone involves or is adjacent to
eloquent cortex, functional mapping should be performed to delineate
eloquent cortex and thereby permit a safe and complete resection.
•• Mapping is usually performed when resection is contemplated in or near
eloquent cortex that includes the central area (motor and sensory cortices),
dominant inferior frontal cortex, dominant temporal lobe posterior to the
precentral sulcus (language cortex) and the dominant parietal lobe and
occipital lobe (visual and association cortex).
•• Mapping may be done pre-operatively during invasive video-EEG telemetry
and by other methods mentioned above.
•• Stimulation mapping may also be done intra-operatively in selected cases
with good patient co-operation.
•• Direct cortical stimulation with bipolar electrode stimulators under propofol
anaesthesia can be used to readily identify the motor cortex during surgery.
•• Monopolar cortical stimulators are also used with EMG recording electrodes
placed in advance in the major muscle groups.
•• Intra-operative mapping of the language cortex is more elaborate and
requires patient co-operation with awake craniotomy.
1480
•• Somatosensory evoked potentials (SSEPs) are utilised to demarcate the

central sulcus, by the identification of phase reversals.
•• Standard anatomical landmarks will aid in the identification of the central
sulcus, as well as eloquent cortex prior to neurophysiological mapping.
Awake Craniotomy
•• Awake craniotomy, electrocorticography, functional brain mapping were the
standard procedures utilized by the pioneers of epilepsy surgery Penfield,
Rasmussen, Falconer, etc.
•• Patient co-operation and an anaesthesiologist familiar with the technique
are essential.
•• This technique provides continuous feedback, while the patient is
maintained awake during resections adjacent to language, primary motor
and sensory areas.
•• An awake craniotomy is difficult to perform in children who, therefore, may
require an implanted grid and extra-operative mapping of the eloquent
areas.
Electrocorticography
•• It refers to intra-operative recording of EEG directly from the cortical surface.
•• It has been used to identify the epileptogenic area and guide the extent
of resection.
•• The resection is extended to include all of the cortical areas showing active
interictal spikes (so-called “spike chasing”).
•• In addition, information regarding the presence of spikes in the rim of the
resection or at a more distant location has been used for prognosticating
seizure outcome after surgery.
•• It is mostly performed for extratemporal epilepsies.
•• The major disadvantage of ECoG is its duration, limited to brief intra-
operative periods and often complicated by anaesthetic effects.
Neuronavigation
•• One of the most significant advances in lesional epilepsy surgery has been
neuronavigation.
•• Evidence suggests that seizure outcome correlates with the extent of
lesion resection.
•• In this regard, the ability of neuronavigation to optimise the surgical
approach and confirm the extent of resection has been invaluable.
•• It is particularly useful during the surgical planning and resection of
hypothalamic hamartomas associated with gelastic seizures.
•• Neuronavigation can be used to select the optimum side for the parasagittal
craniotomy for corpus callosotomy, as well as to assess the completeness
of callosotomy from rostrum to splenium.
SURGICAL PROCEDURES
•• Surgical procedures (Table 3) for epilepsy may be classified as resective
procedures with an aim to stop seizures or palliative procedures that
disconnect various regions of the brain to prevent seizure spread (Fig. 1).
•• While the former is employed if the pre-surgical evaluation identifies a
single safely removable epileptogenic zone, the latter are employed when
seizures are multiregional or overlap eloquent cortex.
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Table 3: Surgical procedures to treat epilepsy

• Lesionectomy
• Corticectomy
• Lobectomy
• Multilobar resection
• Hemispheric resection and disconnection
• Multiple subpial transections
• Corpus callosotomy
• Radiosurgery
• Vagal nerve stimulation
• Deep brain stimulation
Fig. 1: Epilepsy surgery: Indications, approaches and results
•• Temporal lobe resections make up approximately two-thirds of all

procedures currently performed at epilepsy surgery centres, reflecting the
predominance of adult patients with intractable TLE.
•• In paediatric epilepsy surgery centres, a greater proportion of patients
undergo extratemporal, multilobar and hemispheric resections or discon-
nections.
Lesionectomy
•• Lesionectomy for epilepsy is a surgical procedure that is directed at the
structural lesion, believed to be the aetiology of the seizure disorder.
•• Complete resection of the lesion appears crucial for freedom from seizures
in lesional epilepsy surgery.
•• The operative strategy may include:
–– Lesionectomy, i.e. complete lesion excision, as determined by MRI,
without attempting to resect the epileptogenic zone.
–– Extended lesionectomy, i.e. resection of the lesion with “margins”.
–– Resection of the lesion and the epileptogenic zone, as determined by
ECoG.
–– Resection of the epileptogenic zone alone.
•• The most common resection strategy involves excision of the lesion with
a “margin” around the lesion.
1482
•• The extent of the resection may be determined by different criteria: (1) intra-
operative visualisation of the tissue; (2) radiological margins determined by
MRI signal abnormalities; (3) histologic margins based on intra-operative
frozen section evaluation of the tissue and (4) electrocorticographic margins
based on intra-operative ECoG or a combination of these techniques.
•• Incomplete resection can be due to poor differentiation of the lesion from the
normal brain. It is probable that systems that provide “image-guided surgical
capabilities” or intra-operative imaging will help to solve this problem.
•• The second cause of incomplete resection is the extension of the structural
abnormalities to a functional area; multiple subpial transections have
reportedly been successful in alleviating this problem.
Lobar/Cortical Resections
•• Temporal lobe resections are discussed in detail in the Chapter 202.
Frontal Lobe Resections

•• In frontal lobe epilepsy, the localisation of an ictal onset area is difficult and
is facilitated when a lesion is present on imaging.
•• When the epileptogenic zone is diffuse, a complete frontal lobectomy
anterior to the precentral sulcus can be performed under general
anaesthesia.
•• The location of the central sulcus is determined using SSEPs or cortical
stimulation.
•• In the dominant hemisphere, Broca’s area should be identified and
preserved. This is best performed under local anaesthesia or with the use
of a subdural grid.
•• Resection of the supplementary motor area leads to transient contralateral
weakness and apraxia.
•• On the non-dominant side, extensive resection of the orbitofrontal cortex
can be performed. The intersection of the optic nerve and olfactory nerve
is used as the posterior limit of the resection.
Central Resections
•• In central type epilepsy, resective surgery is performed, preferably under
local anaesthesia with monitoring of motor function.
•• A focal resection is performed if the ictal onset area is circumscribed and
involves the primary face motor or sensory cortex or trunk or leg area.
•• Resection of the primary face area does not cause any significant deficit.
•• Resection of the hand area leads to severe disturbance in hand function.
•• Resection of the hand sensory cortex results in impaired position sense
and stereognosis.
•• Resection of the motor leg area leads to a footdrop; this usually improves
and most patients can walk independently.
•• The vascular supply of the primary motor area should not be disturbed and
the geometry of the white matter tract is respected.
Parietal and Occipital Resections

•• Seizures originating in the parietal and occipital lobes are rare.
•• Somatosensory aura, pain, vertiginous sensations, aphasia or disturbance
of body image are suggestive of parietal origin of the seizures.
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•• The ictal manifestations are varied and reflect the quick spread to the
frontal lobe in superior parietal epilepsies and to the temporal lobe in
inferior parietal cases.
•• Interictal and ictal scalp EEG recordings are not reliable markers for parietal
lobe epilepsy.
•• In patients with occipital lobe epilepsy having hemianopsia, resective
surgery carries little risk.
•• In the case of dominant hemisphere epilepsy, the speech-related cortex
should be identified and spared.
•• When a circumscribed lesion is found, lesionectomy can yield satisfactory
results.
•• In non-lesional cases, the ictal onset area should be precisely localised
using invasive electrodes. These are used in addition to mapping of the
calcarine cortex and speech-related cortex. With this strategy, visual deficits
can be minimised.
Multilobar Resections
•• Multilobar resections are indicated for the control of pharmacologically
refractory seizures, in the presence of widespread epileptogenicity involving
more than one lobe in patients with preserved neurologic function.
•• These patients have various types of lesions, including cerebral gliosis,
atrophy (porencephaly), dysplasia (heterotopia, cortical dysplasia
and hemimegalencephaly), Sturge-Weber syndrome or Rasmussen
encephalitis.
•• Patients with non-progressive disorders (e.g. atrophy, gliosis, dysplasia),
with presence of fine-finger movements and foot-tapping are potential
candidates for multilobar resections, as hemispherectomy is contraindicated
in these patients.
Hemispherectomy
•• Hemispherectomy is generally indicated in patients with widespread
unilateral EEG abnormalities, diffuse unilateral structural abnormality and
clinical evidence of hemiparesis and hemianopia.
•• Three aspects of the aetiology may have an impact on the decision for and
results of surgery: whether the condition is congenital or acquired, strictly
unilateral or possibly bilateral, progressive or static.
•• Congenital pathologies, such as large porencephaly resulting from in utero
or perinatal insult or the Sturge-Weber syndrome, which are usually strictly
unilateral, have a better prognosis with surgery than a congenital lesion,
such as hemimegalencephaly, which may be associated with some degree
of contralateral involvement.
•• Acquired unilateral pathology, such as Rasmussen’s chronic encephalitis,
has a better prognosis than infectious processes, which usually have
bilateral involvement.
•• Various surgical techniques are employed to treat hemispheric
epilepsy syndromes and include anatomic hemispherectomy, functional
hemispherectomy, hemispherotomy and hemidecortication.
•• Hemispherotomy may be more suitable for patients with perinatal stroke
and Rasmussen syndrome, whereas a modified functional or anatomic
technique may be better suited to patients with hemimegalencephaly and
cortical dysplasia.
1484
•• The choice of technique depends in part on the patient’s age, type of lesion,
size of the hemisphere and lateral ventricle and the surgeon’s expertise.
Corpus Callosotomy
•• In patients with symptomatic or cryptogenic generalised epilepsies, such as
the Lennox-Gastaut syndrome, bilateral cerebral dysfunction and bilateral
seizure onset, focal cortical resection is of no use.
•• Atonic, tonic and tonic-clonic seizures may, in some patients, respond to
corpus callosotomy, the rationale being interruption of the rapid secondary
bilateral synchrony that underlies these seizures types.
•• The indications for corpus callosotomy are not standardised, but patients
with drop attacks usually respond best. Recurrent episodes of convulsive
status epilepticus are also eliminated in most cases.
•• A complete callosotomy is performed in those children who are devel-
opmentally retarded and who have no or very limited speech. A partial
callosotomy can be reserved for those children with partial speech pres-
ervation.
•• Radiosurgical corpus callosotomy may be a promising alternative treatment
to open callosotomy.
•• A complete callosotomy is preferable to a partial callosotomy, in terms of
long-term seizure control. However, the former may lead to debilitating
functional impairments.
•• The goal of surgery with callosal section is different from that of other
epilepsy surgeries, in that it is usually palliative, rather than curative.
Multiple Subpial Transections

•• The multiple subpial transections (MST) may be carried out to eliminate
seizure propogation in eloquent brain regions.
•• The technique takes into consideration the organisational anatomy of the
cerebral cortex.
•• It has been known for some time that neuronal function passes through
vertical columns of the cortex, while the horizontal columns are thought to
be important for the propagation of seizure activity.
•• Multiple subpial transections disrupt the horizontal fibres that propagate
seizure activity but maintain functional vertical columns.
•• The Landau-Kleffner syndrome of acquired epileptic aphasia is a rare
disorder characterised by regression of language in early childhood,
prominent EEG abnormalities that involve the language cortex and often,
seizures.
•• In some children with impaired language who fail to respond to medical
treatment, multiple subpial transections of perisylvian cortex on one side
may be of benefit.
Radiosurgery
•• Radiosurgery delivers focused radiation using stereotactic guidance to
targets within the brain.
•• Seizure reduction was documented when vascular malformations and
hypothalamic hamartomas have been treated with radiotherapy.
•• For patients who are not suitable or not willing to undergo surgery,
radiosurgery is an effective alternative.
1485
•• Stereotactic radiosurgery improves seizure outcome in the majority of

patients and more than half of the patients with medically intractable partial
epilepsy had an excellent seizure outcome after radiosurgery.
•• The safety and efficacy of Gamma Knife surgery in mesial TLE has been
documented in a prospective study.
Neurostimulation
•• Electrical stimulation to treat seizures in patients who are not suitable for
resective surgery is a novel idea.
•• Electrical stimulation is reversible. If it does not work, it can be discontinued
and the electrodes can be removed.
•• Neuronal tissue need not be destroyed or resected, except for the tissue
directly along the tract of the stimulating electrodes.
•• Stimulation can occur within seconds, enabling patients to turn the
stimulator on at the beginning of a seizure.
•• Despite these theoretical advantages, electrical stimulation is still far from
being an established and effective therapeutic technique. Earlier experience
with superior cerebellar stimulation utilising implanted electrodes failed
the test of time.
Vagal Nerve Stimulation

•• Vagal nerve stimulation (VNS) is a technique that is used in patients with
epilepsy that cannot be lateralised or localised.
•• Several reports suggest that VNS can be used in both adults and children
with intractable epilepsy, with varying degrees of success.
•• Vagus nerve stimulation is an accepted method of treatment with low
morbidity and mortality, which improves seizure control in at least 30% of
patients, together with concomitant improvements in QOL.
Deep Brain Stimulation

•• Electrical stimulation of relay nuclei may influence electrical activity in
widespread regions of the brain and is useful for multifocal seizure types.
•• Stimulation of deep brain targets in the cerebellum, caudate nucleus,
diencephalon, anterior and centromedian nuclei of the thalamus, the
subthalamus and mesial temporal structures, is practical.
•• There are indications that deep brain stimulation (DBS) improves seizure
control in a group of patients previously not suitable for resective surgery
and this methodology has enormous potential.
•• Questions regarding the best target sites, best candidates for stimulation
as well as the efficacy and safety of the stimulation have not yet been
answered.
Stereotactic Surgery
•• Stereotactic lesionectomy and radiofrequency lesioning have been reported
with variable safety and success rates in controlling refractory seizures.
•• Stereotactic craniotomy is used for the excision of small lesions causing
epilepsy and for lesions which are close to eloquent regions of the brain.
•• A major advantage of the stereotactic technique is the capability of resecting
deep-seated intracranial lesions involving the functional or eloquent cortex,
with a low surgical morbidity.
1486
•• A well-defined lesion can be resected stereotactically with much less

morbidity than the conventional approach.
COMPLICATIONS
•• The general complications of any neurosurgical procedure include acute
post-operative haemorrhage, retraction injury, wound infection and
the usual peri-operative sequel, such as anaesthetic and medication
intolerance, deep vein thrombosis and infections of the bladder, lung or
intravascular lines.
•• Surgical complications include cerebral infarction, intracranial haemorrhage,
intracranial infection, and direct cranial nerve or cerebral injury, possibly
resulting in temporary or permanent neurologic deficits.
•• Morbidity and mortality vary according to the patient’s age and type of
surgery; risks appear to be slightly higher in children compared with adults
and in hemispherectomy and corpus callosotomy, compared with anterior
temporal lobectomy and extratemporal resections.
•• In general, such complications are rare after well planned and performed
epilepsy surgery by a competent, experienced team.
Seizure Outcome
•• Surgery is widely accepted as an effective therapy for selected individuals
with medically refractory epilepsy.
•• Careful patient selection even with non-invasive investigations can aid in
obtaining a good outcome in patients with extratemporal epilepsy.
•• A four-part classification system, called the Engel classification, categorising
post-operative seizure outcome to Class I (free of disabling seizures), Class
II (rare disabling seizures), Class III (worthwhile improvement) and Class
IV (no worthwhile improvement) is still in widespread use today.
•• Temporal lobe resections and lesional non-temporal lobe resections have
a very high probability of success.
199
CHAPTER
Surgery for
Temporal Epilepsy
Bhaskara Rao Malla • Jayanti Mani
INTRODUCTION
•• Temporal lobe epilepsy (TLE), especially mesial TLE (MTLE) is the most
common form of human epilepsy.
•• The pathological substrate of MTLE is usually hippocampal sclerosis, the
most common epileptogenic lesion encountered in patients with medically
refractory epilepsy.
•• The disabling seizures associated with MTLE are typically resistant to
antiepileptic drugs but can be abolished in most patients by surgical
treatment.
•• Anteromesial temporal resection, therefore, is the most common surgical
procedure performed to treat epilepsy.
•• The benefits of surgery for TLE have been well demonstrated in terms of
seizure control, cognitive function and quality of life (QOL).
PATHOLOGY
•• The most common pathology observed in nearly two-thirds of resected
temporal lobes was MTS.
•• In MTS, the hippocampal neurons were lost in the CA1 and CA3 regions
and the dentate hilus.
•• Sommer was the first to describe the neuropathological changes in
Ammon’s horn (cornu ammonis, CA) of patients with chronic epilepsy,
predominantly characterised by a loss of pyramidal cells in the CA1 sector
(often called the Sommer sector).
•• Margerison and Corsellis, in their study of TLE, observed two types of
hippocampal sclerosis: (1) classical Ammon’s horn sclerosis (with neuronal
loss and gliosis in the CA1 sector and the dentate gyrus) and (2) end folium
sclerosis involving the CA3 and CA4 sectors.
•• Low-grade neoplasms such as ganglioglioma and dysembryoplastic
neuroepithelial tumour, focal cortical dysplasia and vascular malformations
comprised the rest.
•• In endemic areas for cysticercosis, calcified cysticercous granulomas as a
cause for refractory partial epilepsy are not uncommon.
•• The spectrum of pathology in the paediatric population of TLE is different
to adults.
•• In a multinational report on paediatric epilepsy surgery, the most common
pathology in the resected specimens was a tumour followed by cortical
dysplasia and then hippocampal sclerosis. Thus, at an earlier age,
developmental lesions are much more common than hippocampal sclerosis.
1488
PRE-SURGICAL EVALUATION
•• A non-invasive protocol for evaluation of patients with medically refractory
TLE is provided in Table 1.
•• Today, a majority of patients with TLE can be selected for surgery, based
on the results of non-invasive methods such as scalp EEG, video-EEG,
MRI and neuropsychological findings.
•• Concordance of MRI and scalp EEG abnormalities correlates with an
excellent post-operative seizure outcome.
•• A sub-group of patients with MRI-negative TLE can also be evaluated and
selected for surgery, by using clinical history and scalp-recorded inter-ictal
and ictal EEG data.
•• The attributes of these patients are antecedent history of febrile seizures,
strictly unilateral anterior inter-ictal epileptiform discharges and concordant
type 1 ictal EEG pattern.
Non-invasive Evaluation
Seizure Semiology, Lateralisation and Localisation
•• Detailed study of the seizure semiology, as part of the video EEG
evaluation, provides confirmation of the epileptic nature of the seizures
and also provides valuable lateralising and localising information regarding
seizure onset.
•• This procedure involves continuous recording of synchronous scalp EEG
and video over a period of 24 hours to 7 days, with the aim of recording
inter-ictal EEG and clinical seizures with corresponding ictal EEG.
•• Medications are gradually withdrawn with the aim of recording habitual
seizures.
•• The seizures associated with TLE consist of simple partial seizures without
loss of awareness and complex partial seizures with loss of awareness.
The partial seizures may secondarily generalise.
•• They occur either as isolated events or as the first event that evolves into
more elaborate seizures. Auras are more frequent in TLE.
Table 1: A non-invasive protocol for the evaluation of patients with

medically refractory temporal lobe epilepsy
Review the history, past AED treatments, seizure frequency and EEGs
Medical and neurological examinations
16-channel awake and sleep scalp EEG recordings
Neuropsychological évaluation
Psycho-social evaluation
Psychiatric evaluation
Visual field testing
MRI with protocol for hippocampal volume loss and sclerosis
Long-term video-scalp EEG monitoring
Wada test in selected patients
Abbreviation: AED—antiepileptic drug; EEG—electroencephalogram; MRI—magnetic resonance imaging

Chapter 199 • Surgery for Temporal Epilepsy
1489
•• The epigastric or abdominal auras are considered to be typical of MTLE,

although extratemporal origin of epigastric auras has also been noted.
•• Psychic auras of fear and dèjà vu are related to the amygdala.
•• Gustatory and olfactory auras are quite characteristic of TLE.
•• Motionless stare with a behavioural arrest is the first evidence of the onset
of seizures in a large number of patients with TLE.
•• Oro-alimentary automatisms consisting of lip smacking, chewing and
swallowing are common in TLE.
•• Hand automatisms may be bimanual and when unilateral, they are often
ipsilateral to the side of seizure onset.
•• Contralateral arm dystonic posturing and forced contralateral version of
the head and eyes are strongly lateralising features in TLE with specificity
more than 90%. The latter is particularly useful when it occurs just prior to
secondary generalisation of the seizures.
•• Secondarily generalised tonic clonic seizures are rare in MTLE.
•• Post-ictal phenomena, like nose wiping, spitting, coughing and vomiting,
have been shown to occur in seizures from the non-dominant hemisphere,
whereas post-ictal aphasia lateralises the seizure to the language dominant
hemisphere.
•• Auditory auras are seen in seizures from the lateral temporal neocortex.
•• Early secondary generalisation and clonic phenomena involving the face
and hands are also more frequent with lateral temporal epilepsy.
•• Thin coronal oblique slices through the temporal lobe, of 1.5–2 mm
thickness with no gap using spoiled gradient recall images (SPGR) are
recommended.
•• On MRI, decreased hippocampal size on T1-weighted images increased
signal on T2-weighted and on fluid-attenuated inversion recovery (FLAIR)
images characterise hippocampal sclerosis.
•• High-resolution MRI shows hippocampal atrophy in many patients with
TLE by visual analysis alone.
•• Hippocampal atrophy is bilateral in 10–15% of cases.
•• Volumetry is used by some investigators to demonstrate asymmetry,
although controversy exists as to the need for this quantitative technique.
Neuropsychological Evaluation
•• The information obtained through neuropsychological testing helps in
counselling patients about the potential risk of post-operative memory
impairment and is also valuable in assessing progress in the follow-up
period.
•• The Wada test is undertaken prior to temporal lobectomy to lateralise the
distribution of language and memory function between the two hemispheres
and to thereby predict the post-operative language and memory outcome.
•• While language assessment during the Wada test is simple and straight-
forward, interpretation of memory deficit is complex and requires a carefully
designed protocol.
•• Inadequate memory support during the Wada test is not an absolute
contraindication to ATL and should be considered within the context of
the patient’s basal neuropsychological functioning and the impact of the
expected post-operative deterioration on one’s QOL.
1490
•• Restricting the Wada test to patients with suspected bilateral temporal

dysfunction, as evidenced by neuropsychological testing or MRI findings,
may be a cost-effective approach in developing countries. In the near
future, non-invasive evaluation with fMRI and PET may obviate the need
of the Wada test.
•• Currently, the risk of severe post-operative memory decline, following
unilateral ATL, can be predicted with reasonable accuracy.
•• The risk is higher when the following factors are present: (1) ATL on the
language dominant side; (2) no hippocampal atrophy or sclerosis on the
side of proposed resection; (3) a higher pre-operative memory performance;
(4) evidence of bilateral hippocampal atrophy on pre-operative imaging;
(5) seizure onset at an older age; (6) surgery performed at an older age;
(7) functional assessments (e.g. Wada test) that suggest greater residual
pre-operative function of the left temporal lobe and (8) left handed or
ambidextrous patients.
•• Thus, the risk would be highest for patients undergoing left temporal
lobectomy with left cerebral language dominance, absence of left
hippocampal atrophy/sclerosis, high baseline verbal memory, absence of
unilateral left temporal lobe hypo-metabolism in the PET and the presence
of high memory performance with right intracarotid amobarbitol injection,
but low memory performance with left injection.
Functional Imaging in Temporal Lobe Epilepsy
•• Non-invasive mapping procedures, such as single photon emission
computed tomography (SPECT), positron emission tomography (PET),
functional MRI (fMRI), magnetic resonance spectroscopy and magneto-
encephalography, may provide information complementary to that provided
by EEG, video-EEG and MRI.
•• Peri-ictal SPECT studies are obtained by injecting a radiotracer during (ictal)
or soon after the seizure activity (post-ictal), which necessitates electro-
clinical correlation utilising continuous video-EEG monitoring.
•• Hyperperfusion of the epileptic temporal lobe occurs during the ictus and
persists for up to one minute into the immediate post-ictal period.
•• Ictal SPECT studies of temporal lobe seizures yield over 90% correct
lateralisation of the epileptogenic focus.
•• The findings of complex partial seizures of temporal lobe semiology,
anterior temporal inter-ictal sharp waves arising in the mesial temporal
structures, without evidence of extratemporal epileptiform activity on EEG
and unilateral MTS on MR imaging without extratemporal lesions, together
yield the diagnosis of MTLE.
•• Vascular lesions, such as cavernous angiomas and arteriovenous malfor-
mations, focal developmental abnormalities, hamartomas and low-grade
neoplasms, may involve the medial or lateral parts of the temporal lobe.
•• Selecting patients with TLE for the appropriate operation begins by first
using MRI to classify them into the three anatomical substrate categories
noted above: (1) hippocampal atrophy (MTLE with presumed MTS); (2)
lesions (LTLE) or (3) normal anatomy (CTLE).
•• Patients with long standing lesions (e.g. developmental, atrophic or benign
neoplastic lesions) may develop hippocampal atrophy (dual pathology).
•• The primary lesion, the secondary hippocampal sclerosis or both, may be
responsible for the seizures.
1491
Invasive Evaluation
•• Patients with TLE may require invasive monitoring, when the results of non-
invasive methods such as scalp EEG, video-EEG and MRI are conflicting.
•• Several types of intracranial recording electrodes, such as subdural strip
and grid electrodes, epidural electrodes, intracerebral depth electrodes or
their combination, may have to be utilised to define the site of seizure origin.
•• Exclusive use of either intracerebral or subdural electrodes may occasionally
result in erroneous localisation because of insufficient sampling.
•• Patients with suspected MTLE, with bilateral temporal inter-ictal and
ictal abnormalities and/or bilateral MTS, often will require bilateral depth
electrode placement to the mesial temporal structures.
•• When neurosurgical procedures encroaching the neocortical sensory, motor
and speech areas are planned, functional mapping using fMRI or during
surgery with the patient awake or extra-operatively after placing intracranial
electrodes is performed to circumscribe the area of resection, in order to
avoid post-operative neurological deficits.
SURGICAL TREATMENT
Surgical Approaches
•• A diversity of operations has been undertaken for the management of
refractory TLE (Table 2).
•• ATL pioneered by Penfield is the most common surgical procedure
undertaken.
•• For patients with unilateral or predominantly unilateral seizures, most
centres perform a standard ATL in which the anterior temporal neocortex,
anterior hippocampus and lateral amygdala are resected.
•• Intra-operative electrocorticography (ECoG) and cortical stimulation are
used at some centres to tailor the lateral temporal resection, according
to the extent of EEG abnormality and the location of the language cortex.
Table 2: Surgical techniques for the treatment of medically

refractory temporal lobe epilepsy
Anterior temporal lobectomy with amygdalohippocampectomy
Standard
Tailored
Selective amygdalohippocampectomy
Transcortical-transventricular approaches
Through superior temporal gyrus
Through middle temporal gyrus
Through inferior temporal gyrus
Trans-Sylvian approach
Subtemporal approach
Selective lateral temporal (neocortical) resection
Lesionectomy
Multiple subpial transections
1492
•• Selective amygdalohippocampectomy (SAH), sparing the lateral temporal

neocortex, is performed at some centres.
•• Other centres perform only lateral neocortical resections, sparing the
amygdala and hippocampus.
•• The aim of modified temporal resections is to reduce post-operative
cognitive deficits.
Anterior Temporal Lobectomy
•• Anterior temporal lobectomy is also known as standard or tailored ATL and
anteromedial temporal lobectomy.
•• Anterior temporal lobectomy includes resection of the neocortex, extending
up to 3.5–4.0 cm from the temporal pole on the dominant side and 4.0–4.5
cm on the non-dominant side along the Sylvian fissure.
Selective Amygdalohippocampectomy (SAH)
•• Amygdalohippocampectomy is a selective resection of the amygdala,
uncus and hippocampus posteriorly to the level of the superior colliculus.
•• Amygdalohippocampectomy can be performed via different approaches.
With this approach, the lateral temporal cortex is not resected.
•• Several modifications of this technique have been proposed. In trans-
Sylvian approach, the Sylvian fissure, the temporal ventricular horn is
entered through the temporal stem in the inferior semicircular sulcus,
followed by the resection of mesiotemporal structures.
•• Others comprises sub-temporal, zygomatic, subtemporal trans-parahip-
pocampal, trans-Sylvian-transcisternal and even retrolabyrinthine-presigmoid
approach, etc.
•• The indications for SAH are as follows: (1) a lesion confined to the medial
temporal structures; (2) evidence of ipsilateral medial temporal onset of
partial complex seizures; (3) indications that some of the patient’s memory
function was subserved by the operated temporal lobe, possibly more so
in the dominant temporal lobe.
•• The contraindications for SAH are as follows: (1) a lesion outside of the medial
temporal structures; (2) a lesion confined to the medial temporal structures,
but too large or too posterior; (3) a patient in whom neurophysiological
evidence indicates a regional seizure onset within the temporal lobe;
(4) a patient in whom the contralateral temporal lobe carries all or most of
the recent memory function.
Lesional Temporal Lobe Epilepsy
•• In patients with various types of developmental, neoplastic or vascular
lesions responsible for epilepsy, three surgical solutions are possible.
•• First, only the lesion may be removed; second, the lesion and some portion
of the medial structures may be removed to assure a margin of resection;
and, finally, a formal antero-mesial temporal resection may be performed
in addition to removal of the lesion.
Stereotactic Procedures
•• Stereotactic amygdalotomy was performed upon a sizable number of
patients with improvement in control of seizures, as well as behaviour
disorder. However, this procedure did not receive wider acceptance.
•• Currently, stereotactic techniques are widely used to implant electrodes in
the temporal lobe, to determine the laterality and extent of the epileptogenic
zone in patients with intractable TLE.
1493
•• Placement of depth electrodes can be performed using the orthogonal

approach or an occipital approach.
•• Both frame-based and frame-less stereotactic systems can be used for
depth electrode placement.
•• Frameless stereotaxy can be used for SAH.
Alternate Surgical Procedures

•• For lesions located in close proximity to eloquent areas, such as motor and
speech areas, multiple subpial transection is a safe option to reduce the
seizure frequency without causing morbidity.
•• Children with Landau-Kleffener syndrome may show substantial recovery
of speech, following multiple subpial transections.
•• The role of deep brain stimulation to treat epilepsy is being investigated.
•• For refractory epilepsy patients in whom resective surgical treatment is
not an ideal option, neurostimulation therapies hold promise of improving
seizure control, without the adverse effects of multiple antiepileptic
medications.
•• Vagus nerve stimulation is currently an approved method of treatment for
medically refractory epilepsy in adults and children who are not candidates
for resective surgery.
Complications
•• Specific complications of ATL include homonymous superior quadrantano-
psia, due to involvement of either the optic tract or radiation and language
deficits and manipulation hemiplegia, due to vascular injury or spasm
involving the Sylvian vessels, anterior choroidal artery branches supplying
the cerebral peduncle or the perforators supplying the internal capsule.
These complications may be minimised if care is taken to avoid damage
to the branches of the anterior choroidal artery and the branches of the P2
segment of the posterior cerebral artery.
•• Disabling visual field defects are more likely to result from damage to or
spasm of the vessels that supply the optic tract, than from direct injury to
Meyer’s loop.
OUTCOME ASSESSMENT
Determinants of Post-operative Seizure Outcome
•• The attributes of ideal surgical candidates for ATL with amygdalohip-
pocampectomy are listed in Table 3.
Table 3: Ideal candidates for anterior temporal lobectomy or

selective amygdalohippocampectomy
Prolonged febrile seizures during childhood
Normal neurological examination and IQ
Stereotyped semiology of the complex partial seizures
Unilateral temporal spikes in scalp EEG
MRI showing hippocampal atrophy/sclerosis
Site of seizure origin same as scalp EEG and MRI abnormalities
EEG—electroencephalogram; IQ—intelligence quotient; MRI—magnetic resonance imaging
1494
•• Nearly 90% of patients with unequivocal unilateral MTLE (TLE associated

with MTS) achieve excellent seizure outcome, following this procedure.
•• While an MRI or histopathologically verified lesion is a strong predictor of
a favourable seizure outcome, a normal MRI and absence of pathology in
the resected specimen are often associated with post-operative seizure
recurrence.
•• The seizure remission is better in those patients with a complete lesion
removal, when compared to those with post-operative residual lesions.
•• A number of factors predictive for good seizure control have been reported
as follows: (1) clear abnormality on MR imaging; (2) absence of status
epilepticus; (3) MR imaging confirmed ganglioglioma or DNT; (4) concordant
lateralising memory deficit and (5) absence of dysplasia on MR imaging.
Section XVI: Cerebral Palsy
200
CHAPTER Stereotaxy for
Cerebral Palsy
Kanaka TS • Balasubramaniam V • Sampathkumar M
INTRODUCTION
•• Cerebral palsy is a complex neurological syndrome involving intellectual,
locomotor and postural functions. When intellectual retardation is prominent,
the only method of treatment available is education at special institutions,
but when the intellect is preserved and the motor aspects of the disease, like
hypertonus and involuntary movements predominate, stereotaxic surgery
may be helpful in relieving these features.
DEFINITION
•• Cerebral palsy is defined as ‘a persisting qualitative motor disorder
appearing before the age of 3 years due to a non-progressive damage
of the brain’.
•• Cerebral palsy is a persistent, but not unchanging disorder of posture and
movement due to dysfunction of the brain (excluding dysfunction due to
progressive disease) present before the growth and development of the
brain are complete. Many other clinical features may also be present.
AETIOLOGY
•• The disease complex known as cerebral palsy is due to many aetiological
factors the most common being trauma during birth.
•• The birth trauma may occur due to excessive moulding of the head during
delivery, resulting in multiple haemorrhages due to venous obstruction
and brain distortion.
•• Hypoxic damage can also result from placenta praevia, delayed second
stage of labour, cord round the neck, neonatal aspiration or neonatal
convulsions.
•• However, cerebral palsy has often been noted in children whose delivery
was uncomplicated and non-cyanotic.
•• Soon after birth, kernicterus can give rise to damage to the basal ganglia
and result in dystonia and hypertonus.
•• In the first few years of infancy and childhood, many diseases can damage
the brain, the most common being encephalitis or ‘hypertoxic state’ as
it is called now. The child suffers from a sudden rise of temperature
and perhaps exhibits generalised seizures for 1 or 2 days. This may be
followed by neurological deficits, like spasticity and mental retardation with
behaviour problems. In most of these cases, special virological studies
prove inconclusive.
Section XVI • Cerebral Palsy
1496
•• In another group of cases, the patient develops high temperature with

focal seizures.
•• On recovery there is usually hemiplegia.
•• In those cases, it is quite likely that the major insult is to the arteries
(a form of obliterative arteritis) or to the veins (as thrombophlebitis). In some
cases, a global damage also results.
•• Head injury during the first few years of life may also lead to cerebral palsy.
CLINICAL FEATURES
•• This condition is essentially a non-progressive one but, in an occasional
case, it may be apparently progressive when a hypotonic patient becomes
hypertonic or when a hypertonic patient develops contractures or disuse
atrophy of muscles due to lack of physiotherapy.
•• The clinical features of cerebral palsy could be classified into those due to:
–– Disorders of tone
–– Disorders of movement.
•• These are often in addition to varying degrees of other deficits like speech
disorders, disorders of vision, cranial nerve palsies and disorders of hearing.
•• Associated seizures, mental retardation or frank behavioural abnormality
may be seen in some cases.
•• Arrest of cerebral development, early in life, results in the persistence of
primitive reflexes like Moro’s reflex. The tonic neck reflexes may often be
elicited.
Disorders of Tone
•• These are of two types, viz., a. hypotonic, b. hypertonic.
•• The hypotonic variety is seen in the classical ‘floppy infant’. There is
generalised absence of tone in the axial as well as in the apendicular
system. In some cases, the tone returns as the child grows and the child
may have hypertonicity. All these children have mental retardation.
•• Hypertonic cases may have spasticity, rigidity or a combination of both. This
may involve one or more limbs and, often, the neck and the trunk. During
passive movement of the limb, uniform hypertonus indicates rigidity and
a sudden reduction of the hypertonus on continuing passive movement
points to spasticity.
•• It is not always possible to decide the type of hypertonus by clinical
examination alone; surface EMG is useful in differentiation.
•• The degree of hypertonus may vary from time to time and different
observers may differ in their assessment if the examination is done at
different times.
Abnormal Movements
•• Involuntary movements may co-exist with hypertonus and/or mental
retardation.
•• The common varieties are choreoathetosis, athetosis, torsion dystonia
and intention tremor.
•• Athetosis refers to slow writhing movements particularly affecting the distal
portions of the limbs, involving alternately the agonists and antagonists.
There is always an element of hypertonus in these movements.
•• Choreic movement is characterised by frequent jerky, quasi purposive
movements predominantly of the distal parts of the limbs.
Chapter 200 • Stereotaxy for Cerebral Palsy
1497
•• The term ‘choreoathetosis’ is applied when the movements cannot be classi-

fied as choreic or athetotic and when there is a combination of both elements.
•• Ballistic movements are more rapid, forceful, projectile and involve mainly
the proximal parts of the limbs, rotating the limb in a wide arc. Intention
tremors may also be seen in some patients. Some children exhibit
involuntary movements that are made worse by sensory stimuli like
touch, noise, light or questioning. The movements may also be induced
on attempts at voluntary acts. Left alone, the child is quiet and relaxed,
but when the examiner asks the child to do something like putting out the
tongue, the entire body goes into a severe dystonic posture.
•• Dystonia implies an abnormal fixity of posture due to sustained muscular
contraction. When the posture continues to change, the abnormal fixity
involves fresh sets of muscles, resulting in dystonic movements.
TREATMENT
•• Stereotaxic surgery does not replace physiotherapy.
•• Physiotherapy, occupational therapy, education of the child and speech
therapy (wherever needed) are ancillary treatments carried out pre-
operatively and post-operatively.
•• Surgery for cerebral palsy was, earlier, confined to orthopaedic operations
on muscles, tendons and selected neurectomies of peripheral nerves.
•• Division of selected nerve roots may help in relieving localised severe
muscular hypertonus.
•• However, all these operations give only partial relief and do not alter the
central mechanisms responsible for the hypertonus.
Criteria for Selection of Cases for Stereotaxic Surgery

•• Patients with hypertonus and/or involuntary movements may be considered
for stereotaxic surgery straight away if they are not grossly mentally
retarded.
•• For mild hypertonus, physiotherapy and orthopaedic corrective procedures
may suffice. If after such a course of treatment, the hypertonus still interferes
with function, stereotaxic surgery is considered.
•• Patients with severe mental retardation, incontinence of urine and faeces,
pseudobulbar signs or fixed contractures are not suitable for surgery.
•• Patients with severe hypertonus and gross mental retardation are at times
given the benefit of stereotaxic surgery mainly to ease the nursing care.
Pre-operative Assessment
•• In the pre-operative motor assessment, the Johnson’s motor-age test and
the severity index suggested by Beals are of value to provide the base line
to judge the degree of improvement during treatment.
Electromyographic Studies
•• To choose appropriate targets for making the surgical lesion it is necessary
to have an accurate idea of the degree and variety of hypertonus.
•• This information is objectively provided by surface EMG.
•• As mentioned above, hypertonus can be of the following types: rigidity,
rigidospasticity, spasticity and spastorigidity.
•• Although clinically it may be easy to distinguish extremes of hypertonicity
like spasticity or rigidity, surface electromyography is necessary for
1498
recognition of rigidospastic states and to have an objective assessment

of the other types.
•• EMG studies are also useful to determine the amount of hypertonicity present
in cases with involuntary movements and to have comparable quantitative
graphic records of the hypertonus before and after the operation.
Psychometric Assessment
•• The result of treatment of cerebral palsy depends to a large extent on the co-
operation of the patient and, hence, the child should be sufficiently intelligent
to follow the instructions during physiotherapy and occupational therapy.
•• Psychometric assessment helps in decisions regarding surgery and
prognosis.
Timing of the Operation

