CENTRAL NERVOUS SYSTEM

CNS – Brain
Spinal Cord

Brain – Cerebrum
Cerebellum
Pons
Medulla oblongata

Histology – Brain – Neurons

Neuroglial Cells

Neurons – Specialized cells – responsible for conduction of impulses

Neuroglial Cells – include Astrocytes, Oligodendrocytes & ependymal cells.

Glial cells provide support & nutrition to neurons

Brain Coverings – Dura Mater

- Arachnoid mater & Piamater - leptomeninges

Cerebrospinal fluid: CSF – produced by choroid plexus within ventricles

(lateral, 3rd, 4th)

 Normal volume – 120 to 150 ml

 Exits from fourth ventricle through foramina into subarachnoid space
 Re-absorbed through dural venous sinuses

CSF –
- Transports metabolites to cells of CNS
- Clears metabolic waste
- Protects / cushions structures within skull
 Hydrocephalus – an excessive accumulation of CSF within the
ventricular system leading to dilation of ventricles & raise in Intracranial
pressure

Causes:
- Excessive Production of CSF – e.g. : Tumors of choroid plexus
-Impaired resorption of CSF [Most common cause]

1. Non-communicating Hydrocephalus is characterized by obstruction to the

flow of CSF out of ventricles
E.g.: a. Congenital stricture of Aqueduct of Sylvius
b. Acquired – Neoplasms (choroid plexus tumors,
medulloblastoma)
-Scarring at the base of the brain due to meningitis &
hemorrhage
2. Communicating (non obstructive) Hydrocephalus :
- Due to excessive accumulation of CSF caused by impaired reabsorption
by arachnoid villi
- May develop as a complication, of Subarachnoid haemorrhage,
meningitis & spread of tumor within subarachnoid space

Morphology: Ventricles of brain dilated and cortex is thinned

Clinical Features:
 Hydrocephalus, in utero / infancy – before closure of cranial sutures
results in separation of cranial sutures & enlargement of head
-Symptoms of increased intracranial pressure – usually absent.
 Hydrocephalus developing later, is associated with expansion of
ventricles & increased Intracranial pressure.
-No enlargement of head
-Increased intracranial pressure is characterized by headache,
vomiting, papilledema

Complications – In the absence of treatment, it slowly progresses

resulting in irreversible brain damage & death.
INFECTIONS:
Meningitis Encephalitis Meningo-encephalitis
Inflammation of Inflammation of Inflammation of both
meninges Parenchyma of brain meninges &
parenchyma of brain

 Organisms – causing infection – viruses, Bacteria, Parasites

 Infection may be – Acute or Chronic

Routes of Infection:
1. Haematogenous (most common)
- through septicaemia & septic embolism (Arterial Circulation)
- through Retrograde spread – occurs through veins of the face
2. Direct Implantation: - Usually follows trauma / is associated with
congenital malformations (e.g.: meningomyelocele)
3. Local Extension – from adjacent structures like air sinuses, an infected
tooth, cranial / spinal osteomyelitis
4. Transport along peripheral Nervous system – in certain viral infections
as rabies & herpes zoster

MENINGITIS:
- Inflammation of meninges (mainly within the space between pia &
arachnoid mater)

Causes:
A. Infectious (most common)
Acute
Pyogenic (bacterial / purulent)
Causative agent
E.coli, Group B Streptococcus,
Chronic
Tuberculous
Syphilitic (Treponema pallidum)
Cryptococcal – Crypto coccus
 H.Influenzae, Meningococcus

Aseptic (Usually viral)

- Entero virus, HIV, Mumps virus, Epstein Bars virus, Herpes simplex
virus

B. Chemical Meningitis:
- Due to nonbacterial irritant introduced into subarachnoid space

Pyogenic / Bacterial Meningitis:

Clinical features: commonly- Headache, Vomiting, Fever & convulsions
(especially in children)

Classical Signs of Meningitis:

- Cervical rigidity / Neck stiffness
- Kernig’s Sign: Knee pain with hip flexion
- Brudzinski’s sign: Knee / Hip flexion when the neck is flexed

Laboratory Tests:
Examination of CSF by lumbar puncture shows – (CSF findings)
- Appearance – Normally clear. In Ac. Meningitis – cloudy / Frankly
purulent
- Pressure: Increased ( >180mm H2O)
- Cells: Neutrophils in CSF is the most definitive feature of meningitis-
count may be around 90,000/microLiter
- Protein concentration : Increased (>50mg / dL)
- Glucose – Markedly decreased (< 40mg / dL)
- Smear – Bacteria may be seen on a smear (Gram stain) or can be
cultured.
Complications of Bacterial Meningitis
- Obstructive Hydrocephalus
- Thrombophlebitis of Leptomeningeal veins
- Chronic Adhesive Arachnoiditis
- Cerebral Abscess
- Water House Friderichsen Syndrome – Meningitis associated septicaemia
– hemorrhagic infarction of adrenal glands & cutaneous petechiae
-Subdural Empyema
-Epilepsy
Acute Aseptic (Viral) Meningitis:
 Patient has symptoms of acute meningitis, in the absence of recognizable
organisms
 Age: Common in children & young adults
 Clinical Features: It presents with fever & headache
 C.S.F Findings: Appearance – clear
Protein: Moderately increased (>40 mg/dL)
Glucose: Always normal
Microscopy: 10 – 100 lymphocytes / microL
 Prognosis: Usually self – limiting

