Najeeb’s Neuroanatomy &

Neurophysiology
Lecture Notes
Sean Cheok
4/23/2016
CONTENTS
About This Book ...................................................................................................................................... 2
Introduction to Neuroanatomy .............................................................................................................. 3
Meninges................................................................................................................................................. 8
CSF & Ventricular System...................................................................................................................... 14
Development of Nervous System ......................................................................................................... 25
Autonomic Nervous System.................................................................................................................. 33
Sensory System & Ascending Tracts ..................................................................................................... 43
Motor And Descending Tracts .............................................................................................................. 55
Upper & Lower Motor Neuron Lesions................................................................................................. 67
Spinal Cord Lesions ............................................................................................................................... 72
The Basal Ganglia .................................................................................................................................. 96
The Cerebellum ................................................................................................................................... 106
Basic Brain Stem & Cranial Nerve Concepts ....................................................................................... 116
Medulla ............................................................................................................................................... 128
Pons..................................................................................................................................................... 139
Midbrain.............................................................................................................................................. 144
Diencephalon ...................................................................................................................................... 149
Thalamus ............................................................................................................................................. 152
Hypothalamus ..................................................................................................................................... 158
Auditory System .................................................................................................................................. 168
Vestibular System ............................................................................................................................... 183
Visual System ...................................................................................................................................... 190
Extraocular Muscle Nerve Palsies (CN III/ CN IV/ CN VI)..................................................................... 213
Trigeminal System and Lesions ........................................................................................................... 219
Facial Nerve and Its Lesions ................................................................................................................ 224
Blood Supply to Central Nervous System ........................................................................................... 236
Seizures and Epilepsy .......................................................................................................................... 243
Aphasia and Dysprosody ..................................................................................................................... 263

1
ABOUT THIS BOOK
This unofficial short text was prepared as an accompaniment to Najeeb’s Neuroanatomy and
Neurophysiology lecture videos. Please circulate it freely to anyone who may find it useful.

It should be used alongside the official videos as well as with a good gross anatomy textbook for
Head and Neck for an appreciation of the distal distributions of the cranial nerves.

The videos for Glossopharyngeal Nerve Palsies and Vagus Nerve Palsies have not been covered due
to time contraints; anyone is welcome to update the text with these chapters or errata.

You can contact me regarding errata at: SEAN0010@e.ntu.edu.sg.

Sean

LKCMedicine 2018

2
INTRODUCTION TO NEUROANATOMY
Components of the Nervous System & Their Interactions

 The nervous system compromises two main components: the Central Nervous System (CNS)
and the Peripheral Nervous System (PNS)

 The CNS includes the brain and spinal cord, while the peripheral nervous system includes nerves.

 The peripheral nervous system itself has two main components: sensory and motor.

 The CNS and PNS interact as follows:

 The CNS receives sensory input about the self and environment through the sensory
part of the peripheral nervous system

 It integrates sensory input by comparing present information to past information

 It generates motor responses and implements them by sending signals back through the
motor peripheral nervous system.

Sensory Nervous System of PNS

 The sensory nervous system receives information about the self and environment through
special senses and general senses

 Special senses are elicted from specific parts of the body, while general senses are
elicted from many parts of the body.

 The special senses are olfaction, taste, vision, hearing and balance (or sense of
equilibrium). Balance and hearing are sensed by different parts of the ear. Classically but
somewhat arbitrarily, olfaction and taste are said to be special visceral senses, while
vision, hearing and balance are special somatic senses.

 The general sensations can also be visceral or somatic in nature. Visceral sensations are sensed
by the viscera in deep parts of the body. Somatic sensations are sensed in superficial parts of the
body, including the skin and components of the locomotor system (such as joints and muscles).

 The general visceral sensations include sensations like dull pain and distension. Visceral
pain is often more diffuse (poorly localized) and less intense than somatic pain.

 The general somatic sensations include Fine touch, vibrations, two-point discrimination,
proprioception, pain, temperature, crude touch, sexual sensations, itch and tickle.
Proprioception may be described as the sensation of the orientation of our body parts in
space; notably it receives stimuli mainly from the locomotor system.

 Not all sensory input reaches the level of consciousness. The cerebral cortex of the brain
determines which sensations reach the level of consciousness and which do not.

3
Motor Nervous System of PNS

 The motor nervous system implements somatic and autonomic motor responses.

 The somatic motor responses trigger voluntary responses; they carry out their effector functions
through skeletal muscle.

 The autonomic responses trigger involuntary responses. They carry out their effector functions
primarily through effects on smooth muscle, cardiac muscle and glandular secretions
(secretomotor activity).

 The autonomic system has three main arms:

 The sympathetic arm is associated with a “fight or flight” response

 The parasympathetic arm is associated with a “rest and digest” response.

 The enteric nervous system is a third component of the autonomic system innervating
the GI tract.

Central Nervous System

 The central nervous system has two main components, the brain and spinal cord.

 The brain can be further subdivided into three main components:

 The forebrain arises from the embryonic prosencephalon (pro = before). The
prosencephalon is further divided into a more superficial telencephalon, which forms
the cerebrum, and a deeper diencephalon, which gives rise to the thalamus,
hypothalamus, subthalamus and epithalamus.

 The midbrain arises from the embryonic mesencephalon (meso = middle).

 The hindbrain arises from the embryonic rhombencephalon. The rhombencephalon

gives rise to the pons, medulla and the cerebellum.

 The midbrain and hindbrain together are collectively known as the brainstem.

4
5
Cellular Basis of the Nervous System

 The cells of the nervous system can be broadly divided into neurons and neuroglial cells.

 Neurons are cells with cell bodies and long processes called axons that extend from the cell
body. They are responsible for the main function of the nervous system, which is to send and
receive signals in the form of action potentials.

 Within the central nervous system, a collecting of cell bodies is called gray matter. It can be
found in three forms:

 Covering the surfaces of the brain, in which it is called cortex. These include the cerebral
cortex and cerebellar cortex.

 In isolated collections within the deeper parts of the brain, surrounded by the white
matter that forms the central core of the brain. These are called nuclei. The term
nucleus here has a different meaning from the organelle of a cell.

 In a central column of the spinal cord, that extends as far superiorly as the brainstem.

 Within the central nervous system, a collection of axons is called white matter. White matter
can also be said to be found in three forms:

 Ascending and descending tracts, which conduct signals within the central nervous
system in a craniocaudal axis.

 Commisural fibers, which conduct signals within the central nervous system from one
part to another laterally.

 Association fibers, which conduct signals within the central nervous system in an
anterioposterior or posteroanterior direction.

 In parts of the CNS, notably the brainstem, there are collections of ascending and descending
tracts travelling between the spinal cord and CNS that decussate from one side of the brainstem
to the other, disrupting the central core of gray matter. This region thus has a mixture of gray
and white matter, and is known as a reticular formation.

 Within the peripheral nervous system, collections of cell bodies are called ganglia. Collections of
axons are called nerves.

 Neuroglial cells can be said to be the supporting cells of the nervous system, and form part of
the connective tissue of the nervous system. They perform many functions, one of which is
myelination, or the insulation of axon fibers in order to increase conduction speed.

 In the CNS, myelination is done by oligodendrocytes. In the PNS, myelination is done by

Schwann cells. It is important to distinguish between the two, because some pathologies only
attack one type of cell rather than the other, and thus cause pathologies only in the CNS or PNS.

6
Neuroglial Cells

 The macroglial cells include

 Astrocytes, which form the connective tissue substance of the CNS and have processes
whose feet sit on the capillary junctions, and contribute to formation of the blood brain
barrier

 Oligodendrocytes, which are the myelinating cells of the CNS, and extend multiple
processes that allow them to myelinate multiple segments of multiple neurons

 Schwann cells, which are the melinating cells of the PNS, and are able to form the myelin
sheath of a single segment of a single neuron only

 Ependymal cells, which are tall columnar epithelium lining the spinal canal and the
ventricles

 Microglial cells are the resident macrophages of the CNS, and descend from the monocyte-
macrophage line of cells.

7
MENINGES
Introduction

 The three main meningeal layers from superficial to deep are known as the

 dura mater, which is formed of a relatively tough and thick layer.

 arachnoid mater, which is relatively avascular.

 the pia mater is relatively avascular, and is closely adhered to the surface of the brain.
Processes called trabeculae extend from the arachnoid to pia mater.

 The dura mater is derived from mesoderm, and the arachnoid and pia mater, collectively
known as the leptomeninges, are derived from neural crest cells.

 There are two layers of dura mater which are closely related to each other. The more superificial
periosteal dura is strongly adhered to the surface of the bone; the deeper meningeal dura is
closely adhered to the arachnoid mater below it.

 Three main meningeal spaces are defined:

 The extradural space is a potential space between the periosteal dura and the inner
table of bone.

 The periosteal and meningeal dura are closely adhered at most locations, but may
separate to form dural venous sinuses in some places.

 The subdural space does not exist physiologically; however it may develop due to
pathology resulting in dissection of the meningeal dura into a superficial layer which
remains attached to the periosteal dura, and a deep layer which remains attached to the
arachnoid membrane. It is sometimes loosely described as a space between the
meningeal dura and the subarachnoid membrane, however this is not entirely accurate.

 The space between the arachnoid and pia mater is known as the surbarachnoid space.
The subarachnoid space is a true, realised space under physiological conditions. This
space is filled with cerebrospinal fluid. The brain, which is closely adhered to the pia
mater, floats around in this CSF space, which provides cushioning to it.

 Bleeding can occur into any one of the meningeal spaces, or additionally can occur in the
substance of the brain itself (intracerebral bleed).

8
Epidural/ Extradural Hemorrhage

 The meningeal arteries run within the periosteal dura layer.

 Rupture of the middle meningeal arteries can cause an extradural hemorrhage, in which there is
a collection of blood in the space between the periosteal dura and the inner table of bone.

 It most commonly involves the anterior branch of the middle meningeal artery which
lies deep to the pterion where the suture lines of the frontal, sphenoidal, parietal and
temporal bones meet.

 Trauma to the skull in this fragile region (i.e. blow to the temple) can result in skull
fracture with damage to the anterior branch of middle meningeal artery.

 Clinically such patients present with:

 History of skull trauma to the temporal region

 An acute loss of consciousness may or may not occur following the blow. If it occurs, it is
likely due to acute contusion to the brain, but recovery follows quickly.

 A subsequent asymptomatic lucid interval usually follows while the hematoma develops

 Once the hematoma has enlarged, the patient begins to experience gradual loss of
consciousness defined by lower scores on Glasgow coma scale.

 CT investigations usually reveal a bi-concave “lens-shaped” hematoma that is restricted by

sutural lines. This occurs because the dural layers are closely adhered by sutural ligaments that
extend deeply from the sutural lines, resulting in a high pressure hematoma that bulges inward
into the cranial cavity.

 Treatment involves drilling burr holes to evacuate the epidural hematoma to reduce intracranial
pressure.

9
Subdural Hemorrhage

 Cerebral veins lie in the substance of the brain, but drain via bridging veins which traverse all
three dural layers to empty into the dural venous sinuses.

 These bridging veins are most strongly adhered where it passes through the dura mater.

 Of the meningeal layers, the meningeal dura and arachnoid mater are closely related to each
other, while the pia mater adheres most closely to the surface of the brain. Between the pia
mater and arachnoid mater is the sub-arachnoid space, which is CSF-filled.

 The brain and pia mater float in this CSF-filled cavity. In sudden deceleration injuries, the brain
may move rapidly within the cavity and tear the bridging veins.

 When the bridging veins tear, they end to tear at the the meningeal dura because they are most
strongly attached here. This results in hemorrhage that can dissect the meningeal dura layer into
two, producing a subdural hemorrhage.

 Risk factors include:

 Being prone to falls (e.g. epileptics and alcoholics)

 Elderly age, due to fall risk as well as because their brains are smaller and have greater
mobility in the CSF-filled cavity.

 Anticoagulant use. This type of bleeding can progress very slowly; an anti-coagulative
profile leads to likelihood of prolonged bleeding which might otherwise be
asymptomatic.

 Symptomatically, patients present with a gradual loss of consciousness; however unlike in

extradural hemorrhage, this can present from days to years after the initial deceleration injury
and the onset is insidious. Thus, a fall history may not be recalled by the patient or family;
subdural hemorrhage should be suspected in unexplained gradual loss of consciousness
particularly in those with associated risk factors.

 CT should show a crescent-shaped hematoma (due to lower pressured bleed from bridging veins)
that may tract past sutural lines.

10
Subarachnoid Hemorrhage

 The subarachnoid space is a CSF-filled space with trabeculae in which the cerebral arterial
system runs.

 Two common etiologies for subarachnoid hemorrhage include:

 Berry aneurysms, which commonly develop in the circle of willis, particularly at branch
points of arteries. These commonly occur as a hereditary weakness of the blood vessels.

 Congenital arteriovenous malformations. These are fistulae between arteries and veins
without an interconnecting capillary bed. The lack of a capillary bed results in exposure
of the veins to undampened high pressures which can cause rupture.

 Clinically the patient presents with a sudden onset of extremely severe headache due to
spontaneous rupture of a vessel. There is no necessity for a history of head trauma.

 CT scan should show a more diffuse hemorrhage than either extradural or subdural hemorrhage;
often it will reveal outlines of the sulci of the brain.

 Depending on whether the CT shows structural shifts in the brain, a lumbar puncture may be
contraindicated due to raised intracranial pressure which puts the patient at risk for brain
herniation.

 However, if conducted the LP will reveal the presence of RBCs in the CSF.

Intracerebral Hemorrhage

 Intracerebral hemorrhage occurs due to bleeding of the branches of the cerebral artery which
have penetrated the pia mater to travel in the substance of the brain.

 Risk factors for intracerebral hemorrhage include chronic hypertension, which cause formation
of microaneurysms in these vessels.

 It presents with neurological deficits in the specific part of the brain affected.

Dural Partitions

 The four main dural partitions are the falx cerebri, falx cerebelli, tentorium cerebelli and
diaphragma sellae.

11
 The tentorium cerebelli is a horizontal dural partition.

 Its attachments are along the groove for transverse sinuses on the occipital bone
posteriorly, the superior border of the petrous part of temporal bone laterally, and the
posterior and anterior clinoid processes anteriorly.

 It separates the posterior part of the cerebrum (occipital lobe) supratentorially, from
the hindbrain (medulla oblongata, pons and cerebellum) infratentorially.

 The supratentorial and infratentorial regions communicate through the tentorial notch,
through which the midbrain passes.

 The falx cerebri and falx cerebelli are sagittal dural partitions.

 The attachment of falx cerebri is from the crista galli of ethmoid bone anteriorly, to the
middle of the tentorium cerebelli posteriorly.

 The attachment of falx cerebelli is from the middle of the tentorium cerebelli superiorly,
to the internal occipital crest inferiorly.

 The functions of the falx cerebri and falx cerebelli are to partition the cerebral and
cerebellar hemispheres, and in doing so mainly provide stability to reduce movement of
the brain within the cranial vault.

 The diaphragma sellae covers the hypophyseal fossa in the sella turcica of the sphenoid bone,
with a small opening through which the infundibulum of the pituitary gland passes.

 The dura mater is highly sensitive to pain. Intracranial lesions that stretch or damage the dura
mater lead to pain in different areas:

 The dura mater of anterior cranial fossa is innervated by ophthalmic division of

trigeminal nerve (CN V1). Thus, pain from lesions in this region is referred to the region
of the forehead.

 The dura mater of middle cranial fossa is innervated by mandibular division of

trigeminal nerve (CN V3) laterally and maxillary division of trigeminal nerve (CN V2)
medially. Pain caused by lesions in this region is referred to maxillary and mandibular
regions.

 The dura mater of the posterior cranial fossa is innervated by meningeal branches of
vagus (CN X) nerve and meningeal branches of anterior rami of C1-C3 spinal nerves.
Pain caused by infratentorial lesions is referred to the back of the head and neck.

12
Meningeal Features of the Spinal Cord

 Special features of the pia mater in the spinal cord include:

 Presence of denticulate projections or ligaments (teeth-like processes) that extend

laterally from the pia mater on each side of the spinal cord. They pass through the
subarachnoid space and through the arachnoid mater to attach on to the dura mater,
and in doing so prevent excessive motion of the spinal cord in the vertebral canal.

 Terminates at the level of LI/ LII at the conus medullaris of the spinal cord, but extends a
long thin process that extends inferiorly through the subarachnoid space to attach to the
arachnoid membrane, which ends at level of SII.

 The subarachnoid space terminates at the level of about SII.

 The interval between the conus medullaris and the inferior termination of the
subarachnoid space can be used to draw CSF fluid via lumbar puncture for 2 reasons: it
avoids the spinal cord at these levels, and the vertebral canal is incomplete at lumbar
levels, with spaces between the vertebral arches for insertion of a needle.

 However, as the spinal cord can extend as far as LIII in adults (and even further in
children), usually the LIV/LV intervertebral space is used for LP. LIII/ LIV may also be used
in adults.

 Special features of dura mater in the spinal cord:

 Below the termination of the subarachnoid CSF space at SII, the filum terminale
continues as the dural part of the filum terminale, which extends inferiorly to insert onto
the coccyx.

 The dura of the spinal cord lacks a periosteal layer, and only has a meningeal layer.

 The extradural space in the spinal cord is not a potential space, it is a true space. This
space is filled with loose areolar connective tissue, fat, lymphatics and venous plexuses.

13
CSF & VENTRICULAR SYSTEM
The Ventricular System & Spinal Canal

 Within the spinal cord, a central spinal canal lined by ependymal cells is a CSF-filled space

 The superior extension of this spinal canal into the brain forms the ventricular system

 In the embryological development of the brain, a number of ventricles develop:

 Two lateral ventricles, each positioned in one of the cerebral hemispheres, are the
ventricles of the telencephalon. They each open into the third ventricle via foramina of
Monro. Each lateral ventricle has a frontal horn (cavity of frontal lobe), body (cavity of
parietal lobe), posterior horn (cavity of occipital lobe) and temporal horn (cavity of
temporal lobe).

 The third ventricle is positioned in the midline between the two thalami. It is the
ventricle of the diencephalon.

 The cerebral aqueduct is the inferior extension of the third ventricle; it is not itself a
ventricle, but may be considered the central canal of the mesencephalon.

 The cerebral aqueduct opens into the fourth ventricle, which is the ventricle of the
rhombencephalon. The rhombus-shaped fourth ventricle is the etymology for the name
of the rhombencephalon. The fourth ventricle is located on the posterior aspect of the
pons and medulla oblongata, but anterior to the cerebellum.

 The fourth ventricle is continuous inferiorly with the spinal canal, which may terminate
in a slight dilation known as the terminal ventricle.

14
Production of Cerebrospinal Fluid (CSF)

 Cerebrospinal fluid is produced by specialized structures known as choroid plexuses which exist
in the walls of the lateral ventricle, the roof of the third ventricle and the roof of the fourth
ventricle.

 Specialized capillary tufts, covered by pia mater (together called the tela chorioidea) extend into
the walls and roofs of the relevant ventricles

 The tela choriodea are covered by ependymal cells, which line the ventricular system, to form
the choroid plexuses

 The tela choriodea produce a filtrate of the capillary plasma into the extravascular space; this
fluid is then transported across the ependymal cells with some modifications

 The ependymal cells transport the fluid across the ependymal epithelial layer by:

 Secreting Na+ ions, which is passively followed by Cl- and water.

 K+ anions are transported in reverse (from CSF to capillaries).

 Glucose is also transported, but inefficiently; thus CSF has a glucose concentration of
about 66% that of capillary plasma

Circulation of CSF

 CSF flows as follows: from lateral ventricles, via foramina of Monro into third ventricle, via
cerebral aqueduct to fourth ventricle. From the fourth ventricle it also circulates into the spinal
canal which it is continuous with inferiorly. This flow is aided by cilia of the ependymal cells.

 CSF exits from the fourth ventricle via a number of foramina, which open into expanded cisterns
of the subarachnoid space

 The foramina of Luschka are lateral openings of the fourth ventricle, which open into
the cerebellopontine cistern

 The foramen of Magendie is a posterior opening of the fourth ventricle, which opens
into the cerebellomedullary cistern

15
 Other major cisterns in the subarachnoid space include:

 The interpeduncular cistern which is anterior to the midbrain, between its two cerebral
peduncles. The cerebral penducles are two large bundles of white matter connecting the
brainstem with the cerebrum.

 The superior cistern is posterior to the midbrain

 The interpenducular and superior cisterns are connected by the ambient cistern, which
is a channel passing anteroposteriorly through the midbrain

Recycling of CSF into Circulatory System

 About 550ml of CSF is produced daily; however the total capacity of the ventricular system is
only about 130ml.

 The CSF is thus replaced three to four times daily; this volume must be removed from the
ventricular system in order to prevent excessive pressures

 CSF, upon circulating through the subarachnoid space, is returned to the superior sagittal sinus
by arachnoid granulations, each composed of a tuft of multiple arachnoid villi, which project
through the meningeal dura into the superior sagittal sinus

 These arachnoid villi are lined by an epithelium with large paracellular channels through which
CSF can flow; additionally the cells have pinocytotic activity which may allow them to transport
CSF and proteins across the arachnoid layer

16
 For CSF to drain from the subarachnoid space into the superior sagittal sinus, the pressure in the
subarachnoid space must exceed that of the superior sagittal sinus by about 1.5mmHg. Greater
pressures results in greater rates of flow.

 If the pressure difference between the superior sagittal sinus and the subarachnoid space falls
below 1.5mmHg, the arachnoid granulations and villi become compressed, and CSF will fail to
drain from the subarachnoid to the superior sagittal sinus. This mechanism prevents backflow of
CSF from the sinus into the subarachnoid space.

 Normally, small amounts of cells (RBCs, WBCs) in the CSF may be able to pass across the
arachnoid granulations and return to the circulation; however if there is excessive numbers of
cells in the CSF due to subarachnoid hemorrhage or inflammation, these may clog up the CSF
drainage system

Functions of the CSF

 The CSF functions as a cushion that dampens forces that may arise between brain and the skull
in trauma injuries. Excessive forces may however overcome this cushioning effect, and result
primarily in two different types of brain contusion:

 Coup injuries arise due to depressed skull fractures at the site of injury, which result in
brain contusions to the brain immediately deep to the site of impact

 Contre-coup injuries are brain contusions which occur on the side opposite to the site of
impact (e.g. blow to the back of the skull results in brain contusion of the frontal lobes).
Contre-coup injuries occur at lower forces than coup injuries, because they do not
require skull fracture to occur.

 Even in the absence of external forces, the CSF is important in allowing for buoyancy of
the brain so that gravity does not cause traction of the brain or spinal nerves against the
surfaces of the cranial vault and the vertebral canal. Due to the buoyancy, weak
arachnoid trabeculae and dentate processes are sufficient to provide structure support
to the CNS and prevent excessive abrasive forces. If excessive CSF is withdrawn during a
lumbar puncture, a patient may complain of headache due to the traction forces on
intracranial structures. Thus, after a lumbar puncture patients are required to lie supine
for at least one hour. These “spinal headaches” may be treated by injecting sterile saline
back into the CSF space.

17
 The CSF is a cushion whose volume can be adapted to regulate the total volume of intracranial
contents.

 In mild instances of brain swelling, intracranial pressure rises, and CSF clearance can
increase to bring total CSF volume down so as to accommodate the enlarged brain and
dampen the rise in intracranial pressure.

 In cases of brain atrophy, e.g. with old age, brain volume may decrease, and CSF volume
may increase to accommodate this and fill the extra space in order to function
effectively as a cushion.

 The CSF is a fluid that also functions as a vehicle for metabolic exchange, and is akin to the
circulatory system of the brain; the pia mater does not pose a significant barrier between the
brain substance and the CSF, and metabolic substances diffuse freely across it.

 The capacity of the circulatory system to nourish the brain is less than optimal because
of the existence of the blood-brain barrier, which limits the diffusion of substances
across brain capillaries with continuous tight junctions

 The CSF is produced by the choroid plexus which is not subject to the blood brain barrier.
Thus, the CSF is an important source of nourishment to the brain, which equilibrates
with the interstitial fluid of the brain. That said, the choroid plexus does not efficiently
transport all nutrients either; CSF glucose concentration is only 66% that of capillary
plasma.

 The CSF aids in removal of metabolic waste products from the brain by recirculating such
substances into the blood.

 The CSF aids in the transport and circulation of signalling hormones intracranially.
Melatonin secreted by the pineal gland, for example, circulates through the CSF to
regulate activity of the pituitary gland.

Lumbar Puncture Procedure

 The patient is positioned in the (left or right) lateral position, hugging his legs, with his knees
brought to his chin in order to best expose the lumbar intervertebral spaces.

 The site for LP is identified by locating the LIV/ LV intervertebral space (alternatively LIII/LIV in
adults may also be used) in the midline.

 A local anesthetic is applied to the region of LP.

 A needle is inserted at the site, with trajectory pointing towards the patient’s navel. The
structures pierced from superficial to deep are the skin, subcutaneous fascia, supraspinous
ligament, interspinous ligament, ligamentum flavum, epidural fat layer, dura mater and
arachnoid mater. Multiple resistances will thus be encountered along the way, resulting mainly
from the skin and subcutaneous fascia, ligaments and finally the dura.

18
 Once the needle has been inserted, a manometer may be attached to measure the CSF pressure.
Subsequently, three bottles of up to 10ml of CSF fluid may be withdrawn using sterile, clean vials.

 Subsequently, the needle is removed, and the patient is kept in the supine position to
convalesce for one hour. This prevents excessive traction forces on the brain and spinal nerves
on the bony surfaces of the cranium and vertebral canal, which can cause a headache.

Contraindications to Lumbar Puncture

 The main contraindication to Lumbar Puncture is raised intracranial pressure, which can result
in a herniation of the brainstem through the foramen magnum due to imbalance between
intracranial and intraspinal CSF pressures.

 Lumbar Puncture must thus be avoided if there is clinical suspicion of raised intracranial
pressure, e.g. unexplained loss of consciousness might suggest epidural hemorrhage.

 If there is such a suspicion, the clinician should check for following signs of raised ICP:

 Unexplained headache that occurs upon waking up. This occurs due to the flow of CSF
fluid to the head after the patient has been lying supine for an extended period of time.

 Focal neurological symptoms or seizures.

 Bilateral papilledema, which is defined as edema of the optic discs. The optic discs are
the terminations of the optic nerves in the eye, and may be observed to have ragged
rather than distinct edges by ophthalmoscopy in papilledema. This occurs because the
optic nerve is covered along its length by all three layers of meninges, and the
subarachnoid space of the brain communicates freely with that of the optic nerve.
(Indeed, the optic nerve is not a true cranial nerve; rather, it is a CNS tract, with
oligodendrocyte rather than Schwann cell myelination.) The optic artery and vein pierce
the dura mater and arachnoid mater to travel in the subarachnoid space along the
length of the optic nerve; under high CSF pressures the optic vein is compressed but not
the optic artery. This results in papilledema.

 When CSF pressure exceeds mean arterial pressure (MAP), the cerebral arteries are
compressed. This results in raised CO2 and reduced pH which is detected by the
medullary chemoreceptors, which stimulates a sympathetic outflow in order to increase
heart rate and contractility. The vastly increased stroke volume leads to a widened pulse
pressure. However, the high blood pressure stimulates a compensatory increase in
parasympathetic vagal outflow, which counteracts the sympathetic stimulus for heart
rate only. Thus blood pressure rises unopposed, but heart rate falls. This combination of
a widened and increased pulse pressure and reduced heart rate is known as Cushing’s
reflex.

 Brainstem herniation may result in disruption of the GIT regulatory centers in the
medulla and irritation to the vagus nerve. This can cause excessive parasympathetic
stimulation resulting in projectile vomiting.

19
Properties of CSF

 The normal volume of CSF in the ventricular system and subarachnoid space is normally about
130ml. The daily production of CSF is about 550mlday-1. Thus, the CSF is replaced three to four
times over daily. The maximum volume of CSF that can be withdrawn safely in LP is about 30ml.

 Upon inserting a needle for LP, a manometer can be attached to measure the CSF pressure,
which has a normal range of between 60-160mmH2O.

 The normal composition of CSF and its changes in various pathological conditions are described
in the table overleaf.

Hydrocephalus

 Hydrocephalus may be defined as an accumulation of CSF intracranially, either in the

ventricular system, the subarachnoid space or both.

 It may rarely occur due to a problem of overproduction of CSF, in a rare tumour of the
choroid plexus.

 Most causes of hydrocephalus are caused by problems of abnormal circulation and drainage.
They can be divided generally into communicating and non-communicating hydrocephalus.

 Non-communicating hydrocephalus results from an obstruction that occurs at or above the

level of the openings of the fourth ventricle into the subarachnoid space; they thus result in
enlargement of one or more of the ventricles.

 Obstruction at either of the foramina of Monro can occur due to the formation of a
choroid plexus cysts, in which fluid is trapped within a choroid plexus. These choroid
plexus cysts cause intermittent hydrocephalus because they may repeatedly block
and dislodge from the foramina of Monro. They produce a unilateral enlargement
of the lateral ventricle. As the cranial cavity cannot expand, the brain substance
atrophies to accommodate the expanded ventricle, resulting in a thin shell of
cerebral cortex surrounding the ventricle, which can be observed on CT.

 Obstruction of the cerebral aqueduct can occur due to congenital obstruction or due
to tumours in adults. They produce symmetrical enlargement of the lateral and third
ventricles. In adults, the cranial cavity cannot expand to accommodate the increased
CSF volume, and atrophies. In congenital stenosis however, the cranial bones of
infants have not yet formed strong fibrous suture joints, and the cranium may also
expand, disrupting normal development.

 Obstruction of the foramina of Luschka or the foramen of Magendie can result in

symmetrical enlargement of the lateral, third and fourth ventricles. These usually
occur due to cerebellar tumours, and produce atrophy of the cerebrum.

20
 Normal values Pyogenic Tuberculous Viral Subarachnoid Autoimmune
meningitis (caused meningitis meningitis hemorrhage Disease
by non-tuberculous
bacteria)
Appearance Clear, colourless fluid Yellow, turbid fluid Turbid fluid. Clear, Xanthochromia (clear, Clear, colourless
of fluid Fibrin web may colourless fluid yellow fluid) due to fluid
be observed. bilirubin produced by
heme degradation
Neutrophils 0 cells/ cm3 High Slightly raised Slightly raised High Absent
Lymphocytes <5 cells/cm3 Slightly raised High High High Absent
RBCs 0 cells/ cm3 Absent Absent Absent High Absent
Glucose 66% of capillary plasma < 50% capillary < 50% capillary > 50% capillary Equal to capillary Normal
glucose concentration. plasma glucose plasma glucose plasma glucose plasma glucose
Capillary plasma glucose must
be taken at the same time to
assess normal values.
Proteins 40mg/dL in CSF fluid. > 1000mg/dL due > 1000mg/dL due Raised, but Equal to capillary Raised due to
(7000-8000mg/dL in capillary to inflammatory to inflammatory < 1000mg/dL plasma protein immunoglobulins
plasma) exudate exudate

21
 Communicating hydrocephalus results from an obstruction that occurs below the level of the
openings of the fourth ventricle into the subarachnoid space; they thus result in minimal
enlargement of the ventricles.

 This may occur due to obstruction of the subarachnoid space near the base of the
brain, particularly in tuberculous meningitis due to caseous necrotic tissue and
fibrosis and formation of fibrous adhesions

 Alternatively, this may result from obstruction of the arachnoid granulations by RBCs
in subarachnoid hemorrhage or by inflammatory WBCs and necrotic tissue in
meningitis and encephalitis, with subsequent fibrosis that permanently impairs CSF
drainage. This causes a special type of hydrocephalus known as normal pressure
hydrocephalus; it is thought that with chronicity the brain atrophies to the extent
that a raised CSF pressure cannot be measured. Normal pressure hydrocephalus is
additionally associated with lesions to the regions directly adjacent to the superior
sagittal sinus, resulting in dementia, abnormal gait and loss of control of the
external urinary sphincter leading to incontinence (Wacky, Wobbly and Wet).

 This may also occur due to venous sinus thrombosis, which would result in raised
venous sinus pressure and compression of the arachnoid villi such that drainage of
CSF is impaired

 Finally, it may occur rarely due to internal jugular vein obstruction by tumours at the
base of the cranial cavity. As an aside, if one were to compress the internal jugular
vein during an LP procedure, a raised CSF pressure would be measured.

 Treatment of the basic forms of hydrocephalus is done by a silicone tube shunt, which can
shunt CSF to the right atrium (ventriculoatrial shunt) or to the peritoneum
(ventriculoperitoneal shunt).

 Hydrocephalus ex vacuo is a type of hydrocephalus that is not due to any abnormality in CSF
production, circulation or drainage. It results from atrophy of the caudate nucleus, which is
closely related to and forms the floor and lateral wall of the frontal horn and body of the
lateral ventricles, and the roof of the temporal horn of the lateral ventricles, which occurs as
part of Huntington’s Disease. This results in ventricular enlargement secondary to the
atrophy associated with motor deficits.

22
 Pseudo tumour cerebri is a syndrome which presents typically in young, obese women.

 It presents with raised CSF pressure, papilledema, vision problems and slit-like
ventricles observed on CT/ MRI scan.

 These features suggest the presence of a tumour and raised intracranial pressure.
However, upon further investigation no tumours can be found. The pathogenesis of
this disease is unknown.

 Finally, some types of vertebral column tumours external to the CNS may compress upon
the subarachnoid space along the spinal cord, leading to a communicating hydrocephalus
obstruction at that level.

 However, as a result of the compression, the subarachnoid space above and below
the lesion do not communicate with each other, and thus upon lumbar puncture a
raised CSF pressure is not observed.

 This can be confirmed by asking the patient to cough or by obstructing the internal
jugular vein, which would normally cause an immediate rise in CSF pressure;
however due to the lack of communication this does not occur. This is known as a
positive Quekenstedt’s sign.

23
Blood-Brain Barrier

 The blood-brain barrier (BBB) is the result of tight junctions between the capillary endothelium
of the brain which prevent the passage of some substances through it. It was previously thought
that the foot processes of astrocytes and the basement membrane contributed to the BBB, but
this is no longer the case.

 Lipophilic substances like O2, CO2, alcohol and many anesthetic drugs pass freely across the BBB

 The transport of hydrophilic substances across the BBB is mediated by transporters, including
AQP1 and AQP4 for water, GLUT1 for glucose, and various transporters for amino acids and
electrolytes.

 The main function of the BBB is thought to be to limit the fluctuations of ionic concentrations,
which have a significant impact on the resting membrane potential and function of neurons, as
well as to prevent the diffusion of some toxic substances into the brain (e.g. bilirubin).

 Three locations in the brain have capillary vessels which are not subject to the BBB, and are
known as circumventricular organs:

 Median eminence of hypothalamus, which samples and measures levels of hormones in

the blood and allows release of hormones

 The pineal gland

 The area postrema, which senses toxins in the blood and communicates this information
to neurons responsible for producing the sensation of nausea.

 Subfornical organ and Organum vasculosum of lamina terminalis (OVLT) are

osmoreceptors

 However, the BBB is not fully developed in neonates, and if hyperbilirubinemia occurs, bilirubin
can diffuse into the brain and cause CNS damage. It can damage the basal ganglia causing a
motor deficit, and the cerebral cortex causing mental retardation. This is known as kernicterus.

 The BBB is also not developed in leaky vessels of hypervascular brain tumours, and can be
breached in sites of inflammation due to meningitis or encephalitis. The disrupted BBB in these
locations allows for the delivery of drugs that would not normally cross the BBB.

Blood-CSF Barrier

 The blood CSF level is formed by tight junctions between the choroid epithelial cells surrounding
the choroid plexus, which are specialized ependymal cells. However these tight junctions do not
exist in the ependymal cells covering the rest of the ventricular system.

 However, once substances are in the ventricles, the may pass freely back into the brain
substance and equilibrate with the interstitial fluid of the brain. This is because the pia mater
and ependymal cells in regions other than the choroid plexus do not pose a significant barrier to
diffusion, and substances can pass freely across it.

24
DEVELOPMENT OF NERVOUS SYSTEM
Development of Embryo
Before we can discuss the development of the nervous system, a brief review of the stages of
embryology is helpful.

 Assuming a normal 28 day menstrual cycle, the Graffian follicle releases the ovum into the
uterine tubes on the 14th day. It subsequently becomes the corpus luteum.

 At this stage the ovum is arrested at metaphase of the second meiotic division.

 The ovum is surrounded immediately by a zona pellucida, which is a glycoprotein coat, and
superficial to that, by other cells forming the corona radiata.

 In the process of fertilization, the sperm release degradative enzymes to degrade the corona
radiata and zona pellucida in order to penetrate the layers and reach the ovum.

 A number of sperm compete for the fertilization of the ovum; the first sperm to penetrate the
corona radiata and zona pellucida is able to fuse its membrane with that of the ovum. It releases
its nucleus into the cytoplasm of the ovum, which is now called the male pronucleus.

 Upon fusion of the cell membranes of the ovum and sperm, the female nucleus is triggered to
complete the second meiotic division. One of its daughter nuclei is now discarded as the polar
body. The other becomes the female pronucleus.

 The female nucleus and the male pronucleus subsequently fuse to become the zygote.

 The zona pellucida still surrounds the zygote and restricts growth in volume; thus cell division
results in a decrease in individual cell volume. The conceptus proceeds through the two, four
and eight cell stages. These stages are collectively known as the blastula stage.

 At the sixteen-cell stage it is now called a morula (morula = mulberry). The cells begin to
differentiate into a central core called the inner cell mass and a surrounding outer cell mass.
The inner cell mass will eventually form the trilaminar disc; the outer cell mass contributes to
formation of the placenta.

 Subsequently, the outer cell mass becomes a hollow sphere, which expands faster and becomes
separated from the inner cell mass, except by an attachment at one point. The hollow sphere
becomes a fluid-filled cavity; at this stage the conceptus is known as a blastocyst.

 The outer cell mass of the blastocyst develops into a villous structure called the trophoblast. The
villi become particularly prominent at the embryonic pole of the blastocyst.

 The central core of each villus is formed by a column of cells known as the cytotrophoblast. The
cells on the surface of the villus fuse their plasma membranes together, to become the
syncytiotrophoblast, which is a collection of cell nuclei floating in a collective sea of cytoplasm.

 The process from fertilization to formation of the blastocyst takes about one week.

25
Implantation of the Blastocyst

 The first important task of the trophoblast is to release degradative enzymes that allow the
blastocyst to implant in the uterine lining of the mother. This occurs between days 8-10.
Implantation usually occurs in the superior and posterior part of the uterus.

 The second important task of the trophoblast is to ensure the continued maintenance of the
vascular, secretory state of the uterine lining, which has been maintained up to this point by
progesterone secreted by the corpus luteum. This is necessary, because without further support
the corpus luteum will begin to degrade after about 10 days, exactly around the time of
implantation.

 This is accomplished by the secretion of Human Chorionic Gonadotropin (HCG), which is

secreted by the cytotrophoblast. Under the influence of HCG, the corpus luteum proliferates to
become the corpus gravidum, ensuring the continued secretion of progesterone.

 HCG for pregnancy tests is detectable in the serum from about 8 days and in the urine from
about 10 days onwards.

 Eventually the trophoblast itself will take over the production of progesterone.

Formation and Development of the Bilaminar Disc

 The central mass of cells begins to proliferate, and forms a double-layered bilaminar disc that
spans the central fluid filled disc and divides it into two. The two layers of the disc are known as
the epiblast and the hypoblast.

 The fluid filled cavity above the epiblast becomes the amniotic sac; the cavity below the
hypoblast becomes the yolk sac.

 Towards one end of the bilaminar disc, the two discs are closely adhered together; this region is
known as the prechordal plate, which eventually becomes the mouth. The cephalic and caudal
ends of the fetus are thus defined.

 Near the middle of the bilaminar disc, an area of epiblast cells begin to degenerate. This area is
known as the primitive node. A linear streak of cells extending caudally from the primitive node
also degenerates. This streak becomes known as the primitive streak.

 Epiblast cells begin to move towards the region of the primitive streak and node, and
subsequently pass into it, invading the space between the epiblast and the hypoblast. It replaces
both epiblast and hypoblast, differentiating to form ectoderm, mesoderm and endoderm.

26
Development of Neural Tube

 Cephalic to the primitive node, the invading mesoderm forms a linear column of cells called the
notochord, which extends cephalically as far as the prechordal plate. The remnant of the
notochord in adults is the nucleus pulposus of the vertebral discs, which is surrounded by a
fibrous anular ring. In the fetus, however, the notchord plays an important role in the
development of the nervous system.

 The notochord secretes growth factors that stimulate the overlying ectoderm to proliferate and
differentiate into a thickened plate known as the neural plate. This neural plate subsequently
develops into the nervous system.

 The lateral edges of the neural plate begin to elevate, forming neural folds at their junctions
with the rest of the ectoderm lateral to it.

 The median line of the neural plate is depressed downwards, forming a linear neural groove.

 Some cells escape from the crests of the neural folds and migrate laterally; these become neural
crest cells.

 The neural folds continue to elevate, and subsequently extend medially to meet each other and
fuse. Thus, the neural tube is formed.

 The central canal of the neural tube corresponds to the CSF-filled cavity that develops into the
spinal canal and ventricular system of the brain.

 Fusion of the neural tube begins in the middle, and extends cephalically and caudally.

 Closure of the neural tube at the anterior end occurs on day 26, and closure at the
posterior end occurs on day 27.

 Deficiency of serum folic acid in the mother can lead to failure of the neural tube to
close.

 The most rostral part of the closed neural tube corresponds to the lamina terminalis in
the adult brain.

27
 Failure to close the posterior neural pore results in a group of diseases known as spinal bifida, in
which there is a failure of the vertebral arches to close around the spinal cord.

 In the most severe case (myelocele), the spinal cord itself does not form correctly; even
where the spinal cord forms, the incomplete closure results in failure of the
mesenchyme forming the vertebral arches to migrate to surround the spinal cord.

 These can result in spinal cord and meningeal herniation out of the vertebral body
(meningomyelocele), only meningeal herniation (meningocele) or neither (spinal bifida
occulta).

 Failure to close the anterior neural pore leads to anencephaly. Anencephaly is incompatible with
extrauterine life.

28
Development of the Brain

 Once the neural tube has formed, the cephalic end of the neural tube develops three of
balloonings, called primary vesicles.

 From cranial to caudal, these primary vesicles correspond to the prosencephalon,

mesencephalon and rhombencephalon that develop onto the forebrain, midbrain and hindbrain.

 Subsequently, a number of secondary vesicles develop from the primary vesicles.

 The prosencephalon develops into the telencephalon and diencephalon. The

telencephalon vesicle expands much more rapidly than the diencephalon and the other
secondary vesicle structures, and forms two large sacculations.

 The mesencephalon remains unchanged, developing into midbrain.

 The rhomboncephalon develops into the metencephalon and myelencephalon, which

become the pons + cerebellum and the medulla oblongata respectively.

 Development of the diencephalon includes the following structures:

 Thalamus and its medial/ lateral geniculate bodies, Hypothalamus, Subthalamus,

Epithalamus and pineal gland

 pituitary gland

 Visual structures including the retina and uveal tract, which consists of the ciliary body,
iris and choroid.

 The first part of the telencephalon does not expand as much as the other structures, and
becomes the insular cortex, which is responsible for general visceral afferent sensations.

 Rostral to the insular cortex, the rest of the telencephalon expands most rapidly, forming the
cerebral hemispheres; it folds in such a manner forming the following lobes from caudal to
rostral: the frontal, parietal, occipital and temporal lobes. This manner of development is the
embryological basis of the formation of the lateral ventricles in a “spiral”; the ventricular system
is essentially a continuation of the central canal of the spinal cord into the brain.

29
Cellular Basis of Brain Development

 Primary neuronal cells arise from the ventricular zone and develop under the influence of
growth factors from the notochord

 These primary neuron cell bodies originate in the deep regions of the neural tube initially, in the
ventricular zone

 In order to form the gray matter cortex of the brain, these neurons must migrate outwards

 They do so with the assistance of radial glial cells, which extend fibers peripherally to the
marginal zone

 The primary neuronal cells then migrate along the radial glial fibers to the cortical plate, where
they differentiate

 Six individual waves of migration occur, which form the 6 layers of the cerebral cortex

30
Development of Spinal Cord

 Cells in the neural tube of the more caudal region develop into the spinal cord.

 Cell bodies in neural tube form the alar plate, which develops into the dorsal sensory horn, and
the basal plate, which develops into the ventral motor horn.

 Some of the neural crest cells that migrated away from the neural crests now develop into the
dorsal root ganglia; they extend central processes proximally to the secondary sensory neurons
in the dorsal horn, and peripheral processes distally to the sensory organs.

 The secondary sensory neurons may extend their axons in three different ways:

 posteriorly in the dorsal column, to become ascending tracts

 by crossing over to the contralateral side, to ascend in the lateral column as lateral
tracts

 by crossing over to the contralateral side, to ascend in the anterior column as anterior
tracts

 Other features formed in the spinal cord include the ventral median vissure and dorsal median
sulcus.

31
Development of Brainstem

 The brainstem is the superior continuation of the spinal cord. Its development can be visualised
as being derived from the basic structure of the spinal cord: By placing one’s fingers in the dorsal
median sulcus of the spinal cord and prying it apart, the structure of brainstem would be derived.

 The result of this is that the alar plates are arranged laterally and basal plates medially:

 Decussations from ascending and descending tracts in the brainstem split the gray matter into
the reticular formation and various nuclei

 Many of these are nuclei of the cranial nerves

 Due to the embryological origin of sensory nuclei from the alar plate and motor nuclei from the
basal plate, sensory nuclei of cranial nerves are arranged laterally while motor nuclei are
arranged medially.

Derivatives of Neural Crest Cells

 Neural Crest Cells develop into a wide variety of structures including:

 Sensory ganglia (dorsal root ganglia)

 Autonomic ganglia (comprising ganglia of cranial nerves and peripheral spinal nerves,
e.g. sympathetic chain ganglia, parasympathetic ganglia). A specialized postganglionic
neuroendocrine structure is the adrenal medulla.

