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Rodica Blaa

MAJOR
NEUROLOGICAL
SYNDROMES

University Press, Trgu Mure


2012

Foreword
Although neurology of the XXI century benefits from
modern diagnostic methods, knowledge and especially timely
recognition of neurological syndromes remains a challenge
and a fundamental prerequisite of physicians and medical
students.
Neurological diagnosis inevitably passes through two
successive and complementary phases. In a first phase, the
clinical diagnosis of the syndromes and diseases will be
established. In the second stage, based on laboratory
examinations, the already established clinical diagnosis may
be confirmed or rejected (positive or negative diagnosis) and
therefore differential diagnosis can be made.
Clinical neurological diagnosis can be accurately
established if at least two basic conditions are met: a)
existence of an important neurological knowledge base
(anatomo- physiology, pathology, pathophysiology, semiology,
sindromology); b) use of pragmatic medical thinking and lack
of hesitation.
In the modern era both the medical doctor but especially
the neurologist must reach the diagnosis as quickly and as
safely as possible by following a commonly obstacle-ridden
road.
The first (analytical) step of storage, is based on a clear
protocol for examination of the signs and symptoms.
The second step (synthetic) comprises in its turn two
subsequent phases, a) a first phase of establishing the
syndrome diagnosis; b) in the second phase, by properly
assembling syndromes, diagnosis of the disease is reached.
Obviously, it is optimal time for the use of laboratory
examinations, which will be recommended according to clinical
data.
I

Reconsideration of neurological syndromes facilitates


topographic diagnosis of lesions wherever they are located in
the central nervous system and/ or peripheral nervous system.
Consequently, neurology must remain equally a science
and an art, therefore presentation of major neurological
syndromes attempts to demonstrate the urgent necessity for
them to be acquired both by the Romanian students and by the
students involved in English programmes, at a time when the
beauty and nobility of clinical neurology must find its welldefined position in the heap of electronic diagnosis devices.

Rodica Blaa

II

CONTENTS

I. UPPER MOTOR NEURON SYNDROMES1


II. LOWER MOTOR NEURON SYNDROMES........ 9
III. SOMATOSENSORY SYNDROMES.. 13
IV. AUTONOMIC NERVOUS SYSTEM SYNDROMES....23
V. CRANIAL NERVES SYNDROMES.........33
VI. SPINAL CORD SYNDROMES........55
VII. BRAIN STEM SYNDROMES.65
VIII. VESTIBULAR SYSTEM SYNDROMES.77
IX. CEREBELLAR SYNDROMES......81
X. THALAMIC SYNDROMES..89
XI. EXTRAPYRAMIDAL SYNDROMES95
XII. INVOLUNTARY MOVEMENTS SYNDROMES..117
XIII. CEREBRAL LOBES SYNDROMES.149
XIV. ISCHEMIC CEREBROVASCULAR SYNDROMES...199
XV. MENINGEAL SYNDROME..223
XVI. INTRACRANIAL HYPERTENSION .233
XVII. COMA239
SELECTIVE REFERENCES.......251

III

I.UPPER MOTOR NEURON SYNDROMES

Upper motor neuron (corticospinal tract, pyramidal tract)


contains about one million nerve cells and fibers and has a phasic
function to control voluntary movements and a tonic function to
control muscular tonus.
The upper motor neurons (corticospinal tract) reside in the
precentral gyrus of the frontal lobe and are arranged in a
stereotypical fashion (only 60-80% of corticospinal fibers).
Neurons which control movements of face and mouth are
located near the sylvian (lateral fissure) and neurons
which control the muscle of the thighs and legs are located
near the medial longitudinal fissure and within the central
sulcus.
The upper motor neuron axons extends all the way from
the cortex down to the spinal cord.
Other sources of corticospinal tract include:
Supplementary motor area on the medial side of the
hemisphere.
Premotor cortex on the lateral side.
Somatosensory cortex.
Superior parietal lobule.
Motor homunculus is a body map, near the fissure of
Rolando, based on the amount of cerebral cortex used to
process the different motor outputs of human central nervous
system.
The homunculus has very large face and mouth because
there are many upper motor neurons which innervate
these parts of the body.
During its descent through the brain stem, the corticospinal
tract gives off fibers which active motor cranial nuclei,
notably those serving the muscle of the face, jaw and tongue
(the corticonuclear tract).
About 80% of corticospinal fibers cross the midline in the
pyramidal decussation.
These fibers descend on the controlateral side of the
spinal cord as the lateral corticospinal tract
(crossed pyramidal tract).

About 10% of fibers do not cross the midline in the


pyramidal decussation and enter the anterior
corticospinal tract (straight pyramidal tract), which
occupies the anterior funiculus at cervical and upper
thoracic levels.
These fibers cross the white commisure and supply
motor neurons serving deep muscle in the neck.
About 10% of the pyramidal fibers enter the lateral
corticospinal tract on the same side.
In spinal cord, about 55% of pyramidal fibers stop at
cervical level, about 20% stop at thoracic level and about
25% stop at lombosacrat level.
Upper motor neuron syndromes (UMNS) or pyramidal
syndromes (PS) result from lesions of corticospinal tract
(pyramidal tract) somewhere along its course in the central
nervous system
(cell bodies in motor cortex or axons in
corona radiata, internal capsule, brain stem and spinal cord).
N.B.:
If lesions occur above the level of the pyramidal
decussating, the signs will be detected on the opposite
side of the body.
If lesions occurs below the pyramidal decussating, the
signs will be detected on the same side.
Impairment of active motility (power) = motor deficit
(weakness):
Paresis/paralysis:
Paresis is elective (Wernicke-Mann law).
Extensors > Flexors in upper limb.
Flexors > Extensors in lower limb.
Paresis is more evident on upper limb and at distal
part of the limbs.
Paresis for upper limb is predominant on supinators,
external rotators and abductors of arm and forearm
and extensors of arm.
Paresis for lower limb is predominant on abductors
and extern rotators of thigh, flexors of shank and
dorsal flexors of foot.
If the lesion is unilateral, the motor deficit does not
affect axial musculature of the body.
Central facial paresis by affecting the corticonuclear
tract.

Paresis of swallowing and speech will appear only in


conditions of bilateral lesions of corticonuclear tract.
Grading the strength muscle:
0 = no movement.
1 = only a flicker of movement.
2 = muscle can move only if the resistance of gravity is
removed.
3 = muscle strength is reduced and joint can be moved
only against gravity with resistance completely
removed.
4 = muscle strength is reduced but muscle contraction
can still move joint against resistance.
5 = muscle contracts normally against full resistance.
Terminology:
Partial motor deficit (weakness) = paresis.
Total motor deficit(weakness) = paralysis/plegia.
Monoparesis/monoplegia = paresis/plegia of an upper
limb or a lower limb.
Hemiparesis/hemiplegia = paresis/plegia of both
upper and lower limb on the same side.
Paraparesis/paraplegia = paresis/plegia of both lower
limbs.
Diparesis/diplegia = paresis/plegia of both upper
limbs.
Tetraparesis/tetraplegia = paresis/plegia of all limbs.
Impairment of passive motility (muscle tone) =
spasticity:
Spasticity (muscular contraction) can be present from the
onset of lesion: a) if these was developed slowly after 1-3
weeks from the onset of lesion; b) if these was developed
suddenly, when was an initial flaccid (floppy) paralysis
(muscular atonia/hypotonia + hyporeflexia loss of
muscle tone).
Spasticity is elective (Wernicke-Mann law).
Flexors > Extensors in upper limb.
Extensors > Flexors in lower limb.
Spasticity following a stroke characteristically affects the
antigravity muscles.
Spasticity is predominant at distal part of the limbs.

Spasticity for upper limb is predominant on hand flexors,


forearm flexors, forearm pronators, arm adductors and
arm internal rotators.
Spasticity for lower limb is predominant on foot
extensors, shank extensors, thigh adductors and thigh
internal rotators.
Spasticity has an elastic character (continuous giving up).
Spasticity has the tendency to return at initial posture
(claspknife phenomenon).
Spasticity has tendency to exaggerate in emotion, cold and
orthostatic position.
In orthostatic position the patient with spastic hemiplegia
has a characteristic aspect = the upper limb with arm in
adduction, forearm and hand in flexion, while lower limb
in extension and internal rotation.
Clonus can often be elicited at the ankle/wrist (it consist
of rhythmic contraction of the flexor muscles 5-10
times/sec in response to sudden passive dorsiflexion).
Impairment of automatic motility:
Automatic motility is decreased or abolished on the
paretic side (e.g.: blinking, balancing of upper limb during
walking).
Impairment of pathologic associated reactions :
Synkineses are involuntary movements of some paretic
limb segments accompanying physical efforts or voluntary
movements of healthy limb segments.
Global synkineses: involuntary movements of paretic
limbs accompanying physical efforts (e.g.: cough,
sneeze, open-mouthed).
Imitation synkineses: paretic limb segments imitate
forced movements of healthy limb segments.
Coordination
synkineses:
some
involuntary
movements in paretic limbs associated with voluntary
movements of the same paretic limbs.
Impairment of deep tendon reflexes (muscle stretch
reflexes, myotatic reflexes):
Deep tendon reflexes are exaggerated (brisk reflexes,
hyperreflexia):
Hyperreflexia has the following features:
The reflexes appear at small mechanical stimulus.

The reflexes appear more rapidly after mechanical


stimulus.
The reflexes have a great amplitude and vigour.
The muscular contraction has a prolonged period.
The reflexogen zone has bigger extension.
Upper limb reflexes:
Biceps reflex (C5/C6).
Triceps reflex (C7/C8).
Brachiradialis (supinator) reflex (C6).
Ulnaris (pronator) reflex (C8/D1).
Lower limb reflexes:
Patella (knee) reflex (L3/L4).
Ankle (Achilles) reflex (S1/S2).
Medioplantar reflex (L5-S2).
Grading deep tendon reflexes:
0 = no response; always abnormal.
1 = a slight but definitely present response.
2 = a brisk response; normal.
3 = a very brisk response.
4 = a tap elicits a repeating reflex (sustained clonus > 3
beats); always abnormal.
Impairment of skin reflexes :
Skin reflexes are decreased/abolished:
Abdominal skin reflexes:
Superior (D7/D8).
Middle (D8/D9).
Inferior (D10-D12).
Other skin reflexes:
Cremasteric (L1/L2).
Plantar (S1/S2).
Pathological pyramidal reflexes and signs:
Upper limb = finger flexion reflexes:
Manoeuvres of Rosner, Hoffmann, Trmner.
Lower limb = dorsiflexion of the big toe (Babinski sign)
signe de lvantail.
Others manoeuvres for Babinski sign: Chaddock, Bing,
Oppenheimer, Gordon.
Orofacial (bilateral lesions of corticonuclear tracts):
Palmomental reflex (Marinescu-Radovici reflex).
Buccal reflex (snouting reflex, orbicularis oris reflex,
Toulouse reflex).

Triple flexion (Marie-Foix reflex) in tetraplegia/paraplegia


(severe bilateral lesions of pyramidal tracts at spinal cord
level).