•• Some workers prefer to postpone surgery till the child is 5 or 6 years
old, treating the child in the meantime with intensive physiotherapy, but,
generally, once neurosurgical treatment is considered useful, it is better to
do it as early as possible even in children less than 5 years old.
•• Early relief from hypertonicity and dyskinesias is conducive to better
physiological growth of the limbs and an earlier commencement of the
overall training programme of the child.
•• Further, as many of these children may require multiple-staged operations,
much time is lost if the surgical treatment is started late.
•• The timing of surgery is also guided by the intensity of the disability. In
severe cases, stereotaxic surgery has to precede other measures.
•• In patients who need bilateral surgery on the thalamus, it is desirable to
have an interval of at least 6 months between the two operations. This
time-interval is not essential when a cerebellar lesion is to be combined
with a thalamic lesion.
Pathophysiology and Choice of the Target

•• The disturbance of neural mechanisms in the brain of a patient with cerebral
palsy is widespread and varies in each individual patient, although the
resulting overall picture is one of movement and postural disturbance mixed
with mental retardation.
•• Such disturbances in the central mechanisms interfere with finely co-
ordinated influences that act on the spinal motor neuron, upsetting its
balanced precision, but the exact mechanisms are still controversial.
•• Hypertonus has been ascribed by some to gamma motor neuron
hyperactivity and by others to hypoactivity.
•• The hypertonus may also be explained by central activation of the
large motor neurons, through the alpha route and by gamma activation
independent of muscle stretch.
•• The imbalance between the dynamic and static activity is responsible for
various types of hypertonus seen in cerebral palsy.
•• The choice of the target depends on the type of hypertonus of the muscles
and the presence and nature of involuntary movements.
Rigidity
•• Rigidity is relieved by a lesion in the ventrolateral (VL) nucleus of the
thalamus (Voa and Vop of Hassler).
•• The lesions in both the Voa and Vop and the sub VL areas and VIM.
Chapter 200 • Stereotaxy for Cerebral Palsy
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Rigidospasticity and Spasticity

•• In cases with rigidospasticity and spasticity, thalamotomy alone fails to
help, neither does pallidotomy influence significantly the cases with a
spastic pattern.
•• In such cases, the addition of a lesion in the dentate nucleus of the
cerebellum gives adequate relief.
•• The cerebellum, as the only structure that receives the afferent influx from
the annulospiral endings of the muscle spindle and from Golgi tendon
organs, is of great importance in both the static and dynamic phases of
muscle activity.
•• This is seen clinically by the relief of rigidity, as well as spasticity after
dentatectomy.
Sensory-induced Dystonia
•• In cases where the dystonic movements are aggravated by sensory stimuli
(like a noise, flash of light or a question), a lesion in the centrum medianum
(CM) nucleus in addition to the one in the VL-sub-VL area gives relief.
•• Many fibre systems converge on the CM nucleus. It receives collaterals from
all sensory pathways indirectly through the connections with the reticular
formation. Some fibres of the spinothalamic tract also terminate in this
nucleus. Its efferents pass to the caudate and putamen, through which it
probably influences the motor cortex.
•• Although still poorly understood, the physiologic role of the CM nucleus
appears to be the integration and modulation of heterogeneous sensory
and cerebellar impulses.
•• The aggravation of the dystonia by sensory input is due to a lowering of the
‘threshold for transmission from sensory to motor system’.
•• A lesion in the CM nucleus interrupts various converging fibre systems and
destroys the cells of origin of the efferent neurons to the putamen, both of
which may be critical in the genesis of movement disorders.
Dyskinesias
•• In cases with various dyskinesias, a lesion in the VIM (Ventralis intermedius
externus of Hassler) nucleus is helpful when combined with VL and CM
lesions.
•• The VIM nucleus receives fibres from and the impulses project to area
3-a. The exact function of this nucleus is not known. That it is a part of
the tremerogenic zone is certain, as tremors are facilitated or produced
on stimulation of this area. VIM e
xternus lesions have been found to be of
value in normotonic tremors.
Infantile Hemiplegia with Athetosis

•• Among the conditions, which prove recalcitrant to treatment, infantile
hemiplegia with athetosis is one.
•• In the hands of most workers, neither thalamotomy nor dentatectomy alone
has given consistently good results.
•• A combination of dentate and VIM lesions, ‘dentatothalamotomy’ has been
found to give satisfactory results.
•• This suggests the existence of a servo-mechanism for correcting the
position of the limbs in the dentate–VIM connections.
1500
•• Spinocerebellar fibres and afferents from the cerebellum probably play a

role in this mechanism.
•• To summarise:
–– For rigidity the best results are obtained with VL and sub-VL lesions.
–– Rigidospastic patients need thalamotomy and/or dentatectomy,
depending on whether rigidity or spasticity predominates.
–– Spasticity is relieved by dentatectomy.
–– Sensory induced involuntary movements need CM thalamotomy for
their relief. Normotonic involuntary movements are relieved by VIM
lesions.
–– Infantile hemiplegics with spasticity and athetosis do very well with
a combination of ipsilateral dentatectomy and contralateral VIM
thalamotomy.
201
CHAPTER
Surgery for Spasticity
AK Purohit • Jagan Mohan Reddy K
MECHANISM OF GENERATION OF
SPASTICITY AND BASIS OF ACTION OF
VARIOUS PROCEDURES
•• The exact mechanism of generation of spasticity and difference in spasticity
generated due to brain and spinal cord pathologies is still not known.
•• The following are the two levels of control of muscle tone.
Suprasegmental Control
•• The reticular system of the brainstem plays a central role in the maintenance
of normal tone.
•• It consists of both an excitatory and an inhibitory centre.
•• The excitatory centre is located in a diffuse area extending from the basal
diencephalon, central gray and tegmentum of the midbrain and the pons
and the lateral bulbar reticular formation outside the inhibitory field.
•• The spinal projections of this system involve the ventral half of the cord
and descend as the medial reticulospinal tract. This centre is supposed to
be autonomous and is not under any cortical control.
•• The inhibitory centre is located in the caudal brainstem and is under the
control of the motor cortex and to a lesser extent is also influenced by the
cerebellar cortex and fastigial nucleus.
•• The spinal projections of this system involve the dorsal half of the lateral
funiculus and are conducted by the dorsal reticulospinal tract.
•• Normal tone consists of a balance between inhibitory effects on stretch
reflexes, mediated by the dorsal reticulospinal tract and facilitatory effects
on extensor tone, mediated by the medial reticulospinal tract and, to a
lesser extent, by the vestibulospinal tract.
•• In cortical and capsular lesions, some of the drive on the inhibitory centre
in the caudal brainstem is lost, resulting in spasticity.
•• In partial spinal lesions like demyelinating disorders, there is involvement
of both the pyramidal tracts and dorsal reticulospinal tracts, giving rise to
severe spasticity due to the unopposed action of the medial reticulospinal
and vestibulospinal tracts.
•• In severe or complete cord lesions, there is loss of all supraspinal influences
on the cord.
•• During the period of spinal shock, the muscles remain flaccid, toneless
and areflexic. After this period, there will be gradual development of
hypertonia and hyper-reflexia due to the plasticity within the spinal cord,
namely receptor hypersensitivity and sprouting of the axon terminals.
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This hypertonicity is different from the velocity dependent spasticity seen

in partial cord lesions that results in virtually continuous flexor spasms.
Segmental Control
•• All these tracts normally inhibit the spinal myotatic monosynaptic circuit,
through their influence on gamma motor neurons that are found amongst
various anterior horn cells.
•• The gamma motor neurons, by nature, continuously discharge impulses
(autogenicity) that travel through the anterior roots and peripheral nerves to
reach muscle spindles located parallel to striated muscle fibres (extrafusal
muscle fibres).
•• The spindles by nature can sense the length of the muscle fibres and
send the message via fibres that are located in the peripheral nerves and
posterior roots.
•• The message reaches alpha motor neurons that are found in the anterior
horn cells. They in turn send the message via anterior roots to the extrafusal
muscle fibres. The circuit is facilitatory in nature.
•• The tone in the muscles is the product of a balance between suprasegmental
and segmental control mechanisms.
•• In people with spasticity, the suprasegmental control gets altered and this
results in generation of spasticity, whereas, the segmental control remains
intact. However, it becomes overactive because of loss of suprasegmental
inhibition.
•• Therefore, the ideal treatment of spasticity is regeneration or implantation
of damaged neural tissue that constitutes suprasegmental control. This
development is yet to take place.
•• However, the neuro-stimulation procedures performed presently on the
brain or spinal cord, indeed, act by restoring suprasegmental control to
some extent.
TREATMENT PROTOCOL
Physical Methods
•• Physiotherapy, occupational therapy—to improve control, balance,
functions and muscle tone
•• Orthotic device application
•• Special education
•• Psychological assessment and treatment
•• Speech therapy
•• Ophthalmologist’s consultation
•• Control of seizures and other neurological problems
•• Management of resistant spasticity: Resistant spasticity is managed by
various methods that will be discussed now in this chapter.
Selection of Cases
•• During clinical examination, the following features should be noted:
I. Non-progression of neurological deficits
II. Harmful spasticity
1. Disabling spasticity
2. Complications of spasticity and disfigurement
3. Discomfort, pain and high energy consumption
III. Resistant spasticity
Chapter 201 • Surgery for Spasticity
1503
IV. Safety and usefulness of the procedure

V. Goals.
•• Detection of non-progression of neurological deficits.
•• There are various non-progressive disorders like cerebral palsy and injury
to the central nervous system (CNS).
•• Also, there are some diseases such as infections, vascular insult, neoplasm
and lathyrism that, after treatment, may leave a person with some non-
progressive neurological deficits like spasticity.
•• Careful clinical and investigative procedures are advised to detect and
differentiate these from partially treated progressive disease or incurable
progressive degenerative, metabolic and hereditary diseases.
•• Surgical procedures are mostly indicated only for non-progressive
disorders.
•• However, if the disorder is very slowly worsening and producing harmful
spasticity, certain selected procedures can be considered.
Detection of Harmful Spasticity
1. Disabling spasticity:
–– Mostly, motor performance of the person is adversely affected by the
presence of spasticity.
–– For example, a person with spastic paraplegia in extension may be
able to maintain an upright standing posture. He may be able to walk
with the help of the spasticity, in spite of poor control in the lower limbs.
–– Similarly, spastic elbow flexion is helpful in performing most of the
activities of daily living.
–– For example, clinical tests like squat to stand and stand to squat can
reveal the true degree of control.
–– People who are able to perform such tests several times, by repeat-
edly interrupting the movements, are considered to have good control,
while those who are unable to even initiate the movement are said to
have poor control.
–– Tests of similar nature can be applied to detect control of the trunk
and upper limbs.
2. Development of complications of spasticity:
–– Long standing spasticity can produce musculoskeletal complications
like organic shortening of muscles, dislocations, etc.
–– They may adversely affect motor activities and, therefore, the results of
neuro-intervention. Such complications can also affect the appearance
of the affected part.
3. Discomfort, pain and high energy consumption:
–– Severe spasticity can cause discomfort and pain.
–– Persons may get tired easily due to high-energy consumption. These
factors adversely affect motor functions and performance during
physiotherapy. In such cases, relief can be obtained following neuro-
interventional methods, by improving functions.
Detection of Resistant Spasticity
•• The patient is evaluated and treated for any nociceptive stimuli in the
body like a spastic bladder, urinary tract infection, urolithiasis, chronic
constipation, fissure in ano, perianal infection and bedsores.
•• Sometimes, serial plaster of Paris cast application, temporary neural
blocks, ice application and botulinum toxin injections, can also be tried to
relieve spasticity.
1504
•• If residual spasticity persists despite all these measures for a sufficient pe-
riod of time (usually 6 months), a person is said to have resistant spasticity.
•• These measures may, in fact, either reduce the number and extent of
surgical interventions or improve the person with spasticity to such an
extent that surgery is not required.
Detection of Probable Safety and
Usefulness of the Procedure
•• Surgical exposure should be safe. Therefore, in the presence of
kyphoscoliosis, spondylolisthesis and poor trunk control, a laminectomy
for intraspinal procedures is contraindicated.
•• Relief of spasticity is also contraindicated in the presence of severe ataxia,
dystonia and athetosis, because these neurological deficits may become
more apparent after reduction in tone.
•• Non-motivated people with spasticity may not be trainable by physiotherapy
and, therefore, motor function improvement may not be possible.
•• The presence of major and/or multiple musculoskeletal complications
hamper motor performance, despite optimisation of the spastic tone.
•• In some cases, however, improvement in motor performance may not be
possible, but surgery can help in relieving pain, discomfort and improving
nursing care.
Detection and Discussion of Goals
•• Neuro-intervention for optimisation of the spastic tone is indicated only
in those people who have non-progressive, harmful, resistant spasticity.
•• The team should ascertain the safety and usefulness of the procedure and
clearly discuss the goals with the person with spasticity and his relatives.
•• Ideal case: A well-motivated person having non-progressive, harmful,
resistant spasticity with good control in the affected part and who has
no musculoskeletal complications is considered as an ideal candidate
for optimisation of the spastic tone by neuro-intervention, especially by
ablative methods.
Neuro-interventional Procedures
Ideal Method
•• The ideal method to treat non-progressive harmful spasticity is regeneration
or transplantation of the damaged neural tissue, prior to development of
irreversible histochemical and structural changes in the neural structures
and the musculoskeletal system.
•• Short of regeneration or transplantation, other surgical methods can be
considered; ideally, this surgical method should produce a calculated,
reversible reduction in spasticity.
•• In other words, it should produce optimum tone that is beneficial to the
person, with least possible invasion and without adversely affecting the
normal and potentially normal functions of the nervous system.
•• The procedure should be safe, not too time consuming or expensive, and
technically easy to perform.
•• There are various procedures in practice (Table 1) but none of them
satisfy all the above mentioned criteria. However, presently, they are of
tremendous help to people with spasticity.
1505
Table 1: Classification of neuro-interventional procedures for

optimisation of spastic tone
Site Non-ablative Ablative
I. Segmental (Spinal Circuit)
A. PNS
1. Extra-craniospinal Myoneural junction — Botulinum toxin
Peripheral nerves Temporary neural Permanent neural
block block
Peripheral nerve Fasciculotomy
2. Intra-spinal Spinal root stimulation (Neurotomy)
— Rhizotomy
B. CNS
Intra-spinal Spinal cord Intrathecal baclofen Drezotomy
Myelotomy
II. Supra-segmental
A. CNS
Spinal cord Spinal cord —
stimulation
1. Intraspinal
2. Intracranial Brain Thalamic Thalamotomy
stimulation Pulvinarotomy
Cerebellar Dentatectomy
stimulation Fastigii lesions
Abbreviation: PNS – Peripheral nervous system, peripheral procedure; CNS – Central nervous system, central procedure
CLASSIFICATION
•• The neuro-interventional procedures are classified according to the site
and the nature of the neuro-intervention (Table 1).
Anatomical Classification
Control Pathways
•• Suprasegmental: The procedures that act on suprasegmental control of
tone are called suprasegmental procedures. These are performed on the
central nervous system (e.g. spinal cord stimulation).
•• Segmental: The procedures that interrupt the spinal circuit responsible
for the maintenance of tone are called segmental procedures. These are
performed on the peripheral (e.g. fasciculotomy) or central nervous system
(e.g. myelotomy).
Location
•• Central: When surgery is performed on the brain or spinal cord.
•• Peripheral: When surgery is performed on cranial nerves, spinal roots or
peripheral nerves.
Physiological Classification
•• The procedures are classified into two types, depending on their effect on
the nervous system.
–– Non-ablative: A reversible neural response is obtained without creat-
ing a lesion with the help of neuro-stimulation or chemical substances
(e.g. spinal cord stimulation).
1506
–– Ablative: An irreversible lesion is created in the neural tissue (e.g.

rhizotomy, fasciculotomy, etc.).
Non-ablative Segmental (Spinal Circuit) Procedures

Peripheral Procedures
•• Temporary peripheral (nerve) blocks:
–– Chemical substances like bupivacaine are used on the peripheral
neural structures to relieve spasticity, by reducing excessive gamma
fusimotor drive.
–– In the closed method, easily accessible nerves like the obturator, tibial,
peroneal, musculocutaneous, ulnar and median nerves can be blocked
by infiltration of chemical substances around the nerve.
–– In the open method, inaccessible nerves are exposed surgically and
a catheter that is connected with a reservoir for repeated injections is
introduced, so as to obtain the effect of the drug for a long time.
Central Procedures
•• Intrathecal baclofen (ITB): Baclofen is a GABA-B agonist drug that gets
bound to the receptors on the superficial layers of the posterior horn. This
inhibits presynaptic transmitter release, by depolarising the action potential
induced calcium conductance.
•• Various kinds of pumps have been devised, to provide a smooth and
sustained release of the drug.
•• Under general or local anaesthesia, an intrathecal tube is passed from the back
through the lumbar intervertebral space and left in the subarachnoid space.
•• It is brought out at a convenient site on the abdomen through a subcu-
taneous tunnel and is connected to a reservoir that is implanted into the
abdominal wall.
•• Good and sustained reduction in spasticity of spinal origin has been dem-
onstrated with the use of intrathecal baclofen (ITB) in a number of studies
conducted in the recent past.
•• Spasticity of cerebral origin is also reduced, but the effect is less than in
spasticity of spinal origin.
•• Higher doses of baclofen can reduce spasticity further, but it causes
weakness in the lower limbs and leads to other adverse events.
•• An important positive aspect of ITB is that it is a non-ablative, reversible
method and the reduction in spasticity can be titrated.
•• ITB improves motor performance in the activities of daily living and in
existing functions.
•• Unconsciousness to the extent of coma and respiratory failure, infection,
disconnection of the tubes, geographical dependency and high expenses
are the limiting factors for the use of this procedure.
Non-ablative Supra-segmental
Procedures—Central Procedures
Neural-stimulation
1. Spinal cord (dorsal column, posterior column) stimulation:
–– The mechanism of relief of spasticity, resulting from spinal cord stimu-
lation, is not yet clear.
–– Stimulation of descending inhibitory pathways, blockade of nociceptive
afferent influences on long loop reflexes and influence on the ascend-
ing and descending reticular systems, have been proposed.
1507
–– Electrodes are implanted in the midline posteriorly at the cervical, tho-

racic or lumbar epidural space by an open surgical procedure or by a
closed method under fluoroscopy.
–– The electrodes are connected to a receiver that is implanted subcuta-
neously in the subclavicular or sub-costal region.
–– The frequency of stimulation is adjusted through an external spinal
cord stimulator system called transmitter, which is a four electrode
system using Lithium rechargeable Nickel-Cadmium batteries.
–– Leakage of current, displacement of electrodes, infection, CSF leak,
pain at the stimulation site, geographical dependency and high ex-
penses, are the possible problems related to the use of this system.
2. Thalamic stimulation: Stimulation of the sensory relay nuclei of the
thalamus has been tried for relief of spasticity.
3. Chronic cerebellar stimulation: This includes:
–– Stimulation of the cerebellar cortex: Electrodes are implanted
on the posterior lobe of the cerebellum, under general anaesthesia
through small bilateral craniotomies and are connected to a receiver
pacemaker implanted subcutaneously in the sub-clavicular region.
–– Dentate nuclei stimulation: Spinal cord stimulation and ablative pro-
cedures are producing encouraging results and, therefore, the central
neuro-stimulation procedures have not received wide acceptance.
Besides the equivocal results, these implantable devices are very
expensive and have not stood the test of time.
Ablative Segmental (Spinal Circuit) Procedures

Peripheral Proceduress
1. Peripheral nerve blocks:
• Ablative peripheral neural blocks can be done on the peripheral
nerves.
• Botulinum toxin blocks the release of acetylcholine (ACh) at the my-
oneural junction and, thereby, reduces spasticity.
• It is effective in dystonia, affecting the small muscles of the face and
neck.
• It reduces spasticity of limb muscles also, but high doses are needed.
• It can be helpful in selected young children with cerebral palsy who
have only focal spasticity, but quadriplegic patients having severe dif-
fuse spasticity are not the right candidates.
• The drug is of no use in the presence of contractures. It can be com-
plimentary to physical methods of treatment.
• The toxin is injected at the myoneural junction. Sometimes, especially
for small muscles, ENMG is required to localise the exact site of drug
administration.
• There are no major side effects when injected into the limb muscles.
However, recurrence is seen quite often. Therefore, repeated injec-
tions are required. In such cases, sometimes, antibodies against the
drug can develop and then it becomes ineffective.
• Presently, the drug is very expensive.
• There is a reduction in spasticity for a short duration.
2. Neurotomy (neurectomy, fasciculotomy): Classification: This includes
the following:
•• Closed procedures: Radiofrequency (RF) lesion
1508
•• Open procedures: This procedure has been classified into the following
types:
–– Non-functional
¾¾ Total neurotomy
¾¾ Partial neurotomy
–– Functional
¾¾ Functional neurotomy (Selective neurotomy, Selective motor
fasciculotomy)
–– In this procedure, the function of different nerve fascicles is determined
by intra-operative stimulation and the appropriate fascicles are divided.
–– Specific indications, selection criteria and goals:
¾¾ In general, this procedure is indicated for optimisation of focal
spastic tone.
¾¾ However, the procedure can be performed on multiple nerves even
in people with diffuse spasticity of the lower limbs when rhizotomy
is contraindicated.
¾¾ For example, in children with diffuse spasticity of the upper limbs,
this procedure is preferred to cervicothoracic rhizotomy, because
a laminectomy to expose the cervicothoracic rootlets can cause
cervical spinal deformity.
¾¾ People with good control in the affected muscles are operated for
improvement and gain in motor functions. People having only fair or
poor control, may or may not improve in motor functions.
¾¾ However, they may get secondary benefits, like prevention of
contracture, relief of discomfort and pain, improvement in the ap-
pearance of the limb and less fatigability.
Results
•• Functional improvement occurs, depending on pre-operative voluntary
muscle control and motivation of the child.
•• The presence of orthopaedic complications and previous orthopaedic
surgery adversely affect the outcome. SMF (selective motor fasciculotomy)
improves the posture of the limb and the body.
•• Improvement in pre-operative voluntary motor functions is observed very
often following SMF.
•• SMF of the lower limb nerves gives rise to improvement in sitting, crawling,
standing and walking.
•• Similarly, SMF of the upper limb nerves gives rise to improvement in upper
limb functions related to activities of daily living and prehensile activities.
•• Usually, the maximum improvement is seen in the first six months.
•• The long-term follow-up shows that spasticity does not recur and the
improvement is maintained.
•• Functional improvement is seen more often in people having spasticity in
the lower limbs compared to the upper limbs.
•• The procedure is quite useful in children who have diffuse spasticity in the
upper limbs, wherein cervicothoracic rhizotomy cannot be done due to the
risk of developing swan neck deformity.
•• The procedure is quite cost effective because hardly any disposables are
used and just a nerve stimulator is enough, as a special instrument that is
also not an expensive tool.
•• Positive side effects: The procedure is found quite safe, simple and cost
effective. In the upper limbs, interestingly, improvement in prehensile and
shoulder movements is observed, following SMF of elbow flexors, pronators
1509
and wrist flexors. Improvement in a person’s cooperation, behaviour and

psychological functions also occur.
•• Negative side effects and complications: Paraesthesia, limb oedema,
deep vein thrombosis, hypotonia, injury to vascular structures, wound
gaping and infection are the possible rare complications.
3. Rhizotomy:
• Rhizotomy means ablation of a spinal root.
• Depending on whether the posterior (dorsal, sensory) or the anterior
(motor) root is ablated, the procedure is named accordingly.
• In selective rhizotomy, especially when the posterior root is selected
for ablation to relieve spasticity, it is split into its component rootlets
and each one is stimulated with bipolar current.
• The intensity of the response to the threshold current and the train
stimulus is recorded. The rootlet that shows hyperactive response is
considered for ablation.
• Depending on these responses, the clinical picture and the goals of
therapy the extent of ablation is performed.
• If the goals are to improve motor functions, usually under correction
is preferred, because one can always reduce the spasticity further by
either physical methods or extraspinal peripheral procedures like SMF,
but over correction cannot be undone.
• Usually for this purpose 25–40% of the rootlets are ablated.
• Ablation is performed by sectioning the rootlet through and through.
• Cauterisation of the stump(s) is not required.
• In an open method, laminectomy is performed to expose the spinal
roots.
Indications and Specific Selection Criteria and Goals
•• People having diffuse spasticity in the lower or upper limbs are considered
for lumbosacral or cervicothoracic rhizotomy, respectively.
•• In children, cervical laminectomy is preferably avoided because they are
likely to develop spinal deformity.
•• Classification: Rhizotomies can be classified into the following types:
•• Open surgical method:
–– Lumbosacral: This is done to relieve diffuse spasticity of the
lower limbs. A limited T12 and L1 (Fasano’s technique) or L2 to L5
(Peacock’s technique) laminectomy and bilateral L2 to S2 SPR are
performed.
–– Cervicothoracic: This is done to relieve diffuse spasticity involving
both the upper limbs. C5 to T1 laminectomy and bilateral C5 to T1 SPR
are performed. The procedure was also performed in non-traumatic
cases.
–– Sacral: This is indicated for spastic bladder. L5 laminectomy and
partial removal of the sacrum are performed. All the sacral roots are
stimulated and detrussor contractions are observed through cystom-
etry or through some indirect methods. The goals vary from voluntary
voiding to self-evacuation during socially acceptable timings.
•• Closed surgical method:
–– Percutaneous radio-frequency posterior rhizotomy: Thermoco-
agulation of the posterior roots perhaps blocks the conduction of ‘A’
delta and ‘C’ fibres and reduces pain and spasticity. A skin incision, 6
cm lateral to the midline and at the level just below the site of passage
1510
of the posterior roots, responsible for carrying impulses to generate

spasticity, is made. It can be considered in high-risk people with focal
spasticity. A high rate of recurrence has limited its use.
•• Non-surgical method:
–– Chemical rhizotomy: Intrathecal alcohol was first used to relieve
intractable pain. Five percent phenol in glycerine, added to a water-
soluble contrast medium, was also advised for this purpose. Chemical
rhizotomy is indicated only in people with spasticity who are suffering
from severe intractable painful spasms in the lower limbs, having no
useful lumbosacral neural functions like bladder and bowel control
and who have a short life expectancy, along with inability to withstand
major surgery.
Results
Spasticity and Spasms
•• Optimum reduction in hypertonicity can be achieved following SPR.
•• The reduction in spasticity occurs immediately; however, it is well appreci-
ated only after 3–4 days of surgery, i.e. after reduction in pain of surgical
trauma.
•• At this time, hypotonia may be present, due to electrical shock of the nerve
roots that were stimulated during the surgery.
•• SPR weakens the monosynaptic myotatic spinal reflex arc and produces
quite an effective reduction in hypertonia, whereas, it produces no signifi-
cant reduction in spasms, spastic patterns and mass reflexes, because
they are mediated through multisynaptic pathways.
•• Long-term follow-up reveals no recurrence in spasticity.
Motor Functions
•• Pre-surgical motor functions show considerable improvement within 3–9
months following SPR.
•• New motor functions may also develop in ideal cases.
•• The improvement is noticed in posture, balance, duration and ease of
doing the activities.
•• The awkward look also improves.
•• Long-term follow-up reveals that the improved clinical picture is maintained.
•• Rhizotomy is contraindicated in the presence of significant ataxia, dystonia
and athetosis.
•• It is relatively contraindicated in the presence of multiple severe contrac-
tures, severe mental retardation, poor control in the lower limb, trunk and
neck, and diseases of the spine, where laminectomy has to be performed.
Relief in helpful spasticity can cause deterioration in the person’s condition.
Side Effects
1. Useful (positive) side effects: There are many beneficial side effects,
which have been observed following SPR:
a. Improvement in upper limb function to the extent of picking of hair and
threading the needle, bowel habits, swallowing and squint
b. Clarity of speech
c. Smooth flow and easy initiation of urination
d. Decrease in seizures
e. Improvement in respiratory functions and decrease in chest complications
f) Improvement in social skills.
1511
2. Harmful (negative) side effects:

• In a few cases troublesome post-operative numbness and paraes-
thesia have been observed. Usually they subside within a few days.
Sometimes, mostly in adults, it may last for a few weeks to months and
may require medications like carbamazepine or amitryptyline.
• Hypotonia can occur if an excess number of rootlets are sectioned.
• Rarely, touch, pain or kinaesthetic sensory impairment can occur.
Microsurgical Drezotomy (MDT)—(Selective Posterior Rhizotomy in
DREZ)
•• Lesions in the dorsal root entry zone (DREZ) were first used for the relief
of pain.
•• At DREZ, the fine myelinated and unmyelinated nociceptive fibres and
large ‘A’ alpha myotatic fibres are rearranged more centrally and laterally.
During Drezotomy, these fibres are sectioned.
•• A lesion at 45 degree into the DREZ spares the lemniscal fibres, responsible
for carrying touch and kinaesthetic sensations.
•• Although drezotomy is being described here under the central procedures,
please note it is a technique in which peripheral neural fibres are sectioned
inside the cord.
•• Under general anaesthesia a hemi- or complete laminectomy, opposite the
selected segments of the spinal cord, is performed. The dura is opened and
the correct site of the selected segments is confirmed by electro-stimulation
of the roots/rootlets.
•• Under magnification, the selected posterior rootlets are retracted dorsome-
dially from the dorsolateral sulcus, so as to reach the ventrolateral region
of the DREZ.
•• A two mm deep incision is made at a 45 degree angle into the DREZ, with
the help of a sharp knife. The area is coagulated with low intensity short
duration bipolar cautery.
•• The procedure is indicated for adult people with spasticity, who have
severe painful intractable diffuse spasticity involving one or both lower or
upper limbs.
•• The results are significantly better in people having spasticity due to
pathology other than cerebral lesions.
•• A highly significant reduction in spasticity and even painful spasms has
been reported along with appreciable improvement in motor functions.
•• Side effects like CSF leak, impairment of sensations and related compli-
cations, respiratory deterioration, urinary problems and weakness of the
limbs have been observed.
Longitudinal Myelotomy
•• Longitudinal myelotomy relieves severe spasticity of the lower limbs.
•• The cord anterior to the attachment of the dentate ligaments on both the
sides is divided into anterior and posterior halves from L1 to S1 segments.
•• The results were good in people suffering from severe frequent spasms
and intractable spasticity in the lower limbs.
•• In this technique there was a potential risk of damage to the pyramidal
tracts.
•• The incidence of spasms and of haematomyelia was less with the
stereotactic procedure.
Section XVII: Miscellaneous
202
CHAPTER Anaesthesia for
Neurosurgery
Gupta D • Srivastava S
INTRODUCTION
•• The critical homeostasis of the pathological brain may be easily disturbed
by variations in cerebral blood flow (CBF), cerebral metabolic rate (CMR),
cerebral perfusion pressure (CPP), CO2 reactivity and auto-regulation due
to the effects of anaesthetic drugs and techniques.
CEREBRAL PHYSIOLOGY
•• The brain is a converter and consumer of energy. It converts substrates
supplied as metabolic fuel into usable forms of energy, which supports
and regulates synaptic connections, voltage dependant ion channels and
synthesis, transport and packaging of neurotransmitters.
•• The CNS receives about 15% of the resting cardiac output (750 mL/min)
and consumes about 20% (170 µmol/100 g of brain/min) of oxygen required
by the body at rest, whereas the weight of the brain is only 2–3% of the
total body weight.
•• The brain consumes one quarter (i.e. 31 µmol/100 g of brain/min) of the
total glucose consumed by the body.
•• Lack of substrate storage in the brain and a high metabolic rate makes the
brain relatively sensitive to the effects of ischaemia.
•• Brain metabolism can be split into two parts: the portion that drives the work
of the brain, that is synaptic transmission (activation metabolism) and, the
portion necessary for cellular integrity (basal metabolism), in approximately
60% and 40% of total energy consumption, respectively.
•• The larger portion of basal metabolism is devoted to the maintenance of
transmembrane ionic gradient (i.e. Na+–K+ pump).
CEREBRAL BLOOD FLOW AND ITS

REGULATION
•• Average cerebral blood flow (CBF) in an adult is approximately 50 mL/
100 g of brain/min.
•• Regional blood flow varies from 20 mL/100 g to 80 mL/100 g of brain/min.
•• There is approximately fourfold difference in CMRO2 and CBF between
cortical grey and white matter (80 mL/100g/min and 20 mL/100g/min,
respectively).
•• A rapid and precise regulatory system has evolved in the CNS, whereby
instantaneous increase in the metabolic demand can be rapidly met by a
local increase in CBF and substrate delivery.
Chapter 202 • Anaesthesia for Neurosurgery
1513
METABOLIC CONTROL
•• Under physiological conditions, fluctuations in cerebral glucose utilisation
and oxygen consumption are based upon regional electrical activity
differences, matched by changes in CBF. This is known as CMRO2-CBF
coupling.
•• CMRO2 is influenced by several factors in the neurosurgical environment,
including the functional state of the nervous system, anaesthetic drugs
and temperature.
•• When the cerebral function is depressed (as in a comatose patient or
during hypothermia), both CBF and substrate delivery are less than in the
fully conscious state.
•• In contrast, during a seizure, the demand for glucose and oxygen increases
dramatically and must be met by an increase in CBF. In the latter situation,
CBF and CMRO2 change in the same direction but increase in CBF is much
higher than the change in metabolic rate.
•• In many pathophysiological processes, the CBF-CMR coupling may be
deranged selectively in focal areas, such as the area around a tumour,
in subarachnoid haemorrhage (SAH) and in the region around the
epileptogenic focus.
•• Adenosine and nitric oxide are the proposed mediators of flow-metabolic
coupling. Adenosine increases cyclic AMP production that causes cerebral
vasodilatation, whereas nitric oxide (an intercellular messenger in the
peripheral circulation and in CNS) causes smooth muscle relaxation and
inhibition of platelet aggregation.
AUTO-REGULATION
•• In the normal brain, auto-regulation refers to the ability to maintain a
relatively constant CBF over a range of perfusion pressure (independent
of the CBF-CMR coupling).
•• Thus CBF is constant between an mean arterial pressure (MAP) of
50–150 mmHg (under auto-regulatory range).
•• Above and below this range, CBF is pressure dependant (pressure passive)
and varies linearly with CPP.
•• Auto-regulation maintains the internal milieu of the CNS.
•• It appears that change in the CPP involves a myogenic response of the
vascular smooth muscles (Bayliss effect). This myogenic response may
consist of two separate mechanisms: one responding to the MAP changes
and the other being sensitive to pulse pressure.
•• Pathological states of the brain, pharmacological agents and physiological
alterations may impair auto-regulation.
•• Chronic hypertension shifts the auto-regulatory curve to a higher range.
•• Intracranial tumour, head injury, brain lactic acidosis, hypercapnia and
cerebral vasodilators impair auto-regulation.
•• Auto-regulation will cause cerebral vasodilatation, leading to a rise in
brain volume. This, in turn, will lead to a further rise in ICP and induce the
vicious cycle described by the vasodilatation cascade, which results in
cerebral ischaemia.
•• Raising the CPP by elevating MAP can break this process, inducing the
vasoconstriction cascade. Thus, maintenance of arterial blood pressure at
adequate level by careful monitoring and rapid correction is of paramount
importance.
Section XVII • Miscellaneous
1514
CARBON DIOXIDE
•• Carbon dioxide is a powerful modulator of cerebral venous resistance.
•• At normotension, there is nearly a linear response of CBF at a PaCO2
between 20 mmHg and 80 mmHg (CBF changes about 2–4% for each
mmHg change in PaCO2).
•• Vasodilation by CO2 is probably mediated by nitric oxide and cGMP
pathways in adults and by prostaglandins and cAMP in neonates.
•• Hypocapnia reduces CBF and, hence, CBV and ICP, although the CO2
induced cerebral vasoconstriction wanes over a period of 6–10 hours.
•• Hypocapnia, however, may adversely affect cellular metabolism and shifts
the oxy-haemoglobin dissociation curve to the left.
•• While hypocapnia is maintained, there is a gradual increase in CBF towards
control values, which will lead to cerebral hyperaemia (over-perfusion) if
the PaCO2 is returned rapidly to normal levels.
•• When long-term ventilation is required, only mild hypocapnia (34–38 mmHg;
4.5–5.1 kPa) should be induced.
•• Response of CBF towards CO2 is attenuated below a PaCO2 of 25 mmHg.
•• CBF cannot be further reduced, as the ischaemic vasodilatation effect
counteracts the hypocapnia induced vasoconstrictor response. Therefore,
there is no advantage in inducing further hypocapnia.
OXYGEN
•• Low arterial oxygen tension also has profound effects on CBF. When the
former falls below 50 mmHg (6.7 kPa), there is a rapid increase in CBF
and cerebral blood volume.
NEUROGENIC CONTROL
•• Autonomic factors do not appear to control CBF, but they may modify other
regulatory responses.
•• Perivascular innervation of the cerebral resistance vessels and the specific
neurotransmitters contained within the perivascular nerve fibres, also
modulate vascular responses to changes in the blood pressure.
•• The innervation of the cerebral vasculature is extensive and involves
serotonergic, adrenergic and cholinergic systems of both intracranial and
extracranial systems.
•• Although acetylcholine is the most abundant perivascular neurotransmitter,
other mediators in this neural response include norepinephrine,
neuropeptide Y, cholecystokinin, vasoactive intestinal peptide and calcitonin
gene related peptide.
•• Sympathetic stimulation can shift the auto-regulatory curve to the right,
thus protecting the brain against severe elevations of MAP.
•• Stimulation of parasympathetic fibres promotes a vasodilatory reaction
to ischaemia.
•• The protective response against ischaemia however, is overshadowed by
hyperaemia mediated by the same fibres.
CEREBRAL PERFUSION PRESSURE

•• The brain and its blood vessels are encased in the rigid cranium and
subjected to surrounding pressure, i.e. ICP.
1515
•• Therefore, net cerebral perfusion pressure (CPP) is defined as the

difference between MAP and ICP. CPP = MAP - ICP.
•• CPP represents the blood pressure gradient across the brain’s vascular
bed and thus determines blood flow through the brain. MAP determines
the “head of pressure” perfusing the brain.
•• Normal CPP is 80 mmHg, but when reduced to less than 50 mmHg, there is
metabolic evidence of ischaemia and reduced electrical activity. Inadequate
CPP (less than 70 mmHg) has been shown to be a major factor in poor
outcome of patients with raised ICP.
•• Assessment of CPP is vital and possible, either by measurement of both ICP
and MAP or by measuring MAP and making a reasonable estimate of ICP.
•• During anaesthesia, therefore, if ICP is raised, a fall in blood pressure must
be avoided or treated quickly by volume replacement or catecholamines
(whichever is relevant).
Rosner Concept or Edinburgh Concept