 Parafollicular C cells of the thyroid gland which secrete calcitonin

 Schwann cells

 Leptomeninges, forming the pia-arachnoid meninges (Dura mater is derived from

mesoderm)

 Bones of the neurocranium and odentoblasts in the teeth

 Melanocytes

 Conotruncal cushions and aortopulmonary septum of the heart.

32
AUTONOMIC NERVOUS SYSTEM
Introduction

 The autonomic nervous system is known as the General Visceral Efferent (GVE) arm of the
motor PNS. It thus stimulates involuntary motor activity.

 The autonomic nervous system innervates all innervated structures in the body except skeletal
muscle, which is innervated by neuromuscular junctions from the Somatic Visceral Efferent arm
of motor PNS. This includes

 Secretomotor activity of all glands

 Smooth muscle innervation

 Myocardium, including cardiomyocytes and specialized conductive cells in the AV nodes,

SA nodes and purkinje fibres

 The autonomic nervous system comprises three arms:

 Sympathetic

 Parasympathetic

 Enteric nervous system, which receives input from the sympathetic and
parasympathetic systems, and is itself divided into the submucosal and myenteric
plexuses which supply the glands and smooth muscle of the GI tract respectively.

Activation of Autonomic Command Centers

 Perception of environmental stresses from higher brain centers occurs in various parts of the
brain, and is the primary stimulus for activation of autonomic command centers:

 Auditory input from auditory cortex in temporal lobe

 Visual input from visual cortex in occipital lobe

 Comparison of input to past experiences and memory from parietal lobe

 Unpleasant thoughts from the frontal lobe

 Pain from pain pathways, particularly slow pain pathways

 These brain centers send signals to the limbic system, which is concerned with emotion,
short term memory, smell and primitive behaviours associated with survival and
perpetuation of the species.

 The limbic system integrates these responses; the relevant centers (e.g. fear centers) may
become activated. These centers then send signals to the hypothalamus, which is the center
for command of the autonomic nervous system.

33
  The hypothalamus is split into two divisions:

 An anteromedial parasympathetic center

 A posterolateral sympathetic center

 These two divisions are in balance with one another; an external stimulus may upregulate
one and downregulate the other to shift the balance.

Sympathetic System

 From the sympathetic center in the hypothalamus, a polysynaptic pathway descends in the
spinal cord, to synapse on pre-ganglionic sympathetic neurons located in the lateral horn of
gray matter at thoracolumbar levels (Usually TI to LII).

 These pre-ganglionic sympathetic neurons send fibers that exit via anterior roots of spinal
nerves, and pass into the paravertebral sympathetic trunks via white rami communicantes at
thoracolumbar levels. From there, the fibers may:

 Synapse immediately in the sympathetic ganglia at the same spinal cord level, or
ascend/ descend a few levels before synapsing. These subsequently return to the
spinal nerves via gray rami communicantes. Ascent and descent is necessary to
provide sympathetic innervation to spinal nerves at cervical and sacral levels. This
includes the cardiac splanchnic nerves.

 Pass through the sympathetic ganglia without synapsing, but instead run in thoracic
or lumbar splanchnic nerves to synapse in prevertebral ganglia, before being
distributed to abdominal viscera via the prevertebral plexus.

 Pass through the sympathetic ganglia and prevertebral ganglia without synapsing,
but synapse onto the adrenal medulla, where the modified post-ganglionic cells
neuroendocrine cells secrete adrenaline and noradrenaline into the bloodstream.

 The pre-ganglionic sympathetic fibers use acetylcholine as their neurotransmitter. They

often synapse directly onto the post-ganglionic sympathetic fibers which secrete
noradrenaline, but may also synapse onto an intermediate dopaminergic neuron first.

 The sympathetic stimulation is received at tissues as follows:

 Most tissues to be activated by sympathetic stimulation have α1 receptors. The heart,

juxtaglomerular apparatus of kidneys and adipocytes have β1 receptors instead.

 Most tissues to be inhibited have β2 receptors; platelets, parts of the GIT (pancreatic
β cells) and presynaptic nerve endings have α2 receptors instead.

34
  Effects of sympathetic stimulation include:

 At the peripheries: activation of arrector pili muscles, sweat glands and

vasoconstriction at all vascular beds except skeletal muscle beds which vasodilate.

 Skeletal muscle: Overactivation of muscle spindles leads to de-synchronisation of

intra- and extra-fusal muscle spindle fibers. This leads to poorer estimation of the
muscle stretch, and leads to muscle tremors due to poorer coordination between
agonistic and antagonistic muscles.

 Eyes: Activation of radial muscle of iris to dilate pupils, inhibition of ciliary muscles to
accommodate for far vision.

 Respiratory: Tachypnea due to activation of respiratory centers, as well as smooth

muscle bronchodilation and mast cell inhibition.

 Cardiovascular system: Increased chronotropic, dromotropic and inotropic effects.

Note that aside from vasoconstriction at the peripheries and vasodilation of skeletal
muscle beds, coronary and cerebral blood supply are largely unaffected by
autonomic innervation, and are largely controlled by local autoregulation.

 GIT: Decreased secretomotor effects, constriction of sphincters and inhibition of

peristalsis. Metabolically, there is stimulation of lipolysis in adipocytes by β3
receptors, upregulation of glycogenolysis and gluconeogenesis, and inhibition of
glycogenesis in the liver. Release of insulin by pancreas is inhibited by α2 receptors.

 Urinary Bladder: Inhibition of detrusor muscle, contraction of urethral sphincters.

 Genitalia: Ejaculation occurs in men if there is a prior erection. In women, α1

receptors in the myometrium normally cause contractions to promote uptake of
semen; in pregnancy however, β2 receptors are produced due to the effects of
estrogen and progesterone, leading to inhibition of contractile activity so as to
preserve the conceptus.

Singalling Pathway of Adrenergic and Acetylcholine Receptors

These pathways are well covered in standard physiology textbooks and are not covered here.
Additional interesting points are mentioned here:

 Caffeine acts as a stimulant by inhibiting phosphodiesterase enzymes, and in doing so enhances

Adrenergic Gs cAMP-mediated signalling by preventing cAMP breakdown.

 Thyrotoxicosis leads to upregulation of adrenergic receptors and leads to higher sensitivity to

sympathetic stimulation.

35
Parasympathetic System

 As with the sympathetic system, higher command originates from the hypothalamus, but this
time from the anteromedial parasympathetic center.

 The parasympathetic center sends descending fibers in a polysynaptic tract that synapse on pre-
ganglionic craniosacral nuclei in the spinal cord.

 The pre-ganglionic parasympathetic fibers produce acetylcholine (Ach)

 They synapse distally on postganglionic neurons, which may be found in distinct ganglia,
or found diffusely in intramural structures e.g of GIT, heart.

 The cranial nerve nuclei include the Edinger-Westphal nucleus in the midbrain, the
superior salivatory nucleus in the pons, and inferior salivatory nucleus and dorsal
motor nucleus of Vagus in the medulla.

 The sacral parasympathetic nuclei can be found in the lateral horn of the SII to SIV
segments of the spinal cord.

36
 The Edinger-Westphal nucleus in the midbrain gives off parasympathetic fibers that run in the
oculomotor nerve (CN III).

 It synapses distally in the ciliary ganglion.

 The postganglionic fibers pierce the sclera and run between the sclera and choroid,
supplying the circular muscle of the iris and ciliary muscles.

 The preganglionic fibers run in the superolateral parts of CN III; thus supratentorial
space-occupying lesions can compress upon it and cause irritation or damage.

 Irritation to the parasympathetic fibers leads to increased firing, leading to myosis and
pupil constriction; these are neurosurgical emergencies.

 Complete damage to the parasympathetic fibers results instead in pupil dilation.

 The superior salivary nucleus in the midbrain gives off parasympathetic fibers that run in the
facial nerve (CN VII).

 It synapses on the pterygopalantine ganglion.

 Some postganglionic fibers exit via the inferior orbital fissure to supply the lacrimal
gland and via sphenopalatine foramen to supply nasal/ palatine mucosal glands.

 Others exit via chorda tympani to supply the submandibular and sublingual glands.

 The inferior salivary nucleus gives off parasympathetic fibers running in the glossopharyngeal
nerve (CN IX).

 It synapses on the otic ganglion.

 Postganglionic fibers run in the auriculotemporal nerve to supply the parotid gland.

 The dorsal nucleus of vagus supplies parasympathetic fibers via the Vagus nerve (CN X). It
supplies several structures, including

 Neck structures, like the pharynx, larynx and esophagus

 Thoracic viscera, including the heart and lungs. Importantly, the right vagus nerve
supplies the SA node while the left supplies the AV node; transection of the left and right
vagus lead to different clinical consequences.

 Abdominal viscera, including the foregut and midgut and accessory GI organs (liver and
pancreas).

 The sacral parasympathetic nuclei are located in the lateral horn of SII to SIV and provide
parasympathetic fibers running in pelvic splanchnic nerves.

 These provide parasympathetic supply to the hindgut, bladder and genitalia (erection/
vaginal secretions).

37
Important Differences Between Sympathetic and Parasympathetic Systems

 The sympathetic system is associated with thoracolumbar outflow while the parasympathetic
system is associated with craniosacral outflow

 The sympathetic pre-ganglionic fibers are shorter, and usually synapse in more proximal ganglia;
the parasympathetic pre-ganglionic fibers are longer and synapse in distal ganglia close to the
target tissue.

 Sympathetic activation is usually associated with a diffuse, global effect on all target structures;
individual structures cannot be activated independently. Parasympathetic activation of the
target organs can occur independently. (E.g. one does not have to salivate, defacate and urinate
while crying at the same time.)

 The effect s of the two systems are often not exactly opposite. Whereas the sympathetic
nervous system has an effect on both heart rate (chronotropic, dromotropic) and contractility
(inotropic), the parasympathetic system only has an effect on heart rate but not contractility.

 An overactivation of both sympathetic and parasympathetic systems (e.g. in the Cushing reflex
due to increased intracranial pressure) leads to a paradoxical reduction in heart rate with
concomitant increase in blood pressure.

Integration of Autonomic and Somatic Motor Systems – Micturition

 Micturition is under the control of three muscles:

 The detrusor muscle and internal urethral sphincter are under autonomic control. The
existence of the internal urethral sphincter is poorly defined in females.

 The external urethral sphincter complex is under voluntary control.

 During the filling of the bladder, the detrusor muscle relaxes to allow expansion of the bladder
to prevent a rise in pressure. The internal urethral sphincter constricts to prevent micturition.
The external urethral sphincter, which is under voluntary control, may also be constricted to
assist the internal urethral sphincter.

 Micturition is under the control of a combination of parasympathetic, parasympathetic and

somatic motor control, all of which are themselves regulated by other centers.

 As the bladder expands and there is increased stretch, the 1o sensory neuron is stimulated.

 It participates in a direct spinal cord reflex arc to increase parasympathetic outflow and
stimulate micturition, synapsing directly on parasympathetic neurons in the lateral horn.

 Additionally, it also crosses over and synapses on a 2o sensory neuron, which ascends in
the lateral column of white matter to the cerebral cortex, which brings the sensation to
consciousness, and to the pontine and midbrain micturition centers.

38
 If higher brain centers determine that the time and place for micturition is inappropriate, it
triggers sympathetic outflow from the autonomic centers of the hypothalamus and through
preganglionic nuclei located at lumbar levels of the spinal cord.

 Sympathetic stimulation to the detrusor muscle results in relaxation (β2 receptors).

 Sympathetic stimulation to the internal urethral sphincter results in constriction (α1

receptors).

 These serve to overwhelm and counteract the parasympathetic stimulus to micturate.

 Unlike most forms of sympathetic outflow which has relatively global effects, this
sympathetic control is relatively specific and independent of other autonomic control.

 As the bladder expands further, sympathetic stimulation alone may be insufficient to counteract
the parasympathetic reflex arc.

 At this time, the urge to micturate is extremely strong, and somatic activation of the
external urethral sphincters is necessary to maintain continence.

 This somatic activation is controlled by a specific somatic nucleus known as the nucleus
of Onuf, which is located in the anterior horn gray matter.

 The sympathetic, parasympathetic and somatic motor control are all themselves under the
influence of the pontine micturition center, which is stimulatory for micturition.

 The pontine micturition center receives input from the 2o sensory neuron directly, as
well as from higher centers in the cerebral cortex.

 If higher centers decide that the time and place for micturition is appropriate, or if there
is excessive direct stimulation from 2o sensory neuron, the pontine micturition center is
stimulated.

 Its effects are to inhibit sympathetic outflow from lumbar levels, increase
parasympathetic outflow from sacral levels, and inhibit nucleus of Onuf.

 The detrusor muscle contracts slightly, and the internal urethral sphincter begins to
relax. The external urethral sphincter also relaxes.

 Urine is allowed to trickle into the neck of the bladder, which is heavily innervated by
sensory fibers. A strong positive feedback parasympathetic reflex arc is triggered, and
the micturition reflex is completed.

 In men, the bulbospongiosus muscle may additionally contract under somatic control to
extrude the last drops of urine.

 The midbrain micturition center also receives input from the 2o sensory neuron; its actions are
inhibitory for the micturition reflex.

39
Clinical Applications to Micturition

 In syphilis infection, tabes dorsalis can occur in which there is inflammation and fibrosis of the 1o
sensory fibers in the region of the dorsal roots of the spinal cord. This causes deafferentation of
the urinary bladder.

 As there is no sensory input to the higher brain centers or the pontine micturition center,
there is no stimulus for the pontine micturition center to stimulate micturition.

 Furthermore, there is no sensory input to the parasympathetic reflex arc at sacral levels.

 Midbrain micturition centers are likely constitutively active, resulting in urinary retention.

 Once the bladder reaches maximum capacity, overflow incontinence develops; the
bladder enlarges.

 There is no urge to void.

 In cauda equina syndrome, lesions to the cauda equina lead to denervation of the bladder,
which eliminates both sensory and motor (autonomic and somatic) outflow to the bladder.

 Control of the bladder is purely under myogenic autoregulation. This is known as

automatic bladder.

 When the bladder reaches a certain pressure, there is a purely myogenic stimulation to
micturate. Micturition proceeds without control, but there is incomplete bladder
emptying.

 However, as bladder emptying is incomplete, the bladder constitutively faces a relatively

high pressure at all times, only emptying above that pressure. This leads to hypertrophy
of the bladder and a small bladder.

 There is no urge to void.

 In spinal cord transection, there is an interruption of higher center inhibitory control of the
sacral parasympathetic nuclei.

 The lower motor neurons in the parasympathetic nuclei are no longer innervated. The
initial effect is a loss of a trophic stimulus on the parasympathetic neuron, and as a
result it enters a shock phase where they fire less than usual. The bladder becomes
loose and flaccid.

 Subsequently, these lower motor neurons recover, and begin to overfire.

 Overfiring at the local level leads to a spastic bladder. The local reflex arc is still active,
and the bladder hypertrophies in response to the trophic stimulus and is also small.

 This is similar to what occurs in an upper motor neuron lesion.

 There is no urge to void as there is also an interruption of afferent fibers.

40
Other Clinical Correlates

 Hirschprung’s Disease

 results from failure of neural crest cells to migrate and form postganglionic
parasympathetic fibers in the distal GIT.

 Usually presents in newborns. Can extend from the rectum as far proximally as the
descending colon.

 There is a failure of peristalsis and accumulation of faeces proximal to the aganglionic

segment, leading to pathological distension described as megacolon.

 Familial Dysautonomia

 Is an autosomal recessive disease usually found in Jews due to intermarriage in this

religious/ ethnic isolate.

 Progressive neural degeneration in autonomic and sensory ganglia.

 Results in abnormal sweating, fluctuations in BP, GIT hypotonia, poor feeding and
sensory loss.

 Shy-Dragger Disease

 Progressive neural degeneration in sympathetic pre-ganglionic fibers.

 Results in sweating deficiency, orthostatic hypotension, incontinence and impotence

due to inability to ejaculate.

 Raynaud’s Disease

 Oversensitivity of autonomic stimulation in peripheral vessels, leading to hyper-

responsiveness to cold and emotional stimulus causing vascular hyperspasticity

 Characterised by initial vasoconstriction (white), cyanosis (blue) and subsequent

hyperemia (red).

 Described as Raynaud’s phenomenon when found to be secondary to some other cause.

41
 Botulism

 Clostridium botulinum releases botulinum toxin, which impairs cholinergic nerve endings.

 Normally, synaptotagmin proteins on vesicles bind with synaptobrevin or syntaxin

proteins on the internal plasma membrane when Ca2+ influx changes the configuration
of the latter.

 Botulinum toxin is a proteolytic enzyme that breaks down syntaxin, preventing vesicle
fusion.

 There is failure of cholinergic transmission at NMJs, causing muscle flaccidity, and

autonomic system.

 Not to be confused with tetanus toxin, which inhibits the same mechanism in inhibitory
glycinergic interneurons called Renshaw cells, which fail to inhibit somatic motor
neurons. These somatic motor neurons overfire and lead to muscle spasticity.

 Latrotoxin

 Produced by black widow spiders

 Causes hyperfusion of synaptotagmin with syntaxin and synaptobrevin, leading to

cholinergic crisis, in which the ANS is overactivated.

42
SENSORY SYSTEM & ASCENDING TRACTS
Overview of Organisation of Sensory System

 The main function of the sensory system is to receive information about the self and
environment and transmit this information to the CNS

 This information (a stimulus) is first detected by receptors, which may be free nerve endings or
composed of specialised groups of cells. Receptors are biological transducers which convert
energy from the environment (e.g. electromagnetic energy, sound energy) into electrochemical
energy in the form of action potentials

 This action potential is transmitted by the 1o sensory neuron via peripheral processes of the
sensory neuron, to the cell body itself at the dorsal root ganglion. From the dorsal root ganglion,
central processes extend inward to the dorsal horn of the gray matter in the spinal cord, where
they may or may not synapse.

 From the dorsal horn, axons extend into the white matter of the spinal cord which ascend
towards the brain. These bundles of axons are called ascending tracts.

 The white matter of the spinal cord is anatomically divided by the central gray matter column
into the dorsal columns, lateral columns and anterior columns.

 Functionally, the dorsal column is distinct and exclusively contains ascending tracts that
transmit information from the PNS in a cephalic direction towards the brain.

 The lateral and anterior columns are collectively known as the anterolateral tract
system; they carry both ascending tracts transmitting sensory information and
descending tracts transmitting motor information.

 Not all sensations transmitted reach the level of consciousness. For example, proprioceptive
information is sent to both the cerebral cortex and the cerebellum; however even if the
pathways to the cerebrum are not active and do not reach the level of consciousness, pathways
to the cerebellum can continue to transmit proprioceptive information for activities like walking
and running at a subconscious level.

43
Dorsal & Anterolateral Ascending Tract Systems

 The tracts of the spinal cord are analogous to roads. The dorsal ascending tracts are more
recently evolved, and may be thought of as the highways of sensory information; the
anterolateral ascending tracts are more analogous to primitive dirt roads.

 The dorsal ascending tract highways:

 transmit information about sensations which are more recently evolved. Such sensations
include fine touch, vibration, 2-point discrimination and proprioception.

 Carry high speed information. Their neurons are heavily myelinated which allows them
to carry sensory information to the brain more quickly.

 Their tracts are anatomically organised in a discrete, topographical fashion within the
dorsal column. This is analogous to the well-demarcated lanes on a highway.

 This is associated with good localisation of the anatomical origin of the stimulus.
Additionally, such sensations are typically associated with finer gradation, that is, there
is better differentiation between weak and strong stimuli.

 The dorsal column tracts ascend throughout the spinal cord uncrossed on the ipsilateral
side of origin.

 The anterolateral ascending tract dirt roads:

 Transmit information that is more primitive, and also wider in variety (everything from
donkey carts to older cars may be found on dirt roads, but only new cars are found on
the highway). These sensations include crude touch, pain, temperature sensation (hot
and cold), ticklish sensations, itch and sexual sensations.

 Carry relatively lower speed information. Their fibers are poorly myelinated and thus
transmission is slower.

 There is poor topographical organisation of the tracts.

 This corresponds to a poor localisation of these types of sensations as well as a poor

gradation of the strength of the stimulus.

 The anterolateral tracts cross to the contralateral side of the spinal cord at or slightly
above/ below the level of entry of the 1o neuron; they thus ascend in the spinal cord
crossed and on the contralateral side of origin.

44
Dorsal Column Medial Lemniscus Pathway

 The dorsal column medial lemniscus pathway is the full pathway by which fine touch, two-point
discrimination, vibration and propriception sensations are transmitted from the peripheral
receptors through the dorsal column system to the brainstem and then to the brain.

45
 The peripheral sensory receptor receives information about the self or the environment and
triggers an action potential in the peripheral process of a 1o sensory neuron. Receptors include:

 Meissner’s corpuscles for fine touch

 Pacinian corpuscles for vibration and pressure

 Golgi tendon organs for proprioception

 Muscle spindle fibers for proprioception

 This action potential is sent to its cell body located in the dorsal root ganglion.

 The cell bodies of the 1o sensory neuron in the dorsal root ganglion sends central processes into
the medial division of the dorsal root. They do not synapse in the dorsal horn gray matter, but
pass immediately into the ipsilateral dorsal column of the spinal cord.

 The dorsal column tracts are topographically organised as follows: the fibers originating from
inferiormost levels are arranged most medially, while the fibers originating from superiormost
levels are arranged most laterally.

 The fibers are arranged into two main tracts:

 The fasciculus gracilis located medially carries fibers from the lower limbs and the trunk
up to the dermatome of T6

 The fasciculus cuneatus is located laterally and carries fibers from the upper limbs and
trunk from the level of T5 upward.

 As such, the fasciculus cuneatus is found only in relatively more superior sections of the spinal
cord, while the fasciculus gracilis is also found in more inferior sections of the spinal cord.

 In the medulla, the fasciculi gracilis and cuneatus tracts synapse onto 2o cell bodies located in
the nuclei gracilis and cuneatus respectively.

 From the nuclei gracilis and cuneatus, arcuate fibers are projected which decussate into the
contralateral side of the medulla, forming the medial lemniscus tract. While fasciculi are used to
denote round bundles of axons, lemnisci describe tracts that are flattened in shape.

 The medial lemniscus thus ascends on the contralateral side of the origin of the stimulus,
eventually synapsing onto the ventro-posterior lateral nucleus of the thalamus

46
 We digress briefly to discuss the neuroanatomy of the thalamus:

 It is divided by internal medullary laminae of the thalamus, which are basically white
matter sepata, into an anterior nucleus, a medial nucleus and a lateral group

 The lateral group itself is divided into a ventral group and dorsal group

 Important nuclei in the ventral group include the ventroanterior (VA) nucleus,
ventrolateral (VL) group (sometimes known as the ventrointermediate group) and the
ventroposterolateral (VPL) and ventroposteromedial (VPM) nuclei.

 The ventroposteromedial nucleus (VPM) is a relatively small nucleus responsible for

receiving 1. general somatic afferent sensations from the head and neck and 2. receiving
the special sense of taste.

 The ventroposterolateral nucleus (VPL) is larger than the VPM, and receives the general
somatic afferent sensations from the rest of the body, and is thus where the DCML
pathway synapses onto. The other nuclei will be discussed elsewhere subsequently.

 From the VPL of the thalamus, the 3o neurons extend white matter tracts via the posterior limb
of the inner capsule

 In order to describe the inner capsule, we must describe the relations of the thalamus, the
lateral ventricles, the caudate nucleus and the lentiform nucleus.

 The thalami (in red) are two egg-shaped structures of gray matter immediately lateral to
the third ventricle and superior to the midbrain.

 Lateral to the two thalami are the caudate nuclei (in green); the caudate nucleus is a C-
shaped structure which sits on the inside of the C-shape of the lateral ventricles.

 The lentiform nucleus (in blue) is composed of the putamen and the globus pallidus, and
is located posterolateral to the head of the caudate nucleus. It is thus also lateral to the
thalamus.

47
  The lentiform nucleus is surrounded by a capsule of white matter, which has two parts: a
more medial inner capsule and a more lateral outer capsule.

 The inner capsule thus separates the lentiform nucleus from the thalamus.

 The inner capsule is said to have an anterior limb, posterior limb and a genu, which is
the “knee” of the inner capsule (the angle at which the anterior and posterior limbs
meet)

 The 3o neuron fibers extend from thalamus into the posterior limb; from the posterior limb they
radiate outwards in the coronal plane as the corona radiata, and no longer form a distinct tract.

 The corona radiate synapses onto neurons in the postcentral gyrus where the somatic sensory
cortex is located.

48
Lateral Spinothalamic Tract

 The lateral spinothalamic tract transmits pain and temperature sensations, and ascends in the
lateral column of the spinal cord.

 It begins with a stimulation of free nerve endings (for pain) or thermoreceptors (for
temperature) in the periphery, which triggers an action potential in the peripheral process of the
1o sensory neuron.

 Inflammatory mediators that stimulate pain include 5-HT, Histamine, Bradykinin, Acid
and Potassium. (Recall that high extracellular potassium indicates membrane damage,
which is a sign of cell injury.)

 Mediators that reduce the threshold for pain but do not necessarily cause pain directly
are prostaglandin E2 and Substance P.

 The speed of transmission of PNS neurons may be classified by the Erlanger-Gasser classification.

 A fibers have the greatest degree of myelination, B fibers have a lesser degree of
myelination and C fibers have no myelination. Thus, A fibers are the fastest and C fibers
are the slowest.

 A fibers are further classified by their speed of transmission. Aα, Aβ and Aγ fibers are all
relatively well myelinated, but run in decreasing order of axon diameter and thus have
decreasing levels of speed. Aδ fibers are poorly myelinated and are the slowest fibers;
however they are still faster than B fibers in general.

 It is not necessary to know the fiber transmission speeds of all neurons in the PNS, but it
is relevant for the discussion of the lateral spinothalamic tract.

49
 Two main types of 1o neuron fibers are found in the lateral spinothalamic tract responsible for
the transmission of both pain and temperature.

 Aδ fibers are lightly myelinated, and carry the sensation of fast pain (as occurs in a
pinprick) or temperature. These sensations are usually relatively well localised
compared to sensations transmitted by C fiber pathways. They can be triggered by
mechanical and thermal stimuli, and transmit sensations from the skin only.

 C fibers on the other hand are unmyelinated and are the slowest fibers, they carry the
sensation of slow pain (often described as diffuse, throbbing dull or burning). They carry
the most poorly localised sensations and can be triggered by chemical stimuli in addition
to mechanical and thermal stimuli. They transmit sensations from skin and viscera.

 The action potential is transmitted along the 1o sensory neuron, from the peripheral processes,
past the dorsal root ganglion and into the CNS via central processes.

 The central processes extend axonal branches that ascend or descend in the spinal cord
by a few levels, forming a small local Tract of Lissauer, before synapsing onto 2o sensory
neurons. This partly accounts for the somewhat poorer localisation of lateral
spinothalamic tract sensations in comparison to dorsal column sensations.

 Glutamate and Substance P are the main neurotransmitters used by the Aδ and C fibers.

 The central processes of Aδ fibers synapse on the 2o sensory neuron cell body located in
the nucleus proprius in the dorsal horn of gray matter.

 The central processes of C fibers synapse on cell bodies located in the substantia
gelatinosa, named for its gelatinous appearance due to the lack of myelination of fibers
in this area. However, at this point the signals are transmitted through multiple orders of
intermediate neurons before reaching the main 2o projection sensory neuron; in doing
so, the exact localisation of pain and temperature is further lost. This explains why slow
pain is even more poorly localised compared to fast pain.

 The 2o sensory neurons of both fast and slow pain pathways extend axons that cross
over in the anterior commissure to the contralateral lateral column to ascend in the
lateral spinothalamic tract.

 Sensations from inferior parts of the body are carried by fibers running in the lateral part
of the lateral column, while sensations from superior parts are carried by fibers running
in the medial part of the lateral column. However, overall the topographical organisation
is poorer than in the dorsal columns.

50
Anterior Spinothalamic Tract

 The anterior spinothalamic tract transmits the sensation of crude touch.

 Peripheral receptors are stimulated, which trigger an action potential in the 1o sensory neuron.
The central process of the 1o sensory neuron extends local tracts of Lissauer as in the lateral
spinothalamic tract, and synapses in the dorsal horn of the spinal cord.

 The 2o sensory neuron’s axon crosses over in the anterior commissure, anterior to the crossing
of the lateral spinothalamic tract, to the contralateral anterior column. It then ascends in the
anterior spinothalamic tract.

 Sensations from inferior parts of the body are carried by fibers running in the lateral part of the
lateral column, and sensations from superior parts are carried by fibers running more medially.

Spinotectal Tract

 The spinotectal tract transmits sensory information from the periphery to the tectum of the
midbrain, which comprises two posterior midline swellings known as the superior colliculus and
inferior colliculus. This sensory input is used in spino-visual reflexes, in which peripheral
sensations (e.g. a pinprick) triggers visual reflexes to look at the site of stimulation.

 The 1o sensory neuron, as in both the anterior and lateral spinothalamic tracts, synapse on 2o
neurons in the dorsal horn of gray matter.

 The 2o axons cross to the contralateral side to ascend in the spinotectal tract, which runs in the
anterolateral region of white matter. (Positioned lateral to the anterior spinothalamic tract and
anterior to the lateral spinothalamic tract).

Spinal Lemniscus

 The anterior spinothalamic tract, lateral spinothalamic tract and spinotectal tract ascend in the
spinal cord on the contralateral side to the origin of stimulus and merge at the level of the
medulla to form the spinal lemniscus, which runs superiorly to terminate at the thalamus.

 Fibers from spinotectal tract exit the spinal lemniscus just inferior to its termination, at the level
of the midbrain, to synapse onto the superior and inferior colliculi of the midbrain.

 Fibers from the anterior and lateral spinothalamic tracts synapse onto the ventroposterolateral
(VPL) nucleus of the thalamus.

 3o neurons send out fibers via the posterior limb of the internal capsule, which radiate out as the
corona radiata to the somatic sensory cortex in the post-central gyrus.

51
Other Terminations of the Lateral Spinothalamic Tract

 VPL fibers emerging from the posterior limb of internal capsule also synapse onto the cingulate
gyrus, and is thus responsible for the emotional component of pain. (The cingulate gyrus is part
of the limbic system.) The cingulate gyrus is located superior to the corpus callosum.

 VPL fibers emerging from the posterior limb of internal capsule, particularly those arising from
slow pain pathways, also synapse onto the insula cortex, which is responsible for general
visceral sensations (nausea, visceral pain) and triggering autonomic responses to pain including
sympathetic (tachycardia, sweating) and parasympathetic (e.g. vomiting) responses.

Spinoreticular Pathway – Controlling Receptiveness to Pain

 The reticular formation has many functions; one important function is to act as a switch for the
responsiveness of the cerebral cortex. Upon stimulation, it activates the cerebral cortex (via the
thalamus as discussed below) and renders it responsive to stimuli.

 Some of the 2o axons in the spinal leminiscus exit the lateral column to terminate on the
reticular formation located in the brainstem.

 The 3o neuron of the reticular formation in turn synapses onto the intralaminar nuclei of the
thalamus, which are foci of gray matter located in the white matter septa dividing the thalamus.
Some 2o neurons in the spinal lemniscus also directly synapse onto the intralaminar nuclei.

 The 4o neuron of the intralaminar nuclei of the thalamus then sends out fibers which synapse
onto various parts of the cerebral cortex, especially the frontal and parietal lobes.

 Activity of the cerebral cortex is generally highest just before waking, and wanes throughout the
day. During sleep, its activity is minimal; this is the reason why sensory input does not normally
reach a conscious level during sleep. A large enough stimulus can awaken the cerebral cortex via
the reticular formation.

 It is thus appropriate that Aδ and C fibers, apart from sending information to the sensory cortex
itself, should activate the sensory cortex via the spinoreticular tract to render it receptive to
stimuli. A similar mechanism is used by the reticular formation to activate the primary visual and
auditory cortices.

 The pathway described above shows crossed fibers; the spinoreticular pathway may also include
uncrossed fibers, wherein the 2o neuron is located in the dorsal horn, and its axon ascends in the
ipsilateral lateral column.

52
Gate Control Theory

 It has been known for centuries now that when a person is suffering from pain, providing some
sort of alternative stimulus (e.g. massage, acupuncture, liniment creams that irritate the skin or
even electrical stimuli), even to sites other than the location of the lesion causing pain, would
temporarily reduce the perceived intensity of pain.

 It was postulated that some sort of gate controlled the pathway through which pain signals were
sent; the gate could somehow be temporarily closed by providing an alternative stimulus.

 The cellular basis for this theory is now understood to be the synapsing of other sensory neurons
(e.g. 1o DCML neurons) onto local interneurons in the gray matter, which then synapse onto and
inhibit 2o lateral spinothalamic tract neurons.

Descending Analgesic Pathways

 It has been found that some paraventricular, paraaqueductal and assorted midline nuclei like
the nucleus Raphe extend descending pathways that synapse onto the 2o sensory neuron in pain
pathways.

 They secrete endogenous painkillers like enkephalins and endorphins which inhibit the
transmission of pain.

 It is proposed that these are psychogenic models of pain modulation, and explain the healing
power of a listening ear and the goodness of the physician.

Spinocerebellar Pathways

 The spinocerebellar pathways serve mainly to transmit proprioceptive information from the
periphery directly to the cerebellum, without ascending to cerebral consciousness.

 The main receptors involved in the spinocerebellar pathways are golgi tendon organs, muscle
spindles and pressure receptors.

 Anatomically, the cerebellum is attached by superior, middle and inferior peduncles to the
brainstem. The superior peduncle attaches to the midbrain, the middle to the pons and the
inferior to the medulla oblongata. These serve as structures through which tracts can enter the
cerebellum.

53
 The dorsal spinocerebellar pathway receives sensory inputs from the inferior part of the body
and sends this information directly to the cerebellum.

 1o neurons in the inferior part of the body send central processes that synapse onto the
dorsal nucleus of Clarke (which is a column in the posterior gray horn).

 The dorsal nucleus of Clarke extends from TI to LIII spinal segments; thus, central
processes of 1o neurons from dermatomes below this level must ascend in the spinal
cord before synapsing.

 The 2o neurons in dorsal nucleus of Clarke sends fibers in the dorsal part of the
ipsilateral lateral column, which ascend to the level of the medulla to enter the inferior
cerebellar peduncles.

 The cuneocerebellar pathway is the upper limb counterpart to the dorsal spinocerebellar
pathway.

 Instead of synapsing on the dorsal nucleus of Clarke, the 1o neurons ascend in the lateral
white column and then synapse onto accessory Cuneate nuclei in the medulla, not to be
confused with the nucleus Cuneatus.

 The accessory Cuneate nuclei sends cuneocerebellar fibers to the cerebellum via inferior
cerebellar peduncles.

 The anterior spinocerebellar pathway involves the decussation of the 2o neuron’s fibers to
ascend in the contralateral anterior lateral column. However, these fibers ascend to the level of
the midbrain, enter the superior cerebellar peduncle, and recross within the substance of the
cerebellum to the opposite side.

 Finally, the spino-olivary tract involves the decussation of the 2o neuron’s fibers to ascend in the
contralateral lateral column. However, these fibers, upon ascending to the level of the medulla,
synapse on the olivary nucleus. The 3o neurons then decussate back to the original side, and
enter the inferior cerebellar peduncle.

 Thus, it may be said that the cerebellum always receives sensory information from the ipsilateral
side.

54
MOTOR AND DESCENDING TRACTS
Descending Tracts

 Descending tracts are tracts that bring information from higher levels of the CNS to the
periphery where an effector function is produced.

 The two main arms of the motor PNS are the autonomic system and the somatic motor system.
Only the latter is discussed here.

 The somatic motor system is comprised of lower motor neurons (LMNs), upper motor neurons
(UMNs) and planning centers.

 Lower motor neurons are neurons in the CNS that extend their axons to the periphery to
synapse on neuromuscular junctions (NMJs).

 Upper motor neurons are neurons from higher levels in the CNS that exert an effect on
LMNs, either through a direct monosynaptic connection, or an indirect disynaptic
connection via an interneuron.

 While upper motor neurons activate single muscles or groups of muscles, planning
centers orchestrate the firing of upper motor neurons in a coordinated fashion in order
to produce meaningful movement. If upper motor neurons are the keys of a piano, the
planning center is the pianist.

 Upper motor neurons may reside in the cerebral cortex (cortical UMNs) or in nuclei within the
CNS (subcortical UMNs).

 The UMNs of cortical origin collectively give rise to tracts known as the pyramidal tracts. Those
of subcortical origin give rise to tracts known as the extrapyramidal tracts.

Anatomy of Cerebral Cortex

55
 On the superolateral surface of the cerebral cortex, a central sulcus divides the precentral gyrus
anteriorly from the postcentral gyrus posteriorly.

 The postcentral gyrus contains the primary somatic sensory cortex.

 The precentral gyrus contains the primary motor cortex.

 Anteriorly to the precentral gyrus, two sulci divide the frontal area further into the superior
frontal gyrus, middle frontal gyrus and inferior frontal gyrus.

 These regions are mainly anatomical features; the area occupied by the superior, middle and
inferior frontal gyri can be divided into separate functional areas.

 The region of these gyri immediately anterior to the primary motor cortex is occupied by the
premotor cortex and supplementary motor cortex; these are the planning centers.

56
Planning Centers and Overview of Motor System

 The thought of performing a voluntary action is first conceived in the prefrontal cortex. The
prefrontal cortex sends this information to planning centers located in the premotor and
supplementary motor cortex.

 The two planning centers are the premotor cortex and supplementary motor cortex; however
the types of movement they plan are slightly different.

 The premotor cortex is associated with more recently evolved programs for the control
of limbs and other fine movements like speech.

 The supplementary motor cortex is associated with primitive motor programs associated
with axial and trunk movements. Unlike the premotor cortex, these areas control
movements bilaterally, rather than only for the opposite hemisphere.

 The planning centers produce a “proprioceptive image” of what the final intended position of
the body should look like at the end of the movement.

 It communicates this intended proprioceptive image to the cerebellum. The cerebellum

itself also receives a current proprioceptive image based on live updated information
via the ventral/ dorsal spinocerebellar and cuneocerebellar tracts.

 The cerebral cortex also receives current proprioceptive information directly via DCML.

 By comparing the current and intended proprioceptive images, the cerebellum aids in
selecting a motor program. It sends an output back to the planning centers via thalamus.
In this manner, mental rehearsal can be performed before program is even executed.

 The planning centers send this information to the basal ganglia, which also contains part of the
circuitry of the motor program for adjusting fine motor control and initiation of the movement.

 The basal ganglia then sends output via the thalamus to stimulate or inhibit the appropriate
upper motor neurons in such a sequence so as to produce meaningful movement.

 UMNs run in descending tracts to synapse onto LMNs; LMNs in turn synapse onto
neuromuscular junctions to trigger muscle activation.

57
Planning Functions for Specific Areas in the Premotor and Related Areas

 The premotor cortex is arranged in a homunculus, such that specific areas are associated with
storage of programs for different parts of the body. Lesions to specific parts of the premotor
cortex may thus cause predictable loss of function in specific parts of the body.

 The Broca’s Speech Area is located just anterior to the inferior part of the premotor cortex.

 It is responsible for planning the movements required to produce speech.

 Lesions to this area result in an inability to produce proper coordinated speech, despite
the person knowing what words he wants to say.

 The left and right Frontal Eye Fields are found just anterior to the superior part of the premotor
cortex of each cerebral hemisphere and are responsible for lateral movement of the eyes.

 Activation of one frontal eye field results in movement of both eyes in the contralateral
direction. (e.g. if the left field is activated, both eyes will look to the right.)

 The position in which both eyes are pointed is the result of the relative intensity of
activation of the left and right fields; that is, when the eyes are pointed straight ahead,
both left and right fields are equally activated.

 Lesions like tumours or infection in this area can cause overstimulation of one frontal
eye field, resulting in the turning of eyes away from that direction.

 Eventually, these lesions may completely damage the frontal eye field such that it
underfires, resulting in the eyes turning towards that direction.

58
Corticospinal Tract

 The corticospinal tract is the most major pyramidal descending tract; it is the main tract
responsible for the control of the limbs and fine movements.

 Being a pyramidal tract, its UMNs are of cortical origin.

 Surprisingly, only 30% of upper motor neurons arise in the primary motor cortex.

 30% arise from the premotor area and supplementary motor area combined. These
neurons are not to be confused with those in the same area that perform the function of
planning centers.

 40% arise from the primary somatosensory area. These neurons are not to be confused
with those that perform the function of receiving sensory input in the ascending tracts.

 Cortical UMNs are found in the 5th lamina of the 6-layered cerebral cortex.

 The UMNs in the primary motor cortex have a few special characteristics.

 They are distinctly arranged in a homunculus: the inferolateral most parts of the cortex
correspond to muscles in the superior parts of the body, while the superomedial most
parts of the cortex correspond to muscles in the inferior parts of the body. This is similar
to (but not exactly the same as) the homunculus found in the primary somatosensory
cortex for sensory input, as well as in the planning centers.

 10% of primary motor cortex UMNs are Betz cells. Betz cells are extremely large motor
neurons found only in the primary motor cortex. Their cell bodies are 60 microns large
(about 7 times the size of an RBC) and their axons are thick and heavily myelinated.
Typical upper motor neurons are smaller in size and not as heavily myelinated.

While typical upper motor neurons make a disynaptic connection to the LMNs (or α-
motor neurons) via interneurons called internuncial interneurons, Betz cells synapse
directly onto the α-motor neurons.

59
 All of the upper motor neurons from the cerebral cortex (from premotor, supplementary motor,
primary motor and somatosensory areas) send axonal fibers via the corona radiata that
converge in the posterior limb of the internal capsule to form the corticospinal tract.

 The posterior limb of the internal capsule is supplied by the lenticulostriate arteries.

 Other tracts running through the internal capsule include the thalamocortical pathways,
which is the terminal continuation of the DCML and spinothalamic tracts.

 Disruption in supply from the lenticulostriate artery can cause damage to all of these
tracts, resulting in massive motor and sensory deficits. These deficits all occur on the
contralateral side of the body due to the decussation of fibers. Weakness in one side of
the body is called hemiparesis; complete loss of motor function in one side is
hemiplegia.

 The fibers descend inferiorly in the posterior limb of the corticospinal tract to pass through the
middle 3/5 of each of the crus cerebri of the midbrain.

 The midbrain is divided into a tectum posteriorly, a tegmentum in the middle and the
crus cerebri anteriorly.

 The tectum is posterior to the cerebral aqueduct, and is comprised of the superior and
inferior colliculi. The superior colliculis is involved in visual reflexes (either spinotectal or
tectospinal), while the inferior colliculis is involved in auditory reflexes.

 The tegmentum extends from the cerebral aqueduct posteriorly to the substantia nigra
anteriorly.

 The substantia nigra is a strip of dark tissue that is implicated in the pathogenesis of
parkinson’s disease.

 The crus cerebri is in the area anterior to the substantia nigra.

 As the fibers of the corticospinal tract are compacting into the central 3/5 of each of the
left and right crus cerebri, lesions to this area can result in massive motor deficits. These
motor deficits occur in the contralateral side of the body due to subsequent decussation.

60
 From the midbrain, the fibers extend inferiorly to the pons.

 Another pathway running through the pons is known as the corticopontine pathway.
Fibers of this pathway originate from cell bodies in the cerebral cortex, and connect to
pontine nuclei in the pons. From the pontine nuclei, they enter the cerebellum via the
middle cerebellar peduncles.

 Briefly, the function of the corticopontine pathway is for the cerebral cortex to convey
the intended motor programs for execution to the cerebellum, where it is adjusted
according to the most updated proprioceptive image of the body.

 The relevance of the pontine nuclei here is that they are widely dispersed, and
consequently the corticospinal fibers passing through the pons disperse around them.

 Focal lesions to the pons may only affect some of the corticospinal fibers rather than the
entire tract, and may not result in massive motor deficits to all parts of the body.

 From the midbrain, the corticospinal fibers run into the medulla oblongata where they are once
again compacted, this time into the pyramids of the medulla anteriorly.

 Lesions to the medial part of the medulla cause damage to the pyramidal tracts, one of
which is the corticospinal tract.

 Lesions to the lateral part of the medulla (olives) do not affect the pyramidal tracts.

 As the corticospinal fibers enter the spinal cord, a pyramidal decussation occurs at the junction
of the pons and spinal cord.

 90% of the corticospinal fibers decussate to the contralateral side in the major motor
crossing and run in the lateral column of white matter to form lateral corticospinal tract.

 10% of the corticospinal fibers do not decussate, but run in the ipsilateral anterior
column of white matter to form the anterior corticospinal tract.

 Lesions to one side of the spinal cord usually cause massive motor deficit to the
ipsilateral side of the body below the level of the lesion; however small motor deficits to
the contralateral side of the body can occur.

61
 Fibers from the lateral corticospinal tract enter the ventral gray horn to connect with the α-
motor neurons.

 Fibers from the anterior corticospinal tract are still running in the ipsilateral side of origin; they
decussate at the level of termination to connect with α-motor neurons in the contralateral
ventral gray horn.

 Fibers in both pathways include typical UMNs and Betz cells.

 Betz cells synapse onto LMNs directly.

 Typical UMNs first synapse onto internuncial interneurons, which in turn synapse onto
the LMNs. This disynaptic connection allows UMNs to inhibit LMNs that should not fire.

 While the lateral corticospinal tract supplies most of the limbs and muscles required for fine
movements, the anterior corticospinal tract supplies axial back muscles.

 The anterior corticospinal tract is primitive and controlled by planning centers in

supplementary motor cortex.

 The lateral corticospinal tract is more recently evolved and is controlled by planning
centers in premotor cortex.

62
Corticonuclear Fibers

 The corticospinal tract originates from UMNs in the cerebral cortex that synapse onto LMNs in
the spinal cord.

 The other major group of UMNs in the cerebral cortex synapse onto LMN nuclei located in the
brainstem. These fibers are called corticonuclear fibers.

 The corticonuclear fibers supply LMNs that are responsible for the motor function of the cranial
nerves supplying the head and neck.

 These brainstem nuclei may be found in the midbrain, pons (corticopontine fibers) or medulla
(corticobulbar fibers).