Hemiplegic gait:
Typical posture during walking:
The forearm and fingers are flexed.
The leg on same side is in extension with plantar
flexion of the foot and toes.
When waking, the patient will hold his or her arm to
one side and drag his or her affected leg in a semicircle
(circumduction).
Recovery of motor deficit of paresis starts with
rhizomelic musculature of lower limb.
Topographic diagnosis:
UMNS at the cortical level (cortical PS):
Hemiparesis is on the opposite side of lesion.
Hemiparesis can be limited only at face and upper limb
or only at lower limb.
Hemiparesis is frequently associated with other
cortical signs (aphasia in the dominant hemisphere,
apraxia, agnosia, jacksonian epileptic seizures,
hemianopsia etc).
Etiology: a) cerebrovascular diseases; b) cerebral
tumor; c) cerebral trauma; d) encephalitis.
UMNS at the internal capsule level (capsular PS):
Hemiplegia is on the opposite side of posterior limb
lesion.
Hemiplegia is equal in both upper and lower limbs.
Spasticity is more precocious and more severe than in
cortical pyramidal syndrome.
Facial paralysis is present on the same side with
hemiplegia (lesion of both posterior limb and genu of
internal capsule.
Recovery of motor deficit is more difficult and more
slowly than in cortical pyramidal syndrome.
Etiology: a) cerebrovascular diseases; b) cerebral
tumor.
UMNS at the brain stem level = alternate syndromes:
Hemiparesis/hemiplegia is contralateral of the lesion.

Paresis/paralysis of one or more motor cranial


nerves (e.g.: III, VII) are ipsilateral of the lesion.
Can be frequently associated with other brain stem
signs (e.g.: vestibular, cerebellar).
Etiology: a) cerebrovascular diseases; b) cerebral
tumor; c) multiple sclerosis.
UMNS at the spinal cord level:
Spinal hemiplegia = half spinal lesion above cervical
enlargement.
Motor deficit is ipsilateral to lesion.
Spinal tetraplegia (quadriplegia):
Complete spinal lesion above cervical enlargement =
bilateral motor deficit.
Spinal crural monoplegia = half spinal lesion below
cervical enlargement (motor deficit affecting lower
limb is ipsilateral to lesion).
Spinal paraplegia = complete spinal lesion below
cervical enlargement (motor deficit is on both lower
limbs).
Etiology: a) spinal cord trauma; b) spinal cord tumor;
c) multiple sclerosis.

II. LOWER MOTOR NEURON SYNDROMES

Lower motor neuron is an efferent neuron which has its body


located in the anterior gray column of spinal cord or in brain
stem nuclei and its axon passing by way of peripheral nerves or
cranial nerves to skeletal muscles (final common pathway).
Lower motor neurons are the neurons bringing the nerve
impulses from the upper motor neurons out to the muscle.
Glutamate released from upper motor neurons triggers
depolarization in the lower motor neurons in the anterior
horn of spinal cord which in turn causes an action
potential to propagate the length of the axon to the
neuromuscular junction where acetylcholine is released to
carry the signal across the synaptic cleft to the contact.
Lower motor neurons are classified based on the type of
muscle fiber they innervate:
Alfa motor neurons innervate extrafusal muscle fibers, the
most numerous type of muscle fiber and the one involved
in muscle contraction.
Gamma motor neurons innervate intrafusal muscle fibers,
which together with sensory afferents compose muscle
spindles (part of system for sensing body position =
proprioception).
Lower motor neuron syndromes (LMNS) result from lesions of
lower motor neuron somewhere along its course (cell bodies in

brainstem and anterior horn of spinal cord, axons in brainstem,


cranial nerves, spinal roots and peripheral nerves).
Impairment of active motility = motor deficit (weakness):
Paresis/paralysis:
Paralysis include all voluntary and reflex movements
dependent on affected motor neuron.
Motor deficit of the muscles is proportional to number
of affected motor units.
Motor deficit can be limited (e.g.: mononeuropaty) or
extended (e.g.:polyneuropaty, polyradiculoneuropaty).
Mononeuropaties:
Axillary (C5/C6) arm abduction.
Musculocutaneous (C5/C6) elbow flexion.
Radial (C6-C8) elbow extension.
Ulnar (C8/T1) finger abduction/ adduction.
Femoral (L2-L4) hip flexion + knee extension.
Obturator (L2-L4) hip adduction.
Superior gluteal (L4-S1) hip abduction.
Sciatic (L5-S2) knee flexion.
Deep peroneal (L4/L5) ankle dorsal flexion.
Anterior tibial (S1/S2) ankle plantar flexion.
Posterior tibial (L4/L5) foot inversion.
Superficial peroneal (L5/S1) foot eversion.
Impairment of passive motility (muscle tone):
Hypotonia:
Hypotonia is on the same muscle with weakness.
Diminution/disappearance of muscle aspects.
Reduction of muscle tone.
Exaggeration of passive movements of the affected
limbs.
Impairment of automatic mobility:
Automatic mobility (e.g.: blinking, balancing of upper limb
during walking):
Decreased or abolished on paretic muscles.
Impairment of muscular trophicity:
Muscular atrophy (muscular wasting):
Appears after some weeks from lower motor neuron
lesion.
Appears more rapidly after cutting than compression
of lower motor neuron.

In progressive lesion, muscular atrophy appear before


motor deficit.
Impairment of deep tendon reflexes:
Deep tendon reflexes are diminished or abolished:
Diminished/abolished of deep tendon reflexes is
present only on the territory of affected lower motor
neuron.
Intensity diminution of deep tendon reflexes is
dependent on number of affected motor units.
If the lower motor neuron lesion progress, the
diminished deep tendon reflexes become abolished.
Involuntary movements:
Fasciculations:
Fasciculations, which are visible twitchings of small
groups of muscle fibers in the early stage of wasting.
Fasciculations appear only after slowly iritative lesions
of lower motor neuron at the level of nerve cell body.
They arise from spontaneous discharge of motor
neurons with activation of motor units.
Fibrillations:
Fibrillations, which are minute contractions detectable
only by needle electromyography.
They are the result of denervation supersensitivity.
Impairment of muscles contraction and structure:
Muscular contraction is in normal limits until muscle
atrophy do not reach an important degree.
Needle EMG abnormalities:
Poor EMG recording.
Fibrillation potentials.
Fasciculation potentials.
Denervation potentials.
Muscle biopsy:
Denervation muscle atrophy is corresponding to
lesion of motor units.
Reduction in the size of muscle fibers (group atrophy).
Enlargement of intact motor units.
Degenerative changes in some muscle fibers.
Topographic diagnosis:
LMNS at the anterior horn level:
Paralyses have a radicular distribution.
In acquired diseases, the paralyses are asymmetrical.

In hereditary diseases, the paralyses are symme-trical.


Fasciculations are present in slowly iritative lesions of
nerve cell bodies.
Etiology: a) chronic poliomyelitis; b) progressive
spinal muscular atrophy.
LMNS at the anterior spinal roots level:
Paralyses have a radicular distribution (radiculitis)
Fasciculations are not present.
Frequent associated with signs of posterior roots lesions.
Etiology: a) Pott disease; b) spinal trauma; c) spinal
tumors; d) spinal disc herniation; e) polyradiculoneuropaty (e.g.: Guillain-Barr syndrome).
LMNS at the plexuses level:
Paralyses have an intermediate distribution between
radiculitis and neuritis.
Constant associated with sensitive and autonomic
signs.
Etiology: a) polyradiculoneuropaty.
LMNS at peripheral nerves:
Paralyses have a neuritis distribution.
Polyneuritis distribution: a) symmetrical; b) predominant distal; c) predominant at lower limbs level.
Constant associated with sensitive and autonomic
signs.
Only motor signs if nerves has only motor fibers (e.g.:
hypoglossal, accessory) or if the pathogen agents have
a motor tropism (e.g.: lead).
Etiology: a) mononeuritis (e.g.: traumatic); b) mononeuritis
multiplex
(e.g.:
immunological);
c)
polyneuritis
(e.g.:
diabetes
mellitus,
toxic,
immunological, hereditary, vitamin deficiency).

III. SOMATOSENSORY SYNDROMES


Somatosensory system include the nervous structures that
ensure total somatosensory functions and is organized on three
levels: a) receptor level (sensory receptors); b) transmitter level
(sensory tracts), c) perception level (sensory cortex).
Receptor level include specialized endings of afferent
neurons or separate cells that affect ends of afferent neurons
for
touch,
temperature,
nociception
(pain)
and
proprioception (body position).
Sensory receptors cover the skin and epithelia, skeletal
muscle, bones and joints, internal organs, including
cardiovascular system.
The sensory system reacts to diverse stimuli using
different receptors (e.g.: tactile-, thermo-, noci-, mechano-,
chemoreceptors).
The receptors collect information about external and
internal environment in various energy forms
(stimulus).
Stimulus energy is transformed into an electrical response
(stimulus transduction).
Each receptor is specific to a certain type of stimulus,
which is called its adequate stimulus.
Specificity also exists in the range of stimulus energies
that the receptor responds.

A receptor can be activated by a nonspecific stimulus if its


intensity is sufficiently high.
Transmitter level has two separate levels, first in peripheral
nervous system and second in central nervous system.
In peripheral nervous system a single afferent neuron
with all its receptor endings makes a sensory unit.
The first neuron always has its cell body in the dorsal root
ganglion of spinal nerve (if sensation is in head or neck, it
will be the trigeminal nerve ganglion or the ganglia of
other sensory cranial nerves).
In central nervous system afferent axons diverge and
synapse upon many interneuron and ends in the second
neurons.
The neurons ascending axons will cross (decussate) to the
opposite side either in the spinal cord or in the brain stem.
These afferent neurons are called sensory (ascending)
pathways and have three components, regarding the type
of stimulus:
Spinothalamic pathways (anterior and lateral tracts)
exteroceptive sensation = pain, temperature, nondiscriminative touch.
Dorsal column pathway in the spinal cord and medial
lemniscus in brain stem conscious proprioception =
joint position, vibration, deep pressure, discriminative
touch;
Spinocerebellar pathways (anterior and posterior
tracts) unconscious proprioception.
The axons of many of these neurons terminate in ventral
posterior nucleus of thalamus where is the third neuron,
which ends in the postcentral gyrus of parietal lobe.
Perception level (primary somatosensory area) in human
cortex is located in the postcentral gyrus.
Areas of this part of human brain map to certain areas of
the body, depend on amount or importance of
somatosensory input from that area (e.g.: there is a large
area of cortex devoted to sensation in the face and hands,
while the back has a much smaller area (sensory
homunculus).
Somatosensory system syndromes result from lesions of
sensory system somewhere along of sensory pathways courses

(peripheral nerves, cranial nerves, spinal roots, spinal cord,


brainstem, thalamus, thalamocortical tracts, cortex).
Positive sensory disorders:
Pain = an unpleasant subjective sensory and emotional
experience associated with or described in terms of actual
or potential tissue damage.
Acute pain = can be brief, lasting moments or hours, or
it can be persistent, lasting less than 30 days, until the
disease or injury heals.
Subacute pain = persistent pain (continuous or
recurrent) that lasts from one to six months.
Chronic pain = persistent pain (continuous or
recurrent) of more than six months.