Chronic Meningitis:
 Bacterial – Tuberculous (M. tuberculosis)
Syphilitic (T. pallidum)
 Fungal – Cryptococcal
Tuberculous Meningitis:
 Infection of meninges by tubercle bacilli
 Mode of Infection – Hematogenous route, most commonly from lungs
 Meningitis as a result of miliary spread
 Direct spread from adjacent site like vertebral body
Morphology:
Gross – Subarachnoid space contains a greenish, gelatinous / fibrinous exudate,
most prominent at the base of the brain & surrounding cranial nerves.
- Leptomeninges may show white granules of tubercles.
Microscopy – Granulomas consisting of epithelioid cells, Langhans giant cells
surrounded by lymphocytes.
- Show, central area of caseous necrosis
- AFB stain may show acid fast bacilli
Clinical Features: Headache, Malaise, Mental Confusion, Vomiting, Neck
Rigidity.
CSF Findings: Clear, Colourless; forms cob web on standing due to coagulation
of fibrinogen
CSF Pressure : Raised above 300 mm H2O
Protein – Raised; from 50 – 150 mg / dL
Glucose – Moderately reduced or normal (20 – 50 mg / dL)
Chloride – Decreased (450 – 600 mg /dL)
Cells – Moderate CSF pleocytosis (500 – 700 cells /microL) mainly
lymphocytes
Complications : Hydrocephalus ; Nerve root damage, Tuberculous encephalitis

CSF findings Normal Acute Acute Viral Tuberculous

Pyogenic
Physical Clear Turbid & Clear Clear, forms
examination colourless forms cobweb on
coagulum standing
CSF Pressure 60-150mm >180mm >250mm >300mm
H2O H2O H2O H2O
Total Protein 20-40 mg/dL 50-200 >40mg /dL 50-150 mg
mg/dL /dL
Glucose 45-80 mg /dL 0-20 mg /dL Normal 20-50 mg /dL
Chlorides 720-750 600-700 Normal 450 - 600
mg/dL mg /dL mg/dL
Polymorphs Absent 1500-2000 Absent 0 – 5 cells
/uL /microL
Lymphocytes 0-5 cells / 5-50 cells / 10-100 / 500-700
microL microL microL cells /microL
Gram – Stain -ve Bacteria + Stain-ve AFB +
Stain/ZN
stain

Encephalitis – Acute inflammation of brain parenchyma

 Encephalitis with meningitis – Meningoencephalitis
 Cause – Viral (most common)
e.g.: Rabies, herpes simplex, Polio virus, Measles virus
 Bacterial & Other agents –
Bacterial – meningitis spreading directly to brain or may be a
complication of syphilis
Parasitic & Protozoal infestations such as toxoplasmosis, malaria /
primary amoebic meningoencephalitis (in immune compromised people)
 Clinical features:
In adults: Acute onset of fever, headache, confusion & sometimes,
seizures
In younger children / infants – present with irritability, poor appetite &
fever
- CSF fluid shows increased Protein & WBCs with normal glucose

CEREBROVASCULAR DISEASES
 Group of diseases of the blood vessels of brain
 Includes stroke (Ischemic and Haemorrhagic) and cerebrovascular
anomalies
 Cerebrovascular diseases may cause – Ischemia
- Infarction
- Haemorrhage

Factors determining extent of brain damage.

 - Brain needs constant blood supply for supplying glucose & oxygen
- Diseases of blood vessels of brain – may impair blood supply &
oxygenation of brain

STROKE (CEREBRO VASCULAR ACCIDENT)

 Group of diseases that begin suddenly and cause neurologic damage due
to focal ischemia or haemorrhage. It is a common medical emergency.
 Clinical Classification: depending on duration & evolution of symptoms
1. Transient Ischemic Attack (TIA) – A stroke in which CNS
disturbances last for less than 24 hrs
2. Progressing stroke (Evolving stroke) – wherein, the focal neurological
deficits worsens after the patient first presents
3. Completed stroke – characterized by persistence of focal deficit which
does not progress