 Although strictly speaking these fibers do not pass through the pyramids of the medulla, they
are still classically described as pyramidal tracts due to their similarity in function to the
corticospinal tracts.

63
Collateral Pathways of Corticospinal Tract
The corticospinal tract also gives off fibers in a number of collateral pathways.

 Collateral pathways from corticospinal fibers that return to the cerebral cortex itself near the
site of origin allow the cerebral cortex to stay informed about motor processes currently being
executed.

 Fibers to the cerebellum via the olives of the medulla allow the cerebellum to be kept informed
of the current motor processes being executed, for fine adjustment of motor programs. This is
distinct from the corticopontine fibers which send information about planned motor processes
to the cerebellum.

 Fibers from the corticospinal tract to the vestibular nuclei and red nuclei allow these nuclei to
provide fine adjustment of background muscle tone via their own respective extrapyramidal
tracts. These will be subsequently discussed.

 Fibers from the corticospinal tract also extend to the reticular formation.

 The reticular formation extends fibers to the intralaminar nuclei of the thalamus, which
subsequently sent fibers to the rest of the cerebral cortex to keep the brain active and
prevent lapse of attention during potentially dangerous motor actions.

 The reticular formation is also involved in descending tracts that provide fine adjustment
of background muscle tone.

64
Descending Tracts of Subcortical Origin

 These tracts are collectively known as the extrapyramidal tracts; they arise from gray matter in
brainstem nuclei rather than the cerebral cortex.

 The tectospinal tracts originate from the superior and inferior colliculus and synapse onto LMNs
in the ventral gray horn.

 Those from the superior colliculus are responsible for visual-spinal reflexes e.g. moving
to avoid an object that you see being thrown at you. These should not be confused with
spino-visual reflexes in the spinotectal pathway (e.g. looking at a pin one has stepped
on).

 Those from the inferior colliculus are responsible for auditory-spinal reflexes e.g.
turning towards the source of a loud noise.

 All of the other descending extrapyramidal tracts are associated with maintaining muscle tone.
These originate from the bilateral vestibular nuclei and red nuclei, and the reticular formation.

 Those responsible for maintaining muscle tone of the extensor muscles are the vestibulospinal
tract and the pontine reticulospinal tract.

 The vestibular nuclei traverse both the pons and medulla; they extend uncrossed
descending tracts in the anterior columns to supply LMNs in the anterior gray horn.

 The pontine reticular nuclei are a diffuse group of nuclei found in the pontine regions of
the reticular formation. They also extend uncrossed descending tracts in the anterior
columns to supply LMNs in the anterior gray horn. However, they play more of an
accessory role and assist the vestibular nuclei.

65
 Those responsible for maintaining muscle tone of the flexor muscles are the rubrospinal tract
and the medullary reticulospinal tract.

 The red nuclei are found in the midbrain. They extend tracts that decussate immediately
to the contralateral side, and descend in the brainstem and lateral columns of the spinal
cord white matter to supply LMNs in the ventral gray horns.

 The medullary reticular nuclei are the medullary counterparts to the pontine reticular
nuclei. They extend uncrossed descending tracts in the anterior columns to supply LMNs
in the anterior gray horn. Similarly, they play an accessory role to the red nuclei.

 Fine movements are mainly controlled by the corticospinal tracts.

Decorticate and Decerebrate Posturing

 In patients with widespread brain infarction, muscle tone is maintained largely by the
extrapyramidal system.

 Decorticate posturing occurs when lesions occur above the level of the red nucleus, and the
rubrospinal tract is preserved.

 The rubrospinal tract mainly controls the flexors of the upper limbs, and has a greater
constitutive tone than the extensor extrapyramidal tracts. Thus upper limbs are flexed.

 Its innervation to the lower limbs is somewhat limited, and therefore the lower limbs
are extended due to extensor extrapyramidal tract tone.

 Decerebrate posturing occurs when lesions occur below the level of the red nucleus, and the
rubrospinal tract is disrupted.

 In the upper limbs, extensor tone prevails, and upper limbs are extended.

 In the lower limbs, extensor tone also prevails. Lower limbs are extended.

 Decerebrate posturing indicates more severe brainstem involvement than decorticate posturing,
and scores lower on the Glasgow coma scale for the motor criteria.

66
UPPER & LOWER MOTOR NEURON LESIONS

Deep Tendon Reflex

 The bulk of the force of contraction of a skeletal muscle is contributed to by extrafusal muscle
fibers.

 A small number of intrafusal muscle fibers, also known as muscle spindles, are sensory
receptors that detect changes in length of a muscle caused by stretch.

 The muscle spindles are encapsulated by connective tissue and lie in parallel to the extrafusal
muscle fibers. When the muscle is stretched, the muscle spindle itself is stretched.

 The muscle spindle is innervated by a Ia general somatic afferent fiber. Upon stretching, the
afferent neuron is stimulated to fire, and relays this information to the spinal cord.

 In the spinal cord, the afferent fibers take one of a few pathways.

 Some fibers enter the dorsal column medial lemniscus tract to bring proprioceptive
information to the higher cortex and to consciousness. (Not shown in diagram.)

 Some fibers enter the dorsal/ ventral spinocerebellar or cuneocerebellar tracts to bring
proprioceptive information to the cerebellum. (Not shown in diagram).

 Some fibers remain at the same level of the spinal cord, turn and synapse onto α motor
neurons of the homonymous muscle of origin in a monosynaptic reflex arc.

 Some fibers remain at the same level of the spinal cord, turn and synapse into inhibitory
interneurons. These inhibitory interneurons synapse onto α motor neurons of the
antagonistic muscle, constituting an inhibitory reflex arc. This is a disynaptic reflex arc.

67
 α motor neurons innervate the extrafusal muscle fibers. The nett result is that the homonymous
muscle contracts while the antagonistic muscle relaxes.

 γ motor neurons innervate the intrafusal muscle spindles. When UMNs stimulate the α motor
neurons to contract, they also stimulate γ motor neurons of the same muscle to contract. This
ensures that the muscle spindles remain at the same length as the extrafusal fibers so that they
will be sensitive to new changes in muscle length.

 This reflex arc allows a muscle to react to a stretching force by opposing it, in order to provide
some resistance to external forces stretching a limb.

 Deep tendon reflexes are thus used to test integrity of the reflex arc. They involve tapping on a
tendon lightly to cause a transient, brisk stretch of the muscle. Tendon reflexes are positive
(normal) when the homonymous muscle contracts in response. Examples include:

 Biceps tendon reflex (CV – CVI via the brachial plexus and musculocutaneous nerve)

 Triceps tendon reflex (CVII – CVIII)

 Patellar tendon reflex (LII – LIV)

 Ankle jerk reflex (SI – SII)

Golgi Tendon Reflex

 Whereas deep tendon reflexes are mediated by muscle spindles, golgi tendon reflexes are
mediated by golgi tendon organs.

 In contrast to the muscle spindles, golgi tendon organs are innervated by Ib general somatic
afferent fibers.

 Upon stretching of the muscle, the afferent fibers are stimulated to fire.

 Fibers may enter the DCML to provide proprioceptive information to cerebral cortex or
the spinocerebellar/ cuneocerebellar tracts to the cerebellum.

 Some fibers remain at the same level of the spinal cord, turn and synapse onto inhibitory
interneurons. These inhibitory interneurons synapse onto α motor neurons of the
homonymous muscle.

 Some fibers remain at the same level of the spinal cord, turn and synapse directly onto α
motor neurons of the antagonist muscle.

 The end result is the exact opposite of the deep tendon reflex; in response to a muscle stretch,
the homonymous muscle relaxes and the antagonistic muscle contracts.

 However, the deep tendon reflex is only activated when forces become extremely high. This sets
an upper limit to the maximum amount of force the agonist muscle can oppose, and prevents
the tendon-bone connection from being compromised.

68
Clasp Knife Reflex

 The clasp knife reflex is the culmination of the activation of the deep tendon reflex at lower
forces and the golgi tendon reflex at higher forces.

 Higher-than-normal levels of force are required before the clasp-knife reflex is activated; thus
this is a pathological sign that only occurs in hypertonia. If the sign is positive, the limb is said to
exhibit spasticity.

 It can be elicted by applying an increasing level of force to flex or extend the limb.

 Initially, the deep tendon reflex allows for increasing levels of resistance to match and
oppose the external force.

 Eventually, a point is reached where the golgi tendon reflex is activated. The resistance
appears to suddenly give way, mimicking the closing of a clasp knife.

Plantar Reflex & Babinski Sign

 The Babinski reflex is stimulated by stroking the lateral region of the sole of the foot. It is
positive if it leads to a dorsiflexion at the ankle and withdrawal of the leg. It is also known as the
upward plantar reflex.

 The sign is physiologically positive in infants; however around the time the infant begins to learn
to walk, the reflex normally becomes inhibited by pyramidal and extrapyramidal tract neurons
which become myelinated and active.

 Under the influence of UMNs, the reflex is reversed; instead, the stimulus leads to plantarflexion
of the foot and allows the infant to grasp the ground with his feet as he learns to walk, rather
than to withdraw from it. This is known as the downward plantar reflex.

 UMN lesions result in loss of inhibition of the infantile reflex. Thus, a positive Babinski sign in
those above the age of three is a pathological indication for UMN lesion.

Denervation Atrophy, Fasciculations & Fibrillations

 Normally, a skeletal muscle receives constitutive levels of cholinergic stimulation via general
somatic efferent neurons, which provides a trophic stimulation (growth signals) to muscle.

 Loss of the stimulus leads to dramatic muscle wasting (70% to 80% loss in muscle mass) known
as denervation atrophy. Atrophy occurs by autophagy at a cellular level.

 When denervation of the NMJ occurs in LMN lesions, the muscle begins to overexpress
neuromuscular nicotinic acetylcholine receptors.

 The neuromuscular nicotinic receptors (Nm) are ligand-gated sodium/ potassium channels, which
when activated lead to increased conductance of these ions and firing of an action potential.

 When Nm receptors are overexpressed, simple tapping of a muscle can lead to ion flux across the
membrane; this may be observed physically as fasciculations and on EMG as fibrillations.

69
Upper & Lower Motor Neuron Lesions

 Upper motor neuron lesions can occur in the cerebral cortex/ subcortical nuclei(where cell
bodies are located), in the white matter of the brain and brainstem (before decussation of the
lateral spinothalamic tract), or in the spinal cord.

 Lower motor neuron lesions can occur in the ventral horn gray matter, in the ventral root, the
spinal nerve trunk, the nerve ramus, any nerve plexuses or nerve branches and at the
neuromuscular junction.

 When the axon of a neuron is injured by trauma, the distal stump of the neuron undergoes
wallerian degeneration.

 This has different effects on motor function dependent on whether the lesion is to the UMN or
the LMN.

LMN Syndrome

 LMN lesions tend to affect individual muscles.

 The spinal reflex arcs are no longer intact and there is complete arreflexia.

 This may be demonstrated by loss of deep tendon reflexes in both upper and lower
limbs.

 Loss of the downward plantar reflex may also be demonstrated in the lower limb if the
lesion affects LMN supplying this region.

 Denervation atrophy results from the loss of trophic stimulus, with a dramatic loss of muscle
mass (70% to 80%). Atrophy from disuse also contributes to this process.

 There is a complete loss of power and force of contraction of the muscle.

 There is hypotonia (low muscle tone) and muscle flaccidity. Muscle tone is the passive
resistance of a muscle to movement and is normally maintained by a basal level of stimulation
via α motor neurons; loss of the LMN results in loss of muscle tone.

 Fasciculations and fibrillations may be present.

70
UMN Syndrome

 UMN lesions tend to affect control of groups of muscles.

 The LMN and spinal reflex arcs are intact; indeed, UMN lesions manifest as hyperreflexia.

 This occurs because UMNs normally exhibit a basal level of inhibition on LMNs to
suppress spinal reflexes. They do so by making a disynaptic connection on LMNs via
inhibitory interneurons called Renshaw cells.

 The hyperreflexia may manifest as a vigorous deep tendon reflex, a positive Babinski
reflex and ankle/ patellar clonus.

 Clonus refers to a rhythmic, alternating activation of flexors and extensors at these joints
due to repeated, alternating activation of flexor and extensor deep tendon reflex arcs.

 In UMN lesion the skeletal muscle continues to receive a basal, trophic stimulus by the
cholinergic innervation of the LMN. However a 20% to 30% loss of muscle mass still occurs as
part of disuse atrophy.

 Unopposed firing of the LMNs manifests as muscle rigidity and hypertonia.

 If the UMN lesion affects corticospinal pathways (pyramidal lesion), the hypertonia is
significant and spasticity can be demonstrated by presence of the clasp-knife reflex.

 If the UMN lesion affects subcorticopsinal pathways (extrapyramidal lesion), as in

Parkinson Disease, the hypertonia is less significant and manifests as lead-pipe rigidity
throughout the range of motion, without the clasp-knife reflex.

 A special case of lead-pipe rigidity occurs when the testing of flexion and extension is
interrupted by intermittent tremors, as occurs in Parkinson Disease. This manifestation
is known as cog-wheel rigidity.

 Fasciculations and fibrillations are absent.

71
SPINAL CORD LESIONS
Lesion of Anterior Horn

 Anterior horn lesions produce a pure LMN syndrome with no sensory deficit. There is:

 Dennervation atrophy and fasciculations.

 Hypotonia.

 Hyporeflexia and no clonus, downgoing plantar reflex.

 Reduced power.

 Normal sensation.

 No ataxia, no cerebellar signs.

 Bilateral etiologies include:

 Poliomyelitis, in which the poliovirus has an affinity for the anterior horn cells to
produce a primarily LMN syndrome, although some sources contend that it can
subsequently attack the corticospinal tracts to produce a mixed UMN LMN presentation.
It may be suggested by an exposure history e.g. unclean water, unsanitary conditions,
known outbreaks in the region.

 Werdnig Hoffman disorder or progressive infantile muscular atrophy, an inherited

disorder of LMN disease suggested by onset in first year of life and a family history.

 Kugelberg Walender Disease or Juvenile hereditary LMN disease, a similar inherited

disorder of LMN disease suggested by later onset in childhood and a family history.

 Guillan Barre Syndrome, which is a symmetrical ascending segmental demyelination

polyneuritis of LMNs resulting in progressive weakness from lower limbs, to respiratory
muscles and upper limbs or even face. It occurs due to molecular mimicry and cell-
mediated immunity against the Schwann cells, resulting in demyelination. There is often
a preceding history of respiratory/ GIT infection, especially by Campylobacter jejuni
although other organisms are possible. Due to inflammation of the anterior roots
increased CSF proteins may be seen, but CSF inflammatory cells are not (Albumino-
cytologic dissociation). It is self resolving, and unlike many autoimmune disorders does
not recur.

72
Corticospinal pathway

 Corticospinal pathway degeneration alone produces a pure UMN syndrome with normal
sensation and no cerebellar signs.

 Disuse atrophy with no fasciculations.

 Clasp knife hypertonia.

 Hyperreflexia with clonus and upgoing plantar reflex.

 Reduced power.

 Normal sensation.

 No ataxia, no cerebellar signs.

 Hereditary spastic paraplegia is one such cause of bilateral UMN syndrome; it is a hereditary
disease resulting in UMN degeneration (thus the lesion is not strictly isolated to a specific part of
the CNS, occurring in the cortex, posterior limb of internal capsule, brainstem and lateral
corticospinal tract). It may be suggested with a positive family history.

73
Mixed UMN and LMN Syndrome

 Mixed UMN and LMN disease results from involvement of both UMNs and LMNs, producing a
confounding mixture of UMN and LMN signs in dfferent limbs but with normal sensation.

 There may be either disuse atrophy or denervation atrophy with fasciculations.

 There may be clasp-knife hypertonia or hypotonia.

 There may be hyporeflexia with no clonus and downgoing plantar reflex or hyperreflexia
with clonus and upgoing plantar reflex.

 Power is reduced.

 Sensation is normal.

 There are no cerebellar signs.

 Motor Neuron Disease is one cause of bilateral mixed UMN LMN syndrome, of which
amyotrophic lateral sclerosis is the most common. Amyotrophic describes the combination of
significant muscle atrophy characteristic of LMN syndrome, while lateral sclerosis describes
sclerosis of the lateral corticospinal tract.

74
Dorsal Column Syndrome

 Dorsal Column Syndrome results in normal motor function, but loss of dorsal column
sensations. There is:

 Normal musculature and no fasciculations.

 Normal tone.

 Normal reflexes with no clonus and downgoing plantar reflexes.

 Normal power.

 Ipsilateral loss of fine touch, vibration and proprioception at the level of the lesion, but
normal pain and temperature sensation.

 There are no cerebellar signs.

 Rhomberg’s sign is positive and there may be some unsteadiness of gait.

 Bilateral and unilateral disease can occur, often secondary to demyelinating diseases. Recall
that the dorsal columns are highly myelinated and are particularly susceptible to injury by
demyelinating disease.

75
Lateral Spinothalamic Tract Lesions

 Lateral Spinothalamic tract lesions produce normal motor function but loss of lateral column
sensations. There is:

 Normal musculature with no fasciculations.

 Normal tone.

 Normal reflexes with no clonus and and downgoing plantar reflexes.

 Normal power.

 Loss of contralateral pain and temperature sensation one spinal segment below the level
of the lesion, but with intact fine touch, vibration and proprioception. This occurs due to
the oblique crossing of the lateral spinothalamic tract by one spinal segment.

 No cerebellar signs.

76
Anterior Spinothalamic Tract Lesions

 Anterior spinothalamic tract lesions produce normal motor function but loss of crude touch:

 Normal musculature and no fasciculations.

 Normal tone.

 Normal reflexes with no clonus and downgoing plantar reflexes.

 Normal power.

 Loss of contralateral crude touch sensation 3-4 spinal segments below the level of the
lesion, once again due to oblique crossing of the anterior spinothalamic tract, but intact
dorsal column and lateral column sensations.

 No cerebellar signs.

77
Dorsal Spinocerebellar

 Dorsal spinocerebellar tract lesions produce normal motor function, normal sensation but
ipsilateral lower limb dystaxia (Note dorsal nuleus of Clarke was omitted from above diagram):

 Normal musculature with no fasciculations.

 Normal tone.

 Normal reflexes with no clonus and downgoing plantar reflexes.

 Normal power.

 Normal dorsal column and anterolateral system sensations

 Dystaxia, likely manifesting as dysmetria and dysdiadachokinesia on the ipsilateral lower

limb due to loss of cerebellar input.

 Note that these problems manifest because 50% of the spinocerebellar input from that
lower limb is lost, despite the remaining 50% from the anterior spinocerebellar tract.

78
Anterior Spinocerebellar Tract

 Anterior spinocerebellar tract lesions produce normal motor function, normal sensation but
conralateral lower limb dystaxia:

 Normal musculature with no fasciculations.

 Normal tone.

 Normal reflexes with no clonus and downgoing plantar reflexes.

 Normal power.

 Normal dorsal column and anterolateral system sensations

 Contralateral dystaxia, likely manifesting as dysmetria and dysdiadachokinesia on the

ipsilateral lower limb due to loss of cerebellar input.

79
Irritative Lesions of Dorsal Root Ganglion

 Irritative lesions of dorsal root ganglion result in hyperesthesia, hyperalgesia and potentially
even hyperreflexia due to hyperfunction of the dorsal root ganglion.

 There is normal musculature and no fasciculations.

 There is normal tone.

 There may be hyperreflexia, but plantars should remain downgoing.

 Power is normal.

 There is hyperesthesia and hyperalgesia, i.e. all sensations are heightened, in the
affected region.

 There are no cerebellar signs.

 Etiologies are usually due to reactivation of a viral infection.

 Herpes zoster results in hyperalgesia and hyperesthesia in a unilateral, dermatomal

pattern (especially T5 to T10 dermatomes) that does not cross the midline, with pruritic
and painful vesicles.

 Disseminated zoster may not respect the midline of the body, and may result in bilateral
involvement.

 HSV reactivation results in a similar hyperesthesia and hyperalgesia, but with

herpetiform clusters of vesicles that do not strictly follow a dermatomal pattern, but
which should not cross the midline.

80
Destructive Lesions of Dorsal Root Ganglion

 Destructive lesions of the dorsal root ganglion result in deafferentation of that dermatome.

 There is normal musculature and no fasciculations.

 Tone is normal.

 Hyporeflexia may be observed, but plantars should be downgoing if elicited.

 Power is normal.

 Fine touch, vibration, proprioception, pain and temperature will all be lost.

 Rhomberg sign may be positive if a large enough region is involved.

81
Anterior Root Irritative Lesions

 Anterior root irritative lesions result in overfiring of the LMN and spasticity, in the absence of
other UMN signs.

 Musculature is normal and there are no fasciculations.

 Hypertonia is observed and there may be clasp knife spasticity.

 Reflexes are normal, there is no clonus and plantar reflexes are downgoing.

 Power is reduced.

 Sensations are all normal.

 There are no cerebellar signs.

82
Charcot Marie Tooth Disease/ Peroneal Muscular Atrophy

 Charcot Marie Tooth Disease is the most common inherited peripheral neuropathy; however it
may also exhibit aspects of anterior horn and dorsal column involvement.

 Peroneal nerve peripheral neuropathy with LMN signs is the most classic site involved,
although other peripheral nerves can potentially be involved as well.

 Anterior horn involvement may result in LMN signs in a myotomal pattern.

 Dorsal column involvement can lead to loss of dorsal column sensations, including fine
touch, vibration and proprioception.

 Clinically, there may be:

 Foot drop.

 Dennervation atrophy and fasciculations of the anterior and lateral compartments of the
legs, as well as any other myotomally involved regions.

 Hypotonia in myotomally involved regions.

 Hyporreflexia of any myotomally involved regions.

 Reduced power on ankle dorsiflexion, as well as of any other myotomally involved

regions.

 Loss of fine touch, vibration and proprioception if the dorsal columns are involved.

 No cerebellar signs.

 Rhomberg sign may be positive if dorsal columns are involved.

83
Intervertebral Disc Herniation

 Intervertebral disc herniation of the nucleus pulposus may occur due to weakening of the
annulus fibrosus especially in the posterolateral direction, resulting in impingement and
irritation of the dorsal roots and anterior roots. Failure to correct may result in the lesion
becoming destructive and a reversal of signs.

 The lesion most commonly occurs just above or below L5 vertebra (90%), or just above
or below C6 vertebra (10%).

 History of mechanical back strain e.g. excessive twisting, bending may be suggestive
especially for L5 lesions.

 The patient may thus present with back pain and shooting leg pains and paresthesias,
as well as weakness of the lower limbs.

 Examination may reveal:

 Normal musculature and no fasciculations if the lesion is at the irritative stage,

otherwise denervation atrophy and fasciculations may subsequently occur.

 Spasticity is initially observed, but subsequently may give way to flaccidity (hypotonia).

 Hyperreflexia is initially observed due to the dorsal root irritative lesion; subsequently
LMN syndrome may result in hyporeflexxia.

 Power is reduced.

 Hyperesthesia and hyperalgesias of all sensations may be found.

 There are no cerebellar signs.

 Rhomberg sign is probably negative as the input from a single root is minimal.

84
Cervical Spondylosis with Myelopathy

 Cervical spondylosis is an osteoarthritic degenerative change of the cervical vertebrae, resulting

in formation of osteophytes that may invade into the already narrow cervical vertebral canal. It
can also occur due to calcification of degenerated annulus fibrosus.

 Like intervertebral disc herniation, it initially results in ventral and dorsal root irritation
and possibly subsequent destruction.

 It may further progress to myelopathy by compressing on the spinal cord itself, resulting
in compression of the corticospinal pathways and UMN syndrome in the lower limbs.

 It is the most common cause of myelopathy.

 Physical examination may reveal:

 Initially, spasticity in the neck, and/ or upper limb, with neck and upper limb shooting
pain.

 Subsequently, LMN syndrome of the upper limb due to destruction of the ventral roots.

 Subsequently, UMN syndrome of the lower limb due to corticospinal tract compression
from myelopathy.

85
Tabes Dorsalis

 Tabes dorsalis occurs as part of a syndrome of tertiary syphilis. It is characterised by a

progressive involvement of:

 Bilateral dorsal root ganglia and dorsal horns, causing first:

 Irritative lesions with radicular pain and hyperreflexia, and subsequently

 Destructive lesions with reduced sensation at the level of involvement, hyporeflexia and
potentially positive rhomberg sign if enough levels are involved, as well as urinary
incontinence and impotence due to loss of sensation.

 Dorsal column degeneration results particularly in loss of fine touch, vibration and
proprioception.

 Spinocerebellar involvement results particularly in dystaxia, although this would potentially

already be involved from the dorsal root destruction.

86
Brown Sequard Syndrome – Hemisection of Spinal Cord

 Hemisection of spinal cord results in different types of lesions at and below the level of the
lesion.

 Below the level of the lesion:

 Ipsilateral UMN syndrome occurs due to involvement of the lateral spinothalamic tract,
with disuse atrophy, no fasciculations, hypertonia with clasp-knife spasticity,
hyperreflexia with clonus and upgoing plantar reflex, reduced power.

 Ipsilateral loss of dorsal column sensations resulting in loss of fine touch, vibration and
proprioception.

 Contralateral loss of anterolateral sensations, including pain and temperature.

 At the level of the lesion:

 Ipsilateral LMN syndrome.

 Ipsilateral anesthesia to all sensations.

 If the lesion occurs at the level of about T1 in particular, the ciliospinal nucleus of Budge may be
involved, resulting in ipsilateral Horner Syndrome, with:

 Ipsilateral miosis that is fixed to light resulting in anisocoria

 Ipsilateral partial ptosis and apparent enopthalmos

 Ipsilateral anhydrosis of the face and of the upper quadrant of the body.

87
Complete section of Spinal Cord

 Complete section of spinal cord comes with varying consequences depending on the level of
involvement. Generally speaking, there is:

 Bilateral UMN syndrome below the level of the lesion with disuse atrophy, no
fasciculations, hypertonia with claspknife spasticity, hyperreflexia with clonus and
upgoing plantar reflexes, reduced power.

 Bilateral LMN syndrome at the level of the lesion, which is likely comparatively mild.

 Bilateral anesthesia below the level of the lesion.

 Urinary and fecal incontinence with reflex emptying and loss of voluntary control.

 Anhydrosis and loss of vasomotor tone below level of lesion can also occur due to loss
of sympathetic innervation.

 Additional consequences can occur depending on the level of the lesion:

 C1-C3 lesions cause exitus lethalis due to paralysis of the phrenic nerve supplying the
diaphragm, resulting in complete respiratory paralysis.

 C4-C5 lesions produce quadriplegia with respiratory compromise.

 T1-T2 lesions produce spastic paralplegia with bilateral Horner Syndrome.

 T3-L1 lesions produce spastic paraplegia.

88
Anterior Spinal Artery Occulsion

 Anterior spinal artery occlusion results in infarction of the anterior 2/3 of the spinal cord; the
regions most susceptible are T4 and L1 due to these regions receiving the least collateral supply.

 Dorsal columns and dorsal horns are spared.

 Generally speaking, there is:

 Bilateral UMN syndrome below the level of the lesion with disuse atrophy, no
fasciculations, hypertonia with claspknife spasticity, hyperreflexia with clonus and
upgoing plantar reflexes, reduced power.

 Bilateral LMN syndrome at the level of the lesion, which is likely comparatively mild.

 Bilateral loss of anterolateral sensations at and below the level of the lesion, mainly
pain and temperature, with preservation of dorsal column sensations of fine touch,
vibration and propriception.

 Urinary and fecal incontinence with reflex emptying and loss of voluntary control.

 Anhydrosis and loss of vasomotor tone below level of lesion can also occur due to loss
of sympathetic innervation.

89
Filum Terminale Syndrome, Medullaris Conus Syndrome, Epiconus
Syndrome and Cauda Equina Syndrome

 Filum terminale Syndrome results from a thickening of the filum terminale and its adherence to
the sacrum posteriorly, resulting in a tethering of the spinal cord that causes undue traction on
the lower segments (due to the presence of denticulate ligaments which hold the rest of the
spinal cord in place). This results in:

 Sphincter dysfunction and incontinence due to involvement of the sacral

parasympathetic outflow.

 Gait disorders due to abnormal interaction of UMN and LMNs.

 Bilateral foot deformities due to abnormalities of muscle tone.

 Conus medullaris syndrome results from intramedullary tumours or metastases or hemorrhagic

infarcts, in the region of S3 – C0.

 Sacral parasympathetic outflow compromise leads to paralytic bladder with fecal

incontinence and male impotence – this is the LMN syndrome equivalent of the
autonomic nervous system.

 Bilateral saddle-shaped region of anesthesia in the anogenital region.

 Lower limbs are spared.

 Epiconus syndrome occurs due to a similar lesion at the level of L4-S2.

 Sacral parasympathetic outflow is also impaired, but this time leading to spastic
bladder, the UMN equivalent of incontinence. There is also fecal incontinence and male
impotence.

 Bilateral saddle-shaped region of anesthesia in the anogenital region.

 Lumbosacral plexus involvement leads to LMN syndrome in the lower limbs except the
hip flexors and knee extensors. There is loss of sensation of the L4 to S2 dermatomes.

90
 Cauda Equina Syndrome usually occurs due to intervertebral disc herniation or a tumour
resulting in impingment of the nerves on one side.

 Irritative dorsal root lesions result in intense radicular pain in the lower limbs, which
may eventually progress to destructive lesions and loss of sensation at that level.

 Irritative anterior root lesions may lead to spasticity without other UMN signs.

 There is no significant bladder impairment as there is only unilateral involvement of the

nerves supplying the bladder.

91
B12 Deficiency – Subacute Combined Degeneration

 Subacute combined degeneration occurs secondary to B12 deficiency, with demyelination of

both ascending and descending columns, hence the term “combined degeneration”. The horns
are spared.

 It results in:

 Bilateral UMN syndromes with disuse atrophy, no fasciculations, hypertonia and clasp-
knife rigidity, hyperreflexia with clonus and upgoing plantars, and reduced power.

 Bilateral loss of sensations with loss of fine touch, vibration, proprioception, pain,
temperature and rhomberg’s positive.

 Dystaxia due to loss of spinocerebellar pathways.

 Pernicious anemia remains.

92
Frederich’s Ataxia

 Frederich’s ataxia is the most common inherited autosomal recessive cause of ataxia. It results
from increased trinucleotide amplification of the GAA codon, resulting in production of the
fraxitin protein and abnormal lifespan of certain neurons.

 Corticospinal degeneration leads to UMN syndromes with disuse atrophy, fasciculations,

hypertonia with clasp-knife rigidity, hyperreflexia with clonus and upgoing plantars, and
reduced power.

 Purkinje cell involvement in the cerebellum causes severe ataxia.

 Most common inherited autosomal recessive cause of ataxia.

 Cardiac, foot abnormalities ad kyphoscoliosis are also accompanying features.

93
Syringomyelia and Syringobulbia

 Syringomyelia is an abnormal cavitary dilatation of the spinal cord central canal, occurring most
commonly at the cervical region secondary to Arnold chiari malformation with herniation of the
cerebellum through the foramen magnum which impairs CSF drainage. It results in progressive
sequential degeneration of:

 Anterior commissure, leading to loss of anterolateral column sensations, especially pain

and temperature in the region of the finger tips. Dorsal column sensation is preserved,
and many patients do not realise they have lost sensation, classically burning their
fingers without realising it.

 Anterior horns resulting in LMN syndrome at the level of the cervical region, with
wasting of the interosseous muscles and lumbricals.

 Lateral corticospinal tracts resulting in UMN syndrome of the lower limbs.

 Lateral hornsand ciliospinal nucleus of budge resulting in bilateral Horner Syndrome.

 Syringobulbia is a similar dilatation that extends superiorly to involve the brainstem; it can result
in various cranial nerve palsies.

94
Multiple Sclerosis

 Multiple sclerosis is the most common demyelinating disease in the USA; however, its
prevalence is low at the equator and increases as one moves further away, possibly reflecting an
environmental component.

 It involves the recurrent autoimmune destruction of oligodendrocytes, potentially resulting in

demyelination of any central nervous system tract.

 It is so named for the development of multiple patches of sclerosed white matter, distributed in
both time and space in the CNS. Virtually any CNS tract can be involved.

 Optic neuritis is the most common manifestation; recall that the optic nerves are not true
nerves, but are CNS tracts of the diencephalon.

 Medial Longtitudinal Fasciculus involvement can lead to internuclear opthalmoplegias.

 Corticospinal involvement can lead to UMN syndromes at any site.

 Dorsal column involvement can lead to loss of fine touch, vibrations and proprioception,
possibly with positive Rhomberg.

 Spinothalamic involvement leads to loss of pain and temperature.

 Spinocerebellar involvement leads to dystaxia.

 It is a disease of recurrent attacks; corticosteroids may speed the rate of recovery, but there is
no way of actually decreasing the risk of attacks.

95
THE BASAL GANGLIA
Anatomy of Basal Ganglia & Related Structures

 The basal ganglia are a heterogenous group of nuclei located at the base of the cerebral
hemispheres. The term “ganglia” is something of a misnomer, as these gray matter collections
are surrounded by white matter within the CNS, rather than located outside the CNS.

 The thalami are two egg-shaped structures located just lateral to the third ventricle and superior
to the midbrain.

 Slightly lateral to each thalamus is a caudate nucleus, which is a C-shaped structure that sits on
the inner curve of the lateral ventricles. It is composed of a head, body and tail.

 The amygdala is located at the tail of the caudate nucleus.

 The lentiform nucleus is located just lateral and posterior to the head of the caudate
nucleus.

 The lentiform nucleus is composed of the putamen, globus pallidus externa and globus pallidus
interna from lateral to medial.

 The lentiform nucleus is surrounded by a white matter capsule medially and laterally.

 The medial part of the white matter capsule is known as the inner capsule, and
separates it from the thalamus.

 The lateral part of the white matter capsule is known as the outer capsule, and
separates it from the claustrum.

96
 The claustrum is a thin sheet of gray matter situated lateral to the outer capsule. Lateral to the
claustrum lies another white matter layer known as the extreme capsule.

 Lateral to the claustrum is the insular cortex, which is an area of cerebral cortex lying in the
lateral sulcus, which separates the temporal lobe from the parietal and frontal lobes.

 The thalamus is separated from the midbrain by the subthalamus between them.

 In cross-section, the midbrain reveals bilateral strips of particularly dense gray matter known as
the substantia nigra (black substance).

 The substantia nigra is more dense posteriorly, where it is known as substantia nigra pars
compacta, and is mixed with some white matter anteriorly to form the substantia nigra pars
reticulata.

Definition of Basal Ganglia

Classically, the anatomical classification of the basal ganglia comprises:

 The caudate nucleus

 The lentiform nucleus (with its putamen, globus pallidus externa and globus pallidus interna)

 The claustrum

With the advancement of the understanding of the functional relations of the basal ganglia, its
components have been clinically regrouped and redefined as follows:

 The caudate nucleus, putamen, globus pallidus externa and interna are now collectively known
as the corpus striatum. The corpus striatum is divided into:

 Neostriatum, which includes the caudate nucleus and the putamen, which are
functionally related. When the term striatum is used, it generally refers to the
neostriatum.

 Paleostriatum, which includes the globus pallidus externa and interna.

 The subthalamus and substantia nigra are now considered part of the basal ganglia.

 The claustrum is no longer considered part of the basal ganglia.

97
Motor Functions of Basal Ganglia in Context

 Broadly speaking, the basal ganglia contains the circuitry where motor programs are stored.

 The basal ganglia receives information about the final intended position of the body from the
cerebral cortex.

 Based on this information, its circuitry selects the appropriate UMNs that need to be activated
or inhibited to produce meaningful movement. It relays this information via the thalamus back
to the cerebral cortex.

 The other main storage site of motor programs is found in the cerebellum. The cerebellum’s
circuitry also aids in selection of the appropriate UMNs to be activated/ inhibited by comparing
the final intended position of the body to current proprioceptive input. It sends an output back
to the cerebral cortex as well.

 The outputs of the basal ganglia and cerebellum are integrated, before being sent to the UMNs
for execution of the program.

98
Basic Circuitry of the Basal Ganglia

 The above diagram depicts a schematic of the basal ganglia circuitry in a unilateral hemisphere.

 The inputs and outputs of the putamen in the schematic collectively represent those of
the neostriatum as a whole.

 The substantia nigra pars reticulata is now recognised to have the same functional
connections of the globus pallidus interna, and may be considered an anatomically
displaced component of the latter.

 In this circuit, all the GABAergic neurons (drawn in blue) are inhibitory and all the glutaminergic
neurons (drawn in red) are stimulatory.

 Neurons from the premotor and supplementary motor cortex (in green) send fibers to the
glutaminergic neurons found in the cerebral cortex.

 These stimulatory glutaminergic form corticostriatal pathways; they synapse onto and stimulate
GABAergic neurons found in the neostriatum.

 From the neostratium, two different pathways are produced: a direct and indirect pathway.

99
 The direct pathway results in stimulation of the UMNs in the motor cortex, thereby facilitating
movement. In the direct pathway,

 The GABAergic neurons in the neostriatium project onto GABAergic neurons in the
globus pallidus externus which are constitutively active.

 GABAergic neurons in the globus pallidus externus project onto glutaminergic neurons
in the ventroanterior (VA) and ventrolateral (VL) nuclei in the thalamus.

 Glutaminergic neurons in the VA and VL nuclei project back to the cortex, where the
stimulate UMNs in the motor cortex.

 The nett effect of triggering the direct pathway is stimulation of UMNs in the motor
cortex.

 The indirect pathway eventually results in inhibition of UMNs in the motor cortex.

 The GABAergic neurons in the neostriatium project onto GABAergic neurons in the
globus pallidus internus.

 GABAergic neurons in the globus pallidus internus project onto glutaminergic neurons
in the subthalamus.

 Glutaminergic neurons in the subthalamus project onto GABAergic neurons in the

globus pallidus externus.

 GABAergic neurons in the globus pallidus externus project onto glutaminergic neurons
in the VA and VL nuclei in the thalamus.

 Glutaminergic neurons in the VA and VL nuclei project back to the cortex, where the
stimulate UMNs in the motor cortex.

 The nett effect of triggering the indirect pathway is inhibition of UMNs in the motor
cortex.

 It has been proposed that the direct and indirect pathways, rather than simply providing an
overall stimulation or inhibition to the motor cortex, may serve different functions:

 Triggering the direct pathway may stimulate UMNs corresponding to muscles that
should contract in the desired motor sequence.

 Triggering the indirect pathway may inhibit UMNs corresponding to muscles that should
relax in the desired motor sequence.

 In this way, part of the motor programme may be encoded in the basal ganglia circuitry.

 The thalamic nuclei act as a relay station; aside from input from the basal ganglia, the VL nucleus
also receives and integrates input from the cerebellum before producing output to motor cortex.

 The current understanding of the basal ganglia is thought to be an oversimplification, and the
true nature of the basal ganglia circuit is not yet clearly understood.

100
Modulation of Basal Ganglia Circuit by Dopaminergic Neurons

 The basal ganglia’s circuitry is additionally modulated by dopaminergic neurons in the

substantia nigra pars compacta.

 They may be thought of as being important for two reasons:

 They modulate activity of the direct and indirect pathways to refine motor control.

 They are important in facilitating the initiation of movement.

 They refine motor control as follows:

 Dopaminergic neurons from the substantia nigra pars compacta synapse onto GABAergic
neurons of the neostriatum via nigrostriatal pathways.

 These dopaminergic neurons stimulate the striatal GABAergic neurons of the direct
pathway via D1 receptors, but inhibit the striatal GABAergic neurons of the indirect
pathway via D2 receptors.

 The final effect is to upregulate firing of UMNs under the control of both the direct and
indirect pathways.

 In doing so, it opposes the effect of the glutaminergic corticostriatal neurons, whose role
is to stimulate the firing of UMNS under the control of the direct pathway but inhibit the
firing of UMNs under the control of the indirect pathway.

 Thus, the balance between the nigrostriatal and corticostriatal neurons determines the
ultimate balance between the force of contraction of flexor and extensor muscles,
thereby refining motor control.

 The substantia nigra pars compacta itself receives inputs from the cerebral cortex that
help it decide to what extent it should modulate motor control.

 Secondly, the CNS activates all movements through some balance of nigrostriatal fibers and
corticostriatal fibers.

 It follows that if the nigrostriatal fibers malfunction, the action of the corticostriatal
fibers alone may be insufficient to initiate movements, presuming the CNS does not
compensate with increased corticostriatal firing.

 This is exactly what occurs in Parkinson Disease, in which there is hypokinesia due to
degeneration of dopaminergic neurons of the substantia nigra pars compacta.

101
Cholinergic Modulation of Basal Ganglia Circuitry

 Cholinergic modulation arises from cholinergic neurons residing in the neostriatum, which are
thought to perform the exact opposite role of the dopaminergic nigrostriatal fibers.

 These cholinergic neurons inhibit the striatal GABAergic neurons of the direct pathway,
but stimulate the striatal GABAergic neurons of the indirect pathway.

 In doing so, the final effect is to downregulate activation of UMNs associated with both
agonistic muscles and antagonistic muscles.

 The cholinergic and dopaminergic neurons work together to modulate the balance of
action between agonistic and antagonistic muscles to produce finer control of the force
of movements.

 The cholinergic neurons are probably also under regulation by the cerebral cortex.

Parkinson Disease – A Hypokinetic Disorder

 Parkinson Disease is a degenerative disease of the CNS which results in the death of, amongst
other neurons, the dopaminergic neurons of the substantia nigra pars compacta.

 Death of these dopaminergic neurons is responsible for many of the motor symptoms of
Parkinson disease; the disease may be conceptualised as a relative imbalance of dopamine
compared to cholinergic neurons.

 Round α-synuclein Lewy bodies may be observed in the affected neurons.

 Parkinson Disease is characterised by a triad of:

 Hypokinesia

 Lead pipe rigidity

 Pill-rolling Tremors

102
 Hypokinesia occurs because the dopaminergic nigrostriatal neurons, working in conjunction
with the corticostriatal neurons, are required to facilitate initiation of movement.

 This manifests as difficulty initiating movements. Some basic repetitive movements e.g.
walking, once initiated, can be maintained without further difficulty; this may be the
result of poorly defined reverberating circuits running in the basal ganglia or elsewhere.

 This initiation of movement may be enhanced by external cues, e.g. visual cues or rituals
or other psychological triggers that enhance the process.

 However, just as it is difficult to initiate a movement, once initiated, it can be difficult for
the movement to be stopped or altered. For example, patients may find it difficult to
stop walking once initiated, or to change their course of direction. This may be due to
difficulty in altering reverberating circuits once they have been initiated.

 Physical signs of this hypokinesia include a shuffling gait, mask-face (due to impaired
facial expressions) and serpentine stare (due to reduced blinking).

 Parkinson Disease is associated also with lead pipe rigidity.

 It is thought that the reduced stimulation of the cortex by the direct and indirect
pathways results in reduced firing of UMNs that normally inhibit the pontine and
medullary reticulospinal tracts.

 Recall that the pontine and medullary reticulospinal tracts are extrapyramidal tracts
that work to maintain flexor and extensor muscle tone respectively.

 Reduced inhibition of corticoreticular tracts leads to overfiring of these pathways,

resulting in hypertonia and lead pipe rigidity.

 The hypertonia is less than that caused by UMN lesions and does not cause spasticity;
however when interspersed with pill-rolling tremors can lead to cog-wheel rigidity.

 The resting, pill-rolling tremors occur at a frequency of 4-7Hz.

 One hypothesis holds that there are reverberating circuits that exist within the basal
ganglia-subthalamic-thalamic loop which are normally under dopaminergic inhibition.

 A relative imbalance of dopaminergic to cholinergic modulation leads to oscillating,

alternating firing of agonistic and antagonistic muscles, leading to a characteristic tremor
that occurs at rest. Interestingly, the initiation of movement causes tremors to reduce.

 Postural instability is an additional feature in late stages.

 Dementia also occurs in late stages.

 Parkinsonism disorders involve similar symptoms secondary to other etiologies that cause
reduced dopaminergic transmission, e.g. dopaminergic antagonists (used as antipsychotics),
and MPTP-associated Parkinson, in which MPTP (a heroin cutting agent) kills nigrostrial neurons.

103
Hyperkinesia – Huntington Disease and Diseases Causing Chorea/ Athetosis

 Huntington Disease results from the preferential degeneration of GABAergic striato-external

pallidal neurons of the indirect pathway.

 These neurons are physiologically different from the GABAergic striato-internal pallidal neurons
of the external pathway in that the former also expresses enkephalins, and the latter expresses
Substance P. The reason for preferential degradation of one neuron over the other is unknown.

 Degeneration of the putamen of the striatum in particular manifests as hydrocephalus ex vacuo.

 It is an autosomal dominant disorder resulting from mutations in the Huntington gene (HTT).

 There is trinucleotide expansion of CAG repeats, occurring during spermatogenesis.

 This can lead to anticipation, in which each subsequent generation is associated with a
greater number of trinucleotide repeats, greater toxicity and earlier disease onset.

 This protein causes degeneration of the GABAergic striato-external pallidal neurons of the
indirect pathway and unintentional release of multiple motor programs in a haphazard manner.

 This unintentional release of motor programs may manifest as a chorea, in which there
is rapid transition from one unintentionally released motor program to another,
producing uncontrollable, involuntary and purposeless dance-like movements.

 Chorea may also be observed in rheumatic fever, in which S. pyogenes cause production
of self-reactive antibodies to, amongst other things, these neurons. This is known as
Sydenham’s chorea or St Vitu’s Dance. Sydenham’s chorea is far more likely to be seen
in patients under 30YO, while Huntington is far more likely to be seen over 30YO.

 Chorea can also be observed in Wilson Disease, in which accumulation of copper

damages, amongst other things, these neurons.

 Any of these diseases may also manifest as athetosis rather than chorea; athetosis
simply results from a slower transition from one motor program to another, producing
slow, rhythmic dance-like movements.

 A combination of chorea and athetosis may be described as choreoathetosis.

 Additionally, some cholinergic neurons are targeted in Huntington Disease, and it is thought that
this contributes to the motor problems as well as depression and dementia.