Nociceptive pain = pain caused by stimulation of


peripheral nerve fibers that respond only to stimuli
approaching or exceeding harmful intensity (e.g.:
thermal, mechanical, chemical, visceral, deep somatic,
superficial somatic).
Somatic pain = nociceptive pain in musculoskeletal
system (the localization of pain is precise).
Visceral pain = nociceptive pain in an internal organ
(the localization of pain is diffuse, generally on the
anatomic territory of the affected internal organ).
Referred pain = visceral pain is often felt in places
remote from the location of the affected organ (e.g.:
referred cardiac pain). The referred pain is known as
viscero-somatic convergence.
Neuropathic pain = pain caused by damage or disease
affecting any part of the nervous system involved in
bodily feelings (the somatosensory system).
Neuralgia = peripheral neuropathic pain felt in the
distribution of a nerve root, due usually to a proximal
lesion of that nerve and is often described as burning,
tingling, electrical, stabbing or pins and
needles.The characteristics of such pains tend to be
constancy in their intermittency, brevity, severity and
explosive onset in the territory supplied by the nerve.

Primary neuralgia (unknown origin) = pain appear in


crises without pain between crises and without
hypoesthesia on affected nerve territory.
Secondary neuralgia (known origin) = pain appear in
crises with obscure pain between crises and with
hypoesthesia on affected nerve territory.
Radiculalgia = neuralgia caused by irritation to the
sensory root of a spinal nerve and is radiated along the
radicular dermatome.
Phantom pain = pain from a part of the body that has
been lost or from which the brain no longer receives
signals (phantom limb pain is a common experience of
amputees).
Psychogenic pain (psychalgia, somatoform pain) =
pain caused, increased or prolonged by mental,
emotional or behavioural factors.
Causalgia is a sympathalgia = spontaneous burning
sensation (shooting pain) in the distribution of the
injured nerve with increased sensitivity to painful
stimuli.
Causalgia is a pain that develops after a relatively
minor injury to an arm or leg, after an initiating
noxious event or a cause of immobilization, but lasts
much longer and is much more severe than would
normally be expected and the pain is continuous and
may be heightened by emotional or physical stress.
The symptoms vary in severity and duration.
Hyperalgesia = when threshold to pain appears
lowered.
Hyperpathia = pain threshold elevated, but once
reached, the painful stimulus is excessively felt.
Hyperesthesia = an abnormal increase in sensitivity to
stimuli.
Paresthesia = a sensation of tingling, burning, pricking
or numbness (pins and needles).
Dysesthesia = an unpleasant, abnormal sense of touch.
Allodinia = a pain due to a stimulus which does not
normally provoke pain.
Negative sensory disorders:
Decreased/abolished sensation:

Hypoesthesia = partial loss of sensitivity to sensory


stimuli.
Anesthesia = total loss of sensitivity to sensory stimuli.
Posterior horn syndrome:
Pure sensory disorders:
Ipsilateral segmental sensory loss, especially of pain
and temperature.
Preservation of pain and temperature sensation below
the level of damage.
Spontaneous attacks of pain may develop in the
analgesic area.
Posterior root and spinal ganglion syndromes:
Pure sensory disturbances:
Lancinating pain.
Abolition of all sensory modalities in the corresponding dermatomes.
Hypotonia in the corresponding muscles.
Hypo/areflexia of the stretch reflexes in the
corresponding affected roots.
Etiology: a) spinal trauma; b) herpes zoster infection.
Anterior and posterior roots syndromes:
Mixed (sensory and motor) disturbances:
Abolition of all sensory modalities.
Flaccid paralysis in corresponding dermatomes and
myotomes.
Areflexia.
Occasionally pain.
Etiology: a) Guillain-Barr syndrome (acute
inflammatory demyelinating polyradiculoneuropathy).
Guillain-Barr syndrome (GBS):
The major clinical manifestation is weakness, which
evolves more or less symmetrically over a period of
several days or a week or two.
Proximal as well as distal muscles of the limbs are
involved, usually the lower extremities before the upper
(Landrys ascending paralysis).
At an early stage, the arm muscles may be less weak than
the leg muscles or are spared entirely.
The trunk, intercostal, neck and cranial muscles may be
affected letter.

Frequently, the lower cranial nerves may be affected,


leading to facial diplegia, bulbar weakness and oropharyngeal dysphagia
The weakness can progress to total motor paralysis with
death from respiratory failure within a few days.
More than half of the patients complain of pain and aching
discomfort in the muscles, mainly in hips, thighs and back.
Objective sensory loss occurs to a variable degree during
the first days and in a few is barely detectable when such
loss is present, deep sensibility (touch-pressure-vibration)
tends to be more affected than superficial sensibility
(pain-temperature.
In fact, pain is a common symptom and usually is mild.
Reduced and then absent tendon reflexes are consistent
findings.

In severe cases of GBS, loss of autonomic function is


common, manifesting as wide fluctuations of blood
pressure, orthostatic hypotension, cardiac arrhythmias,
loss of sweating or episodic profuse diaphoresis and
urinary retention.
In CSF it is an albumin-cytological dissociation with
elevated protein level (reaching a peak in 4 to 6 weeks),
without increased cell count (few lymphocytes).
GBS is due to an immune response to foreign antigens
through a phenomenon called molecular mimicry.
Thoracic outlet syndrome (TOS):
TOS is a compression of the subclavian artery and the
brachial plexus nerves at the superior aperture of the
thorax.
TOS includes several separate syndromes such as:
Scalenus atticus syndrome.
Cervical rib syndrome.
Costoclavicular syndrome.
Clinically:
Pain ( sharp, burning or aching) in the arms and hands.
Pain can involve only part of the hand, as in 4th and 5th
finger only or all of the hand.
Pain can involve the inner aspect of the forearm and
upper arm.

Pain can also be in the side of the neck, the pectoral


area below the clavicle, the axillary area and upper
back, as in the trapezius and rhomboid area.
One hand colder than the other hand is common.
Edema of the arm and venous distension is relatively
rare.
Raynauds phenomenon, decoloration, cold and
trophic changes are occasionally significant.
Etiology:
The compression may be positional caused by
movement of the clavicle and shoulder girdle.
The compression may be static caused by
abnormalities, enlargement or spasm of various
muscles surrounding the arteries, veins and brachial
plexus, including a first rib fixation and a cervical rib.

Peripheral nerves syndromes:


Mixed (sensory and motor) disturbances:
Pains.
Hypoesthesia/anesthesia in the territories of affected
nerves, generally predominant for temperature and
touch.
In some polyneuropaties (e.g.: diabetes mellitus) there
is an elective alteration of proprioceptive sensory.
In polyneuropaties, the disturbance of sensory are
bilaterally, symmetrically and
with distal
accentuation.
Etiology: a) trauma; b) compression; c) toxic,
infectious, vitamins deficiency, metabolic or immunity
factors.
Carpal tunnel syndrome (CTS):
CTS is an entrapment median neuropathy.
Clinically:
Intermittent numbness and tingling (pins and
needles) and/or pain in the hand thumb, index long
and radial half of ring finger (innervated by the
median nerve).
The numbness often occurs at night.

Weakness of the thumb, hypotonia and atrophy of the


tenar muscles may occur if the condition remains
untreated.
Raynauds phenomenon and acrocyanosis are rare.
Etiology:
CTS represents a compression neuropathy of the median
nerve (intrinsic factors that exert pressure within tunnel
repetitive use of the hand wrists and extrinsic factors that
exert pressure outside the tunnel benign tumors and/or
vascular malformation)
Complex regional pain syndrome (CRPS):
CRPS type I (reflex sympathetic dystrophy, Sudeck
atrophy, reflex neurovascular dystrophy, algoneurodystrophy) does not have demonstrable nerve lesions and
is characterized by:
Presence of continuous pain, allodynia or hyperalgesia.
Muscle spasms.
Local swelling.
Abnormally increased sweating.
Changes in skin temperature (usually hot but
sometimes cold) and colour (bright red or a reddish
violet).
Softening and thinning of bones.
Joint tenderness or stiffness and/or restricted or
painful movement.
Moving or touching the limb is often intolerable.
CRPS type II ( formerly known causalgia) has evidence of
obvious nerve damage.
Posterior spinal cord column syndrome:
Lancinating pains in the legs.
Areflexia of the patellar and ankle stretch reflexes.
Tabetic dissociation:
Loss of conscious proprioception and discriminative
touch;
Perseverence of pain, temperature and nondiscriminative touch.
Sensory gait ataxia (worse in darkness or with eyes
closed).
Rombergs sign.
Etiology:
Tabes dorsalis.

Central spinal cord syndrome:


Syringomyelic dissociation:
Bilateral vest-like (suspended) loss of pain,
temperature and non-discriminative touch.
Perseverence of conscious proprioception and
discriminative touch.
Etiology: a) syringomyelia; b) hematomyelia.
Brain stem sensory syndromes = alternate syndrome:
Lesion of trigeminal nucleus induces loss of total sensory
of ipsilateral face.
Lesions of spinothalamic tract and medial lemniscus
induce loss of total sensory of contralateral body.
Etiology:
Cerebrovascular diseases.
Thalamic syndrome:
Subjective disorders:
Contralateral pain, but face is exceptional affected.
Numbness, burning and tingling sensations is
severe, persistent, paroxysmal and often
intolerable.
Burning and tingling is accompanied by hypersensitivity.
Less commonly, some patients develop severe ongoing
pain with little or no stimuli.
Objective disorders:
Contralateral hypoesthesia more accentuate for
proprioception.
Etiology:
Cerebrovascular diseases.
Cortical sensory syndromes:
Objective disturbances:
Contralateral hypoesthesia
more accentuate for
proprio-ception.
Touch sensory is moderate affected.
Temperature sensory often remain intact.
Etiology: a) cerebrovascular diseases; b) cerebral
tumor; c) craniocerebral trauma.

IV. AUTONOMIC NERVOUS SYSTEM


SYNDROMES.
Autonomic nervous system (ANS) regulates the functions of
heart muscle, smooth muscles, secretory glands and hormone
secretion.
ANS consists of two different functional and anatomical
divisions, the sympathetic (SNS) and parasympathetic (PNS)
nervous system.
The SNS and PNS regulate visceral functions as an
interactive, dynamic network to meet the requirements of
the outer and inner environment and to maintain the
homeostasis of the body.
A 2-neuron chain characterizes the structure of ANS.
The cell body of primary (presynaptic or preganglionic)
neuron, located within the CNS, sends its axon out to
synapse with the secondary (postsynaptic or
postganglionic) neuron located in one of the outlying
autonomic ganglia, whence the postganglionic axon passes
to its terminal.

Since the postganglionic outnumber the preganglionic


neurons by ratio of ~32:1, a single primary neuron may
serve to discharge a number of ganglion cells thus, ANS
functions of a rather extensive terminal area may be
controlled by relatively few central connections.
Functionally, ANS is divided into sensory (afferent) and
motor (efferent) subsystems.
Within these subsystems, there are inhibitory and
excitatory synapses between neurons.
SNS and PNS typically function in opposition to each
other.
But this opposition is better termed complementary in
nature rather than antagonistic.
At the effector organs, sympathetic ganglionic neurons
release noradrenaline.
The preganglionic neurotransmitter for both divisions of
ANS is acetylcholine.
In the same time, acetylcholine is a postganglionic
neurotransmitter of parasympathetic neurons.

SNS has, as general action, mobilization of the bodys nervous


system (fight-or-flight response) which corresponds with
arousal and energy generation and inhibits digestion.
It is, however, constantly active at a basal level to maintain
homeostasis.
The shorter preganglionic neurons originate from
thoracolumbar region (intermediolaterale cell column) of
the spinal cord (T1-L2, specifically).
The axons of these cells (preganglionic fibers) are mostly
myelinated fibers.
After traversing the ventral roots, they form the white
communicating rami of the thoracic and lumbar nerves,
through which they reach the trunk ganglia of the
sympathetic chain.
Branches from the sympathetic trunk may be classified as
follows:
Those composed of postsynaptic fibers (mainly
unmyelinated) gray communicating rami join all of
spinal nerves.