•• During head injury, when CPP is maintained within the range of 75–95 mm
of Hg, auto-regulatory vasoconstriction is induced, which decreases ICP,
provided cerebrovascular auto-regulation is intact.
•• Patients with a shift of the auto-regulatory curve towards the right
(i.e. those in whom a higher mean arterial pressure is required to maintain
the perfusion to the brain) are the ones most benefited by this concept
(as elevation in CPP returns the pressure flow relationship into the auto-
regulatory range).
Lund Concept
•• A group of head injured patients with defective BBB and cerebrovascular
auto-regulation is benefited from a reduction in precapillary hydrostatic
pressure, as well as cerebral venous constriction. This reduces CBV and
thus decreases brain oedema.
•• This concept aims at stabilisation of CPP within the range of 65–70 mm of
Hg by means of proper sedation, administration of osmotic diuretics and
vasopressors, and maintenance of normovolaemia.
•• Continuous monitoring of jugular venous bulb oxygen saturation (SjVO2)
monitors the adequacy of cerebral perfusion.
•• As CBF and the delivery of oxygen is reduced below a critical value, the
brain, in order to maintain its oxygen supply, extracts more oxygen from
the blood. This leads to a fall in venous oxygen saturation.
•• The principle constituents within the skull are brain (80%), blood (12%)
and CSF (8%).
•• Normal intracranial pressure is less than 15 mm of Hg and is considered
as being abnormally high when a sustained elevation greater than 20 mm
of Hg occurs.
•• Abrupt and marked increase in the ICP leads to systemic hypertension and
baroreceptor mediated bradycardia (called Cushing reflex).
•• Although this reflex is designed to increase perfusion, it eventually
aggravates intracranial hypertension.
1516
PHARMACOLOGY OF ANAESTHETIC DRUGS

Inhalational Agents
•• Volatile anaesthetic agents like halothane, enflurane, isoflurane, sevoflurane
and desflurane cause cerebral vasodilatation with an increase in CBF.
•• They also produce some uncoupling of the normal relationship between
metabolism and blood flow.
•• When CMRO2 decreases, local blood flow falls, as there is a reduced
requirement for oxygen delivery and carbon dioxide removal. The latter is
the indirect effect of these agents.
•• Volatile agents uncouple or disconnect this relationship in a dose dependent
way.
•• The overall effect on cerebrovascular tone therefore, is the sum of both the
direct vasodilatory effect and any indirect residual vasoconstrictor effect.
Hence, at low doses, CBF is not elevated but, at higher doses, there is an
increase of CBF. An important consequence of this is that any dilatation in
turn raises cerebral arterial volume and increases brain volume.
•• The normal auto-regulatory mechanism is gradually abolished, as the
concentration of the volatile agent is increased and CBF becomes blood
pressure dependent. Thus, as MAP rises, CBF increases and cerebral
vasodilation occurs.
•• In contrast, when blood pressure falls, there is no mechanism to sustain
flow by a reduction in the cerebrovascular resistance.
•• The volatile agents also affect the CO2CBF relationship, causing the curve
to be shifted to the left.
•• Hypocapnia is still able to reduce CBF and, therefore, to oppose the
vasodilation. However, if CO2 is allowed to rise, there is a much more rapid
increase in CBF.
Halothane
•• It is a moderately insoluble agent (blood gas solubility being 2.5 and the
MAC, i.e. the minimal alveolar concentration at which reflex to skin incision
abolishes, of 0.75%).
•• Halothane is a potent cerebral vasodilator and in the presence of cerebral
swelling, it produces a large rise in ICP. Fortunately, hyperventilating the
patient for 10 minutes before the introduction of halothane can prevent
this rise in ICP.
•• It is reasonably safe to use halothane in a hyperventilated patient up to a
concentration of 0.5% in conjunction with nitrous oxide.
•• It should be avoided, if possible, by using alternative techniques; before
the duramater is opened in patients who have a raised ICP.
•• Halothane sensitises the myocardium to catecholamines making the patient
more prone to developing arrhythmia, especially when adrenaline is used
for local infiltration.
Enflurane
•• It has similar effects as halothane, but appears to be a less potent cerebral
vasodilator and a more potent depressant of CMR, but it does cause
cerebral seizure activity, particularly when the patient is hypocapnic.
•• Epileptic activity is harmful as it induces a massive increase in CMR, which
in turn increases CBF and hence cerebral swelling.
•• Enflurane increases ICP by increasing the rate of production of CSF and
also decreasing its reabsorption.
1517
Isoflurane (Blood Gas Solubility 1.4 and MAC 1.2%)

•• It is the least potent cerebral vasodilator and the most potent metabolic
suppressant.
•• It causes both respiratory and cardiovascular depression, the latter
occurring predominantly due to a fall in systemic vascular resistance.
•• CBF and CBV are not affected by concentrations of 0.6–1.1 MAC isoflurane,
but a 1.6 MAC doubles CBF.
•• In higher concentrations, it also causes an increase in ICP. There is less im-
pairment of auto-regulation and CO2 reactivity when compared to halothane.
•• There is evidence of uncoupling between the direct vasodilator effect and
indirect vasoconstriction effect of isoflurane on the cerebral vasculature.
•• Therefore, up to 1.6 MAC, the vasoconstriction effect predominantly
prevents CBF from rising.
Sevoflurane (MAC 1.7–2% and a Low
Blood Gas Solubility 0.6)
•• It has similar properties to isoflurane on the brain, CBF, CBV and ICP.
•• Response to PaCO2 and auto-regulation appear intact up to 1 MAC.
•• Low blood gas solubility may have an advantage for rapid awakening even
after many hours of surgery.
•• Sevoflurane is also metabolised (5%), increasing blood fluoride
concentration.
•• So far no renal complications have been reported.
•• When sevoflurane is used with soda-lime (used for absorption of expired
CO2 in the anaesthesia machine) in a circle system, a toxic compound is
produced.
•• Sevoflurane is the volatile agent of choice for induction of anaesthesia,
because of its faster onset of action and non-irritant nature.
Desflurane (MAC 5–10% and
Blood Gas Solubility, 0.4%)
•• It is also similar to isoflurane in many respects.
•• Like sevoflurane, its main advantage is in providing rapid recovery from
anaesthesia.
•• It is expensive like sevoflurane and is only economically viable if used in a
sophisticated low-flow system.
•• However, in contrast to sevoflurane, it is more irritant to the tracheobronchial
tree and requires a special vapouriser, but it is not metabolised or affected
by soda-lime.
Nitrous Oxide
•• It was believed to have minimal effect on CBF.
•• Nitrous oxide alters cerebral auto-regulation, the effect depending on the
other anaesthetic agents it is used with.
•• Its stand alone action impairs auto-regulation but not when added to
sevoflurane 1.5 MAC.
•• Cerebral auto-regulation improves when nitrous oxide is added during
propofol anaesthesia.
•• Carbon dioxide reactivity is preserved when nitrous oxide is used in
combination with volatile anaesthetic agents and also with propofol, which
allows manipulation of CBF during anaesthesia. This property permits the
safe use of nitrous oxide in clinical practice, as the increase in blood flow
resulting from its use may be nullified by hypocapnia.
1518
•• Despite the fact that N2O increases ICP in patients with intracranial tumours,
it may be safely used in most neurosurgical patients, as it causes minimal
cerebral swelling.
•• N2O allows a reduction in the concentration of potent inhalational agents,
although the effect of an equipotent combination of N2O and isoflurane on
ICP and CBF may actually be worse than that of isoflurane alone.
Hypnotics
•• Hypnotics are agents that induce sleep. They are used for induction as well
as for maintenance of anaesthesia.
•• In general, intravenous anaesthetics decrease CBF and CMR.
•• These agents are not cerebral vasoconstrictors. The decrease in CBF is
due to decrease in CMR consequent to cerebral functional depression.
Barbiturates
•• They reduce CBF by direct cerebral vasoconstriction and by a reduction
in metabolism.
•• They cause dose dependent reduction in CMR which ultimately leads to
a reduction in CBV.
•• Burst suppression dose of thiopentone decreases both CBF and CMRO2
to about 40% (near maximum reduction) of the awake value in humans.
•• There is a fall in ICP, possibly because of this change in CBF and CBV.
•• Thiopentone has multiple uses.
•• It is used for anaesthesia, to treat raised ICP in head injured patients, as
an anticonvulsant and for neuroprotection in areas of focal ischaemia.
•• Large doses of barbiturates must be used with caution in patients with raised
ICP as they also cause a marked fall in blood pressure, which will lead to
a fall in CPP and may delay recovery from anaesthesia.
•• Barbiturates may also decrease production of CSF and resistance to CSF flow.
Etomidate
•• It resembles thiopentone in its effects on CBF and CMR.
•• It has less cardiovascular side effects than thiopentone.
•• The maximum reduction of CBF is more rapid than the maximum reduction
of CMR, suggesting that it has an intrinsic vasoconstrictive property.
•• Its adverse effects include adrenocortical suppression and involuntary
muscle activity.
•• Etomidate in low concentration appears to activate seizure foci in epileptic
patients and should be used cautiously in these patients.
Propofol
•• It is an alkylphenol, which has hypnotic properties and has a potency 1.8
times that of thiopentone.
•• It has been prepared in intralipid and causes both respiratory and cardio-
vascular depression.
•• Propofol reduces CBF, CBV, ICP and CMR in a dose related manner.
•• The drug is rapidly metabolised in the liver and a little amount is cleared
by the kidneys.
•• Anaesthesia, when maintained by propofol infusion is followed by rapid
recovery when the drug is not used for more than 3–4 hours.
•• Prolonged use of propofol may cause systemic acidosis, progressive
cardiac failure and even death in children. It should therefore be used
cautiously in children.
1519
•• Propofol is a very useful agent for maintenance of anaesthesia in

neurosurgical patients, particularly when nitrous oxide is to be avoided.
•• Propofol infusions are expensive and require sophisticated infusion pumps.
•• More recently, the concept of target controlled infusions (TCI) has been
introduced, where a specially designed syringe pump using a pre-
programmed algorithm injects the drug at a rate necessary to achieve the
blood level set by the clinician.
Ketamine
•• It is a derivative of phencyclidine that induces dissociative anaesthesia.
•• It stimulates the cardiovascular system with minimal respiratory depression.
•• It increases CMRO2, CBF and ICP in patients with intracranial decom-
pensation.
•• It is a non-competitive antagonist at NMDA receptors and may therefore
offer protection from the adverse effects of cerebral ischaemia.
•• Ketamine should be avoided in neurosurgical patients especially in those
with raised ICP and decreased intracranial compliance.
Narcotics
•• Narcotics are used for their analgesic actions.
•• Their effect over CBF, CMR and ICP are variable and depend on the
background anaesthetics.
•• In spontaneously breathing patients, narcotics will depress respiration,
indirectly increasing CBF and ICP by raising PaCO2; however, if ventilation
is supported, then the direct effect of narcotics on CBF is minimal.
•• With controlled ventilation and in the presence of cerebral vasodilators (like
halothane), opioids produce a decrease in CBF and CMR.
•• When given along with cerebral vasoconstrictors or when given alone,
opioids have either no effect or they increase CBF and CMR.
•• An ideal narcotic has a predictable, short lasting effect.
•• Most of the newer opioids cause skeletal muscle rigidity when given in
large doses.
•• Seizures have been reported in some circumstances with opioid agents.
Fentanyl
•• It has a peak effect that starts 4 minutes after injection and lasts for more
than 15 minutes.
•• Suppression of the cardiovascular response to painful stimuli can be
achieved using 1.5–2.5 µg/kg.
•• There is usually no change in CBF or ICP, but if a large bolus is given, a
small decrease in arterial pressure can lead to a similar change in CPP.
•• Fentanyl may accumulate in the body when used for prolonged periods
and the duration of action may be up to 60 minutes or more.
•• Chest rigidity may result with induction doses of fentanyl.
•• When used in combination with droperidol, it induces neuroleptanaesthesia
(Neuroleptanaesthesia is characterised by trance like immobility in an
outwardly tranquil patient who is dissociated to the surroundings).
Pethidine
•• It is a synthetic opioid with properties similar to other narcotics, with
additional atropine like effects.
•• It can cause marked hypotension (when given rapidly), an important
consideration in a patient with high ICP.
1520
•• The duration of action is intermediate, i.e. 2 hours with a plasma half-life

of 3–4 hours.
•• Therefore, pethidine is not an ideal agent and is not in common use in
neuroanaesthesia. The usual intravenous dose is 0.5 mg/kg.
Alfentanil
•• It is a more recently introduced opioid, which is less potent than fentanyl,
but has a very rapid onset and shorter duration. The latter is due to its
rapid excretion.
•• Alfentanil is not widely distributed in the body. As the amount of drug
required to produce an adequate effective concentration is less, it is rapidly
excreted.
•• The effect on CBF and CMR are comparable with fentanyl, but when given
rapidly it decreases MAP, especially in elderly patients or in patients with
compromised circulation.
•• This is especially important when ICP is also increased since the decrease
of MAP decreases the CPP.
Sufentanil
•• It causes 29% reduction in CBF and 22% reduction in CMR.
•• Sufentanil causes an increase in ICP, when rapidly administered.
Remifentanil
•• It is an ultra-short acting opioid.
•• It produces rapid analgesia, and has potency similar to fentanyl.
•• It has typical opioid effects of respiratory depression, bradycardia and
skeletal muscle hypertonus.
•• It is rapidly broken down by circulating and tissue non-specific esterases.
•• Thus, the half-life is 10–20 minutes with a plasma clearance of 3–4 L/min.
•• The recovery is rapid, and is unaffected by the dose or the length of time
the drug has been given.
•• A bolus administered over 1 minutes does not cause a significant rise in
ICP (2–3 mmHg), but may decrease MAP, which may lead to fall in CPP.
•• One of the problems with remifentanil is that residual analgesia does not
occur. Therefore, post-operative pain relief needs careful consideration.
•• The use of infusion techniques of newer narcotics (Remifentanil, etc.) with
propofol, are becoming increasingly popular.
•• With the help of ultra-short acting drugs, anaesthesia is better controlled
as the rate of infusion peaks at maximum stimulation and wears off when
no longer required.
Neuromuscular Blocking Drugs

Suxamethonium
•• It is the only depolarising muscle relaxant useful in clinical practice.
•• It has a rapid onset of action and is the relaxant of choice for rapid
intubation.
•• It has been reported to raise ICP.
•• Therefore, it is avoided in neuroanaesthesia, until absolutely indicated (full
stomach, emergency case, safe and rapid control of airway).
Pancuronium
•• It does not affect CMRO2, CBF or ICP during induction of anaesthesia.
1521
•• It may cause arterial hypertension and tachycardia, which may make

intracranial conditions difficult during surgery (but may be advantageous
for circulatory support in hypotensive patients).
Vecuronium
•• It is an intermediate acting non-depolarising neuromuscular blocking drug.
•• Its principal advantage is that it has negligible effects on the cardiovascular
system and does not induce histamine release.
•• A preliminary report in neurosurgical patients has confirmed that there was
no observed effect on ICP or CPP.
•• Following an induction dose of 0.15 mg/kg, the time of onset for neuro-
muscular blockade is approximately 140 seconds, which is adequate for
elective procedures.
•• Thus, vecuronium appears to have useful properties for inducing
neuromuscular blockade prior to intubation in elective cases.
Atracurium
•• It is an intermediate acting neuromuscular blocking drug, which has the
unique property of spontaneous degradation (Hoffmann degradation) in
the blood and so is preferred in patients with renal or hepatic dysfunction.
•• Its rapid administration causes histamine release. Laudanosine, its
metabolite, is potentially epileptogenic.
Mivacurium
•• It has a brief duration of action (10–15 minutes).
•• Infusion provides stable relaxation without the risk of accumulation.
•• It appears suitable for use in neuroanaesthesia.
•• It causes histamine related hypotension on rapid injection.
Rocuronium
•• It is a steroid and serves as a relaxant with a rapid onset time, but of low
potency.
Choice of Anaesthetic
•• The basic principles of neuroanaesthesia management include:
–– Clear airway
–– Full oxygenation without hypercarbia
–– Smooth induction with no coughing or bucking
–– Careful monitoring of the patient
–– Steady well controlled maintenance of anaesthesia and
–– Well controlled emergence and recovery.
•• Based on the effects of volatile agents on the normal brain either isoflurane,
sevoflurane or desflurane appear to be a better choice than halothane for
patients with intracranial pathology.
•• None of these drugs have adverse effects when mild hypocapnoea is present.
•• Sevoflurane and desflurane have an added advantage for intracranial
neurosurgery, because of faster awakening.
•• Ketamine is probably not appropriate as a sole drug for intracranial
neurosurgery.
•• The issue of the significance of the transient rise in ICP with succinylcholine
remains unaddressed.
•• Studies in acute head-injured patients suggest that the advantages of rapid
intubation, offered by succinylcholine, may offset its potential disadvantage
of ICP rise.
1522
•• Barbiturates lowers CMRO2, thus offering protection during focal ischaemia.

•• Hypothermia also protects against ischaemia.
•• There is a growing thought that the reduction in metabolic rate, produced
by barbiturates, may not be as protective as once thought.
GENERAL ANAESTHESIA: AN OVERVIEW

•• The American Society of Anaesthesiologist’s (ASA) classification of physical
status stratifies the patient’s pre-existing health (Table 1).
History and Physical Examination

•• Assessment should evaluate the history of previous surgery (problems with
airway management, post-operative nausea and vomiting, coagulopathy),
recent medical treatment, present medication, the presence of allergies
and the family history.
•• The degree of difficulty during intubation may be predicted by the Mallampati
scoring system (Table 2), thyromental distances and the restriction of neck
movement.
•• Patients on anti-platelet agents, such as aspirin and clopidogrel, should
have their medications stopped for a week before intracranial surgery,
whereas oral anticoagulant should be switched over to heparin. Clotting
factors and platelets should be made available at the time of surgery.
•• Patients with pan-hypopituitarism may require replacement hormone
therapy. Cushing’s disease may be associated with hypertension, fluid
retention and diabetes mellitus. Acromegaly may present with airway
problems that may need special attention at the time of intubation.
Premedication
•• Neurosurgical patients with intradural pathology may require steroids prior
to surgery.
•• H2-receptor blockers should continue on the morning of surgery to prevent
stress and drug-induced gastritis. All antihypertensive and cardiac medica-
tions (except ACE inhibitors) should be continued on the day of surgery.
•• A mild sedation in the form of benzodiazepines/opioids may be given to
conscious patients who do not have significantly raised ICP.
Table 1: ASA Classification of physical status

No organic, physiologic, biochemical or psychiatric disturbance
Mild to moderate systemic disturbance
Severe systemic disturbance
Severe systemic disturbance that is a constant threat to life
Moribund patient, likely to die with or without surgery
Brain dead organ donor
Table 2: Sampson and Young’s modification of Mallampati grade

Grade I: Soft palate, uvula, tonsillar pillar and fauces seen
Grade II: Soft palate, uvula and fauces seen
Grade III: Soft palate and base of uvula seen
Grade IV: Only hard palate seen
1523
•• None of these sedatives should be given to patients with impaired

consciousness or with raised ICP, because these drugs may cause
hypercapnia, hypoxia and airway obstruction.
•• On the other hand, non-premedicated, anxious patients may have systemic
hypertension, leading to increase in CBF. Therefore, it is advisable that
such patients be given intravenous sedative premedication.
General Anaesthesia for Neurosurgical Procedures

•• Comprehensive monitoring during anaesthesia is needed for adequate
assessment of a neurosurgical patient.
•• It includes haemodynamic monitoring in the form of electrocardiogram (to
see the heart rate and detect arrhythmias), arterial blood pressure (invasive
or non-invasive) and central venous pressure monitoring.
•• The CVP catheter placement is considered to be useful when there is a
risk of venous air embolism (VAE), coexisting cardiovascular disease,
anticipation of substantial blood loss or with the use of ionotropic drugs.
•• Pulse oximetry measures oxygen saturation and end tidal CO2 monitoring
(capnography) measures CO2 concentration in the expired air. The latter
may be useful in detecting air embolism, as well as in assessing partial
pressure of CO2 in arterial blood and its effect on CBF.
•• A precordial Doppler ultrasound, pulmonary artery catheter and
transoesophageal echocardiography (TEE) are useful in cases with
coexisting cardiac disease, as well as in cases with the risk of air embolism
and operation in the sitting position.
•• BIS monitoring (Bispectral assay) may also be used to measure the
level of hypnosis or sedation. Varieties of EEG signals are analysed and
interpretation is done in the form of numerical values, called the BIS index.
•• The primary goals during induction are: (a) control of PaCO2; (b) control
of blood pressure (adequate depth of anaesthesia); (c) prevention of
outflow obstruction of jugular venous blood; (d) adequate oxygenation and
hyperventilation and (e) prevention of awareness.
•• The typical scheme for smooth induction include intravenous administration
of thiopentone (4–7 mg/kg), propofol (2–2.5 mg/kg) or etomidate (0.3 mg/
kg) to produce hypnosis and, an opioid (fentanyl 1–2 µg/kg, sufentanil or
ramifentanil), to produce analgesia to maintain strict haemodynamic control
during intubation.
•• For muscle relaxation, vecuronium bromide or atracurium bysilate is pre-
ferred because of minimal cerebral haemodynamic alterations. The use of
succinylcholine should be reserved for patients in whom intubation difficulties
are anticipated or when rapid sequence induction is absolutely unavoidable.
•• Direct laryngoscopy and intubation cause an increase in heart rate, arterial
pressure and in many cases, arrhythmias.
•• The response may be minimised by deepening of anaesthesia by an
additional dose of propofol or thiopentone, fentanyl 2 µg/kg, lignocaine
1–1.5 mg/kg, β-blocker esmolol 150 mg or vasodilators, like sodium
nitroprusside or nitroglycerine.
•• Application of head pins during patient positioning is a painful stimulus.
This can be abolished by deepening the anaesthesia (e.g. thiopentone 1
mg/kg or propofol 0.5 mg/kg) or by administering an analgesic (bolus of
fentanyl 1–3 mg/kg, alfentanyl 10–20 µg/kg or remifentanil 0.25–1 µg/kg)
in conjunction with local anaesthetic infiltration of the pin site, to prevent
undesirable CNS arousal and haemodynamic activation.
1524
Tight Brain during Surgery

•• Adequate brain relaxation facilitates neurosurgery and reduces the need for
excessive brain retraction. A swollen brain is prone to develop ischaemic
injury. In addition, brain swelling interferes with surgery and, on occasion,
may prevent the closure of the dura-mater.
•• The following manoeuvres may be instituted to treat this urgent problem:
–– Check ventilation. Moderate hypocapnia (target PaCO2 25–30 mmHg)
will produce cerebral vasoconstriction and consequently reduce brain
swelling.
–– Ensure normal oxygenation.
–– Control blood pressure. The target is normotension (within 10% of
baseline blood pressure).
–– Ensure adequate venous drainage from the brain. Neck torsion or
the placement of endotracheal tube ties around the neck can impede
venous drainage from the brain.
–– Head elevation (30° optimum).
–– Check intrathoracic pressure. Rule out pneumothorax (especially if a
central line has been placed).
–– Maintain adequate neuromuscular relaxation.
–– Administer intravenous mannitol.
–– Make sure that the concentration of the volatile anaesthetic agent is
less than 0.5 MAC.
–– Discontinue the administration of N2O.
–– Switch to an intravenous anaesthetic technique. A combination of
propofol and opioid infusion is ideal.
–– If the brain swelling does not abate, then the probability of intracranial
hypertension in the post-operative period is high. Barbiturates (pento-
barbital) may be administered until either the swelling is reduced or
burst suppression of the EEG is attained.
–– On rare occasions, the surgeon may elect to amputate non-eloquent
brain or to close the scalp without closing the dura or replacing the
bone flap.
•• The goal of fluid therapy during neurosurgical procedures is to maintain
normotension and normovolaemia.
•• Neurosurgical patients often receive diuretics (e.g. mannitol and/or furosem-
ide) to reduce intracranial hypertension or brain oedema pre-operatively.
•• Large amounts of intravenous fluid are required to correct pre-operative
dehydration and to maintain intra-operative and post-operative haemo-
dynamics.
•• Hyperglycaemia may increase neurological damage during cerebral
ischaemia and may worsen outcome from both focal and global ischaemia.
•• Crystalloid solutions do not contain any high molecular weight compound
and have an oncotic pressure of zero. Non-glucose containing iso-osmolar
0.9% normal saline is the solution of choice for intracranial surgeries.
•• Colloids have an oncotic pressure similar to that of plasma and both contain
large molecules that are relatively impermeable to the capillary membranes.
•• Dextran and hetastarch (hydroxyethylstarch) are dissolved in normal
saline, so the osmolarity of the solution is approximately 290−310 mOsm/L.
It, therefore, is suitable for use as a plasma expander.
1525
Emergence from Anaesthesia

•• The emergence of the neurosurgical patient from anaesthesia may be
affected by depression of the central respiratory drive, decrease in the tone
of airway muscles, rise in ICP by hypoxia or hypercarbia and sympathetic
stimulation, leading to systemic hypertension and further increase in ICP.
•• The emergence should be aimed at having minimal effects on the MAP,
CBF, ICP, PaCO2 and temperature.
•• Neostigmine (an anticholinesterase drug) is given to reverse neuromuscular
block and anticholinergic drugs (like atropine or glycopyrrolate) are added
to counteract its cardiac side effects.
•• The extubation is facilitated by a small top-up dose of intravenous
anaesthetics or analgesics and a short burst of volatile agents, to prevent
coughing or bucking on the endotracheal tube, during its removal.
•• If the patient is not responding even after 20–30 minutes of cessation of
all the anaesthetic agents and opioids (delayed emergence), a CT scan or
MRI scan may be done to rule out intracranial bleeding, cerebral oedema,
pneumocephalus or cerebral infarction.
ANAESTHETIC CONSIDERATIONS FOR DIFFERENT

TYPES OF NEUROSURGICAL SITUATIONS
Intracranial Tumours where ICP is a Concern
•• Traditionally, anaesthetic agents that increase CMR or CBF result in
increased CBV and ICP. However, the relationship between these agents
and ICP is complex and adjuvant techniques (e.g. hyperventilation) and
medications (mannitol) often mitigate the possible adverse effects.
•• Among the volatile agents, isoflurane, sevoflurane or desflurane would be
considered as a better choice than halothane for patients with intracranial
pathology.
•• However, none of the drugs appear to have adverse effects when hy-
pocapnia is present.
•• Sevoflurane and desflurane appear to have advantages for intracranial
neurosurgery, because of the possibility of faster awakening.
•• Nitrous oxide is also a poor choice when closed air-filled cavities are present
(e.g. pneumothorax, air embolism and pneumocephalus) because nitrous
oxide diffuses into these cavities, thereby increasing the mass effect.
•• The role of ketamine also remains controversial because of its property of
increasing CBF and ICP.
•• The disadvantage of the transient rise in ICP brought about by succinylcholine
administration in acute head-injured patients and other emergency situations
is counterbalanced by its rapid action that facilitates emergency intubation.
Posterior Fossa Surgery

•• The common positions for posterior fossa surgery are prone, park bench
or sitting.
•• Additional monitoring would include end tidal CO2, precordial Doppler and
trans-oesophageal echocardiography (TEE), especially when the patient
is at risk of venous air embolism (VAE), during posterior fossa surgery.
•• Mid right atrial placement of central venous catheter is required for
aspiration of air in case VAE occurs during surgery.
1526
•• Neurophysiological monitoring of brain stem auditory evoked response may

be done for the assessment of VIII nerve function, during cerebellopontine
angle surgery; somatosensory evoked potential monitoring for the
assessment of brainstem function and, electromyography for the function
of trigeminal, facial and lower cranial nerves.
•• The neurophysiological monitoring requires adjustment of the anaesthetic
technique.
•• The depth of anaesthesia should be adjusted to an optimal level, to obtain
adequate recordings. In case an EMG is being performed, then the effect
of the muscle relaxant should be minimal.
•• While placing the patient in the sitting position, hypotension may occur,
unless the patient has been adequately hydrated prior to anaesthesia. The
pontomedullary area of the brain stem has the cardiorespiratory control
centre. The patient may develop dysrhythmia or haemodynamic changes
during dissection of the tumour in this region.
•• At the end of the surgery, the endotracheal tube should not be removed until
the patient shows signs of reversal and evidence of airway reflex activity.
•• Post-operative intubation and ventilation may be required in case the
surgical time has been prolonged, there have been profound intra-operative
haemodynamic perturbations, the patient was in altered sensorium prior to
being anaesthetised, and/or handling of the region around the respiratory
centre and lower cranial nerves (IX, X, XI and XII) has been done.
Aneurysmal Subarachnoid Haemorrhage

•• ICP may be higher (approximately > 30 mm Hg) in poor grade (modified
Hunt and Hess grade III-IV) patients after aneurysmal SAH; on the other
hand, it may be normal in grade 0–II.
•• Following SAH, there is a reduction in CBF to 30−40% of the normal values.
Global reduction in CBF is proportional to the severity of the clinical grade.
Auto-regulation is also impaired in proportion to the clinical grade. CO2
reactivity of the vessels is preserved, unless there is severe physiological
compromise. Electrolyte imbalances are a frequent occurrence. Treatment
should be aimed at correcting the electrolyte abnormality, while maintaining
a normal intravascular volume.
•• The anaesthetic goals of the management, during clipping of the aneurysm,
are maintaining adequate CPP, preventing rebleeding and cerebral
ischaemia, providing cerebral protection, and maintaining good brain
relaxation. The MAP should be meticulously maintained in the higher range,
especially in patients in poor Hunt and Hess grade.
•• Suzuki advocated a combination of mannitol (500 mL of a 20% solution or
100 g), vitamin E (500 mg) and dexamethasone (50 mg), popularly called
Sendai cocktail for prevention of the effects of ischaemia during temporary
arterial occlusion.
•• In addition, pharmacological metabolic suppression with thiopentone
5–6 mg/kg or etomidate 0.4–0.5 mg/kg administered before temporary
occlusion, decreases CMR of the tissue distal to occlusion and increases
the tolerance to ischaemia.
•• The complications of aneurysm surgery include premature aneurysmal
rupture (as high as 17.5%), delayed recovery, seizure, pneumocephalus,
hypernatraemia, hyponatraemia, delayed neurological deficit and infection.
1527
Spinal Surgery
•• Cervical spinal pathology may be associated with restricted neck
movements and may require awake fibreoptic intubation.
•• During spinal surgery, emphasis must be placed on preventing instability
and minimising blood loss and, occasionally, venous air embolism.
•• In the prone position, proper care should be taken to facilitate ventilation
and avoid venous engorgement, by avoiding excessive intra-abdominal
pressure.
•• The trans-thoracic approach may require separation of two lungs by the
placement of a double lumen tube and one lung ventilation. There is a need
for replacing the double lumen tube with a single lumen endotracheal tube
at the end of surgery.
Paediatric Neuroanaesthesia
•• In children, the physiological and pharmacological responses of the CNS
during anaesthesia are different from that in adult patients.
•• Newborn children have a CBF of 40–42 mL/100 g of brain/min, which
increases to 90 mL/100 g of brain/min at 6–40 months, 100 mL/100 g of
brain/min at 3–12 years of age and 50 mL/100 g of brain/min thereafter.
•• The metabolic rate for oxygen consumption in children is 5 mL/100 g of brain
per minute as compared to 3–3.5 mL/100 g of brain per minute in adults.
•• CBF is coupled to the metabolic demand and both increase immediately
after birth.
•• Auto-regulation in children occurs at a lower absolute value of MAP when
compared with adults.
•• The response of CBF to arterial CO2 tension is similar to that in adults.
•• Open fontanelles and cranial sutures make the intracranial space more
compliant. This will lead to the masking of increase in the ICP (by a tumour
or haemorrhage). Therefore, due to this masking of the clinical signs and
symptoms of raised ICP in children, tumours may not be detected until they
are in a fairly advanced stage.
•• Infants less than 6 months do not show separation anxiety from parents
and may not require any premedication. Children between 6 months to
6 years do not tolerate separation and are difficult to handle. The latter
group of children may be premedicated with oral midazolam 0.5–0.75 mg/
kg, oral fentanyl citrate 20 µg/kg and oral promethazine 0.5 mg/kg.
•• General anaesthesia may be established by inhalation of a mixture of
sevoflurane, nitrous oxide and oxygen. Alternatively, if the patient has an
intravenous access, anaesthesia may be rapidly induced with sedative/
hypnotic drugs, such as thiopental (5–8 mg/kg).
•• Patients with a full stomach and difficult airway should have a rapid-
sequence induction of anaesthesia with thiopental or propofol, following
which muscle relaxants like succinylcholine or rocuronium should be added.
•• Normovolaemia should be maintained throughout the procedure as fluid
restriction, blood loss during surgery and diuretic therapy for brain relaxation
may lead to haemodynamic instability.
•• Normal saline is commonly used as the maintenance fluid during
neurosurgery, because it is mildly hyperosmolar (308 mOsml/kg).
1528
Post-operative and Intensive Care

Mechanical Ventilation
•• The aim of mechanical ventilation should be decided and may include either
support for airway protection, ventilation (CO2 elimination) or oxygenation.
•• Ventilation may be inadequate due to coexisting primary lung diseases,
depression of ventilatory drive or residual effect of anaesthetic drugs.
•• Ventilatory assistance may be provided with the following modes:
A. Controlled mode of ventilation (CMV, to be used in patients with no
spontaneous breaths)
B. Assisted/controlled mode of ventilation (AMV, in patients who initiate
spontaneous breaths but cannot maintain adequate minute ventilation
without support)
C. Synchronised intermittent mandatory ventilation (SIMV, when ventila-
tor breaths are delivered synchronised with the patient’s breaths)
D. Pressure support ventilation (PSV, that augments spontaneous
breaths by pressurising the ventilator circuit to a preset value until the
inspiration is terminated) and
E. Pressure controlled ventilation (PCV, that delivers a pressure-limited,
time cycled breath which helps in limiting lung injury).
•• Oxygenation can be improved by applying PEEP (positive end expiratory
pressure, that keeps the alveoli open at the end of expiration) or by inverse
ratio ventilation (that increases the proportional time of inspiration when
compared with expiration). This will lead to improved functional residual
lung capacity and reduced ventilation perfusion mismatch.
•• During mechanical ventilation, it is mandatory to use pulse oximetry to
monitor oxygen saturation, capnography to assess the end tidal CO2 level
and serial arterial blood gas monitoring to assess arterial oxygen and CO2
concentration, pH and electrolytes.
Sedation and Analgesia
•• In an intensive care setting, many sedative and analgesic drugs have been
administered by continuous infusion.
•• Midazolam, a water soluble, non-analgesic benzodiazepine with a rapid
onset of action, induces sleep, reduces anxiety and decreases muscle tone.
•• The loading dose is approximately 0.1–0.2 mg/kg followed by continuous
infusion of 0.05 mg/kg/h.
•• Propofol in a dose of 2– 4 mg/kg/h produces satisfactory sedation without
any harmful effects on CPP.
•• In the narcotic group, morphine in the form of intermittent boluses (2–4 mg
IV) or continuous infusion (2–3 mg/h) may be given.
•• Synthetic opioids like fentanyl (1 µg/kg/h) and alfentanyl (24 µg/kg/h) have
a limited duration of action, due to a short elimination half-life and a small
volume of distribution.
•• Haemodynamic effects are minimal and recovery from respiratory
depression is rapid.
•• Intermittent supplementation with midazolam (0.1 mg/kg) can also be used
for sedation along with these agents.
Haemodynamic Management
Hypertension
•• It may occur following reversal with the risk of precipitating cerebral
haemorrhage and myocardial ischaemia.
1529
•• An antihypertensive agent may be selected from amongst short acting

vasodilators like sodium nitroprusside (SNP) and nitroglycerine (NTG);
ganglionic receptor antagonist like trimethaphan; rapidly acting beta
adrenergic blocker like esmolol or metoprolol; a longer acting vasodilator
like hydralazine (10–20 mg 4–6 hourly) or calcium channel blockers.
•• SNP infusion is started in a dose of 0.5–10 µg/kg/min.
•• Infusion of SNP and NTG lead to rebound hypertension when the infusion
is terminated. ICP and level of consciousness should be carefully monitored
during SNP infusion, as rapid infusion may lead to raised ICP when
intracranial compliance is reduced. Both the drugs may cause increased
ICP, because cerebral capacitance vessels dilate and increase CBV.
•• Trimethaphan has a short half-life (1–2 minutes.) and it seldom increases
ICP in patients with reduced intracranial compliance, because ganglionic
blockade spares the cerebral circulation.
•• Esmolol in the dose of 500 µg/kg bolus and 50–200 µg/kg infusion has been
used successfully in controlling hypertension after craniotomy. It can be
safely used in patients with hepatic and renal disease. Its action dissipates
quickly in the post-operative period.
•• Metoprolol caused no change in ICP, CBF and CMRO2, when administered
to patients with increased ICP after head injury.
•• Nefidipine, nicardipine and hydralazine are difficult to titrate and may lead
to intracranial hypertension.
Hypotension
•• During hypotension, the first step is to assess the patient for hypovolaemia.
•• Clinical assessment and invasive monitoring are used to measure the
intravascular volume.
•• Volume replacement is done with crystalloids, preferably normal saline
(0.9%) and colloids.
•• Fluid therapy is guided with CVP monitoring and pulmonary artery pressure
monitoring in patients with LV dysfunction.
•• If there is no response to fluid therapy, ionotropic drugs are infused.
•• If left ventricular (LV) function is good and there is peripheral vasodilatation,
phenylephrine in the dose of 2–10 µg/kg/min is given.
•• Dopamine infusion (2–20 µg/kg) is a good choice if LV contractility is not
good.
•• Noradrenaline can be added if peripheral vasodilatation exists.
Management of Disorders of Sodium Concentration
•• Sodium is an osmotically active, primary cation in the extracellular
compartment. It contributes 90–95% of extracellular osmotic activity.
•• Clinical disorders of sodium concentration, i.e. hypernatraemia and
hyponatraemia, usually reflect alterations of body water content and not
the state of sodium balance.
•• Regulation of sodium concentration is achieved by plasma volume receptors
(atrial natriuretic peptide), endocrine and renal mechanisms (ADH and
aldosterone).
Hyponatraemia (Na+ ≤ 135)
•• Symptoms and signs depend on both the rate and severity of decrease in
serum sodium level.
•• Levels less then 120 mEq/L usually result in CNS symptoms like
disorientation, lethargy, and coma.
1530
•• Acute hyponatraemia may result in brain oedema.