 Causes of Stroke :
Ischemic stroke : 85% are ischemic type
- Caused by reduced blood flow to a part or entire brain
- Reduced blood flow ultimately results in infarction
Haemorrhagic Stroke: 15% of strokes are haemorrhagic type
 Bleeding may occur – into brain tissue (intraparenchymal / intra cerebral
haemorrhage) / Into spaces surrounding brain (subarachnoid /
intraventricular spaces)
 Haemorrhagic stroke – 2/3rd are due to subarachnoid haemorrhages
-1/3rd due to intracerebral haemorrhages
 Haemorrhage may be due to -
-Rupture of CNS blood vessels
-Or Ruptured aneurysm and arteriovenous malformations

Ischemic Stroke:
 Cerebral arterial occlusion – causes reduced Blood supply & Ischemia of
specific area supplied by that artery.
 If ischemia continues – Infarction develops at that area
Causes:
-Cerebral artery occlusion due to thrombus & embolus are responsible for 65%
of all strokes.

1. Thrombosis- Atherosclerosis predisposes to thrombosis

Cerebral infarction is mostly due to thrombosis in the
 Major extracranial arteries (carotid artery & aortic arch)
 middle cerebral artery
 basilar artery

2. Embolism – most common type is thrombo-emboli. Origin of emboli may

be
 Heart – Thrombi in the heart chamber is the most common source of
emboli
-Important predisposing factors for thrombi in the heart are
-Myocardial Infarct
-Valvular Disease
-Atrial fibrillation
 Arteries: Thrombo-emboli may arise from thrombus developed on
atheromatous plaques within the carotid arteries.
* Other sources of emboli:
- Paradoxical emboli – e.g.: in children with cardiac anomalies
- Other emboli like tumor, fat or air

Generalized Arterial Disease:

 Vasculitis may cause – narrowing of lumen
-Cerebral Infarcts
[Infections: e.g.: Syphilis, Tuberculosis
Non-Infectious: e.g.: Polyarteritis nodosa] -cause vasculitis
Morphology:
Classification:
Haemorrhagic (Red) Infarction Non-Haemorrhagic (Pale, bland,
 anaemic) Infarcts
Seen with embolic events Associated with thrombosis
Multiple, petechial haemorrhages
seen

Gross:
Initial Changes:
Infarcted area appears pale, soft, swollen with loss of boundary between normal
& infarcted area
Later – Involved area of brain undergoes
Liquefactive necrosis; becomes – gelatinous & friable
-Boundary between normal & infarcted area becomes more prominent

 Microscopy:
- Liquefactive necrosis with progressive infiltration by neutrophils
- Neutrophils are replaced by macrophages that remove all the necrotic
tissue
- Haemorrhagic infarction shows blood extravasation & resorption,
additionally
Clinical features:
 Neurologic symptoms depend on the region of brain involved
 Develops rapidly, over minutes & may continue to evolve over hours.

INTRACRANIAL HEMORRHAGE
Intracerebral Subarachnoid
Haemorrhages within the brain Bleeding into the subarachnoid space
parenchyma
Majority caused by rupture of a small Causes: Rupture of saccular (berry)
intraparenchymal vessel aneurysm
Major cause of rupture of vessel is Trauma
 Hypertension
Usually spontaneous & occur in Extension of a hypertensive
middle to late adult life (peak during intracerebral haemorrhage into
60 years) ventricular system
Hematologic Disorders
Vascular malformation
Neoplasms

Clinical Features:
Subarachnoid haemorrhage is associated with
Sudden, severe headache followed by loss of consciousness

PARAPLEGIA
- Impairment in motor / sensory functions of the lower extremities,
resulting in
- Complete paralysis of lower half of the body including both legs
Causes:
- Trauma to spinal cord with damage
- Non Traumatic – Spinal Tumours
Scoliosis (abnormal side ward curving of spine)
- Congenital: Spina Bifida (Spinal bones do not come together properly
affecting neural elements)

Clinical Features:
- Depends on level & extent of spinal damage
- Paraplegic patients have varying degrees of loss of sensation in affected
limbs
- Patients are dependent on wheel chairs & other supportive measures
- Patients have various degrees of urinary and faecal incontinence
Complications:
- Pressure sores ( Decubitus ulcers)
 - Thrombosis
- Pneumonia

In quadriplegia – both arms & legs are affected by paralysis

In monoplegia – one limb is affected

HEMIPLEGIA
- Total paralysis of the arm, leg & trunk on one side of the body (same)

Areas Involved: If damage is on the right side of the brain – hemiplegia will be
on the left side & similarly, if left side of brain is damaged – hemiplegia is on
Rt side.
Causes :
In elderly people, strokes are the most common cause of hemiplegia
Other causes :Spinal cord injury, Brain infections (e.g.:viral), Tumors