Through these rami, vasomotor, pilomotor and sweat


gland innervation is distributed throughout the
somatic areas.
Branches of the superior cervical sympathetic ganglion
enter into the formation of the sympathetic plexuses
about the internal and external carotid arteries for
distribution of sympathetic to the head.
The superior cardiac nerves from the 3 pairs of cervical
sympathetic ganglia pass to the cardiac plexus at the base
of the heart and distribute accelerator fibers to the
myocardium.
Branches from the upper 5 thoracic ganglia pass to the
thoracic aorta (vasomotor) and the posterior pulmonary
plexus, through which dilator fibers reach the bronchi.
Those composed of presynaptic fibers are mainly
myelinated.
The splanchnic nerves arising from the lower 7 thoracic
ganglia pass to the celiac and superior mesenteric ganglia,
where synaptic connections occur with ganglion cells
whose axons than pass to the abdominal viscera via the
celiac plexus.
The lumbar splanchnic nerves arising from trunk ganglia
in the lumbar region convey fibers to synaptic stations in
the inferior mesenteric ganglion and small ganglia
associated with the hypogastric plexus, through which
postsynaptic fibers are distributed to the lower abdominal
and pelvic viscera.
Function of SNS:
Diverts blood away from gastrointestinal tract and
skin via vasoconstriction.
Blood flow to skeletal muscles and the lungs is
enhanced;
Dilates bronchioles of the lung.
Increased heart rate and the contractility of cardiac
cells;
Dilates pupils and relax the ciliary muscle to the lens,
allowing more light to enter the eye and far vision.
Provides vasodilatation for the coronary vessels of the
heart;
Constricts the intestinal and the urinary sphincters.
Inhibits peristalts.

PNS promotes a rest and digest response calming of the


nerves return to regular function and enhances digestion.
PNS arises from preganglionic cell bodies in the gray
matter of the brain stem and the middle 3 segments of
sacral cord.
The PNS, in contrast to that of SNS, is confined entirely to
visceral structures.
Most of preganglionic neurons run without interruption
from their central origin to the wall they supply or to
where they synapse with terminal ganglion cells
associated with plexus in the intestinal tract.
Nerves conveying parasympathetic fibers (craniosacral)
consist of:
Vagus nerve (cranial nerve X), which distributes its
autonomic fibers to the thoracic and abdominal viscera
via prevertebral plexuses.
Sacral nerves (S2-S4), which forms pelvic nerve and
distributes parasympathetics to most large intestine
and pelvic viscera and genitalia via the hypogastric
plexus.

Cranial
nerves
III
(ciliary
ganglion),
VII
(submandibular and pterigopalatine ganglia) and IX
(otic ganglion), which distribute para-sympathetics to
the head.
Function of PNS:
Dilates blood vessels leading to the gastro-intestinal
tract, increasing blood flow.
Constricts the bronchiolar diameter.
Controls the heart.
During accommodation, the PNS causes constriction of
the pupil and contraction of the ciliary muscle to the
lens., allowing for closer vision.
Stimulates salivary gland secretion and accelerates
peristalts and mediates digestion of food and
indirectly, the absorption of nutrients.
It is involved in erection of genitals.
Stimulates sexual arousal.
Peripheral ANS is controlled by the central nervous system
(CNS) via complex neuronal interconnections functioning in

relation to each other to form a functional entity called


central autonomic network (CAN).
CAN has tonic, reflex and adaptative control over autonomic
functions. In addition, it regulates endocrine, behavioral
motor, pain-controlling response and contributes to the
regulation of attention and emotional behaviour.
In CAN may be included:
Insular cortex - lying deep in the temporal lobe is
mainly a viscerosensory cortex (left insular cortex
seep to be predominantly responsible for PNS effects,
whereas right insular cortex is more likely to produce
SNS responses).
Prefrontal cortex.
Amygdala.
Hypothalamus.
Midbrain.
Medulla oblongata.
Spinal cord.
Autonomic regions of the prefrontal cortex include
ventromedial prefrontal cortex and the anterior cingulate
gyrus.
The ventromedial prefrontal cortex is involved in the
regulation of high level emotional and cognitive
functions whereas the anterior cingulate (infralimbic)
cortex constitute an autonomic premotor area.
In the amygdala with adjacent areas (extended amygdala)
integrates autonomic responses with emotional factors.
Its functions are to interpret the emotional significance of
incoming sensory information and to generate the
appropriate autonomic, behavioral, motor, endocrine and
pain-suppressing responses to environmental stimuli.
The amygdala receives cardiopulmonary information
and has direct projections to autonomic control sites,
such as hypothalamus, parabrachial region, nucleus
tractus solitarius (NTS) and the dorsal motor nucleus
of the vagus which may be the anatomical substrate for
descending control over the ANS.
The preoptic region of the hypothalamus form an
anatomicofunctional unit essential for integration of

autonomic, endocrine and behavioral responses critical


for homeostasis and reproduction.
In hypothalamus, the periventricular area controls
neuroendocrine functions as well as biological
rhythms.
The medial area has regulatory function over
homeostasis and reproduction.
The dorsomedial nucleus especially contributes to the
integration of cardiovascular responses to stress.
The lateral area regulates behavioral functions, as well
as vagal functions including cardiovascular,
gastrointestinal motility, secretion and insulin release.
The zona incerta merging ventromedially with the
lateral hypothalamic area has been implicated in
arousal, locomotion and autonomic regulation.
The paraventricular nucleus innervates all autonomic
centers.
All the midbrain areas are in connection with autonomic
centers in brain stem and spinal cord.
Periaquaductal gray matter in the midbrain integrates
autonomic responses with antinociceptive and
behavioral reactions.
The parabrachial region in the pons functions as a
mediator in processing visceral and somatosensory
information and it plays a major role in
cardiorespiratory regulation and stimulation of it
produces an increase in arterial blood pressure and
inhibition of the baroreflex.
The lateral part of the parabrachial region has
connections to cerebellum.
The cerebellar uvula has been implicated in the control of
cardiovascular and respiratory function.
In medulla oblongata NTS plays a critical role in medullary
reflexes and relay viscerosensory information to all
regions of CAN.
There are several areas in the medulla that participate
in the control of vasomotor tone, cardiac function and
respiration (e.g.: the rostral ventrolateral medulla).
ANS syndromes (dysautonomia):
Dysautonomia (autonomic dysfunction) is a broad term that
described any disease or malfunction of the ANS.

Dysautonomia include:
Horner syndrome.
Adie syndrome.
Postural orthostatic tachycardia syndrome.
Inappropriate sinus tachycardia.
Vagovagal syncope.
Pure autonomic failure.
Neurocardiogenic syncope.
Shy-Drager syndrome.
N.B.: All the diseases included in Multiple system atrophy
(e.g.: Shy-Drager syndrome, sporadic olivopontocerebellar
atrophy, striatonigral degeneration) have different degrees of
dysautonomia.
Horner syndrome (HS) = Claude Bernard-Horner
syndrome:
HS is an oculosympathetic palsy.
Clinically (ipsilateral):
Partial ptosis of the upper lid.
Miosis.
Enophthalmos.
Anhidrosis of the face.
Flushing of the face (warm skin of the forehead,
conjunctival hyperemia, epiphora and nasal
stuffiness).
Ocular hypotonia.
Increased accommodative amplitude.
Etiology:
First-order neuron disorder (central lesion that
involve the hypothalamospinal tract transaction of
the cervical spinal cord).
Second-order neuron disorder (preganglionic lesions
compression of the sympathetic chain by a
laterocervical or thoracic tumor).
Third-order neuron disorder (postganglionic lesions at
the level of the internal carotid artery (a tumor in the
cavernous sinus or a carotid artery dissection).
Adie syndrome (AS) = Adie tonic pupil:
AS presents three hallmark symptoms (ipsilateral):
Unilateral dilated pupil (mydriasis) which does not
constrict in response to light.
Accommodation is normal, slow or tonic.

Absent of deep tendon reflexes (generalized or to knee


and ankle).
Orthostatic hypotension.
Generalized sudorimotor impairment (excessive
sweating or hypohidrosis).
The women are more susceptible to this disease.
N.B.: mydriasis + loss of tendon reflexes + excessive sweating
= Ross syndrome
Etiology:
Lesions (viral or bacterial inflammation
degeneration) of postganglionic cells and fibers of the
parasympathetic system (ciliary ganglion and/or the
ciliary nerve fibers).
Degeneration of cell bodies in dorsal columns.
Shy-Drager syndrome (SDS):
SDS is a degenerative disorder of brain and spinal cord
affecting the autonomic nervous system of multiple
system atrophy.
Clinically:
SDS affects both sexes with a preference for male.
Blood
pressure
variations
with
orthostatic
hypotension:
a) a demonstrable drop in blood
pressure on standing of at least 30/20 mm/Hg;
b)
dizziness; c) severe attacks of syncope.
Sphincter dysfunctions: a) urinary
and fecal
incontinence; b) nocturnal dieresis; c) urinary
retention; d) chronic constipation.
Impotence and/or loss of libido.
Extrapyramidal syndrome: a) masked face; b) pillrolling tremor; c) cogwheel rigidity (bilateral and
symmetrical).
Corticobulbar and corticospinal syndrome:
a)
Babinski sign; b) hyperreflexia; c) dysarthria;
d)
brisk jaw jerk; e) forced laughing and crying;
f)
swallowing difficulties.
Cerebellar syndrome: a) intention tremor; b) gait
ataxia; c) ataxic dysarthria or scanned speech .
Secretory disorders: a) marked impairment of
sweating (anhidrosis); b) diminished lacrimation;
c) excessive salivation; d) seborrhea.

Heat intolerance: a) intolerance to heat and/or to cold.


Miscellaneous signs and symptoms: a) fatigability; b)
iris atrophy; c) Horner syndrome; d) external ocular
palsies with diplopia.
Dysautonomia in multiple sclerosis:
Impaired thermoregulation:
Inappropriate increases or decreases in body
temperature (heat sensitivity).
Cardiovascular dysfunction:
Postural hypotension.
Dizziness.
Light headedness.
Bladder dysfunctions (detrusor-sphincter dyssynergia and
detrusor hyperreflexia):
Urinary retention.
Incomplete emptying.
Imminent voiding.
Bowel dysfunction:
Impaired stomach mobility.
Abnormal colonic motor activity.
Anorectal dysfunctions: a) constipation and/or
fecal incontinence.
Sexual dysfunctions:
Impotence.
Alter orgasmic capacity.
Lower libido.

V. CRANIAL NERVES SYNDROMES


The cranial nerves (CN) provide sensory and motor
innervations for the head and neck, including general and special
sensory and voluntary and involuntary muscle control.