•• Hyponatraemia with a normal or high osmolarity results from the presence
of non-sodium solutes like glucose, mannitol, urea or toxins.
•• The treatment requires reduction of elevated concentration of the
responsible solute.
•• Hyponatraemia with hypo-osmolarity is associated with high total sodium
like in congestive cardiac failure and renal failure. It is treated with sodium
and water restriction, increase in cardiac output and increase in renal
blood flow.
•• Hyponatraemia with low total body sodium is associated with non-renal or
renal loss of sodium (e.g. adrenal insufficiency). This condition is treated
by restoration of blood volume, eliminating excessive sodium losses and
by treatment of the adrenal insufficiency.
•• Euvolemic hyponatraemia is associated with a relatively normal total body
sodium and extracellular volume.
•• The syndrome of SIADH is associated with excessive release of ADH. It is
treated using water restriction, loop diuretics and haemodialysis.
•• Neurological symptoms due to severe hyponatraemia (Na+ < 115 mEq/L)
and water intoxication may require aggressive therapy with hypertonic (3%)
saline and intravenous furosemide.
•• Saline, administered at the rate of 1–2 mL/kg/h increases plasma sodium
by 1–2 mEq/L/hr.
•• CNS signs and symptoms usually improve within 24−72 hours.
•• Excessively rapid correction of hyponatraemia may result in cerebral
haemorrhage, congestive heart failure and a permanent neurological
condition called central pontine myelinosis or the osmotic demyelination
syndrome.
Hypernatraemia
•• Hypernatraemia (Na+ > 150 mEq/L) indicates an absolute or relative water
deficit, loss of water or gain of sodium in excess of water and is always
associated with hypertonicity.
•• Brain tissue dehydration produces mental lethargy and seizures.
•• Hypernatraemia can be associated with hypervolaemia, euvolaemia or
hypovolaemia and is treated accordingly.
•• Hypernatraemia is corrected slowly due to the risk of cerebral oedema and
seizures and sodium levels are reduced by not more than 1–2 mEq/hr.
•• After pituitary surgery, patients have high chances of developing transient
or permanent diabetes insipidus (DI).
•• Hypernatraemia secondary to diabetes insipidus is managed, depending
on whether it is due to a central or nephrogenic cause.
•• Central diabetes insipidus may require exogenous replacement of ADH
with either desmopressin (DDAVP in doses of 1–4 µg every 12–24
hours subcutaneously or intranasal in five times higher dose or aqueous
vasopressin 5–10 µg subcutaneously 4–6 hourly).
•• Total body water deficit can be estimated from plasma Na by the following
equation (TBW = 0.6 × body weight in Kg) – (140 ÷ actual Na+) × 0.6 ×
body weight in Kg.
•• Replacement of half the deficit should be started and further deficits should
be evaluated on an hourly basis.
•• The fluid therapy is guided by serum and urine osmolality, Na+, K+ and
glucose levels.
203
CHAPTER Positioning in
Neurosurgery
Indira Devi • Nitin Garg N • Shukla D
POSITIONING FOR NEUROSURGERY

•• Proper positioning for neurosurgical procedures is:
–– To provide an adequate exposure of the operative site without exces-
sive retraction of the brain.
–– To make surgery ergonomical and less tiring for the surgeon. The more
comfortable the surgeon is the better are the surgical results.
–– To ensure patient safety and comfort, so as to reduce the post-opera-
tive discomfort of the patient.
–– To permit free access to the anaesthetist for maintaining safe anaes-
thesia and ability to continuously monitor the patient.
–– To permit extension of the operative field if required.
–– To ensure adequate venous drainage from the brain in case of cranial
surgery.
–– To avoid undue pressure on vital tissues, especially during spinal
surgery.
•• The principles/steps to be followed during positioning of the patients are:
–– The operative site should be easily accessible.
–– The operative field should be least dependant. This makes operating
on the area of interest comfortable and less stressful. The area should
also have a direct line of sight. This avoids undue retraction of the
brain.
–– The operative field should be at a higher position than the heart. This
helps reduce venous congestion and oozing, thus providing a blood-
less field. There should be no pressure on the neck vein during cranial
surgery and no compression of the abdomen while the patient is in the
prone position.
–– Making use of gravity to help in retracting the brain. This reduces re-
traction induced injury to the brain and the morbidity associated with it.
–– The patient should be comfortable throughout the procedure.
–– Proper space should be available for adjuncts, such as self-retaining
retractors, CUSA, drills, operating microscope, endoscopic equipment
and intra-operative monitoring.
–– The position of the scrub nurse is also important. It should be such as
to make the transfer of instruments easy, safe and unhindered during
surgery.
–– Positioning of the patient is a dual responsibility of the surgeon and
the anaesthetist. Accessibility to the anaesthetists has to be taken into
consideration, while positioning.
1532
–– Special precautions to be taken in elderly patients: excessive rotation

of the neck should be avoided as they may have spondylotic spines
with compromised spinal canals.
–– The head can be placed on a head-rest (horse shoe) or can be fixed
with skull fixation systems (Sugita or Mayfield-Kees skull fixation sys-
tems). The horse shoe should be soft and adequately padded. Special
care should be taken while positioning the patient prone to avoid undue
pressure on the eyeballs. While using the skull fixation systems with
pins, care should be taken to avoid the midline, the frontal sinuses, the
squamous temporal bone and temporalis muscle.
–– The head and neck position have significant effect on the intracranial
pressure. Excessive rotation and flexion of the head and head down
position result in significant raised ICP, by increasing the cerebral
venous pressure by impeding the cerebral venous drainage. Patients
with compromised ICP are more easily affected during identical
manoeuvres than those with normal compliance. Although there are
pharmacological means to control or reduce the ICP, proper position-
ing can itself significantly reduce the raised ICP. Studies have shown
significantly higher ICP in the prone than in supine position. A reverse
Trendelenburg position by 10 degrees itself reduces the ICP without
compromising the CPP.
Cranial Procedures
Supine Position
•• The supine position with varying degrees of rotation of the head can
provide adequate access to procedures for frontal, pterional, temporal,
interhemispheric, trans-sphenoidal and transbasal approaches.
•• Various craniotomies which can be done in this position are:
–– Bifrontal or unilateral frontal craniotomy
–– Frontotemporal, pterional and Falconer’s craniotomy
–– Temporal and temporoparietal craniotomy
–– Trans-sphenoidal approaches
–– Frontal/frontoparietal parasagittal craniotomies
–– Burr hole placements for drainage of chronic subdural haematoma and
ventriculoperitoneal shunts.
Prone Position
•• The prone position is used for posterior fossa procedures, such as midline/
suboccipital craniectomy, posterior interhemispheric approaches, occipital,
parieto-occipital craniotomies, Poppen’s and Krause approach.
•• This position requires more care and time for positioning.
•• Various craniotomies done in this position are:
–– Midline/paramedian suboccipital craniectomy/craniotomy.
–– Occipital/parieto-occipital craniotomy.
•• Some modifications of the prone position are followed, as per the
convenience of the surgeon. These are:
–– The three-quarter position (3/4th prone): This is used by some
surgeons for the parieto-occipital, vermian and supratentorial posterior
interhemispheric approaches (Poppen’s approach).
–– Concorde position: This position is used for the infratentorial suprac-
erebellar approach (Krause’s).
Chapter 203 • Positioning in Neurosurgery
1533
Lateral Decubitus Position

•• This position is used for retromastoid craniectomy for cerebellopontine
angle tumours and for far-lateral approaches.
•• Some surgeons are more comfortable in using this position for temporoparietal
craniotomy and frontoparietal craniotomy for interhemispheric approaches.
Sitting Position
•• There has been significant decline in the use of this position due to risks
such as air embolism.
•• The current indication for the sitting position is supracerebellar infratentorial
approach to the pineal region.
•• This position gives excellent exposure to midline structures with minimal
cerebellar retraction, which is facilitated by gravity.
•• The distinct advantages are bimanual dissection as there is no need of
suction because of gravity drainage of CSF and blood.
•• Moreover, as the face is uncovered, it is directly accessible to monitor
cranial nerve functions.
•• The complications are hypotension, air embolism, tension pneumocephalus,
subdural haematoma and quadriplegia.
•• Other complications are peripheral nerve palsies (common peroneal,
sciatic and recurrent laryngeal nerves), macroglossia, and haemarthrosis
of the elbow.
Spinal Procedures
•• For transoral approaches, the supine position is used.
•• The patient is more to the right of the operating table.
•• Following the transoral decompression, most of these patients require
posterior fusion.
Cervical Spine
•• The supine position is used for the anterior cervical approaches for
discectomies, corpectomy and fusion procedures.
•• The prone position: This is used for posterior approaches to the cervical
spine as for laminectomy, laminoplasty and laminotomy and foraminotomy.
It is preferable to use skull fixation for laminectomy. This provides a rigid
fixation of the head and avoids unnecessary jarring movement while doing
the bone work.
Thoracic Spine
•• The prone position is used for posterior approaches to the thoracic spine,
guided by similar principles and indications outlined above.
•• Thoracotomy is done in the lateral decubitus position.
Lumbar and Sacral Spine
•• The prone position is used for posterior approaches, such as laminectomy,
fenestration and discectomy, foraminotomy and posterior interbody fusion.
•• Thoraco-abdominal approaches give access to D12-L1 level.
•• Transabdominal approaches are used for surgery at L2-L5 level.
•• A left-sided approach is preferred to avoid manipulation of the inferior vena
cava and the liver.
•• For L5-S1 access, a direct ventral approach is used. The Trendelenburg
position allows the peritoneal contents to move upwards.
204
CHAPTER Operation Theatre for
Neurosurgery
Rahmathulla G • Ajaya Nand Jha
GENERAL PRINCIPLES OF PRE-OPERATIVE CARE

AND OPERATING THEATRE USE:
WHO GUIDELINES
Infection Prevention in the Operation Theatre
•• Prudent use of an aseptic technique should be made to prevent infection.
These are:
•• Prevent open wound contamination
•• Isolate the operative site from the surrounding unsterile environment
•• Create and maintain a sterile field in which surgery can be performed safely.
•• Aseptic technique usually refers to:
–– Proper patient preparation for clinical procedures
–– Hand washing
–– Surgical hand scrub
–– Using barriers such as gloves and surgical attire
–– Maintaining a sterile field
–– Using a good surgical technique
–– Maintaining a safe environment in the surgical procedure area.
Pre-operative Care and Patient Preparation

Pre-operative Processes
•• Assessment for infection:
–– Whenever possible, identify and treat all possible infections remote
from the surgical site prior to elective surgery and postpone surgery,
until the remote infection has resolved.
–– Adequately control blood sugar prior to surgery and avoid hypergly-
caemia.
–– Tobacco cessation should be encouraged, with the patient made to
abstain for 30 days prior to an elective surgery.
Antiseptics for Preparation of the Skin and Hands

•• The common antiseptics used in the operation theatre (OT) with their
advantages and disadvantages are:
Chapter 204 • Operation Theatre for Neurosurgery
1535
1. Alcohol (60–90% ethyl or isopropyl): Effective against a broad range

of organisms, e.g. bacteria and mycobacteria.
– Advantages
� Rapid acting
� Non-staining
� Less expensive
� Effective in reducing vegetative organisms
� Effectiveness only moderately reduced in the presence of blood
or other organic material.
– Disadvantages
� Has a drying effect on the skin
� Cannot be used on mucous membranes
� Evaporates rapidly and makes contact time difficult to achieve
� No prolonged activity, but the reduction is so significant that it
takes sometime for re-growth.
2. Chlorhexidine gluconate (4%): Effective against a broad range of
micro-organisms but less so against gram negative bacteria and fungi
and minimal against mycobacteria.
– Advantage: Has a longer duration of action of 6 hours and is effec-
tive even in the presence of blood or other organic material.
– Disadvantage: Effectiveness reduced in the presence of hard wa-
ter, hand creams and soaps. Stains fabric brown in the presence of
chlorine based disinfectants.
3. Iodine compounds including tincture iodine (iodine and alcohol):
Effective against a broad range of micro-organisms.
4. Iodophors (solutions such as povidone iodine, e.g. betadine®):
Iodine in a complex form making it non-toxic and non-irritating. Effec-
tive against a broad range of microbes except mycobacteria.
– Advantage: Less irritating than tincture iodine and can be used on
the mucous membranes.
– Disadvantages:
� Effectiveness reduced in the presence of blood or other organic
material
� Release of the active iodine takes about 2 minutes and hence
needs to be left there for a few minutes prior to the procedure
� Less persistent activity when compared with chlor-hexidine.
Principles to Maximise Antibiotic

Benefit Pre-operatively
•• An antibiotic to prevent infection does not substitute for good infection
control practices and surgical technique.
•• Antibiotics should be used in situations where an infection would be
catastrophic.
•• Should be safe, inexpensive and provide adequate cover against the most
probable intra-operative contaminants.
•• Administer the initial dose at the time of surgery.
•• Maintain therapeutic serum and tissue concentrations till a few hours after
surgery.
1536
•• Do not prolong antibiotic use, as there is no evidence that this practice offers
an advantage. It may promote the growth of resistant bugs.
Pre-operative Skin Preparation of

Operation Theatre Personnel
•• Surgical hand-washing performed prior to surgery is essential and varies
from 7 to 9 minutes with older hand scrubs and between 3 and 5 minutes
with newer agents.
•• This prevents the growth of microbes within the warm, moist environment
of the gloves.
•• Use of an alcohol hand scrub prior to wearing gloves lowers the quantity of
the skin flora so significantly, that they take several hours to grow.
Indications
•• Should be done before any invasive procedure from urinary catheterisation,
introducing central lines and minor/major surgeries
•• All personnel should perform antisepsis.
Environment and Infrastructure of a Modern

Neurosurgical Operating Theatre
•• Factors influencing the development of nosocomial infections are:
–– The microbial agent
–– Patient susceptibility
–– Environmental factors
–– Bacterial resistance
•• The operating rooms have to be designed to fulfil the following criteria:
–– Minimum filtration chain
–– International standards for particulate classification
–– Particulate decontamination kinetic classification
–– Use of easily decontaminable material
–– Unidirectional flow
–– Air exchange of the room more than 50 vol/h
–– Target bacteriological classification.
Neurosurgical Operating Room

Mayfield Frame
•• It is a three pin fixation device, where the head is interposed between the
three pins.
•• It should be tightened by about three threads onto an adult skull as each
thread is about 20 lb/in.
•• The pins should preferably be over areas not covered with muscle.
•• There are different sized pins for adult and paediatric patients.
Sugita Frame
•• It is a 4–5 pin head holding frame, which we feel is more versatile, less
cumbersome, easy to use and provides more stability.
Chapter 204 • Operation Theatre for Neurosurgery
1537
Brain Suite: (Integrated Operating Room with the

Intra-Operative MRI)
•• The development of active shielding of superconducting magnets enabled
the integration of surgery in the fringe fields with high field MRI.
•• A high field MRI may not only improve the quality of the intra-operative
images, but also adds the facility of functional MRI’s, diffusion weighted
imaging and MR spectroscopy.
•• Operating theatres have to be large enough to accommodate the
equipment, which includes all the accessories for navigation, as well as
microsurgical work.
•• The use of ferromagnetic materials is to be avoided and non-ferromagnetic
materials like aluminium, titanium and ceramics can be used.
•• All equipment has to be compatible with MRI.
•• Anaesthesia and monitoring equipment have also been redesigned for the
operative environment.
The Future
•• Robotics and the introduction of more sophisticated devices seem to be
incorporated in the OT of the future.
•• Trends toward minimalism are evident in the development of robotics such
as microelectromechanical systems (MEMS), with products that have
diminutive physical dimensions.
•• Refinements in robotic devices naturally lead to the intriguing prospects
of bionic integration. Bionics refers to instruments that are part biological
and part machine. Bionic devices continue to be an integral part of medical
practice.
•• Ventricular assist devices, artificial blood substitutes, and orthopaedic
prostheses are all familiar examples.
•• Subretinal implantable chips can simulate the function of the photoreceptors.
•• Cochlear implants are also being used with increasing regularity.
•• The ultimate operating theatre of the future will be functionally complicated
with regard to the technology, but simple in use when it comes to the
operating surgeon.
205
CHAPTER Basic Neurosurgical
Instruments
Sanjay Behari • Singh RK • Lyngdoh B • Jain S • Chhabra DK
HEAD FIXATION SYSTEM

• The Mayfield’s head-holder (Fig. 1) is a three-pin fixation device and the
Sugita head-holder is a four-pin fixation device (Fig. 2).
• Care must be taken to see that the pins are not placed at the thin
temporal bones, the venous sinuses, the temporalis muscle (where a
rigid fixation is not possible), the skin overlying the tubing and chamber
of ventriculoperitoneal shunt systems, and the bones overlying the frontal
and the mastoid air sinuses. In children, special paediatric pins are utilised.
Fig. 1: Mayfield head-holder
Fig. 2: Sugita head-holder

Chapter 205 • Basic Neurosurgical Instruments
1539
• The advantages of the pin-head-holders are:

– Multiple self-retaining retractor systems with flexible arms on them
can be fixed.
– Arm-rests can be fixed to avoid arm-fatigue and tremors during
prolonged operations.
– The patient can be positioned in a variety of ways including the park-
bench and the sitting positions.
– Skin sores that may develop when the face rests on a padded head
support for a long period can be prevented.
– Electromyography of the facial muscles and somatosensory and
auditory evoked potentials can be done since the electrodes may be
fitted on the exposed face.
– Intra-operative fluoroscopy and angiography is possible with the use of
head-holders made of radiolucent materials.
– Intra-operative MRI can be performed with the use of non-metallic
graphite head-holders.
– When the head is rigidly fixed, registration errors while using intra-
operative neuronavigation are minimised.
• The precautions that must be taken during fixation of the head-holder are:
– Taking care that the pins do not penetrate the inner table of the
skull since they may cause cerebrospinal fluid leak, meningitis,
osteomyelitis, an intracerebral abscess or, an extradural, subdural or
– The patient’s head should not be in close contact with the head-holder as
this may lead to pressure necrosis of the scalp during prolonged surgery.
OPERATING TABLE
• Operating tables (Fig. 3) are electrically operated and the patient’s position
(during initial positioning for surgery and also during the microsurgical
procedure) can be altered with ease.
• It is possible to move the table up and down; head down (Trendelenberg)
and up (reverse Trendelenberg); and whole body rotation to the right or left.
MICROSURGICAL OPERATING CHAIRS

• The height as well as the position of the operator’s position in relation to
the operating table can be adjusted in the conventional chairs (Fig. 4).
• Sugita has devised an operating chair with side arms to support the elbows
in order to avoid fatigue and tremors (Fig. 5). It has an up and down
movement that can be controlled by a pedal.
Fig. 3: Operating table

1540
Fig. 4: Conventional operating chair Fig. 5: Sugita operating chair
INSTRUMENT TABLE
• For microsurgical procedures, an instruments table has also been devised
that has various divisions, where the instruments being utilised for different
sections of the operative procedures are kept in separate compartments
(Fig. 6).
• This table over-rides the operating table and is, therefore, more convenient
than the one placed on the side of the table.
• The height of the nurse’s platform is electrically changeable depending
upon the patient’s head position. A moving chair on the platform lessens
the fatigue of the scrub nurse.
RETRACTOR SYSTEMS
Self-Retaining Brain Retractor System
• A semicircular basal frame is fixed perpendicular to the head holder (Fig. 7).
• Screws are placed on the frame for holding conventional flexible self-
retaining retractors (Leyla-Yasargil).
• Tapered brain retractors of three sizes (the tips being 2 mm, 4 mm and 6
mm in width) are fixed on the flexible Leyla retractors.
• Two holes at each end of the frame may be used to fix the hand rests and
instrument holders.
• Specific purpose retractor systems may be used for performing specific
surgical procedures, for instance, Boyle-Davis mouth gag (Fig. 8) that
opens the mouth and simultaneously keeps the tongue retracted may be
used for transoral surgery.
• The Hardy’s nasal speculum and trans-sphenoidal retractor systems
(Fig. 9) that retract the nasal mucosa during trans-sphenoidal surgery.
• The Cloward’s self-retaining retractor system (Fig. 10) that retracts the
carotid sheath and sternocleidomastoid muscle laterally and the trachea-
oesophagus and strap muscles medially may be used for performing
anterior cervical discectomy and corpectomy.
1541
Fig. 6: Instrument table
Fig. 7: Self retaining brain retractor system
Fig. 8: Boyle Davis mouth gag for transoral surgery
Fig. 9: Hardy’s nasal speculum for trans-sphenoidal surgery

1542
FIBRE OPTIC LIGHT SOURCE

WITH HEADLIGHT
• During the initial part of the exposure where microsurgical dissection is
required, illumination may often be provided by a fibre optic headlight
(Fig. 11).
• It is lightweight and facilitates transmission of light with maximal efficiency.
Suction
• The suction tip is chosen keeping in mind both the length and the diameter
(Fig. 12).
Fig. 10: Cloward self-retaining retractors
Fig. 11: Fibre optic light source with headlight
Fig. 12: Suction canula

1543
• For superficial procedures, a length of 8 cm is used; for most of the

microsurgical procedures, a length of 10 cm is required; and for deep
procedures a length of 13–15 cm is required.
• The diameter of the suction tube is 3 French (3 French is 1 mm outer
diameter) for very small vessel and nerve anastomosis; 5–7 French for
most of the neurosurgical procedures and 8 French diameter for heavy
bleeding, extradural work and for rapid tumour resection.
• A wide angle between the handle and the shaft allows the suction tube
to be held in a pencil-holding grip so that the ulnar surface of the hand
rests comfortably on the border of the wound and thus provides stability
to the hand.
COAGULATION FORCEPS
• Electric current passing through the tissues produces heat proportional to
the distribution of the electrical power used.
• When heat is applied externally to blood vessels in order to achieve
haemostasis, it usually produces a tissue coagulum that proceeds from
outside inwards in the vessel; and, also promotes intravascular clotting
within the vessel proximal to the point of application of heat.
• The coagulum may, however, slough off and restart bleeding; and, the
heat spread from outside to within may also spread to the surrounding
tissues. Thus, there was a need for an instrument that permitted coagulum
formation within the vessel; and, the heat generated at the contact point
would remain confined to the narrow limits close to the contact points and
not spread to the surrounding tissues (Fig. 13).
• In the Bovie’s monopolar machine, the current generated by the active
electrode returns by the dispersive electrode also known as the ground
plate. The current flow from the active electrode to the ground plate passes
through the intervening conductive tissue including blood vessels, muscles,
bones, neural structures and body fluids.
• Heat may be generated at considerable distances from the point of
coagulation. Thus, it cannot be used in delicate areas like the brainstem
Fig. 13: Bipolar coagulation forceps

1544
• Greenwood, in 1940, devised a machine that permitted the return path of

the electric flow between the two-point coagulation system that formed the
basis of the bipolar system.
• In this system, the blades of the forceps were insulated from one another.
One side of the forceps was attached to the active side of the current
generator and the other to the ground generator.
• Thus, current could flow through the tissues between its blades. The ground
plate of the Bovie’s system was, therefore, not required.
• While in the monopolar system, the generated current from the active
electrode flows to the ground, in the bipolar system, current only flows
between the forceps tips.
• Thus, a bipolar forceps may also be used in delicate regions of the
brain. Irrigation of the bipolar forceps cools the area, prevents heat from
disseminating to the surrounding normal tissue while further decreasing
any chance of the forceps adhering to the tissue.
• Malis, later on, developed a low power spark gap system that utilised
winding coils and transformers to achieve optimum coagulation.
• According to Malis, the factors required for a superior bipolar generator are:
– Proper waveform
– Lowest possible generator impedance
– Isolated output so that heat does not spread
– Rigidly stabilised voltage output
– Control totally in the hands of the surgeon.
• Malis also introduced a self irrigating system for the bipolar forceps.
• A newly developed tungsten alloy forceps tip material has a surface polish
and hardness far better than one made of stainless steel, titanium, or even
nickel, as well as a much higher melting point. These new forceps show
no wear or change after long testing.
• When the bipolar device is not in use, the tips are submerged in the mannitol
solution. Mannitol reduces the coefficient of surface tension between the
char and bipolar tips.
• In addition, saline dissolves the char by disrupting electrostatic forces
within the char. Storing the biopolar tips in a mannitol-saline solution thus
reduces char adsorption.
SCISSORS
• Different types of scissors are used for different purposes (Fig. 14).
• For excision of large tumours, Metzenbaum scissors are used.
Fig. 14: Microscissors

1545
Fig. 15: Bayoneted and tissue forceps
• In microsurgery, curved or straight stainless steel microscissors are used.

• For superficial microvascular procedures such as extra-intracranial arterial
anastomosis, straight handle scissors are required.
• For surgery in the deeper planes, the bayoneted scissors are used so
that the hand holding the scissors does not obstruct the visualisation of
the scissors tip.
• In deep cavities, it may not be possible to align the straight or curved
scissors blades for the desired line of action and so angled blades are
used to visualise their tips.
• Alligator type scissors, with a long shaft, are used for deep and narrow
opening such as in trans-sphenoidal surgery. Their blades are oriented in
different directions to facilitate cutting in all directions.
Forceps
• For superficial operations, the jeweller’s forceps may be used, but these
are too short for most neurosurgical procedures.
• The longer straight or bayoneted forceps with a length ranging from 7 cm
to 10 cm is ideal for most procedures (Fig. 15).
• The bayoneted forceps with an angle between the shaft and the handle
prevents the surgeon’s hand from obscuring the surgical field.
• Forceps with teeth, called the tissue forceps are used for grasping tissues
including the dura.
• Forceps with cross serrations, known as the dressing forceps may be used
for endarterectomy.
• Upward and downward angled tips may be used to dissect around the
back of an aneurysm.
MICRODISSECTORS AND RING CURETTES

• The Penfield microdissectors and Rhoton’s microdissectors are more
frequently used for microneurosurgery (Fig. 16).
• The straight dissectors are used since rotating them will still keep their tip
localised to one place, whereas the tip of a bayoneted dissector rotates
through a wide arc.
• The various microdissectors that may be used are the round, spatula or flat
tip dissectors, the right angled nerve hook, the straight needled dissector,
the cup shaped micro-curette or the straight or angled tear-drop dissectors.
1546
Fig. 16: Microdissectors
Fig. 17: Ring curettes

• The ball-dissector is useful for manipulating nerves and vessels.
• The angled dissectors are useful for separating tumour from the bone in
narrow canals or to develop a plane between the tumour and its capsule.
• For trans-sphenoidal surgery, ring curettes (Fig. 17) with angled handles
are preferred as the field of view of the surgeon is not blocked by his hand
manipulating the handle of the dissector.
• The blunt ring may be used to gently ease out the tumour from the lateral
margins of the sella and from the supraellar regions. The tips of these
curettes may have an angled ring, a straight ring or a loop with a diameter
ranging from 3 to 9 mm.
Needle Holders and Sutures

• Suturing of blood vessels and nerves usually requires 8-0 to 10-0 nylon
sutures on a variety of needles from 50 microns to 130 microns (Fig. 18).
• The handle of the needle holders should be round so that rotating them
between the thumb and the index finger is smooth.
• A lock or a catch in the needle holder is not preferred. This is because,
releasing the lock or catch causes the tip of the needle holder to jump and
be misdirected thus causing tissue damage.
• The straight needle holders are utilised for handling the micro-needle at the
cortical surface, while bayoneted needle holders (with the bayonet shaft
ranging from 8 to 11 cm) are used while working at the depth.
1547
Fig. 18: Needle holders Fig. 19: Cup forceps
Fig. 20: Biopsy forceps
Cup Forceps and Biopsy Forceps

• The fine cup forceps are used for grasping and removing tumours in deep
and narrow exposures (Fig. 19).
• No traction should be applied on the tissues, otherwise the normal
structures may be pulled with the tenacious tumour.
• The cup may be straight or angled upwards or downwards.
• The cup diameter ranges from 1 to 4 mm for microneurosurgical applications.
• Biopsy forceps have long handles and a cup for grasping tissues at the
depth of the surgical field (Fig. 20). They may be used for microsurgery at
a depth like trans-sphenoidal surgery.
ANEURYSM CLIPS AND APPLICATORS

• The most frequently used aneurysm clips have been designed by Yasargil,
Rhoton, Sugita, Sundt, Spetzler and McFadden.
• Optimally the aneurysm clips must be designed to satisfy the following criteria:
– Their closing force must be sufficient to obliterate the lumen of the
aneurysm against arterial pressure pulsations
– They must be non-corrosive and biocompatible
– They must not produce artifacts on MRI.
• The commonly available clips are made of cobalt chrome nickel and/or
molybdenum alloys, e.g. Yasargil clips, Sundt clips McFadden clips, Sugita
clips and Heifetz clips.
1548
• These materials are durable, biocompatible and non-ferromagnetic, yet

they produce artifacts that degrade the quality of MRI scans. The newer
titanium clips, while retaining the same design cause less artifacts on MRI.
• Dujovny et al. have classified aneurysm clips based on their design.
• The alpha class having the shape of the Greek letter “alpha”, have a
crossed leg design.
• The Mayfield, Drake, McFadden, Rhoton, Sundt, Yasargil, Spetzler and
Sugita clips have a similar configuration. The clip is usually a single piece
except that the Yasargil, Rhoton and Sugita clips have an additional small
ringlet as an alignment guide.
• The blades of pivot clips rotate around a central pivot with a separate coil
spring providing the closing force.
• The Heifetz clip is a prototype of the pivot clip. The mobile fulcrum clip,
of which the Scoville clip is an example, consists of an integral spring coil
which acts as a fulcrum around which the blades rotate.
• Temporary clips (Fig. 21) are used to achieve temporary vascular occlusion
without damaging the vascular endothelium.
• They are applied to control bleeding from vessels prior to the application
of the permanent clips, to isolate the aneurysm during dissection and also
to test for the adequacy of occlusion of the aneurysm.
• The blades of a temporary clip open wider than that of a permanent clip.
• The permanent clips are of many shapes and sizes and their occlusion
force is more than that of the temporary clips (Fig. 22).
• For large and giant aneurysms, frequently, fenestrated clips that encircle
the parent blood vessel harbouring the aneurysm are used (Fig. 23). These
obliterate the neck of the aneurysm without occluding the lumen of the
parent artery. If the parent vessel or neural structures obscure direct access
to the aneurysm, a fenestrated clip is especially chosen.
Fig. 21: Temporary aneurysm clips
Fig. 22: Permanent aneurysm clips

1549
Fig. 23: Fenestrated aneurysm clips
Fig. 24: Aneurysm clip applicators
• Booster clips are often placed in order to augment the primary clips.
• Occasionally, malleable rather than spring clips are used when
dealing with broad based or fusiform aneurysms in order to perform an
aneurysmorrhaphy.
• The clip applicators may be used for ordinary, mini and ultra large clips
and may be straight or angled (Fig. 24).
• The Sano multipurpose clip applicator may be moulded depending upon
the trajectory that the surgeon wants to adopt for clip application since it
is multi-jointed.
NEUROSURGICAL DRILLS
High Speed Drills
• The pneumatic microsurgical drills have a vane type of motor (Fig. 25).
• The motors have a rotor spindle placed eccentrically in its covering. Slots
in the rotor spindles have vanes installed in them.
• These vanes move in and out of their slots to trap air while the rotor rotates
within its covering in an eccentric position.
1550
Fig. 25: High speed drill
• A foot operated control regulates the speed of an air driven hand piece that
rotates rapidly the cutting or the drilling dissecting tool attached to the end
of the hand piece. The flow of compressed air both to and from the hand
piece is regulated by the footswitch.
• The electrical drill systems with rotation speeds in the range of 90,000 rpm
do not require a pneumatic gas source as the motor is driven by electricity.
• The drill systems have two types of dissecting tools.
• The cutting tools drill the bone fast, but may cause bleeding from the soft
tissues and may injure the dura.
• The diamond tools, on the other hand, require more time and pressure to cut
the bone but may be used with much greater safety over the dura and soft
neurovascular structures as they resist dissection of the soft tissues. The
diamond tools also facilitate haemostasis while drilling the trabecular bone.
Ultrasonic Bone Curette

• Ultrasonic surgical aspirators with longitudinal and torsional tip, apart from
removing soft tissue tumours, may also be used to cut and scrape bone
structures in skull base and spinal surgeries.
• It comprises of a lightweight hand piece which is stable and easy to handle,
a power supply unit with irrigation and suction, and a foot switch.
• Only minimal tip–bone surface pressure is needed to cut the bone.
• The longitudinal vibration amplitude can be varied from 120 to 365 mm
at an ultrasonic frequency of 25 kHz. The tips (1.9 mm and 2.8 mm wide)
operate in a scratching motion to resect bone.
• The irrigation fluid (cool-controlled at 20°C) can be applied from the tip
with suction equipment.
• The ultrasonic curette is a useful instrument for procedures performed near
the dura mater or other neural tissue without excessive heat production
or mechanical injury.
• Its advantages include the lightweight of the hand piece, fine motion in
scratching and cutting bone tissue, no grabbing of cotton pledgets and an
easy preservation of dura and epidural venous plexus at the tips.
• Its disadvantages lie in less manoeuvreability because of short and fixed
tips in a key-hole exposure and the possibility of injuring the neural tissue
due to long duration or high energy use.
1551
KERRISON’S PUNCHES AND RONGEURS

• The bayoneted osseous punches (Kerrison’s punches) (Fig. 26) have been
constructed in standard sizes.
• The 1–5 mm sized punches are especially useful.
• These have a very thin small foot plate set at either a 90° or a 45° angle.
• The instrument can easily be slipped under the part of the anterior clinoid
process protecting the carotid artery for biting off a portion of the clinoid
process.
• In anterior cervical disc excision, lateral dissection near the nerve root is
facilitated by grasping the posterior longitudinal ligament as well as the
osteophytic spurs overlying the nerve root with the osseous punch.
• The bayoneted punch is also helpful in lumbar microdiscectomy.
• The larger punches can be used to remove the portion of the ligamentum
flavum in the lateral recess overlying the nerve root.
• In trans-sphenoidal hypophysectomy, a longer extension of the distal
portion of the instrument is useful in removing the bone from the sphenoid
sinus as well as from the anterior portion of the sella.
• In transoral odontoidectomy the bone edges can be grasped with the small
osseous punches while the bayoneted curettes are used to free the odontoid
from the underlying connective tissue.
• The angled micro-curettes are made with either a 90° or 45° angle.
• The bayoneted offset allows visualisation of the cutting edges at its end
under the operating microscope. These are especially useful while removing
a tumour from the sella-suprasellar region in the trans-sphenoidal approach.
• The single and double action rongeurs (Fig. 27) may be used to remove
bone from the vertebral body and in removing the lamina during a
laminectomy; for performing a craniotomy as in removing the lesser wing
of the sphenoid during the frontotemporal approach; and, during skull base
surgery for nibbling the bone of the calvarium and skull base.
Fig. 26: Kerrison’s punches
Fig. 27: Rongeurs

1552
EQUIPMENT FOR ENDOSCOPE

ASSISTED MICROSURGERY
• A neuroendoscopic system that includes rigid, semiflexible, and flexible
scopes, bright cold light sources, a high-resolution video camera system,
effective instruments, and irrigation devices may be combined with
microsurgery to improve vision, illumination and minimal invasiveness
(Figs 28 to 30).
• Rigid scopes have four different angles of view (0°, 30°, 70° and 120°).
The 0° and 30° scopes are used for inspection and manipulation; the 70°
and 120° scopes are used for inspection only (“looking around a corner”).
COAXIAL MICROSURGICAL INSTRUMENTS

• The newly designed coaxial instruments contain a coaxial shaft that is
made up of a coupled tube and rod rotating in opposite directions along
their major axis (Fig. 31)
• This rotational movement is achieved by compressing and releasing a
spring-loaded handle.
• The tips of the instrument are obtained by flanging the two elements of
the shaft.
• The length of the tips varies between 6 mm and 10 mm and the width
between 2 mm and 3 mm.
Fig. 28: Rigid and fibre optic endoscope
Fig. 29: Light source and camera for endoscope

1553
Fig. 30: Monitor for endoscope
Fig. 31: Coaxial microneurosurgical instruments
• The instrument has all the three variations, the straight and angled tip as
well as a variation of the straight one in which the distal third is curved.
• The instruments include microscissors and micro forceps, tumour grasping
forceps as well as aneurysm clip applicators.
• The diameter of the shaft ranges between 2 mm and 3 mm and the length
may be 90 mm, 100 mm and 130 mm.
OPERATING MICROSCOPES
• Operating microscopes (Fig. 32) offer a three-dimensional magnified
stereoscopic (binocular) vision in a narrow field at depth.
• The interpupillary distance of the surgeon is maintained by the microscope,
so that the images produced by the objective and eyepiece lenses of the
two sides respectively are merged into a single three-dimensional image.
• The microscope provides a good magnification without significant
aberrations.
1554
Fig. 32: Operating microscope
• Modern microscopes have a motorised zoom system that consists of dual

movable lenses which move with respect to one another so that the desired
focal length may be adjusted.
• Another important feature of the microscope is that it provides good
illumination at narrow depths and around corners of the surgical field without
producing excessive heat.
• Fibre optic coaxial illumination is its property of aligning the front surface of
mirrors to produce even light distribution and avoiding shadows in the op-
erating field. The illumination, however, decreases at higher magnification.
• Modern microscopes have incorporated the modification of increasing the
illumination in proportion to the magnification used.
• The cameras attached to modern microscopes permit recording of high
definition surgical procedures.
• Microscopes may have the capacity to incorporate neuronavigation that
permits the surgeon to determine his actual position during surgery with
the previously acquired three-dimensional imaging data set of the patient.
• It can also display magnetic resonance images, angiograms, and com-
puterised tomography scans simultaneously and combine the information
intra-operatively.
• The simultaneous use of an endoscope with an operating microscope
during surgery is facilitated by its “picture in picture” facility that permits
the simultaneous display of both the microscopic and endoscopic images
on the eyepiece and the microscope display panel.
• A blue light illumination permits visualisation of malignant gliomas in patients
who have been given 5-aminolevulinic acid orally.
• An intra-operative angiography may be performed by detecting within the
focused blood vessels intravenously injected indocyanine green.
• This real-time access to multiple types of imaging data facilitates
spontaneous decision making by the surgeon in the operating room.
• Thus, a good microscope must have a clear stereoscopic view, ample
homogeneous illumination, interchangeable lenses, variable magnification,
well-balanced movement, coaxial illumination and provision for add-on
accessories.
206
CHAPTER Navigation in Brain and
Spinal Surgery
Ajaya Nand Jha • Rahmathulla G
INTRODUCTION
•• ‘Navigate’ defined by the Oxford dictionary means ‘to drive a ship’.
•• Just as these tools were required here, a brain navigation system to reach
pathology at difficult locations was developed by the pioneers of stereotaxy.
•• The term ‘Stereotaxic’ is derived from Greek roots for ‘three dimensional’
(stereo) and ‘system’ or ‘arrangement’ (taxis). In Latin ‘stereo + tactic’
means to touch.
•• Lesions that were located at a depth or traversed eloquent cortical areas
could be safely reached without causing a permanent neurological sequel.
•• This has been made possible with parallel advances in imaging techniques
and instrumentation.
•• The stereotactic atlas can now be superimposed on the patient’s
brain images and various target nuclei specifically located with great
accuracy.
•• The ultrasound was followed by the CT and then the MRI for imaging.
•• The introduction of the CT scanner and the MRI created a revolutionary
change in the way navigational systems were used.
•• Navigation has evolved from frame based systems to interactive image
guided surgery.
•• Real time intra-operative imaging utilising an intra-operative MRI (BRAIN
SUITE) is now a reality.
•• Using this technology to couple surgical skill with detailed anatomical
images, specific targets can be identified and located, avoiding critical areas
and maximising the benefits and safety of any neurosurgical procedure.
•• The risk of damage to the adjacent vital structures is minimised, allowing
a small craniotomy to be made over the lesion.
•• This reduces operative time, bleeding, risk of infection and damage to
vital cortex.
•• The surgeon can maintain three-dimensional orientation of the anatomy
and, when differentiation of the pathological lesion from adjacent normal
brain is a problem, imaging at surgery is a boon, such as in low-grade
gliomas.
GENERAL PRINCIPLES
•• The principle behind a navigational system is to locate a specific intracranial
target point, in relation to a constant external coordinate reference system.
•• Initially, various skull landmarks were used as a guide to locate pathological
lesions and craniotomies were performed in relation to these landmarks.
1556
•• Lines connecting various points were used to locate the Sylvian fissure
and adjacent structures (Taylor Haughton lines) and these were a guide
to the surgeon.
•• Then came the frame based system, where a base ring is attached to the
patient’s head, and a three-dimensional frame placed over this. The lesion
is usually calculated/identified in relation to this external coordinate frame.
The target point is calculated in relation to this using imaging software.
•• Following this, frameless systems are now used.
•• The external coordinate reference points consist of ‘fiducial markers’, either
placed on the patient or by registration of surface points directly.
•• The imaging sequences are done with the fiducial markers or the scan
has to cover the entire face/surface contour, which will be used to register
the patient.
•• The location of various targets in relation to this reference system can be
plotted out and probes can be used to reach the target along a particular
trajectory, making procedures, such as biopsy and lesioning of nuclei in
movement disorders.
ELEMENTS OF STEREOTAXIS
•• Geometry, reference points and surgical instruments are the three basic
elements which have evolved to produce modern stereotactic surgery.
Brain in a Geometric (Cartesian) System

•• A Cartesian co-ordinate system is a three-dimensional grid with a centre
point (origin) that can be used to map locations in space.
•• The position an object occupies in space is determined by its relative position,
with respect to a given point which is arbitrarily chosen as the reference point.
•• Adding 3 orthogonal planes to intersect at this reference point which is now
taken as zero point, establishes a system of reference axes (x, y, z).
•• The location of any point in this system can be measured in relation to the
zero point in all 3 axes.
•• This concept, which is intrinsic to geometry, is being used, following the
application of the Cartesian system of coordinates by Clarke.
Reference Points
•• Visible targets, such as tumours, are located by interfacing a stereotactic
frame on the patient with CT/MRI.
•• Targets which are not visible, like the ventrolateral thalamic nucleus, can
be localised indirectly by using atlases.
Stereotactic Frame
•• Most frames consist of two elements, the coordinate frame and the aiming
device.
•• The frame is a rigid metallic platform attached to the skull by means of head
pins, which pierce the outer table of the skull, so that no displacement can
occur (Figs 1A to D).
•• The aiming device is usually attached to this and may have a number of
moving parts which bear the probe holder.
•• This can usually be moved multi-directionally to point at a specific target in
the skull.
•• The stereotactic systems in use are either ‘’ systems or ‘arc centred’ systems.
Chapter 206 • Navigation in Brain and Spinal Surgery
1557
A B
C D
Figs 1A to D: Four basic types of apparatus (A) Translation system; e.g.