104
Hyperkinesia – Hemiballismus

 Hemiballismus usually results from damage to the subthalamus, oftening secondary to

hypertension or diabetes which increases risk of thrombosis and haemorrhage, which can result
in infarction.

 Unlike Parkinson and Huntington, which are bilateral diseases, damage to the subthalamus can
occur unilaterally; it results in movement disorders on the contralateral side to the lesion.

 It results in axial, hip and shoulder girdle movements. These movements appear to be especially
under the control of the subthalamus.

Hyperkinesia – Tardive Dyskinesia

 Tardive Dyskinesia, in contrast to Parkinsonism, results from upregulation of dopamine receptors.

 This can occur due to withdrawal effects after stopping the use of dopamine receptor blockers,
used in treatment of psychosis.

 Thus, dopamine receptor blockers may cause a Parkinson-like hypokinesia during use, but a
Tardive Dyskinesia or hyperkinesia upon withdrawal

 A hypersensitivity to dopamine results in overactivation of motor programs via direct pathway

 It is characterised by fly-catching movements, smacking of the lips and other abnormal oral-
facial movements affecting the lips, tongue and jaw.

105
THE CEREBELLUM
Gross Anatomy of Cerebellum

 Anatomically, the cerebellum is divided into three main lobes: an anterior lobe (purple),
posterior lobe (green) and flocculonodular lobe (yellow).

 The primary fissure separates the anterior lobe from the posterior lobe; the dorsolateral fissure
separates the posterior lobe from the flocculonodular lobe.

 From the posterior view, it can be seen that a sagittal depression runs down the center of the
cerebellum. This depression is called the vermis (vermis = worm).

 The vermis divides the cerebellum into a left and right hemisphere laterally. Each of the left and
right cerebellar hemispheres, unlike the cerebral hemispheres, are responsible for functions in
the ipsilateral side of the body.

 Two regions immediately lateral to the vermis lying in each of the left and right hemispheres are
called the left and right paravermal areas. These are also called the intermediate zones.

 Importantly, unlike the cerebrum, the cerebellar hemispheres perform functions for the
ipsilateral side of the body. Correspondingly, lesions to one hemisphere lead to clinical signs and
symptoms in the ipsilateral body.

106
Functional Divisions of Cerebellum

 Functionally, the cerebellum is divided into the vestibulocerebellum, spinocerebellum and

cerebrocerebellum, each of which correspond to one of three major cerebellar functions.

 Lesions to each of the three functional divisions thus cause different types of loss of function.

 The vestibulocerebellum:

 Is the least evolved of the three and is also called the archicerebellum.

 Anatomically, the vestibulocerebellum is comprised of the flocculonodular lobe.

 Its function is to maintain balance and equilibrium, particularly of the head and neck as
well as the movement of the eyes.

 The spinocerebellum:

 Is the next most primitive, and is accorded the phylogenetic name of paleocerebellum.

 Anatomically the spinocerebellum comprises most of the vermis and paravermal areas.
Some authors describe it as corresponding simply to roughly the anterior lobe.

 It is responsible for the maintenance of muscle tone.

 The cereberocerebellum:

 Is most recently evolved, and is accorded the name neocerebellum.

 The cerebrocerebellum corresponds anatomically to the lateral hemispheres, excluding

the paravermis. Some authors describe it as corresponding simply to the posterior lobe.

 It is concerned with coordination of movement.

 The spinocerebellum is arranged into two separate homunculi.

 The homunculus of the anterior lobe is arranged upside down, while the homunculus of
the posterior lobe is arranged right side up.

 The two homunculi are arranged such that the vermis is associated with the functions of
the axial skeleton, that is, comprising the head, neck, trunk, shoulder and hip girdles.

 The paravermal areas are more associated with the functions of the upper and lower
limbs, particularly the hands and feet.

 Thus, lesions to specific parts of the spinocerebellum produce loss of function in

predictable parts of the body.

 The cerebellum has a superficial layer of gray matter called the cerebellar cortex, and deep
cerebellar nuclei which are surrounded by axonal white matter tracts.

107
Spinocerebellum and Cerebrocerebellum in the Context of Motor System

 The thought of performing a voluntary action is first conceived in the prefrontal cortex. The
prefrontal cortex sends this information to planning centers located in the premotor and
supplementary motor cortex.

 The planning centers produce a “proprioceptive image” of what the final intended position of
the body should look like at the end of the movement.

 It communicates this intended proprioceptive image to the cerebellum. The cerebellum

itself also receives a current proprioceptive image based on live updated information
via the ventral/ dorsal spinocerebellar and cuneocerebellar tracts.

 The cerebral cortex also receives current proprioceptive information via the DCML.

 By comparing the current and intended proprioceptive images, the cerebellum aids in
selecting a motor program, and sends an output back to the planning centers via the red
nucleus and thalamus (not shown in diagram). In this manner, a mental rehearsal can be
performed before the program is even executed.

 The planning centers send this information to the basal ganglia, which also contains part of the
circuitry of the motor program, which provides fine motor control and initiates the movement.

 The basal ganglia then sends output via the thalamus to stimulate or inhibit the appropriate
upper motor neurons in such a sequence so as to produce meaningful movement. The
cerebellum may also directly modulate basal ganglia output at the thalamus.

 When the UMNs fire, some collateral fibers also synapse onto ascending spinocerebellar
neurons that ascend back to the cerebellum and inform it of the final program being executed.
This second-check mechanism allows it to confirm the selected program matches the intended
movement and that its instructions were well-received.

 Finally, as the movement is being executed, current proprioceptive information is continuously

updated in the cerebellum as well as cerebral cortex; based on this, it predicts in advanced if the
movement is on course to reaching the final intended image, and continuously refines the
instructions sent the the cerebral cortex.

108
Internal Circuitry of Cerebellum

 The gray matter of the cerebellum comprises a cerebellar cortex and deep cerebellar nuclei.

 The cerebellar cortex is also known as my personal garden. It is split into three layers from
superficial to deep: the molecular, purkinje and granular layers.

 The deep cerebellar nuclei sit surrounded by white matter.

 Any fibers that pass into the cerebellum must synapse onto it and say hello before
approaching the cortex.

 The deep cerebellar nuclei are responsible for producing the final output of cerebellum.

 The inputs of the cerebellum come from white matter tracts entering the cerebellum. These can
be divided into climbing fibers and mossy fibers.

 Climbing fibers are like Spartans who climb olive trees (shown in green).

 They originate from the inferior olivary nucleus, and may thus be called olivocerebellar
fibers. The inferior olivary nucleus itself receives inputs from elsewhere such as spino-
olivary fibers.

 They say hello and provide collateral fibers to the deep cerebellar nuclei, and then climb
all the way to synapse onto the outermost layer of the cerebellar cortex.

 Their main neurotransmitter of use is aspartate.

 Mossy fibers are like “mousey” mice who come from everywhere (shown in red).

 They encompass fibers and tracts originating from all sources other than inferior olivary
nucleus, including anterior/ dorsal spinocerebellar, cuneocerebellar, tectocerebellar,
pontocerebellar, reticulocerebellar, vestibulocerebellar and corticocerebellar fibers.

 They say hello and provide collateral fibers to the deep cerebellar nuclei, but after that
are relatively lazy and synapse only onto the deepest layer of cortex.

 Their main neurotransmitter is glutamate.

109
 From the above diagram, it can be seen that three groups of cells synapse onto the deep
cerebellar nuclei:

 The green aspartate climbing fibers which are stimulatory to the deep cerebellar nuclei

 The red glutaminergic mossy fibers which are stimulatory to the deep cerebellar nuclei

 The blue GABAergic purkinje fibers which are inhibitory to the deep cerebellar nuclei.

 The purkinje fibers are not incoming fibers to the cerebellum, but rather take origin from the
purkinje cells in the cerebellar cortex. These are flasked-shaped cells (drawn in blue).

 Their cell bodies are located in the purkinje layer.

 They extend dendrites into the molecular layer.

 Their axons synapse onto the deep cerebellar nuclei.

 Although the climbing and mossy fibers are directly stimulatory to the deep cerebellar nuclei,
some of them also synapse onto the purkinje cells and in doing so also exert an indirect
inhibitory effect on the deep cerebellar nuclei.

 Each climbing fiber makes its way to the molecular layer, and synapses onto a single
purkinje cell. It is thus fairly faithful to the purkinje cell.

 Each mossy fiber stops at the granular layer and forms multiple synapses onto multiple
granular cells, which are stimulatory cells.

 Each granular cell extends an axon to the molecular layer, bifurcates into two fibers
which run parallel to the folia (wrinkled gyri) of the cerebellum, and again makes
multiple synapses onto multiple purkinje cells.

 The “mousey” mossy fibers, and their associated granular cells, are thus very
promiscuous indeed, and have no family values at all!

 In this manner, each climbing fiber provides a single stimulatory and single inhibitory
input to the deep cerebellar nucleus; each mossy fiber makes a single stimulatory but
multiple, diffuse inhibitory inputs to the deep cerebellar nucleus.

110
 The mossy-granular system additionally has a number of inhibitory interneurons.

 The golgi cells are found in the granular layer, and serve as autoregulators that dampen the
multiplied but diffuse inhibitory output of the mossy-granular system.

 They are stimulated by mossy cells and granular cells themselves.

 They inhibit granular cells, and in doing so keep the amplification of the mossy-granular
system in check by autoregulation.

 The basket and stellate cells are found in the molecular layer, and serve to sharpen the diffuse
inhibitory signals produced by the granular cell axons.

 Each granular cell synapses onto multiple purkinje cells; for each purkinje cell it synapses
onto, it will also synapse onto a few surrounding basket and stellate cells.

 Whenever the granular cell fires, the basket and stellate cells serve to inhibit other
purkinje cells in the area surrounding the central purkinje cell, thus sharpening its signal.

 The deep cerebellar nucleus is the final integrator of all signals in the cerebellar cortex circuit,
and subsequently sends the output of the cerebellum.

111
Inputs and Outputs of Cerebellum

 Each of the vestibulocerebellum, spinocerebellum and cerebrocerebellum receives different

inputs, integrates this information, and produces different outputs that define their functions.

 The inputs are:

 From the vestibular system to the vestibulocerebellum

 From the spinocerebellar pathways to the spinocerebellum

 From the cerebral cortex to the cerebrocerebellum

 The outputs are produced from different deep cerebellar nuclei.

 The fastigial nucleus is located most medially, and produces the output for the
vestibulocerebellum

 The globose and embolliform nuclei, located lateral to the fastigial nucleus, are
collectively known as the interposed nuclei and produce output for spinocerebellum.

 The dentate nucleus is located most laterally and produces the output for
cerebrocerebellum.

112
Vestibulocerebellum Inputs and Outputs

 The vestibulocerebellum input is received from:

 Directly from the vestibular organs

 Indirectly from vestibular organs via the vestibular nucleus

 These inputs enter the vestibulocerebellum via the infererior cerebellar peduncle

 The vestibulocerebellum output is produced via the fastigial nucleus.

 The fastigial nucleus sends output to the red nucleus and vestibular nucleus.

 Collectively, the red nucleus and vestibular nucleus integrate this information and send
rubrospinal and vetibulospinal tracts targeted at maintaining resting muscle tone for
balance.

 Some fibers are also sent to the VPM nucleus of thalamus, and relayed to the cerebral
cortex via thalamocortical fibers for the conscious perception of equilibrium.

 Additionally, the vestibular nucleus sends an ascending medial longtitudinal fasciculus

to communicate with the CN III, IV and IX nuclei so as to provide information on head
movement and inform the vestibuloocular reflexes so as to maintain fixed gaze.

113
Spinocerebellum Inputs and Outputs

 The spinocerebellum receives proprioceptive input from:

 The dorsal spinocerebellar pathway

 The cuneocerebellar pathway

 The ventral spinocerebellar pathway

 The spino-olivary and olivocerebellar pathways

 The spinocerebellum produces output via the globose and emboliform nuclei to:

 The red nucleus, which sends descending rubrospinal tracts to maintain muscle tone.

 The ventrolateral nucleus of thalamus, both directly via the cerebellothalamic fibers as
well as indirectly via the rubrothalamic fibers.

 The ventrolateral nucleus of thalamus may either directly modify the output of the basal
ganglia, or send thalamocortical fibers to the cerebral cortex to further correct motor
programs in the planning centers.

 In doing so, they are able to refine and adjust motor programs that are currently in
execution or in planning using updated information from peripheral receptors.

114
Cerebrocerebellum Inputs and Outputs

 The cerebrocerebellum input is received from:

 Corticopontine and pontocerebellar pathways

 These pathways provide information about motor programs in planning

 The cerebrocerebellum output is produced via the dentate nucleus, but targets similar nuclei as
the spinocerebellum:

 There are cerebellorubral fibers to the red nucleus, and rubrothalamic fibers to the
ventrolateral nucleus of thalamus.

 There are also direct cerebellothalamic fibers to the ventrolateral nucleus.

 The ventrolateral nucleus sends thalamocortical fibers to the cortex for the correction
of motor programs.

Conclusion

 The vestibulocerebellum receives information about balance and equilibrium from the vestibular
system, and via its circuitry modifies the activity of LMNs in order to maintain balance and
equilibrium in flexor muscle tone and in the extraoccular muscles.

 The spinocerebellum receives proprioceptive information about movements currently in

progress from the peripheral receptors. Via its circuitry, it modifies the activity of UMNs in order
to refine motor programs currently in progress.

 The cerebrocerebellum receives information about motor programs being planned in the
cerebral cortex. Via its circuitry, it modifies the activity of UMNs in order to refine motor
programs that are currently being planned.

115
BASIC BRAIN STEM & CRANIAL NERVE CONCEPTS
This chapter integrates material from the basic concepts of brainstem and cranial nerves.

Review of Brainstem Anatomy

 The brainstem consists of the medulla (meyencephalon), pons (metencephalon) and midbrain
(mesencephalon) from inferior to superior.

 The medulla has two medial ridge-like structures called pyramids, and two bulging
olives immediately lateral to them.

 The junction between the pons and medulla is marked distinctly by a pontomedullary
sulcus.

 The midbrain has two posterior bilateral swellings, the superior and inferior colliculi.

 The cerebellum (also arising from metencephalon) attaches to the brainstem via bilateral
superior, middle and inferior cerebellar peduncles. Peduncles are bundles of white matter that
connect the brainstem to either the cerebellum or the cerebral hemispheres.

 The inferior cerebellar peduncles attach to the medulla.

 The middle cerebellar peduncles attach to the pons.

 The superior cerebellar peduncles attach to the midbrain.

 At the level of the medulla, the groove between the pyramid medially and olive laterally is
known as the pre-olivary sulcus. The groove between the olive anteriorly and the inferior
cerebellar peduncle posteriorly is known as the post-olivary sulcus.

 The brainstem attaches to the cerebral hemispheres by the two cerebral peduncles of the
midbrain.

 Inbetween the two cerebral peduncles lies the interpeduncular fossa, which when covered by
the overlying arachnoid mater is transformed into the interpeduncular cistern, which is an
expanded CSF-filled space.

 Of the 12 pairs of cranial nerves, only CN III to XII attach to the brainstem.

116
Origins of Cranial Nerves I and II

 Cranial Nerve I (Olfactory Nerves) is not a single nerve; indeed each individual possesses 15 to
20 pairs of olfactory nerves, which extend from the nasal mucosa.

 The neurons of the olfactory nerves are bipolar neurons with peripheral processes and
central processes.

 The peripheral processes are receptors for the sense of smell, and thus carry SVA
information to the CNS.

 The central processes pass through the cribiform plate to convey this information to the
CNS. They synapse onto mitral cells of the olfactory bulb.

 The olfactory bulb is a central nervous system tract derived from the telencephalon; it
runs posteriorly and terminates as two or three olfactory stria.

 The lateral olfactory stria terminates at the uncus of the temporal lobe where the
piriform cortex is located. It is responsible for the sense of smell.

 Cranial Nerve II (Optic Nerve) is defined anatomically to extend from the lamina cribrosa
sclerae of the back of the eye, posteriorly as far as the optic chiasma.

 CN II is unique in that it is not a true cranial nerve, but rather an extension of a central
nervous system tract; it is derived from the diencephalon itself.

 Histologically, it is myelinated by oligodendrocytes rather than Schwann cells;

thus it is affected by demyelinating diseases of the CNS but not by demyelinating
diseases of the PNS.

 It is covered by all three layers of the meninges and is surrounded by a CSF-filled

space continuous with that of the brain.

 The optic nerves carry visual SSA information. Information from the left or right visual
field of each eye is conveyed via the optic chiasma and optic tract to the contralateral
lateral geniculate body of the thalamus.

 The information is then conveyed via optic radiations to the primary visual cortex. The
visual cortex of each hemisphere thus collects information about the contralateral visual
field of each eye (but the ipsilateral half of each retina).

117
Origin of Cranial Nerves III to XII from the Brainstem

 CN III (oculomotor nerve) originates from the medial side of the cerebral peduncles of the
midbrain, exiting anteriorly from the interpenduncular fossa.

 CN IV (trochlear nerve) originates from the posterior midbrain at the level of the inferior
colliculus, before hooking around the brainstem laterally and anteriorly.

 It is the only cranial nerve to exit from the posterior aspect of the brainstem; it is thought
that it used to provide innervation to the pineal gland superoposterior to the brainstem,
before evolving to perform its role in the modern eye.

 The pineal gland was a primitive eye structure that continues to receive fibers from the
optic tract in modern humans; it measures daylight exposure and secretes melatonin in
order to maintain the circadian rhythm.

 CN V (trigeminal nerve) has a large sensory root and a small motor root that both take origin
from the anterolateral aspect of the mid-pontine region. The sensory root originates slightly
superior to the motor root, but fibers from both run together in the same nerve. The trigeminal
nerve is named for the three nerves it gives rise to:

 V1 is the ophthalmic nerve, which is purely sensory.

 V2 is the maxillary nerve, which is purely sensory.

 V3 is the mandibular nerve, which contains both sensory fibers and all the fibers from
the motor root.

 

118
 CN VI (abducens nerve), CN VII (facial nerve) and CN VIII (vestibulocochlear nerve) take origin
from the pontomedullary sulcus from medial to lateral.

 Lesions to the medial aspect on the pontomedullary junction affect both CN VI and CN
VII, because the CN VII fibers within the brainstem are closely related to the CN VI
nucleus, as well be demonstrated later.

 Lesions to the lateral aspect of the pontomedullary junction affect both CN VII and CN
VIII, because after emerging from the brainstem the fibers from these two nerves run
closely together.

 CN IX (glossopharyngeal nerve), CN X (vagus nerve) and the cranial aspect of CN XI arise from
superior to inferior in the groove between the olives of the medulla and the inferior cerebellar
peduncles, known as the post-olivary sulcus.

 The vagus nerve is named for its wandering characteristics (the “vagabond”) as, unlike
the other cranial nerves, it innervates structures outside the head and neck.

 CN XI is classically described to have two parts, a cranial part taking origin from the
brainstem as described, and a spinal part taking origin from the superior spinal cord.

 The spinal component of CN XI takes origin from the spinal cord posterior to the ventral
roots and anterior to the dorsal roots of spinal nerves CI to CIII.

 However, fibers from the cranial part of CN XI travel only briefly with the fibers from the
spinal part; they quickly separate again to join fibers of CN X, the vagus nerve.

 The distal part of CN XI is thus composed of fibers taking origin only from the spinal
component. CN XI is thus named the spinal accessory nerve.

 CN XII (hypoglossal nerve) takes origin from the groove between the pyramids and olives known
as the pre-olivary sulcus.

119
Course of Cranial Nerves Through Skull

 CN I is formed of 15-20 pairs of olfactory nerves, whose central processes leave the nasal cavity
to enter the cranium through the cribiform plate and connect to the CNS.

 CN II leaves the cranium through the optic canal.

 CN III, IV, VI (those controlling the extraocular muscles) and V1 (ophthalmic division of trigeminal
nerve) leave the cranium through the superior orbital fissure.

 CN V gives off three branches:

 V1 (ophthalmic division) exits through the superior orbital fissure.

 V2 (maxillary division) exits through the foramen rotundum.

 V3 (mandibular division) exits through the foramen ovale.

 CN VII and VIII exit via the internal acoustic meatus.

 CN XI, X and XI exit via the jugular foramen.

 CN XII exits via the hypoglossal canal.

120
Basic Organisation of Brainstem

 All levels of the brainstem (medulla, pons, midbrain) are organised into three segments from
anterior to posterior, the basis, tegmentum and tectum.

 The basis contains the all of the descending tracts while the tegmentum contains the ascending
tracts and the nuclei of the cranial nerves.

 The brainstem may be thought of as a superior extension of the spinal cord. However, the
transverse section of the brainstem is arranged differently.

 This rearrangement may be visualised by placing one’s fingers in the posterior median
sulcus of the spinal cord and prying it apart.

 This results in formation of the fourth ventricle in the rhombencephalon, and

 Arrangement of the somatic motor, autonomic and sensory horns from medial to lateral,
derived from basal and alar plates respectively.

 Decussating fibers at the level of the brainstem disrupt gray matter into discrete brainstem
nuclei for the cranial nerves. In some regions the gray matter is even more diffusely distributed
and forms the reticular formation.

 In addition to the GSE, GVE, GSA and GVA neurons found in the spinal cord, the brainstem has
SVE, SVA and SSA nuclei. Other subcortical accessory nuclei include the olives of the medulla
(shown in green in the final diagram), the pontine nuclei, and the substantia nigra & red nucleus
of the midbrain.

121
Motor Cranial Nerve Nuclei

 The General Somatic Efferent nuclei (analogous to the ventral horns in spinal cord) are located
most medially within the brainstem. From superior to inferior, they are:

 The oculomotor nucleus is found in the midbrain, and provides GSE supply via CN III
(oculomotor nerve) to most of the extraocular muscles of the eye other than those
receiving innervation from CN IV and VI.

 The trochlear nucleus is found in the midbrain, and provides GSE supply via CN IV
(trochlear nerve) to the contralateral superior oblique muscle. The trochlear nucleus
supply crossed fibers to the contralateral trochlear nerve which exits posteriorly from the
brainstem, and is the only cranial nerve nucleus to do so.

 The abducens nucleus is found in the pons, and provides GSE supply via CN VI
(abducens nerve) to the lateral rectus muscles for abduction of the ipsilateral eye.

 The hypoglossal nucleus is found at the level of the medulla, and provides GSE supply
via CN XII (hypoglossal nerve) to the musculature of the tongue.

122
 The General Visceral Efferent nuclei (analogous to the lateral horns in spinal cord) are located
immediately lateral to the GSE nuclei. Recall that all GVE fibers from the cranial outflow are
parasympathetic. From superior to inferior, they are:

 The Edinger-Westphal Nucleus is found in the midbrain, immediately lateral to the

oculomotor nucleus. It provides parasympathetic outflow to the eye via CN III
(oculomotor nerve) and the ciliary ganglion.

 The lacrimatory nucleus and superior salivatory nucleus are merged as a single nucleus
anatomically and are found at the level of the pons.

 The lacrimatory nucleus constitutes the superior half, and provides GVE
parasympathetic supply via CN VII (facial nerve) and the pterygopalatine
ganglion to the lacrimal glands.

 The superior salivatory nucleus constitutes the inferior half, and provides GVE
parasympathetic supply via CN VII (facial nerve) and the submandibular gaglion
to both the submandibular and sublingual glands.

 The inferior salivatory nucleus is found at the level of the medulla and provides GVE
parasympathetic supply via CN IX (glossopharyngeal nerve) and the otic ganglion to the
parotid gland and controls salivation.

 The dorsal motor nucleus of Vagus is found at the level of the medulla and provides GVE
parasympathetic supply via CN X (Vagus nerve) to many head and neck, thoracic and
abdominal structures.

 The Special Visceral Efferent nuclei provide a special type of motor innervation that includes
both voluntary and involuntary movements, to special musculature arising from the branchial
arches, known as branchiomeric musculature. They are displaced anteriorly from the back row
of nuclei that we have described so far. From superior to inferior they include:

 At the level of the pons, the trigeminal branchiomotor nucleus provides the SVE supply
via CN V3 (mandibular branch of trigeminal nerve) to the muscles of mastication
derived from the first branchial arch.

 At the level of the pons, the facial branchiomotor nucleus provides SVE supply via CN VII
(facial nerve) to the muscles of facial expression derived from the second branchial arch.

 At the level of the medulla, the nucleus ambiguus was named because of its unusual
location and unknown function; it innervates structures derived from the third, fourth
and sixth branchial arches.

 It provides SVE supply via CN IX to the stylopharyngeus muscles.

 It provides SVE supply directly via CN X to muscles of larynx and pharynx.

 It provides SVE supply via fibers which first pass through CN XI before diverging
to joint CN X to the soft palate.

123
Sensory Cranial Nerve Nuclei

 Immediately lateral to the dorsal motor nucleus of Vagus is the Nucleus Tractus Solitarius (NTS).
The NTS is functionally divided into:

 A more superior Special Visceral Afferent portion receives taste sensations from the
anterior 2/3s of the tongue via CN VII, from the posterior 1/3 of the tongue via CN IX and
from the very back of the tongue via CN X.

 The inferior General Visceral Afferent portion receives visceral sensations from the
lungs, aortic and carotid baroreceptors/ chemoreceptor bodies, the heart and the gut
via CN IX and X. It thus mediates many reflexes (e.g. chemoreceptor, baroreceptor, lung
inflation reflex).

 The nucleus tractus solitarius sends GVA and SVA information to the VPM nucleus of the
thalamus via the tractosolitariothalamic fibers, which run in the central tegmental tract.

 Lateral to the nucleus tractus solitarius are three nuclei receiving Special Somatic Afferent
information from the vestibulochoclear nerve CN (VIII):

 The vestibular nucleus complex has superior, inferior, medial and lateral components
and receives information about balance and equilibrium.

 The dorsal and ventral cochlear nuclei are positioned dorsal and ventral to the inferior
cerebellar peduncles respectively, and receive auditory information.

124
 Lateral to the Special Somatic Afferent nuclei are the General Somatic Afferent Trigeminal
Nerve Nuclei, which has three components:

 The principle pontine nucleus of trigeminal system is found in the pons, and receives
mainly fine touch sensations from CN V (trigeminal nerve).

 The mesencephalic nucleus of trigeminal system extends superiorly into the midbrain
from the principle pontine nucleus, and receives mainly proprioceptive information from
CN V.

 The spinal nucleus of trigeminal system extends inferiorly into the medulla and receives
mainly pain and temperature sensations, from CN V, VII, IX and X.

 All three nuclei receive information from each of the three branches of the trigeminal
nerve. The trigeminal ganglion is a collection of cell bodies from the 1o neurons
supplying the trigeminal nerve.

 Collectively, all three nuclei receive fibers via the trigeminal tract, and send fibers to the
VPM nucleus of the thalamus via the trigeminal lemniscus.

 Motor fibers from the trigeminal motor nucleus described above run with the sensory
fibers of only the CN V3 mandibular division of trigeminal nerve.

125
Summary of Brainstem Cranial Nerves and Their Nuclei

 CN III (oculomotor nerve) carries:

 GSE fibers from oculomotor nucleus to the extraocular muscles of the eye except the
lateral rectus and superior oblique.

 GVE parasympathetic fibers from the Edinger-Westphal nucleus to the ciliary ganglion
to the constrictor pupili muscle and the ciliary bodies.

 CN IV (trochlear nerve) carries GSE fibers from trochlear nucleus to superior oblique muscles.

 CN VI (abducens nerve) carries GSE fibers from abducens nucleus to lateral rectus muscles.

 CN V (trigeminal nerve):

 All branches (CN V1-3) carry GSA fibers to the trigeminal nuclei, with proprioception
going to the mesencephalic nucleus, fine touch to the principle pontine nucleus and pain
and temperature going to the spinal nucleus predominantly.

 V3, the mandibular branch, additionally carries SVE fibers from trigeminal motor nucleus
to the muscles of mastication.

 CN VII (facial nerve) carries:

 GVE parasympathetic fibers from the lacrimatory nucleus to the pterygopalatine

ganglion and the lacrimatory glands, as well as from the superior salivatory nucleus to
the submandibular ganglion, to the submandibular and sublingual glands. (A separate
sublingual ganglion can sometimes be distinguished).

 SVE fibers from the facial motor nucleus, which pass posteromedially to the abducens
nucleus and hook around it before exiting the brainstem. These fibers primarily supply
muscles of facial expression.

 GVA taste fibers from the anterior 2/3 of the tongue to the superior part of NTS.

 GSA fibers from the external ear to the spinal nucleus of trigeminal system.

 CN VIII (vestibulochoclear nerve) carries SSA fibers regarding hearing and sense of equilibrium
from the vestibular nucleus and the dorsal and ventral cochlear nuclei.

126
 CN IX (glossopharyngeal nerve) carries:

 GVE parasympathetic fibers from inferior salvatory nucleus to the otic ganglion and
parotid gland.

 SVE fibers from the nucleus ambiguus to the stylopharyngeus muscles.

 SVA taste fibers from the posterior 1/3 of the tongue to NTS.

 GVA fibers from the carotid sinuses and bodies to the NTS.

 GSA fibers from the external ear to the spinal nucleus of trigeminal system.

 CN X (vagus nerve) carries:

 GVE parasympathetic fibers from dorsal motor nucleus of vagus to many structures in
the neck, thorax and abdomen.

 SVE fibers from the nucleus ambiguus to the larynx and pharynx.

 SVA fibers from the posteriormost part of the tongue to the NTS.

 GSA fibers to the spinal nucleus of trigeminal system. These fibers may come from many
structures, including from the ear and from the thoracic and abdominal viscera. Indeed,
irritating fibers of the ear may trigger a reflex bradycardia via the parasympathetic fibers
of the vagus nerve.

 CN XI (cranial part of accessory nerve) carries SVE fibers from the nucleus ambiguus that run
briefly with the spinal part of the accessory nerve, but which quickly diverge to run with the
vagus nerve to supply the soft palate.

 CN XII (hypoglossal nerve) carries GSE fibers from the hypoglossal nucleus to the tongue.

127
MEDULLA
Review of Medulla Anatomy

 The medulla is the part of the brainstem that extends from the pontomedullary sulcus
superiorly to the decussation of the pyramidal tracts inferiorly.

 It is attached to the cerebellum by the inferior cerebellar peduncles posteriorly.

 On its anterior surface, it bears two bilateral longitudinal swellings: the pyramids medially and
the olives laterally.

 The groove between each pyramid and ipsilateral olive is the pre-olivary sulcus, and the groove
between each olive and its ipsilateral inferior cerebellar peduncle is the post-olivary sulcus.

 The reticular formation is a superior extension of the spinal cord gray matter that has been
disrupted by white matter decussation to produce a poorly-defined gray and white mixture. It is
present at all levels of the brainstem.

 One primary function of the reticular formation is to maintain the consciousness and
wakefulness of the different parts of the cerebral cortex.

 It receives information about peripheral GSA stimulation from spinoreticular pathways

that indicate the cerebral cortex should be alert and become responsive to stimuli.

 It activates the cerebral cortex via the ascending reticular activating system, which
sends fibers to the intralaminar nuclei of the thalamus via the central tegmental tract.

 The intralaminar nuclei send fibers to the rest of the cerebral cortex to stimulate it and
maintain its responsiveness to stimuli.

 Thus, providing a person with sufficient peripheral sensory stimulation (e.g. causing him
intense pain) will cause him to wake up and become responsive to peripheral stimuli.

128
 Specifically, the medullary part of the reticular formation contains four important autonomic
centers: the cardiac, vasomotor, respiratory and peristaltic GIT centers.

 These centers maintain some of the basic functions required for life, including
maintaining an appropriate heart rate, blood pressure and ventilation.

 This is a site that can be targeted by pharmacological therapy; for example, some
centrally-acting antihypertensives target the vasomotor center.

 Damage to the medulla is almost certainly fatal due to vital functions performed by
these medullary centers; conversely, lesions to the cerebral cortex that leave the
medulla intact may be compatible with life. This part of the brainstem is usually
damaged in hanging and ensures a rapid death.

 Directly posterior to the GIT peristaltic center, in the floor of the fourth ventricle, lies the
area postrema, and within it the chemoreceptor trigger zone (CTZ). The area postrema
acts as a vomiting center and is involved in the sense of nausea.

 The blood brain barrier is disrupted in the chemoreceptor trigger zone; this allows it to
sense the chemical composition of blood, and detect toxins in the blood.

 Upon detection of these toxins it communicates this information to the GIT peristaltic
centers in the medullary reticular formation.

 The GIT peristaltic centers then induce reverse peristalsis and emesis (vomiting).

 The area postrema and CTZ are thus responsible for the emetic response to many drugs
as well, particularly chemotherapeutic drugs.

129
Brief Review of Ascending Tracts Within Medulla

 The three main groups of ascending tracts all pass through the tegmentum of the medulla. They
are:

 The dorsal column medial lemniscus (DCML) tract.

 The lateral and anterior spinothalamic tracts, and the tectospinal pathway.

 The cuneocerebellar and dorsal and ventral spinocerebellar tracts. These will be
discussed separately as the ascending cerebellar tracts.

 Briefly recall that in the DCML, the 1o sensory neuron ascends in the ipsilateral dorsal column of
origin before entering the medulla.

 In the caudal medulla, it synapses on either the nucleus gracilis or nucleus cuneatus.

 The internal arcuate fibers from these nuclei decussate to the contralateral side within
the medulla.

 These fibers then ascend in the contralateral medulla (and through the brainstem) as the
medial lemniscus.

 Thus, only lesions at the very caudal levels of the medulla, inferior to the level of the
decussation result in loss of dorsal column sensations to the ipsilateral side of the body.

 Lesions to the brainstem superior to the level of the decussation of the internal arcuate
fibers result in loss of dorsal column sensations to the contralateral side of the body.

 Recall that the 2o sensory neurons of the lateral and anterior corticospinal pathways, as well as
the spinotectal pathway, all decussate to the contralateral white matter columns near the level
of entry.

 In the medulla, all three tracts unite to form a single spinal lemniscus that ascends
through the entire brainstem.

 Lesions to any level of the medulla (and indeed, any level of the brainstem) involving
spinal lemniscus causes loss of anterolateral sensations to contralateral side of the body.

130
Descending Motor Tracts

 At the level of the medulla, both the lateral and anterior corticospinal tracts are compressed to
form pyramids. The pyramids are located anteriorly in the basis of the medulla.

 Fibers from the lateral tract decussate at the inferior limit of the medulla to form the
major motor crossing.

 Fibers from the anterior tract descend in the anterior white column before decussating
to the contralateral side at the level of supply.

 Thus, lesions to the pyramids of the medulla always cause UMN syndrome in the
contralateral side of the body.

Ascending Cerebellar Tracts

 The cuneocerebellar pathway provides proprioceptive information from the upper limbs to the
cerebellum.

 The 1o neuron ascends in the ipsilateral lateral white column of the spinal cord.

 At the level of the medulla, it synapses on the accessory cuneate nucleus.

 The accessory cuneate nucleus gives off 2o fibers that enter the ipsilateral inferior
cerebellar peduncle via the cuneocerebellar tract.

131
 The spinocerebellar pathways provide proprioceptive information from the lower limbs to the
cerebellum.

 The nuclei of the 2o neurons of the dorsal and ventral spinocerebellar tracts are both
found in the dorsal gray horn of the level of origin of the stimulus.

 The 2o neurons of the dorsal spinocerebellar tract ascend in the ipsilateral lateral white
column. In the medulla it enters the ipsilateral inferior cerebellar peduncle.

 The 2o neurons of the ventral spinocerebellar tract cross over at the level of stimulus to
ascend in the contralateral lateral white column. It does not enter the cerebellum at the
level of the medulla, but instead ascends to the level of the midbrain to enter via the
superior cerebellar peduncle. Within the cerebellum it crosses back to the ipsilateral side
of origin.

 Thus, of the ascending cerebellar tracts:

 The only nucleus found at the level of medulla is the accessory cuneate nucleus.

 Lesions to the cuneocerebellar and dorsal spinocerebellar tracts may cause ipsilateral
upper and lower limb ataxia respectively, with a positive Rhomberg test.

 Lesions to the ventral spinocerebellar tract at the level of the medulla may cause
contralateral lower limb ataxia with positive Rhomberg test.

 The cuneocerebellar and dorsal spinocerebellar tracts exit at the level of the medulla
through the inferior cerebellar peduncle, while the ventral spinocerebellar tract ascends
through the medulla without exiting.

132
Descending Cerebellar Tracts

 The descending cerebellar tracts include those from the cerebral cortex and those from
subcortical nuclei.

 The cerebral cortex sends information about movements in the planning stage to the cerebellum
(specifically the cerebrocerebellum). It does so via a number of tracts:

 The cortico-ponto-cerebellar pathway involves cortical fibers synapsing on pontine

nuclei, and the pontine nuclei sending fibers to the cerebellum via the middle cerebellar
peduncles in the pons. This is less relevant to our discussion of the medulla.

 A medullary version of the cortico-ponto-cerebellar pathway is known as the cortico-

arcuato-cerebellar pathway. The arcuate nuclei may be thought of as inferiorly
displaced pontine nuclei present in the medulla. Essentially the pathway is the same,
except that the arcuate nuclei fibers enter the cerebellum via the inferior cerebellar
peduncles.

 The red nucleus sends information about control of muscle tone to the cerebellum as well. It
does so via the rubro-olivo-cerebellar pathway.

 Fibers from the red nucleus descend in the central tegmental tract.

 They synapse onto the olivary nucleus in the medulla.

 The fibers from the olivary nucleus enter the cerebellum via the inferior cerebellar
peduncles.

133
Review of Cranial Nerves & Their Nuclei in Medulla

 Four cranial nerves exit in medullary regions: the CN XII exits in the pre-olivary sulcus, where
CN IX, X and XI exit in the post-olivary sulcus from superior to inferior.

 CN XII (Hypoglossal nerve) receives GSE fibers from the hypoglossal nuclei. These GSE fibers
run anteriorly towards the pre-olivary sulcus and exit from the medulla at that point to form
CN XII.

 CN X (Vagus nerve) conveys both motor and sensory fibers:

 It conveys parasympathetic GVE fibers from the dorsal motor nucleus of Vagus
towards the periphery.

 It conveys SVE fibers from the nucleus ambiguus to the branchiomeric muscle of the
soft palate, larynx and pharynx.

 It receives GVA fibers from the periphery and conveys them to the medial part of
Nucleus Tractus Solitarius (NTS).

 It receives SVA fibers carrying taste sensations from the posteriormost part of the
tongue, and conveys them to the lateral part of NTS.

 It receives a small number of GSA fibers from the external ears, and conveys somatic
sensations to the spinal nucleus of trigeminal system. Thus, removal of ear wax can
irritate some of these fibers and actually cause a slowing of the heart rate.

134
  CN IX (Glossopharyngeal nerve) exits superior to the vagus, and has both motor and sensory
components:

 It conveys parasympathetic GVE fibers from the inferior salivatory nucleus to the
parotid gland. The precise location of the inferior salivatory nucleus is unknown.

 Like the vagus, it conveys SVE fibers from the nucleus ambiguus. These fibers supply
the stylopharyngeus muscle.

 It receives SVA fibers carrying taste sensations from the posterior 1/3 of the tongue,
and conveys them to the lateral part of NTS.

 It receives GSA fibers carrying somatic sensations from the posterior 1/3 of the tongue,
and conveys them to the spinal nucleus of trigeminal system.

 CN XI (Cranial part) exits inferior to the vagus, and carry only SVE fibers. These SVE fibers are
also destined for branchiomeric muscles in the larynx and pharynx.

Nuclei of Medulla

 The major nuclei present at the level of the medulla include the glossopharyngeal nucleus,
dorsal motor nucleus of vagus, nucleus tractus solitarius, nucleus ambiguus, the inferior part of
the vestibular nuclei, the cochlear nuclei and the spinal nucleus of trigeminal system.

135
Sections of the Medulla

 Sections of the medulla can occur at the level of the major motor decussation, the level of the
internal arcuate fiber decussations, or superior to both decussations, as exemplified by the
mid-olivary section.

 At the inferiormost limit of the medulla, the following structures are present in cross-section:

 The major motor pyramidal crossing, conveying descending corticospinal fibers.

 The bilateral nuclei gracilis and cuneatus, with the superior parts of the dorsal column
fibers synapsing onto them, conveying dorsal column sensations.

 The spinal lemniscus conveying anterolateral sensations.

 The dorsal and ventral spinocerebellar tracts and the accessory cuneate nucleus
(poorly-defined and not shown).

 The spinal nucleus of trigeminal system (present at all levels of medulla but not
shown).

136
 At the level of the major sensory decussation of the internal arcuate fibers, the following
structures are visible:

 Corticospinal pyramids.

 The decussation of the internal arcuate fibers.

 The spinal lemniscus.

 The dorsal and ventral spinothalamic tracts.

 The inferior part of the hypoglossal nucleus, the nucleus ambiguus and the olivary
nucleus.

 The spinal nucleus of trigeminal system (present at all levels of medulla but not
shown).

137
 At the midolivary section, the following structures are visible:

 Pyramidal bundles.

 Medial lemniscus (shown centrally).

 Spinal lemniscus (not shown).

 The inferior cerebellar peduncles conveying the spinocerebellar and cuneocerebellar

fibers.

 The hypoglossal nucleus, dorsal motor nucleus of vagus, nucleus tractus solitarius,
inferior part of vestibular nucleus, the cochlear nuclei, and the spinal nucleus of
trigeminal system (shown in this diagram).

 Medial longtitudinal fasciculus (shown posteriorly).

138
PONS
Anatomy and Relations of Pons

 The pons is separated from the midbrain superiorly by the superior pontine sulcus, and from the
medulla inferiorly by the inferior pontine sulcus, also referred to as pontomedullary junction.

 Posterior to the pons is the cerebellum.

 The pons attaches to the cerebellum by the middle cerebellar peduncles.

 The middle cerebellar peduncles are superficial to and overlie the superior and inferior
cerebellar peduncles.

 The basis of the pons contains many pontine nuclei.

 Corticopontine fibers from all regions of the cerebral cortex descend into the basis of
the pons to synapse onto the pontine nuclei.

 The pontine nuclei send fibers into the contralateral middle cerebellar peduncle. The
pons, which means “bridge”, is so named because it acts as a bridge from one cerebral
hemisphere to the contralateral cerebellum. The transverse pontocerebellar fibers
forming the bridge are visible from an anterior view, as they pass posterolaterally from
the pons into the middle cerebellar peduncles.

 The entire pathway is named the cortico-ponto-cerebellar pathway.

 Pathways from specific lobes of the cerebral cortex may be named as the fronto-,
parieto-, occipito- or temporo-ponto-cerebellar pathway respectively.

 Anteriorly, the transverse pontocerebellar fibers are visible. In the median plane lies a shallow
longitudinal depression within the transverse fibers for the basilar artery, which forms from the
union of the two vertebral arteries.

 The main cranial nerves exiting from the pons are the trigeminal nerve on the anterolateral
surface of the midpontine level, and the abducens, facial and vestibulocochlear nerves from
medial to lateral in the pontomedullary sulcus.

139
Fourth Ventricle & Related Structures

 The fourth ventricle has a roof, which projects into the cerebellum, and a floor, formed by the
pons and medulla.

 A posterior view into the fourth ventricle, with the cerebellum (and hence the roof) removed,
reveals that it is rhomboid-shaped, hence the name rhombencephalon for the embryological
hindbrain.

 In the floor of the fourth ventricle, transverse fibers from the inferior pons called striae
medullaris divide the floor into the pontine part superiorly and the medullary part inferiorly.

 In the midline of the fourth ventricle, a depression called the median sulcus can be seen.

 Two more bilateral depressions called the sulci limitans are also visible.

 Between the median sulcus and the two sulci limitans is a medial eminence on each side.

 Inferiorly, each medial eminence terminates as a swelling known as the facial colliculus.

 The facial colliculus forms as a result of the hooking of the CN VII facial nerve fibers
posteriorly around the abducens nucleus of CN VI, such that it forms a posterior swelling
into the roof of the fourth ventricle.

 At the superior part of the median eminence lies another swelling, blue-grey in colour,
known as the substantia Ferruginea.

 The substantia ferrugenia overlies a nucleus of noradrenergic neurons, called the locus
ceruleus, which send fibers to numerous parts of the CNS. It is responsible for the strong
emotional elements associated with the sympathetic response.

 Lateral to the sulcus limitans on each side is the vestibular area, because it overlies the area
where the vestibular nuclei are found.

140
Central Auditory System

 Components of the central auditory system are present from the pons superiorly onwards.

 At the level of the pontomedullary junction, the cochlear component of the vestibulocochlear
nerve enters the brainstem (via CN VII). Its fibers synapse onto the ventral and dorsal cochlear
nuclei.

 Some fibers (predominantly the ventral cochlear nuclei, but also the dorsal cochlear nuclei to
some extent) decussate to the contralateral side of the pons; the crossing of fibers here forms
the trapezoid body.

 The fibers may synapse onto small nuclei of trapezoid body found within the trapezoid
body itself.

 The dorsal and ventral cochlear nuclei are present only at inferior sections of the pons.

 The trapezoid body is visible at all levels (transverse sections) of the pons.

 Some fibers (predominantly from dorsal cochlear nuclei) do not decussate to the
contralateral side, but ascend in pathways to the ipsilateral cerebral cortex. Damage to
one side of the central auditory system may not cause complete hearing loss in one ear.

 After decussating to the contralateral side, the fibers ascend in a bundle as the lateral lemniscus.

 The fibers synapse onto the superior olivary nucleus before continuing to ascend.

 Those fibers then synapse on nuclei in the inferior colliculus of the midbrain. The
inferior colliculus mediates audio-spinal reflexes.

 The lateral lemniscus is visible at all levels (transverse sections) of the pons.

 Fibers from the inferior colliculus then pass to nuclei in the medial geniculate body of the
thalamus via the inferior brachium, which is also a bundle of axons.

 from there the information is relayed via auditory radiations to the auditory cerebral cortex
found in the temporal lobe.

141
Summary of Descending Tracts

 All descending tracts run in the basis of the pons (and indeed, the brainstem).