CN have both sensory (afferent) and motor (efferent)


components. Individual nerve may be purely sensory, purely
motor or mixed.
CN carry five distinct modalities (three sensory, two motor):
Somatic sensory (which perceives touch, pain,
temperature,
pressure,
vibration,
proprioceptive
sensation).
Visceral sensory ( which perceives sensory input, except
pain, from viscera).
Special sensory (which perceives smell, vision, taste,
hearing, balance).
Somatic motor (which innervates the muscles that
develop from somites and from brachial arces).
Visceral motor (which innervates the viscera, including
glands and all smooth muscles parasympathetic
efferent).
Olfactory nerve syndromes:
Olfactory disorders:
Changes in olfactory function frequently go unnoticed and
often do not present to a clinician.
However, olfaction is critically important for safety ,
nutritional status and quality of life.
Olfactory
dysfunction
can
be
the presenting
sign/symptom of neurodegenerative disease (e.g.:
Parkinson disease, Alzheimer disease) or an intracranial
mass lesion.
Disorders can manifest as:
Anosmia ( total loss of smell).
Hyposmia (partial loss of smell).
Dysosmia (distortions of odorants).
Phantosmias ( spontaneous olfactory hallucinations).
Foster Kennedy syndrome:
Optic atrophy in the ipsilateral eye.
Papilledema in the contralateral eye.
Central scotoma in the ipsilateral eye,
Anosmia ipsilaterally.
Etiology:
Optic nerve compression.
Olfactory nerve compression.

Increased intracranial pressure secondary of a frontal


lobe tumor, meningioma or plasmacytoma in olfactory
groove.
Kallman syndrome:
Hypogonadotropic hypogonadism.
Hyposmia or anosmia.
Optic nerve syndromes:
Optic nerve:
Vision is critical for human function and, therefore visual
loss, which can be sudden or gradual and may or may not
be associated with pain.
The intraorbital portion is surrounded by the
subarachnoid space and dura that extend from
intracranial cavity.
Optic neuropathy:
Anterior ischemic optic neuropathy (AION):
AION includes inflammatory diseases of the blood vessels
that affect the optic nerve head and cause swelling of the
optic disc.
Sudden rapid visual loss in one eye.
The vast majority of AION are nonarteritic (NAION):
Diabetes mellitus.
Elevated intraocular pressure.
Hypercoagulate states.
Drop in blood pressure.
Onset of AION or NAION is in patients over 50 years.
Optic neuritis:
Inflammation of optic nerve, which is associated with
swelling and destruction of myelin sheath covering the
optic nerve.
Young adults, usually females, are most commonly
affected.
Symptoms in affected eye include pain on eye movement,
sudden blurred or foggy vision and decrease in color
vision (especially red).
Optic neuritis, when combined with the presence of
multiple demyelinating white mater brain lesions on MRI,
is suspicious for multiple sclerosis (clinically isolated
syndrome).
Compressive optic neuropathy:

Tumors, infections and inflammatory processes can cause


lesions within the orbit and, less commonly, optic canal.
These lesions may compress the optic nerve, resulting
optic disc swelling and progressive visual loss.
Patients often have bulging out the eye (proptosis) with
mild color deficits and almost normal vision with disc
swelling.
Etiology:
Meningiomas.
Hemangiomas.
Lymphangiomas.
Inflammatory orbital pseudotumori.
Metastasis.
Multiple myeloma.
Thyroid ophthalmopathy.
Infiltrative optic neuropathy:
The optic nerve can be infiltrated by a variety of
processes, including tumors, inflammation and infections.
Tumors that infiltrate the optic nerve can be:
Primary (optic gliomas, capillary hemangiomas,
cavernous hemangiomas).
Secondary (sarcoidosis, metastatic carcinoma, nasopharyngeal carcinoma, lymphoma, leukemia).
Traumatic optic neuropathy:
The optic nerve can be damaged when exposed to direct
or indirect injury.
Direct optic nerve injuries are caused by trauma to the
head or orbit (e.g.: bullet that physically injures the optic
nerve).
Indirect injuries, like blunt trauma to the forehead
transmit force to the optic nerve without transgressing
tissue planes.
The most common site of injury of the optic nerve is the
intracanalicular portion of the nerve.
Mitochondrial optic neuropathies:
Genetic mutations in mitochondrial DNA, vitamin depletion,
alcohol and tobacco abuse and use of certain drugs can cause
derangements in efficient transport of mitochondria, which
can cause a primary or secondary optic neuropathy.
Nutritional optic neuropathies:

Months of depletion are usually necessary to deplete


stores of most nutrients.
Patients who suffer from many nutritional optic
neuropathy may notice that colors are not as vivid or
bright as before and that the color red is washed out.
Undernourished patients often suffer from many vitamin
and nutrient deficiencies and have low serum protein
levels.
The optic neuropathy associated with pernicious anemia
and vitamin B12 deficiency can even be seen in wellnourished individuals (e.g.: gastric bypass surgery may
also cause a vitamin B12 deficiency from poor
absorption).
Peripheral neuropathy is often seen in patients with
nutritional optic neuropathies.
Toxic optic neuropathies:
Etiology:
Methanol intoxication.
Ethylene glycol.
Ethambutol.
Amiodarone.
Tobacco exposure.
Hereditary optic neuropathies:
The inherited optic neuropathies typically manifest as
symmetric bilateral central visual loss.
Optic nerve damage in most inherited optic neuropathies
is permanent and progressive.
Lebers hereditary optic neuropathy is the most frequent
occurring mitochondrial disease and this inherited form of
acute or subacute vision loss predominantly affects young
males.
Optic atrophy (OA):
OA is the final common morphologic endpoint of any disease
process that causes axon degeneration in the retinogeniculate
pathway.
Clinically, OA manifests as changes in the color and the
structure of the optic disc as dissociated with variable
degrees of visual dysfunction.

Pathologic classification of OA:


Anterograde degeneration Wallerian degene-ration
(e.g.: toxic retinopathy, chronic simple glaucoma).
Retrograde degeneration (e.g.: optic nerve compression);
Transsynaptic degeneration (e.g.: occipital damage).
Ophthalmoscopic classification of OA:
Primary OA (e.g.: tabes dorsalis, pituitary tumor, optic
nerve tumor, traumatic optic neuropathy, glaucoma,
Lebers disease, ischemic damage, drug intoxication,
multiple sclerosis)
Secondary OA (e.g.: papillitis, papilledema
intracranial hypertension).
Etiologic classification of OA:
Hereditary atrophy (e.g.: Lebers disease, Behrs
disease).
Consecutive atrophy (e.g.: chorioretinitis, pigmentary
retinal dystrophy, cerebromacular degeneration)
Circulatory atrophy (e.g.: ischemic optic neuropathy in
central retinal artery occlusion, in carotid artery
occlusion and in cranial arteritis).
Metabolic atrophy (e.g.: thyroid ophthalmopathy,
juvenile diabetes mellitus Wolfram syndrome,
nutritional amblyopia, toxic amblyopia, tobacco excess,
methyl- alcohol, ethambutol, sulphonamides).
Demyelinating atrophy (e.g.: multiple sclerosis, Devics
disease).
Pressure or traction atrophy (e.g.: glaucoma,
papilledema).
Postinflammatory atrophy (e.g.: optic neuritis,
perineuritis secondary to inflammation of the
meninges, sinus and orbital cellulites).
Traumatic atrophy (e.g.: optic nerve avulsion and
transection, optic nerve sheath hematoma, optic nerve
impingement from a penetrating foreign body or bony
fragment).
Idiopathic atrophy.

Neuromyelitis optica (NMO):


NMO is an autoimmune inflammatory disorder.
Clinically:
Optic neuritis.
Transverse myelitis.
Ocular motor nerves syndromes:
Disorders that produce dysfunction of oculomotor nerves
(cranial nerves III, IV and VI) may be located anywhere from
the ocular motor nuclei to the termination of the nerves in the
extraocular muscles within orbit.
Cranial nerve III
The oculomotor nerve:
It enters the lateral wall of cavernous sinus and divides
into a superior and inferior branch as it enters the orbit
through the superior orbital fissure.
Cranial nerve III palsy:
Interpeduncular damage to the oculomotor nerve may be
partial or complete.
Damage of its subarachnoid portion may occur as:
Isolated pupillary dilatation with reduced or absent
light reaction (exceptionally rare).
Ophthalmoplegia
with
pupillary
involvement
(common).
Ophthalmoplegia with normal papillary size and
reactivity (rare).
Opthalmoplegia with pupillary involvement :
Ipsilateral ptosis.
Ipsilateral dilated pupil (mydriasis) with minimally or
absent reaction to light.
Affected eye is in divergent or temporal position.
External or divergent strabismus out and down.
Horizontal crossed diplopia (horizontal heteronymous
diplopia).
Ipsilateral there will be limitation of elevation,
depression and adduction.
Cranial nerve IV
The trochlear nerve:
It is the only nerve to arise from the dorsal aspect of brain
stem.

It enters to the lateral cavernous sinus and then enters the


orbit through the superior orbital fissure.

Cranial nerve IV palsy:


Paralysis of the trochlear nerve is far less commonly than
paralysis of either the oculomotor or abducens nerves.
Trochlear nerve palsy can be partial or complete.
Clinically:
Vertical strabismus.
Vertical diplopia (is greatest in downgaze and to the
opposite side.
The patient have a rotational and outward position of
affected eye, particularly when the eye is in abduction.
The most patients with trochlear nerve palsy have
torticollis (tilt the head to the site opposite the
paralyzed superior oblique muscle.
Cranial nerve VI
The abducens nerve:
It enters the cavernous sinus lateral to the internal carotid
artery and finally enters the orbit through the superior
orbital fissure.
Cranial nerve VI palsy:
Location and course of abducens nerve, rather than its
length, are the major factors that lead to its frequent
involvement.
Abducens nerve palsy can be partial or complete,
Clinically:
Horizontal uncrossed diplopia (direct, homonymous
diplopia) which worsens at distance.
The patient will have an abduction in the involved eye
(internal or convergent strabismus)
The head is compensatory rotated to the affected eye.
Etiology of ocular motor nerves palsy:
Aneurysms usually arise from junction of the internal
carotid and posterior communicating arteries.
Aneurisms located at top of basilar artery.
Aneurisms located at the junction of basilar artery and
superior cerebellar artery.
Carotid-cavernous sinus fistula.
Tumors or other compressive lesions.

N.B.: diabetes mellitus, often produce an oculomotor


nerve palsy that spares the pupil.