Horseley and Clarke’s, Talairach’s and Narabayashi’s; (B) Arc system; e.g.
Leksell; (C) Burr hole mounted; (D) Interlocking arcs, e.g. Brown-Robert-
Well’s (BRW) and Cosman-Robert-Well’s (CRW) frames
•• In the translation rectilinear type, both the entry point for the surgical
procedure and the target are located in relation to an external frame. The
stereotactic device is attached to the frame and examples are the Horseley
and Clarke system and Speigel and Wycis frames.
•• In the arc centred variety of frame based systems, the target is located
in relation to the frame and is always at the centre of the apparatus. The
Leksell and Laitinen frames are examples of such devices.
•• Frame-based systems have their benefits in that they are stable, can hold
a trajectory probe and can be used in pre-operative simulation.
•• The limitations with these systems are that they are temporary, restrictive,
sometimes complex to use and bulky, making the patient uncomfortable.
Targets are limited to one trajectory at a time. Real time updates are not
possible with these systems.
Applications
•• The various applications of neuronavigation are:
A. Functional: Surgery for movement disorders
– Parkinson’s disease.
– Hemiballismus.
– Dystonia.
– Choreoathetosis.
– Intention tremors.
– Intractable pain.
– Psychosurgery.
1558
B. Anatomical applications
– Tumour localisation and biopsy.
– Craniotomy guided by stereotaxy.
– Interstitial brachytherapy.
– Radiosurgery.
– Clipping of intracranial aneurysms.
– Stereotactic third ventriculostomy using endoscopy.
– Epilepsy—implantation of depth electrodes.
•• Imaging prior to surgery gives the surgeon a two- dimensional idea of the
lesion in relation to various bony and soft tissue landmarks.
•• Earlier, a surgeon would localise a target based on the Taylor-Haughton
lines and the corresponding set of images and place the craniotomy flap
in an approximate location.
•• This could lead to a larger craniotomy, damage to vital structures, inability
to localise the lesion and define the extent of the resection or the ability to
locate deeper structures.
Frame-based Systems
•• The Cosman-Robert-Well’s (CRW) frame is a common, simple and widely
used system.
•• It is ideal in situations where only specific target points have to be located,
e.g. a thalamic lesion and other target nuclei for movement disorders and
deep brain stimulation.
•• The components are, however, common to most of the systems in use.
•• A base ring, which has pins (graphite) with which it is fixed to the skull.
•• Over this, is fixed a localising unit, which has two vertically and one
diagonally placed rod, in an array around the head. These act as the fiducial
‘picket fence’ pattern.
•• The base ring has to be fixed onto the gantry table of either the CT or MRI
and the operating table. A fixation device does this.
•• A phantom device on which the target point and the probe should meet
concurrently, to confirm the exactness of the coordinates.
•• During the surgery, a frame attaches to the base ring and is the interface
between various instruments.
•• Software on the computer (stereocalculator) to compute the final target
from the set of co-ordinates fed in.
•• Usually, there are nine points starting from X1, Y1 up to X9, Y9 with x being
the 9 o’clock position usually The final target is taken as X, Y.
•• Each of these values is fed into the computer, which calculates the final
target.
•• Various instruments are available to work on this platform and the commonly
used ones are: Needle coring device, side cutting needles, spiral needle,
cup forceps, interfaces for the use of endoscopic instrumentation and a
microdrive for implanting deep brain stimulation electrodes.
•• The CRW frame can be used for:
–– Biopsy.
–– Planning of craniotomy flaps overlying the surgical site.
–– Aspiration of a colloid cyst along with the endoscopes.
–– Drainage of deep seated abscesses, cysts.
–– Brachytherapy.
–– Instilling chemotherapeutic agents in cystic lesions.
1559
–– Lesioning of nuclei for movement disorders, such as pallidotomy and

thalamotomy.
–– Placement of deep brain stimulating electrodes for movement disor-
ders and pain.
–– Depth electrode recordings (EEG) for cases of intractable non-local-
ised epileptic foci.
–– Radiosurgery for small well defined or remnant lesions.
•• The limitations of these systems are that they are cumbersome and
require the co-operation of the patient during frame fixation and during
local anaesthesia.
•• Leksell G frame:
–– The frame is engraved with a rectilinear coordinate scale, graduated
in millimetres.
–– The scale conforms to X, Y, Z directions used in CT and MRI scanning.
–– Origin (X, Y, Z = 0) is located outside the frame at a point superior,
posterior and lateral to the frame on the patient’s right side.
–– The frame is versatile and can be used for all stereotactic procedures,
as well as target location and planning of gamma knife radiosurgery.
Stereotactic Biopsy
Technique
•• Stereotactic biopsy (STB) has proven to be highly accurate and safe, with
least tissue invasion and proven tissue sampling.
•• STB is often associated with a lower diagnostic yield in non-neoplastic
lesions and the yield is much higher for those lesions with clear-cut margins
and homogeneous character.
•• It has a role in the diagnosis of a variety of lesions in AIDS, such as
toxoplasmosis, lymphomas, focal encephalopathy and is a useful diagnostic
tool in tuberculomas and other infections.
Indications
•• Multiple intracranial masses, e.g. metastases, inflammatory lesions,
lymphomas, multicentric gliomas.
•• Diffuse ill-defined intra-axial masses.
•• Deep seated intra-axial lesions which are inaccessible, such as thalamic/
hypothalmic gliomas, brainstem lesions.
•• Lesions in eloquent locations, such as the motor or speech areas.
•• Unresectable invasive lesions.
•• Potentially radiosensitive lesions, such as germ cell tumours.
•• Candidates for brachytherapy and radiosurgery.
Contraindications
•• Suspected vascular lesions.
•• Large lesions with significant mass effect require an open craniotomy and
decompression.
•• Altered bleeding parameters.
•• Extra-axial lesions, such as meningioma.
•• Lesions close to the Sylvian fissure, suprasellar region and the third
ventricle and most posterior fossa tumours.
Complications
•• Haemorrhage.
•• New neurological deficits.
1560
•• Seizures.
•• Infection.
Prevention
–– Only one trajectory and one plane.
–– Not for vascular lesions.
–– Narrow instruments.
–– Proper choice of probe track.
•• Stereotactic guided craniotomy uses the same principle and the steps
are almost similar, except that the patient is under general anaesthesia.
•• A craniotomy flap is marked over the site of the probe, directly overlying the
target lesion. It can also be used to map out the location of the eloquent
cortex.
Frameless Stereotaxy
(Interactive Image Guided Surgery)
•• Frameless stereotaxy or ‘interactive image guided surgery’ is a relatively
new navigational modality in which there is no frame fixed on the patient’s
head.
•• The basic principles had already been established in the preceding
50 years, with frame based systems, and technology evolution and
implementation to stereotaxy brought about these changes.
•• Neuronavigation is only a tool which is utilised to optimise the approach
while minimising morbidity.
•• Technology enables us to identify functional cerebral locations in relation
to the lesions and approach and resect these lesions without damaging
the eloquent areas.
•• There are computer softwares which could be utilised to manipulate data
from images from either a CT/MRI. Spatial accuracy has improved to almost
1 mm, with reasonably good speed.
•• Low cost equipment, in which three-dimensional digitisers could be used
as pointing devices during surgery, is available.
•• The steps in utilising these systems are almost similar:
–– Patient selection.
–– Fiducial placement.
–– Imaging.
–– Data transfer.
–– Pre-surgical viewing.
–– Identification-registration of markers.
–– Planning and intra-operative navigation.
•• Patient selection is an important factor, as all cases do not require the use
of navigation to locate the lesion.
Imaging
•• CT and MRI scans are obtained as three-dimensional volumetric data-
bases, even though they are displayed as two-dimensional slices along
an axis.
•• Surface reference markings that are usually external adhesive markers (called
fiducials) are placed at various points to cover a wide area of the scalp and
imaging is done with either CT or MRI.
•• Additional contrast-enhanced studies may have to be performed, depending
on the type of lesion being delineated.
1561
•• Fine 1–2 mm slices on the CT may also be required to increase the accuracy.
These images are recorded on digital media in the DICOM format.
•• The fiducials are placed so that they cover a wide area, they should also
be multiple, not linear and placed in relatively immobile scalp regions.
•• Other imaging modalities such as fMRI and PET scans can also be
performed if required.
•• The present generation systems do not require external fiducials and
various surface landmarks can be utilised for registration.
•• Once the imaging has been completed, the data is transferred to the intra-
operative guidance computer.
•• Prior to registration, the surgeon analyses the image data to decide the
location, size and type of scalp flap, which would be planned.
•• The ideal location for a burr hole and biopsy would be over a gyrus, and
away from any vessels.
•• The surgeon’s plan can be recorded and used following the registration.
•• The patient’s head is rigidly fixed on the table with either a Mayfield or a
Sugita frame.
•• A reference star is attached and the position of this star cannot be changed
throughout the procedure.
•• Registration involves placing the points in one image volume (patient’s
fiducials) onto the points of another volume (images taken pre-operatively).
•• The fiducials in principle act like the picket fence target in frame-based
systems and these are entered into the operating room space.
•• The different methods of registration include:
–– Point-based: Intrinsic, extrinsic, non-rigid fiducials, rigid fiducials or a
stereotactic frame.
–– Curve and surface methods.
–– Moment and principle axis.
–– Correlation methods.
–– Interactive.
–– Atlas.
•• Once the registration has been completed, the next step would be to
visualise the approach and underlying structures with the help of the
navigating pointer.
•• The margins of the lesion can be defined and its relation to the scalp flap
delineated.
•• The depth of the lesion can be measured from the surface, using a virtual
probe.
Disadvantages
– It is not in real-time.
– Inaccuracies may occur due to brain shift.
– Increased operating time.
– Per-operative imaging is mandatory.
Uses
– Glioma resection and localisation.
– Deep seated tumour localisation.
– Drainage of cysts and abscesses.
– Placement of a reservoir for chemotherapy.
– Surgery for epilepsy.
– Guidance to the ventricles.
1562
BRAIN SUITE: INTRA-OPERATIVE

MAGNETIC RESONANCE IMAGING AND
REAL-TIME NEURO-NAVIGATION
•• The operating theatre has to be large enough to accommodate the
equipment, which includes all the accessories for navigation, as well as
microsurgical work.
•• The use of ferromagnetic materials is to be avoided and non-ferromagnetic
materials like aluminium, titanium and ceramics can be used.
•• All equipment has to be compatible with MRI.
•• Anaesthesia and monitoring equipment has also been redesigned for the
operative environment.
•• Intra-operative MRI has a wide range of applications for the surgeon for:
–– Gliomas resection.
–– Pituitary tumour ablation.
–– Complicated tumour resection.
–– Epilepsy surgery.
–– Intracranial cyst surgery.
–– Biopsy with and without a frame.
–– Catheter placement.
–– Vascular surgery.
–– Functional imaging.
–– Diffusion tensor imaging.
Benefits of the Intra-operative Magnetic Resonance Imaging
•• High field MRI has a number of advantages, such as instant real time
feedback in the OR, superior image quality and acquisition time and
advanced MR sequences.
•• Data can be incorporated into decision-making at the time of surgery.
•• It has the potential for unlimited research and the ability to drive new imaging
techniques.
•• Also important are the improved medical outcomes with the use of intra-
operative MRI, shorter hospitalisation, and better and faster procedures
with fewer complications.
•• Certain economic and practical barriers impede the use of intra-operative
MRI, but with increased volumes the cost efficacy barrier can be overcome
after looking at the benefits.
Future Developments of Intra-operative
•• Full patient access during the surgical procedure.
•• No need to move either the patient or the magnet.
•• Highest image quality with reduced acquisition time.
•• Ergonomics that incur no delays for serial or continuous scanning.
•• Integration of all pre-operative and intra-operative imaging data for
interactive navigation.
•• With the introduction of high field MR systems intra-operative diffusion
imaging can demonstrate early ischaemic damage during procedures and
can be used to monitor vascular procedures.
•• Diffusion MRIs can be complemented with perfusion MRIs and surgery and
embolisation of AVMs will be made safer by keeping an eye on blood flow,
while the blood vessels are being manipulated.
1563
•• In aneurysm surgery, 3D visualisation can help identify the position of the

clips and their relation to the neck of the aneurysm.
Neuronavigation
•• Neuronavigation is an aid to 3D visualisation of the object, entry and
planning of surgical treatment.
•• The Zeiss Opmi Pentero microscope which is floor mounted on wheels,
in combination with a ceiling mounted navigation system (Vector vision
sky—Brain lab) which are optimally integrated, are used.
•• The initial sequencing protocol may be standard T1WI, T2WI and other
sequences depending on what is specifically required.
•• Functional data and magnetoencephalography, which is obtained a day or
two prior to surgery, can be incorporated with the anatomical data registered
in the sequences.
•• fMRI and magnetoencephalography data is used simultaneously to identify
eloquent cortical areas.
•• The ability to identify intra-operative swelling, brain shifts, resection margins
and volumes and adjacent functional areas makes intra-operative MRI a
useful adjunct to surgery.
•• It contributes to greater tumour volume resection in gliomas. The ideal
treatment for low-grade gliomas is complete resection and this is an ideal
modality to achieve a high cure rate.
•• One of the advantages of intra-operative MRI in guiding procedures, such as
brain biopsy, is that it can definitively show when the biopsy needle is in the
lesion, which guarantees success in obtaining a representative specimen.
•• Intra-operative MRI guided surgery is at present superior to any form of
neuronavigation system, having the potential to acquire spectroscopic and
angiographic data, which could lead to different surgical techniques and
surgical goals.
•• It has the ability to compensate for brain shifts, which will occur due to CSF
loss, diuretics or tumour/brain being resected and is accurate.
•• The process of updating these images enables a study of these shifts and
their continuous monitoring during tumour resection.
•• Mapping of motor and other functional areas helps in avoiding of these
areas and prevent permanent neurological deficits.
NAVIGATION IN SPINE SURGERY

•• Spine surgery also has areas where the surgeon is not completely oriented
to the complex anatomy of the region and it is here that computer-aided
image guidance during surgery plays a big role.
•• Fluoroscopy has been the conventional guide for the surgeon in these
situations, the drawback being that it gives us the trajectories in two
dimensions and the surgeon has to extrapolate the third dimension.
•• Although the lateral view may be easy to interpret, the AP view makes it
difficult to estimate the depth at which one needs to work. This so called
‘dead reckoning’ can lead to varying degrees of inaccuracy when doing
instrumentation at various spinal levels.
•• Utilising routine radiography to place pedicle screws has been shown to be
unreliable at the lumbosacral level with penetration of the cortex ranging
from 21% to 31%.
1564
•• The principles of image guided navigation for spine surgery remain the
same as that for the cranial component, with regards to a number of
components.
•• The components which are common to both are the image processing
workstation interfaced with an optical infrared localiser.
•• The optical localiser can either be the source of infrared light which is
reflected by the instruments back to the camera or can track infrared light,
emitted by the LED.
•• The computer workstation then utilises this information to calculate the
precise location of the instrument in the surgical field, as well as the location
of the specific anatomical target in relation to the instrument resting on it.
•• Prior to spinal fixation, a pre-operative CT scan of the various levels has
to be performed.
•• The images should be a three-dimensional volume acquisition of a
continuous dataset with slices 1–2 mm thick.
•• MRI data images may also be used and this data is transferred to the
workstation via a CD format.
•• The application of navigation to spine surgery requires that fixed bony
landmarks are utilised as the fiducial frames of reference.
•• Two separate registration techniques can be harnessed, while using spinal
navigation.
•• The first would be the ‘paired point registration’ technique where a
series of points on the CT or MRI imaging datasets are pre-selected and,
on exposing the spine, fixed bony points are selected.
•• Any intra-operative landmarks that can be easily identified, along with its
corresponding radiological counterpart, are the reference points for further
image-guided navigational projections.
•• The best and easiest would be the tips of the spinous processes and
the transverse process, at the levels at which instrumentation is to be
performed.
•• Alternatively, other bony landmarks, such as osteophytes or the facet joint
can be used.
•• Registration is then performed prior to any surgical decompression or
manipulation thus preserving the anatomical landmarks and facilitating an
easy and accurate registration process. Three separate points are required
for registration.
•• Alternatively, a second technique called ‘surface mapping’ can be used
for registration.
•• Here, multiple non-discreet points on the exposed and debrided surface of
the spine, within the surgical field, are selected.
•• No pre-selection of points from the imaging dataset are required and to
increase the accuracy of this technique, a greater number of points are
required from both the dataset and the surgical field.
•• The positional information of these points is transferred to the workstation
and this is used to create a topographic map and match it to the imaging
dataset.
•• For this method, about 10–15 minutes is required, whereas, for the paired
point-based technique only 10–15 seconds are required. This can prolong
the duration of surgery.
•• Once the registration has been performed, a spatial relationship has been
processed between the surgical space and the image space.
1565
•• Movement of the patient following this will cause spatial distortion and
navigation errors.
•• This is usually minimised by using a spinal tracking device, consisting
of separate LED or passive reflectors, which are attached to the spine.
•• This frame can be continuously tracked by the camera and any change in
position will alert the navigation system, thus maintaining the accuracy of
the registration and eliminating the need for redoing the entire process.
•• Disadvantages of the tracking device are:
–– It comes in the way of the surgical field.
–– It should always be in the line of site of the camera.
–– Additional surgical time is needed for its attachment.
•• Sometimes, the tracking system could be avoided but absolute care has
to be taken, to avoid leaning on the patient, changing the position of the
table and respiration of the patient.
Clinical Applications of Spinal Navigation

•• Metastatic spinal tumours through the posterior or the posterolateral route
makes visualisation of its anterior limits and extent difficult and could result
in damage to the adjacent soft tissue structures. Optimised excision with a
minimum chance of soft tissue damage is aided by navigation.
•• Pedicle screw fixation and spinal stabilisation, for both tumour and non-
neoplastic pathologies, such as spondylolisthesis is another important
use. This prevents the chance of injury to the nerve roots and neurological
damage and optimises proper screw placement.
•• Transarticular screw fixation at C1 to 2 is another very important use, where
navigation helps identify the position of the vertebral artery, in relation to the
screws being placed and the small space being utilised.
•• This can also be used for transoral decompression of the odontoid.
•• Anterior screw fixation for odontoid fractures.
•• To fix pedicle screws at the thoracic level.
•• Anterior thoracolumbar decompression and fusion procedures
•• Cervical corpectomy and resection of cervical neoplasms via the posterior
approach.
Pitfalls of Image Guided Surgery

•• The registration process is critical for accuracy and best outcomes.
•• It is not a replacement of the surgeon’s own familiarity with spinal anatomy
and technique.
•• It merely serves to confirm estimation of the non-exposed anatomy.
•• System variations for intra-operative functionality should be factored in.
•• It takes a longer duration and OT time due to the learning curve and
registration process.
207
CHAPTER Endoscopy in Brain
Tumour Surgery
Manas Kumar Panigrahi
•• In 1969, George Smith and Willard Boyle invented the first charged couple
devices (CCDs) at Bell Laboratories.
•• The CCDs are solid-state devices, usually a silicon chip, which are capable
of converting optical data into electrical current.
•• The CCDs are ideal for use in low-light environments and are readily
incorporated into the system’s apparatus, resulting in both improved quality
of the transmitted images and decreased size of the endoscopic systems.
•• The success of neuroendoscopy in past few decades relied heavily on the
success of endoscopic third ventriculostomy (ETV) for the treatment of
obstructive hydrocephalus.
•• Now, however, the field of neuroendoscopy has extended itself beyond
just ventriculostomy procedures and is being used for the treatment of
various types of neurosurgically treatable disorders like intraventricular
tumours, skull base tumours, craniosynostosis, degenerative spine disease,
intracranial cysts and rare subtypes of hydrocephalus.
USES IN NEURO-ONCOLOGY
•• The use of endoscopy for the management of brain tumours has evolved
from simply treating the associated hydrocephalus, to sampling of tumour
tissue, to tumour resection.
•• The subsequent technical development, both of endoscopes and of an
increasing range of dedicated instruments have expanded the scope of
neuroendoscopy in both diagnostic and therapeutic roles.
Instruments
•• In general, there are two classes of neuroendoscopes: (1) rigid and (2)
flexible.
•• Huw Griffith of Bristol, England, pioneered rigid neuroendoscopy in 1970s.
Takanori Fukushima is credited with introducing flexible neuroendoscopy.
•• Rigid endoscopes have superior optics and working channels, but lack
steerability. To overcome lack of manoeuvrability, angled rod lenses (0,
30, 70 and 120 degrees) have been developed to look around corners.
•• Flexible endoscopes have better manoeuvrability at the expense of a
significant reduction in the amount of light transmitted and image clarity.
•• Table 1 enumerates the advantages and disadvantages of both scopes.
•• Currently, two types of CCDs are in use: (1) single chip camera and (2)
three-chip camera.
Chapter 207 • Endoscopy in Brain Tumour Surgery
1567
Table 1: Advantages and disadvantages of rigid and flexible scopes

Rigid scopes Flexible scopes
Advantage Better image Steerability
Higher resolution
Wider view
Better colour
Better light transmission
Disadvantage Less manoeuvrable Poor image
Pixel granules
Narrower view
Less true colour
Worse light
Small working channel
Limited selection of scopes
and instruments
Table 2: Advantages and disadvantages of the scope holder

Free hand Rigid holder
Advantages More freedom of movement particu- Surgeon can use both hands
larly when configuration needs to be Minimises accidental movements
frequently or continuously changed, and tremor
e.g. tumour removal
Disadvantages More fatigue for surgeon More static
Risk of accidental movements Inconvenient when frequent reposi-
tioning is needed
•• Three chip cameras provide better picture quality; however, camera size
is larger and it is expensive. Illumination is provided by a fibreoptic cable
connected to a high intensity light source such as xenon.
•• Energy sources for endoscopic dissection include monopolar and bipolar
coagulators and a number of fibreoptic lasers.
•• Two lasers, which are most commonly used for neuroendoscopic
procedures are neodymium doped yttrium aluminium garnet (Nd:YAG)
laser and potassium titanyl phosphate (KTP) laser because of their ability
to work through water and transmit through the miniature fibreoptic cables.
•• Neuroendoscopy can be done either free hand or using a rigid holder.
The most commonly used holders are the pneumatic holder produced by
Aesculap or Leyla retractor arms.
•• Table 2 describes the advantages and disadvantages of the scope holder.
IMAGE-GUIDED ENDOSCOPY (TABLE 3)

•• Standard intra-operative C arm fluoroscopy can, on occasion, help to
monitor the position of the tip of the endoscope.
•• Ultrasound can provide more information about the location of the
endoscope relative to intra-cranial structures. In infants, an ultrasound probe
can be placed directly on the open anterior fontanelle. In older patients, the
probe can be placed at a burr hole or a small craniotomy. Small probes
have been developed specifically for ultrasound-guided neuroendoscopy.
•• Stereotactic guidance systems can be combined with both rigid and flexible
neuroendoscopes.
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Table 3: The entry point for tumours in different locations

Tumour location Entry point
Lateral ventricle—Frontal horn 2−3 cm parasagittal, coronal to 2 cm pre-coronal
Body 2−3 cm parasagittal, coronal to 2 cm pre-coronal
Trigone 2−3 cm parasagittal, 4−6 cm pre-coronal
Foramen of Monro 3−5 cm parasagittal, 2−4 cm pre-coronal
Third ventricle—Anterior 1−2 cm parasagittal, coronal
Posterior 1−2 cm parasagittal, 4−6 cm pre-coronal
•• Recently, frameless stereotaxy has been used to guide the neuroendoscope.

The principle of frameless stereotaxy is to define a three-dimensional co-
ordinate space for a pre-operative imaging modality and translate this to
the three-dimensional co-ordinate space of the operative field.
Management of Ventricular Tumours and Cysts
•• Endoscopy can be used in tumour management for the following various
purposes:
–– Ventriculoscopy: Inspection of ventricular walls for seedling and CSF
sampling
–– Relief of tumour associated hydrocephalus by ETV
–– Tumour biopsy
–– Tumour resection
–– Endoscopy-assisted microneurosurgery.
Ventriculoscopy
•• The prognosis of some primary intracranial tumours is dependent on the
presence or absence of ependymal spread of tumour.
•• Patients with primitive neuroectodermal tumours, for example, fall into the
high-risk group rather than the low-risk group if there is evidence of spinal
or ventricular ependymal seedling.
•• Although, MRI is reliable in the detection of ependymal tumour spread in
most cases, some patients may have ependymal spread without radiological
evidence.
•• Ventriculoscopy can be more sensitive than MRI with little added morbidity.
•• Through a frontal or parietal burr hole, one can access the lateral ventricle,
examine the surface, document any findings with colour photography,
and even biopsy suspicious areas. This takes substantially less time than
needed for an MRI examination.
•• Furthermore, if present, definitive treatment of CSF obstruction can be
achieved by either third ventriculostomy or tumour resection at the same
sitting.
•• The ETV is a reasonable option to treat the secondary hydrocephalus
before definitive treatment of the primary tumour.
•• A CSF sample can be taken at the time of surgery and one can also explore
the ventricle and take biopsies, if necessary.
•• Importantly, ETV may be the definitive treatment if the obstruction is caused
by a tumour that does not require removal such as a tectal plate tumour.
•• The situations in which bilateral ventricular enlargement exists due to a
tumour situated in the anterior third ventricle at the foramen of Monro, an
endoscopic septostomy can eliminate the need for biventricular catheters
or for CSF shunting altogether.
1569
Neuroendoscopic Biopsy
•• There are definite advantages of endoscopic biopsy over stereotactic
needle biopsy like:
–– Direct visualisation of the tumour allows more accurate and safer sam-
pling. A region for biopsy can be chosen under endoscopic vision, and
vessels can be avoided.
–– The specimen obtained is larger and not subjected to as much me-
chanical artefact. It does not need to be sucked through a needle or
manipulated.
–– Any resultant bleeding can be controlled by either coagulation or pack-
ing under direct visualisation.
–– If the tumour is relatively avascular, it may be removed totally by en-
doscopic techniques.
–– Other procedures can be performed at the same operation (e.g. ETV,
septostomy).
•• Surgical planning is critical for successful endoscopic tumour procedures.
The most critical aspect is selecting an entry site that offers the most direct
intraventricular, linear route to the target. This principle avoids undue torque
on the cortical and intraventricular surface.
•• A relatively anterior entry site with reference to the coronal suture is most
important for lesions situated in the posterior third ventricle or pineal region.
•• With respect to laterality, most entries should be on the non-dominant side.
The exceptions to this recommendation are the following: (1) hypothalamic
lesions, which are best targeted using a contralateral approach and (2) in a
situation in which there is significant ventricular asymmetry in which case
the preference is to enter the side with greater ventricular size.
Endoscopic Fenestrations of Intracranial Cysts

•• Intracranial cystic lesions, like arachnoid cysts, tumour-associated cysts
(craniopharyngioma), porencephalic cysts, multiloculated hydrocephalus,
septum pellucidum cysts and pineal cysts, are amenable to endoscopic
management.
Endoscopic Resection of Intraventricular Tumours

•• Tumours with following characteristics are ideally suited for endoscopic
resection:
–– Moderate to low vascularity
–– Soft consistency
–– Less than 2 cm in diameter
–– Associated secondary hydrocephalus
–– Histologically low grade
–– Situated in lateral ventricle/third ventricle.
Colloid Cyst
•• Endoscopic surgery should be considered as the first line surgical modality
for the treatment of colloid cysts as it offers the advantages of direct tumour
visualisation while being a minimally invasive technique.
•• Rigid endoscopes are superior to flexible endoscopes in colloid cyst
surgery due to high definition image and magnification and availability
of multiple viewing angles that allow one to look around the corners and
behind obstructions.
1570
•• In most patients, a single portal endoscopic approach is sufficient for

tumour removal.
•• The main technical factor that affects colloid cyst removal is the density
of the cyst contents.
•• This can best be estimated using non-contrast CT.
•• Hypodense or isodense contents are usually fairly liquid and can be re-
moved through the small apertures of the endoscope without difficulty. A
small suction catheter attached to a 10 or 20 mL syringe may help in this
regard.
•• Hyperdense cysts may have more tenacious contents, which can prove
more difficult to remove with the endoscope.
•• On MRI, high signal on T1-weighted imaging correlated with higher
cholesterol content, thicker consistency, and more difficult removal.
•• Limitations of the endoscopic approach are the difficulty of working when
the foramen of Monro is small and when the cyst is lying posteriorly. Such
cases can be recognised pre-operatively on MRI and they should be
probably best managed via standard microsurgery. Overall complication
rate is very low. Reported complications include injury to the fornix, epilepsy
and short-term memory problems.
Endoscopic Pituitary Surgery

•• Endoscope assisted trans-sphenoidal operation refers to the microscopic
procedure in which the endoscope is used as an adjunct to the microscopic
removal of a tumour.
•• The endoscope may simply be used to perform an anterior sphenoidotomy
prior to inserting the nasal speculum and using the microscope.
•• Pure endoscopic trans-sphenoidal surgery refers to the removal of tumour
without the use of the operative microscope.
•• Endoscopic sphenoidotomy is performed by using 0 or 30 degrees rigid
rod endoscopes.
•• Although surgery can be performed through a single nostril, which acts as
a portal for the endoscope and the surgical instruments, the dual-portal
technique allows superior manoeuvrability, flexibility and efficiency over a
single portal approach.
Microscopic Adenomectomy versus

Pure Endoscopic Adenomectomy
Microscopic Adenomectomy
Advantages
•• Familiarity to neurosurgeons
•• Three-dimensional view with easily manipulated zoom and focus
•• Easy maintenance of the appropriate trajectory to the sella once it is defined
•• Nasal speculum used for microscopic surgery protects the nasal mucosa
from injury by instruments
•• Microscope being out of the surgical field, the view does not suffer from red
out when bleeding fills the surgical field and it does not obstruct the entry
or manoeuvring of instruments into or out of it.
Disadvantages
•• Field of view is narrow and visualisation is limited by line of sight.
1571
•• The surgeon cannot see around corners neither towards the cavernous
sinus or the suprasellar space and optic chiasm.
•• Sinonasal complications due to sublabial or trans-septal approaches like
anosmia, alveolar numbness, saddle nose deformity and nasal septum
perforations.
•• Post-operative nasal packing may cause facial pain and headache.
However, minimally invasive approaches of the septal pushover and direct
sphenoidotomy do not require nasal packing and are associated with fewer
sinonasal complications.
Endoscopy Assisted Surgery for Skull Base Lesions

•• Cranial base endoscopic surgery presents unique challenges not
encountered within the ventricular system, for example:
–– Unlike with intraventricular endoscopy there is the lack of significant
true or expandable space through which one can manipulate multiple
instruments
–– One must navigate around the lattice of nerves and arteries not pre-
sent within the ventricles
–– Instruments are usually not passed through working channels of the
endoscope or portals as they are during intraventricular surgery, but
rather must be passed alongside the telescope.
•• Prerequisites to make full use of this subarachnoid space are correct
positioning of the patient’s head to support gravity-related self-retraction of
the cerebrum or cerebellum, careful release of CSF from the cisterns and, if
applicable, from the ventricular system at an early stage of the procedure,
and cautious debulking of the tumour.
•• Endoscope is well suited for dealing with deep midline tumours like
craniopharyngiomas and epidermoid tumours, lesions of the posterior fossa
and cerebellopontine angle.
•• It is a very useful adjunct in surgery of acoustic schwannoma. Other
indications include microvascular decompression of the cranial nerves,
vestibular neurectomy and an assortment of intrinsic and extrinsic lesion
involving the brainstem.
•• Advantages of endoscopy in surgery for vestibular schwannoma are:
–– Improves visualisation of bony, neural and vascular relationships while
minimising retraction
–– When one is attempting to preserve hearing, it is critical that the intra-
osseous endolymphatic sac and posterior semicircular canal are not
violated when the posterior wall of the IAC is removed.
–– The main use of endoscope is to visualise the lateral end of the IAC,
which helps the surgeon to minimise the drilling of the petrous bone
with lower risk of entering the posterior semicircular canal and the
vestibule
–– Inspection of the IAC with angled endoscopes for residual remnants. It
can also minimise the bony removal of posterior lip of the canal while
achieving excellent visualisation of the fundus
–– Angulated endoscope is also very useful when directed into the oppo-
site direction, i.e. towards the brainstem and even anterior to it to the
prepontine area. It is particularly useful in patients with far prepontine
extension of epidermoid tumours.
208
CHAPTER
Orthotics
PK Sethi
FUNCTIONS
•• Similar to the basic functions of an orthosis, which are correction, protection,
stabilisation and immobilisation; spinal orthoses have corrective and
protective functions.
•• They support and thus stabilise the spine, as well as immobilise and thus
rest the spine.
•• Following surgery or injury, the spinal orthosis protect the cord and nerve
roots, and carry out the functions that intrinsic structures of the spine and
the muscles normally achieve.
BIOMECHANICS
•• The spine can be considered mechanically as a series of semi-rigid bodies
(vertebrae) separated by viscoelastic linkages (discs and ligaments).
Movements of the Spine

•• The Cervical Spine is the most mobile part of the spine. It has flexion,
extension, lateral flexion, rotation and gliding (translatory) movements
at different levels. Females show slightly greater movement than males.
•• The Thoracic and Lumbar Spines have similar movements as that of the
cervical spine like flexion, extension, lateral flexion and rotation (Table 1).
•• Above the age of 50 years, the range of motion gradually starts reducing
and by the age of 80 years the range reduces by 10 degrees.
Balanced Horizontal Forces

•• Horizontal forces provide efficient bending movement for correction of
lateral curvature and immobilisation of the spine. This can be expressed
as three-point loading system.
Table 1: Motion of cervical, thoracic and lumbar spine (in degrees)

Movement Cervical Thoracic Lumbar Total
Flexion 60 15 40 55
Extension 80 15 25 40
Lateral Flexion (Right) 45 15 20 35
Lateral Flexion (Left) 45 15 20 35
Rotation (Right) 75 40 5 45
Rotation (Left) 75 40 5 45
Chapter 208 • Orthotics
1573
•• Three forces are applied along the length of the spine, two in one direction
and one in the opposite direction. Since the system is in equilibrium, the sum
of the forces and sum of the bending movement they create remains zero.
•• The sum of forces at B and C has to be equal to the force at A (B + C = A).
•• In order to have the same skin pressure, the size of the skin pad should
be proportional to the pressure applied through it.
Fluid Compression
•• Pascal’s law states that fluids in a closed chamber behave like solids and
the pressure applied at any point is transmitted equally in all directions.
•• This principle is utilised in supporting the spine by compressing the
abdominal cavity by a tightly applied corset or abdominal support.
•• This increases the intra-abdominal cavity pressure and produces a
distracting force, thereby effectively distracting the lumbar spine.
Traction
•• By applying traction alone it is possible to achieve a certain amount of
immobilisation and stability of the spine even if there is lateral instability.
Sleeve Principle
•• It is caging the patient between two semicircular fixation points, one above
and the other below.
•• Between these two semicircular fixation points there are various uprights.
•• The uprights may be in front, at the sides of the patient, posterior or
paraspinous. These uprights serve as a sleeve, splint or distracter.
Skeletal Fixation
•• This is the most effective method of applying reliable control on the spine.
Halo traction and halo pelvic fixation devices are the examples.
•• After the diagnosis is made the clinician decides the specific goals to be
achieved, whether to support, immobilise or correct the spine and what
degree of freedom is to be controlled, to what extent and in which manner.
NOMENCLATURE
•• Spinal orthoses can be grouped as orthoses, corsets, belts and braces.
•• They are best described using generic names; referring to the anatomical
level they are capable of controlling and treating.
1. CO = Cervical orthosis
2. HCTO = Head cervico thoracic orthosis (SOMI)
3. TLO = Thoraco-lumbar orthosis
4. LSO = Lumbo-sacral orthosis
5. TLSO = Thoraco-lumbo-sacral orthosis
6. CTLSO = Cervical thoraco-lumbo-sacral orthosis.
•• Based on the effectiveness of the control applied by the orthosis, they are
also grouped as minimum control, intermediate control and most effective
control orthosis.
Corset and Belts