Clinical features :
Hemiplegia patients show a characteristic gait
- Leg on affected side is – extended & internally rotated
- To move the affected leg forwards – it is swung in a wide, lateral arc,
cannot be lifted as in normal people
- Upper limb on the same side is adducted at the shoulder, flexed at the
elbow, pronated at wrist with thumb tucked into the palm & fingers
curled around it. (rotation of hand so that palm faces down / back)
- Difficulty in balance while standing / walking
- Having difficulty with motor activities like holding, grasping, pinching
- Increasing stiffness of muscles & muscle spasms
- Difficulty in speech
- Difficulty in swallowing food
Prognosis – It is a non-progressive disorder, except in progressive lesions like a
growing brain tumor.
Usually symptoms do not worsen.
Complications :
- Muscle & joint stiffness,
- Loss of aerobic fitness
- Muscle spasms
- Bed sores

- Pressure ulcers
- Thrombosis

Central Nervous System Tumors

Common Tumors
Gliomas Poorly Meningeal Metastatic
differentiated Tumors Tumors
Neoplasms
Astrocytoma Medulloblastoma Meningioma
Oligodendrogliom
a
Ependymoma

Gliomas – Most common (primary brain tumors)

Derived from glial tissue
Astrocytoma :
- Derived from astrocytes
- Form 80% of primary brain tumors (adults)
- Sites – usually, cerebral hemispheres; others – cerebellum, brainstem,
spinal cord
- Age : usually 4th to 6th decades
- Classification : based on histologic grades (differentiation), Clinical
outcome & increasing anaplasia
Diffuse Astrocytoma – Anaplastic Astrocytoma Glioblastoma – Grade
Grade II - Grade III IV
Gross: Poorly Microscopy : Increased Variable consistency &
demarcated tumor cellularity color
Infiltrates surrounding Cellular & Nuclear Microscopy : same as
normal brain tissue Pleomorphism Anaplastic astrocytoma
 C/S – gray & firm Anaplasia + serpentine type of
necrosis, surrounded by
palisading tumor cells
which is known as
pseudo-palisading
[garlanding] &
endothelial cell
proliferation.
Microscopy – Glial Increased Mitotic
tumor cells (astrocytes) figures
with variable nuclear
pleomorphism
Fibrillary back ground Rapid growing tumors

Clinical Features – Seizures, headaches

- Focal neurologic deficits are related to anatomic site of involvement &
growth rate of tumor.
Prognosis :
- Well differentiated diffuse Astrocytomas may remain static / progress
only slowly over a number of years
- Glioblastoma has a very poor prognosis

Oligodendroglioma (WHO grade II)

- 5-15% of gliomas
- Age: Common in 4th – 5th decades
- Morphology: Gross : well circumscribed, gelatinous, gray tumor.
(common in cerebral hemispheres- white matter)
- Microscopy: Sheets of small, round, regular cells with spherical nuclei.
- Nuclei surrounded by a clear halo of cytoplasm (fried egg appearance)
- Calcification (calcospherites) is common

Poorly Differentiated Neoplasms

Medulloblastoma – highly malignant poorly differentiated
Age : Predominantly in children, towards end of first decade.
Morphology :
Gross : exclusively in cerebellum as well circumscribed, gray, friable tumor
Microscopy : Extremely cellular
- Sheets of small, anaplastic cells with scant cytoplasm & hyper chromatic
nuclei

- Homer – wright rosettes (pseudorosettes) may be seen

Clinical features:
Presents with cerebellar dysfunction & Hydrocephalus

Prognosis: Dissemination through CSF is common & prognosis poor.

Meningiomas – benign intracranial tumors arising from meningothelial cells of

arachnoid
Incidence: 20% of primary intracranial neoplasms
Age: Peak in 4th – 5th decades
Sex Ratio- Female : Male ratio – 3 : 2
Morphology: Site – occur at any intracranial site both on external surfaces of
brain as well as within the ventricular system
Gross : Well circumscribed, rounded masses – variable size.
- Usually attached to dura with broad base
- Compress underlying brain, but do not infiltrate it, can be easily separated
Microscopy – Whorled pattern of meningothelial cell arrangement
- Psammoma bodies seen (laminated, spherical calcospherites)

Histological Types (No Prognostic significance)

- Syncytial (meningothelial) type
Shows whorled clusters of polygonal cells without visible cell
membranes[syncytial]
-Other types – Fibroblastic ; Transitional / mixed ; Psammomatous ;
secretory ; Angioblastic etc.
Most of meningiomas are considered as WHO Gr. I.
Metastatic Tumors:
Most common intracranial Neoplasms
- Most commonly from primary sites like
-Carcinoma lung, Breast, Skin (Melanoma), Kidney & Gastro
intestinal tract.
Route of spread – metastatic tumors reach the intra cranial compartment
through blood stream, generally in patients with advanced cancer.
Morphology – Gross : Multiple, sharply demarcated masses
- Usually seen at the junction of gray matter & white matter

Microscopy : Appearance is similar to that of primary tumor

Prognosis : Poor .