Fisher syndrome (FS):


FS is characterized by:
Relatively symmetrical external ophthalmoplegia.
Limb ataxia severe enough to cause problems with
ambulation.
Areflexia.
Cerebrospinal fluid: albumino-cytological dissociation
with elevated protein level, without increased cell count.
N.B.: FS is a variant of Guillain-Barr disease.
Trigeminal nerve syndromes:
The trigeminal nerve is the biggest cranial nerve and it
carries sensation from the face and mucosal surfaces, cornea
and supratentorial dura, as well as providing motor
innervations to the muscles of mastication.
The trigeminal nerve has 3 main branches: ophthalmic
(V1), maxillary (V2) and mandibular (V3).
V1 leaves the cranial cavity through the superior orbital
fissure, V2 through the foramen rotundum and V3 through
the foramen ovale.
The first-order cell bodies carrying modalities of pain,
temperature, pressure and light touch in all 3 branches
are located in trigeminal (gasserian) ganglion in Meckels
cave (near the petrous apex of temporal bone).
The trigeminal nerve and its branches mediate the
afferent limb of corneal blink and lacrimal reflexes and
both afferent and efferent limbs of the jaw-jerk reflex.
Primary trigeminal neuralgia (classical, typical):
Paroxysmal episodes of intense facial pain that last from a
few seconds to several minutes, affecting one or more
divisions of trigeminal nerve.
Pain is generated spontaneously or by touching a trigger
area.
Attacks of pain is like stabbing electric shocks, burning,
crushing or shooting.
Wind, loud noises, chewing or talking can aggravate facial
pain,

Pain tends to occur in cycles with remissions lasting


months or even years.
Approximately 90% of trigeminal neuralgia is unilaterally.
Pain usually involves a single trigeminal division
(frequently the second or third divisions).
Attacks are stereotyped in the individual patient.
Between attacks there is no pain.
There is no clinically evident sensory or motor deficit.
Not attributed to another disorder.
Neurovascular compression is now accepted as being the
commonest cause of trigeminal neuralgia unresponsive to
medical therapy.
Secondary trigeminal neuralgia (in context of trigeminal
palsy):
Generally, indistinguishable from classical trigeminal
neuralgia.
Paroxysmal attacks of pain with or without persistence of
aching between paroxysms.
Loss of facial sensation.
Paresis of both masseter and pterygoids muscles.
Corneal reflex is diminished or abolished.
Etiology of trigeminal neuralgia and trigeminal palsy:
Trigeminal nerve symptoms are most often found in
association with other clinical features.
Neurovascular compression.
Tortuous branches of the posterior circulation vessels
(e.g.: superior cerebellar artery).
Trigeminal neurinomas.
Acustic neurinomas.
Meningiomas.
Arachnoid cysts.
Epidermoid cysts.
Carotid aneurisms.
Cerebellopontine angle tumors.
Metastatic tumors.
Granulomatous or inflammatory diseases.
Cavernous sinus syndromes.
Atypical trigeminal neuralgia (Type 2 trigeminal
neuralgia, Atypical facial pain ATFP):
ATFP is a syndrome encompassing a wide group of facial
pain problems.

ATFP, often described as burning, aching, cramping or as


migrainous neuralgia, occurs on one side of the face, often
in the region of the trigeminal nerve and can extend into
the upper neck or back of the scalp.
Although rarely as severe as trigeminal neuralgia, facial
pain is continuous for ATFP patients, with few, if any
periods of remission.
ATFP can be bilateral, though the character of pain is
usually different on two sides at any time.
Ophthalmoplegic migraine (now is considered a cranial
neuralgia) presents long-lived severe headache, followed
by a third or, much more rarely, sixth or fourth nerve
palsy.
Depression and anxiety are frequently comorbid with
ATFP.
Etiology:
Vascular compression.
Post herpetic neuralgia.
Atypical odontalgia.
Infections of the sinuses.
Raeder paratrigeminal syndrome (RPS) = Raeder paratrigeminal neuralgia:
Main clinical features:
Severe, unilateral facial pain and headache in
distribution of the ophthalmic division of trigeminal
nerve.
Horner syndrome (oculosympathetic palsy).
Limited or no disturbance of sweating over the
ipsilateral face.
Occasional involvement of the parasellar nerves
(second, third, fourth and sixth cranial nerves).
Cavernous sinus syndrome (CSS):
Cavernous sinuses are paired, venous structures located on
either side of the sella turcica.
They receive venous tributaries from superior and
inferior orbital vein and drain into superior and inferior
petrosal sinuses.
Cavernous sinus contains the carotid artery, its
sympathetic plexus and the oculomotor nerves (III, IV and
VI).

In addition, the ophthalmic branch and occasionally the


maxillary branch of the fifth nerve traverse the cavernous
sinus.
The nerves pass through the wall of the sinus while the
carotid artery passes through the sinus itself.
CSS consist of various combinations of oculomotor palsies
and sensory loss in the first (occasionally second) divisions of
the trigeminal nerve, usually accompanied by signs of
increased pressure or inflammation of venous sinus.
Cranial nerves are affected first on one side only, but any
of the processes that infiltrate or obstruct the sinus may
spread to the other side.
Clinically:
Unilateral and isolated III, IV or VI cranial nerve palsy.
Combination patterns of ophthalmoplegia.
Painful ophthalmoplegia.
Proptosis (pulsating exophthalmos suggests a direct
carotid-cavernous fistula).
Ocular and cranial bruits.
Conjunctival congestion.
Ocular hypertension.
Anesthesia in the ophthalmic division of the trigeminal
nerve (V1).
Decreased or absence of corneal reflex.
Possibly anesthesia in the maxillary division of the
trigeminal nerve (V2).
Horners syndrome or the pupil in midposition and
nonreactive if both sympathetics and parasympathetics systems are affected.
Cavernous sinus tumors:
Cavernous sinus tumors are the most common cause of
CSS.
Metastatic lesions (most often from breast, prostate or
lung):
Isolated or combined ophthalmoplegia.
Painful ophthalmoplegia.
Anesthesia in the ophthalmic nerve.
Pituitary tumors:
Isolated or combined ophthalmoplegia (lateral
extension).
Endocrine signs as acromegaly, galactorrhea.

Unilateral or bilateral visual field defects.


Primary tumors includes: a) meningiomas or neurofibromas; b) locally spreading tumors from nasopharyngeal carcinoma or pituitary tumors.
Cavernous sinus aneurysms:
Carotid-cavernous aneurysms do not involve a major risk of
subarachnoid hemorrhage.
Their rupture can result in direct carotid-cavernous fistulas,
which may lead to cerebral hemorrhage.
These aneurysms, which are more frequent in the elderly
population, present with indolent ophthalmoplegia.
Carotid-cavernous fistulas (C-C fistulas):
C-C fistulas are of 2 types:
Direct fistulas occur if the carotid artery and
cavernous sinus are in continuity with high blood flow
(venous pressure increases) and manifest with abrupt
onset of massive and pulsatile proptosis, chemotic
conjunctival injection, lid congestion, bruit and thrill,
visual loss, ocular hyperpension, optic neuropathy,
optic disc edema, retinal venous congestion, retinal
hemorrhage and ophthalmoplegia.
Indirect fistulas (dural arteriovenous fistulae) occur
with communication between cavernous sinus and
dural branches of internal carotid artery, external
carotid artery or dual supply from both arteries
(fistulous connection is within the wall of the
cavernous sinus) with low blood flow; b) insidious
onset, mild orbital congestion, proptosis and low or no
bruit; c) lesions may fluctuate and may resolve
spontaneously.
Carotid sinus thrombosis:
In addition to local (paranasal sinuses and/or orbital
cellulitis) and systemic infection, the following may be
seen:
Isolated or combined ophthalmoplegia.
Painful ophthalmoplegia.
Orbital congestion.
Visual loss;
Unilateral optic disc edema.
Signs of meningeal irritation.
Etiology:

Primary intracranial tumors (meningiomas, neurofibromas, chondromas).


Localized spread tumor (nasopharyngeal, pituitary).
Metastatic tumors (brest, prostate, lung).
Cranio-cerebral trauma.
Carotid-cavernous aneurysms.
Carotid-cavernous fistulas.
Miscellaneous inflammatory syndromes: a)TolosaHunt syndrome; b) herpes zoster; c) sarcoidosis.

Tolosa-Hunt syndrome (THS):


Clinically:
Unilateral acute retroorbital or periorbital pain
(gnawing or boring pain), which characterizes the
onset of the disorder.
Ophtalmoparesis (various combinations of ocular
motor nerve palsies) or ophthalmoplegia (diplopia
usually follows the onset of pain).
Papillary dysfunction (oculosympathetic paralysis).
Sensory loss in the distribution of the ophthalmic (V1),
with loss of the ipsilateral corneal reflex and
occasionally maxillary (V2) division of the trigeminal
nerve.
Intracranial extension of the inflammation into orbit at
the orbital apex can occur (rare) and can affect the
maxillary (V2) and mandibular (V3) branches of the
trigeminal nerve, the optic nerve and the facial nerve;
Lid swelling and mild proptosis may result if the orbit
is affected.
Spontaneous remissions and exacerbations.
Etiology:
Nonspecific inflammation, granulomatous or nongranulomatous, within the cavernous sinus or superior
orbital fissure.
International Headache Society criteria for THS:
One or more episodes of unilateral orbital pain lasting
for an average of 8 weeks if left untreated.
Third, fourth and/or six cranial nerve palsy, which
begins with two weeks of the onset of orbital pain.
Symptoms that resolve within 48-72 hours of initiation
of steroid therapy.

Exclusion of other etiologies by appropriate


investigation, including neuroimaging.
Facial nerve syndromes:
The first branch of seventh cranial nerve is the greater
superficial petrosal nerve.
This branch travels to sphenophalatine and pterygopalatine
ganglion and carries parasympathetic fibers to innervate the
lacrimal gland of the eye.
The geniculate ganglion containing the cell bodies of
general somatic afferent and special visceral efferent neurons
is located in the temporal bone within facial canal.
The facial nerve exit the cranium through the stylomastoid
foramen and enters to parotid gland.
Facial nerve palsy (FNP):
FNP is defined as an unilateral facial nerve paralysis.
FNP is usually acute in onset.
FNP is characterized by:
Facial drooping (drooping eyelid and corner of the
mouth) on the affected half.
Mild to moderate to severe weakness of facial muscles.
Difficulty in drinking, chewing and blowing.
Drooling of saliva on the affected side.
Trouble speaking.
Inability to close the eye on the affected side.
Discomfort or pain behind the ear on the affected side.
Increased sensitivity to noises in the ear of the affected
side.
Impaired sense of taste in 2/3 of the tongue for sweet,
sour and salt.
Dryness of eye or mouth.
Excess tear formation in the eye on affected side.
Etiology:
Idiopathic (Bells palsy).
Trauma.
Herpes zoster oticus (Ramsay Hunt syndrome).
Acute and chronic otitis media.
Mastoiditis.
Lyme disease.
Mononucleosis.
Diabetes.
HIV infection.

Autoimmune disorders.
Sarcoidosis.
Ramsay Hunt syndrome (RHS):
RHS is a peripheral facial nerve impairment (motor
and/or sensory) due to varicella-zoster virus, with or
without associated rash and is associated with otologic
manifestations other neurologic complications,
including cranial polyneuropathy or meningitis.
RHS is a specific form of herpes zoster that often presents
with pre-eruptive (pre-herpetic) pain, allodinia, burning
or itching generally localized to the ear and mastoid
region.
Facial palsy may precede, occur simultaneously with, or
follow erythematosus maculopapular rash.
A small patients with facial palsy associated with
varicella-zoster infection do not have a rash (or at least no
rash in the expected location in the internal auditory canal
or on the tympanic membrane).
Facial palsy can be associated with decreased lacrimation
and decreased taste (dysguesia) on the anterior two third
of the tongue.
RHS is more likely than Bell palsy to be associated with a
complete clinical facial paralysis.
Otologic complications in RHS include otalgia, tinnitus,
sensorineural hearing loss, hyperacusis (dysacusis),
vertigo, nystagmus and skew deviation with diplopia.
RHS may occur as a cranial polyneuropathy, involving
especially cranial nerves VII and VIII, but also III, V, VI, IX,
X, XI and XII, plus C2-C3 sensory dermatomes.
Etiology:
Varicella-zoster inflammation of the geniculate
ganglion (geniculate neuralgia) and of the skin .
Melkersson-Rosenthal syndrome (MRS):
MRS is characterized by the triad:
Recurrent and sometimes bilateral facial palsy.
Recurrent swelling of orofacial structures.
Furrowed tongue.
Etiology:
Noncaseous granulomas with perivascular and
lymphatic inflammatory cell infiltration.
Glossopharyngeal nerve syndromes:

The ninth nerve is predominantly sensory nerve, but also


contains some motor and parasympathetic fibers.
The root of ninth nerve leaves the skull through the
jugular foramen.
The superior and petrosal ganglia of ninth nerve are in
the jugular foramen.