Corsets
•• Corsets are flexible orthoses made of fabrics with vertical stays.
1574
•• They are adjustable by means of laces, hooks and elastic abdominal straps.
•• They are effective for management of pain due to muscle strain by relieving
the activity of spinal and abdominal muscles.
•• However, long-term use of corsets may lead to atrophy of these muscles.
Belts
•• Sacroiliac belt is a 5−10 cm wide belt encircling the pelvis between the iliac
crest and the greater trochanter and helps in stabilising the sacroiliac joints.
•• An abdominal belt is a 10 cm wide belt and is worn by weight lifters to
prevent collapse of the vertebrae.
Orthoses
Cervical Orthoses
•• There are three types of cervical orthoses:
1. Collars
2. Poster devices and
3. Custom made.
•• Collars restrict excessive movements, especially flexion of the cervical
spine, through a feedback system and acts as a reminder to restrict
movement.
•• Poster cervical orthoses provide more control and provide more rigid
immobilisation because of mandibular and occipital pads, and sternal and
thoracic pads.
•• Custom-made cervical orthoses are made to relieve the weight of the head
on the cervical spine.
Soft cervical collars: The therapeutic rationale is that it restricts motion,
reduces body heat loss and keeps the neck warm and thereby relieves
muscle spasm. It maintains the head directly over the centre of gravity and
reduces the cervical lordosis, which opens the intervertebral foramen and
reduces nerve root pressure.
Philadelphia collar: This is a soft type of collar and provides better support
due to the width of the collar that surrounds the neck. It also has anterior and
posterior stiffeners to provide additional support.
Hard cervical collars: These are made of rigid material like low-density
polyethylene. They reduce cervical movements better in the sagittal plane
than a soft collar. However, they provide little control on lateral flexion and
rotation, and may be of fixed or adjustable width.
Four-post cervical collar: This is a flexion extension control orthosis.
Anteriorly there is a chin support and a sternal support and two turnbuckle
uprights. Posteriorly there is an occipital support thoracic plate connected
together with two turnbuckle uprights. The uprights are adjustable in height
and made of aluminium. A traction force is applied between the cervical and
the shoulder rings, which restricts flexion and extension and thus maintains
the specific position as required.
Sternal occipital mandibular immobiliser (SOMI) orthosis [head
cervico thoracic orthosis (HCTO)] is commercially available and consists of
a sternal plate, shoulder strips, mandibular pad, occipital pads and support
bars. It has good control on flexion but allows a little extension and rotation.
Halo cervicothoracic orthosis: It consists of a halo ring fixed to the skull
with pins, chest jacket and connections between them. This provides the
Chapter 208 • Orthotics
1575
most effective control on cervical movements. It allows inter-segmental

movements; still this is the best option for fractures of the cervical spine.
Minerva Jacket provides total control of movements including inter-
segmental control. They are individually made moulded appliances and
restrict flexion, extension, lateral bending, as well as rotation and, the weight
of the head is relieved from the cervical spine.
Thoraco-Lumbar Orthoses
•• It consists of two posterior paraspinal uprights extending up to the
interscapular region.
•• Uprights are attached to the full front abdominal corset.
•• An interscapular band holds the uprights and serves as an attachment
for axillary straps, which pass under the axilla coming over the shoulder
and attached to the upper end of the uprights posteriorly with the help of
a buckle or Velcro fasteners.
•• It controls flexion and extension of the thoraco-lumbar spine, but does not
prevent lateral flexion and rotation.
Lumbo-Sacral Orthoses (LSO)
•• Lumbo-sacral flexion and extension control orthosis (LSO)
•• Lumbo-sacral flexion, extension and lateral control orthosis (LSO).
Thoraco-Lumbo-Sacral Orthoses
•• Thoraco-lumbo-sacral flexion-extension control orthosis (TLSO) (Taylor):
•• Jewett’s Orthosis
•• Anterior spinal hyperextension orthosis
•• Thoraco-lumbo-sacral flexion-extension and lateral control orthosis (TLSO)
(Knight-Taylor)
•• Thoraco-lumbo-sacral flexion, lateral and rotary control orthosis (TLSO)
(Cow Horn).
Cervical Thoraco-Lumbo-Sacral Orthoses
•• This is a commonly prescribed orthoses for the management of spinal
deformities.
•• This can correct the curves up to 40−45 degrees during the growth period.
•• However, this is contraindicated where bony maturity has been completed.
Milwaukee Orthosis (CTLSO): It is a posteriorly open orthosis used to
control and correct spinal curvatures like scoliosis and lordosis. It is like an
exoskeleton and consists of a pelvic girdle, head support, one anterior and
two posterior uprights and corrective pads.
MECHANISM OF ACTION
•• All spinal orthoses produce three basic effects:
–– Reduce trunk movements
–– Improve skeletal alignment
–– Increase intra-cavity pressure.
APPLICATIONS OF ORTHOTICS
•• Low back pain
•• Spinal deformities: Scoliosis, kyphosis, lordosis
•• Spinal surgery: Pre-operative and post-operative, disc surgery without
fusion
1576
•• Fractures
•• Inflammatory spinal arthritis
•• Juvenile spinal osteochondritis (Scheuermann’s disease)
•• Infectious disorders of spine: Osteomyelitis and tuberculosis
•• Tumours of the spine
•• Paralytic disorders: Poliomyelitis and dystrophies involving the trunk
•• Paraplegia
•• Spina bifida
•• Spondylolisthesis: Congenital (Developmental) spondylolisthesis and
degenerative spondylolisthesis
•• Cervical conditions: Sprains, torticolis, cervical spondylosis and cervical
spondylitis, fracture dislocation.
POSITIVE EFFECTS OF SPINAL ORTHOSES

•• There are three positive effects of spinal orthosis:
–– Trunk support
–– Motion control
–– Realignment.
NEGATIVE EFFECTS OF SPINAL ORTHOSES

•• Weakness and atropy
•• Contracture
•• Psychological dependence
•• Aggravation of symptoms.
RECENT ADVANCES
•• With the advent of newer materials, plastic is now replacing the metallic
frame of the orthosis.
•• There also have been improvements in reinforcing these orthosis with
glass fibre or carbon fibre.
•• Carbon fibre reinforced spinal orthoses are rigid and as strong as steel.
•• The plastic moulded frames are pre-fabricated and provide adequate
support even if they are flexible. Their flexibility is useful and can take the
shape of the contours of the body.
•• Pneumatic cervical spinal orthosis is also a new concept where the orthosis
is inflated after wrapping it around the neck and is considered to be more
useful in transporting patients with a cervical spine injury.
209
CHAPTER Principles of
Physiotherapy
Sangeetha Ranganath
INTRODUCTION
•• Neuroplasticity is the ability of the nervous system to modify its structural
and functional organisation post-injury or surgery.
•• Collateral sprouting of new synaptic connections, unmasking of previously
redundant pathways and release from inhibition facilitate reorganisation
of cortical maps.
•• This may account for considerable recovery as this plasticity can be
influenced by proper external stimuli.
•• During learning, the brain records patterns of synaptic connections that
define an event or object, related events, the body’s exploration of the
environment, the body’s reaction to the event, etc. in both “motor and
perceptual schemas”.
•• Physiotherapy administered to patients can be divided into two parts:
1. Physiotherapy in intensive care
2. Functional rehabilitation.
PHYSIOTHERAPY IN INTENSIVE CARE

•• Physiotherapy should be seen as an integral part of the multidisciplinary
team in the intensive care unit (ICU).
•• Care has to be taken while administering physiotherapy for the intubated
patient.
•• The haemodynamic and metabolic status of the patient has to be carefully
monitored.
•• There can be an increase in the heart rate, blood pressure, intracranial
pressure, increased oxygen consumption, increased carbon dioxide output,
etc. as part of an exercise like response and an increased sympathetic
output during multimodality physiotherapy.
Treatment Techniques
•• An important component of physiotherapy in the ICU deals with respiration.
•• This entails: Positioning—includes side lying, postural drainage, getting
the patient upright, etc.
•• All this helps to increase lung volumes and reduce the work of breathing;
enhances mucociliary clearance, especially if the respiratory system is
depressed.
•• Percussion and vibration: Manually vibrating, clapping, shaking or
compressing the chest wall during expiration is believed to increase the
clearance of airway secretions.
1578
•• Suction: To remove secretions by suctioning if a tracheostomy has been

done for the patient.
•• Manual hyperventilation: Manual hyperventilation is used to prevent
pulmonary collapse, improve oxygenation and lung compliance and
increase movement of secretions towards the central airways, in patients
on the ventilator or with a tracheostomy.
•• Mobilisation and limb exercises: Can be passive, active assisted, or active
depending on the level of sensorium of the patient. It would include limb
exercises, turning, sitting up, standing, transfer from bed to chair, etc.
FUNCTIONAL REHABILITATION
Sensory Stimulation and Arousal Therapy
•• This should begin as soon as the patient is medically stable. Various
sensory modalities can be used like auditory, tactile, visual, olfactory, etc.
•• Auditory stimuli like familiar family voices and names, music, ringing bells
and so on.
•• Visual stimuli like family photographs, flash cards, bright colours, etc.
•• Olfactory stimuli like fragrances, coffee and food.
•• Taste of swabs of familiar flavours, sugar, salt, etc.
•• Tactile stimuli like temperature (warm and cold), touch (feel of different
fabrics), pressure, etc.
•• The neurological therapist has to deal with various perceptual, cognitive
and behavioural issues.
•• After a good sensory and motor assessment (can use motor assessment
scale, or stroke rehabilitation assessment of movement) the next step is
to move on to motor training.
•• There are many theories of motor control and motor recovery. Hence, there
are various approaches to motor training, like the neurodevelopmental
theory, motor relearning model by Carr and Shepherd that the neurotherapist
can use.
•• The activities can be broken down into various components starting with
activities in bed, grasping, reaching out, segmental rolling and attempting
to sit.
•• The therapist can then progress to sitting balance, active trunk control,
weight bearing on arms and activities while sitting. The next step is to train
the patient in standing (with full support if needed), balance and walking.
Constraint Induced Therapy

•• It is found that over a period of time patients develop a learnt non-use of
the affected limb in addition to the deficit that they have.
•• So strapping the normal arm for example, for several hours during the day
enables, or rather forces the patient to attempt the use of his affected arm
for various activities. This has found to produce good results.
Soft Tissue Flexibility

•• Alteration in tone or spasticity does have its role in causing motor
dysfunction.
•• It is typical for paralysed limbs to remain motionless for long periods of
time in one position.
Chapter 209 • Principles of Physiotherapy
1579
•• This causes changes in the properties of muscle fibres and connective

tissues. Muscles persistently held in the shortened position develop length-
associated changes.
•• The clinical resistance to passive stretch is now considered to be due to a
reduced compliance of muscles.
•• Hence, it is critical to start early task oriented mobilisation to maintain a
sufficiently flexible musculoskeletal system.
•• There has been an attempt here to point out a growing shift in rehabilitative
strategies, from passive movements and exercises in bed to a more
dynamic approach involving activities of daily living.
•• Hence, rehabilitation should be planned to maximise regaining of motor
competence and integrate the patient back into his environment as early
as possible.
Index
Page numbers followed by ‘f ’ and ‘t’ indicate figures and tables respectively.
A Acidophil stem cell adenoma 909, 910,

913, 1113
Abbreviated injury score 334t
ACoA syndrome 599
Abdominal
Acoustic neuroma 8, 10, 1294
auras 1489
Acoustic Schwannomas
discomfort 970, 987
clinical features 1189
disease 784
raised intracranial pressure
extension 777
headache 1191
fat 313, 1116, 1117, 1244, 1275
papilloedema 1191
injury 389
vestibular 1189
mass 1315
differential diagnosis 1194
muscle 335, 742
epidemiology 1186
organs 737
investigations
pain 257, 401
reflexes 742 imaging 1193
regions 760, 1226 neuro-otological workup 1191
sepsis 439 management
striae 1104 fractionated stereotactic
surgeon 391 radiotherapy 1203
trauma 303 observation 1195
visceral 1433 radiosurgery 1202
wall 298, 593, 1344, 1349, 1506 suboccipital, translabyrinthine
Abducens palsy 974, 997, 1247 approach 1198
Ablative segmental endoscopy 1198
peripheral proceduress 1507 facial nerve preservation 1200
closed procedures 1507 hearing preservation 1202
neurotomy (neurectomy, post-operative
fasciculotomy) 1507 complications 1198
open procedures 1508 subtemporal transtentorial
peripheral nerve blocks 1507 approach 1198
rhizotomy 1509 management surgery 1196
specific indications, selection criteria middle fossa approach 1196
and goals 1508 retrolabyrinthine approach
results 1197
complications 1509 retromastoid suboccipital
negative side effects 1509 approach 1197
positive side effects 1508 transcanal approach 1198
Abrasion types of translabyrinthine approach
age of 264 1197
contact 264 pathology 1188
crushing 264 Acquired immunodeficiency syndrome
friction 264 clinical features 530
grazes 264 neurological manifestations 531
impact abrasions 264 pathogenesis 529
imprint 264 Acrocephaly 139
pressure abrasions 264 ACTH
scratches 264 dependent 1106
Accessory neurenteric canal (ANC) 149 independent 1106
Acetazolamide challenge test 173 secreting carcinoma 1148
1582
Activated microglia secrete cytokines 528 Alpha fetoprotein 143, 942, 1150
Acute disseminated encephalomyelitis Alpha-fetoprotein 1082
92, 93 Alzheimer’s disease 1406
Acute instability 355, 355t American Spinal Injury Association 374,
Acute lung injury 545 386
Acute pain following amputation 1440 Ammon’s Horn 1487
Acute respiratory distress syndrome 545 Amniotic cavity 101, 103f
Acute spinal injuries Amygdala 1405
assessment 332 Amygdalae and stria terminalis 1397
clinical evaluation 333 Amygdalohippocampectomy 1493
emergency management 332 Amygdalo-hypothalamic influences 1399
evaluation 333 Amygdalotomy 1404
medical 345 Amyloid neuropathy 426
pharmacologic 345 Anaesthesia
surgery 347 choice 1521
triage 333 considerations 815, 1525
Acute subdural haematomas history 1522
aetiopathogenesis 270 physical examination 1522
clinical spectrum 271 premedication 1522
imaging features 271 preoperative evaluation 1522
surgical management 272 Anaplastic
Adamantinomatous 914 astrocytoma 866, 1040, 1067
Adamkiewicz 705 ependymoma 866
Adenohypophysis 906 ganglioglioma 866
Adenomas of haemangiopericytoma 868
Cushing’s disease 910 oligoastrocytoma 866, 1067
Nelson’s syndrome 910 oligodendroglioma 866
Adenomas producing growth hormone 909 Aneuploid tumours 887
Adenomatous polyposis coli 876 Aneurysmal
Adenovirus 12 877 bone cyst 751, 787
Adjuvant therapies for malignant brain sac 617, 633, 644, 650
tumours 1065 SAH 633
Adrenocorticotropic hormone cell 904, subarachnoid haemorrhage 600,
910, 1147 1526
Advanced Aneurysms
spondylosis with myelopathy 7 basilar apex 622
trauma life support 332 carotico-ophthalmic 587
Aerodigestive tract 299 carotid bifurcation 622
Afferent stimulation for abolition of pain cavernous internal carotid artery 622
1437 communicating artery 614, 621, 622,
Ageing changes 793 624, 627, 635, 636, 644
Agenesis of corpus callosum 115 development 633
Aicardi syndrome 953 distribution 635
AIDS in the eighth and ninth decade 553
biopsy 536 middle cerebral artery 622
dementia complex 534 ophthalmic segment 622
encephalopathy 534 risk factors 633
Aihara (1998) classification of lumbosacral shape 617
dislocation 394t siphon or transitional 588
Alar ligament 359f superior hypophyseal 587
Albendazole 502 ventral or posterior wall 587
Ale-Brown obsessive compulsive score vessel 617
1405 with severe vasospasm 647
Allergic rhinitis 310 Angiocentric glioma 866, 992
Alloplastic hydroxyapatite 301 Angiofibroma 1162
Alloplastic metal 301 Angiogenesis 913
Alloplastic polymethylmethacrylate 301 Angioglioma 991
Index
1583
Angiographically occult pre-operative evaluation 1327

arteriovenous malformations 659 surgical anatomy 1327
vascular malformation 682, 692 spinal arteries 564
Angiolipoma 781 spinal axis 705
Angiosarcoma 868 supracallosal fibres 1402
Angular movement 215 Anterolateral cordotomy 1433
Angulated endoscope 1571 Anteroposterior view 338
Animal tissues 316f Anthrax meningoencephalitis 91
Ankylosing spondylosis 372 Antibiotic therapy 640
Annulus fibrosus 790 Antibiotics 320
Annulus fibrosus 790 Anticonvulsants 320
Anterior Antidiuretic hormone 250
annular tear 381f Antidiuretic hormone (ADH) deficiencies
arch of C1 359f 1166
cerebral Antidiuretic hormone 1132t
artery 548, 591, 597, 606 Antioxidants 581
discectomy complications 802 Antiseptics for preparation of the skin and
discectomy with fusion 802 hands alcohol
surgery complications 815 ethyl or isopropyl (60–90%) 1535
choroidal 592 chlorhexidine gluconate (4%) 1535
communicating artery disadvantage 1535
aneurysms 596 iodine compounds including tincture
aetiology 596 iodine (iodine and alcohol)
approaches 602 1535
blister-like 604 iodophors (solutions such as povidone
clinical features 598 iodine) 1535
complications 605 Antley-Bixler syndrome 139
fusiform 604 Apanese Orthopaedic Association 810
giant 604 Apert syndrome 139
incidence 596 Apical ligament of dens 359f
investigations 600 Apoptosis 564, 913
kissing 605 Apparent diffusion coefficient 85, 796,
management 601 1178
pre-operative measures 602 Aqueduct
side of approach 603 stenosis 158
surgical technique 602 reconstruction complications 166
complex microsurgical anatomy Arachnoid cyst 780
597 Arachnoid cysts 127, 1165
cord syndrome 336 Arachnoiditis 459, 707
cranial base reconstruction 1351 Arbeitsgemeinschaft Für osteosynthese
cranial fossa floor 1352 fragen 385
encephalocoeles 125, 126 Arginine vasopressin 1128
inferior cerebellar artery 615, 1451 Arterial
interhemispheric fissure 549 embolisation 704
ischaemic optic neuropathy 973 hypertension 545
longitudinal ligament 353, 359f, 792 stenosis 639
marginal tear 326 Arteriovenous
perforated substance 608 fistula 701
skull base transfacial transmaxillary malformation 538, 615, 634, 652
approaches to Articular pillar fracture 381f
anaesthesia 1328 Artificial disc technology 829
bilateral 1330 Ascending reticular activating system 1414
classification 1328 Aspergillosis 519
combined 1330 Aspergillus infection 94
complications 1332 Astroblastoma 866
indications 1326 Astrocytomas
lateral 1329 aetiology 994
medial 1328 anaplastic 999
1584
classification 991 midbrain implants 37

clinical features 963, 996 system 30, 31
desmoplastic infantile 992 Autonomic
duration 996 dysfunction 768
gemistocytic 993 nervous system 1412
grading 991 system management 344
histological variants 992 Autosomal dominant polycystic kidney
histopathology 963 disease 547
investigations 998 AVM nidus 657, 658, 665, 668, 670
low-grade 998 Avulsion of epiphyseal plate 381f
microscopic pathology 992 Axial controlled traction 377
neuroimaging 963 Axis (C-2) fractures 340
pathogenesis 994 Axonal neuropathy 1
pathology gross 990 Axonotmetic grades 422
pilocytic 992 Axoplasmic membrane 225f
pilomyxoid 993
prognosis 1006 B
progression 996 B cell markers 942
protoplasmic 992 Bacterial meningitis 438
recurrences Bailey-Badgley technique 803
clinical features 1007 Balloon
imaging 1007 remodelling catheters 649
treatment 1007 test occlusion 588, 623, 643, 649
spread 991 Band heterotopias 117
subependymal giant cell 992 Barbiturates 576
treatment 1000 Basal ganglia 503
uncommon presentations 998 Basic neurosurgical instruments 1538-
carotid atherosclerosis study 722 1552
dural arteriovenous fistula 676 Basilar artery 614
Ataxia telangiectasia 1229 Basolateral limbic circuit 1403
Atlantoaxial Batson’s plexus 1055
dislocation 342 Beck depression inventory 1405
rotatory instability 342 Beevor’s sign 335
Atlanto-dens instability 342 Bell’s
Atlantodental interval 364 cruciate paralysis syndrome 336
Atlas fractures palsy 525
classification 363, 363f Bending moment 351
clinical presentation 363 Benign
diagnosis 363 intracranial
treatment 364 hypertension 1299, 1300, 1301t
Atrial natriuretic peptide 253 tension 1299-1302
Atypical melanocytomas 1294
adenoma 912 tumours 1307
choroids plexus papilloma 866 chondroma 1308
CPP 954 giant cell 1308
papilloma 952 haemangiomas 1307
teratoid/rhabdoid tumour 867 osteoclastoma 1308
Auditory osteoma 1307
brainstem Benzel point system 355f
implant 36 B-human chorionic gonadotrophin 1082
surgery 36 Bicoronal synostosis 139
contraindications to ABI 37 Bifrontal decompressive craniectomy 284
indications for 35 Bilaminar embryonic disc 101f
lateral suboccipital approach 36 Bilateral
middle cranial fossa 36 acoustic neurofibromas 1204
pre-operative evaluation 36 amygdalotomy 1405
trans-labyrinthine approach 36 facet dislocations 374
Index
1585
lesions of the nucleus tractus solitarius metastasis 925

1459 natriuretic peptide 253, 561
Binasal hemianopia 26 oedema following trauma 934
Bioactive coils 650 plasticity 658
Biochemical swelling 200
changes 794 tumour
terminology 349 advanced neuroimaging of
testing anaplastic oligodendroglioma 71
methods 351 choriocarcinoma 71
dynamic 351 diffusion
static 351 tensor imaging 73
Biomechanics weighted imaging 73
axial traction 356 ependymoma 71
future 358 functional magnetic resonance
bone grafts 357 imaging 73
cord injury 357 glioblastoma multiforme 71
spinal implants 357 ipsilateral subarachnoid space 71
spine deformity 357 perfusion imaging 72
trauma 357 spectroscopy 72
Bipolar stem cells 996
electrical stimulation mapping 50 susceptibility weighted imaging
neurons 402 74
Bischloroethylnitrosourea 1005 vascular malformations 652
Blood Brainstem
flow imaging 50 auditory evoked potentials 7, 46, 1265
oxygen level dependent 69, 217 classification 1016
supply 791, 1089 clinical features 1020
Blood–brain barrier gliomas
anatomy 929 management of diffuse tumours
cell cycle 1066f 1023
chemotherapeutic agents 1066t mapping of the cranial nerve
drug-drug interaction 1065 nuclei 1022
tumour pathology
heterogeneity 1065 cystic tumours 1020
resistance 1066 diffuse 1018
Bolus method 174 exophytic tumours 1020
Bone focal 1018
defects reconstruction 1346 management 1021
dust 1348 neuroradiology 1021
grafts 804 tectal plate gliomas 1020
morphogenic protein 98, 807 haemangioblastomas 1284
Bone-marrow derived stem cells 1409 injury 271
Bony anomalies 178 surgical approaches 1022
Brachial plexus injuries 416 Broad spectrum antibiotics 400
Brachycephaly 139, 1005 Bromocriptine therapy 1118
Bragg-peak 1396 Bromodeoxyuridine 897
Brain Brown Sequard syndrome 336
abscess Burrholes 279
develops 437
microbiology 439 C
and leptomeninges 712 Cabergoline 1096, 1101
and spinal cord 101 Cable nerve graft 424
aquaporins 931 Calcific stages 88
damage 292 Calcified stage 89
derived neurotrophic factor 408 Calcitonin gene related
effects 970 peptide 1411
injury mechanism 317 polypeptide 1417
1586
Calcium malformation 781

channel blockers 568 sinus surgery 642
entry blockers 578 Cell
classification 578 adenoma 909
mechanism of protection 579 based therapy 795
Calculation of Evans ratio 171f lineage identifying 940t
Caldwell view 304 prolactin 909
Caloric response 204, 246 proliferation markers 942
Calvarial surface antigens 942
growth 137 Cellular
reconstruction 269 differentiation 111
Canadian C-spine 334 migration 111
Candidiasis 93, 520 multiplication 111
Cap splint 305 organisation 111
Capillary telangiectasia 690 Central nervous system lymphomas 918
management 691 Central cell body 402
Capsule formation 440 Central cord syndrome 337
Carbamezapine 1455 Central effector neurons 402
Carbon dioxide 1514 Central neurocytoma 964, 965
Carcinoembryonic antigen 894, 942 Cerebellar astrocytic tumours histological
Cardiac subtypes of 1011t
bypass 619 Cerebellar astrocytoma
disorder 640 clinical presentation 1012
output 545 incidence 1010
Cardiogenic pulmonary oedema 545 management 1013
Cardiopulmonary resuscitation (CPR) 229 neuroradiology 1012
Cardiovascular effects 657 pathology
Care in the ICU 239 gross pathology 1010
Carotico-cavernous fistula (CCF) 642, histological types 1011
1355 malignant astrocytomas 1011
Carotico-ophthalmic aneurysms 548 microscopic pathology 1010
Carotid prognosis 1015
angiography 318 surgery
arteries 1091 adjuvant therapies 1015
circulation aneurysms 650 approach 1014
cavernous sinus fistula choosing the surgical
anatomy of arteries 693 approach according to
anatomy of veins 694 the location of 1014
classification 694 complications 1014
investigations 696 goal 1014
prognosis and complications 699 tumour excision 1014
symptoms and signs 695 tumour biology 1011
treatment Cerebellar
endovascular therapy 697 dysfunction 1200
radiosurgery 698 injury 221
surgical approaches 698 liponeurocytoma 866
Carotidynia 719 Cerebellopontine angle 971, 1174, 1187,
Carpal tunnel syndrome 9, 10 1219
Carpenter syndrome 139 Cerebral spinal fluid 152, 1147
Cartesian co-ordinate system 349 Cerebritis 84
Casoni’s intradermal skin test 501 Cerebrospinal fluid
Cauda equina syndrome 337, 836 absorption pathways 152, 174
Causes of drainage 572
brain damage 197t examination 921
congenital malformations 112t leak 1270
Cavernomas of the brain 682-687 markers 1000
Cavernous opening pressure 173
angioma of cavernous sinus 1160 opening pressure measurement 173
Index
1587
otorrhoea 313 Cervicocephalic syndrome 381

production 152 Chamberlain’s line 58
rhinorrhoea Chediak-Higashi syndrome 918
diagnosis 310 Chemical carcinogens 878
investigations Chemonucleolysis 828
computerised tomography Chemosis and Bruit 1355
scan 311 Chiari malformation 165
magnetic resonance imaging Chiari malformation 182, 183, 185, 186,
311 187, 188, 189
radionuclide cisternography Chiasmal injury 330, 331
311 Childhood craniopharyngiomas 1172
leakage of 309 Chloroethyl-cyclohexyl-nitrosourea 1005
pathophysiology 309 Choline compounds 1078
treatment 312 Chondromyxoid fibroma 736
indications for surgery 312 Chondrosarcoma 753
extracranial approach 313 Chordoid glioma of the third vertical 866
intracranial approach 312 Chordomas 1151, 1152
operative technique 312 Choreoathetosis 1497, 1557
conditions 1576 Chorionic gonadotropin 1114
curvature index 812 Choristomas of the sellar region 1155
disc disease 797, 801, 801 Choroid plexus
disc herniation 434 aetiology 952
flexure 105 carcinoma 866, 952, 955
internal carotid artery 647 clinical features 953
laminectomy 806 differential diagnosis 955
myelopathy 799t incidence 952
myeloradiculopathy 6 macroscopy 954
ossification papilloma 866, 952
aetiopathogenesis 807 papillomas 1294
clinical presentation 810 pathology 954
cytokines 807 prognosis 955
growth factors 807 site 952
incidence 807 tumours
management 811 clinical course 1077
natural history 810 investigations 1077
outcome 816 treatment 1078
pathogenesis 808 WHO classification 1079t
pathology 807 Choroidal arteries 614, 653
prevalence 807 Chromogranin 942
treatment Chromosomal locus 633
conservative 812 Chromosome 19q 1033
operative 812 Chromosomes 1p 1033
radiculopathy 799t Chronic cerebellar stimulation dentate
spine nuclei 1507
acceleration injury 381f Chronic di/siadh 1132
fusion 803 Chronic implantation 1367
injury 398 Chronic regional pain syndrome 1422
posterior approach 806 Chronic stump 1440
radiographs 382 Cingulate gyrus 1397, 1402
spondylosis Cingulotomy 1402
anterior approach 802 Cingulumotomy 1436
clinical features 797 Circumferential
diagnosis 797 tears 793
imaging evaluation 799 wrapping 589
medical management 801 Cisternal form of NCC 89
surgical management 801 Cisternography 311
vertebrae 352 Cladosporium 512
1588
Classical lissencephaly 114 incidence 1071

Classification of incidental colloid cyst 1071
Bilateral investigations 1073
beals and joganic 1331 location 1072
extended transfacial subcranial neuroendoscopic treatment of 1075
approach 1331 pathology 1072
facial degloving 1331 regional embryology of third ventricle
facial translocation 1330 1071
lateral treatment 1074
combined medial and inferior Colloidal stage 89
extended facial translocation Combination fractures of c1-c2 342
1330 Commissural agenesis 110
combined medial extended facial Commissural myelotomy 1434
translocation 1330 Complex craniofacial deformities 139
extended osteoplastic maxillotomy Complex repetitive discharges 4
1329 Complex tentorial meningioma
standard facial translocation 1329 basal approches to tentorial
total maxillectomy 1329 meningiomas 1256
medial maxillectomy 1328
cerebellopontine angle meningioma
medial mini-facial translocation 1329
1256
head injuries 193t
parasellar and cavernous meningioma
Clip alone 589
1256
Clipping debate 601
petroclival meningioma 1256
Clival chordomas 1322, 1323
pineal meningioma 1256
Closed-lip (type i) schizencephaly 115
Compound muscle action potential 1, 46
Cloverleaf 139
Concept of instability 388
Cloward technique 803
Concussion brain 215
Cns malformations 111
Concussion grading scales 218t
Cns tumours 940t
Concussive wave 397
Cobblestone lissencephaly 114
Condylar fractures 362
Cochlear implant
Congestive heart failure 545
complications of 35
Connective tissue disorders 616
components 34
Consumption
contraindications surgery of 34
selection criteria 34 coagulopathy develops 270
steps of surgery rate of oxygen 233
cochleostomy 35 Contact injuries 193
incision 35 Contemporary endovascular treatment
insertion of electrode array 35 647
posterior tympanotomy 35 Continuous intracranial pressure
simple mastoidectomy 35 monitoring 174
well for receiver-stimulator 35 Contralateral hemiparesis 271
Cognition Contrast-enhanced magnetic resonance
deficits 170 venography 1238
dysfunction 997 Contrecoup contusions 194
impairment 169 Controlled continuous lumbar drainage
Coiling debate 601 174
Colles’ fracture 426 Contusion
Colloid cyst age of 264
clinical features 1072 contrecoup 197
differential diagnosis coup 197
intraventricular extra-axial lesions fracture 197
1074 gliding 197
intraventricular intra-axial lesions herniation 197
1074 index 197
lesions with basal origin but third Conus medullaris syndrome 337
ventricular extension 1074 Convection enhanced delivery 1009
Index
1589
Conventional nerve 334, nerve 339

angiography 601 deficit 642
radiology neuropathies 642, 1199
caldwell view 54 tumours 944, 967
craniostenosis 57 vault tumours
fronto-occipital view 54 anatomical considerations 1304
increased vascularity 55 classification 1304
intracranial calcification 54 diagnostic evaluation
localised areas of bony erosion or cerebral angiography 1306
sclerosis 55 computed tomography 1305
plain x-ray of the skull 53 magnetic resonance imaging
posteroanterior view 54 1306
raised intracranial pressure 56 plain skull films 1305
submento-vertical view 54 vault tumours management
Towne’s view 54 chemotherapy 1307
Convexity cysts 132 operative treatment 1306
Convexity meningiomas radiation therapy 1306
anterior 1232 anomalies 297
clinical features 1232 deformities
differential diagnosis 1234 classification 138
imaging history 137
angiography 1233 radiology 140
computed tomography 1233 terminology 138
electroencephalogram 1233 Craniofacial dysostosis 57
magnetic resonance 1233 Craniopharyngioma
x-rays 1233 clinical features 1165
incidence 1231 imaging 1166
location 1231 incidence 1165
median 1232 management 1168
posterior 1232 other treatment modalities 1170
surgical management pathology 1164
complications 1234 pre-operative evaluation 1168
postoperative care 1234 surgical management
preoperative protocol 1234 associated hydrocephalus 1168
prognosis 1235 complications 1170
recurrence 1235 operative approaches 1168
scalp incision 1234 radiotherapy 1170
Convexity meningiomas temporal 1232 Craniopharyngioma treatment 1167
Cord Craniopharyngiomas 59, 1143
compression pathophysiology of 736 Cranioplasty
lesions in closed injury 211 aetiology of the cranial defect 297
Coronary stent grafts 650 alloplastic material 300
Cortical neurons 402 anatomy of the defect 298
Corticosteroids response 1290 choice of material for 299
Cortico-striato-thalamic pathways 1403 critical size of defect 298
Cortico-striato-thalamocortical circuitry fixation 301
1400 importance of adequate skin cover
Corticotropin releasing hormone 40, 1102 299
Cosman-Roberts-Wells material 297
system 1367 need for reconstruction 298
frame 1558 preservation of autografts 298
Costen’s syndrome 1455 timing of reconstruction 299
Cramp discharges 4 Craniosynostosis 140, 141
Cranial Craniotomy and fenestration 134
arteries 562 Craniovertebral junction
irradiation classification 179, 182, 208
acute reactions 1057 clinical features 360
adverse reactions 1057 clinical symptomatology 180
1590
embryological anatomy 178 Debris 1348

injuries 359 Decerebrate posture 248
surgical anatomy 359 Decompression and spinal fusion 837
surgical management 181, 187 Decompression and timing of surgery 389
syndromic abnormalities 179 Decompressive craniectomy 242
trauma 367 Deep brain stimulation 447, 1436, 1437
Craniovertebral junction trauma surgical Deep hypothermia 583
procedures 367 Deep hypothermia systemic effects 583
Creutzfeldt-Jakob disease 92, 525 Deep vein thrombosis 348
Cribriform plate of the ethmoid 309 Degenerative disc disease
Crista galli 1237 aetiology 795
Crouzon syndrome 139 clinical features 823
Crouzon’s disease 57 signs 824
Cryosurgery of bone 229 symptoms 823
Cryptic 692 differential diagnosis 824
Cryptic arteriovenous malformations 692 investigations 824
Cryptococcal meningitis 1055 computerised tomography 825
Cryptococcosis 519 discography 825
Cryptococcus neoformans 93 electromyogram 826
CSF magnetic resonance imaging 825
drainage 242 myelography 824
otorrhoea 247 nerve conduction 826
pathways 968 radiographs of the lumbar spine
tap test 175 824
Cubital tunnel 429 management
Current guidelines for inph diagnosis 175 conservative management 827
Cushing’s microdiscectomy 827
disease aetiopathology 1102 minimally invasive spinal surgery
syndrome 827
classification 1103t options for a patient 826
clinical features 1103, 1104t pathophysiology of 822
confirmation 1105 Delayed
diagnostic evaluation 1106 cerebral ischaemia 559
magnetic resonance imaging 1106 ischaemic neurological deficits 563
management 1107 neurological deficit 637
Cutaneous ectoderm 101 neurological deterioration 401
Cyberknife 672 Demyelinating neuropathy 1
Cyclin dependant kinases (CDK) 874 Denis three column theory 356
Cyst aspiration 1170 Depth electrode recordings 1559
Cystic vestibular schwannoma 1203 Derivatives of the cranial neural crest 106t
Cysticercal Dermal sinus 151
meningitis 492 Dermatome 96f
vasculitis 492 Dermoids 1178-1181
Cysticercosis 490-498 Dermomyotome 96f
Cysts and haematomas aspiration 1366 Desmoplastic infantile
Cytokinetic studies 994 astrocytoma 866, 963
Cytological examination 231 ganglioglioma 963
Cytomegalovirus (CMV) 527 Detachable
Cytosine deaminase gene 888 balloons 619
Cytotoxic oedema 83, 932 platinum coils 648
Developing
D myotome 97f
Dandy Walker neural tube 95f
syndrome 158 Development of the
malformation 165 basal and alar lamina of the spinal
de Morsier syndrome 115 cord 108f
Deafferentation pain syndromes 1438 brain vesicles 105f
Index
1591
caudal spinal cord 107f surgical considerations 607

central nervous system 101 treatment 610
meninges 108 trans-sylvian 610
notochord 102 Diuretics 579
skull 99 DNA analysis 912
somite 95f DOI procedures 420
spinal cord 107 Dolichocephaly 138
three primary brain vesicles 105f Dolicocephalic 57
vertebra 97f Doll’s head ocular movement 246
vertebral column 95 Dopamine agonists 1101
Dexamethasone suppression test 1105 Dorsal
Diabetes insipidus 221, 321, 600, 1117, column stimulation 1431, 1438
1132t root entry zone 1415, 1430, 1432
Diabetes mellitus 426, 454 root ganglion 1412
Diagnosis of SIADH and CSW 240t Dorsolateral posterior synaptic pathway
Diaphragma sella 1090 1415
Diencephalic syndrome 1140-1143 Dorsolateral tract of lissauer 1414
Diencephalon 1140 Dorsomedial nucleus 1403
Diffuse Dorsomedial part 96f
astrocytoma 866 Down’s syndrome 994, 1080
axonal injury 202t Drain cerebrospinal fluid 228f
brain Drosophila melanogaster 98
damage 199 Dura mater 968
injury 224 Dural and soft tissue defects reconstruction
hypoxic 224 1349
idiopathic skeletal hyperostosis 371 Dural arteriovenous 700-701
large B cell lymphoma 920 Dynamic
melanocytic neoplasms fusion 805
contraindications 1298 imaging 339
indications 1298 testing 29, 30
parenchymal injury 222 Dysembryoplastic neuroepithelial tumour
swelling 200, 224 765, 766
vascular injury 199, 224 Dysfunction
weighted images 444, 451 frontal lobe 980
Disc disease 790 parietal lobe 980
Disc regeneration 795 Dysplastic gangliocytoma of cerebellum
Diseases 866, 962
acute pancreatitis 229 Dystonia
connective tissue disease 635 indications for surgical treatment of
diabetes 230 1388
fatty liver 230 results 1388
immunosuppression 230 surgical options in 1388
Raynaud’s disease 427
sickle cell anaemia 229 E
sickle cell disease 635 Early brain injury 562
smoking 635 Ebstein-Barr virus 1287
Dislocation injuries 374 Echinococcosis 510
Disorder congenital disorders 635 Ectodermal cells 1174
Disorders of the peripheral nerves 6 Ectopic acth syndrome 1106
Dissecting aneurysms 649 Edically refractory temporal lobe epilepsy
Distal non-invasive protocol for the evaluation
aneurysms 619, 638, 639 of patients with 1488
anterior cerebral artery aneurysm surgical techniques for the treatment
anatomy 608 of 1491
clinical characteristics 606 Edinburgh concept 1515
clinical features 608 Ehlers-Danlos syndrome 547
investigations 607, 609 Elbow flexion test 430
1592
Electrocorticography replacement therapy 1120

advantages of 12 Endocrinological symptoms 323, 600
major limitations of 12 Endoderm 103f
Electrodiagnosis 1 Endogenous analgesic system 1417
lectrodiagnostic findings 5, 6 Endoscopic
Electroencephalography applications 11 assisted microneurosurgery 135
Electromyography 2, 418, 800 assisted surgery for skull base lesions
Electrophysiological 1571
evaluation 413 controlled microneurosurgery 135
testing 31, 32 fenestrations of intracranial cysts
Elements of stereotaxis 1569
applications 1557 fibreoptic 162
brain in a geometric system 1556 in brain tumour surgery image-guided
frame-based systems 1558 endoscopy 1567
frameless stereotaxy 1560, 1561 instruments 1566
reference points 1556 interlaminar decompression 837
stereotactic biopsy 1559 management of brain tumours 1566
stereotactic frame 1556 neuroendoscopic biopsy 1569
Elevated arm stress test 434 neurosurgery 135
Embolisation of spinal vascular optic nerve decompression 330
malformations pituitary surgery 1570
classification of 705 resection of intraventricular tumours
clinical presentation 707 1569
investigations 708, 709 rigid 162
treatment 710 surgery colloid cyst 1569
vascular supply of the spinal cord 705 third ventriculostomy 163, 1566
Embryonic ventricular tumours and cysts
disc 102f management of 1568
period 110 ventriculoscopy 1568
Empty sella syndrome 916, 1134 Endothelial
Empyema 86 damage 621, 638
Encephalitic form 92 nitric oxide 570
Encephalocoeles Endothelin 570
anterior 122 Endovascular
associated clinical features 123 aneurysm treatment 649
associated pathology 121 coil occlusion 631
classification 120 coiling 647
clinical presentation 121 management 619, 620, 641
embryology 119 obliteration 619
incidence 119 treatment 589, 595
investigations 123 treatment 631, 647
management 124 Endplate spikes 3
prognosis 126 Energy transfer 315
systemic abnormalities 121f Enkephalin 1374
Encephalo-duro-arterio-synangiosis 725 Entrapment
Encephalo-omental-synangiosis 725 neuropathies 425
Encephlomyosynangiosis 725 neuropathy 425
End plates 790, 791 Environmental factors role 996
Endochondral ossification 137 Enzyme-linked immunosorbent assay
Endocrinal abnormalities (ELISA) tests 38, 467
pathogenesis 322 Eosinophilic granuloma 750, 787
screening 321 Ependymoglial precursor cell 1038
investigations 323 Ependymoma 1037-1040
Endocrine Epidermal growth factor 935
assessment 1143 Epidermoid and dermoid cysts 775
evaluation 1105 Epidermoid
manifestations 1166 cysts 1165
Index
1593
clinical features 1176 Epithelial cysts 1165