 The corticopontine fibers descend into and synapse onto pontine nuclei in the basis of the pons;
transverse pontocerebellar fibers on the anterior surface of the pons extend posterolaterally to
form the middle cerebellar peduncles.

 Corticonuclear and corticospinal fibers pass inferiorly through the basis of the pons (and
brainstem) to eventually synapse onto GSE motor nuclei in the brainstem and in the anterior
gray horn of the spinal cord.

Summary of Ascending Tracts

 The trapezoid body separates the basis of the pons anteriorly from the tegmentum of the pons
posteriorly.

 The ascending tracts run in the tegmentum.

 In the anterior tegmentum, from medial to lateral, the ascending tracts are the medial
lemniscus, spinal lemniscus, lateral lemniscus and the ventral spinocerebellar tract
(represented by a star).

 Recall that the ventral spinocerebellar tract is the only ascending cerebellar tract that does not
exit at the level of the inferior cerebellar peduncles, but ascends through the brainstem.

Cranial Nerves & Nuclei at Inferior Pontine Sections

 The nuclei associated with CN VI, VII and VIII are present mainly at inferior pontine sections close
to the pontomedullary junction.

 CN VI (Abducens Nerve) receives innervation from the abducens nucleus found in the posterior
tegmentum, just beneath the floor of the fourth ventricle. CN VI exits as the most medial part of
cranial nerves at the pontomedullary junction.

 CN VII (Facial Nerve) transmits information to and from a number of brainstem nuclei:

 It conveys SVE fibers from the facial motor nucleus to the muscles of facial expression
and the stapedius muscle. From the facial motor nucleus, these fibers pass posteriorly

142
 and medial to the abducens nucleus, hooking around it before passing anteriorly again.
Thus, lesions to the abducens nucleus is often associated with lesions to the tract
conveying the facial nerve fibers as well due to their close relations.

 It conveys parasympathetic GVE fibers from the superior salivatory nucleus, also known
as the lacrimatory nucleus. These fibers are directed via the pterygopalatine ganglion
towards the lacrimatory glands, as well as via the submandibular ganglion towards
sublingual and submandibular glands.

 It receives taste sensations from the anterior 2/3 of the tongue via SVA fibers, which
pass to the lateral part of the nucleus tractus solitarius (NTS).

 It receives touch pain and temperature sensations from the external ear which are
transmitted to the spinal nucleus of trigeminal system.

 CN VIII (Vestibulocochlear nerve) conveys SSA fibers concerning hearing and sense of
equilibrium to the vestibular and cochlear nuclei. The choclear nuclei contribute to the fibers
forming the trapezoid body.

 In the posterior part of the tegmentum, the medial longtitudinal fasciculus is also visible. It
allows for intercommunication between brainstem nuclei, particularly the 3rd, 4th and 6th nuclei,
to ensure conjugate movement of the eyes. As it only connects brainstem nuclei, it is naturally
found in the posterior part of the tegmentum where the nuclei are found.

Superior Pontine Sections

 At superior pontine sections, the ascending and descending tracts are still present.

 With regards to the local anterolateral cranial nerve systems, only CN V (trigeminal nerve) is
visible at midpontine levels.

 It conveys SVE fibers from trigeminal motor nucleus.

 It conveys GSA fibers to the trigeminal system of sensory nuclei. The principle pontine nucleus is
visible at midpontine levels; superior or inferior to that the mesencephalic or spinal nuclei of
trigeminal system may be visible instead.

143
MIDBRAIN
Review of Anatomy of Midbrain

 The midbrain comprises two cerebral peduncles that attach the brainstem to the cerebral
hemispheres.

 A transverse section of the midbrain reveals two important landmarks: the substantia nigra and
the cerebral aqueduct.

 Anterior to the substantia nigra lies the crus cerebri, which forms the basis of the midbrain. The
crus cerebri thus contains the descending tracts that pass through the midbrain.

 Posterior to the substantia nigra but anterior to the cerebral aqueduct lies the tegmentum.

 Posterior to the cerebral aqueduct lies the tectum of the midbrain.

 On the posterior surface of the tectum there are two pairs of swellings known as colliculi.

 The bilateral superior colliculi are responsible for visual reflexes; the bilateral inferior
colliculi are responsible for auditory reflexes. These reflexes are collectively known as
spinotectal and tectospinal reflexes.

 Spinotectal reflexes involve receiving general sensations and looking towards the source
of the stimulus. These were discussed in the ascending anterolateral system.

 Tectospinal reflexes involve seeing or hearing something (e.g. a loud noise) and
producing a movement in response to that stimulus (e.g. protecting oneself from the
source of the stimulus).

 Tectospinal reflexes are thus mediated by UMNs from the tectum that synapse onto
LMNs to exert their effects.

 Anteriorly, an interpeduncular fossa is visible between the two cerebral peduncles.

144
Transverse Section at Level of Inferior Colliculus

 The substantia nigra separates the crus cerebri anteriorly from the tegmentum posterior to it;
the cerebral aqueduct separates the tegmentum anteriorly from the tectum posteriorly.

 The substantia nigra is composed of a pars compacta and pars reticulata.

 The pars compacta is a pigmented collection of dopaminergic neurons that plays a role
in regulating the motor function of the basal ganglia. Lesions to the substantia nigra are
responsible for Parkinson Disease.

 The pars reticulata may be thought of as an inferiorly displaced globus pallidus internus.
Both the pars reticulata and compacta are discussed in the basal ganglia chapter.

 The cerebral aqueduct is the CSF-filled cavity of the midbrain.

 Surrounding the cerebral aqueduct is a collection of gray mater known as the

periaqueductal gray. The reticular formation may also be visualised in this region.

 The dorsal tegmental nucleus and nucleus Raphe are nuclei considered part of the
periaqueductal gray, responsible for the release of endogenous morphine-like
substances e.g. enkephalins, endorphins at synapses throughout the spinal cord to
inhibit pain transmission.

 The locus ceruleus is also found at midbrain levels; it is a pigmented blue-grey nucleus
involved in the production of noradrenaline in the CNS.

 All descending tracts of the midbrain pass through the crus cerebri anterior to the substantia
nigra.

 The corticospinal tracts pass through the median part of each crus cerebri.

 The corticonuclear tracts are accompanied by some corticopontine fibers in the medial
part of each crus cerebri.

 The rest of the corticopontine fibers run in the lateral part of each crus cerebri.

145


 The dentorubrothalamic pathway involves fibers running from the dentate nucleus to the red
nucleus, thalamus and finally to the cerebral cortex.

 It is one of the outputs of the cerebellum via which it modulates the motor activity of
UMNs in the cerebral cortex. This is discussed further in the cerebellum chapter.

 It is a bilateral pathway that ascends in the brainstem, decussating anterior to the

cerebral aqueduct at the level of the inferior colliculi. This decussation is visible in the
midline of the tegmentum at that section, directly posterior to the substantia nigra.

 At the level of the superior colliculi it synapses onto the contralateral red nucleus,
before ascending to the thalamus.

 Immediately lateral to the decussation of the dentorubrothalamic tracts lie the medial lemnisci.

 Immediately lateral to the medial lemnisci are the spinal lemnisci.

 The lateral lemnisci are not found throughout the midbrain but synapse onto the inferior colliculi.

 The inferior colliculus, and hence the terminations of the medial lemnisci, are found only
at inferior sections of the midbrain, in the tectum.

 The inferior brachium tracts may be seen extending superiorly from the inferior colliculi.
They ascend to the medial geniculate bodies of the thalami.

 A commissure of inferior colliculus runs between the two inferior colliculi to allow them
to communicate.

 Another important tract is the central tegmental tract, which comprises ascending
reticulothalamic fibers in the reticular activating system, as well as descending rubroolivary
fibers.

 Anteriorly, between the peduncles, there is an interpeduncular nucleus.

 This nucleus has connections to the habenular nucleus just posterior to the thalamus via
the habenula-interpeduncular pathway, also known as the fasciculus retroflexus.

 The habenular nucleus connects also to the hypothalamus.

 All three structures participate in the habenula system responsible for the regulation of
appetite. It is discussed in detail in the hypothalamus chapter.

146
 The trochlear nucleus provides GSE motor fibers to CN IV. Its fibers are unique amongst the
spinal nerves for two reasons:

 They exit posterior to the brainstem

 The fibers cross within the brainstem, before exiting to supply the contralateral nerve.

 The mesencephalic nucleus of the trigeminal system is present at all levels of the midbrain.

Transverse Section at Level of Superior Colliculus

 The descending tracts, medial lemnisci, spinal lemnisci and central tegmental tracts all run in the
same position through to superior levels of the midbrain.

 The mesencephalic nucleus is still visible at this level.

 The inferior colliculi have been replaced by the superior colliculi at this level.

 They may be seen receiving fibers via the superior brachium from areas like the frontal
eye fields, occipital eye fields and the retina.

 The frontal eye fields are responsible for searching movements and the occipital eye
fields are responsible for object-tracking movements.

 The inferior colliculus integrates these inputs in order to produce visual-spinal reflexes
via the tectospinal tract.

 It also receives GSA input from the periphery via spinotectal tracts to produce spino-
visual reflexes (e.g. looking towards the source of a stimulus that has caused pain).

 The superior colliculi are interconnected by the superior commissure.

 At the level of the superior colliculus, the decussation of the dentorubral tracts is no longer
visible; instead they may be seen synapsing onto the contralateral red nucleus.

147
 The oculomotor nucleus replaces the trochlear nucleus at this level. it gives off fibers that pass
through the red nucleus, substantia nigra and crus cerebri to exit as CN III from the medial sides
of the cerebral peduncles (and thus from the interpeduncular fossa).

 Its fibers are responsible for control of all of the extraocular muscles except the lateral
rectus and superior oblique, controlled by CN IV and CN VI respectively.

 As with the third, fourth and sixth nerve nuclei and the vestibular nucleus, it is
associated with the medial longitudinal fasciculus medially.

 Immediately lateral to the oculomotor nucleus lies the Edinger-Westphal nucleus, responsible
for the parasympathetic GVE output to the eye via CN III.

 The Edinger-Westphal nucleus receives innervation posteriorly from both the left and
right pretectal nuclei. (Not to be confused with the posterior tegmental nucleus, which
as previously discussed is part of the periaqueductal gray and is involved in pain
modulation.)

 The pretectal nuclei themselves are interconnected by the posterior commissure. (Not
to be confused with the superior and inferior commissure of the superior and inferior
colliculi.)

 The pretectal nuclei in turn receive innervation from the retina. Depending on the
amount of light stimulus detected, they can stimulate the Edinger=Westphal nucleus to
induce pupillary constriction.

148
DIENCEPHALON
Embryology of Diencephalon

 The three primary vesicles that form from the neural tube are the prosencephalon,
mesencephalon and rhombencephalon.

 The prosencephalon subsequently develops into two secondary vesicles: the diencephalon
caudally and the telencephalon cephalically.

 The telencephalon expands much more rapidly than the diencephalon, and thus comes to
surround and envelop it. Stated differently, the diencephalon is buried within the telencephalon.

Anatomy of Diencephalon

 The CSF-filled cavity of the diencephalon is the third ventricle.

 Thus, derivatives of the diencephalon may be defined as the structures surrounding the third
ventricle.

 The posterior part of the floor of the third ventricle is formed by the midbrain.

149
 Lateral to the third ventricle on each side, and just superior to the midbrain, are the two thalami.
The two thalami are collectively and more traditionally known as the dorsal thalamus.

 The two thalami are connected in the midline by interthalamic gray matter adhesions
that cross over the third ventricle.

 Lateral to each thalamus lie the medial and lateral geniculate bodies.

 The medial geniculate bodies connect to the inferior colliculus, while the lateral
geniculate bodies connect to the superior colliculus, and are involved in visual and
auditory reflexes.

 Each thalamus sits just superior to a sheet of gray matter known as the subthalamus, which lies
between it and the midbrain.

 A number of structures lie posterior to the third ventricle:

 On the posterior surface of the third ventricle lies a single midline projection called the
pineal gland or pineal body; it is associated with the production of melatonin and
regulation of circadian rythms.

 On the top two posterior corners of the third ventricle lie the habenular nuclei, involved
in the habenula system associated with control of appetite.

 The habenular nuclei are connected by a habenular commissure along the superior
border of the posterior face of the third ventricle; the commissure thus passes through
the superior part of the stalk of the pineal gland.

 The habenular commissure is not to be confused with the posterior commissure, which
connects the pretectal nuclei located in the midbrain. (The commissure itself rises just
above the level of the midbrain.)

 The habenular nuclei and the pineal gland are collectively known as the epithalamus.

 The anterior part of the third ventricle has its walls and floor formed by a sheet of gray matter
known as the hypothalamus.

 The more posterior part of the hypothalamic floor gives origin to two bilateral swellings
known as the mammillary bodies.

 The more anterior part of the hypothalamic floor gives origin to the tuber cinereum, and
immediately anterior to that, the median eminence.

 The median eminence gives origin to the stalk of the pituitary gland, known as the
infundibulum.

 It should be noted that while the posterior pituitary gland (neurohypophysis) is a

derivative of the diencephalon, the anterior pituitary (adenohypophysis) is a derivative
of the epithelium of Rathke’s pouch from the roof of the mouth.

150
 The hypothalamic sulcus (or sulcus of Monro) is a groove in the lateral wall of the third ventricle
marking the boundary between the thalamus and hypothalamus.

 Immediately anterior to the hypothalamic sulci are the interventricular foramina, or foramina
of Monro.

 The optic nerve and tract are also derivatives of the diencephalon.

 The optic nerve (CN II) is not a true nerve; it is actually a CNS tract. It is myelinated by
oligodendrocytes rather than Schwann cells, and is covered in the meningeal layers.

 The optic chiasm lies just anterior to the third ventricle.

 The optic tract lies lateral to the third ventricle.

 The close relation of the optic chiasm to the pituitary gland allows pituitary tumours to
damage the optic chiasm.

 Lesions to the optic chiasm cause bitemporal hemianopia in which there is blindness in
the lateral parts of both visual fields.

151
THALAMUS
Relations of Thalamus

 The two thalami (classically named the dorsal thalamus) are located immediately lateral to the
third ventricle.

 Its external surface is related to two sheets of white matter:

 The stratum zonale superiorly, and

 The external medullary lamina laterally.

 The superior relations of the thalamus are as follows:

 Above the stratum zonale lies the body of the c-shaped caudate nucleus.

 The caudate nucleus runs along the inside of the c-shaped lateral ventricles. Thus, in
coronal sections of the thalamus, the body (parietal part) of the lateral ventricle is
shown superior to the caudate nucleus.

 The fornix is a tract of white matter that runs along the outside of the c-shape of the
lateral ventricles. Thus, in the same coronal slice the fornix is observed superior to the
lateral ventricle. The fornix is discussed in greater detail subsequently.

152
 The lateral relations of the thalamus are as follows:

 Lateral to external medullary lamina lies the internal capsule of white matter, with its
anterior limb, posterior limb and genu.

 Lateral to the internal capsule lies the lentiform nucleus, composed of the globus
pallidus and the putamen.

 The head of the caudate nucleus passes over and lateral to the internal capsule to touch
the lentiform nucleus.

 The tail of the caudate nucleus passes inferior and lateral to the internal capsule to end
in a piece of gray matter known as the amygdala.

 The amygdala itelf extends another c-shaped structure, a string of white matter called
the stria terminalis, that runs between the caudate nucleus and the inside of the c-
shaped lateral ventricle. The stria terminalis is not shown in the diagram above.

 Inferiorly, each thalamus is related to a sheet of gray matter called the subthalamus. The
subthalamus sits between the thalamus and the tegmentum of the midbrain.

 Posteriorly, each thalamus is related to the epithalamus. The epithalamus is composed of:

 The pineal gland, which is a single midline structure lying posterior to the third ventricle.

 The habenular nuclei, which are bilateral and positioned in the superior posterior
corners of the third ventricle.

 Anteriorly, each thalamus is separated from the hypothalamus covering the walls of the third
ventricle by the hypothalamic sulcus. Just anterior and superior to the hypothalamic sulci are
the foramina of Monro.

153
Anatomy of Thalamus

 The thalamus is subdivided by a y-shaped sheet of white matter called the internal
medullary lamina into a medial part, anterior part and a lateral part. The internal medullary
lamina contains axons interconnecting different nuclei of the thalamus.

 Within the internal medullary lamina lie additional gray matter nuclei called the
intralaminar nuclei.

 The intralaminar nuclei receive stimuli directly from the lateral spinothalamic tracts
and spinal nucleus of trigeminal system, conveying pain and temperature, as well as
from these systems indirectly through the reticular formation.

 The largest of these is located at the junction of the Y-shape, and is named the
centromedian nucleus of the thalamus; it additionally receives stimuli from all
thalamic nuclei, as well as the primary motor cortex and the basal ganglia.

 The intralaminar nuclei, when stimulated, in turn arouse the sensory cerebral cortex
to maintain alertness and consciousness. They thus form a central component of the
reticular activating system responsible for maintaining consciousness.

154
 The main nucleus of importance in the medial part of the thalamus is the dorsomedial
nucleus of thalamus. It is responsible for adjusting the thoughts, behaviour and physical
state of the person in response to various sensory experiences.

 It receives sensory input from all senses except the olfaction system via the VPL and
VPM nuclei of thalamus, to allow for response to sensory experiences.

 It receives input also from the motor systems (e.g. from basal ganglia) via the VA and
VL nuclei of thalamus, to allow for responses to postural muscle tension.

 It also receives input from the Papez circuit about memory of recent events via the
anterior nucleus of thalamus.

 All these inputs travel via the internal medullary lamina.

 Its main output is to the prefrontal cortex responsible for the behaviour, thoughts
and personality of the person.

 The lateral part of the thalamus is divided into a ventral and dorsal part.

 Of the ventral nuclei,

 The ventroanterior and ventrolateral nuclei are involved in the motor systems as
discussed in the motor chapters.

 The ventroposterolateral nucleus receives sensory input from the body below the
head and neck, and the ventroposteromedial nucleus receives sensory input from
the head and neck.

 The dorsal part is expanded into a large pulvinar nucleus.

 Lateral to each pulvinar nucleus are the medial and lateral geniculate bodies.

 The medial geniculate body receives sensory input from the inferior colliculus, and is
part of the auditory relay system.

 The lateral geniculate body is connected to the superior colliculus and is involved in
the visual system.

 The two thalami are connected by interthalamic gray matter adhesions medially, which
pass over the third ventricle.

155
 Each thalamus has an external gray matter capsule laterally known as the thalamic reticular
nucleus.

 The thalamic reticular nucleus receives input from all ascending (thalamocortical)
and descending (corticothalamic) fibers passing through the thalamus.

 It modulates transmission of these inputs through the thalamus via GABAergic

activity.

 It can thus disconnect the thalamus from the cerebral cortex, especially during tonic
discharges of neurons that can occur in sleep.

156
Papez Circuit

 The anterior nucleus of the thalamus acts as an important component of the Papez circuit,
responsible for adjusting mood in response to memory of recent events.

 The primary input of the system is the hippocampal/ parahippocampal system. The
hippocampus is a collection of gray matter situated in the temporal lobe. The
emotional content of various sensory inputs (e.g. speech) is conveyed by the various
sensory cortices to the hippocampus/ parahippocampus.

 Input from the hippocampal/ parahippocampal system is conveyed via a c-shaped

structure of white matter called the fornix. This fornix runs along the outside curve
of the c-shaped lateral ventricle.

 The fornix provides input to the mammillary bodies found in the hypothalamus.

 The mammillary bodies send this input to the anterior nucleus of the thalamus,
which in turn relays it via a sheet of thalamocingulate fibers to the cingulate gyrus.

 Recent memories with a strong emotional content tend to reverberate in these

circuits strongly, and are kept in short term memory longer and are also better
transferred to long term memory.

 Lesions to this circuit result in anterograde amnesia; this can occur especially in
Wernicke-korsakoff syndrome due to vitamin B1 (thiamine) deficiency, which can
occur especially in the malnourished and in alcoholics (alcohol interferes with its
absorption).

 Thiamine has two main functions: maintenance of CNS tract myelination, especially
of the Papez circuit, and for glucose metabolism. Thus, if glucose is to be
administered to any person, thiamine must be given beforehand to prevent
depletion of potentially already low B1 levels and lesions to the Papez circuit.

157
HYPOTHALAMUS
Primary Functions of Hypothalamus

 The hypothalamus is involved in three main groups of functions:

 It is involved in the limbic system and the functions of emotion, behaviour and memory.

 It serves as the higher control center of the autonomic nervous system

 It serves as the higher control center of much of the endocrine system, through the
pituitary gland.

158
Anatomy of Hypothalamus

 The hypothalamus is formed of a sheet of gray matter that surrounds the lateral walls, anterior
wall and floor of the third ventricle.

 Its anterior wall is immediately posterior to the optic chiasma.

 The posterior limit of its lateral walls is the hypothalamic sulcus or sulcus of Monro,
which separates it from the thalami posteriorly.

 On the surface of its floor, a number of swellings may be found:

 A single midline swelling anteriorly is known as the tuber cinereum, which connects
inferiorly to the pituitary gland via the infundibulum or pituitary stalk.

 The posterior part of the tuber cinereum is particularly enlarged, forming the median
eminence.

 The posterior pituitary and infundibulum are derivatives of the diencephalon, whereas
the anterior pituitary is a derivative of Rathke’s pouch. The pituitary gland as a whole is
not considered part of the hypothalamus.

 Posterior to the tuber cinereum, bilateral swellings called the mammillary bodies are
found, each one just anterior to the ipsilateral thalamus.

 Two white matter tracts, called the fornices, originate from the subiculum in the
parahippocampal formation. They form a loop along the outside of the C-shape of the lateral
ventricles, and eventually embed in the substance of the hypothalamus.

 These fibers travel through the hypothalamus to synapse onto nuclei within the
mammillary bodies.

 From the mammillary bodies, they pass posteriorly via a mamillothalamic tract to the
anterior nucleus of thalamus.

 These connections form part of the Papez circuit discussed in the thalamus, and are not
described further here.

 However, importantly the mamillothalamic tracts and the ends of the fornices lie in a
plane that separate each of the left and right hypothalamus further into a medial and
lateral hypothalamus.

159
Lateral Hypothalamus

 Running through the lateral hypothalamus is the medial forebrain bundle. The medial forebrain
bundle contains fibers that originate from two regions:

 The orbito-frontal cortex, located in the frontal cortex just overlying the orbital plates of
the anterior cranial fossa. Its function is associated with personality and motivation.

 The septal area, which is the anterior wall of the hypothalamus.

 These nuclei supply fibers that run through the lateral hypothalamus towards the
midbrain, to the ventral tegmental area.

 Also found in the lateral hypothalamus is the lateral hypothalamic nucleus.

 The lateral hypothalamic nucleus contains the hunger center and thirst center. It
contains glucose receptors (and presumably osmoreceptors) that can sample blood to
determine if blood glucose concentrations and osmolarity are high or low.

 Aside from inducing a sense of hunger, it also has output via polysynaptic connections to
increase sympathetic activity. This explains why patients with hypoglycaemia exhibit
signs of increased sympathetic outflow such as sweating and tachycardia.

 It also has outputs to the dorsal medial nucleus, found in the medial hypothalamus (to
be described later), which serves as an anger center. It is thus true that extreme hunger
increases irritability, and a hungry man is an angry man.

 The counterpart to the hunger center, the satiety center, is the ventral medial nucleus,
also found in the medial hypothalamus.

 The preoptic nucleus is present in both the lateral and medial hypothalamus; it is best discussed
in the context of the latter.

160
Medial Hypothalamus

 The above picture depicts the left medial hypothalamus from its medial surface; a sagittal
section was made through the hypothalamus in the midline, and third ventricle was removed.

 From anterior to posterior, the medial hypothalamus is divided into four main sections:

 The preoptic region lies just anterior to the optic chiasma.

 The supraoptic region lies superior to the crossing of the optic chiasma and the optic
tracts that pass posteriorly from it.

 The tuberal region lies superior to the tuber cinereum and its median eminence.

 The mammillary region lies over and includes the mammillary bodies.

Preoptic Region

 The pre-optic region contains the preoptic nucleus. The preoptic nucleus, as previously
described, lies in both the medial and lateral hypothalamus. It relates mainly to sexual functions:

 It is a secretor of GnRH, which it releases into the capillary plexus of the median
eminence. It is conveyed by the hypothalamic hypophyseal portal venous system to the
anterior pituitary, where it exerts its effects on FSH and LH secretion by the
gonadotroph cells.

 The preoptic nucleus contains another nucleus, called the sexually dimorphic nucleus. It
is thought to be involved in determining sexual orientation. This determination occurs in
utero, and is thought to be influenced by level of exposure to androgens in utero.

161
Supraoptic Region

 The supraoptic region contains a number of nuclei:

 The anterior hypothalamic nucleus is located just anterior to the beginning of the third
ventricle.

 The paraventricular nucleus is located on the lateral wall of the third ventricle.

 The suprachiasmatic nucleus is located superior to the optic chiasma.

 The supraoptic nucleus is located superior to the optic tracts.

 The anterior hypothalamic nucleus is one of the thermostats of the hypothalamus, and senses
changes in temperature with respect to a set point.

 It may be thought of as an air-conditioner, which responds to increases in temperature

above the set point. It has a heater counterpart, found in the mammillary region, which
responds to drops in temperature below the set point.

 Its output is mainly via the sympathetic nervous system, which increases the activity of
sweat glands.

 It also possesses some parasympathetic outflow, which may stimulate gut motility,
defecation or micturition.

 The suprachiasmatic nucleus plays a role in the regulation of circadian rhythms.

 Its main input is fibers from the visual system via the optic chiasma.

 The suprachiasmatic nucleus compares the ratio of daylight exposure to darkness.

 Its primary output is to the habenular nuclei and the pineal gland. The pineal gland’s
secretions include melatonin, 5HT and CCK. Amongst these, melatonin is the primary
factor implicated in the sleep-wake cycle.

 The supraoptic nucleus contains osmoreceptors that are able to detect the osmolarity of blood.

 It responds to increased osmolarity above a set point by the secretion of ADH via
supraopticohypophyseal pathway to the posterior pituitary gland. It also contains
neurons that secrete small amounts of oxytocin.

 ADH secretion can also be stimulated by low blood pressure, sensed by pressure
receptors of the atria.

 ADH is responsible for increasing the expression of aquaporins (via V2 receptors) in the
late distal convoluted tubule and the collecting duct, which increase its permeability to
water and allow for greater reabsorption of water.

 ADH also has a vasoconstrictive effect by its activity at V1 receptors; thus, its other name
is vasopressin.

162
 The paraventricular nucleus is the main secretor of oxytocin, although it also secrets small
amounts of ADH, via the supraopticohypophyseal pathway to the neurohypophysis.

 Oxytocin increases contractility of smooth muscle in the uterus during delivery.

 It also causes contraction of the myoepithelial cells surrounding the glands of the breast,
which results in the letdown of milk. (Note that the actual production of milk is
stimulated by prolactin.

 Oxytocin is secreted in response to afferent stimulation at the nipples during suckling;

alternatively, it may also be secreted in response to input from the limbic system, when
a mother hears the cry of her baby for example.

 The paraventricular nucleus also secretes some CRH.

Tuberal Region

 The tuberal region contains the arcuate nucleus, the ventral medial hypothalamic nucleus and
dorsal medial hypothalamic nucleus.

 The arcuate nucleus is arguably one of the most important hypothalamic nuclei, and is
responsible for the secretion of the pituitary releasing or release-inhibiting hormones.

 It is located in the inferiormost part of the tuberal region, near the median eminence,
into which its neuroendocrine neurons secrete the pituitary releasing or release-
inhibiting hormones.

 These hormones diffuse into the primary capillary bed, and are transported via a
hypothalamic-hypophyseal portal system into a second capillary bed in the anterior
pituitary. This collectively is described as the tuberohypophyseal pathway.

 The cells of the anterior pituitary respond directly to these hormones by secreting the
appropriate pituitary hormones.

 GnRH is secreted by both the preoptic nucleus and the arcuate nucleus; it is responsible
for stimulating the gonadotrophs to secrete FSH and LH.

 CRH is secreted by both the paraventricular nucleus and arcuate nucleus; it is

responsible for stimulating cortocotrophs to secrete ACTH.

 GHRH is secreted by the arcuate nucleus and is responsible for stimulating GH secretion.

 TRH is secreted by the arcuate nucleus and is responsible for stimulating TSH secretion.
It also independently decreases dopamine secretion by the arcuate nucleus.

 Dopamine is secreted by the arcuate nucleus and inhibits prolactin secretion. Thus,
increases in TRH result in decreases in dopamine, and a disinhibition of prolactin.

 Somatostatin is secreted by the arcuate nucleus. Its action is to inhibit the secretion of
GH, TSH and prolactin by the somatotrophs, thyrotrophs and lactotrophs.

163
 The ventral medial hypothalamic nucleus is the satiety center, the counterpart to the hunger
center in the lateral hypothalamic nucleus.

 Like the lateral hypothalamic nucleus, it has glucose receptors to detect blood glucose
levels.

 It also has receptors for leptin, the satiety hormone secreted by fat cells.

 The ventral medial hypothalamic nucleus has a set point of leptin sensitivity; it is
thought that decreases in leptin sensitivity may result in hunger and play a role in the
development of obesity. This hypothesis has also been used to explain why 90% of
people who lose weight gain it all back in the long term.

 The satiety center is also associated with the reward system; this also explains why food
makes us happy and why it is the way to a man’s heart.

 Some tumours of the hypothalamus or the pituitary may ascend, causing destruction to
both the arcuate nucleus and the ventral medial hypothalamic nucleus. These patients
may demonstrate hunger and a savage-like rage.

 The dorsal medial hypothalamic nucleus is the anger center.

 It receives inputs from the lateral hypothalamic nucleus, and is thus stimulated in times
of extreme hunger, producing irritability.

Mammillary Region

 The mammillary region contains the mammillary nucleus and the posterior hypothalamic
nucleus.

 The mammillary nucleus is connected to the papez circuit, and is involved in the production of
chewing movements.

 Clinically, its main importance is that it is one of the areas affected by Wernicke-
Korsakoff Syndrome, which occurs when there is Vitamin B1 (thiamine) deficiency.

 This occurs most commonly in alcoholics, because alcohol interferes substantially with
the absorption and storage of vitamin B1 via the GIT and the liver respectively. It can
occur also in the malnourished, or those who eat polished rice in which there is no
Vitamin B1.

 An acute episode may be caused by the administration of glucose in a hypoglycemic

patient who is an alcoholic. This is because glucose metabolism consumes thiamine, and
may deplete already low reservoirs.

 Thus, any history suggesting alcoholism is indication for co-administration of glucose

with thiamine.

164
  Thiamine deficiency causes the development of hemorrhagic lesions in the mammillary
bodies, para-aqueductal gray matter and associated CN III/ IV nuclei, the dorsal medial
nucleus of thalamus and the superior and inferior colliculus.

 This leads to the development of ocular palsies, ataxia, a confusional state, and amnesia.
Patients may produce confabulations, in which they make up stories to fill up gaps in the
memory.

 Finally, the posterior hypothalamic nucleus is the heater counterpart to the anterior
hypothalamic nucleus, and also possesses thermostat function. It responds primarily to cold.

 Its outputs are also via the sympathetic nervous system.

 These include vasoconstriction, tachycardia, anxiety as well as shivering or tremors.

Autonomic Nervous System

 The higher command of the autonomic system, aside from the thermostat function, is
performed by the hypothalamus.

 Higher command of the parasympathetic autonomic nervous system is located in the ventral
medial hypothalamus.

 Higher command of the sympathetic autonomic nervous system is located in the posterolateral
regions of the hypothalamus.

165
Clinical Correlate: Craniopharyngioma

 There are many tumours that can arise in the region of the pituitary gland and hypothalamus;
the most common is a craniopharyngioma, which arises from remnants of Rathke’s pouch to
form a congenital epidermal tumour. It is the most common supratentorial tumour in children.

 Craniopharyngiomas can invade and destroy tissue of the hypothalamus and pituitary gland,
resulting in hypothalamic syndrome. Signs and symptoms include:

 Lesions to the optic chiasma resulting in bitemporal hemianopia.

 Impaired temperature control (either hyperthermia or poikilothermia) and autonomic

nervous system abnormalities due to lesions of either the ventral or dorsal hypothalamic
nuclei.

 Hunger and rage, or loss of appetite, due to lesions of the lateral hypothalamic nucleus
or ventral medial hypothalamic nucleus.

 Anterior pituitary endocrine disorders due to disturbances especially of the arcuate

nucleus, as well as diabetes insipidus due to lesions of supraoptic nucleus.

 It is frequently calcified, and thus can be seen easily on X-ray.

166
External Connections of Hypothalamus

 The external connections of the hypothalamus include:

 Those related to the Papez circuit:

 The fornix conveys information from the subiculum in the parahippocampal formation
regarding recent memory to the mammillary bodies. Its parts include the alveus (a sheet
of white matter), the fimbriae, crus, body and columns of the fornix.

 The amygdaloid bodies are involved in sexual behaviour and aggression. They convey
information to the hypothalamus via the stria terminalis and the ventral amygdalofugal
pathways.

 The mammillary bodies, in turn, convey information to the anterior thalamic nucleus via
the mamillothalamic tract, and to the dorsomedial nucleus of thalamus via the inferior
thalamic peduncle.

 The mammillary bodies also send fibers to the dorsal tegmental nucleus, ventral
tegmental nucleus and nucleus raphe via the mamillotegmantal dract. In turn, they
receive fibers from the same nuclei via the mammillary peduncle.

 The medial forebrain bundle, which connects the frontoorbital cortex and septal area to the
nucleus raphe, locus ceruleus and respiratory and vasomotor centers.

 The connections to the posterior and anterior pituitary glands, via supraopticohypophyseal
pathways and tuberohypophyseal pathways.

 The connections to the autonomic system are carried by:

 Polysynaptic connections to PANS nuclei via the dorsal longitudinal fasciculus.

 Polysynaptic connections to SANS nuclei via the hypothalamospinal pathway.

167
AUDITORY SYSTEM
Review of Anatomy of the Ear

 The ear is composed of an external ear, middle ear and inner ear.

 The external ear is composed of the auricle and the external auditory meatus.

 In lower animals, the auricle can be moved by the extrinsic and intrinsic auricular
muscles so as to better localise the direction of origin of sound.

 In humans, the innervation of the extrinsic (anterior, superior and posterior auricular
muscles) and intrinsic auricular muscles is rudimentary and therefore this function is
limited. The posterior auricular muscle however retains some innervation from the
posterior auricular nerve from the facial nerve.

 The external auditory meatus is lined by skin with modified sebaceous glands that
produce cerumen or ear wax. Cerumen evolved as a type of insect repellent, but an
excessive buildup can occlude the canal and cause conductive deafness.

 The middle ear is a chamber separated laterally from the external ear by the tympanic
membrane, and medially from the inner ear by the bony labyrinthine wall.

 It communicates anteromedially via the pharyngotympanic tubes (aka auditory tubes,

Eustachian tubes) to the pharynx.

 It communicates posterolaterally via the aditus to mastoid antrum to the mastoid

antrum and air cell system.

 The inner ear is composed of a number of bony canals, called the bony labyrinth, which include
the cochlear, vestibule and three semicircular canals.

 Residing within these bony canals is a series of ducts which constitute the membranous
labyrinth.

 The inner ear communicates with the posterior cranial fossa via the internal auditory
meatus.

 CN VII (facial nerve) and CN VIII (vestibulocochlear nerve) pass through the internal
auditory meatus.

 The vestibulocochlear nerve divides into a vestibular part, which supplies sensory
innervation to the vestibule and semicircular canals for the sense of equilibrium, and the
cochlear part, which supplies sensory innervation to the cochlear for sense of hearing.

 The facial nerve does not innervate the inner ear.

 The external, middle and inner ears all lie beneath the middle cranial fossa. However, the inner
ear communicates via the inner auditory meatus to the posterior cranial fossa.

168
Anatomy of Middle Ear

 Going further, the external ear will not be discussed in greater detail, and the focus will be on
the middle and inner ears.

 The middle ear may be visualised as a chamber with a roof, floor and anterior, posterior, medial
and lateral walls. The detailed anatomical relations of each of these are important in
understanding how lesions spread from one structure to its neighbours to cause pathologies of
hearing and equilibrium.

 The middle ear communicates via an opening on its anterior wall to the auditory tubes and the
pharynx, and via an opening on its posterior wall to the mastoid antrum.

 Their main function of the auditory tubes is to equilise pressures between the middle
ear and the inner ear, so as to maintain the pressure on the ossicular chain and the
tympanic membrane.

 The mastoid antrum provides a reservoir of air that also provides a buffer for changes in
middle ear pressures.

 However, these open communications provide a route of infection from the pharynx to
the middle ear, and from the middle ear to the mastoid antrum posteriorly, where they
can cause mastoiditis.

 In infants, pharyngeal infection can cause swelling of the mucosa and obstruction of the
Eustachian tubes. This can prevent normal drainage of secretions from the middle ear
membrane, causing an accumulation of fluid and conductive deafness.

 The roof of the middle ear is the tegmen tympani, which separates it from the middle cranial
fossa where the temporal lobes of the brain lie.

 The tegmen tympani is very thin; infections of the middle ear can spread superiorly
through the tegmen tympani to the middle cranial fossa.

 Middle ear infections are the most common cause of brain abscesses, which spread to
the temporal lobe superiorly.

 Middle ear infections are the second most common cause of meningitis, after
meningococcal infection.

 Thus, middle ear infections must be treated urgently to prevent these complications.

169
 The floor of the middle ear is the jugular wall, as it is separated from the internal jugular vein
which passes posteriorly, inferior to the middle ear.

 The jugular wall is thicker than the tegmen tympani; thus infections passing through the
wall to the internal jugular vein are rarer.

 If they do occur, infections of internal jugular vein may spread back to the jugular
foramen, where they can cause CN IX, CN X and CN XI palsies, due to the close relation
of these structures through the jugular foramen.

 The lateral wall is formed by the tympanic membrane.

 The tympanic membrane is formed by a core of connective tissue, a lateral covering of

skin and a medial covering of mucous membrane.

 The core of connective tissue is formed mainly by dense connective tissue; however this
dense connective tissue begins at the inferiormost limit of the tympanic membrane, and
ascends only superiorly up to a point. Above this, the core is formed by a thin layer of
thin connective tissue.

 This accounts for the superior part of the tympanic membrane being more flaccid (pars
flaccida) than the part inferior to it (pars tensa).

 The border between the pars flaccida and pars tensa is marked by anterior and posterior
malleolar folds.

 When viewed from its lateral surface with an otoscope, the tympanic membrane reveals
a reflection of light off the membrane, called the cone of light, in the anterior 5 or 7 o’
clock position.

170
 On the medial wall, a number of structures are visible:

 Centrally, a large promontory is visible due to the impression of the basal turn of the
cochlear bony labyrinth on the middle ear.

 Posterior to the promontory, the terminations of the scala vestibuli and scala tympani
onto the medial wall of the inner ear are visible as the oval window and the round
window respectively.

 Posterosuperiorly to the oval window, the prominence of the horizontal part of the
facial canal through which the facial nerve runs can be seen.

 Posteriosuperiorly to the horizontal part of facial canal, the prominence of lateral

semicircular canal can be seen to make an impression on the middle ear wall.

 Infections of the middle ear can cause lesions to the footplate of stapes and the oval
window and the round window, causing leakage of perilymph from the inner ear,
resulting in conductive deafness.

 Infections can also cause inflammation of the lateral semicircular canal, leading to
labyrinthitis, which causes vertigo.

 Infections can cause lesions to the facial nerve, causing facial nerve palsy.

171
 Vibrations are transmitted through the air of the external ear, through the tympanic membrane
to the solid ossicular chain of bones (malleus, incus and stapes) in the middle ear, through the
oval window to the fluid filled labyrinth of inner ear.

 The vibrations are transmitted through air (gas), bone (solid) and then perilymph of the
inner ear (fluid).

 The footplate of the stapes is held by special joints with elastic tissue to allow for good
transmission of vibrations. In old age, the joint may be ossified by neogenesis of spongy
bone, causing otosclerosis, another type of conductive deafness.

 The vibrations at the oval window pass through the fluid-filled scala vestibuli canal,
through the cochlear, and back via the scala tympani canal back to the round window.
(The two canals are continuous at the helicotrema, or the tip of the cochlear spiral).

 As fluid is not compressible, vibrations at the oval window are conjugated closely to
vibrations at the round window.

 As the tympanic membrane has a larger surface area than the oval window, low force
vibrations over a large area are converted into high force vibrations over a smaller
surface area.

 The normal range of frequencies that can be detected by the ear ranges from 20 to
20000 Hz. Normal conversational frequencies range from 300 to 3500 Hz.

172
 Two muscles control vibration of the ossicular chain: the tensor tympani and the stapedius.

 Tensor tympani takes origin from a canal superior to and paralleling the auditory tube, and thus
enters the middle ear from the anterior wall.

 It then passes laterally to insert onto the handle of the malleus. Its function is to
maintain tension on the tympanic membrane and thereby enhance reception of
vibrations from the air.

 It is innervated by CN V3. Loss of innervation to tensor tympani thus results in

hypoacusis (reduced hearing).

 Stapedius takes origin from the posterior wall (mastoid wall) of the middle ear, at the pyramidal
prominence.

 It inserts onto the neck of stapes. Its action is to increase tension on the stapes, which
reduces the transmission of vibrations through stapes to the oval window.

 Stapedius is innervated by a branch from CN VII, which exits along the vertical portion of
the facial canal. Loss of innervation to Stapedius results in hyperacusis, where ordinary
sounds are perceived to be louder than normal and cause irritation.

173
Inner Ear Anatomy

 The inner ear is located within a bony labyrinth formed by the vestibule, three semi-circular
canals and the cochlear.

 The vestibular system, which is involved in sense of equilibrium, includes the vestibule and the
three semicircular canals.

 The three semicircular canals are the anterior (or superior), posterior and lateral (or
horizontal) semicircular canals.

 The lateral ring lies in the transverse plane. The anterior and posterior rings lie in vertical
planes, with the anterior ring rotated 45o towards the side of the ear from the saggital
plane, and the posterior ring rotated 135o towards the side of the ear from the saggital
plane.

 This is demonstrated above in the anterior view of a model of of the right inner ear.

 The cochlear system, responsible for the sense of hearing, is found in the cochlear canal. It is is a
spiral shaped canalwhich winds around a central column of bone called the modiolus.

 It is attached to the modiolus along its length by a thin plate of bone, called the spiral
lamina, which winds around the modiolus like the tract of a screw.

 The cochlear spiral makes between 2.5 to 2.75 turns around the modiolus, and as a
whole forms a cone shape, with a base and an apex.

 The base is directed posteromedially towards the internal auditory meatus.

174
Cochlear System

 The cochlear system is involved in the sense of hearing.

 Within the bony labyrinth canal, a membranous cochlear duct runs through its length, almost up
to the end.

 When viewed in cross section, the cochlear duct is attached superficially to the wall of the canal
by the spiral ligament, and deeply to the spiral lamina of the modiolus.

 This divides the bony cochlear canal into three parts:

 The scala media is another name for the lumen of the membranous cochlear duct.

 The scala vestibuli runs superior to the scala media, separated from it by the vestibular
membrane, also called Reissner’s membrane.

 The scala tympani runs inferior to the scala media, separated from it by the basilar
membrane. A small portion of the bony spiral lamina also separates the scala tympani
from the scala vestibuli.

 The scala vestibuli and tympani are actually continuous at the helicotrema, at the apex
of the bony cochlear canal, as the scala media does not extend all the way to tip of the
apex of the bony canal.

 When viewed from the medial wall of the middle ear, the scala vestibuli terminates at the oval
window, while the scala tympani terminates at the round window.

 When the ossicular chain of the middle ear transmits a sound to the oval window, it creates a
vibration in the fluid of the scala vestibuli, called the perilymph. (The fluid within the
membranous duct or scala media is called endolymph).

 The vibration is transmitted along the scala vestibuli to the apex of the cochlear, where it is
continuous with scala tympani at the helicotrema. The vibration then continues back down the
cochlear canal via the scala tympani.

175
 The organ of hearing, called the organ of Corti or spiral organ, is found in the basilar membrane.

 The Reissner membrane is stiffer than the basilar membrane and does not vibrate much
as vibrations pass through the scala vestibuli.

 Thus, sound is detected only when vibrations are returning from the apex of the
cochlear back to the round window via the scala tympani.

 In transverse section of the scala media, the basilar membrane may be observed to have:

 A row of supporting cells at the base of the membrane.

 Hair cells sitting on top of the supporting cells, which are divided into one row of inner
hair cells and three rows of outer hair cells, separated by the tunnel of Corti. The rows
of inner and outer hair cells run throughout the length of the scala media alongside the
tunnel of corti.

 A membrana tectoria lies just over the hair cells and separates them from the lumen of
the scala media.

 Each hair cell has a number of processes extending superiorly with it. It expresses K+ channels on
the membrane of only one side of each process.

 When sound vibrates through the scala tympani, the basal membrane vibrates, causing the hair
cells to rub against the tectorial membrane above them.

 When the processes of hair cells bend in a direction away from the side which expresses
potassium channels, the potassium channels open. When the processes of hair cells bend
towards the side expressing potassium channels, the channels close.

176
 When a vibration is detected, the hair cells rub against the tectorial membrane so as to reduce
potassium efflux from the cell. As potassium accumulates within the hair cell, it triggers a
depolarisation of the hair cell, producing microphonic cochlear potentials.

 The hair cell receives innervation from the peripheral processes of bipolar neurons whose cell
bodies are found in the spiral ganglion, along the spiral lamina. These bipolar sensory neurons
then return an action potential via the cochlear part of CN VIII towards the central nervous
system.

 The hair cells thus transduce mechanical energy into electrochemical energy.

 The volume of a vibration, measured in decibels, is detected by a change in amplitude of the

vibration of the basilar membrane.

 The frequency of a vibration, measured in Hz, is detected by different hair cells along the length
of the basilar membrane as it runs through the bony cochlear canal.