Glossopharyngeal palsy:
Isolated glossopharyngeal neuropathy is rare as lesions
often involve other cranial nerves in close proximity (VIII,
X, XI and XII).
Quality of speech: a) nasal; b) guttural.
Dysfunction of the secretory parotid gland.
Isolated palsy of ninth nerve can often be asymptomatic,
due to redundant innervations of target structures by the
other cranial nerves.
Clinically:
Difficulty swallowing.
Impairment of taste over the posterior one third of the
tongue for bitter.
Impaired sensation over the posterior one third of the
tongue, soft palate and posterior pharynx.
Absent gag reflex.
Glossopharyngeal neuralgia (GPN):
GPN is a rare pain syndrome, primarily affects the elderly
and is severe and paroxysmal.
Sharp, stabbing pulses of pain in the back of the throat and
tongue, the tonsil and middle ear.
The excruciating pain of GPN can last for a few seconds to
a few minutes.
Paroxysmal pain may return multiple times in a day or
once every few weeks.
Trigger factors:
Swallowing.
Drinking cold liquids.
Talking.
Coughing.
Clearing the throat.

Touching the gum inside the mouth.


GPN can be associated with cardiac dysrhythmia,
bradycardia, hypotension and even asystole and
subsequent syncope.
This effect is similar to that seen in carotid sinus
massage for the treatment of supraventricular
tachycardias (massaging the carotid sinus causes a
hyperstimulation of cranial nerve IX afferent pathway,
resulting in an exaggerated parasympathetic vagal
efferent response).
In an atypical glossopharingeal neuralgia, pain may
radiate in the face, forehead, hypopharynx, larynx and/or
external ear canal.
Etiology:
Microvascular compressions.
Eagles syndrome (cranial nerve IX hyper-excitability
syndrome caused by compression of the nerve against
an elongated of fractured styloid process or a calcified
stylohyoid ligament).
Cerebellopontine angle tumors.
Parapharyngeal space lesions or carcinoma.
Metastasis to petrous temporal bone.
Posttonsillectomy.
Nasopharyngeal carcinoma.
Posterior fossa arteriovenous malformation.
Vagus nerve syndromes:
The vagus nerve exits the brain stem just below the
glossopharyngeal nerve at the pontomedullary junction,
traverses the cerebellopontine angle and exits the cranium
through the jugular foramen.
Innervates all striated muscles of larynx and pharynx
except for stylopharyngeus muscle (innervated by IX) and
tensor veli palatine muscle (innervated by V3).
Sensory input from larynx, pharynx, external auditory
canal, lateral tympanic membrane and posterior fossa
meningeal layers are mediated by the vagus.
Visceral afferent information is conveyed by vagus nerve
from thoracic and abdominal viscera.
Vagus nerve delivers parasympathetic fibers to the
thoracic and abdominal viscera as well, in addition to
larynx and pharynx.

Vagal and superior laryngeal neuralgia:


The two somatic sensory branches of vagus nerve, the
auricular branch and the superior laryngeal nerve can be
the site of a pain syndrome.
Clinically:
Paroxysms of shock-like pain in the side of the thyroid
cartilage, pyriform sinus, angle of the jaw and, rarely, in
the ear.
Occasionally, the pain radiates into the upper thorax or up
into the jaw.
The trigger zone is usually in the larynx and attacks
are precipitated by talking, swallowing, yawning or
coughing.
Swallow syncope or unconsciousness is a rare
complication produced by a vasovagal reflex, with
resulting cardiac inhibition.
Unilateral vagus nerve paralysis:
Hemiparesis of soft palate with hypotonia.
Lueta is deflected by the healthy side of soft palate.
Trouble of swallowing liquids and they will enter the
nasopharinx or trachea.
The vocal cord on the involved side is paralyzed
(recurrent laryngeal nerve paralysis).
Voice is bitonal, hoarse or nasal (recurrent laryngeal
nerve paralysis).
Hemianestesia of soft palate and of the upper third of the
anterior and posterior pillars and corresponding half of
the pharynx.
Loss of velopalatin reflex and of vomiting reflex on the
affected side.
Loss of sensitivity to external auditory meatus and behind
the ear pavilion.
Bilateral vagus nerve paralysis:
Serious disturbances for liquid swallowing.
Pronounced dysphonia that can go up to aphonia.
Autonomic disorders:
Tachycardia or bradycardia.
Severe respiratory disorders with bronchoplegia.
Bilateral recurrent laryngeal nerve paralysis produces
paralysis of both vocal cords, with a whispering voice,
stridor and even death due to tracheal obstruction.

Etiology of uni- and bilateral vagus nerve paralysis:


Meningitis.
Carotid aneurysms.
Neoplasms.
Trauma.
Diphtheria.
Surgery of thyroid neoplasm.
Cervical adenopathy of any cause.
Aortic aneurysm.
Mediastinal tumors.
Accessory nerve syndromes:
The cranial component of cranial nerve XI rapidly joins the
vagus nerve and serves the same function as other vagal
nerve fibers.
In contemporary discussions of the accessory nerve, the
common practice is to dismiss the cranial part altogether,
referring to the accessory nerve specifically as spinal
accesory nerve.
Accessory nerve paralysis:
Atrophy and paralysis of both sternocleidomastoid and
trapezius muscles.
Asymmetric neckline.
Drooping shoulder.
Winged scapula.
Weakness of forward elevation of the shoulder.
Etiology:
Injury of the spinal accessory nerve.
Radical neck surgery.
Cervical lymph node.
Hypoglossal nerve syndromes:
The cranial nerve XII is purely motor in function.
It moves and alter the shape of the tongue by providing
ipsilateral motor innervation to the intrinsic and extrinsic
tongue muscles.
Unilateral hypoglossal paralysis:
Unilateral hypoglossal nerve paralysis is uncommon.
Clinically:
Ipsilateral tongue weakness.
Deviation towards the affected side on tongue
protrusion.

Ipsilateral tongue atrophy (with scalloping or


accentuation of midline groove).
Ipsilateral fasciculation of the tongue.
Bilateral hypoglossal nerve paralysis:
Clinically:
Bilateral tongue weakness.
Tongue atrophy and flaccidity.
Inability to move the tongue from side to side or
vertically.

Multiple cranial nerve syndromes:


Clinical features depend on cranial nerves involved.
Rochon-Duvigneaud syndrome = Superior orbital fissure
syndrome.
Cranial nerves involved: III, IV, V(1st division), VI.
Ophthalmoplegia.
Pain and hypoesthesia in the first division of V.
Exophthalmos.
Vegetative disturbances.
Foix-Jefferson syndrome = Cavernous sinus syndrome.
Cranial nerves involved: III, IV, V1, VI.
Painful ophthalmoplegia.
Exophthalmos.
Gradenigo-Lannois syndrome = Apex of petrous temporal
syndrome.
Cranial nerves involved: V, VI.
Trigeminal neuralgia.
Sensorimotor disturbances.
Diplopia.
Negri-Jacod syndrome = Petreosphenoidal region syndrome.
Cranial nerves involved: II, III, IV, V, VI.
Ophthalmoplegia.
Amaurosis.
Trigeminal neuralgia.
Avellis-Longhi syndrome = Jugular foramen syndrome.
Cranial nerves involved: IX, X.
Paralysis of one vocal cord.
Paralysis of pharynx.

Paralysis of soft palate.


Loss of gag reflex.
Vernet syndrome = Jugular foramen syndrome.
Cranial nerves involved: IX, X, XI.
Dysartria.
Dysphagia.
Weakness of sternocleidomastoid and trapezius
muscles.
Loss of gag reflex.

Tapia syndrome = Jugular foramen + hypoglossal canal


syndrome.
Cranial nerves involved: X, XII.
Paralysis of the pharynx, larynx and tongue.
Sicard-Collet syndrome = occipital condyles syndrome.
Foramen jugular syndrome plus paralysis of XII.
Cerebellopontine angle syndrome:
Cranial nerves involved: V, VII, VIII, IX to XII.
Deafness.
Vertigo.
Nystagmus.
Raised intracranial pressure.
Brain stem symptoms.
Garcin syndrome = Hemibasal syndrome.
Cranial nerves involved: I to XII on one side or nearly all
unilateral cranial nerves.
Garcin syndrome in its complete form is very rare.
There must be at least 7 ipsilateral cranial nerve palsies as
the basis for the diagnosis of the Garcin syndrome.
Usually some nerves and involvement of contralateral
nerves can be found.
Usually lack of pyramidal signs or any rise of intracranial
pressure.
Etiology:
Neoplasm at base of skull.
Paraneoplastic syndrome with multiple cranial nerve
palsies.
Inflammatory lesions at the base of the skull.
Fractures of the base of skull.
Complications of surgery and radiofrequency lesions.

Vascular diseases.
Infections.
Pachymeningitis.
Wagener granulomatosis.
Hyperostossis of the skull.
Gullain-Barr disease.
Metabolic disorders.
Idiopathic cranial neuropathy.

VI. SPINAL CORD SYNDROMES


Spinal cord is a structure of central nervous placed in the
vertebral canal which begins at the occipital bone and extends
down to the space between the first and second lumbar
vertebrae.
The spinal cord has three major functions:
Serve as a conduit for motor information, which travels
down the spinal cord.
Serve as a conduit for cord sensory information, which
travels up the spinal cord.
Serve as a centre for coordinating certain reflexes.
The ventral (motor) and dorsal (sensory) nerve roots
combine to form spinal nerves, one on each side of the spinal
cord and exit the intervertebral foramina.
Each segment of spinal cord is associated with a pair of
ganglia, called dorsal root ganglia, which are situated just
outside of spinal cord.
These ganglia contain cell bodies of sensory neurons.
Axons of these sensory neurons travel into spinal cord,
via the dorsal roots.
Ventral roots consist of axons from motor neurons, which
bring information to the periphery from cell bodies within
CNS.
The gray matter, in the center of the cord, is shaped like a
butterfly and consist of cell bodies of interneurons and
motor neurons. It also consist of neuroglia
cell and
unmyelinated axons.
Projections of gray matter are called horns.

Together, the gray horns and gray commisure form the


gray H.
The white matter is located outside of gray matter and
consist almost totally of myelinated motor and sensory axons
grouped into tracts.
In the upper part of the vertebral column, spinal nerve exits
directly from the spinal, whereas in the lower part of the
vertebral column, spinal nerves pass further down the
column before exiting.
The human spinal cord can be anatomically divided into 33
spinal segments based on the origins of the spinal nerves:
lateral (DL) lower motor neurons in the ventral horn,
which are involved in distal limb control (these DL
neurons 8 cervical segments forming 8 pairs of cervical
nerves:
C1 spinal nerves exit column between occiput and CI
vertebra.
C2 nerves exit between posterior arch of C1 vertebra
and lamina of C2.
C3-C8 spinal nerves through intervertebral foramen
(IVF) above corresponding cervical vertebra, with the
exception of C8 pair which exit via IVF between C8 and
T1 vertebra.
Thoracic segments forming 12 pair of thoracic nerves and
exit spinal column through IVF, below corresponding
vertebra T1-T12.
Lumbar segments forming 5 pairs of lumbar nerves and
exit spinal column through IVF, below corresponding
vertebra L1-L5.
Sacral segments forming 5 pairs of sacral nerves and exit
spinal column through IVF, below corresponding vertebra
S1-S5.
Coccygeal segments( a number of 3) joined up becoming a
single segment forming 1 pair of coccygeal nerves and exit
spinal column through the sacral hiatus.
There are two regions where the spinal cord enlarges:
Cervical enlargement corresponds roughly to the
brachial plexus nerves, which innervate the upper limb
and includes spinal cord segments from about C4 to
T1(the vertebral levels of the enlargement are roughly the
same).