complications 1178 Epithelial membrane antigen 894, 942
incidence 1175 Epstein-barr virus 878
location Epstein-barr virus (EBV) 526
cranial-extradural 1175 ErbB2 receptor inhibitor 1048
extracranial 1175 Erlotinib (TM) 888
intracranial-intradural 1175 Essential hypertension 1459
pathogenesis 1174 Esthesioneuroblastoma 1163
pathology 1175 Ethyl nitrosourea 878
radiological findings Etomidate 578
computed tomography scan 1177 Evans
magnetic resonance imaging flagpole concept 356
1177 index 171
treatment 1178 Ewing’s sarcoma 754, 787, 868
Epidural empyema 86 Excalation of the notochord 102, 103f
Epilepsy Excessive activation 573
basic mechanisms of epileptogenesis Excitatory amino acid receptors 573
1462 Excitotoxic antagonists 581
classification of seizures and epilepsies
Exitatory amino acids 205
1464
Extension injuries 343, 374
commonly used AEDS 1471
External carotid 555
special clinical situations 1473
Extracellular
steps management 1471
fluid 250
surgery for
matrix 547
awake craniotomy 1480
space 928
candidates for pre-surgical
metastases 991
evaluation 1476
Extracranial
complications seizure outcome
intracranial bypass 589
1486
cortical stimulation mapping 1479 shunts 155
definitions 1475 Extradural
electrocorticography 1480 haematoma
functional magnetic resonance clinical presentation 275
imaging 1478 diagnosis 275
surgical procedures epidemiology 274
central resections 1482 management 276
corpus callosotomy 1484 pathophysiology 274
cortical resections 1482 haemorrhage 238
deep brain stimulation 1485 tumours 786
frontal lobe resections 1482 Extramedullary myeloid cell tumour 922
hemispherectomy 1483 Extraventricular neurocytoma 866, 964
lesionectomy 1481 Eye movements 246
multilobar resections 1483
multiple subpial transections F
1484 Fabry’s disease 1230
neurostimulation 1485 Facet
parietal and occipital resections dislocation injuries 377
1482 joints 353
radiosurgery 1484 Facial nerve motor evoked potentials 48
stereotactic surgery 1485 Facial nerve Schwannomas
vagal nerve stimulation 1485 clinical presentation 1220
syndromes 1475 diagnosis 1220
vagus nerve stimulation 1470 management 1220
video-EEG telemetry 1467 surgical approach 1221
seizure 997 Facial trauma series 304
Epileptogenic focus 656 Factors modulating primary brain injury 196t
Epiphyseal surface 381f Fahlbusch 1121
1594
False distribution of 848

aneurysms 642 estimations bone
localising signs 989 biopsy 852
Falx meningiomas 1237 fluoride 852
Familial aneurysms 634 radiology of 852
Fascicular microsuture technique 415 scintigraphic studies 852
Fasciculation potentials 3 serum fluoride 852
Fasciculations 738 urine fluoride 851
Fat and free muscle 1349 excretion of
Fat embolism 202, 229, 230, 232 faeces 848
Fatigue or cyclic load tests 351 sweat 848
Fibrillary astrocytoma 1026 urinary 848
Fibrillation potentials 3 laboratory investigations
Fibroblast growth factor receptor 99, 137 laboratory investigations
Fibrosed nerve segments 413 electrophysiological studies 851
Fibrous fluoride estimations 851
cone 1457 general 851
dysplasia 1163 magnetic resonance imaging 853
compact form 1163 metabolism of
lytic form 1163 sources of fluoride 847
pseudo pagetoid 1163 total daily fluoride intake 847
Fielding and hawkins classification 342 pathology of
First functional muscle transfer 421 gross changes in the skeleton 853
Fisher grading system 562 histopathology of bones 853
Fixation 301 prevention of
Flash visual evoked potential 328 endemic fluorosis 853
Flavi virus 527 industrial fluorosis 854
Flexion sources of
compression injuries 343, 373 air 847
distraction injuries 343 foods 847
extension views 376 water and beverages 847
injuries 343, 373 treatment of
Flexures of the brain 104 medical therapy 854
Flip angle or tip angle 64 surgical 854
Flow modification techniques 619 Focal brain injury 196
Flow-limiting valves 176 Focal brain stimulation 1438
Fluid and electrolyte balance in head injury Focal cortical dysplasia 117
basic physiopathological facts 251 Focal neurological
general considerations 250 deficits 231
hypernatraemia 260 dysfunction 997
hyponatraemia 256 Focal radiotherapy 1291
main clinicopathological categories Focal vasospasm 636
254 Foetal period 110
Fluid attenuated inversion recovery 67, Foix-alajouanine syndrome 707
591 Follicle stimulating hormone 904, 1114
Fluid therapy 254 Food and drug administration 528
Fluid-attenuated inversion recovery 84, Foot drop 432t
1489 Foramen magnum
Flunarizine 579 meningiomas surgical approaches
Fluorescence-guided resection 50 extended endoscopic endonasal
Fluorosis approaches to skull base 1276
absorption of 847 posterior 1273
clinical features 848 posterolateral 1273
dental fluorosis 849 radiosurgery 1276
pre-skeletal stage 849 suboccipital approach 1273
skeletal fluorosis 849 the extreme lateral transcondylar
computed tomography 853 approach 1275
Index
1595
transpharyngeal approach 1274 balance 168

tumours Galactorrhoea-amenorrhoea syndrome
neurophysiological monitoring 1094
1272 Galen aneurysmal malformation 677
general peri-operative clinical Galen malformation 681
evaluation 1272 imaging of the brain 678
Foraminal stenosis 837 imaging of the cerebral vasculature
Foraminotomy 806 678
Forbes-Albright syndrome 1094 systemic effects associated with the
Formation of the malformation 678
cervical and cephalic flexures 105f Galveston orientation and amnesia test
neural groove 103f 289
neural tube 103 Gamma
neurenteric canal 103f knife radiosurgery advantages of
notochordal process 103f 1395
pontine flexure 105f commonly recommended dose
Foster Kennedy syndrome 1240, 1246 prescriptions 1393
Four-dimensional computed tomography complications and side effects
angiography 550 1396
Fourth ventricular outlet obstruction 165 current uses 1395
Fracture of dose selection 1392
apophyseal joint 381f dose-volume histogram 1392
burst 378 medical physics 1391
laminar 378 platforms delivering stereotactic
lateral mass 377 radiosurgery 1396
management 378 procedure 1393
Frameless stereotactic neuronavigation 50 radiation tolerance limits 1393
Free fatty acids 230 radiobiology 1392
Free radical specific steps 1394
release sources 576f functional disorders
scavengers 569, 581 movement disorders and epilepsy
Frontal surgery 1395
horn ratio 171 trigeminal neuralgia 1395
lobe injury 220, 1435 radiation changes
Fronto-hypothalamic fibres 1399 acute 1392
Functional chronic 1392
free muscle transfer 420 subacute 1392
MRI (fMRI) techniques 113 Gangliocytoma
organisation of the basal ganglia and histopathology 962
other pathways sellar region 1155
direct pathway 1377 Ganglioglioma
indirect pathway 1377 histopathology 961
outcome assessment 378 prognosis 962
rehabilitation treatment 962
constraint induced therapy 1578 Gardner’s syndrome 1307
sensory stimulation and arousal Gasserion ganglion 1457
therapy 1578 Gastrulation 101
soft tissue flexibility 1578 GDC coils 620
scores in spinal cord disease 745 Gefitinib 1048
tumours 1129 Gelfoam 1332, 1349
Fungal infections 512-517 Gene for familial cavernous malformations
Furosemide 580 683
Fusiform aneurysm 554, 555, 621 Gene therapy 795, 1070
Genetic
G abnormalities 995
Gait instability 876
abnormality 170 Geniculate neuralgia 1453
1596
Geniculocalcarine pathways 24 Glioblastoma multiforme 999

Genotyping of brain tumours 1035 Gliofibroma 993
Geriatric spine injuries 347 Gliomas
Germ cell tumours growth factors 874
choriocarcinoma 868 location 990
clinical features 1150 low-grade
embryonal carcinoma 868 biopsy 1004
germinoma 868 observation 1003
mixed germ cell tumour 868 resection 1004
pathology 1150 molecular pathogenesis of 872
radiological features 1150 surgery 1003
teratoma 868 Gliomatosis cerebri 866, 994
treatment 1151 Gliosarcoma 994
yolk sac tumour 868 Gliotic reaction 683
Germinomas 1165 Glomus jugulare tumour 1263
GH-secreting carcinoma 1148 Glossopharyngeal neuralgia
Giant epidemiology 1450
aneurysms 616, 617, 618, 620, 621, examination 1451
622, 624, 628, 632, 649, 651 causes 1450
bed capillaries 654 diagnosis 1451
cell treatment
glioblastoma 993 medical management 1451
granuloma surgical management
behaviour 916 complications 1453
clinical features 916 microvascular decompression
differential diagnosis 916 1452
gross 916 nerve root section 1452
microscopic features 916 other ablative procedures
tumour 736, 750, 1161 1452
invasive pituitary adenomas Glycoprotein adenomas 910
clinical presentation 1122 Goel and Laheri/Harms and melcher
extension 1121 fixation 369
invasion 1121 Goldenberg 1397
investigation 1122 Gonadotroph cell adenomas 910, 1113
molecular biology 1122 Gonadotropin-releasing hormone 1155
cytokine interleukin 6 1122 Gradient echo imaging 66
heat shock protein-27 1122 Graft
invasive pituitary adenomas failure 646
1122 problems 645
matrix metalloproteinase-9 Granular cell tumour 915, 1149
1122 Granular nodular 88, 89
nuclear antigen Ki-67 1122 Growth hormone
p53 gene 1122 cell adenomas 1113
proliferative marker MIB-1 clinical features 1098
1122 deficiency 321
protein kinase c alpha-isoform disorders 1098
1122 insulin-induced hypoglycaemia: 40
invasive pituitary adenomas medical treatment 1100
radiation 1124 oral glucose tolerance test 40
treatment 1123 pathogenesis 1098
posterior circulation aneurysms 620 receptor antagonists 1101
Gigli saw 300 releasing hormone 1098
Gillies 307 releasing hormone 909
Glasgow coma scale 235t, 283, 303 secreting adenomas 1098
Glial fibrillary acidic protein 129, 903, 941, surgery 1100
961, 992 systemic changes 1099
Gliding contusions 197, 219 treatment 1100
Index
1597
TRH test 40 Headache 970

Guidelines for intubation 234t Health professionals risks 536
Guillain-Barré syndrome (GBS) 524 Hemiatrophy” of the skull 57
Gunning splint 305 Hemiballismus 1557
Gunshot wounds 412 Hemifacial spasm
Gustatory and olfactory auras 1489 anatomy of the facial nerve 1459
cerebellopontine angle 1459
H selection of patients 1459
H1N1 virus 526 surgical technique 1459
Habenular nuclei 1397 Hemispheric AVMS 653
Habenulointerpeduncular tract 1397 Hereditary
Haemangioblastomas 702 haemorrhagic telangiectasia
Haemangioma 751 diagnosis 691
Haemangiopericytoma genetic counselling 692
age and gender 898 genetics 691
cytogenetics and molecular genetics treatment 691
901 syndromes 994
definition and grading 898 Herniated thoracic discs 819
genetic susceptibility 901 Herniation 988
gross and microscopic features 898 Herpes simplex 1 encephalitis 91
immunohistochemistry 898 Herpes simplex encephalitis (HSE) virus
incidence 898 523
location 898 Heterotopias 117
treatment and prognosis 901 High
Haematogenous metastasis 1314 dose dexamethasone suppression
Haematological test 1106
effects 657 intensity zones 795
malignancies 922 performance liquid chromatography
Haematoma 1199 1105
Haematopoietic system 1409 velocity missile injuries 315
Haemodilution 568, 584 Higher functions disturbance 974
Haemodynamic Highly active antiretroviral therapy 532
arteriovenous malformation 657 Highly active antiretroviral therapy 918
factors 655, 662 High-velocity missiles 400
Haemolytic anaemias 54 Hippocampus 1397
Haemorrhagic necrosis 226 Histiocytosis x 1160
Haemosiderin-Laden macrophages 683 Histogenesis of the neural tube 105
Hamartomas of the HIV
sellar region 1155 diagnosis 535
tuber cinereum 1143 myelopathy 534
Hamilton anxiety rating scale 1405 positive and high-risk patients 537
Hand automatisms 1489 Hodgkin’s lymphoma 922
Hand-Schuller-Christian syndrome 54 Holdsworth two column theory 355
Hangman’s fracture 366 Holoprosencephaly 114
Hard tissue replacement 301 Homeobox genes 98
Head injuries Homer-Wright Rosettes 884
biomechanics 192 Hopkin’s verbal language test 1406
clinical assessment 244 Hormonal assessment 323t
complications and sequelae of Hormonal factors 878
clinical profile and evaluation 290 Hormones 942
evaluation of 289 Hox codes 98
pathophysiology 289 Hox genes 98
post-concussionsyndrome 289 Human
post-traumatic amnesia 288 chorionic gonadotrophin 942, 1082,
treatment 291 1133, 1150
patient 244, 250 cytomegalovirus 996
Head Tilt−Chin lift 233 embryonic stem cells 1409
1598
herpes virus 8 1287 Hyperplasia

immunodeficiency virus 918 corticotroph 917
menopausal gonadotrophin 1133 gonadotroph 917
neurocysticercosis 90 growth hormone cell 917
placental lactogen 942 prolactin cell 917
prion protein 92 thyrotroph 917
tibial nerve 404t Hypertension 584
Humeroulnar aponeurotic arcade 429 Hypertensive crisis 1453
Hunterian ligation 618 Hypertoxic state 1495
Huntington’s disease 1374 Hypertrophied ligamentum flavum 836
Huw Griffith of bristol 1566 Hyperventilation 583
Hyalinised parasitic membranes 492 Hypervolaemia 568, 584
Hydatid disease cerebral echinococcosis Hypnotics, drugs and medications 1518-
499-502 1520
Hydrocephalic extracellular oedema 934 Hypoblast 102
Hydrocephalus Hypocortisolism tests for morning plasma
aetiology 153, 167 cortisol level 41
approach 161 Hyponatraemia
arrested 159 head injury patients 258
causes 492t hyposmotic 257
classification 153 maintenance of maintenance of volume
clinical features 154, 470 aetiopathogenesis 256
criteria for diagnosis 168 hyperosmotic 257
diagnosis 171 isosmotic 257
embryology 152 management 259
endoscopic state differential diagnosis 1130
management 161 Hypophysectomy 1436
treatment 156 Hypopituitarism
ex-vacuo 160 clinical signs 322
guiding devices 163 in traumatic brain injury 323
incidence 167 symptoms 322
instrumentation 162 treatment 324
investigations 154, 470 Hypothalamic
computerised tomography 471 damage 221
magnetic resonance imaging 471 dysfunction 204
management 155 hamartomas
multiloculated 159, 166 clinical features 1155
normal pressure 159, 167 pathology 1155
pathophysiology 153 radiological features 1156
special types 157 hamartomas treatment 1156
stabilisation 163 injury 221
treatment 472 optic nerve gliomas
Hydrocephaly 114 approaches for chiasmal
Hydrostatic oedema 933 hypothalamic glioma 1030
Hydrostatic pulsations 638 clinical features 1027
Hypaxial muscles 97f clinical features
Hyperextension injuries 209 hypothalamic dysfunction
Hyperimmunoglobulin m syndrome 1287 1027
Hyperkinesis 1405 proptosis 1027
Hypernatraemia symptoms of increased
aetiopathogenesis 260 intracranial pressure
clinical manifestations 1028
diagnostic tests 261 visual dysfunction 1027
management 261 incidence 1024
diabetes insipidus 260 indications for surgery 1029
differential diagnosis 260 investigations 1028
Hyperparathyroidism 54
management 1028
Index
1599
chemotherapy 1030 Induced hypotension

for suspected chiasmatic/ agents 585
hypothalamic glioma 1031 complications 585
for suspected intraorbital optic relative contraindications 585
nerve glioma 1031 Infantile
observation 1029 hemiplegics 1500
radiotherapy 1030 presentation 1300
surgery 1029 Infected cranial flaps 297
pathology macroscopic Infective origin intracranial aneurysms
appearance 1024, 1026 629, 630, 634, 638, 647
prognosis 1030 Inferier cerebral artery 608
pituitary-adrenal axis 1102 Inferior colliculus central nucleus 37
Hypothalamotomy 1402, 1435 Inferior petrosal sinus sampling 1106
Hypothalamus physiology 1399 Inhalational agents 1517
Hypothermia 582 Injuries in
Hypothermia mechanism of protection 582 neonates 236
Hypothermic circulatory arrest 619, 626 toddlers 236
Hypovolaemia 252 Injury severity score 333, 334t
Hypovolaemic shock 398 Insertional activity 2
Instantaneous axis of rotation 350
I Instrumented
Iatrogenic injuries 412 fixation for thoracic and lumbar
Immediate hormonal replacement 321 fractures 391t
Immunocompetent individuals fusion 804
chemotherapy 1292 Insulin tolerance test 323
corticosteroids 1291 Integrated operating room 1537
radiotherapy 1292 Intensity modulated radiation therapy
surgery 1291 1170, 1245
Immunodeficiency status 878 Intensive care
Immunoglobulins 942 analgesia 1528
Immunohistochemical markers 940t haemodynamic management
Immunohistochemistry 947, 955, 1114 hypertension 1528
Immunoreactivity 941t hypotension 1529
Immunotherapy classification of mechanical ventilation 1528
antibody-guided therapy 1070 sedation 1528
causes for immunosuppressive state Intercalation of notochord 103t
1069t Intercarotid lines 1123f
cellular mechanism 1069 Interference signs 975
immunotherapeutics agents 1069 Interlaminar clamps 368
mechanism of immune response Intermedullary tumours 788
1068 Intermuscular septum 484
vaccination 1070 Internal auditory canal 1220
Impedance of flow offered 174 Internal carotid
Impulse control disorders 1398 artery 591
In vitro testing 351 bifurcation aneurysms 591
Incidental anatomy 592
aneurysms 632 complications 595
intracranial aneurysms 629 pre-operative evaluation 593
Increased intracranial pressure 1299, Internal microarchitecture 409f
1354 International standards for neurological
Increased systemic blood pressure 712 classification of spinal cord
Increased venous resistance 167 injury 386
Indian shunt systems 156 Interpretation of visual field terminologies
Indocyanine green 20
angiography 593 Intersegmental artery 97f
chorioangiography 611 Interstitial fluid pressure increase 168
1600
Interventional neurosurgery 571 tumours, clinical features 967

Intervertebral disc physiology 792 vascular malformation 667
Intra-arterial digital subtraction angiography Intracystic instillation 1173
550 Intradisc electrothermal coagulation 828
Intracanalicular meningiomas 1266 Intradural extramedullary tumours 761, 788
Intracavernous Intramedullary
aneurysms 642 abscess 453
carotid artery 1454 gliomas 782
Intracavitary haematoma 397
bleomycin injection 1171 metastases 772
irradiation 1171 tumours
Intracellular imaging 768
calcium accumulation 573 investigations 768
space 928 management 769
Intracerebral pain 767
haematoma 279, 282, 591, 609 post-operative complications
haemorrhage 198, 549 management 773
Intracranial pre-operative management 769
rationale of treatment 769
arachnoid cysts 127-129
surgical management 769
anatomy 127
surgical steps 771
embryology 127
symptoms 767
natural history 129
Intramembranous ossification 137
pathology 128
Intranidal aneurysm 656
aneurysms
Intra-operative
diagnosis 548
monitoring
endovascular treatment 619, 627,
bipolar and monopolar electrical
629, 632, 640, 641, 644, 647,
stimulation 46
648, 650 brainstem-auditory evoked
general principles 547 potential 46
genetics 547 Doppler ultrasonography and
in children 552 ultrasound angiography 49,
location 551 611
management 547, 551 magnetic resonance imaging in
pathogenesis 554 neurosurgery 51
post-operative management 557 motor evoked potential 47
treatment 553 MRI 1537
arteries or cranial nerves 1246 neurophysiological monitoring 48
components 13 rupture 593
cysts 130 Intraosseous abscesses 479
management 133 Intraparenchymal catheters 13
manifestations 130 Intrasellar
radiology 132 choristomas 1156
haemorrhage 197, 198 factors 1135
herniations 936 lesion 56
infections 84 Intra-sylvian haematoma 609
lesions management 535 Intravascular volume depletion 545
melanomas 1294 Intraventricular
neurostimulation for pain control 1436 cysts 492
pressure monitoring 17, 18 haemorrhage 549
schwannomas 1219 meningiomas 1278
shunts using tubes 155 surgical management 1279
tuberculomas clinical features 462, NCC 89
463 Intrinsic lesions of the brainstem 986
tuberculomas pathology 460, 461 Invasive
tuberculomas treatment adenoma 911
multi-drug resistant tuberculosis cervical carcinoma 531
464 oncospheres 489
surgical treatment 465 Irregular aneurysm contour 636
Index
1601
Ischaemic brain damage 200 Larmor frequency 64

Ischaemic injury 224 Lars leksell 1404
Ischaemic lesions 231 Lasègue’s sign 834
Isoflurane 578 Late graft occlusion 646
Isolated familial somatotropinomas 1098 Lateral
Isotope studies 124 geniculate body 19
lenticulostriate arteries 593
J skull base 1333, 1334
Jackson-Weiss syndrome 139 selection of approaches 1338-
Japanese encephalitis 527,92 1340
Jaw thrust technique 233 surgical approaches to
JC virus 877 anterior
JE vaccine 528 medullary lesions 1338
Judicial use of electrocautery 1332 subtemporal 1334
Jugular foramen lesions 1210-1213 basal extension of lateral
pathological lesions around the jugular subtemporal craniotomy
foramen 1211t 1336
pathology 1211 extended middle fossa
post-operative complications 1217 approach 1336
related syndromes 1212 ganglion 1337
surgical approaches 1213, 1217 infratemporal fossa interdural
Jugular fossa schwannomas classification 1337
1222t involving
Junghans motion segment 350 mobilisation of the facial
Juvenile nerve 1336
pilocytic astocytoma 1142 sacrifice of hearing 1335
spinal osteochondritis 1576 preserving hearing 1335
presigmoid 1337
K retrosigmoid 1337
Kaposi sarcoma 868, 531 supracondylar infrajugular
Karnofsky scale 661 bulb keyhole 1338
Katzman test 174 transcondylar transclival 1338
Kawase approach 1208, 1335 transtemporal 1335
Kernohan’s notch 200, 248, 275, 1032 surgical considerations 1333,
Kinetic energy 315 1334, 1335
Kleeblattschadel deformity 139 Lead toxicity 401
Klinefelter’s syndrome 1080 Left ventricular dysfunction 545
Klippel-trenaunay-weber syndrome 1230 Leksell
Knight zygoma classification 307 G frame 1559
Knight-taylor 1575 Gamma Knife™ 1391
Knobloch syndrome 123 apparatus technique using the 1367
Knosp-steiner classification 1123 Leontiasis ossea 56
Korean modification 1406 Leprosy surgery 484-487
Kreider 298 Lesion
Kyphoplasty 862 basal ganglia 981
Kyphosis 350, 480 bright on diffusion images 68
cerebellar hemisphere 985
L chemical 1365
Lacerations cold 1365
split 265 corpus callosum 980
stretch 265 cryogenic 1365
Lambdoid synostosis 139 electrolytic 1365
Laminotomy or laminectomy 836 mechanical 1366
Lamotrigine 1407 midbrain 983
Landau-kleffener syndrome 1493 middle cranial fossa 981
Langerhan’s cell histiocytosis 1160 midline brain 982
Lanreotide 1100 near the falx 979
1602
occipital lobe 979 Lymphocytic hypophysitis

parasellar 982 gross 916
posterior midline 984 microscopic features 916
temporary 1365 pathology 1158
Letterer-Siew disease 54 radiographic features 916
Leucaemia 1315 radiological features 1158
Leukocytic pleocytosis 455 treatment 916, 1159
Lhermitte’s sign 738 Lymphoid markers 942
Lhermitte-duclos disease 962 Lymphoma 1315, 756
Life cycle and spinal implantation 505 Lymphomas 918-920
Li-fraumeni syndrome 953, 876 Lymphoplasmocytic-rich mesenchymal
Ligament tumours 892
anterior longitudinal 354 Lyophilised dura 1349
capsular 354
interspinous 354 M
posterior longitudinal 354 Macroscopic appearances 128
supraspinous 354 Magnetic resonance
Ligamentum flavum 354, 838, 359f angiography 550, 601, 568, 592
Ligature and clip 589 contrast-enhanced 68
Light microscopic features 129 cerebrospinal fluid flow studies 172
Limited surgery plus irradiation 1172 diffusion 1000
Linear accelerator 1170, 672 imaging 133, 154, 172, 339, 352, 376,
Lipid peroxidation 575
382, 387, 567, 600, 601, 143,
sources 576f
811, 817, 1220, 1288, 84,
Lipidised glioblastoma 1011
1167, 623
Lipoarabinomannon 467
contrast safety 67
Lipoma 778, 1162, 767, 772
echo time 65
Lissencephaly 114
free induction decay 64
Lobar and higher cognitive functions
instrumentation magnet 65, 66
assessment 980
lattice 64
Local
longitudinal or t1 relaxation 64
flaps 268, 269
newer advanced technique
functions 975
diffusion-weighted imaging 68
Localised melanocytic neoplasms 1294
functional imaging 68
Loh-10 875
magnetic resonance
Long tract deficits 1269
spectroscopy 69
Longitudinal myelotomy 1511
physical principles of 63
Loss of
radiofrequency field 64
fluid and electrolytes 254
repetition time 65
heterozygosity 995, 1033
slice orientation 65
Louis theory 355
Low and high velocity missiles 316f spin-lattice relaxation 64
Lower T2 relaxation or spin-spin
cervical spine syndrome 381 relaxation 64
cranial nerve Schwannomas 1221, perfusion 1000
1223 spectroscopy 1078, 443, 69
Lumbar tomography 361
and lumbosacral injuries 393, 395 Magnetisation transfer ratios 86, 172
canal stenosis 831-835 Major arteries 969
degenerative disc disease 821 Major basal ganglia pathways connections
puncture 169, 542, 591 1375, 1376
SA to lumbar epidural 156 Major criteria 90
vertebrae 352 Making the lesion methods 1365
Lumbosacral radiculopathies 425 Malabsorption syndrome 531
Lund concept 1515 Malformation of cortical development 111
Lundberg’s CSF pressure waves 14f Mallampati grade sampson and young’s
Luteinising hormone releasing factor 1155, modification 1522t
904, 1114 Mammillary bodies 1397
Index
1603
Mammosomatotroph cell adenoma 909, gross pathology 893

1113 hormone receptors 897
Management of disorders of sodium immunohistochemistry 896
concentration 1529 microscopy maningoma 894-896
Manifestations 1227 molecular genetics 896
Mannitol 579 neoplasms related to the meninges
Margerison and corsellis 1487 896
Mass lesions and paresis 503 primary melanocytic lesions 896
Materials used for fusion 804 proliferation 897
Matrix metalloproteinases 792 radiological features 893
Maxillofacial injuries recurrent 897
clinical evaluation of facial injuries site 893
303 Meningitis 86, 533
fracture of the mandible 304, 305 Meningohypophyseal trunk 693
fractures of the zygoma 306 Meningomyelocoele 158
general principles 303 Meralgia paraesthetica 435
imaging 304 Mesencephalon 1140
maxillary fractures 305 Mesenchymal
nasal fractures 307 stem cells 830
Maximise antibiotic benefit pre-operatively tumours 868
principles 1535 Mesial temporal sclerosis 1468
Mayfield’s head-holder 1538 Mesoblast 102
Mcconnell’s capsular arteries 694 Metabolic
Mccormick classification 745 brain disorders 69, 545
Mean arterial control 1513
blood pressure 317, 577 Metabolism 792
Mechanical load injury 795 Metastases 767
Meckel’s cave 1205, 1457 Metastatic
Medial abscess 439
lenticulostriate arteries 593 brain tumours 1050-1053
longitudinal fasciculus 204, 247 carcinoma 906
sphenoid wing or clinoidal meningiomas dissemination 456
1249 tumours 868, 923, 925, 1152
Median nerve entrapment 428 Methods of detection of cell proliferation on
Medullary and mesencephalic tractotomy tissue sections 942t
1434 Methotrexate based protocols 1293
Medulloblastoma 885, 867, 1076, 1048 Methyl methacrylate 301
melanocytic 885 Methylenetetrahydrofolate reductase 179
molecular genetics 1044 Methylprednisolone 345
newer chemotherapeutic agents 1048 Metopic synostosis 139
nodular 884 Meyer’s loop. 1493
pathology 1043 Microbiology of intramedullary spinal
prognostic factors 1045, 1046 abscesses 457t
radiation therapy 1047 Microcystic myelomalacia 212
risk stratification 887 Micro-drezotomy 1416
staging 1045 Microelectromechanical system 358, 1537
Medullomyoblastomas 885 Microencephaly 113
Megalencephaly 113 Microsurgical
Melanotic anatomy 606
elements 1294 drezotomy 1511
MPNST 867 Microtubule associated proteins 941
neuroectodermal tumour 1297 Microvascular decompression 1443, 1448,
Meningeal carcinomatosis 1054, 1055 1456, 1460
Meningeal melanocytoma 1294 Microvascular doppler 593
Meningioma 892, 893 Middle cerebral artery aneurysms 608,
factors associated with recurrence of 538, 548
765, 867, 897t, 1294 Middle fossa base 1351
1604
Midnight plasma cortisol 1106 N

Minerva jacket 346
N-acetyl aspartate 999, 1078
Mini-craniotomy approaches 612
Narcotics 1428
Minimal contralateral cerebellar signs 500
Nasoethmoid type 122
Minor criteria 90
Nasofrontal type 122
Missile
Naso-orbital type 122
crushes the tissue 397
Nasopharyngeal tumours 1313
injuries 397, 316-318
National
wounding physical effects 316
adult social care intelligence service
Mixed
389
demyelinative 1
institutes of health stroke scale 713
growth hormone 909
Navigation in spine surgery
neuronal glial tumours 960
clinical applications of 1565
prolactin cell-growth hormone cell
pitfalls of image guided surgery 1565
adenomas 1113
Neighbouring structures effect 1092, 1093
Modified Frankel scale 387t
Neonatal
Monitoring in ICU 239
adrenoleukodystrophy 116
Morning glory syndrome 123
intensive care unit 568
Motor
Nerve
cortex stimulation 1436, 1437
action potentials 412, 423, 435
evoked potential 612, 770, 788, 1003
conduction velocity 800
function 768
crossing 420
unit action potentials 4
damage in reactions
Movement disorders surgery 1384, 1385
nerve abscess 485, 486
Moyamoya 724
fibre 404
MRI scan 124
grafting 420
MSX genes 100 injury pathophysiology 410
MXS1 and MSX2 98 regeneration 410
Mucocoele 1159 sheath tumours 761, 765
Mucopolysaccharidoses 179 supply 791
Mucormycosis 521, 94 Nervous system
Mucosa-associated lymphoid tissue 919 metastatic tumours 918
Muenke syndrome 139 neoplasias 927
Multidisciplinary team in the intensive care trauma 207
unit 1577 tumours 939
Multilayer reconstruction 1351, 1352 Neural
Multipolar neuron 402, 403f control 354
Multisegmental innervation 738 crest 106f, 106
Musculature role 354 intrajugular compartment 1210
Mycobacterium response telemetry 35
avium complex 460 stem cells 214
tuberculosis 479 structures 178
infection 87 transplantation and stem cell 1408
Mycotic stimulation
abscesses 85 chronic cerebellar stimulation
aneurysms 638, 649 1507
infections 511 spinal cord (dorsal column,
Myeloma 1315 posterior column) stimulation
Myelomeningocoele 165 1506
Myofibroblasts 673 thalamic stimulation 1507
Myokemic discharges 3, 4 Neurectoderm 101
Myopathy 535 Neurenteric
Myotome 96f canal 102
Myxoid stroma 882 cyst 779
Myxopapillary ependymoma 866, 1041, Neurilemmomas 944
1042 Neurinomas 944
Index
1605
Neuroanatomy 586 plasticity 233

Neurobehavioural sequelae tumours 960
boxing injuries 293 Neuro-ophthalmology 19, 20
cognitive impairment 291, 292 Neuro-otology 28, 31
memory impairment 293 investigations for the auditory system
neuroses/neurotic disability 293 30
personality change 292 quantitative tests for vestibular
psychosis 292 function 27
Neuroblastoma 787, 1315 Neuropathic
Neurobrucellosis 90 pain syndromes 1437
Neurocutaneous types 1
angiomatosis 1225, 1229 Neurophysiologic
melanosis 1296 studies 800
Neurocysticercosis 88, 90 examination 418
Neurodegenerative disorders 69 Neurosurgery
Neurodevelopmental theory 1578 anaesthesia 1512
Neuroectodermal dysplasia 1305 auto-regulation 1513
Neuroendocrine markers 942 cranial procedures 1532, 1533
Neuroendocrinologic dysfunction 1048
operation theatre 1534, 1537
Neuroendocrinology
positioning 1531
adrenocorticotropic hormone and
spinal procedures 1533
cortisol 40
Neurosurgical
antidiuretic hormone 43
diseases 6
gonadotropins 42
operating room 1536
growth hormone 39
Mayfield frame 1536
thyroid 42
Sugita frame 1536
Neuroepithelial tissue tumours 866, 867
procedures general anaesthesia 1523
Neurofibroma 949
situations 1525
Neurofibromatosis
team 661
type 2 944, 1278
Neurotransmitter 574f
type i 876
Neurotrophic factors 408
Neurofilament proteins 961
Neurovascular entrapment 434
Neurogenic
Neurulation 104
bladder with conus 151
Neutral zone 356
Neurohypophyseal gliomas 1149
Nexus low risk criteria 334t
Neuroimaging 953, 960, 1082
Nicardipine 569, 579
Neuro-interventional procedures 1504
Nitric oxide synthase 562, 935
classification 1505
N-methyl-D-aspartate 574
Neurological
Nociceptive blink reflex 1446
presentations 535
Non-ablative procedures 1506
assessment 245
Non-functioning
deficit 657, 773
adenomas management 1117
examination 187, 235, 245, 246, 248
pituitary adenomas 1113
function 653, 1003
Non-Hodgkin’s lymphoma 531, 918, 922,
grading system 398t
1286
symptoms 639
Non-pharmacological therapies 582
Neuromas 944 Non-random chromosomal abnormalities
Neuromuscular 1521 886
junction 406, 410 Non-steroidal anti-inflammatory drug 747,
Neuromyotonic discharges 4 1425
Neuron specific enolase 903, 942, 965, Non-syndromic glioma 995
992 Norepinephrine levels 663
Neuronal Normotonic involuntary movements 1500
axon 409 Notochordal canal 102
cell damage 216 Nucleolar organiser regions 897
injury 574f Nucleus pulposus 790
1606
Nucleus Raphe Magnus 1417 Ommaya reservoir 1173