 The tension of the basilar membrane is higher in the basal turns of the cochlear, and
lower in the more apical turns.

 Thus, the natural frequency at which the basilar membrane best resonates is higher in
the basal turns, and lower in the more apical turns.

 As a result, different frequencies cause different parts of the basilar membrane to

vibrate. The corresponding sensory neurons send signals via tonotopically arranged
fibers to the central nervous system, where they are perceived as different pitches.

177
Central Nervous System Auditory Pathway

 An action potential is sent from the spiral ganglion via the central processes of those neurons to
the central nervous system. The signal is received by the dorsal and ventral cochlear nuclei in
the medulla.

 Some fibers from the ventral cochlear nucleus may ascend in the ipsilateral tract to join the
ipsilateral superior olivary nucleus.

 Other fibers may cross over at the level of the ventral cochlear nucleus or the superior olivary
nucleus to join the contralateral tract.

 Fibers from the dorsal cochlear nucleus mostly do not cross, but ascend in the brainstem.
Eventually they join fibers from the superior olivary nucleus to form the lateral lemniscus, which
ascends to synapse onto the inferior colliculus in the midbrain.

 The inferior colliculus sends fibers to the medial geniculate body via the inferior brachium.
Some fibers also cross to thecontralateral side at the inferior colliculus.

 The medial geniculate body then sends fibers via the internal capsule, and subsequently via
coronal radiations that eventually synapse on the transverse gyrus of the temporal lobe. The
transverse gyrus is found in the depths of the lateral sulcus; here, the primary auditory cortex is
found.

 The tonotopic arrangement of fibers allows the primary auditory cortex to distinguish between
sounds of different frequencies, perceived as a change in pitch.

 Lesions occurring below the level of the ventral cochlear nucleus cause a complete unilateral
deafness.

 Lesions occurring above the level of the ventral cochlear nucleus may only result in a partial,
bilateral reduction in hearing due to the crossing of fibers.

178
 The ventral cochlear nucleus is particularly associated with distinguishing the volume of sounds;
lesions to the ventral cochlear nucleus result in abnormal perception of volume.

 The dorsal cochlear nucleus is associated with distinguishing between the frequency of sounds.
Lesions to the dorsal cochlear nucleus results in abnormal perception of pitch.

 The superior olivary nucleus has a number of functions:

 Through its communicating fibers with the contralateral superior olivary nucleus, it is
able to determine which nucleus has detected a sound first, and therefore whether the
sound came from the left or right ear. This allows for the spatial localisation of sound.

 It is also involved in a reflex arc for the contraction of stapedius via CN VII, to reduce the
transmission of loud sounds, as well as the sound of one’s own voice when speaking.
Thus, indeed it is necessary for one to stop talking in order to listen to others!

 Additionally, the dorsal and ventral cochlear nuclei have also been found to have efferent
cholinergic fibers to the outer hair cells.

 They increase the tension in those outer hair cells and the membrane tectoria in certain
regions, and can thereby modulate the sensitivity of the cochlear apparatus to selected
frequencies.

 It is thought that this is a mechanism by which our sensitivity to certain sounds can be
enhanced or decreased by central mechanisms.

179
Types of Deafness

 The two main types of deafness are conductive deafness and sensorineural deafness.

 Conductive deafness is generally associated with lesions to the external and middle ear which
block conduction of sounds. Examples include:

 Foreign bodies or cerumen buildup in the external acoustic meatus.

 Otitis media (infection of middle ear)

 Otosclerosis of the stapes footplate joint at the oval window.

 Sensorineural deafness usually occurs due to lesions of the inner ear. Examples include:

 Presbyacusis, where the basilar membrane, particularly in the basal turns of the
cochlear apparatus, degenerate such that there is reduced perception of high frequency
sounds. This might account for the inability of men to listen to their wives in old age! It is
the most common cause of age-related hearing loss.

 Noise trauma due to exposure to loud sounds can cause damage to the organ of Corti.

 An acoustic schwannoma can invade and cause damage to both the cochlear and
vestibular components of CN VIII, as well as CN VII. If it invades via the internal acoustic
meatus into the posterior cranial fossa, it can also cause CN V and CN IX palsies.

 Meniere’s disease can cause impairment of hearing and equilibrium by increasing

pressure in the cochlear and vestibular duct systems.

 Ototoxic drugs include aminoglycosides. (AMG = A Mean Guy, who hits your ears, kicks
your kidneys and leaves you paralysed!) Tobramycin tends to concentrate particularly in
the vestibular system to cause vertigo, while Amikacin tends to concentrate in the
cochlear system and cause deafness.

 Aspirin also has ototoxic effects when overdosed; it can cause tinnitus.

 A number of infections, including rubella, cytomegalovirus and syphilis can cause

ototoxic effects to foetuses in utero.

180
Tests of Hearing

 The Weber test and Rinne test are used in combination to determine if hearing impairment is
conductive or sensorineural.

 In the Weber test, a tuning fork is placed on the vertex of the head or on the forehead, directly
over the scalp, and is vibrated.

 In a normal person, the sound is heard equally in both ears. There is no lateralisation of
sound.

 In a person with conductive deafness, the sound lateralises towards the ear in which
hearing is normally impaired, as the sound conducts better through the bone of the
cranium through the solid material to the ear.

 In a person with sensorineural deafness, the sound lateralises away from the ear in
which hearing is impaired.

 Thus, a lateralisation of hearing in the Weber test can indicate either conductive deafness in the
side of lateralisation, or sensorineural deafness away from the side of lateralisation.

 In order to distinguish between the two, the Rinne test is performed on the ear towards which
sound is lateralised. In conductive deafness, this ear is impaired, while in sensorineural deafness
this ear is normal.

 The tuning fork is struck and its base placed over the mastoid process on the side of
lateralisation in the Weber test.

 The patient is instructed to raise his hand when he can no longer hear the vibration of
the tuning fork. At this point the tuning fork is immediately removed from the mastoid
process and placed in the air near the auricle of the same ear.

 In a normal ear, the conduction through bone is poorer than the conduction through air;
thus when the tuning fork is placed next to the auricle the patient will still be able to
hear the tuning fork.

 In a ear with conductive deafness, the conduction through bone lasts longer than the
conduction through air. Upon bringing the tuning fork next to the auricle, the patient
will not be able to hear the vibrations of the tuning fork.

181
 The weakness of this test is that it can only detect hearing loss when it is greater in one ear than
the other.

 In another test, by placing electrodes over the scalp of the patient, brainstem auditory evoked
potentials are detected as a series of waves, each representing a depolarisation of one of the
neurons in the series of the auditory system.

 By counting the number of waves, lesions to the central nervous system causing
deafness can be localised to determine which nucleus is failing to relay the signal
forward.

 It is particularly useful for testing infants who are unable to communicate with the
examiner which is necessary in other hearing tests.

 It can also be used to localise lesions in multiple sclerosis.

182
VESTIBULAR SYSTEM
Review of Inner Ear Anatomical Relations

 The inner ear, residing within the petrous part of temporal bone, is composed of a bony
labyrinth, formed by the canal of the cochlear, the vestibule and three semicircular canals.

 The bony labyrinth is filled with perilymph. Within the perilymph, the membranous labyrinth is
suspended.

 The cochlear duct lies within the cochlear canal.

 Two sacs, called the utricle and saccule, lie within the vestibule. The saccule is
communicates with the cochlear duct.

 Three semicircular ducts run within each of the semicircular canals, each ending in an
ampule that connects to the utricle.

 Of the three semicircular ducts, the lateral duct has two independent connections to the
utricle, whereas the anterior and posterior ducts each have one independent connection,
and one shared connection between them.

 The membranous labyrinth is filled with endolymph.

 Whereas the sensory epithelium of the cochlear duct is the spiral organ of Corti, those of the
utricle and saccule are called the maculae and that of the ampulla are called cristae.

 The organ of corti senses hearing

 The maculae sense gravitational pull, static balance and linear acceleration. While the
macula of utricle is found in its floor, the macula of saccule is found in its walls.

 The cristae sense dynamic balance and angular acceleration.

183
Functions of the Maculae

 The maculae consist of a layer of hair cells sitting atop a layer of supporting cells. The hair cells
are covered with a layer of jelly-like material, within which calcium carbonate stones called
otoconia reside.

 Like the hair cells of the organ of Corti, the hair cells of the maculae have a series of cilia from
long to short.

 The longer cilia are called kinocilia and the shorter ones are called stereocilia.

 The cilia possess K+ channels on only one side.

 Moving the stereocilia towards the kinocilia causes closure of the K+ channels (reduced
conductance) and depolarisation due to potassium retention.

 Moving the stereocilia away from the kinocilia causes opening of the K+ channels
(increased conductance) and hyperpolarisation due to increased potassium efflux.

 Membrane potentials are thus controlled mainly by potassium. This is underscored by

the fact that endolymph has a relatively low concentration of sodium in comparison to
potassium, although endolymph potassium is still lower than intracellular potassium.

 If the position of the head is changed, gravity causes the otoconia to roll over the cilia, producing
depolarisation or hyperpolarisation in a specific pattern.

 This stone rolling movement can also be elicited by linear acceleration.

 Linear acceleration in the horizontal plane (e.g. in an accelerating car) is detected by the
utricles, which have horizontally placed maculae.

 Linear acceleration in the vertical axis (e.g. in a lift) is detected by the saccule, which
have maculae along their walls oriented in the vertical axis.

 The specific pattern of depolarisation can be computed by the central nervous system for the
sensation of gravitational pull in static equilibrium, or for linear acceleration.

184
Functions of the Cristae

 The cristae, located in the ampulla of each of the three semicircular ducts, are composed of a
basal layer of supporting cells (not shown), a layer of hair cells, and overlying that is a gelatinous
layer called the cupula.

 During rapid rotational movement of the head, endolymph within the semicircular canals moves
at a different rate than the canal itself due to inertia.

 This results in movement of the copula against the hair cells, resulting in either depolarisation of
hyperpolarisation, depending on the direction of movement and the semicircular canal in
question.

 The three-dimensional rotational movements of the head can be computed based on the
pattern of stimulation of the cristae in each of the three ampulla of each of the two ears.

 All of them are innervated by the central processes of neurons whose cell bodies reside in the
vestibular ganglion.

185
CNS Vestibular System

 The CNS receives signals from the cristae and maculae about the sense of equilibrium via the
central processes of neurons whose cell bodies are found in vestibular ganglion. These central
processes form the vestibular part of the vestibulocochlear nerve (CN VIII).

 Some fibers of vestibular part of CN VIII may pass directly to vestibulocerebellum

(formed of the flocculonodular lobe) and its fastigial nucleus via the juxtarestiform
body, part of inferior cerebellar peduncle.

 Most fibers pass to the vestibular nucleus and then to the vestibulocerebellum.

 The vestibulocerebellum integrates this information, and then returns an output back to the
ipsilateral vestibular nucleus. Some fibers are also given to the contralateral vestibular nucleus.

 From there, the vestibular nucleus produces a number of outputs to:

 The vestibulospinal tract, which synapses on LMNs to maintain extensor tone

 The vestibulo-thalamocortical tract, via the VPM and VPL nuclei of thalamus, to the
primary sensory cortex for conscious perception of equilibrium.

 The vestibulo-ocular tracts to the ocular nuclei, via the medial longitudinal fasciculus,
for the control of gaze independent of head movements.

 The vestibular nucleus also has a two-way connection with the inferior olivary nucleus.

 The inferior olivary nucleus controls some automatic behaviours.

 It receives input also from the lower limbs during the cyclical walking motion.

 It produces an output to the arms to stimulate the cyclical, alternating swinging of the
arms to match the legs.

186
Vestibulo-ocular Reflexes

 In a normal person, the vestibulo-ocular reflexes function to maintain control of gaze

independent of head movements.

 The vestibular nucleus receives information that has been integrated by the
vestibulocerebellum from the vestibular apparatus.

 One of its outputs is via the medial longtitudinal fasciculus to the 3rd, 4th and 6th nuclei
responsible for controlling the extraocular muscles.

 A normal VOR can be observed by performing the head impulse test, in which a person’s
head is rapidly rotated in one direction. The response is for his eyes to move rapidly in
the contralateral direction in order to maintain a fixed gaze.

 Nystagmus is a rhythmic regular oscillation of the eyes.

 Jerk nystagmus occurs when there is a slow drifting of the eyes in one direction,
followed by a rapid corrective jerk in the other direction. Typically, when it occurs
pathologically, the lesion is responsible for the slow drifting phase, but the direction of
the nystagmus is named for the corrective fast phase.

 Pendular nystagmus is rarer and involves slow, pendular oscillations to and fro.

 The optokinetic reflex is an example a physiological nystagmus.

 When sitting in a moving vehicle and gazing outside, the eyes track an object in the
visual field until it passes out of view.

 Immediately after the object has passed out of view, the eyes swing back to the original
position from which the tracking began, and may begin tracking a new object.

 The Barany test can also demonstrate physiological nystagmus while spinning on the spot to test
for vestibular function.

 The patient sits in a chair which is rapidly rotated.

 When a person is spun to the right, his eyes track objects in a slow drift to the left.
However, once the limit of the visual field is reached, the eyes rapidly correct back to
the right in a fast beat, causing a right nystagmus.

 However, upon rapidly stopping a rotational movement, the fluid within the semicircular
ducts momentarily continues moving due to inertia; at this point, the direction of
nystagmus momentarily reverses.

187
 The caloric reflex test can also be used to test for brainstem lesions.

 In the caloric reflex test, cold or warm water is poured into one ear, which causes the
rapid flow of endolymph.

 In a normal person, cold water results in a nystagmus to the opposite side, whereas
warm water results in nystagmus to the same side. This can be remembered by the
acronym COWS.

 In a comatose person without any other brainstem lesions, cold water does not cause a
nystagmus, but causes a persistent gaze to the same side. Warm water does opposite.

 In an isolated medial longitudinal fasciculus lesion, the abducens nucleus continues to work as it
receives innervation from the pontine conjugate movement center, which is stimulated by the
vestibular operators in the vestibulo-ocular reflex. However, it fails to transmit information to
the contralateral oculomotor nucleus.

 When the cold-water caloric reflex test is performed, a person who is otherwise normal
will exhibit nystagmus away from the side of testing, but only of the eye that is
abducting in the direction of nystagmus. The other eye will retain a central position.

 When the cold-water caloric reflex test is performed on a patient that is also comatose,
the patient will exhibit a persistent gaze towards the side of testing, but only of the eye
that is abducting in that direction. The other eye will retain a central position.

 In a complete bilateral lower brainstem lesion, the vestibuloocular reflexes are completely
damaged due to lesions to the vestibular nucleus and/ or its pathways.

 The person will exhibit negative dolls eyes, that is, his gaze will follow exactly the
movement of his head.

 The caloric reflex test does not induce any response.

188
Clinical Correlates of Vestibular System Lesions

 Vertigo is a type of hallucination in which a sensation of relative motion of the self to the
environment (or vice versa) is perceived without external stimulus.

 It may be caused by any number of lesions to the vestibular apparatus, to the vestibular nucleus,
or to the vestibulo-thalamocortical tracts.

 Meniere’s disease occurs when there is an oversecretion or underdrainage of endolymph within

the membranous labyrinth.

 Excessive pressures within the membranous labyrinth can cause damage to the organ of
Corti, the maculae or the cristae. There is a feeling of fullness within the ears.

 Cochlear lesions can result in sensorineural deafness (understimulation) or tinnitus

(overstimulation).

 Lesions to the vestibular apparatus can result in vertigo as well as nausea, due to
communications of the vestibular apparatus to the nausea and vomiting center of the
medulla.

 Labyrinthitis occurs when there is inflammation of the membranous labyrinth.

 Unlike Meniere’s disease which has a specific endogenous cause, labyrinthitis can be
caused by any number of exogenous causes, e.g. infection, use of ototoxic drugs like
quinine, salicylates and alcohol.

 It has a different etiology, but otherwise the same features of Meniere’s disease, except
that Meniere’s disease is more prone to recurrence.

 Benign Positional Vertigo is the most frequent cause of recurrent vertigo.

 It results from dislodgement of the otoconia from the macula of the utricle, into the
ampule of the posterior semicircular ducts. This is known as cuprothiasis.

 It thus causes persistent stimulation of the crista of the posterior semicircular duct,
resulting in vertigo.

 It can be tested for in the Dix-Hallpike test. In this test, the head is turned 45o towards
the affected ear. This aligns the posterior semicircular canal in the sagittal plane for
maximum effect.

 The patient lies down rapidly with the head extended slightly backwards. This should
cause movement of otoconia within the posterior semicircular canal rapidly. A positive
test results when a rotational nystagmus is produced subsequently.

 Vestibular neuritis occurs when there is inflammation to the vestibular nerve.

189
VISUAL SYSTEM
The Optic Nerve (CN II)

 The optic nerve is not a true cranial nerve! It is a CNS tract.

 Its axons are myelinated by oligodendrocytes rather than Schwann cells. Thus, unlike
other cranial nerves it is susceptible to demyelinating diseases of the CNS such as
multiple sclerosis.

 Unlike other peripheral nerves, its axons do not regenerate when damaged.

 Rather than a epineurium, the optic nerve is covered by all three meningeal layers;
indeed, the CSF filled cavity is continuous around the optic nerve.

 Embryologically, it develops as a structure of the diencephalon.

 The optic nerve carries Special Somatic Afferent fibers, which transmit visual information. This
information is received from the light receptors of the retina, the rods and cones, which are
transducers of electromagnetic energy in the form of visible light into electrochemical energy.

 The development of the optic tracts, nerve and retina begin as an outpouching of the
diencephalon to form an optic vesicle.

 It is thus formed from neuroectoderm.

 The optic lens invaginates into the optic vesicle to form an optic cup. The optic lens itself
develops from the optic placode.

 The cup has an outer layer which develops into the choroid layer, and an inner layer
which develops into the retina.

190
Gross Anatomy of Retina

 When observed under fundoscopy, the retina is observed to have an optic disc which is
displaced 3.5mm medially from the center of the fundus.

 The optic disc is the head of the optic nerve; fibers of the ganglion cells in the retina all
converge towards the optic disc. These converging fibers running into the optic disc form
the walls of a cup-shaped optic disc.

 The cup has a rim; alterations in the thickness of the rim change the cup-rim ratio, which
is a sign of pathology.

 The margins of the optic disc are clear cut. Blurring of the margins of the optic disc
reflects edema and some pathology of the optic disc.

 The optic disc has retinal vessels radiating from it. Abnormalities of the retinal vessels
also indicate pathology.

 The optic disc itself has no rod or cone light receptors. Images falling over the optic disc
thus produce no image, and the area of the disc is a physiological blind spot.

 Lateral to the optic disc, a macula lutea (yellow spot) is observed.

 The macula lutea is rich in cones and deficient in rods.

 At the center of the macula lutea is the fovea centralis, in which there is a maximum
concentration of cones. Visual acuity is at a maximum here.

 The fovea centralis does not have bipolar cells or ganglion cells and is very thin; it is
avascular and receives nutrition purely by diffusion from the choroidal plexus.

191
 The rods and cones are the photoreceptors of the retinal layer which are sensitive to
electromagnetic waves.

 They have membrane infoldings containing ion channels and special pigments.

 The rods have rhodopsin as their pigment while the cones have iodopsin pigment.

 Whereas the cones are at a maximum concentration centrally, especially within the
fovea centralis of the macula lutea, the rods are at a maximum concentration in
peripheral regions of the retina.

 The concentration of cones falls as one moves peripherally from the center of the retina,
and the concentration of rods falls as one moves centrally from peripheral areas.
However, in general the rods are more abundant than cones (100 million vs 7 million).

 In well-lit conditions, the pupil constricts and light is focused towards the center of the
retina; thus under such conditions the rods in the periphery may be thought of as having
poorer exposure to light.

 The rods are more sensitive in dim light, and are responsible for scotopic (night) vision.
The cones require illimunating light, and are responsible for photopic (day) vision.

 Scotopic vision is associated with lower definition, monochromic images, while photopic
vision is associated with higher definition colour vision.

192
Four Cellular Layers of the Retina

 The retina is formed as a layer of four main types of cells. From superficial to deep, these are the
pigmented epithelial cells, the photoreceptors, the bipolar cells and the ganglionic cells.

 The structure of the retina is thus described as inverted, because light falls on the
photoreceptors in the back of the retina, and then the signal is transduced and sent back
forward through the bipolar and ganglion cells.

 The retina is thus colourless and transparent for light to pass through to the photorecepters
which are in the most posterior layers of the retina.

 The pigmented epithelial cells separate the retina from the choroidal layer.

 The rods and cones are the photoreceptor cells.

 They have photoreceptors, a nucleus and terminal buttons. The photoreceptors contain
various infoldings, which contain ion channels and either rhodopsin or iodopsin pigment.

 When light energy falls on these pigments to stimulate the cell, a chemical change in the
pigments is induced. This results in reduced Na+ conductance, hyperpolarising rather
than depolarising the cell!

 Rods and cones do not produce action potentials. They produce local graded potentials
across the membrane.

 Upon stimulation, they release glutamate neurotransmitters to stimulatebipolar cells.

 The bipolar cells are the second order cells in the visual pathway.

 These bipolar cells have peripheral processes which connect to the rods and cones,
nuclei and central processes which connect to the ganglion cells. Like the rods and cones,
they are glutaminergic neurons.

 The bipolar cells also do not produce action potentials. Like the rods and cones, they are
sufficiently short that local graded potentials can transmit information across the cell.

 The ganglion cells are the third cells in the visual pathway.

 They also have a bipolar structure, with peripheral processes and central processes.

 The central processes, however, form long axons that converge in the region of the optic
disc, to form the optic nerve. These fibers are eventually bound for the lateral geniculate
bodies of the thalami.

 They are also glutaminergic neurons.

193
Ten-Layered Organisation of Retina

194
 While the retina is formed by four main layers of cells, the organisation of the retinal layers can
be divided further into ten layers. The layers are described from superficial to deep.

 The first five layers are supplied purely by diffusion from the choroidal plexus. The fovea centralis
only contains the first five layers as it lacks bipolar cells and ganglion cells; it is thus avascular.

 The first layer is the pigmented epithelial cell layer.

 The second layer is the layer of rods and cones, formed by the rod and cone receptors of
the rod and cone cells.

 The third layer is formed by the outer limiting membrane, which separates the layer of
rods and cones from the cell bodies of the rod and cone cells.

 The fourth layer is called the outer nuclear layer and is formed by nuclei of the rod and
cone cells.

 The fifth layer is the outer plexiform layer, which is formed by the synapses of the rod
and cone cells onto the bipolar cells.

 The internal five layers are supplied by branches of the central retinal artery.

 The sixth layer is formed by the cell bodies of the bipolar cells, and is called the inner
nuclear layer.

 The seventh layer is formed by synapses of bipolar cells on ganglion cells, and is called
the inner plexiform layer.

 The eighth layer is formed by the ganglion cell bodies and is called the inner ganglion
cell layer.

 The ninth layer is formed by central processes of the ganglion cells and is called nerve
fiber layer.

 The final tenth layer is called the inner limiting membrane, and overlies the nerve fiber
layer.

195
Additional Cells Within Retinal Layers

 There are some additional cells which are present at different layers of the retina.

 Horizontal cells are present within the outer plexiform layer, and interconnect the terminal
buttons of the rods and cones. They serve as interconnections of the outer layer.

 Amacrine cells have their cell bodies present in the region of the inner plexiform layer. They
interconnect bipolar cells to each other and ganglion cells to each other. They serve as
interconnections of the inner layer.

 The horizontal cells and amacrine cells are inhibitory GABAergic cells, in contrast to the
photoreceptor cells, the bipolar cells and ganglion cells which are glutaminergic.

 Muller cells extend from the outer limiting membrane to the inner limiting membrane. These
are modified neuroglial cells of the retina. They are radial glial cells with a similar structure to
astrocytes.

 Finally, the oligodendrocytes are the myelinating cells of the ganglion cell nerve fibers. These
cells are lost in multiple sclerosis, leading to loss of conduction through the optic nerve.

196
Visual Areas of the Retina

 The visual areas of the retina may be described in one of two ways.

 The first method divides the retina into halves and quadrants:

 Each retina (left or right) has a medial nasal hemiretina and a lateral temporal
hemiretina.

 Each hemiretina is further divided into upper and lower nasal quadrants and temporal
quadrants.

 Images of the visual field are projected onto the retina such that they are both vertically
and laterally inverted.

 Thus, for example, the right upper nasal quadrant of the retina is receiving images from
the right lower temporal visual field.

 This pattern of division is more useful when describing lesions to the retina, optic nerves,
optic chiasma, optic tracts and optic radiations.

 The second method involves a concentric division of the retina:

 The macular area, formed by the macula lutea, forms the centremost part of the visual
field.

 Surrounding the macular area is the paramacular area.

 Peripheral to the paramacular area is the monocular area.

 The images projected onto the macula area, paramacular area and monocular area are
received by corresponding parts of the occipital lobe from posterior to anterior. Thus,
lesions to the occipital cortex may produce vision loss in these corresponding divisions.

197
The Visual Pathway

 The visual pathway begins when light strikes the retina, stimulating the photoreceptor cells.

 The photoreceptor cells eventually result in the stimulation of ganglion cells, whose central
processes come together to form the optic disc and optic nerve.

 The optic nerve passes posteriorly into the orbit and through the optic canal to enter the middle
cranial fossa.

 Within the chiasmatic groove of the middle cranial fossa, the two optic nerves converge at the
optic chiasma.

 Within the optic chiasma, fibers originating from each of the left and right nasal
hemiretinas cross over to the contralateral side. However, just before doing so, fibers
from the inferior nasal quadrants of the retina make a short detour into the
contralateral optic nerve before making a U-turn back.

 Thus, all structures proximal to the optic chiasma (optic tracts, lateral geniculate body,
optic radiations and primary visual cortex) carry information about the contralateral half
of each visual field (but the ipsilateral hemiretinae).

 For example, the right optic tract carries information from the left half of each visual
field (left temporal and right nasal visual fields), but these images are projected onto the
left nasal and right temporal hemiretinae.

 From the optic chiasma, the optic tracts run posteriorly.

 90% of the fibers run to the lateral geniculate body, just lateral to the thalamus.

 10% of the fibers enter the superior colliculus and pretectal nucleus of the midbrain via
the superior brachium (not shown).

198
 The lateral geniculate body is split into six layers, numbered 1 through 6 from medial to lateral.

 Information from the ipsilateral eye enters into layers 2, 3 and 5.

 Information from the contralateral eye enters into layers 1, 4 and 6.

 The fibers in the lateral geniculate body run posteriorly via the optic radiations towards the
primary visual cortex found in the occipital lobe.

 The optic radiations of each side are divided into a superior division and inferior divison.

 The superior division of each brain hemisphere carries information about the inferior
and contralateral quadrant of the visual field of each eye.

 For example, the right superior optic radiation carries information from the left inferior
temporal quadrant and right inferior nasal quadrant.

 The superior division runs posteriorly, superior to the inferior division, crossing through
the parietal lobe to the occipital lobe. Here it terminates at the upper bank of the
calcarine fissure.

 The inferior division runs anterolaterally at first, passing through the temporal lobe. This
part of the inferior division is known as Meyer’s loop. Subsequently, it passes posteriorly
through the parietal lobe, to the occipital lobe where it terminates at the lower bank of
the calcarine fissure.

 The primary visual cortex at the calcrine fissure then sends the information to the secondary
and tertiary visual cortices for interpretation.

 The primary visual cortex is located on the posteriormost part of the occipital lobe, in
Brodmann area 17. It is responsible for the reception of visual information.

 The secondary visual cortex is located in Brodmann area 18, immediately anterior to
area 17. It is responsible for the analysis of visual information, including analysis of
colour, shape, patterns etc.

 The tertiary visual area is located in Brodmann area 19, anterior to area 18. It I
responsible for the recognition of current visual information by comparison to images
previously stored in memory.

 The secondary and tertiary areas are collectively known as the visual association cortex.

199
Visual Pathway Lesions

 Scotoma is a term used to refer to a blindspot, usually in a pathological context.

 For the visual field of each eye, images in the nasal half of the visual field fall on the temporal
hemiretina of the same eye. Similarly, images in the temporal half of each visual field fall on the
nasal hemiretina of the same eye.

 Lesions in the left or right temporal hemiretina will produce a unilateral (left or right)
nasal hemianopia respectively.

 Lesions in the left or right nasal hemiretina produce a unilateral (left or right) temporal
hemianopia respectively.

 E.g. Lesions to right temporal hemiretina produce a right nasal hemianopia:

 The optic nerve (CN II) of each eye carries visual information from the ipsilateral eye. Lesions to
the optic nerve (e.g. due to multiple sclerosis) of any eye produce total blindness of that eye.

 E.g. lesion to right optic nerve produces complete right eye blindness.

 However, if the lesion occurs at the posteriormost part of the optic nerve, fibers from
the contralateral inferior nasal hemiretina may also be involved. The contralateral eye
will also experience an upper temporal quadrantanopia in such a situation.

 E.g. lesion to most proximal part of right optic nerve produces complete right eye
blindness and left upper temporal quadrantanopia.

 Lesions to the medial part of the chiasma (described as midline chiasma lesions) can occur with
pituitary tumours.

 The optic chiasma carries both decussating and non-decussating fibers; the decussating
fibers are located medially within the chiasma.

 The decussating fibers carry information from the temporal half of each visual field.
Lesions to the medial part of the chiasma thus lead to bitemporal hemianopia.

200
 Lesions to the lateral part of the chiasma can occur with internal carotid artery aneurysms.

 The non-decussating fibers carry information from the nasal half of each visual field.
These fibers are located laterally within the chiasma.

 Lesions to the lateral part of the chiasma (known as the perichiasmatic area) produce an
ipsilateral nasal hemianopia.

 Thus, unilateral nasal hemianopias may be caused by ipsilateral perichiasmatic lesions or

ipsilateral temporal hemiretina lesions.

 :

 Each optic tract carries information from the contralateral half of each visual field.

 Thus, lesions to the optic tract result in contralateral homonymous hemianopia.

 For example, lesion to the right optic tract results in left homonymous hemianopia.

 The superior division of each optic radiation carries information from the contralateral inferior
quadrant of each visual field.

 Thus, lesions to the superior division of an optic radiation produces contralateral

inferior homonymous quadrantanopia.

 For example, a lesion to the right superior optic radiation produces a left inferior
homonymous quadrantanopia.

 The inferior division of each optic radiation carries information from the contralateral superior
quadrant of each visual field.

 Lesions to the inferior division of each optic radiation produces contralateral superior
homonymous quadrantanopia.

 For example, a lesion to the right inferior optic radiation produces a left superior
homonymous quadrantanopia.

201
 Lesions to the occipital lobe may develop as a result of ischemia. The parts of the occipital lobe
affected depend on the area of distribution of the arteries that have been disrupted.

 As previously described, the occipital lobe has a macular part, a paramacular part and a
monocular part which serve corresponding regions of the retinae.

 All three regions receive blood supply from the posterior cerebral artery (PCA).

 However, the macular part has a dual blood supply, and also receives collateral supply
from the middle cerebral artery (MCA).

 Thus, interruption of either the left or right PCAs result in contralateral homonymous
hemianopia with macular sparing. Macular sparing distinguishes the clinical
presentation from that of lesions to the optic tract.

 For example, interruption of the right posterior cerebral artery produces left
homonymous hemianopia with macular sparing.

 Concussion injuries to the posterior part of the brain may injure the occipital lobe to varying
degrees.

 If only the posteriormost regions of both occipital lobes are injured, visual loss occurs
only in the central, macula area of the left and right visual fields.

 If only the upper bank of both lobes are injured (known as the cuneate gyri), a bilateral
lower altitudinal hemianopia results.

 If only the lower bank of both lobes are injured (known as the lingual gyri), a bilateral
upper altitude hemianopia results.

202
Pupillary Light Reflex

 The pupillary light reflex describes the constriction of the pupils in response to light. It is under
involuntary control, and involves two component reflexes that can be tested:

 In the direct light reflex, light is shone into one eye (e.g. with a pentorch). The direct
reflex is positive when it results in constriction of the ipsilateral pupil.

 In the indirect light reflex, light is shone into one eye. The indirect light reflex is positive
for the eye being illuminated when it results in constriction of the contralateral pupil.

 Thus, if light is shone into the left eye, constriction of the left pupil indicates a positive
left direct reflex, and constriction of the right pupil indicates a positive left indirect reflex.

 The afferent limb of the reflex is mediated by structures of the visual pathway:

 Light is first detected on the retina of the stimulated eye.

 Afferent fibers (composed of ganglion cell central processes) pass posteriorly through
the optic nerve of the stimulated eye.

 At the optic chiasma, nasal hemiretina fibers cross to the contralateral optic tract, while
temporal hemiretina fibers stay on the ipsilateral side. Thus, the afferent limb of the light
reflex may be carried by either of the two optic tracts, which act as collateral pathways.

 From both optic tracts, 10% of fibers leave via the superior brachium, where they pass
to both of the superior colliculi as well as the two pretectal nuclei immediately anterior
to them.

 The pretectal nuclei are interconnected by the posterior commissure.

 The efferent limb of the reflex is as follows:

 The pretectal nuclei send fibers to both of the Edinger-Westphal nuclei.

 The Edinger-Westphal nucleus sends out parasympathetic fibers which run through the
common part of CN III and then its inferior branch to the ciliary ganglion.

 From the ciliary ganglion, postganglionic fibers pass via short ciliary nerves to both the
ciliaris muscles and the sphincter pupillae muscles.

203
The Near Response

 The near response involves changes in the ocular system that occur when a far object being
focused on comes near, or if there is a voluntary shift in visual focus from a far object to a near
object.

 The response is stimulated when the visual association cortex determines that an object is blur,
indicating that it is out of focus.

 The afferent pathway begins with the visual pathway from the retina, through the optic nerves,
chiasma, tract, lateral geniculate bodies and optic radiations to the primary visual cortex of the
occipital lobe, located in Brodmann area 17.

 The central region of Brodmann area 17 relays this information forward to Brodmann area 18,
where the visual association cortex is located.

 The visual association cortex is responsible for determining that the image of an object appears
blur and is out of focus. It occipitotectal fibers to the convergence center located in the midbrain,
as well as to the pretectal nuclei.

 The convergence center directly stimulates the part of the oculomotor nuclei
responsible for controlling the medial rectus muscles. Contraction of the medial rectus
muscles result in convergence of the eyes such that they look medially.

 The convergence center and pretectal nuclei individually stimulate the Edinger-
Westphal nuclei, acting as collateral routes. The parasympathetic output results in:

1. contraction of sphincter pupillae, leading to miosis

2. contraction of the ciliaris muscles, causing the lens to become more globular so that
light is focused for nearer vision.

These changes are collectively known as the accommodation reflex.

 Thus, the near response has three effector responses, all of which occur bilaterally: the
convergence response, effected by the medial rectus muscles, miosis, effected by sphincter
pupillae, and lens thickening, effected by ciliaris muscles.

204
Lesions Producing Abnormal Pupillary Light Reflexes

 Lesions to the afferent limb before the decussation of fibers at the optic chiasma (e.g. in optic
nerve) produce:

 An absent direct light reflex of the ipsilateral eye

 An absent indirect light reflex of the ipsilateral eye

 A positive direct light reflex of the contralateral eye

 A positive indirect light reflex of the contralateral eye

 Lesions to the afferent limb after the decussation of fibers at the optic chiasma (e.g. in optic
tract) leave direct and indirect pupillary light reflexes intact in both eyes.

 This is because there is a collateral afferent pathway provided by the contralateral optic tract,
superior brachium and the interconnection of the pretectal nuclei by the posterior commissure.

 Lesions to the efferent limb (involving connections from pretectal nuclei to the Edinger-
Westphal nuclei, as well as the preganglionic and postganglionic parasympathetic fibers carried
anywhere along CN III) produce:

 An absent direct light reflex in the ipsilateral eye.

 A present indirect light reflex in the ipsilateral eye.

 A present direct light reflex in the contralateral eye.

 An absent indirect light reflex of the contralateral eye.

 Argyll Robertson Pupil, or Prostitute’s Pupil, occurs when the pupillary light reflexes are absent
but the near response is intact. The prostitute “accommodates but does not react”.

 Some conditions, including neurosyphilis, diabetes and SLE, can cause bilateral
degeneration of the connection between the pretectal nucleus and Edinger-Westphal.

 In doing so, they disrupt the efferent limb of the pupillary light reflex, causing absent left
and right, direct and indirect reflexes.

 However, the connection between the convergence center and Edinger-Westphal nuclei
remains intact. Thus, the pupils can still constrict as part of the near response.

 This dissociation between the pupillary light reflex and the near response is known as
the Argyll Robertson Pupil. The acronym ARP should remind us that the Accommodation
Reflexes are Preserved.

 In another congenital condition known as the Ades Pupil, pupillary light reflexes are reduced,
and there is no accommodation reflex. Additionally, it is associated with absent knee jerk and
ankle jerk reflexes.

205
 In multiple sclerosis, a partial impairment of the optic nerve can occur, resulting in a relative
weakness of one optic nerve in comparison to the other.

 If the lesion is not permanent, some recovery can occur.

 In order to test if the recovery is complete, the swinging light reflex test is performed.

 A light is shone first in the eye without the lesion. A positive indirect pupillary light reflex
should be observed in the eye with the lesion.

 Subsequently, the light is shone in the eye with the lesion. If recovery of the optic nerve
is incomplete, the direct pupillary light reflex of that eye may produce a weaker
response, resulting in an apparent dilation of that pupil.

 This test result is known as the Marcus Gun Pupil.

206
Control of Conjugate Movement of the Eyes

 Conjugate eye movements occur when the visual axes of both eyes are directed in parallel such
that the image of an object in space is projected onto homologous points of both retinae so that
a unified image can be produced.

 Conjugation of eye movements requires intercommunication of left and right brainstem nuclei.

 The center responsible for the conjugate movement of the eyes is thought to be the
parapontine reticular formation center (PPRF).

 It lies immediately lateral to each of the abducens nuclei.

 Due to their close proximity, the abducens nucleus and the nucleus for conjugate
movements are sometimes considered as a single complex for simplicity. For practical
purposes we may assume this is the case.

 The PPRF acts as a “pull center”.

 It stimulates the ipsilateral abducens nucleus immediately lateral to it.

 It stimulates the contralateral oculomotor nucleus via an ascending tract that runs
within the medial longitudinal fasciculus.

 Thus, its action is to cause abduction of the ipsilateral eye, and adduction of the
contralateral eye, such that both eyes are “pulled” in its direction.

207
Searching & Tracking Eye Movements

 The PPRF is in turn controlled and manipulated by higher cortical centers which use them to
maintain conjugate movements of the eyes.

 Searching eye movements are controlled by the frontal eye fields.

 The frontal eye fields are located in the cerebral cortex, immediately anterior to the
postcentral gyrus, in the posterior part of the middle frontal gyrus.

 The frontal eye field of each cerebral hemisphere stimulates the contralateral PPRF,
thereby causing abduction of the contralateral eye and adduction of the ipsilateral eye.

 In doing so, it acts as a “push button”, pushing the eyes away from it, in contrast to the
PPRF which is a “pull button”.

 Tracking eye movements are controlled by the occipital eye fields.

 The occipital eye fields are located in the region of the visual association areas, and
control smooth pursuing movements when tracking an object moving in space.

 Like the frontal eye fields, the occipital eye fields connect to the contralateral PPRFs, in
this case work as slower “push buttons”.

Lesions to Searching & Tracking Movement Pathways

 A stable central gaze is maintained when the output of both frontal eye fields and both occipital
eye fields is equal bilaterally.

 Clinically, irritative lesions of either the frontal or occipital eye fields such as inflammation,
tumours and epileptic seizures can cause the gaze to be fixed in a direction away from the side
of the lesion.

 If the pathological process persists and the lesion becomes destructive, the gaze becomes fixed
in a direction towards the side of the lesion.

208
 These relationships are reversed if the lesion occurs to the PPRF rather than the frontal eye field.

 Multiple sclerosis is a central demyelinating disease. Rather than destroying cortices or

brainstem nuclei, it may disrupt the ocular movement pathways at the medial longitudinal
fasciculus (MLF), through which interconnections between the third, fourth, sixth and vestibular
nuclei run.

 The MLF is said to be on the same side as the oculomotor nucleus it is connecting to. (It
is therefore contralateral to the abducens nucleus it connects to.)

 In general, destruction of the MLFs produces a group of conditions known as

internuclear opthalmoplegias. These are in contrast to external and internal
opthalmoplegias, in which there is paralysis of the extraocular or intraocular muscles
due to destruction of their respective controlling nuclei.

 If one MLF is destroyed, the clinical presentation is as follows:

 Conjugate movement of the eyes in the ipsilateral direction are preserved. This is
because the pathway stimulated involves the ipsilateral abducens, the contralateral MLF
and the contralateral oculomotor nucleus, all of which remain intact.

 However, when the patient attempts to look away from the side of the lesion, the
contralateral eye will be able to abduct but the ipsilateral eye cannot adduct.

 This produces a diplopia of the eyes. The CNS detects this diplopia, and attempts to
reverse the movement to correct the image. The result is a horizontal nystagmus of the
abducting eye.

 If two MLFs are destroyed, the clinical presentation is as follows:

 Attempts to look in either direction will result in the ipsilateral eye being able to abduct
but the contralateral eye being unable to adduct.

 Diplopia and horizontal nystagmus of the abducting eye results.

 Note that the convergence pathway remains entirely intact in both scenarios.

 One-and-a-half Syndrome describes a rare scenario in which there is destruction of both MLFs
and one abducens nucleus-PPRF complex.

 The patient will be unable to look in the direction of destruction of the abducens nucleus.

 Upon attempting to look away from the direction of the destroyed abducens nucleus,
the adducting eye will be unable to adduct, while the abducting eye will abduct
intermittently but be involved in a horizontal nystagmus due to the diplopia that results.

209
Vertical Conjugation of Gaze & Vestibuloocular Movements

 Eye movements are conjugated not only in the horizontal axis, but in the vertical one as well.

 The center for vertical gaze resides in the midline of the posterior commissure, at the rostral end
of the MLF.

 It is variously named the rostral interstitial nucleus of MLF, rostral interstitial nucleus of
posterior commissure or simply the nucleus of Cajal.

 It communicates with the oculomotor and trochlear nuclei bilaterally, as these are the
nuclei which control the superior and inferior, rectus and oblique muscles involved in
vertical movements of the eye.

 Tumours of the pineal gland can cause Perinaud Syndrome, in which there are lesions to the
posterior midbrain due to the close proximity of these structures.

 The nearest structure that is usually affected is the nucleus of Cajal, and results in
disturbances of visual gaze.

 The convergence center, which lies just anterior to it, is also commonly affected.

 The nuclei of CN III remain intact at least initially, but may be also become involved
subsequently leading to oculomotor palsies.

 The vestibular nuclei connect to the nuclei controlling the extraocular muscles via the MLF in
order to control vestibulo-ocular movements.

210
Ocular Movements & Centers of Ocular Motility

 There are five main types of extraocular movements.

 The first three of these are conjugate movements, also called yoked movements: the visual axes
of both eyes are directed in parallel such that the image of an object in space is projected onto
homologous points of both retinae so that a unified image can be produced.

 Saccades, involve rapid movements of the eyes as they jump from one point of focus to another,
especially in the horizontal meridian. The eyes move so rapidly between points of movement
that the brain has little time to pick up images on the path inbetween.

 Pursuit movements are mediated by the go-there neurons found in the PPRF, or
parapontine reticular system.

 The PPRF receives input from the contralateral frontal eye field, and provides an output
to the ipsilateral 6th cranial nerve.

 Its role is to act as a “transformer” of the signal, increasing the rate of firing output to
produce a burst of action potentials that significantly speeds up the speed of eye
movements.

 Loss of the PPRF in isolation is rare, but leads to the loss of saccadic movements such
that testing of saccades produces slow, delayed movements (compensated by slow
pursuit tracking movement mechanism).

 Fixation reflex, which involve smooth tracking movements of the eyes especially in the
horizontal meridian as they track a gradually moving object.

 These movements are controlled by the stay-there neurons, located primarily in the
vestibulocerebellum as well as elsewhere in the brainstem.

 They receive input from the occipital eye fields and synapse onto the 6th cranial nerve
nuclei directly to produce slow pursuit.

 Loss of the “stay-there” neurons leads to the phenomenon of central nystagmus.

Clinically, when the patient is asked to look away from the central position of gaze
without moving the head, the eyes have a slow drift phase towards the central position,
regardless of which direction the patient is asked to look in.

 This central nystagmus is thus described as gaze-evoked and multidirectional.

 Optokinetic reflex also involves smooth tracking movements of the eyes and fixation, but
involuntarily on targets while the head is moving, e.g. when looking out the window in a car.

 The neurocircuitry is less well defined, but it is also controlled by a region of occipital
eye field localised to the occipitoparietal border.

 Clinically, damage to this region can be tested by asking the patient to look at a
measuring tape as it is unwound rapidly to determine region of infarct in MCA strokes.

211
 Vestibuloocular movements, which allow the eyes to maintain a fixed gaze while the head is
rotating. As its name suggests, it requires input from the vestibular system.

 It is controlled by input from the vestibular nuclei.

 Damage to the vestibular nuclei, or input from its nerves or apparatus, results in
“peripheral nystagmus”.

 Peripheral nystagmus is unidirectional; there are slow drifting movements towards the
side of the lesion, followed by fast corrective saccades away from the side of the lesion.
However, depending on the severity of the lesion, the nystagmus may not always be
readily apparent, or may be more apparent in some positions of gaze than others.

 Clinically, this is tested with the head impulse test. The patient’s eyes are fixed on the
examiners nose while the head is rotated left and right.

 Initially, the eyes are able to maintain its fixation due to compensation from the fixation
reflex; one should not be fooled by this.

 Rapidly turning the head (ensure no cervical injuries) towards the side of injury results in
the gaze deviating towards that side, followed by a fast corrective saccade back to
central gaze.

 Convergence movements involve an adduction of both eyes to focus on an object as it moves

from a far distance to near.

 This is controlled by a convergence center located in the midbrain, projecting onto the
two third nerve nuclei.

 Clinically it is part of the near response earlier described, and is demonstrated to look
for the prostitute’s pupil, which reacts but does not accommodate.

 All of these nuclei and mechanisms described above are for horizontal eye movements; they
have vertical counterparts located in the midbrain, some more well described than others.

212
EXTRAOCULAR MUSCLE NERVE PALSIES (CN III/
CN IV/ CN VI)
CN III (Occulomotor) palsies

 The oculomotor nerve carries:

 General Somatic Efferent (GSE) fibers from the oculomotor nucleus

 Parasympathetic General Visceral Efferent (GVE) fibers from the Edinger-Westphal

nucleus

 Its fibers exit from the medial side of the cerebral peduncles, emerging from within the
interpeduncular fossa to run in the lateral wall of the cavernous sinus.

 From here, it exits the anterior cranial fossa via the superior orbital fissure, and enters the
orbit.

 Within the orbit, it divides into a superior branch and an inferior branch.

 The superior branch carries GSE fibers to the superior rectus and the levator
palpebrae superioris.

 The inferior branch carries GSE fibers to the medial rectus, inferior rectus and
inferior oblique oblique.

 The inferior branch also carries parasympathetic fibers to the ciliary ganglion, which
eventually provide fibers to the ciliaris and sphincter pupillae muscles.

213
 Loss of GSE fibers in oculomotor palsies leads to the following effects:

 There is loss of innervation of all the extraocular muscles except superior oblique
(CN IV) and lateral rectus (CN VI).

 The action of superior oblique is abduction, depression and internal rotation of the
eye. The action of lateral rectus is abduction of the eye.

 Thus, the affected eye will demonstrate an outward and downward gaze.

 Additionally, the oculomotor nerve provides GSE supply to levator palpebrae

superioris. Although the superior tarsal muscle attached to it is innervated by
sympathetic supply and aids in elevation of the eyelid, levator palpebrae superioris
paralysis is sufficient to cause a complete ptosis.

 Loss of parasympathetic fibers in oculomotor palsies leads to the following effects:

 Loss of innervation to sphincter pupillae leads to pupilar dilation (mydriasis).

Anisocoria describes unequal pupil size in the left and right eyes.

 Loss of innervation to ciliaris muscle leads to failure of accommodation and

cycloplegia.

 However, not all etiologies of oculomotor palsies cause loss of both types of fibers; indeed,
some may cause increased activity rather than decreased activity of some fibers.

 Compression of the oculomotor nerve by supratentorial lesions is one possibility.

 Within the oculomotor nerve, the parasympathetic fibers run mainly in the
periphery of the nerve and surround the GSE fibers. The parasympathetic fibers are
particularly concentrated in the superior part of the nerve.

 Compression of the oculomotor nerve usually leads first to irritation of the

parasympathetic fibers, leading to increased parasympathetic activity.

 Excessive parasympathetic stimulation leads to miosis of the pupil rather than

mydriasis. Unexplained miosis in a single eye is a red flag for compression of the
oculomotor nerve, which is a surgical emergency.

 Eventually, the parasympathetic fibers may be destroyed, leading to loss of

parasympathetic activity; finally, the GSE fibers may also be destroyed.

 Another possible cause of compression of the oculomotor nerve is an aneurysm of the circle
of willis, particularly in the posterior communicating and posterior cerebral arteries.

214
 Finally, diabetes is an important metabolic cause of cranial neuropathies in general.

 In diabetes, it is more likely for GSE fibers to be lost before parasympathetic fibers are
lost.

 Thus, patients may not present with pupilar dilation or cycloplegia.

CN IV (Trochlear) Palsies

 Each trochlear nucleus give fibers to the contralateral trochlear nerve, which exits from the
posterior midbrain at the level of the inferior colliculus, runs in the tentorium cerebelli to pass
into the lateral wall of cavernous sinus. It exits the superior orbital fissure above the tendinous
ring.

 The trochlear nerve innervates the superior oblique muscle.

 The action of the superior oblique is normally to adduct and depress the eye, as well as
cause internal rotation of the eye.

 This adduction and internal rotation is physiologically compensated for by the abduction
and external rotation of the eye by the inferior rectus, which also depresses the eye.

 Failure of the trochlear nerve hence leads to an inward and downward gaze in the affected eye.
Additionally, there is external rotation of the eye.

 The external rotation of the eye may be detected by observing the blood vessels of the
sclera.

 The external rotation, in combination with the inward and downward gaze, lead to
diplopia. The diplopia is especially exaggerated during activities which require a
downward gaze (e.g. walking down the stairs).

 In order to compensate for the external rotation, the patient may tilt his head away
from the side of the lesion.

 Trochlear nerve palsies rarely occur in isolation; they may be present in cavernous sinus
syndrome, to be described subsequently.

215
CN VI (Abducens) Lesions

 The abducens nucleus takes origin from the inferior pons. Its cranial nerve exits from the medial
part of the pontomedullary junction.

 This nerve ascends on the clivus and enters the middle cranial fossa by crossing the
sharp demarcation separating the anterior and posterior surfaces of the petrous part of
the temporal bone.

 Due to its course, it is easily damaged when there are infratentorial lesions, which may
cause downward herniation of the rhombencephalon. This is in contrast to oculomotor
nerve palsies which tend to be affected by supratentorial lesions.

 It subsequently runs in the cavernous sinus with the other cranial nerves controlling the
extraocular muscles.

 The abducens nerve is responsible for abduction of the eye via the lateral rectus muscle. CN VI
lesions thus result in adduction of the affected eye.

Cavernous Sinus Syndrome

 Cavernous sinus syndrome may be caused by an aneurysm of the internal carotid artery as it
runs through the cavernous sinus.

 It may compress on CN III, IV, V1, V2 and IX, which all run through the cavernous sinus.

 Additionally, it may cause loss of sympathetic fibers from the carotid plexus. These provide
sympathetic innervation to

 Lacrimal gland via the deep petrosal nerve.

 Dilator pupillae through a nerve whose fibers may enter the eye directly, run with the
oculomotor nerve or ophthalmic nerve, or pass through the ciliary ganglion.

216
Supratentorial Herniation Syndrome

 Supratentorial herniation occurs when there is a raised intracranial pressure above the level of
the tentorium cerebelli.

 It results in a downward pressure on the cerebral hemispheres, such that the uncus of one
temporal lobe herniates through the tentorial notch.

 In doing so, it disrupts a number of structures, both ipsilaterally and contralaterally.

 It compresses on the ipsilateral oculomotor nerve.

 As the parasympathetic fibers of the oculomotor nerve run on the periphery of the
nerve, particularly in the superior part, they are the first fibers to be affected.

 Initially, an irritative lesion to these parasympathetic fibers occurs, resulting in overfiring

of the parasympathetic fibers. There is thus ipsilateral pupillary miosis.

 Subsequently, a destructive lesion may result, to the parasympathetic fibers and

eventually to the somatic motor fibers. An ipsilateral mydriasis and palsy of the somatic
oculomotor fibers can result. Conjugation of gaze is lost.

 It compresses on the ipsilateral optic tract.

 This results in contralateral homonymous hemianopia.

 Additionally, the ipsilateral posterior cerebral artery may be disrupted, and further
ischemia to the optic tract can exacerbate the problem.

 Due to the herniation, the brainstem bends laterally in such a manner that the contralateral
corticospinal tracts are rubbed against the tentorial notch.

 These corticospinal tracts have not yet crossed, and actually control motor function on
the same side of the body as the side of initial uncal herniation.

 This results in motor weakness or paralysis of the fibers on the same side of the uncal
herniation.

 There may also be damage to the paramedian arteries supplying the brainstem which can cause
Duret brainstem haemorrhage.

217
 Finally, another sign of raised intracranial pressure related to the visual system is papilledema of
the optic disc, leading to blurring of its margins. This was previously described in the chapter on
meninges and CSF.

 Briefly, it occurs because the optic nerve is surrounded by all meningeal layers as well as
a CSF-filled subarachnoid space, which is continuous with that surrounding the brain.

 Raised intracranial pressure results in compression of the optic nerve, as well as the
central retinal vein running within it. The central retinal artery however, remains patent
as it is less compressible.

 This results in congestion in the region of the optic disc, leading to blurred margins.

218
TRIGEMINAL SYSTEM AND LESIONS
Sensory Component of Trigeminal System

 The trigeminal system has both sensory and motor components. The sensory component
receives input from the head and neck via the ophthalmic, maxillary and mandibular divisions.

 CN V1 the ophthalmic division enters the middle cranial fossa from the orbit via the
superior orbital fissure.

 CN V2 the maxillary division enters the middle cranial fossa from the pterygopalantine
fossa via the foramen rotundum.

 CN V3 the mandibular division enters the middle cranial fossa from the base of the skull
via the foramen ovale.

 CN VII, IX and X also send sensory input from the ears via auricular branches to the
trigeminal system.

 The trigeminal ganglion is formed by the cell bodies of sensory neorons from all three divisions.

 It lies in Meckel’s cave, which is a compartment lined by a double-layer of dura mater

found in the medial part of the middle cranial fossa, at the tip of the petrous part of
temporal bone, immediately behind the cavernous sinus.

 Meckel’s cave this lies directly over the opening of the carotid canal and the foramen
lacerum into the middle cranial fossa.

 The trigeminal ganglion is highly unusual, in that it contains cell bodies for neurons
conveying the sense of pain, temperature and fine touch, but neurons conveying the
sense of proprioception do not have a cell body in the trigeminal ganglion; instead, their
cell bodies lie in the CNS directly forming the mesencephalic nucleus of trigeminal system.

 The sensory root arises from the trigeminal ganglion and enters the pons with the motor root.
Within the CNS, different modalities of the sensory system take different paths.

219
 Pain/ temperature are conveyed to the spinal trigeminal nucleus via the spinal trigeminal tract.

 The spinal trigeminal nucleus lies inferiorly in the medulla, and extends as far down as
the superior cervical region of spinal cord.

 The spinal trigeminal nucleus is itself split into a superior part and an inferior part.

 The superior part receives pain/ temperature input specifically for the corneal reflex.
The reflex arc travels from the eyeball via long ciliary nerves, the nasociliary branch, the
ophthalmic division, trigeminal ganglion and sensory root to the superior part of the
spinal trigeminal nucleus, and forms a reflex arc to the facial branchiomotor nucleus to
cause blinking.

 The inferior part receives pain/ temperature input from the rest of the head and neck,
including the ears via the auricular branches of CN VII, IX and X.

 From the spinal trigeminal nucleus, pain and temperature is conveyed upwards via the
ascending ventral trigeminothalamic tract which crosses to the contralateral side. It is
the brainstem equivalent of the anterolateral spinothalamic tract.

 Fine touch is conveyed to the principle pontine nucleus.

 Proprioception is conveyed to the mesencephalic nucleus of the trigeminal system; recall that
the first order neurons for proprioception of the head and neck lie here in the CNS, and do not
lie in the trigeminal ganglion as it does in other peripheral sensory ganglia throughout the body.

 The dorsal trigeminothalamic tract brings fine touch and proprioception from the principle
pontine nucleus and mesencephalic nucleus respectively upwards on the ipsilateral side,
uncrossed. It is the equivalent of the dorsal column medial lemniscus (although the dorsal
column medial lemniscus eventually crosses at the medulla, but to our knowledge the dorsal
trigeminothalamic tract is unusual for ascending all the way to the thalamus uncrossed.)

 The trigeminal lemniscus is formed from the fusion of the contralateral ventral and ipsilateral
dorsal trigeminothalamic tracts, and synapses onto the ventroposteromedial or VPM nucleus of
the thalamus.

 Recall the VPL nucleus conveys GSA sensation from the rest of the body, while the VPM
nucleus conveys GSA sensation from the head and neck as well as taste from the nucleus
tractus solitarius.

 The lateral geniculate body is involved in the transmission of vision.

 The medial geniculate body is involved in the transmission of auditory input.

 Olfactory input is the only sense to bypass the thalamus and associated structures
altogether.

 The posterior limb internal capsule and corona radiata then convey the fibers to the lateral part
of the primary somatosensory cortex located in the postcentral gyrus.

220
Motor Component of Trigeminal System

 The motor component of the trigeminal system involves control by the trigeminal
branchiomotor nucleus, which provides output to the muscles of the first pharayngeal arch:

 Muscles of mastication, including those which close the jaws (temporalis, masseter,
medial pterygoids) and those which open the mouth (lateral pterygoid).

 Mylohoid and anterior belly of digastric.

 Tensor tympani and tensor veli palatine.

 Beware these muscles receive not only motor innervation, but also have sensory
innervation especially for the sense of proprioception which allows perception of the
strength of biting via small movements in position of the teeth, etc.

221
Corneal Reflex

 Corneal reflex is important in protecting the cornea, especially in situations of a CN VII palsy in
which the absence of the corneal reflex increases the risk of exposure keratitis.

 The reflex is tested by using a piece of clean cotton wool to touch the cornea.

 Sensory input travels via the long ciliary fibers, the nasociliary branch, the ophthalmic
division to the trigeminal ganglion and then to the inferior part of the spinal trigeminal
nucleus.

 From here, a reflex arc synapses onto the facial branchiomotor nucleus.

 The output is via the facial nerve and its temporal and zygomatic branches to the
orbicularis oculi, where it produces blinking.

222
Lacrimatory Reflex

 Lacrimatory reflex is induced by touching the conjunctiva.

 Sensory input is conveyed via the ophthalmic division of trigeminal nerve as before.

 Output is via the lacrimatory nucleus, nervus intermedius root of CN VII, the greater
petrosal nerve which leaves the facial canal at the genu, enters the foramen lacerum to
join sympathetic fibers from the carotid plexus to form nerve of pterygoid canal.

 The nerve of pterygoid canal then synapses onto the pterygopalatine ganglion of the
maxillary nerve, travels along its zygomatic branch into the orbit, and then jumps to the
lacrimal branch of the ophthalmic division of the trigeminal nerve to the lacrimal gland,
inducing lacrimation.

Other Reflexes

 The jaw jerk reflex is a deep tendon reflex that tests for UMN syndrome of the trigeminal
branchiomotor output.

 The stimulus is a tap on the chin of the open jaw with a tendon tapper, which stretches
the masseter abruptly, producing a proprioceptive stimulus.

 The stimulus is sent via a reflex arc through the mandibular division of trigeminal nerve
to the mesencephalic nucleus of the trigeminal system.

 A monosynaptic reflex arc is formed by fibers that synapse back onto the trigeminal
branchiomotor nucleus. Recall that proprioceptive input in the trigeminal system does
not have a pseudounipolar cell body in the trigeminal ganglion, and the first order
neuron is in the mesencephalic nucleus!

 The output is for the masseter to contract, jerking the jaw upwards.

 The reflex is normally weak or absent; a strong reflex indicates UMN syndrome.

 Oculocardiac reflex involves a slowing of the heart rate, producing bradyarrythmias, when
traction is applied to the extraocular muscles or the eyeball is compressed. It occurs during
strabismus surgery and is mediated by the dorsal nucleus of vagus.

223
FACIAL NERVE AND ITS LESIONS
Nuclei of Facial Nerve

 CN VII, the facial nerve, conveys fibers between the periphery and 5 brainstem nuclei.

 Facial branchiomotor nucleus supplies SSE fibers. It is located in the posterior pontine region.

 The top half of each facial branchiomotor nucleus that supplies the forehead receives
dual innervation from corticonuclear UMNs of both cerebral hemispheres, and is not
impaired in unilateral UMN injuries. The lower half is innervated by contralateral cortex.

 Its output fibers loop posteriorly and medially around the abducens nucleus before
hooking laterally and anteriorly again to exit the brainstem. Nuclear lesions of CN VII are
likely to occur in the posterior pontine area and are likely to involve CN VI as well due to
their close proximity. Lesions of these nuclei should lead to imaging of this area.

 Posterior colliculus is an elevation of pontine part of the floor of the 4th ventricle formed
from the output fibers of the nucleus as it loops around the abducens nucleus.

 The outputs of the facial branchiomotor nucleus are SSE fibers to the 2nd pharyngeal
arch, including the stapedius, muscles of facial expression, posterior auricular muscle
(vestigial in humans), stylohyoid and posterior belly of digastric muscles.

 Lacrimatory nucleus, which is likely also controlled by UMNs descending in a polysynaptic

connection from the hypothalamus, supplies GVE fibers to the lacrimatory gland, nasal mucosa
and mucosa of the soft/ hard palates.

 Superior salivatory nucleus, which is the inferior counterpart to the lacrimatory nucleus,
supplies GVE fibers to the sublingual and submandibular glands via the chorda tympani.

 Trigeminal nucleus receives GSA fibers from tympanic membrane and external auditory canal.

 Nucleus tractus solitarius receives SVA taste fibers from anterior 2/3 tongue.

 Controversially, it is said that either the nucleus tractus solitarius or dorsal motor nucleus of
vagus may also receive GVA fibers from the soft and hard palate. Clinical relevance is limited.

224
Internal Acoustic Meatus and Facial Canal

 CN VII fibers exit the brainstem at the pontomedullary junction between CN VI and CN VIII, via:

 Facial nerve proper, which carries fibers from the facial branchiomotor nucleus.

 Nervus intermedius, which carries fibers to and from the other four nuclei.

 These fibers can be compromised by cerebellopontine angle lesions.

 They enter the internal acoustic meatus together with CN VIII, and then enter the facial canal.

 The geniculate ganglion is found at the genu (knee, or bend) of the facial nerve as it enters the
facial canal at the medial wall of inner ear, before the fibers pass posteriorly along this wall.

 The geniculate ganglion contains cell bodies akin to those of the dorsal root ganglion, for
the GVA fibers being received from the tympanic membrane and external acoustic
meatus but also for the SVA taste fibers from anterior 2/3 of tongue.

 Not all fibers continue into the facial canal at this point; the parasympathetic GVE fibers
from the lacrimatory nucleus exit at this point, forming the greater petrosal nerve.

 The controversial fibers that supply GVA sensation from the soft and hard palate are
thought to exit with the greater petrosal nerve at the genu, bound for its destination.

 In Ramsay Hunt Syndrome, reactivation of VZV virus from the GSA part of the
geniculate ganglion results in lesions to CN VII.

 The remaining fibers pass posteriorly in the facial canal along the medial wall, until it reaches the
posterior wall.

 At the posterior wall, the fibers turn abruptly to descend inferiorly, to exit in various ways.

 In particular, a general concept is that all parasympathic fibers of CN VII, whether they exit
before or after the genu, distribute via and are closely related to all three branches of the
trigeminal nerve, as we shall see.

225
Greater Petrosal Nerve

 Greater petrosal nerve exits the internal acoustic meatus before the genu of the facial nerve,
just proximal to the geniculate ganglion.

 It carries parasympathetic GVE fibers from the lacrimatory nucleus, and also the
controversial GVA fibers from the soft and hard palate inbound for the dorsal motor
nucleus of vagus or the nucleus tractus solitarius.

 The greater petrosal nerve enters the middle cranial fossa and runs in the groove for
greater petrosal nerve, and then runs towards the carotid artery, joining it in the region
of the foramen lacerum.

 At foramen lacerum, it combines with deep petrosal nerve sympathetic fibers from the
internal carotid plexus to form the nerve of pterygoid canal. The nerve of pterygoid
canal runs through the pterygoid canal of the sphenoid bone to emerge on the other
side in the pterygopalatine fossa.

 Here it supplies fibers to the pterygopalatine ganglion and then jumps to fibers of CN V2
the maxillary nerve, which then split three ways.

 Some fibers exit via the sphenopalatine fossa to innervate nasal mucosa.

 Some fibers join the greater palatine nerves to innervate the mucosa of the hard and
soft palate.

 Some fibers join the zygomaticotemporal nerve to enter the orbit, then jump to fibers
of CN V1 opthalmic nerve’s lacrimatory branch to innervate the lacrimal glands. These
are not to be confused with the parasympathetic fibers of ciliary ganglion running with
the oculomotor nerve.

226
227
Chorda Tympani

 Chorda tympani is a nerve so named because it was thought by early anatomists to be a cable
running through the middle ear.

 It takes origin from the posterior wall of middle ear along the descending part of the
facial canal, and passes anteriorly through the middle ear to exit via its anterior wall.

 It carries superior salivatory parasympathetic GVE fibers and SVA taste fibers to and
from the anterior 2/3 of tongue.

 After exiting via the anterior wall, it joins the lingual branch of CN V3 the mandibular
nerve to supply the sublingual glands, submandibular glands and taste receptors.

228
Other Terminations of Facial Nerve

 GSA fibers being received by the trigeminal nucleus exit via the auricular branch of the facial
nerve within the descending part of the facial canal, to supply part of the tympanic membrane
and part of the external auditory meatus.

 GSE fibers originating from the facial branchiomotor nucleus exit via a number of branches:

 Nerve to stapedius exits along the descending part of the facial canal to supply
stapedius muscle. Contraction of the stapedius results in increased tension on the stapes
bone, whose footplate is attached to the oval window, reducing the transmission of
sound when sounds are too loud. Damage to this function results in hyperacusis.

 Main branch of facial nerve exits via the stylomastoid foramen, and runs in the
substance of the parotid gland to divide into 5 main branches, the temporal, zygomatic,
buccal, marginal mandibular and cervical branches.

 Other less clinically important branches include to the occipital part of occipitofrontalis,
posterior auricular muscle, posterior belly of digastric muscle and the stylohoid muscle.

UMN Supply of Facial Branchiomotor Nucleus

 The facial branchiomotor nucleus, like any other LMNs, receives innervation from UMNs of the
cerebral cortex.

 These corticonuclear fibers (classified as part of pyramidal tracts) descend via corona
radiata, posterior limb of internal capsule, middle 3/5 of crus cerebri of midbrain,
diffusely through the pontine nuclei before synapsing on the facial branchiomotor
nucleus. (It does not pass through the major motor crossing of the medulla unlike
corticospinal pyramidal tracts).

 The top half of each nucleus supplying the forehead, receives bilateral UMN innervation ,
i.e. from both cerebral hemispheres. The lower half of the nucleus receives UMN
innervation only from the contralateral cerebral cortex.

229
Facial Nerve Reflexes

 A variety of facial nerve reflexes exist, with varying levels of clinical relevance.

 Corneal reflex is perhaps the most important and must be tested in any CN VII palsy. The
afferent limb is via CN V and the efferent via CN VII; its impairment is a risk factor for the
development of dry eyes and exposure keratitis of the cornea in particular.

 Suckling reflex is seen in babies: stimulation of the trigeminal nerve by stroking of the cheek
results in a reflex arc via the pontine nucleus of trigeminal nerve to the facial branchiomotor
nucleus to produce activation of the buccinators muscles and a suckling reflex.

 Stapedius sound attenuation reflex occurs in response to loud sounds; the pathway travels from
the organ of corti to the cochlear nerve, cochlear nuclears and ascends in the lateral lemniscus.

 Some fibers terminate on the superior olivary nucleus, which is responsible for the
control of volume.

 The superior olivary nucleus activates the facial nerve to produce contraction of the
stapedius muscles, reducing the volume of sounds.

 Hyperacusis is a feature of facial nerve palsies due to impairment of the stapedius reflex.

 Audionuclear reflex involves physical reflexes in response to loud sounds, as a survival response.
From the cochlear nucleus, some fibers travel to the inferior colliculus, which then descends to
the facial nerve to produce closing of the eyes etc. as part of this reflex.

 Visualnuclear reflex involves blinking in response to light: the afferent limb travels from the
retina via the optic nerve, optic chiasma and optic tract to enter the midbrain, where it synapses
at the superior colliculus.

 Emotional reflexes control the function of the face, with a pathway from the nucleus
accumbens to the facial branchiomotor nucleus. This is responsibly for involuntary facial
expressions in response to emotional stimuli. Loss of the nucleus accumbens is responsible for a
mask-like face in Parkinson Disease.

230
Examination of Motor Component of Facial Nerve

 The motor component of the facial nerve produces the most readily apparent deficits in facial
nerve palsies, and is readily amenable to examination. It also allows for neurolocalisation.

 Examination of the facial nerve involves checking for:

 Facial asymmetry, which is often the first clue available on general inspection that the
facial nerve should be carefully examined. Beware that in diplegias the face may actually
be symmetrical, but there may be loss of the wrinkling of the forehead, ectropion of the
lower eyelid, loss of the nasolabial fold and asymmetry of the corners of the mouth.

 Wrinkling of the forehead by raising his eyebrows or looking up, which tests the
function of the temporal branch.

 Eye closure, which should bury the eyelashes if function is appropriate. This tests the
function of the temporal and zygomatic branches. If the patient is unable to close their
eyes, check for function of the Bell’s phenomenon in which eyeballs roll up and out
during eye closure; loss of the reflex increases risk of corneal exposure keratitis. The risk
of this is reduced by using eyedrops, taping the eyes shut when sleeping at night, using
an eyepatch, lateral tarsorraphy to stitch lateral eyelids together, or plastic surgery.

 Puffing out of the cheeks, which tests for the function of the buccal branch.

 Smile, which tests for function of the marginal and buccal branch. Facial palsy causes
corner of the mouth on affected side to be pulled inappropriately to contralateral side.

 Platysma activation, by asking the patient to pull down the corners of his mouth, tests
the function of the cervical branches. This step is not routinely performed on the 7th
nerve screening as patients may find it difficult to follow this instruction.

 Complications of facial nerve lesions include:

 Dry eyes and possibly exposure keratitis due to failure of closure of the eyes, and
depending on the site of the lesion possibly loss of lacrimation.

 Tearing, usually if lacrimation is till active, can paradoxically occur due to loss of tone in
the orbicularis oculi and ectropion of the lower eyelid, causing a pooling of tears.

 Difficulty chewing due to loss of the buccinator.

 Drooling of saliva due to loss of function of orbicularis oris and related oral muscles.

 Hyperacusis on affected ear due to loss of function of stapedius which maintains resting
tone on the stapes bone and the tympanic membrane to reduce excessive vibration.

 Loss of taste on ipsilateral tongue and dry mouth due to involvement of the SVA taste
fibers and GVE parasympathetic fibers travelling in chorda tympani.

231
Neurolocalisation of Facial Nerve Lesions

 First, determine if the lesion is a diplegia or monoplegia.

 Diplegia results in loss of function of both sides of the face. Differentials include:

 Moebius Syndrome, which manifests with congenital occulofacial paralysis due to

weakness of both CN VI and VII nuclei. Impaired abduction of the eyes leads to
convergent strabismus, which accompanies the facial diplegia.

 Lyme Disease, caused by borrelia burgdoferi, suggested by an appropriate travel history

with tic bites in outdoor areas. There may be other features of Lyme Disease (e.g.
characteristic rash, migratory arthritis, arrhythmias). Note that removal of the tic before
all the bacteria have been transferred may reduce the dose of bacteria received.

 Guillan Barre Syndrome, with an ascending polyneuropathy.

 Sarcoidosis.

 Monoplegia results in loss of function of one half of the face. It is possible to distinguish
between supranuclear (UMN), nuclear (LMN) and infranuclear (LMN) lesions on the basis of the
facial nerve examination and examination of the limbs.

 Supranuclear UMN lesions may occur in the cortex, corona radiata, posterior limb internal
capsule, crus cerebri and superior pons. There is:

 Contralateral facial hemiparesis with forehead sparing. This occurs because the upper
half of each facial nucleus, responsible for forehead wrinkling and eye closure, receives
dual UMN innervation from both hempisheres; the risk of exposure keratitis is reduced.

 Contralateral body hemiparesis with UMN syndrome, as corticospinal UMNs controlling

the hemibody travel in these same structures as the corticonuclear UMNs to the facial
nucleus.

 In particular, these features may be more dense (hemiparesis rather than hemiplegia)
when lesions occur in the region of the posterior limb internal capsule and crus cerebri,
as the descending pyramidal tracts are most condensed in these regions.

232
 Nuclear LMN lesions occur at the level of the pons where the facial branchomotor nucleus is
located. There is:

 Ipsilateral facial hemiparesis without forehead sparing. The entire facial nucleus is
obliterated, and the risk of exposure keratitis is increased.

 Ipsilateral abducens nerve palsy is frequent, due to the close relationship of the facial
branchomotor nucleus and the abducens nucleus. There is failure of abduction of the
ipsilateral eye.

 Contralateral body hemiplegia with UMN syndrome as the pyramidal tracts to the
contralateral body have not yet crossed (they cross at the level of the medulla). This
effect may be relatively diffuse due to the dispersed nature of the fibers as they pass
through the pons, separated by the pontine nuclei.

 Infranuclear LMN lesions occur below the level of the facial branchiomotor nucleus. There is:

 Ipsilateral facial hemiparesis without forehead sparing.

 No abducens nerve involvement and usually no contralateral body hemiplegia, unless

the lesion is caused by some diffuse process (see below).

 Additional clues are often present to further neurolocalise the lesion.

233
Further Neurolocalisation of Infranuclear Lesions.

 Infranuclear LMN lesions can be further neurolocalised depending on the accompanying

features. Lesions from proximal to distal may include:

 Multiple sclerosis can very rarely cause an infranuclear facial nerve palsy.

 This occurs where the proximal part of the facial nerve axons, before it has exited the
brainstem, is myelinated by oligodendrocytes affected in MS.

 There may be other accompanying features of MS, e.g. poor vision, Marcus gunn pupil,
internuclear opthalmoplegias.

 CP angle lesions, either due to acoustic neuromas or meningiomas, often suggested by

accompanying deficits of CN VIII, CN V, CN IX and cerebellum due to proximal extension of the
tumours from the acoustic canal to involve structures of posterior cranial fossa.

 Ramsay Hunt Syndrome, due to reactivation of VZV virus from the GSA part of the geniculate
ganglion.

 There is a characteristic burning pain in the ears; Otoscopy reveals herpetic vesicles on
the tympanic membrane and middle ear hemorrhagic fluid.

 Acyclovir may be prescribed but clinical evidence to support its use is not available.

 Choleasteatoma and chronic supparative otitis media may be seen on otoscopy as well.

 Base of skull lesions may produce involvement of the base of skull club of nerves, including CN
IX, X, XI and XII. Lesions include:

 Tuberculous base of skill meningitis; search for characteristic features of chronic low-
grade fever, night sweats, loss of weight possibly with respiratory symptoms (cough,
purulent hemoptysis), neck stiffness for meningitis and bone pain for gummas.

 Chronic fungal meningitis.

 Base of skull trauma, especially with deep sea diving barotrauma, can also cause a
facial nerve palsy as suggested by the history.

 Parotid gland tumours can result in involvement of facial nerve, and may be palpable.

 Diffuse processes which can involve the facial nerve include:

 Diabetes, as a microangiopathic complication as part of a neuropathy.

 HIV infection and Lyme Disease.

 Polio virus

 Sarcoidosis. CN VII palsy may be the most common CNS complication of sarcoidosis.

234
Diskinesis – Complication of Facial Nerve Palsy Recovery

 Diskinesis is a rare phenomenon of aberrant facial nerve regeneration.

 Under normal circumstances, Wallerian degeneration of the distal stump of the nerve
occurs, and subsequently regeneration of the nerve fibers occurs in sprouts.

 The sprouts of new fibers then attempt to regenerate towards their original site of
action, guided by the Schwann cell architecture and relevant chemokine stimulants.

 Occasionally, the fibers may regenerate to innervate the wrong structure, resulting in
diskinesis.

 There are two main types of diskinesis:

 Autonomic diskinesis may involve aberrant regeneration of the parasympathetic fibers

of the lacrimatory and superior salivatory nuclei, such that fibers to the lacrimatory
gland and salivatory glands are crossed. Stimuli of salivation may result in tearing.

 Branchiomotor diskinesis involves crossed, aberrant regeneration of the branchiomotor

fibers to innervate the wrong structures. Attempts to make one facial movement (e.g. to
smile) may result in another facial movement (e.g. concomitant winking of the eye). It
can be treated with surgery.

235
BLOOD SUPPLY TO CENTRAL NERVOUS SYSTEM
Overview of Arterial Supply to CNS

 Vascular events or disease are the most common cause of neurological dysfunction in the US. An
understanding of the territories of supply by the different blood vessels will allow correlation of
neurological defects with the specific vascular lesion, so that the lesion may be isolated.

 15% of cardiac output is dedicated to the central nervous system. This supply is provided via two
separate but interconnected systems:

 The carotid system, which supplies blood via the internal carotid arteries. It is also
known as the anterior system.

 The vertebrobasilar system, which supplied blood via the vertebral and basilar arteries.
It is also known as the posterior system.

 The carotid system and vertebrobasilar system, upon entry to the CNS, lie in the subarachnoid
space floating in CSF. Thus, ruptured berry aneurysms of these systems cause subarachnoid
haemorrhage. Deep perforating branches from this system penetrates the substance of brain.

 The internal carotid arteries take origin from the common carotid arteries.

 The right common carotid takes origin from the brachiocephalic trunk, whereas the left
takes origin directly from the arch of the aorta.

 Each internal carotid artery ascends through the carotid sheath, and enters the skull
from its base through the carotid canal.

 The vertebral arteries take origin from the first part of the ipsilateral subclavian artery.

 They pass posteriorly into the vertebral compartment of the neck, and ascend through
the foramina transversium of cervical vertebrae CI to CVI.

 They enter the skull through the foramen magnum, piercing dura mater and arachnoid
mater at this point to lie in the subarachnoid space.

236
Vertebrobasilar System

 Upon piercing the dura mater and subarachnoid mater at the foramen magnum, the vertebral
arteries run superomedially on the surface of the medulla.

 They unite at the level of the pontomedullary junction to form the basilar artery.

 The basilar artery ascends to the level of the midbrain, at which point it bifurcates into the two
terminal posterior cerebral arteries just above the origin of the oculomotor nerves. The
posterior cerebral arteries supply posterior cerebral hemispheres and associated midbrain.

 Before uniting to form the basilar artery, the vertebral arteries give off the following branches:

 The bilateral posterior inferior cerebellar arteries (PICA) supply the posterior aspect of
the inferior surface of the cerebellum and the associated lateral part of the medulla.

 The bilateral anterior inferior cerebellar arteries (AICA) supply the anterior aspect of
the inferior surface of the cerebellum and the associated lateral part of the pons. AICA
may either take origin from the distal ends of the vertebral arteries or the proximal part
of the basilar artery.

 Each vertebral artery also gives rise to one contributing branch each to the single
midline anterior spinal artery, which runs inferiorly in the anterior median fissure of the
spinal cord.

 The vertebral arteries also give rise to the bilateral posterior spinal arteries, either
directly, or indirectly as a branch of PICA. They run inferiorly just behind the posterior
roots of the spinal cord.

237
 The anterior spinal artery supply the anterior 2/3s of the spinal cord in transverse section.

 Both anterior and posterior spinal arteries receive collateral supply along their entire
length via segmental branches, from the deep cervical arteries (branch of costocervical
trunk), intercostal arteries and lumbar arteries.

 These segmental branches divide into anterior and posterior reticulate arteries. The
anterior reticulate arteries reinforce the anterior spinal artery, while the posterior
reticulate arteries reinforce the posterior spinal arteries.

 Of these, usually one of the left intercostal arteries gives off an especially large collateral
supply via the Great Medullary Artery of Adamkiewicz, which has a variable origin.

 Even under physiological conditions, however, the anterior spinal cord in the region of
TIV and LI receive relatively low perfusion, being just proximal to the collateral supply.

 In the event of occlusion of the origin of the anterior spinal artery or its contributing
vertebral arteries, the first areas to undergo infarction are the anterior 2/3 of the spinal
cord at the level of TIV or LI.

 The posterior spinal arteries supply the posterior 1/3 of the spinal cord in transverse section.

 It is reinforced by the posterior reticulate arteries of the segmental branches from deep
cervical, intercostal and lumbar arteries.

 Like the anterior spinal arteries, some areas are physiologically underperfused and
highly vulnerable to infarct in the event of occlusion of an anterior spinal artery.

 For the posterior spinal arteries, this area spans the levels of TI, TII and TIII.

 The major branches supplied by the basilar artery, from inferior to superior, are:

 The labyrinthine arteries (shown below) pass laterally from posterior cranial fossa to
enter the internal acoustic meatus, where it provides arterial supply to the inner ear.

 The pontine arteries, which are several in number.

 The superior cerebellar arteries, which arise from the basilar arteries just below the
level of origin of the oculomotor nerves.

 Thus, CN III takes origin between the superior cerebellar arteries and the posterior
cerebral arteries, and may easily be compressed by berry aneurysms arising in the
posterior cerebral arteries (part of the circle of Willis). This can cause oculomotor palsies.

238
The Carotid System & Circle of Willis

 The internal carotid arteries enter the cranial vault through the openings of the carotid canal on
the base of the skull, located on the petrous part of temporal bone.

 It passes anteriorly, emerging into the region of the foramen lacerum. At this point, it turns
superiorly to enter the middle cranial fossa. Note, however, that it does not actually perforate
the foramen lacerum from the base of the skull.

 As it enters the middle cranial fossa, it pierces the periosteal dura mater to enter the cavernous
sinus. From the carvernous sinus, it runs anteriorly, just medial to the anterior clinoid process.

 At a position medial to the anterior clinoid process, it turns superiorly in an abrupt manner, this
time piercing meningeal dura mater and the arachnoid mater to enter the subarachnoid space.

 From here, it bifurcates into its two major terminal branches:

 The anterior cerebral arteries pass anteriorly and superiorly, following the curvature of
the frontal lobes in the median longitudinal fissure separating the cerebral hemispheres.

 The middle cerebral arteries pass laterally, running within the stem of the lateral sulcus.

 The Circle of Willis is formed by interconnecting arteries that form anastomoses between the
bilateral carotid systems, and between each carotid system and the vertebrobasilar system.

 The anterior communicating arteries connect the left and right anterior cerebral
arteries, thus providing the anterior systems with collateral supply.

 The posterior communicating arteries connect each of the internal carotid arteries with
the posterior cerebral arteries, thus forming collateral supply between the anterior and
posterior systems.

239
 The Circle of Willis is the most common site of Berry aneurysms.

 Most of these occur in the anterior communicating artery or at its junction with the
anterior cerebral arteries. These cause compression of the optic chiasm, which may
produce a bitemporal hemianopia.

 Some of these also occur in the posterior communicating arteries, or at their junctions
with the posterior cerebral arteries. As previously mentioned, aneurysms in such a
location can cause compression of the oculomotor nerve with resultant palsies.

 Before bifurcating into its terminal anterior and middle cerebral arteries, the internal carotid
arteries also give off a number of important branches:

 The ophthalmic arteries, which pass through the optic canal with the optic nerve into
the orbit and give off several branches, including importantly the central retinal artery.

 The anterior choroidal artery, which supplies the choroidal plexus for the third and
lateral ventricles for the production of CSF.

 The posterior communicating arteries, previously described.

 The internal carotid system is vulnerable to occlusion by thrombi arising from the left
atrium, the mitral valves or aortic valves, or from atherosclerotic plaques of the ICA
itself. These may enter the carotid circulating and cause anterior carotid circulation
failure.

 One of the commonest manifestations of carotid circulation failure is blindness,

resulting from ischemia due to lack of supply via central retinal artery.

240
Territories of Supply of Anterior, Middle & Posterior Cerebral Arteries

 The anterior cerebral arteries, after arising from internal carotid arteries, run anteriorly, then
superiorly, then posteriorly to arch over the corpus callosum, running in the medial longitudinal
fissure.

 It provides supply over the superomedial parts of the frontal and parietal cortex. Amongst other
things, occlusion of the anterior cerebral arteries causes infarction of the part of the motor
homunculus controlling the lower limbs, and thus leads to contralateral lower limb weakness.

 The middle cerebral arteries, after arising from internal carotid arteries, run laterally within the
stem of lateral sulcus.

 Along its path, it gives off perforating lenticulostriate arteries which supply the corpus
callosum, corpus striatum (comprising caudate and lentiform nucleus) and the internal
capsule.

 In particular, these arteries are thin-walled and easily occluded; ischemia to the internal
capsule can cause contralateral hemiplegia affecting the entire half of the body because
axons from all regions of the motor homunculus pass through the internal capsule.

 It emerges from the lateral surface of the temporal lobe to supply the superolateral
surfaces of the cerebral hemisphere. Occlusion of the middle cerebral artery distal to the
origin of the lenticulostriate arteries may only cause upper limb and head and neck
weakness.

 The posterior cerebral arteries, after hooking around the midbrain posteriorly, also run on the
inferior surface of the cerebral hemispheres in the midline, to supply the midbrain, inferomedial
aspect of the temporal lobes and the occipital lobe.

241
242
SEIZURES AND EPILEPSY
Basic Concepts of Seizures and Epilepsy

 A seizure is an abnormal sensory, motor or psychomotor experience that arises as a result of

abnormal electrical activity in the CNS.

 The CNS is designed in circuits such that when one part of the brain is stimulated, it
inhibits surrounding parts of the brain to prevent the undue spread of electrical activity.

 Seizures occur when there is a failure of this inhibition, resulting in the spread of
electrical activity to cause large areas of synchronous firing. It results from either
overfunction of stimulatory neurons (cholinergic, glutaminergic, aspartate) or
underfunction of inhibitory neurons (GABA neurons).

 Epilepsy is a tendency to develop spontaneous recurrent seizures.

 Almost all brains, under severe acute stresses, will produce seizures; not all occurrences of
seizure indicate epilepsy.

 These are sometimes called provoked seizures, and may occur due to stresses like
severe hypoglycaemia, electrolyte abnormalities and toxic doses of CNS stimulants.

 As the seizure is unlikely to recur, a diagnosis of epilepsy is not warranted as it does not
require treatment and a diagnosis may have implications on social discrimination.

 Clinically, the recurrence of seizures is taken to be indicative of epilepsy, even when

there is a known underlying trigger that can be avoided, as it suggests some sort of
underlying vulnerability, and more importantly has implications on safety and treatment.

 While an isolated seizure does not typically warrant a diagnosis of epilepsy, in the first
instance of seizure it is unknown if the seizure will recur. As such, investigation for
epilepsy should still be carried out in these patients. This will be described subsequently.

 An appreciation of the definitions of seizure and epilepsy, as well as their underlying etiologies,
is essential to prevent overdiagnosis or underdiagnosis of epilepsy.

 Diagnosis of epilepsy, depending on the underlying etiology, is often an indication for

treatment with antiepileptic drugs for an extended period of time. These drugs are
often expensive and can have undesired severe side effects.

 A diagnosis of epilepsy in many countries will result in social discrimination, if not in

one’s personal life, often in his professional life. It often disqualifies candidates for
certain occupations, including heavy machinery operation, vehicle operation (e.g. taxi
drivers, bus drivers, crane operators, pilots).

 Finally, an incorrect diagnosis of the underlying etiology of epilepsy may result not only
in inappropriate treatment, but also delay the patient from receiving a correct diagnosis
and correct treatment.

243
Recognising a Seizure

 In order to consider a diagnosis of seizure or epilepsy in a patient, we must first consider the
signs and symptoms of a seizure so that we can recognise its occurrence as either an observer or
from a clinical history.

 Based on our original definition ofa seizure, a seizure may be recognised on the basis of motor,
sensory or psychomotor symptoms.

Motor Symptoms of a Seizure

 Abnormal motor symptoms may arise due to abnormal electrical activity of the primary motor
cortex located in the precentral gyrus of the CNS.

 The upper motor neurons of the primary motor cortex typically connect to pathways stimulating
either agonist or antagonist muscles.

 A tonic seizure occurs when there is simultaneous stimulation of both the agonist and antagonist
muscles. It is characterised by rigid paralysis of the muscles.

 Sudden contraction of the vocal cords at the beginning of the seizure may cause patients
to cry out at the beginning of a seizure.

 If the diaphragm is involved, there may be respiratory paralysis resulting in hypoxia and
cyanosis.

 Tongue biting may occur in a tonic seizure, and may result in tongue bleeding. It is
extremely useful in distinguishing seizure from pseudoseizure as it is painful and difficult
to fake. A pseudoseizure has the signs and symptoms of seizure, but is not due to an
underlying abnormal electrical phenomenon and may be psychological in nature.

 A clonic seizure occurs when there is alternating stimulation of the agonist and antagonist
muscles. It is characterised by cyclical jerking or flailing motions, especially of the limbs.

 It may be accompanied by urinary or fecal incontinence.

 This may occur due to alternating contraction and relaxation of the urethral and anal
sphincters.

 A tonic-clonic seizure occurs when a seizure has a tonic phase followed by a clonic phase.

 An atonic seizure occurs when there is inhibition of both the agonist and antagonist muscles.

 A myoclonic seizure is typically characterised by a single jerk movement.

 Whereas motor symptoms of a seizure occur only during an attack, they may be distinguished
from dyskinesias like choreas which occur continuously and all the time.

244
Versive Seizures

 Versive seizures, also called oculogyric seizures, are a special type of motor symptom of seizure
that occur due to abnormal electrical activity of the frontal eye fields rather than motor cortex.

 The frontal eye fields are responsible for horizontal conjugate movements of the eyes;
they act as “push buttons” in that activation of one field results in movement of both
eyes in the contralateral direction.

 Seizures of frontal eye fields can lead to prolonged deviation of the eyes in one direction.

Sensory Symptoms of a Seizure

 The sensory symptoms of a seizure may be classified as:

 Abnormal general somatic sensations

 Abnormal general visceral sensations

 Abnormal special somatic sensations, especially vision

 Abnormal general somatic sensations arise in the absence of an environmental stimulus. They
occur due to abnormal electrical activity in the postcentral gyrus in where the primary
somatosensory cortex is located. These include:

 Dorsal column sensations such as fine touch, vibration, 2-point discrimination and
proprioception

 Anterolateral system sensations including crude touch, pain, temperature sensation

(hot and cold), ticklish sensations, itch and sexual sensations

 People may describe sensations in other terms such as abnormal tingling sensations,
heavy pressure, or their arms being on fire.

 Abnormal general visceral sensations occur due to electrical activity in the insula.

 These sensations may be thought of as the “hidden sensations”, and are correspondingly
located in the “hidden cortex”.

 The insular cortex is the deep cortex which may be exposed by separating the frontal
lobe from the temporal lobe at the lateral sulcus all the way to the stem of the sulcus.

 These sensations include abdominal cramping and nausea.