Nucleus tractus solitarius 1460 Oncocytomas 1114
Null cell adenomas 911, 1114 Oncofoetal
Numerical classification 405t markers 941, 942
Nurick proteins 940
scale of myelopathy 810t Oncogenes 913
grading for cervical myelopathy 745 Oncogenic viruses 876
Nutrition 792 Onyx 675
Oophorectomised women 840
O Open
Obsessive compulsive disorders 1398 spine 142
Obstructive hydrocephalus 163, 165 window corpectomy 815
Occipital Operating theatre
condyle fractures 340 general principles 1534
encephalocoele 125, 126 infection prevention 1534
neuralgia 1454 personnel pre-operative skin
Occipitocervical preparation
dislocation 339, 360f, 361 indications 1536
instability 361 Ophthalmodynamometry 720
lateral mass polyaxial rod 369 Optic
Occlusive hyperaemia 664 atrophy 974
Occupancy ratio 811 chiasm 1091
Octreotide 1100 nerve
Ocularmotor decompression 329
nerve function 246
paresis 1354 injury
palsy 204 anatomical considerations 325
Oculoplethysmography 720 injury 326, 327
Odom’s criteria of scoring 378t sheath decompression 1303
Odontoid neuropathy 1354
fractures radiations 24
treatment 366 arrangement of fibres in the
process 359f parietal lobe 25
fuses 178 temporal lobe 25
Oedema 934 tract and lateral geniculate body 24
Olfactory Optochiasmatic arachnoditis 492
groove meningioma 1240 Orbital
surgical management pseudotumour 696
complications tumours
cerebrospinal fluid leak and choice of operative approach (t)
infection 1242 1357
postoperative seizures 1242 clinical features 1353, 1357
vascular injury 1242 different
visual loss 1242 arteriovenous malformations
stimuli 1578 1361
Oligoastrocytoma 866 cavernous haemangioma
Oligodendrogliomas 1032-1034 1359
cytogenetic and molecular studies dermoid 1360
1033 epidermoid cysts 1360
gross morphological features fibrous dysplasia 1360
1032 intraorbital ophthalmic artery
immunohistochemistry 1033 aneurysms 1361
microscopic features 1033 lacrimal gland tumours 1360
ultrastructural features 1033 lymphangioma 1359
prognosis 1036 meningioma
radiology 1034 more diffuse dural
treatment 1034, 1035 involvement 1358
Index
1607
optic sheath 1358 treatment 859

orbital 1358 conservative management 861
metastatic tumours 1361 drug therapy for
mucocoele 1361 alendronate 860
neurofibroma 1357 bisphosphonates 860
optic nerve glioma 1359 calcitonin 860
osteoma 1360 ibandronate 860
pseudotumours 1362 raloxifene 860
vascular lesions 1361 risedronate 860
venous varix 1361 strontium 860
investigations 1355, 1356 teriparatide 860
management 1356 general measures 860
principles in the treatment of 1356 medical 859
surgical approaches 1357 Osteoporotic
Orbitofrontal cortex 1403 vertebral compression fracture 861,
Orbitopterional 602 862
Orbitozygomatic 602 compression fractures 863
Oro-alimentary automatisms 1489 spine 863, 864
Orthosis internal fixation 863t
applications of 1575 Osteosarcoma 752
basic functions of 1572 Other benign tumours
biomechanics aneurysmal bone cyst 1309
balanced horizontal forces 1572 benign osteoblastoma 1309
fluid compression 1573 calvarial lipomas 1309
motion of cervical, thoracic and cavernous haemangioma of the skull
lumbar spine 1572 1309
movements of the spine 1572 myxomas 1310
skeletal fixation 1573 ossifying fibromas 1309
sleeve principle 1573 osteoblastomas 1309
traction 1573 Otogenic abscess 438
nomenclature belts Outcome scores 348
corsets 1573 Oxycephaly 139
collar 1574 Oxygen
soft cervical collars 1574 extraction factor 565
sternal occipital mandibular -free radical
immobiliser 1574 scavengers 582f
thoraco-lumbar orthoses 1575 protective mechanism 576
Osler-weber-rendu (OWR) role 575
syndrome 1230
disease 691 P
Osmolarity of the ecf 252 Pachygyria 116
Osmoreceptors 252 Pachymeningitis 459
Osmotic oedema 933 Paediatric
Osseofibrous tunnel 484 head injuries 233
Ossification of neuroanaesthesia 1527
ligament flavum 816 spinal tumours 782
posterior longitudinal ligament spine injuries 347
classification 808 Paget’s disease 54
Osteoarticular tuberculosis 475 Pain
Osteoblastoma 749, 786 anatomy 1411
Osteogenic sarcoma 787 biostimulation 1424
Osteoid osteoma 748, 786 clinical correlates 1423
Osteolytic metastases 54 definitions 1411
Osteomyelitis 1316 gate control theory 1417
Osteophytosis 849 generation 1411
Osteoporosis 855, 856 grading
investigations 857, 858, 859 colour red analogue 1423
1608
standardise quantification Parenchymal damage 235

unidimensional scales 1423 Parietal spider 53
visual analogue scale 1423 Parinaud’s syndrome 880
peripheral nerve lesions 1419 Parkinson’s disease stereotaxy for
management 1425-1427 physiological basis of the target 1379
narcotics 1428 pre-operative work-up 1380
opioids in cancer 1428 selection of patients 1380
opioids spinal delivery 1429 Parkinsonian syndrome 527
peripheral nerve block 1429 Pasireotide 1100
medical treatment 1441 Pathogenesis of cyst expansion 128
models 1417 Pathological involution 1135
neuromatrix theory 1419 Patients with neurological deficits 389
neuropharmacology 1417 Pax genes 98
nociceptors 1412 Pedicle nerve graft 424
perception cerebral areas 1420 Pedicles 353
peripheral mechanisms 1441 Peduncular hallucinosis 1082
peripheral receptors 1411 Pedunculopontine nucleus 1375
phantom limb 1440 Penetrating injuries of the spine 397
related evoked potentials 1446 Perfluorochemical blood substitutes 581
root 1420 Perforating vessels 615
sensory nerve fibres 1412 Perfusion
surgical computed tomography scan 567
procedures 1430 flow pattern 663
treatment 1442 pressure breakthrough syndrome 664
syndromes with cancer 1442 Periaqueductal grey 1399, 1417
transmission 1411 Perilesional
treatment 1439, 1440 oedema 501
visceral 1412 swelling 282
Paired point registration 1564 Perimesencephalic subarachnoid
Pallidal stimulation haemorrhage 546
complications 1381 Perineurioma
discussion 1381 histopathology 950
Pallidotomy complications 1389 incidence 950
Pallidum develops 1374 localisation 950
Papaverine intra-arterial 571 predisposing factors 950
Papez circuit 1402 prognosis 951
Papillary Periodontal infection 438
craniopharyngioma 914 Persistent idiopathic facial pain 1453
glioneural tumour 961 Petechial haemorrhages 278
glioneuronal tumou 866 Petroclival meningiomas
tumour of the pineal region 867, 959 clinical features 1267
Papilloedema 936, 972 neuroradiological evaluation 1267
Paraclinoid operative details
aneurysms 586, 647 long-term disabilities 1270
classification 587 post-operative radiotherapy 1269
clinical presentation 588 surgical
special radiological considerations approaches 1269
588 complications 1269
therapeutic options 589 Petrous
internal carotid artery 586 bone 1176
Paraganglioma 866, 1162 temporal bone 1457
Parahippocampal gyrus 1397 Pfeiffer syndrome 139
Parasellar cyst 1135 Phakomatoses 1225
Parasitic infestations of the brain 503 Phalen’s test 427
Paraspinal cold abscess 479 Phantom
Paravertebral tumours 736 instruments 1368
Paraxial mesoderm 95f, 103f limb 1439
Index
1609
Pharmacological therapies 576 gland 1088

Pharmacology of anaesthetic drugs 1516 anatomy 1088
Pharmacotherapy 795 pathology 322t
Phenomena secondary 970 hyperplasia microscopic features 916
Phenylethanolamine n-methyl transferace medical treatment 1111
1460 other secreting adenomas 1109
Phenytoin 581 pathology 1109
Philadelphia collar 347 radiological diagnosis 1111
Physical status ASA classification 1522t therapy 1111
Physiological involution 1135 thyroid axis physiology 1109
Pigmented meningioma 1294 tumour
Pilocytic astrocytes 866, 872, 1010 ablation 1562
Pin site scalp infection 447 transforming gene 1095
Pineoblastoma 867, 958 differential diagnosis 906
Pituicytomas differential diagnosis 915 gross 904
Pituitary growth factors 913
abscess 1156 microscopic features 906
adenomas overview 1088
signs 1091
classification 1113
symptoms 1091
clinical
adrenal axis 1125, 1131
characteristics 907t
gonadal 1132
profile 1114
axis 1126
early post-operative evaluation
growth hormone axis 1133
1127
thyroid axis 1125, 1132
endocrine diagnosis 1115
Placental alkaline phosphatase 881,
follow-up 1117
942, 1083
imaging 1115
Plagiocephaly 57
invasion 911 Plain radiography 387
late post-operative evaluation Plain skiagrams 132
1131 Planum sphenoidale 310
malignancy 911 Plasmacytoma 754
management 1125 Platelet derived growth factor 935
markers of biological behaviour Pleomorphic xanthoastrocytoma 866,
912 993, 1011
pathogenesis 1134 Plexus lesion 6
pathological characteristics 907t Plurihormonal adenomas 911, 1114
pathology 1113 Pluripotent stem cells 1409
pre-operative Pneumocephalus 1199
assessment 1125 Pneumonia and pulmonary embolism 545
management 1126 Polyetheretherketone 358
radiation 1117 Polymerase chain reaction 921
surgery 1116 Polymicrogyria 116
treatment 1116 Polyneuritis 486
WHO classification 907t Polyvinyl alcohol 665, 670
adrenal insufficiency 1129 Pontine and midbrain haematomas 733
apoplexy 1118-1120 Pontine paramedian reticular formation
carcinoma 1147, 1148 247
clinical presentation 1109 Poppen’s suture 277
criteria of cure 1112 Positron emission tomography 113, 565,
dynamic testing 1110 568, 1148
dysfunction diagnosis 323t Posteroventromedial 1416
evaluation 1110 Postmeningitic 158
function Potassium titanyl phosphate 1567
assessment general principles Pott’s
1127 disease 478
function recovery 1117 spine 459
1610
Praziquantel 502 Propriospinal multisynaptic ascending

Preadmission spine immobilisation 333 system 1415
Prediction of rupture site 635 Proptosis 974, 1353
Premature craniosynostosis Prosencephalon 1140
aetiology 137 Proton attenuation 92
incidence 137 Proton magnetic resonance spectroscopy
pathogenesis 137 999
Pre-operative care general principles 1534 Protoscolicidal agents 502
Pressure of aneurysm 707 Provocative testing 324
Pre-synaptic Proximal
neurotransmitter 574f aneurysms 639
vesicular release 574f internal carotid artery occlusion 645
Preventive neurosurgery 572 trans-sylvian 610
tumours Pseudoarthrosis 480
benign Pseudo-hurler polydystrophy 427
aneurysmal bone cyst 1304 Pseudoxanthoma elasticum 547
cavernous haemangioma 1304 Psychiatric disorders 1400
chondroma 1304 Psychiatry
dermoid 1304 imaging in 1401
epidermoid 1304 indications for surgery 1401
giant cell tumour 1304 Psychological factors 1440
haemangioma 1304 Psychosurgery
lipoma 1304 amygdala
myxomas 1304 connections of 1398
osteoblastoma 1304 structure of the 1398
malignant amygdalotomy 1404
angiosarcoma 1304 anatomical considerations 1402
bone penetrating Marjolin’s ulcer anterior capsulotomy 1403
1304 cingulotomy 1402
carcinoma of the temporal bone concept of thalamocortical
1304 dysrhythmias 1398
chondrosarcoma 1304 dorsomedian thalamotomy 1404
chordoma 1304 limbic
Ewing’s sarcoma 1304 leucotomy 1404
fibrosarcoma 1304 system anatomy 1397
fibrous histiocytoma 1304 newer modalities of treatment in 1406
orbital rhabdomyosarcomas newer perspectives 1397
1304 nucleus accumbens 1399
osteogenic sarcoma 1304 outcome measurements in 1405
reticulum cell sarcoma 1304 procedures used in modern 1402
sweat gland tumour 1304 subcaudate tractotomy 1403
Primordial vascular plexus 653 transcranial magnetic stimulation
Prognostic markers 921 1406
Programmable valves 177 vagal nerve stimulation 1406
Progressive multifocal leucoencephalopathy Pterional 602
532 Punch-drunkenness 293
Prolactin Pupillary
adenomas 1118 abnormalities 1355
axis 1132 status 246
cell adenoma 909, 1113 Pyogenic
Prolactinomas brain abscesses 457
endocrinology 1094 infections 84
management 1095 ventriculitis 86
signs 1094
surgery 1097 Q
symptoms 1094 Quadrantic field defects 26
Proliferation markers 912 Quality of life 1487
Index
1611
Quantifying thoracolumbar instability 388f Rathke’s cleft cyst

ultrasonography 858 clinical presentation 1154
Quinagolide 1097, 1101 pathology 1153
Quincke 13 radiological features 1154
treatment 1154
R Rebleed prevention 545
Recurrent
Rabies disc herniation 829
encephalitis 92 glioma 1008t
virus 526 Reflex sympathetic dystrophy 1422
Radial Regional
fissures 793 cerebral
nerve entrapment 430 blood flow 283, 1000
Radiation metabolic rate of oxygen 568
effect of 877 oxygen extraction factor 565
radio frequency 877 signs 976
therapy Replanted scalp postoperative assessment
malignant brain tumours 1057 of
induced gliomas 994 clinical examination 269
oncology group 1292 Doppler 269
Radical fluorescein staining 269
cancer surgery 1002 impedance techniques 269
surgery 1169, 1172 thermocouples 269
Radicular pain 401, 454 transcutaneous oxygen measurements
Radiculopathy 6 269
Radiodiagnosis 811 Retained intracranial fragments 319
Radiographic abnormality 347 Retinaculum 484
Radiography 351 Retinal nerve fibre layer 1301
Radioimmunoassay 1105 Retinoblastoma (RB) gene and gliomas
Radiological 875
assessment 337 Retrograde amnesia 288
evaluation 622 Retrosigmoid intradural suprameatal
Radiology intracranial tumours approach 1265
advanced neuroimaging of brain Reye’s syndrome 524, 525
tumours 72 Rhabdoid tumour
approach to brain tumours 71 clinical features 889
histopathology 889
imaging modalities 70
imaging 889
post-surgical imaging 82
molecular genetics 889
radiation necrosis versus tumour
treatment and prognosis 889
recurrence 83
Rheumatoid arthritis 427, 1342
specific tumours 74
Rhiziditomy 1432
tumour-mimicking lesions 82
Rhizotomy
Radionecrosis 1008t
chemical 1432
Radiosurgery basic principles of
percutaneous radiofrequency 1432
conformity 1391
section 1431
selectivity 1391 selective 1432
Radiotherapy Rhombencephalon 1140
external 1004 Rigid fibrescope 163
risks 1005 Risk versus benefit 632
techniques stereotactic radiosurgery Root entry zone 1456, 1457
1058 Rosner concept 1515
Raised intracranial pressure Rostral ventrolateral medulla 1460
effects 968 Rotation with shear (C3) 385
management 320 Rupture of an intrasellar 1135
signs and symptoms 970 Ruptured aneurysms
Ramsay hunt syndrome 524 clinical features 548
Range of movement 350 management 555
1612
S gate control circuit 1418f

nerve
Saccular aneurysms 616, 617, 639, 656
action potential 1, 417, 418
Sacral
fibres 1412
fractures classification 394t
thalamus 1437
injuries 343
Septic
Sacrococcygeal teratoma 777
embolism 85
Saethre-chotzen syndrome 100, 139
intracranial aneurysms 639
Sagittal synostosis 138
Septum pellucidotomy 166
Salivary cortisol level determination 1106
Sequelae of
Sarcoidosis 1159
MIS 400
Saturday night palsy 431
spinal cord trauma 7
Scalp 268, 446
the disease 472
Scaphocephalic 57
Serum
Scheuermann’s disease 1576
markers 1000
Schiller-Duval bodies 881
osmolality and osmolarity 253
Schistosomiasis parasitology
prolactin 1126
S. haematobium 503
Severe spinal cord injury 372
S. japonicum 503
Shear injury 224f
S. mansoni 503
Shimizu reflex 741
Schistosomiasis route of involvement 503
Shunt
Schizencephaly 115
infection 157
Schizotypal disorders 1400
type 176
Schmorl’s nodes 857 Signal transduction pathways
Schwann cell 403, 1456 ERBB receptor signalling pathway
Schwannoma 945-947 886
Sciatic neuropathy 431, 432 neurotrophin signalling pathway 886
Sclerotome 96f, 97 notch signalling pathway 887
Sclerotomic fissure 97f Sonic Hedgehog SHH-PTCH
Scoliosis with myelopathy 7 signalling pathway 886
Screw Wingless (WNT/WG) signalling
fixation pathway 886
anterior atlantoaxial facet 370 Silicone balloons 619
odontoid 369 Simian virus-40 877
placement 369 Simple anomalies 138
Secretory products 942 Simpson scale 1272
Seddon’s classification of Single
nerve injury 407 agent chemotherapy 1292
peripheral nerve injury 411f photon emission computed
Segmental control 1502 tomography 113, 169, 588
Selective small enhancing lesion 492
endovascular occlusion 644 Site of injury 326t
posterior rhizotomy 1511 Site of the lesion post-operative study 1366
Sella Skeletal fluorosis
turcica cerebral ischaemia 851
lesions 905t cranial nerve lesions 850
non-neoplastic lesions 915 myelopathy 850
region neurological manifestations of 849
masses differential diagnosis peripheral neuropathies 850
1145 radiculopathy 850
other tumours 1145 Skip corpectomy technique 815
Sendai cocktail 581 Skull
Sensorimotor contusion 221 base
Sensory reconstruction 1348
abnormalities 768 surgical technique
cortex ablation 1435 extradural complete anterior
evoked potentials 6 clinoidectomy 1249
Index
1613
frontotemporal craniotomy discussion 1504

1249 generation 1501
limited posterior orbitotomy goals 1509
1249 indications 1509
optic canal unroofing 1249 location
optic nerve sheath opening central 1505
1249 peripheral 1505
posterolateral orbital wall management of resistant 1502
removal 1249 mechanism 1501
sphenoid ridge drilling 1249 non-surgical method chemical
convexity rhizotomy 1510
anatomical considerations 1346 open surgical method
reconstruction 1346 cervicothoracic 1509
surgical considerations 1346 lumbosacral 1509
infections 446 sacral 1509
localised tenderness 971 physical methods 1502
neoplasms physiological classification
conditions simulating 1316 ablative 1506
non-ablative 1505
traumatic conditions
procedures 1501
cephal haematoma 1316
results
growing fracture of the skull
motor functions 1510
1316
side effects
leptomeningeal cyst 1316
harmful (negative) 1511
osteomyelitis 448
useful (positive) 1510
radiograph 318
spasticity and spasms 1510
tumours 1305
selection of cases 1502
Smith-Robinson technique 803
specific selection criteria 1509
Snake-eye appearance 816 surgery 1501
Sodium distribution in the body 251 treatment protocol 1502
Soft cervical collar 346 usefulness of the procedure 1504
Solitary instruments
fibrous tumour 901 evoked potential recordings 770
plasmacytomas 922 intra-operative ultrasound 771
Somatosensory evoked potential 6, 419, laser 770
612, 770, 800, 815, 1264 tissue vapouriser 770
Somatostatin analogues 1100 ultrasonic aspirator 770
Sonic hedgehog gene 98 Special technology 770
Sonography 132 Specialised testing
Spasticity alternate binaural loudness balance
anatomical classification 1505 test 1192
classification 1505, 1509 impedance audiometry 1193
closed surgical method percutaneous loudness recruitment 1192
radio-frequency posterior pure tone audiometry 1192
rhizotomy 1509 short increment sensitivity index 1192
control pathways speech discrimination 1192
segmental 1505 Specific
suprasegmental 1505 cell type adenomas 906
detection of glioneuronal element 966
harmful tumours 74-89
development of complications Sphenoid sinuses
1503 conchal type 1090
disabling 1503 presellar type 1091
discomfort, pain and high Sellar type 1091
energy consumption Sphenoidal wing meningiomas
1503 clinical presentation
probable safety 1504 external third or pterional
resistant 1503 meningiomas 1247
1614
inner third sphenoid wing plain radiographs 508

meningiomas 1246 incidence 506
middle third or alar meningiomas life cycle and spinal implantation
1247 505
surgical treatment 1248 medical management
neuroradiology 1247 albendazole 509
treatment surgical mebendazole 509
inner and middle third meningiomas pathogenesis and pathology
1248 E. granulosus 506
results 1248 extraosseous extension 506
surgical complications 1248 intratrabecular space 506
Spinal metacestode 506
bifida 142 microtriches 506
arachnoiditis 468 multiple protoscolices 507
canal 353 protoscolex 507
claudication syndrome 833 syncitium 506
compression valsalva manoeuvre 506
bowel function 740 percutaneous aspiration 510
d i s t u r b a n c e s o f a u t o n o m i c prevention of echinococcosis 510
functions 740 reaspiration 510
involvement of the serological diagnosis
a n t e r i o r n e r v e r o o t a n d antibody titre 509
anterior horns 737 cyst contents 509
long sensory tracts 738 enzyme linked immuno
posterior root 737 absorbent assay 509
motor disturbance 739 imaging diagnosis 509
segmental involvement 738 indirect
sensory disturbances 738 haemagglutination 509
skeletal symptoms and signs 740 immunofluorescence tests
sphincter disturbances 740 509
symptoms and signs of 737 Ziehl Neelsen stain 509
cord surgical management 509
cavitation 185 injury
compression 922 intensive care management 343
i n j u r y w i t h o u t r a d i o g r a p h i c grading systems 335
abnormality 371, 387 patients nutrition 345
involvement 89 syndromes 336
neuropraxia 335 instability 337, 354
organisation lamina 1413 intramedullary
pain pathways 1414 abscesses 456
tumour 7 form 493
evoked potentials 816 tuberculomas 458
cysts leptomeningeal (extramedullary) form
clinical features 136 493
embryology 136 lipomas 778
introduction 135 meningiomas 762-764
radiology 136 neurolysis 1430
treatment 136 orthoses 1576
deformities 773, 768 pathologies 790
dysraphic states 142-144 Schwannomas 761
epidural abscess 453, 454t screening 339
hydatidosis shock 335
clinical features 507 stability 354
imaging stereotaxic surgery 1369
computed tomography 508 surgery 1527
magnetic resonance imaging syndrome 782
508 trauma 339
Index
1615
tuberculoma 459 grading 841

tuberculosis 459 investigations
tumours 782-786 computerised tomography scan
Spine 843
benign tumours 747 discography 843
brief normal anatomy 352 magnetic resonance imaging 843
clinical instability definition 355 plain radiographs 842
imaging of plain x-rays 59 isthmic 840
metastatic tumours 756 management
primary malignant tumours 752 conservative 844
tuberculosis of surgical 844
clinical presentation decompression 844
associated lesions 478 fusion 845
neurological deficit 478 instrumentation 845
imaging reduction 845
magnetic resonance imaging measuring 841f
479 Spurling’s neck 741
plain x-rays 478 Stability test 351
incidence 475 Staphylococcus aureus 447, 451, 454
neurological involvement 476 Stem cell 830, 1408, 1409
pathology and pathogenesis 475 Stent grafts 650
recent trends in the management of Stereotactic
correction of kyphosis 483 angiography 1367
indications of surgical therapy aspiration 1371
483 biopsy 1370
late onset paraplegia 483 brachytherapy 1371
route of infection 475 brain biopsy 921
treatment conformal radiosurgery 1245
ambulation 481 craniotomy 1366, 1372
antibiotic therapy 480 endoscopy 1372
bone grafting 481 external beam radiation therapy
conservative therapy 480 clinical applications 1368
evolution of surgical treatment general concepts 1368
480 guidance 163
excisional therapy and grafting radiosurgery 1005, 1171, 1173
481 advantages of 672
factors influencing results 481 causes of treatment failure 675
instrumentation 481 complications 675
posterior fusion 480 disadvantages of 672
surgery for paraplegia 482 factors related to complete avm
types of lesions occlusion 675
anterior lesions 476 for arteriovenous malformations
appendiceal type 476 674
central type 476 platforms delivering
paradiscal lesion 476 charged particle radiosurgery
Spinomesencephalic tract 1414, 1415 1396
Spinoreticular tract 1414 Leksell gamma knife™ 1396
Spinothalamic tractotomy 1433 Linac based radiosurgery
Split cord malformations surgical technique 1396
150 rotating gamma system 1396
Spoiled gradient recall images 1489 procedure related complications
Spondylolisthesis 674
classification and aetiology 839 radiotherapy 1171
clinical features and their basis 842 ventriculoperitoneal shunting 1303
degenerative 840 radiotherapy 1168, 1170
dysplastic 840 thalamotomy 1434
1616
Stereotaxy investigations 541

brain tumours 1370 management 543
depth recording 1364 misdiagnosis 541
for cerebral palsy 1495 space 610, 1299
general principles 1363 Subcaudate tractotomy 1402
principles 1364 Subdural
stimulation 1364 empyema 86, 450
techniques 1364 haematoma 195, 198, 203, 238
Sternal occipital mandibular immobiliser strips 49
376 Subependymal
Steroids 375, 580 giant cell astrocytoma 866, 876
Stiffness 350 heterotopias 117
Striatal Subpedicular posterior border 841
medullaris thalami 1397 Substantia
afferents innominata 1403
brainstem striatal fibres 1375 nigra afferents 1376
corticostriate fibres 1375 Subthalamic nucleus stimulation/lesion
nigrostriate fibres 1375 discussion 1383
thalamostriate fibres 1375 future therapies 1383
Stroke for surgery surgical procedure 1381
clinical features Sunderland’s classification of nerve injury
carotid territory 719 408
investigations 719 Superficial
vertebro-basilar territory 719 radial 418, 431
investigations 730 cerebellar artery 548
management Superior
cerebral infarct 726 hypophyseal 592
haemorrhagic stroke 728 longitudinal band of cruciate ligament
newer techniques 732 359f
revascularisation procedures 728 orbital fissure 1354
pathophysiology 725, 730 sagittal sinus 1237
prevention temporal gyrus approach 610
complications 723 Superoxide dismutase 575
direct revascularisation Supplemental prognostic tests 175
procedures 721 Supraolivary fossette 1451
extracranial to intracranial bypass Suprasegmental control 1501
723 Sutural growth 137
indirect revascularisation Sutureless repair 423
procedures 724 Suturing of bone pieces 1349
intra-operative monitoring 723 Sylvian fissure cysts 130
surgical Sympathectomy for visceral pain 1433
risk factors 722 Sympathetic plexus 564
technique 722 Synaptophysin 942
vertebro-basilar territory 723 Syncytial plexus 652
Struthers’ ligament 428 Syndromes
Stump pain 1439 carpal tunnel syndrome 425, 426,
Sturge-Weber syndrome 1229 427, 428, 429
Subacute graft occlusion 646 Down’s syndrome 179, 180
Subacute sclerosing panencephalitis 93 Ehlers-Danlos syndrome 616, 629,
Subarachnoid 630, 635
haemorrhage entrapment syndromes 425
acute management 543 fat embolism syndrome 229
aetiology 538 Grisel’s syndrome 179, 180
clinical features 538 Horner’s syndrome 417
Fischer’s grading 541f interosseous syndrome 425
grading scale 540t Morquio syndrome 179, 180
Hunt and Hess classification 540t NPPB syndrome 664
Index
1617
inappropriate ADH secretion 258, non-invasive evaluation 1487, 1488

1132t outcome assessment 1493
pain syndrome 401, 428, 434 pathology 1487
parasellar syndromes 642 pre-surgical
pronator teres syndrome 428 complications 1493
second impact syndrome 217 evaluation
shaken baby syndrome 195, 236 invasive evaluation 1488, 1491
temporary blocked syndrome 665 non-invasive evaluation 1488
thoracic outlet syndrome 433, 425 treatment
Wartenberg’s syndrome 431 alternate surgical procedures
Avellis 1212 1493
Collet-Sicard 1212 anterior temporal lobectomy
Costen’s 1455 1492
Eagle’s 1450 l e s i o n a l t e m p o r a l l o b e
Garcin’s hemibase 1212 epilepsy 1492
Jackson’s 1212 selective amygdalohippo
Ramsay hunt 1453 campectomy 1492
Reader’s 1455 stereotactic procedures 1492
Schmidt’s 1212 surgical approaches 1491
tapia 1212 Temporalis muscle 1350
Tolosa Hunt 1454 Temporary clipping 611
Vernet’s 1212 Temporoparietal fascia 1350
synostosis 137 Temporo-parietal fascial flap. 1325
Syringomyelia Tentorial meningiomas
aetiopathogenesis 182 classification 55, 1252
imaging 186 investigations 1253
management 186 angiography with tumour
natural history 186 embolisation 1253
Syrinx formation 182 locations of 1251f
relevant microsurgical anatomy 1251
T blood supply of the tentorium
T cell markers 942 1252
Tactile stimuli 1578 dural venous sinuses 1252
Tap test 173 tentorium 1251
Target controlled infusions 1519 signs and symptoms 1253
Taylor Haughton lines 1556, 1558 stereotactic radiosurgery 1256
Technetium-labelled methylene surgical approaches 1254
diphosphonate 852 Teratomas 1182-1184
Techniques Tethered cord syndrome
anterior fusion 369 clinical features 145, 146
Brook’s 368 embryogenesis 145
Dickman 368 indications for treatment 147
Gallie’s 368 lipomyelomeningocele 147
Jenkin’s 368 myelocystocele 149
of anterior neurological examination 147
cervical fusion 803f pathogenesis 146
spinal fusion 803 principles of surgery 147
posterior fusion 367 retethering 147
Sonntag 368 surgical technique 148
transarticular screw 368 symptoms 146
Jeanneret 368 Thalamocortical dysrhythmias 1398
Magerl 368 Thalamotomy 1402
Wiring 368 complications 1390
Tectorial membrane 359f Thalamus
Telecephalon 1374 medial paleothalamus 1416, 1434
Temozolomide 1006 neothalamus 1416
Temporal epilepsy surgery for neurophysiology 1417
1618
Theco-peritoneal shunt 156 Todd’s paralysis 976

Theory of Tolosa-hunt syndrome 1454
Gauss 230 Total circulatory arrest 583
Lehman 230 Toxoplasmosis 533
Therapy Traction
based on physiological principles 155 applying 345, 346
emerging 1008 extension 346
gene 1009 flexion 346
goals 1000 neutral 346
molecularly targeted 1008 Tractonucleotomies 1452
Thoracic and lumbar spine injuries Transarterial
classification schemes 384t Doppler 232, 566
Thoracic and thoracolumbar electrical stimulation 47
associated injuries 386 magnetic stimulation 47
injuries 383-389 onyx 704
surgery 390-392 sonography 556
surgical management 389 ultrasonography 173
triage care 389 Transfacial transmaxillary approaches
Thoracic disc prolapse 1326, 1328
clinical features 817 Transforming growth factors 100
complications 819 Transient ischaemic attacks 643
conservative management 820 Transmission electron microscopic
differential diagnosis 818 features 129
investigations 818 Transoesophageal echocardiography
pathology 817 1523, 1525
surgical management 818 Transoral-transpalatopharyngeal route
treatment 818 1342
Thoracolumbar Transpharyngeal approach to the
fractures Magerl’s AO classification craniovertebral junction
385f assessment of nutritional status
injuries 343, 383 co-morbidities 1342
methods of decompression and decision tree for treatment of 1342
fusion 390t delayed complications of
Thoraco-lumbo-sacral flexion 1575 transoropharyngeal surgery
Three dimensional conformal radiation 1345
treatment 1170 dental hygiene 1342
Thromboplastin activator 570 oropharyngeal cultures 1342
Thrombosis of draining vein 707 post-operative management 1344
Thyroid pre-operative cervical traction 1343
basal TSH level 42 prevention and management of
glycoprotein 42 complications 1345
hypothalamic-pituitary-thyroid axis 42 special circumstances 1343
mass spectrometry 42 intradural extension for tumour
newer methods index methods 42 1344
uptake test 42 transoral-transpalatopharyngeal
stimulating hormone 1114 approach 1344
tetraiodothyroxine 42 transpalatal route 1343
thyrotropin-releasing hormone types of craniovertebral abnormalities
stimulation test 42 1343
TRH stimulation test 42 Transport of spinal injured patient 333
tri-iodothyronine 42 Trans-sphenoid encephalocoele 126, 122
Thyrotroph cell adenoma 911, 1114 Transtentorial herniation 271
Tight brain during surgery 1524 Transverse
Tinnel’s sign 1455 carpal ligament 426
Tissue ligament 359f
distortion 168 rupture 364
plasminogen activator 570 of intervertebral disc 381f
Index
1619
Trauma 879 surgical

team 343 anatomy 1205
Traumatic pathology 1206
brain injury 196, 321, 207, 934 techniques 1208
cerebrospinal fluid fistulae 309 middle fossa approach
diffuse axonal injury 226 1208
intracerebral haematomas 283 presigmoid approach
intracranial aneurysms 556 1209
intracranial haemorrhage 278-282 retrosigmoid approach 1208
optic neuropathy 325 Trigonocephaly 139
pneumocephalus 314 Trilaminar embryonic disc 101
spondylolisthesis of the axis 341, 366 Trilateral retinoblastoma 1080
Treatment of Triple-H therapy 568, 584
burst fractures without neurological True and false cystic cerebellar
deficit 390 astrocytoma 1010t
graft occlusion 646 True neurologic TOS 434
individual tumours 1058 TSH-releasing hormone 1109
gliomas 1058 Tubercular infection 534
Tuberculomas 55, 87
medulloblastoma 1061
Tuberculum sella 310
average risk 1062
Tuberin 876
poor risk 1062
Tuberose sclerosis 1225, 1227
recurrent 1067
Tubular cavitations 182
Tremors
Tumour
essential tremor 1385
at different levels
multiple sclerosis tremors 1386
cauda equina syndrome 743
Parkinsonian tremor 1385
cervical region 741
post-traumatic and post-hemiplegic
conus syndrome 743
tremor 1386 differentiation between
the VIM target 1386 extramedullary 744
Trigeminal dorsal lesions 742
nerve 1416 epiconus syndrome 743
neuralgia upper lumbar segments 742
cerebellopontine angle 1443, clinical features of 741
1456, 1457 the foramen magnum 1272
clinical features 1443 angiogenesis factor 874
imaging 1446 fourth ventricle 986
incidence 1443 frontal lobe 976
investigations 1457 lateral ventricle 981, 1280
medical therapy 1446 markers 1082, 885, 939
pathogenesis 1445 choice 939
pathology 1444 classification 939
peripheral procedures 1447 detected in serum/CSF 940
selection of patients 1456 for diagnostic use 941
surgical procedure 1458, 1447 in cells/tissues 941
treatment 1446 in pineal tumours 1083t
schwannomas types 941
clinical presentation 1206 useful for prognostic evaluation
post-operative course 1209 942
radiological diagnosis 1207 uses 939
cerebral angiography 1207 like conditions 1156
computed tomography scans cerebellopontine angle 985
1207 clival 986
magnetic resonance imaging craniovertebral junction 987
1207 hypothalamus 983
plain x-rays 1207 involving the skull by direct extension
role of radiosurgery 1209 1313
1620
mimicking lesions 82 Varicella (chickenpox) virus 524

miscellaneous 1161 Varix 688
metastasising to Vascularity of local tissue
brain 924 abundant 267
spine 924 poor 267
necrosis factor alpha 528 Vasoactive
of meninges 892 intestinal peptide 1411
of meningothelial cells 867 metabolites 168
of the meninges 867 Vasoconstriction 570
of the meningothelial cells meningioma Vasogenic oedema 83, 932
892 Vasopressin 1126, 43
of the nervous system 872 Vasospasm 558-565
of the nervous system classification Vault of the skull 99
865 Vein of Galen malformations
of the pineal region 867 anatomical considerations 677
of the sellar region 868 classification of 677
of the spinal cord clinical features 678
intradural extramedullary 735 diagnostic investigations 679
intramedullary tumours 735 treatment 679-681
primary extradural tumours 735 Veins 968
of the vertebral column 736 Venous air embolism 1523, 1525
oncogenes 873 Venous angioma 688
parietal lobe 977 Venous angiomas 688, 689
posterior Venous congestion stage of
fossa 984 anoxia 280
third ventricle 983 neuronal irritation 280
prepontine 986 oedema 280
removal 1002 Venous hypertension 159
suppressor genes 913, 874 Venous thromboprophylaxis 375
sensorimotor region 977 Ventilation controlled mode 1528
subfrontal 976 Ventilation pressure
third ventricular 1280 controlled 1528
Turricephaly 139 support 1528
Twist gene 100 Ventilation synchronised intermittent
Tyrosine kinase 873 mandatory 1528
Ventral
U lateral nucleus 1416
Ulnar nerve entrapment 428 tegmental
Ultrastructure 947 area 1399
Unicoronal synostosis 138 tract 1417
Unilateral Ventricular
facet dislocations 374 size index 471
neurogenic thoracic outlet syndrome tumours 1279, 1280
10 Ventriculoperitoneal shunt systems 1538
Unipolar neurons 402 Ventriculostomy
Unruptured assessment of effectiveness 164
aneurysms clinical presentation 548 complications 163
intracranial aneurysm 629, 630 patient selection 163
Upper cervical spine injuries 359 third 163
Urinary Ventromedial part 96f
free cortisol excretion rate 41 Ventroposterolateral 1439
fluoride estimation 851 Ventroposteromedial 1439
incontinence 169, 170 Vertigo 972
Vesicular stage 89
V Vessel size 562
Vagal syncope 275 Vestibular function test in unconscious
Valve selection 176 patients 33
Index
1621
Vestibulo-ocular reflex 247 Wide dynamic range 1413

Video-assisted thoracoscopic surgery 483 Widespread thrombophlebitis 451
Vimentin 903 Wilms’ tumour 1044
Viral infections Wilson’s criteria 231
Creutzfeldt-Jakob disease 525 Wiltse-newman-macnab classification of
cytomegalovirus 527 spondylolisthesis 839
Epstein-Barr virus 526 Wingless (WNT) signalling 1044
herpes Wireless instantaneous neurotransmitter
simplex encephalitis 523 concentration system 51
zoster (varicella zoster) 524 Wiskott-aldrich syndrome 918, 1287
Japanese encephalitis 527 Wound
of the brain 91 characteristics 267
Ramsay Hunt syndrome 524 contracture 269
Reye’s syndrome 525 debridement 400
Rhabdoviridae 526 dehiscence 773
Virchow-robin spaces 638 necrosis 269
Virus 529
Visual symptoms 599 X
Vocal cord paralysis 1453 Xanthochromic 1010
Voltage-gated calcium channels 574 Xenon-computed tomography scan 567
Volume expansion agents 584 Xerophthalmia 1270
Volumetric measurements 155 X-rays
Voluntary muscle spasm 1440 dynamic 376
von Hippel Landau static 376
complex 1281
disease 955, 1011, 1225, 1228
Y
von Recklinghausen neurofibromatosis
1225 Yale brace 347
von Voss-Cherstvoy syndrome 123 Yasargil classified vein of Galen
von Willibrand factor 903 malformations 677
von-Hippel-Lindau disease 876 Yellow ligaments 831
Yolk sac tumour 868, 881
W Yttrium aluminium garnet 1567
Wada test 1478

Wada testing 686
Z
Walker-Warburg syndrome 123 Zagga 53
Wall shaggy and opaque 1010 Zeiss OPMI pentero microscope 1563
Wallerian degeneration 202, 212, 225 Zellweger syndrome 116
Walnut type lissencephaly 114 Ziehl Neelsen
Wartenberg’s sign 429 process 459
Water stain 509
distribution in the body 251 Zona fasciculata 40
view 304 Zoonotic parasitic disease 489
Watershed ischaemia 168 Zuccarello 285
Weak spots 668, 669 Zygapophyseal joint capsule injury 381f
Wechsler adult intelligence score 1406 Zygoma 1326, 304
Weinberg’s complement fixation test 501 Zygoma fracture 306
Welcker’s angle 58 Zygomatic
Whiplash arch 1336, 306, 484
complete injury 336 osteotomy 1336
incomplete injury 336 Zygomaticofrontal suture 306
Whiplash injury 380, 381, 381t Zygomycetes 512
Whole brain radiotherapy 1292 Zygomycosis 515

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Ramamurthi & Tandon’s

Prakash Narain Tandon

Pradeep Kumar Jain N

JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD

Jaypee Medical Inc. Jaypee Brothers Medical Publishers (P) Ltd

Jaypee Brothers Medical Publishers (P) Ltd

© 2014, Jaypee Brothers Medical Publishers

In the era of rapid advances in knowledge, techniques and technologies, it is

Prakash Narain Tandon

8. Basic Principles of CT Scan and MRI Scan 60

9. Radiology: Intracranial Tumours 70

10. Radiology: Intracranial Infections 84

SECTION II: CONGENITAL

12. Embryology: Brain and Spinal Cord 101

13. Congenital Malformations of Cerebrum 110

14. Encephalocoeles 119

15. Intracranial Arachnoid Cysts 127

16. Craniofacial Deformities (Craniostenosis) 137

17. Spinal Dysraphic States 142

18. Hydrocephalus 152

19. Endoscopic Management of Hydrocephalus 161

20. Normal Pressure Hydrocephalus 167

21. Bony Anomalies of the Craniovertebral Junction 178

22. Syringomyelia 182

SECTION III: HEAD INJURIES

24. Pathology 196

25. Concussion Brain 215

26. Cerebral Contusions 219

27. Diffuse Axonal Injury 224

28. Fat Embolism 229

29. Paediatric Head Injuries 233

30. Clinical Assessment of a Head Injured Patient 244

31. Fluid and Electrolyte Balance in Head Injury 250

32. Scalp Injuries 263

33. Acute Subdural Haematomas 270

34. Extradural Haematomas 274

35. Traumatic Intracerebral Haematomas 278

36. Traumatic Brainstem Haemorrhage 285

37. Complications and Sequelae of Head Injuries 288

38. Cranioplasty 297

39. Maxillofacial Injuries 303

40. Traumatic Cerebrospinal Fluid Fistulae 309

41. Missile Injuries of the Brain 315

42. Endocrine Abnormalities Following

43. Optic Nerve Injury 325

SECTION IV: SPINAL INJURIES

45. Biomechanics of the Spine 349

46. Injuries of the Craniovertebral Junction and

47. Injuries of Subaxial Cervical Spine 371

48. Whiplash Injury 380

49. Thoracic and Thoracolumbar Injuries 383

50. Lumbar and Lumbosacral Injuries 393

51. Penetrating Injuries of the Spine 397

SECTION V: PERIPHERAL NERVE

53. General Principles of Management of

54. Surgical Anatomy and Management of

55. Management of Injuries to Specific

56. Entrapment Syndromes 425

SECTION VI: INFECTIONS

58. Scalp and Skull Infections 446

59. Subdural Empyema 450

60. Spinal Epidural and Intramedullary Abscess 453

61. Tuberculosis of the Central Nervous System 459