245
 Abnormal special sensations are especially associated with visual phenomena.

 Recall that the primary motor cortex is located in Brodmann 17 and is responsible for
reception of visual information. Abnormal electrical activity here may be perceived as
unformed flashes of light.

 The secondary motor cortex is located in Brodmann 18, and is responsible for the
analysis of visual information. Abnormal electrical activity here may be perceived as
flashes of light with details such as definite colours, shapes or patterns.

Psychomotor Symptoms of a Seizure

 The psychomotor symptoms of a seizure are somewhat less well-defined, and are a group of
symptoms that tend to be produced by temporal lobe seizures.

 The important areas and functions of the temporal lobe that may be impaired include:

 Brodmann 19, which is strictly part of the occipital cortex, but is often affected in
temporal lobe seizures and is discussed here.

 Limbic system, which is partly located in the temporal cortex, as well as in the
hypothalamus. It is described more fully elsewhere.

 Areas responsible for reality testing, sense of familiarity and automatism.

 Brodmann 19 is the tertiary visual cortex. It is responsible primarily for the recognition of
images; abnormal electrical activity here tends to produce well-formed images (e.g. pictures).

 The limbic system may be thought of as being responsible for species survival and perpetuation.

 It is responsible for emotion and recent memory; abnormal electrical activity in the
amygdaloid body in particular has been described to manifest as bursts of rage.

 Interestingly, it has been proposed that the mood regulatory centers of the limbic
system are responsible for small, daily physiological fluctuations in mood, and that
abnormal electrical activity in this region may be responsible for some instances of
bipolar disorder. This has lead to the use of the anti-epileptic drug valproic acid as a
mood stabiliser in some cases of bipolar disorder.

 The limbic system is also responsible for sexual behaviours; abnormal electrical activity
in the amygdaloid body may manifest as inappropriate sexual behaviour.

 The limbic system is responsible for the primitive general visceral senses of taste and
hearing; abnormal electrical activity can lead to gustatory and olfactory hallucinations.

246
 Abnormal electrical stimulation of the cortex responsible for reality testing can lead to an
inability to distinguish between reality and fantasy.

 Indeed, in early age this area is not fully developed, and explains why children may have
difficulty telling the difference between reality and fantasy.

 In combination with the abnormal visual phenomena caused by Brodmann 19 this can
manifest as visual hallucinations.

 Abnormal electrical stimulation of the area responsible for sense of familiarity may manifest as:

 Déjà vu, which is a sense of familiarity with a stimulus, even when it is novel.

 Jamais vu, which isa sense of novelty, even when the stimulus is familiar.

 Abnormal electrical stimulation of the area responsible for automaticsm can lead to abnormal
and unusual behaviours, which may include spinning around the room or spitting on strangers.

Altered State of Consciousness

 The ascending reticular activating system is responsible for maintaining stimulation to the
cerebral cortex, especially in the frontal and temporal regions.

 The reticular formation in the brainstem receives collateral fibers from the sense organs
of the body which are responsible for receiving environmental stimuli.

 It sends fibers to the intralaminar nuclei of the thalamus, which then sends out
thalamocortical fibers to the cerebral cortex to stimulate it.

 Over the course of the day, the reticular formation gradually fatigues and becomes less
sensitive to stimulation; after a period of sleep it recovers this sensitivity.

 Altered states of consciousness can occur when there is involvement of the ascending reticular
activating system in a seizure.

 This may present as simply a temporary reduction in awareness of one’s surroundings,

or the patient falling asleep altogether.

 This usually results from involvement of the intralaminar nuclei of the thalamus.

 Recall that the thalamus originates from the diencephalon; altered states of
consciousness are taken to imply involvement of the diencephalon.

247
Distinguishing Seizure from Pseudoseizure

 A seizure occurs when there are abnormal motor, sensory or psychomotor symptoms secondary
to abnormal electrical activity in the CNS.

 Sometimes, patients may present with pseudoseizure, in which there are seizure-like
symptoms in the absence of abnormal electrical activity in the CNS.

 These are often thought to be psychological phenomena resulting in seizure-like

behaviours, and occur especially in girls with a history of sexual abuse.

 In order to fulfil this criterion, it is necessary to obtain evidence of electrophysiological

abnormalities, typically by EEG monitoring during a seizure attack, or the ictal phase.

 Monitoring a seizure during the inter-ictal phase is considered unreliable; there may or may not
be residual EEG abnormalities, and even if present does not confirm that an attack was a seizure
rather than a pseudoseizure. Video telemetry may be used for long periods of monitoring.

 In the absence of EEG monitoring during the attack, tongue-biting has been shown to have a
high specificity for true seizure activity.

 Tongue biting is extremely painful and difficult to fake.

 Additonally, unlike other seizure symptoms like incontinence, it seldom results from
other causes which may need to be ruled out.

 Pseudoseizure should be considered especially when:

 Diagnosing seizure for the first time

 Encountering epilepsy refractory to treatment. However, it is important to note that

epilepsy refractory to treatment with anti-epileptics can also be the result of epilepsy
secondary to an underlying brain pathology which may have gone unidentified, and does
not rule out true seizure altogether.

Distinguishing Seizure from Epilepsy

 Epilepsy is a tendency to develop recurrent, spontaneous seizures.

 As such, the occurrence of more than one seizure, in the absence of any known significant stress,
is highly suggestive of epilepsy.

 The occurrence of seizure in the first instance may or may not represent epilepsy.

 A single seizure typically does not warrant a diagnosis of epilepsy.

 However, it warrants further investigation, including EEG monitoring during the attack
where possible, and subsequent investigation for underlying causes that may be
suggestive of epilepsy, or for triggers like hypoglycaemia, electrolyte disturbances and
use of CNS stimulants that may suggest seizure that occurred in a normal person.

248
Classification of Epilepsy by Seizure Type

 Once epilepsy has been diagnosed, it is important that it is correctly classified, as the specific
anti-epileptic drug to be used is dependent on the type of seizure experienced.

 The descriptions of the seizure types are applicable to isolated seizures not due to epilepsy as
well, but are less relevant as anti-epileptic drugs are typically not indicated for these.

 Generally speaking, seizures may be divided into partial seizures and generalised seizures.

 Partial seizures are seizures for which the onset of abnormal electrical activity is
referable to one hemisphere of the brain (left or right).

 Generalised seizures occur when the onset of abnormal electrical activity is not referable
to any one hemisphere of the brain.

 Some partial seizures may originate from one hemisphere of the brain and evolve to
involve both hemispheres and become generalised.

 Partial seizures and generalised seizures may be distinguished on the basis of EEG or
clinical presentation; for example, partial seizures typically involve only one side of the
body (mostly contralateral to the hemisphere involved), whereas complex seizures tend
to involve both sides of the body.

Patial Seizures

 Partial seizures are divided into simple and complex seizures.

 Partial simple seizures occur when only one hemisphere of the brain is involved and
there is no loss of consciousness.

 Partial complex seizures occur when only one hemisphere of the brain is involved and
there is loss of consciousness, indicating involvement of the diencephalon.

 Partial simple and complex seizures may be further characterised by their symptoms:

 Partial motor seizures may present as clonic, tonic, tonic-clonic or atonic seizures.
Myoclonic seizures are a presentation of generalised seizures.

 Partial sensory seizures may present as abnormalities of general somatic sensations,

general visceral sensations or vision.

 Partial psychomotor seizures are typically the result of temporal lobe seizures. They
may present with well-formed visual images, gustatory or olfactory hallucinations,
emotions like rage, inappropriate sexual behaviour, automaticism, impaired reality
testing, déjà vu and jamais vu.

 A Jacksonian march occurs when symptoms spread from the distal limb to involve the entire
limb (e.g. clonic jerk beginning at hand, spreading to upper limb). It can be a motor or sensory
jacksonian march. It It represents the spread of the seizure across the motor or sensory cortex.

249
Generalised Seizures

 Generalised seizures are seizures for which the onset of abnormal electrical activity is not
referable to a singe hemisphere of the brain.

 EEG evidence should show that the onset of the seizure was not referable to any one
hemisphere. Secondarily generalised seizures begin as partial seizures but spread to
both hemispheres, and are not true primary generalised seizures.

 Generalised seizures always involve (and indeed are thought to originate from) the
diencephalon; consciousness is always impaired and the label “complex” is unnecessary.

 There are six major types of generalised seizures. They are typically classified by the presence or
absence of motor symptoms.

 Generalised tonic seizures present with rigid paralysis on both sides of the body due to
simulataneous stimulation of agonists and antagonists on both sides.

 Generalised clonic seizures present with limb flailing/ jerking on both sides of the body
due to alternating stimulating of agonist and antagonist muscles.

 Generalised tonic-clonic seizures present with a tonic phase followed by a clonic phase.
These are also called grand-mal seizures.

 Generalised atonic seizures present with flaccid muscle tone on both sides of the body
due to inhibition of both agonist and antagonist muscles.

 Generalised myoclonic seizures present with a single jerk movement. Myoclonic

seizures are nearly always the result of a generalised seizure and are not a presentation
associated with partial seizures.

 Generalised absence seizures present with the absence of motor symptoms, but with a
sudden alteration in consciousness. It is also known as a petit mal seizure.

 Petit mal seizures, or absence seizures, typically involve brief moments of altered consciousness,
without other apparent symptoms, that can occur several times a day.

 If the patient is performing a task or speaking, he or she may stop mid-action or mid
sentence, pause for a moment, and then proceed as if nothing had happened. The
patient retains full muscle tone during the attack and does not fall down or drop objects.

 It typically has a young age of onset, and most patients “grow out” of the absence
seizures with age. Thus, it typically has a young age of presentation.

 However, with age there is a risk that some patients will develop generalised tonic-
clonic seizures as well.

 On EEG, it may be recognised by a characteristic spike-and-wave pattern of 3ms-1, which

is almost diagnostic. It is treated specifically with ethosuximide, a drug which reduces
calcium influx in thalamic neurons responsible for loss of consciousness.

250
 A grand mal seizure is characterised by a prodrome, aura, tonic phase, clonic phase and post-
ictal phase. The prodrome and post-ictal phases occur before and after the seizure respectively,
and are not truly part of the seizure itself.

 Prodrome describes abnormal mood, behavioural or motor changes that occur in the
patient several days before the attack; they are not part of the seizure itself. Prodrome
symptoms are often recognised by people around the patient, but the patient himself
may or may not be aware of them.

 Aura is the initial phase of the attack occurring for seconds before the onset of motor
symptoms. It is characterised by abnormal sensory experiences, often gustatory,
olfactory or visceral in nature. It is perceived by the patient and not by others.

 Tonic phase is characterised by a rapid loss of consciousness, a characteristic cry at the

start of the phase due to the rapid contraction of laryngeal muscles and bilateral rigid
paralysis. There may be cyanosis due to hypoxemia secondary to diaphragm paralysis.

 Clonic phase is characterised by bilateral limb jerking. There may be urinary or fecal
incontinence due to the alternating contraction and relaxation of bladder and anal
sphincters.

 Lateral tongue biting can occur in either of the tonic or clonic phases. One should not
attempt to lodge any objects in the victim’s mouth; it does not improve outcomes and
may even crack and increase risk of injury to the patient. Interestingly, lateral tongue
biting itself is a clinical feature highly specific to grand-mal seizure.

 Post-ictal phase occurs after the seizure. The patient is typically drowsy and fatigued,
but may be irritable and aggressive. The patient must not be left alone because of the
risk of seizure recurrence and lapsing into status epilepticus.

 Status epilepticus is a single seizure that occurs for more than 30 minutes duration, or a
series of seizures during which full function is not regained between ictal events over a
30 minute period. The risk of permanent brain damage and death is greatly increased.

251
Etiology of Epilepsy – Idiopathic, Symptomatic and Provoked Epilepsy

 Epilepsy is a tendency to develop recurrent, spontaneous seizures.

 Idiopathic epilepsy occurs in absence of any identifiable structural lesions or metabolic changes.

 In recent years, many of these previously “idiopathic” seizures have been found to be
due to diffuse abnormalities in neuronal connection. Some are due to genetic causes,
while others are presumed genetic due to their heritability.

 Nevertheless, the term idiopathic has been retained; it now refers to any seizure that is
not due to underlying structural lesions that are grossly identifiable on imaging, or due
to an underlying metabolic cause.

 Idiopathic seizures are much more likely to be associated with childhood onset,
generalised seizures and good response to pharmacotherapy; intuitively these
widespread, inherited defects are more likely to present earlier and affect both
hemispheres of the brain.

 These are important factors to recognise, as the treatment of any underlying cause is
more likely to be effective in these cases than the use of pharmacotherapy.

 Symptomatic epilepsy is due to an underlying structural or metabolic abnormality.

 It is important that the relevant imaging and biochemical investigations are carried out
to investigate for underlying causes of a seizure.

 Symptomatic epilepsy is much more likely to be refractory to treatment, and treatment

of an underlying cause may be more effective. Furthermore, the epilepsy may be only
one of a number of problems that may be caused by the underlying etiology; failure to
investigate may delay urgent treatment of some underlying problem.

 These causes are much more likely to be associated with partial seizures and adult
onset. Intuitively, the risk of acquiring symptomatic epilepsy would increase with age,
and focal lesions would be more likely to produce a partial than generalised seizure.

 Provoked epilepsy occurs due to some identifiable trigger.

 In some cases, the triggers are the same as those causing isolated provoked seizures, but
recurrence of the seizures warrants a diagnosis of epilepsy due to implications on safety
and treatment. Some of these persons may have an underlying vulnerability that
decreases their threshold tolerance to the stimulus as compared to a normal person.

 Other triggers would almost never cause epilepsy in a normal person. These include
bright flickering lights, noise and music, physical/ emotional/ mental exhaustion and
even hot baths.

 Identification of any trigger is essential for avoidance which can improve disease control.

252
Causes and Investigation of Partial Epilepsy

 Idiopathic partial epilepsy is less common than generalised epilepsy, but can still occur. It is a
diagnosis of exclusion by ruling out all other possible causes with thorough investigation.

 Symptomatic epilepsy due to underlying gross structural lesions can be ruled out by CT scan or
preferably MRI, such as embryological defects, tumours, infection, inflammatory conditions,
vascular lesions and trauma.

 Embryological defects include cortical dysgenesis, in which causes abnormal migration of

neurons during intrauterine life in focal areas, producing detectable MRI changes.

 Tumours include:

 Tuberous sclerosis is a mutation of TSC1/ TSC2 tumour suppressor resulting in tumours

on skin and brain.

 Neurofibromatosis type 2 results from mutation of the NF-2 gene, and causes
neurofibromas in the CNS, as opposed to type 1 which produces tumours in PNS.

 von Hippel Lindau disease produces tumours in eyes, brain and kidney – remembered
by the mneumonic “very happy land”. India was once very happy to be taken over by the
British, and their politicians were well regarded in the eyes and mind of the people.
However the people soon rebelled and pissed all over the politicians.

 Infections may be investigated with leukocyte counts and differential:

 Chronic supparative otitis media which can produce a temporal lobe abscess by
penetrating the tegmen tympani, a thin plate of bone separating the middle ear from
the temporal lobe.

 Toxoplasmosis, which can occur due to infection from cats. This parasite also attacks the
retina and produces changes observable on fundoscopy.

 Tuberculoma in the brain. Chest radiograph may be useful in looking for evidence of
tuberculosis infection (e.g. Ghon complexes, consolidation, cavitary lesions).

 Cysticercosis due to infection by cysticerci of taenia solium, the pork tapeworm.

 Subdural empyema, a collection of pus in the subdural space.

 Temporal lobe encephalitis often occurs due to infection by herpes simplex virus.

 HIV-AIDS can directly cause CNS effects.

 Inflammatory conditions may involve:

 Sarcoidosis which can be differentiated from tuberculosis in that it produces non-

caseating rather than caseating granulomas.

 Cerebral vasculitides especially in SLE, which cause ischemia to the brain.

253
 Ischemic lesions can cause hypoxia to the brain; partially ischemic neurons are unable to
maintain their Na+/K+ pumps and therefore become gradually depolarised, but are still alive and
can produce signals, whereas completely dead neurons are unable to so.

 Arterial thrombosis, which are more likely to cause complete infarction than partial
ischemia, and thus less commonly cause epilepsy.

 Emboli to the vessels.

 Cerebral vein thrombosis, which can occur in the veins or in the venous sinuses, are
more likely to cause only partial ischemia due to congestion, and are thus the most
common occlusive cause of epilepsy.

 Trauma is another important cause.

 Mesial temporal sclerosis is a lesion in which the temporal lobe is sclerosed, producing MRI
changes. In this particular cause the treatment is lobectomy.

Causes and Investigations of Generalised Epilepsy

 Idiopathic causes are far more common in generalised than partial epilepsy. They frequently
occur due to inborn errors of metabolism such as Tay Sach’s Disease.

 Gross cerebral lesions can produce generalised epilepsy if they are diffuse, including:

 Hydrocephalus

 Cerebral birth injury due to hypoxia during the birthing process

 Prolonged cerebral anoxia for any reason after birth, e.g. prolonged hypotension,
drowning.

 Alzheimer’s Disease

 Inflammatory conditions like SLE can also cause generalised epilepsy. ESR should be done.

 Drug use is more associated with generalised epilepsy and should be ruled out by drug screen.

 Antimicrobials including penicillin (metabolites block GABAergic channels),

antimalarials, isoniazid

 Cardiac antiarrythmics

 Psychotropic drugs including phenothiazine and the monoamine reuptake inhibitors

tricyclic antidepressants, SSRIs, cocaine, amphetamines. Amphetamine in particular can
cause seizures both during its use and withdrawal.

 Alcohol withdrawal

254
 Electrolyte and metabolic abnormalities should be ruled out by relevant studies:

 Hypocalcemia and hypomagnesemia cause seizure because these ions normally “guard”
sodium channels and prevent sodium ion influx; decreased calcium and magnesium
increase sodium permeability and excitability of the neurons.

 Hyponatremia causes neuron swelling and injury.

 Acute renal failure causes hyperkalemia.

 Chronic renal failure causes accumulation of nitrogenous waste products like urea
which disturbs the CNS.

 Hepatic encephalopathy causes toxic substance accumulation e.g. NH3 irritates the CNS.

 Hypoglycemia reduces Na+/ K+ ATPase activity and therefore depolarises the neuron.

 Infections can cause generalised epilepsy if their effects are diffuse. Serological tests and testing
the CSF may be useful. These infections include:

 Meningitis and encephalitis

 Bovine spongiform encephalopathy occurs due to infectious prions, which are

misfolded beta-pleated sheets that, if they infect an organism, can cause misfolding of
proteins in host cells, thus corrupting their proteins. They cause the brain to become
soft, hence the name.

Patient Counselling

 Patient counselling is the first step in the management of epilepsy.

 The disease must first be explained to the patient. Emotional counselling should be offered
because it can be a disease of stigma in some societies.

 For safety reasons, the patient must avoid operating heavy machinery and vehicles for work. In
particular, he must be advised to report his epilepsy to the traffic police, for which his license
will be revoked at least temporarily, although the license may be restored in some countries if
he undergoes pharmacotherapy and meets a minimum seizure-free period of 2-3 years.

 He should avoid high-risk activities like swimming, working in high areas and mountain-climbing.
He should avoid using a washroom with a locked door, and preferably should be accompanied
by someone as far as possible.

 He may be advised to avoid known triggers if possible.

 He should then be offered pharmacotherapy, which can produce well-controlled symptoms in

up to 80% of patients. However the patient must be advised that he may have to try multiple
drugs at multiple doses with side effects, and will be on therapy for at least 2-3 years or more.
There are also difficulties withdrawing the drug.

255
Principles of Pharmacotherapy of Antiepileptic Drugs

 Pharmacotherapy is best managed by:

 One doctor, who knows the history of treatment of the patient and is best suited to
adjust doses or drugs accordingly

 One drug, to minimise polypharmacy which is associated with more side effects.

 For every epilepsy, there will be a number of drugs available for treatment; doctors should know
at least the first- and second-line drugs of each category.

 For trial of the first-line drug:

 The dosage of the drug is gradually increased over a period of time to at least the
therapeutic level.

 If the symptoms remain well controlled, the treatment is successful and the patient is
kept on the drug.

 If not, the dosage is increased gradually, until either the maximum tolerated dose at
which side effects occur is reached, or the maximum recommended safe dose is
reached (even if there are no side effects at this point).

 If the patient’s symptoms are still not well controlled, the second-line drug is trialed.

 For trial of the second-line drug:

 The first-line drug is continued, sometimes at a slightly lower dose.

 The second-line drug is started and dosage gradually increased to within therapeutic
range. At this point the first-line drug is tapered off.

 The second-line drug dose is increased again, until symptoms are well controlled, or the
maximum tolerated or maximum recommended safe doses are reached.

 If symptoms still cannot be controlled at tolerable and safe doses of the drug, a trial of a
third-line drug may proceed in the same manner.

 In this way, all drugs are trialed one at a time; for the majority of patients, symptoms will be
well-controlled and effects well-tolerated by one of the drugs at a given concentration. If
symptoms are still not well-controlled, combination therapy is considered.

256
Introduction to Anti-Epileptic Drugs

 The focus of the discussion here is not to describe the drugs in full; these have to be studied in
pharmacology for extensive discussion of side effects etc.

 Anti-convulsants seek to either:

 Prevent Na+ entry required for depolarisation (Phenytoin and Carbamezapine)

 Increase Cl- entry to hyperpolarise neurons (Clonazepam, Diazepam, Lorazepam and

Phenobarbital)

 Prevent Ca2+ entry for depolarisation of thalamic neurons specifically for absence
seizures – ethosuximide

 Block glutaminergic AMPA receptors – lamotrigine and topiramate

 Block glutaminergic NMDA receptors – felbamate

 Valproic acid is a generalised anticonvulsant drug that acts via multiple mechanisms. It prevents
Na+ entry, prevents Ca2+ entry, and increased Cl- loading.

 It is thus an extremely broad spectrum drug and is the first or second-line drug for all
types of epilepsy. In cases of multiple epilepsy, or in the case where urgent treatment for
seizure in an as yet undiagnosed patient is required, valproic acid is an excellent drug.

 Due to its multiple modes of action it is the drug which can be taken in the lowest
concentrations as well.

Phenytoin and Phosphenytoin

 Phenytoin is an anticonvulsant that maintains voltage gated Na+ channels in a refractory state.

 Thus, phenytoin does not actually prevent the start of a seizure, but prevents seizure
propagation.

 Phosphenytoin is a related drug that is more water soluble and less likely to cause
thrombophlebitis, and is preferred where available. Their profiles are otherwise similar.

 The pharmacokinetics of phenytoin are complex, and for this reason it is no longer a first-line
drug for any epilepsy; carbamezapine is generally preferred over it for safety reasons.

257
  Phenytoin can reach zero-order kinetics of elimination even at therapeutic doses
because it easily saturates the metabolic processes of elimination.

 For this reason, it has nonlinear kinetics of absorption, meaning that with increasing
dose, the plasma concentration achieved increases rapidly.

 This results it in having a relatively poor safety profile and low therapeutic index.

 Additionally it is a P450 inducer of many drugs, and has many interactions and is also
contraindicated in porphyrias.

 The side effects of phenytoin include:

 CNS depressant effect as a direct effect of its hyperpolarisation

 Osteomalacia due to reduced Vitamin D absorption and activation, as phenytoin

competes with it for hydroxylation.

 Megaloblastic anemia due to reduced folate levels.

 Aplastic anemia due to immune mediated mechanisms; this requires regular complete
blood count to ensure that WBC counts are normal.

 Gingival hyperplasia and hirsutism, a combination highly specific to phenytoin.

 Teratogenic effects are a result of the reduced folate, and cause cleft palate and lip.

Carbamezapine
 Carbamezapine is a drug that also acts to maintain the refractory state of the Na+ voltage gated
ion channel, so as to prevent propagation of a seizure. It is the first-line drug for partial epilepsy.

 It is a P450 inducer like phenytoin, but even autoinduces its own metabolism, such that drug
titration changes may be required over time. However it generally has a better safety profile
than phenytoin because of its first-order kinetics of elimination.

 It shares many side effects with phenytoin, including:

 CNS depressant effect

 Osteomalacia due to low Vitamin D absorption and activation

 Low folate

 Aplastic Anemia requiring regular complete blood count monitoring.

 Rather than gingival hyperplasia and hirsutism, the main disfiguring side effect of carbamezapine
is the risk of exfoliative dermatitis or Steven Johnson Syndrome, a severe autoimmune reaction.

 The low folate levels can lead to both cleft palate/ lip as well as spina bifida.

 It is one of a number of CNS drug that can cause SIADH.

258
Valproic Acid

 Valproic acid is a remarkable antiepileptic drug which acts through multiple mechanisms, and
for this reason is the first or second-line drug in almost all epilepsies, and is excellent for
controlling epilepsies presenting with multiple seizure types.

 It inhibits Na+ loading just like phenytoin and carbamezapine.

 It increases Cl- loading like the benzodiazepines and barbiturates, but by inhibiting
GABA transaminase from destroying GABA receptors, increasing their numbers.

 It inhibits Ca2+ loading, and for this reason can be used in the treatment of absence
seizures like ethosuximide.

 Unlike phenytoin and carbamezapine, it is an inhibitor of P450, and is especially useful for
women on oral contraceptive pills, whose metabolism by P450 would be induced by these drugs.

 Its main side effects are:

 Hepatotoxicity and pancreatitis

 Thrombocytopenia, which should also be monitored with complete blood count.

 Alopecia rather than hirsutism with phenytoin.

 Finally, it is also teratogenic but causes spina bifida only.

Ethosuximide

 Ethosuximide prevents Ca2+ cation loading by blocking T-type Ca2+ channels in thalamic neurons.
It used only in the treatment of absence seizures and is the first line drug.

Pregnancy and Other Considerations

 Women on Phenytoin or Carbamezapine must be counselled that these drugs may induce the
metabolism of OCPs and reduce their efficacy; alternative contraception must be used.

 Valproic acid is the best drug for women on OCPs to use to prevent pregnancy as it is a P450
inhibitor; however like phenytoin and carbamezapine it is teratogenic.

 Phenobarbital is the safest drug to use in pregnancy, but depending on the circumstances the
patient may or may not wish to switch or taper off her anticonvulsant medication.

 In general, anticonvulsant medications cannot be stopped immediately; if they have maintained

a sufficiently long seizure-free period, some patients may consider stopping their anticonvulsant
medications, but there is a significant risk of relapse.

259
Choice of Anti-Epileptic Drugs

 For partial epilepsy:

 Carbamezapine is the first-line drug. A useful way to remember this is that only patients
with partial epilepsy may not lose consciousness, and are the only ones who might take
a risk driving a car.

 Valproic acid is the second line drug.

 For generalised tonic-clonic seizures:

 Valproic acid is the first line drug, as it acts by multiple mechanisms and is more likely to
be active on multiple groups of neurons.

 Lamotrigine is the second line drug and is relatively new.

 For generalised myoclonic epilepsy:

 Valproic acid is the first line drug

 Clonazepam is the second line drug

 For generalised absence epilepsy:

 Ethosuximide is the first-line drug, as it specifically inhibits calcium uptake in thalamic

neurons.

 Valproic acid is the second-line drug.

Considerations for Withdrawal of the Drug

 After a period of 2-3 years, doctors may discuss withdrawal of the drugs with their patients,
which should be performed in a gradual, tapered manner.

 Patients should be advised that of the 80% of patients whose symptoms are well-controlled by
pharmacotherapy, half of them well relapse if medication is discontinued. The following factors
predict a greater likelihood of success in tapering off the drug without relapse:

 Adult onset epilepsy that is due to some underlying cause which has since been treated

 Patients with a normal EEG. An abnormal EEG can be present in some patients even in
the absence of seizure and are predictive of relapse on withdrawal of the drug.

 Patients of a normal IQ. A low IQ suggests multiple diffuse brain lesions that are
predictive of lower success in withdrawal of the drug.

 Patients who have had their driving license restored under pharmacotherapy should be advised
that it will be suspended again for another period of 6 months, and if seizures recur at any time
it will not be restored.

260
Management of Status Epilepticus

 Status epilepticus is either:

 A single continuous seizure lasting for more than 30 min

 The occurrence of multiple seizures without full recovery between ictal events over a
period of 30 min

 The risk of death or permanent brain damage increases significantly with the duration of
seizure; thus, treatment should be started within 5 minutes if the seizure does not stop.

 At presentation, a number of maneuvers should be performed before commencing

pharmacotherapy:

 A secure airway should be obtained

 High flow oxygen should be administered – the patient may have difficulty breathing
during the tonic phase of a seizure

 The semi-prone position can be used to minimise the risk of aspirating pharyngeal
contents.

 If possible, EEG monitoring should be performed, both for diagnosis of the seizure and
to monitor the effects of treatment.

 Thiamine should be administered followed by 50ml of 50% glucose, to pre-empt hypoglycaemia

as a potential cause of the seizure.

 Thiamine can be deficient especially in alcoholics and the malnourished.

 Thiamine has two functions: it is required for metabolisation of glucose, and it is

involved in maintaining myelination of various CNS tracts, especially those of the papez
circuit and the 3rd, 4th and 6th cranial nerve nuclei.

 Administration of glucose in an already thiamine-deficient patient can exacerbate the

deficiency and cause demyelination of these CNS tracts, precipitating Wernicke-
Korsakoff Syndrome which can cause memory and other defects.

 For this reason, glucose administration must always be preceded by thiamine.

261
 Pharmacotherapy should be administered in the following order:

 IV bolus lorazepam or diazepam should be administered, followed by a slow IV infusion.

 At the 10 minute mark, if there is no response phosphenytoin or phenytoin sodium

should be used. They can be used even in women as a one-time dose is unlikely to
produce the previously mentioned side-effects.

 If there is still no response, phenobarbital is used.

 At the 20 minute mark, if there is still no response, general anesthesia is administered.

A general anesthetist must be called early so that he is ready by the 20 minute mark.
Sodium thiopental or barbiturates are used to induce coma. They may need to be
administered repeatedly due to a short duration of action.

 IV propofol is the next drug to be used.

Special Considerations in Women

 Phenytoin and carbamezapine induce OCP metabolism, and should generally be avoided where
possible in women. Alternatives like valproic acid are preferred, or alternative contraceptive may
be offered.

 Valproic acid inhibits OCP metabolism and is preferred if OCPs are being used, but is still
teratogenic.

 In pregnancy, the following considerations should be made in choice of pharmacotherapy:

 If the patient has achieved a seizure-free period of 2-3 years, she may consider
withdrawing the drug.

 If the patient cannot be safely withdrawn from the drug, she should switch to a
nonteratogenic drug like phenobarbitol, diazepam or lorazepam where possible.

 If none of the nonteratogenic drugs can control symptoms at safe or tolerable doses, the
least teratogenic drug should be administered in combination with folic acid
supplements, as many of the drugs interfere with folic acid metabolism.

 Vitamin K should always be administered in the late stages of pregnacy, as many of the
drugs reduce transfer of vitamin K across the placenta, and may result in coagulopathies
of the baby at birth.

262
APHASIA AND DYSPROSODY
Basic Concepts of Language and Hemisphere Lateralization

 Language is the communication of thought and ideas between persons using symbols.

 These symbols may be visual (written communication or hand signs), auditory (verbal
communication) or less commonly tactile (e.g. Braille).

 Some persons assert that less well-defined or abstract modes of communication such as
body language, art and music also constitute language to a certain degree.

 It involves an expressive component in which language is produced, and a receptive

component in which it is received and understood.

 The higher cortical centers responsible for the functions of language, unlike some other areas,
demonstrate significant lateralization of function.

 Classically, the dominant hemisphere is defined as the hemisphere in which language centers
are better developed in. Hemisphere dominance is predicted to a certain degree by handedness:

 For 95% of right-handers, it is the left hemisphere.

 For 70% of left-handers, it is also the left hemisphere.

 For the remainder, is is the right hemisphere.

 The two major language centers in each hemisphere are Wernicke’s area and Broca’s area.

 Wernicke’s area is located in Brodmann area 22, in the posterior part of the superior
temporal gyrus. It plays the role of a “mental dictionary” that can convert thoughts and
ideas into words (e.g. the image of a flower into the word “rose”).

 Broca’ area is located in Brodmann 44 and 45, in the inferior frontal gyrus. It is
traditionally associated with the motor programmes required for the production of
verbal speech.

 It is now thought that no single hemisphere performs all of the functions required for language.

 Rather, the language centers of the dominant and non-dominant hemispheres play
different roles in handling language.

 Wernicke’s area and Broca’s area of the dominant hemisphere are associated with the
handling of the literal components of language.

 Wernicke’s area and Broca’s area of the non-dominant hemisphere are associated with
the handling of the non-literal components of language, which include features like tone,
pitch, inflexion and rate of speech, and may aid in conveying emotion.

263
 In persons who learn a second language, the neuroanatomical pattern of development is highly
dependent on the age at which it is learnt.

 People who learn two languages at the same time in early childhood have a single set of
language centers in each hemisphere (one Broca’s area and one Wernicke’s area) that is
responsible for the mastery of both languages.

 People who learn a second language in adulthood develop a separate Broca and
Wernicke area for the new language. Furthermore, the development of these new
centers in adulthood is extremely difficult.

 Language is not the only cortical function which demonstrates hemisphere lateralization.

 Calculation is thought to be a function of the dominant hemisphere.

 Understanding of geometric shapes is thought to be a function of the non-dominant

hemisphere.

 Internal orientation and external orientation in space are also thought to be primarily
functions of the non-dominant hemisphere.

 Internal orientation is the sense of the orientation of one’s body in space; external
orientation is the orientation of other objects in space. It is thought that the relative
underdevelopment of these areas in childhood is responsible for the difficulty that
children have in dressing themselves.

Wernicke’s Area and Comprehension of Language

 Language is received primarily by one of three modalities:

 Written language (or hand signs) are received through the visual modality

 Verbal language is received through the auditory modality

 Braille can be received through the somatosensory modality.

264
 In each of these modalities, information is processed in the respective sensory cortices, and then
sent to Wernicke’s area for comprehension.

 Wernicke’s area is located in superior temporal gyrus in Brodmann 22

 Its function is that of a “mental dictionary”, which converts words or symbols in any of
the modalities to produce meaning in the form of thoughts or ideas.

 For example, in the visual modality:

 Visual information is received by the primary visual cortex located in Brodmann 17.

 It sends information to the secondary visual cortex in Brodmann 18, responsible for the
analysis of visual information, including shapes, colours and patterns.

 In turn, the secondary visual cortex sends information to the tertiary visual cortex in
Brodmann 19, responsible for the recognition of well-formed images.

 The tertiary visual cortex sends information to Wernicke’s area for processing, where
the visual image of a word is processed into thoughts or ideas.

 In the auditory modality:

 Auditory information is received by the primary auditory cortex located in the superior
transverse temporal gyrus. It sends information to the secondary auditory cortex.

 The secondary auditory cortex is responsible for analysis of auditory information,

including the pitch, volume, length of time of sounds etc. It then sends this information
to the tertiary auditory cortex.

 The tertiary auditory cortex is responsible for recognition of well-formed sounds. It

then sends this information to Wernicke’s area for processing, where the sound of a
spoken word is processed into thoughts or ideas.

 A similar process likely occurs for the comprehension of language in the somatosensory
modality for languages like Braille:

 Tactile information is received by the primary somatosensory cortex located in the

postcentral gyrus in the parietal lobe. It sends information to the secondary
somatosensory cortex.

 The secondary somatosensory cortex analyses tactile information for features such as
smoothness or roughness, the space between dots, etc. and sends this information to
the tertiary somatosensory cortex.

 The teritiary somatosensory cortex recognises a well-formed mental image of the

object being touched, and sends this information to Wernicke’s area for processing,
where it is translated into thoughts or ideas.

265
Broca’s Area and Production of Speech

 The production of speech begins with Wernicke’s area in the superior temporal gyrus.

 Its function is of a mental dictionary.

 In the reception of language, its role is to process sounds, images or tactile information
into thoughts or ideas.

 In the expression of speech, its role is the convert thoughts and ideas into words.

 Words are the sent from Wernicke’s area to Broca’s area.

 It does so via the arcuate fasciculus, which connects Wernicke’s area and Broca’s area.

 Broca’s area stores the motor programmes required for the production of speech, which
it sends to the primary motor cortex via the basal ganglia. (Basal ganglia not shown).

 The basal ganglia also contains part of the circuitry required for the motor programmes
as described in the basal ganglia chapter; it executes the programme by stimulating or
inhibiting the appropriate upper motor neurons located in the primary motor cortex.

 The upper motor neurons synapse onto lower motor neurons, whose cell bodies are found in
the relevant cranial nerve nuclei of the brainstem responsible for controlling the muscles
required for the articulation of speech.

 The cerebellum also forms many interconnections with the cranial nerve nuclei in the
coordination of the muscles required for coordinating the articulation of speech.

 However, there are some problems with this model of speech production:

 It has been shown that lesions to the arcuate fasciculus alone do not significantly impair
spontaneous speech production, but significantly impair repetition of words. It is thus
thought that the arcuate fasciculus allows for the production of speech from a
phonological sound.

 It is postulated that there may be a second route of speech production, via which
concept centers directly access Wernicke and Broca’s areas via transcortical connections.

266
Phonation and Articulation

 Phonation is the process by which the true vocal folds are closed by the action of the laryngeal
muscles during expiration to produce sound.

 The laryngeal muscles are controlled primarily by the recurrent laryngeal nerve of CN X
the vagus nerve.

 The cricothyroid muscle is the exception and is innervated by the external laryngeal
branch of the superior laryngeal nerve of CN X.

 Articulation is the process by which the sounds produced by the larynx in phonation are
manipulated to produce speech. Manipulation is performed by:

 The lips controlled by the muscles of facial expression, innervated by CN VII the facial
nerve.

 The soft palate, innervated primarily by CN X. (Tensor veli palatini is innervated by a

branch of CN V3, the mandibular nerve.)

 The pharyngeal muscles¸innervated primarily by the pharyngeal plexus of CN X.

(Stylopharyngeus is innervated by a a small branch from CN IX, the glossopharyngeal
nerve.)

 The tongue, innervated by CN IX the hypoglossal nerve.

 The actions of these cranial nerve nuclei are coordinated by the cerebellum.

Dysphonia

 Dysphonia is a disorder of phonation. When dysphonia occurs in isolation (i.e. in the presence of
normal articulation), a low volume of speech is produced. It may result from psychological
disorders or organic causes.

 Organic causes of dysphonia may include lesions to:

 Higher cortical centers containing motor programs responsible for phonation. (Broca’s
area is primarily responsible for articulation rather than phonation of speech.)

 Recurrent laryngeal nerve and external laryngeal nerve lesions, especially the former,
which controls the majority of the laryngeal muscles and can be damaged during
thyroidectomy. It is worth noting that damage to the vagus nerve or its nuclei in general
would likely result in dysarthria as well rather than dysphonia in isolation.

 Vocal apparatus, including the vocal folds and the muscles themselves. An example is
singer’s nodule in which overuse of the larynx results in inflammation and formation of
nodules that impair phonation.

267
 Dysarthria is a disorder of articulation, and typically occurs due to some lesion of the motor
systems involved in articulation from the primary motor cortex inferiorly. These lesions may
involve:

 Descending pyramidal and extramyramidal tracts of UMNs controlling the cranial nerve
nuclei. These are known as pseudobulbar lesions, and can occur due to demyelination in
multiple sclerosis.

 CN VII, IX, X and XII nuclei of the brainstem. These are called bulbar lesions.

 CN VII, IX, X and XII nerves, which may be impaired in Guillan-Barre Syndrome, or in Bell
Palsy for CN VII specifically.

 Neuromuscular junction signalling can be impaired in myasthenia gravis.

 Articulatory apparatus, including the lips, facial muscles, soft palate, pharynx and
tongue.

 Cerebellum which is heavily involved in coordination for articulation.

Dysphasia

 Dysphasia is a group of language disorders occurring in the absence of lesions to the visual,
auditory or motor systems. It can occur due to lesions in:

 Broca’s area

 Wernicke’s area

 The arcuate fasciculus

 Basal ganglia

 Thalamus

 Broca’s aphasia occurs due to lesions involving the whole of Broca’s area.

 There is normal comprehension of written and spoken language as Wernicke’s area and
the fibers it receives are fully intact.

 There is non-fluent aphasia. Upon recovery, patients describe that they know what
words they want to use, but are unable or rarely able to articulate these words.

 There is impaired speech repetition. The connections from the arcuate fasciculus are
also damaged, which impairs repetition of words.

268
 Wernicke’s aphasia occurs due to lesions involving the whole of Wenicke’s area.

 There is impaired comprehension of language, whether verbal, written or signed, as the

mental dictionary cannot convert images or sounds to a thought or idea.

 There is fluent aphasia. Concept centers are able to directly access Broca’s area, but are
unable to directly access Wernicke’s area; as such the patient may speak fluently, but
use paraphasias (unintended use of words, syllables or phrases) such as neologisms,
which are novel combination words.

 There is impaired speech repetition, as Wernicke’s area is almost completely destroyed

and words cannot be received to be sent to Broca’s area via the arcuate fasciculus.

 Conductive aphasia classically occurs due to lesions to the arcuate fasciculus alone. This
neuroanatomical basis has since been disputed.

 There is intact comprehension of written and spoken language as Wernicke’s area is

fully intact.

 There is intact spontaneous speech production as concept centers are able to directly
access Wernicke’s and Broca’s areas independently of the arcuate fasciculus.

 There is impaired repetition of words due to impaired communication between

Wernicke’s and Broca’s areas.

 Some neurologists have suggested that these three aphasias can be observed in all families:

 Men listen to and understand when they are being scolded by their wives, but are
unable to articulate their words fluently and cannot argue. (Broca’s aphasia)

 Women do not bother to listen and cannot understand anything they are being told, and
talk a lot but in neologisms and meaningless content. (Wernicke’s aphasia)

 Children can understand their parents perfectly, can talk back to them, but when asked
are unable to repeat any instructions they have been told. (Conductive aphasia)

269
 Transcortical motor aphasia occurs when there are lesions blocking the transcortical
connections of concept centers to Broca’s area.

 There is intact comprehension of speech as Wernicke’s area is intact.

 There is non-fluent aphasia as concept centers are unable to directly access Broca’s area.
Patients know what words they want to use but are unable to articulate them.

 There is intact speech repetition; words which have been recently been spoken to a
patient can be repeated as they are directly sent to Broca’s area from Wernicke’s area
via the intact arcuate fasciculus.

 Transcortical sensory aphasia occurs when there are lesions blocking the transcortical
connections of concept centers to Wernicke’s area.

 There is impaired comprehension of language as Wernicke’s area cannot connect to

concept centers well to deliver meaning to them.

 There is fluent aphasia as concept centers cannot directly access Wernicke’s area for the
appropriate words; patients cannot find the appropriate words and speak in paraphasias.

 There is intact repetition of speech as words conveyed to Wernicke’s area can be

transmitted fluently to Broca’s area, even though the patient cannot actually understand
the meaning of what is being said due to the blocking of connections to concept centers.

270
 Transcortical mixed aphasia occurs when both Broca and Wernicke have blocked transcortical
connections to concept centers.

 There is impaired comprehension of language due to blocking of Wernicke’s area from

concept centers.

 There is non-fluent aphasia as both Broca and Wernicke’s areas are blocked off from
concept centers.

 There is intact speech repetition as the arcuate fasciculus is still intact.

 Nominal aphasia occurs when patients are unable to correctly name objects, but understand
their meaning.

 On being asked to name an object, they typically name it incorrectly or are unable to
find the words.

 On being asked to describe its function, they are able to do so correctly, demonstrating
intact comprehension.

 Speech is otherwise unimpaired.

 The exact locus of the lesion is unclear but has been postulated to be due to focal lesions
in the posterior part of Wernicke’s area.

271
 Global aphasia occurs as a result to widespread lesions involving the entirety of Broca’s area,
Wernicke’s area and the arcuate fasciculus.

 There is impaired comprehension of language.

 There is non-fluent aphasia.

 There is impaired speech repetition.

 Basal ganglia aphasias occur due to lesions to the basal ganglia, especially the caudate and
putamen; the exact role of the basal ganglia in the circuitry of language is unclear, but:

 Anterior basal ganglia lesions produce symptoms resembling Broca’s aphasia

 Posterior basal ganglia lesions produce symptoms resembling Wernicke’s aphasia.

 However, they may be distinguished based on a number of characteristics.

 True Broca’s aphasia is typically associated with damage to nearby motor cortex, and is
highly associated with contralateral facial and often upper limb paralysis. (More often
on the right side as most persons are left hemisphere dominant.)

 True Wernicke’s aphasia is highly associated with damage to the nearby visual pathways,
and is highly associated with contralateral quadrantanopia or even hemianopia. (More
often on the right side than the left as most persons are left hemisphere dominant.)

 In contrast, basal ganglia lesions are highly associated with abnormalities of muscle tone
and posture which are highly regulated by the basal ganglia.

 Thalamic aphasia occurs due to lesions to the thalamus in the dominant hemisphere; again, the
specific role of the thalamus in language circuitry is relatively unclear, but it produces the
following problems:

 Intact comprehension of speech due to intact Wernicke’s area

 Fluent aphasia, as the ventroanterior and ventrointermediate nuclei (both in the lateral
thalamus) are connected with the basal ganglia, and impair speech production.

 Formal thought disorder occurs in these patients and can be mistake for psychosis.

 Intact repetition of speech.

272
 Watershed infarcts occur due to interruption in the blood supply due to prolonged hypotension,
and typically result in infarction of the regions surrounding Broca’s and Wernicke’s area and
their transcortical connections. This can produce unpredictable aphasias depending on the
regions involved.

Dysprosody

 Whereas lesions to the dominant-hemisphere language centers cause aphasias, lesions to the
non-dominant-hemisphere language centers cause dysprosody.

 Dysprosody is a disorder of the non-literal components of language, including elements that

help express emotion such as musicality, pitch, tone, rate and rhythm. Dysprosodies can be
receptive or expressive:

 Receptive dysprosodies result in the inability to appreciate the non-literal components

of spoken language

 Expressive dysprosodies result in the inability to produce he non-literal components of

spoken language, resulting in monotonous speech.

273