Lumbosacral enlargement corresponds to the


lumbosacral plexus nerves, which innervate the lower
limb and comprises the spinal cord segments from L2 to
S3 (the vertebral levels of the enlargement are T9 to T12).
Somatosensory organization:
Spinothalamic tracts (anterior and lateral).
Dorsal column tract.
Spinocerebellar tracts (anterior and posterior).

All sensory pathways use three different neurons


(primary, secondary, tertiary) to get information from
sensory receptors at the periphery to the cerebral cortex.
In all pathways, primary sensory neuron cell bodies are
found in the dorsal root ganglia and their central axons
project into the spinal cord.
Motor organization:
Corticospinal tract (pyramidal system) is divided in two
different tracts: a) lateral corticospinal tract; b) anterior
corticospinal tract.
Lateral corticospinal tract descends in the lateral column
and contains upper neuronal axons which synapse
ipsilateral on dorsal are found specifically only in the
cervical and lumbosacral enlargements).
Anterior corticospinal tract descends ipsilaterally in the
anterior column, where the axons emerge and either
synapse on lower ventromedial (VM) motor neurons in
the ventral horn ipsilaterally or decussate at the anterior
white commisure where they synapse on VM lower motor
neurons contralaterally (the VM lower motor neurons are
located throughout the spinal cord and control the large,
postural muscles of the axial skeleton).
Extrapyramidal tracts are: a) rubrospinal;
b)
vestibulospinal; c) tectospinal; d) reticulospinal.
Rubrospinal tract descends with the lateral
corticospinal tract.
Tectospinal, vestibulospinal and reticulospinal tracts
descend ipsilaterally in the anterior column but not
synapse across the anterior white commisure.
Extrapyramidal tracts only synapse on VM lower
motor neurons ipsilaterally.

The terminal portion of the spinal cord is called the conus


medullaris.
The cauda equina (horses tail) is the name for the
collection of nerves (nerve roots L1-L5 and S1-S5) in the
vertebral column that continue to travel through the vertebral
column below the conus medullaris (located
at ~ L1 level
and end at ~L2-L3).
The cauda equina forms as a result of the fact that spinal cord
stops growing in length at about age four, even though the
vertebral column continues to lengthen until adulthood.
This results in the fact that sacral spinal nerves actually
originate in the upper lumbar region.
Spinal cord transection syndrome:
Spinal shock:
Rapid and complete loss of voluntary movement and
sensation from levels below the cord lesions.
Flaccid, massive, total and homogeneous tetraplegia, if the
lesion is on cervical segments.
Flaccid, massive, total and homogeneous paraplegia , if the
lesion is on thoracic segments.
Upper limit of anesthesias correspond to the level of
lesion.
Signs of affected lower motor neuron at the level of lesion.
Autonomic disturbances:
Initially, retention of urine and feces (since ascending
sensory pathways are interrupted there is no
awareness of bowel or bladder fullness).
Cutaneous blood vessels in the areas below the lesion
do not respond to hot or cold stimuli.
Anhidrosis, paroxysmal cardiorespiratory disorders
(inability to regulate heart rate and blood pressure).
Trophic disorders (muscle atrophy, oedema, galloping
bedsores).
The spinal shock duration can vary between 3 to 6 weeks.
Spinal automatism:
As spinal shock fades it may be replaced by heightened
flexor reflex activity (e.g.: Marie-Foix retraction sign =
pressure on the toes or vigorous plantar flexion at the
ankle leads to flexion at the hip and knee and to attempts
for dorsiflexion of the ankle) in which exaggerated deep

tendon reflexes and Babinski sign occur in response to


noxious or even trivial stimuli.
A mass reflex may develop in which slight stimuli elicit
severe bilateral spasms of the arms and legs accompanied
by evacuation of the bowel and bladder, profuse sweating
and even priapism (a sustained reflexogenic erection).

Automatic reflex activity is also heightened and so filling


of the bladder or rectum may result in increased seating,
flushing of the face, piloerection, shivering, slowing of the
pulse and elevation of blood pressure.
After a period of time the segmental reflex arcs reappear
and become supersensitive to segmental sensory
information, the effects of which easily spread to adjacent
cord levels and the reflex responses are now operating
without the usual controls .
Spastic paralysis begins with Babinski sign and later the
others signs appear (e.g.: increased muscle tone
sometimes in flexion, heightened deep tendon reflexes
and loss of superficial (abdominal and cremasteric)
reflexes below the level of lesion.
Loss of all sensation bilaterally below the level of the lesion
(proprioception, vibratory sense, tactile discrimination,
pain, temperature, light touch and visceral sensibility).
Involuntary and unconscious voiding.
Etiology:
Traumatic spinal injuries.
Spinal tumor.
Vascular disorders.
Spinal epidural hematoma.
Spinal abscess.
Intervertebral disk herniation.
Transverse myelitis.
Topographic diagnosis:
Cervical:
C1/C2: will often results in loss of breathing, necessitating
mechanical ventilators or phrenic nerve pacing.
C3: typically results in loss of diaphragm function,
necessitating the use of ventilator for breathing.

C4: results in significant loss of function at the shoulder


and biceps.
C5: results in potential loss of function at the shoulders
and biceps and complete loss of function at the wrists and
hands.
C6: results in limited wrist control and complete loss of
hand function.
C7/T1: results in lock of dexterity in the hands and
fingers, but allows for limited use of arms.
Thoracic:
T1 to T8: results in the inability to control the
abdominal muscles with trunk instability.
T1 to T12: results in partial loss of trunk and
abdominal muscle control.
Lumbosacral:
Decreased control of: a) the hips and legs; b) urinary
and defecation systems.
Lateral hemisection spinal cord syndrome (Brown
Squard syndrome):
The Brown Squard syndrome is characterized by:
Ipsilateral upper motor neuron syndrome below the
level of lesion.
Ipsilateral anterior horn and roots syndromes at the
level of lesion.
Ipsilateral posterior horn and roots syndromes at the
level of lesion.
Ipsilateral loss of conscious proprioception and
discriminative touch.
Contralateral loss of pain, temperature and nondiscriminative touch below the level of lesion.
Etiology:
Extramedullary trauma.
Extramedullary tumor.
Extramedullary spinal vascular malformation.
Anterior hemisection spinal cord syndrome =
~
anterior artery syndrome:
Anterior spinal cord syndrome is characterized by:
Bilaterally anterior horns syndrome at the level of
lesion.
Quadriparesis /paraparesis below the level of the
lesion.

Loss of pain and temperature sensation at and below


the level of the lesion.
Retained proprioception and vibratory sensation.
Etiology:
Disc herniation.
Anterior spinal artery occlusion.
Aortic dissection.
Posterior hemisection spinal cord syndrome =
~
posterior artery syndrome:
Very rare condition:
Loss of proprioception, vibration sensation and epicritic
sensation (e.g.: stereognosis, graphestesia).
Motor function, sense of pain and sensitivity to light touch
remain intact.
Etiology:
Posterior spinal artery occlusion.
Combined spinal cord syndromes:
Posterior and lateral columns syndrome:
Subacute combined degeneration:
Paresthesias of the feet.
Loss of proprioceptive and vibration sense.
Sensory ataxia.
Upper motor neuron syndrome.
Etiology:
Vitamin B12 deficiency.
Vacuolar myelopathy.
Extrinsec cord compression.
Combined anterior horn cell + pyramidal tract syndrome:
Amyotrophic lateral sclerosis (ALS) syndrome:
Upper motor neuron syndrome.
Lower motor neuron syndrome with lesions at the
anterior horn cell level.
Aran-Duchenne syndrome:
Form of ALS with upper limbs onset.
Bilateral muscle atrophies and muscular fasciculations at
upper limbs, predominant at hands and at 1/3 distal level
of forearms.
Muscular spasticity in different degrees, hyperreflexia and
Babinski sign.
The progress of muscle atrophy induces, in different
phases of disease, particular aspects of the hands (e.g.:

simian hand to claw hand, preacher hand, puppet


hand or cadaveric hand.
Combined posterior tract + spinocerebellar tract
pyramidal tract syndrome = Friedreich ataxia.
Loss of position sense, discrimination and stereognosis.
Spinal ataxia.
Rombergs sign.
Later, spastic paraparesis.
Combined posterior columns + posterior roots +
autonomic system syndrome = tabetic syndrome.
Lancinating pains in the legs.
Severe painful crisis (e.g.: glossodynia, epigastric pain)
Impaired vibration and position sense.
Decreased tactile localization.
Temporal and spatial disturbance (loss of coordination).
Hypotonia of skeletal musculature.
Wide-based and slapping gait.
Sensory gait ataxia (worse in darkness or with eyes
closed).
Areflexia of patellar and ankle stretch reflexes.
Rombergs sign.
Argyll Robertson pupil.
Bladder incontinence and loss of sexual function.
Combined central spinal + anterior horn + pyramidal
tract + autonomic syndrome = syringomyelic syndrome.
Bilateral vest-like loss of pain, temperature and nondiscriminative touch.
Preservation
of
proprioception,
vibration
and
discriminative touch.
Abnormal body temperature or sweating.
Trophic disturbances of the skin.
Segmental neurogenic atrophy, paresis and areflexia
(Aran-Duchenne syndrome) at the level of upper limbs.
Spastic paraparesis below the level of damage.
Scoliosis.
Neuropathic artropathy (Charcot joint) in the shoulders.
Abnormal bowel and bladder control.
Cauda equina syndrome:
Cauda equina syndrome is a serious neurologic condition:

Early bilateral and asymmetrical radicular pain in the


distribution of the lumbosacral roots, increased by
Valsalva maneuver.
Flaccid, hypotonic, amyotrophic, areflexic paralysis (true
peripheral-type paraplegia).
Absence of the Achilles reflexes (S1-S2 roots).
The patellar reflexes (L2-L4 roots) have a variable
response.
Late asymmetrical sensory loss in saddle region,
involving the anal, perineal and genital regions and
extending to the dorsal aspect of the thigh, the
anterolateral area of the leg and the outer aspect of the
foot.
Late sphincter and sexual dysfunctions:
Autonomous neurologic bladder (urinary retention
and post-void residual incontinence).
Decreased anal muscle tone and defecation sensation
(constipation, faeces incontinence).
Erection and ejaculation impaired less often.
Etiology:
Lumbar spine trauma.
Spinal epidural hematoma.
Central disk herniation (L4/L5 or L5/S).
Spinal stenosis.
Primary or metastatic tumors.
Pagets disease.
Ankylosing spondylitis.
Spinal epidural abscess.
Inflammatory demyelinating polyneuropathy.
Conus medullaris syndrome:
Clinically:
Spontaneous pain is: a) uncommon; b) relatively mild;
c) bilateral and symmetrical; d) perineum and thighs.
Sensory findings: a) presents early; b) saddle distribution;
c) bilateral and symmetrical.
Motor findings: a) symmetrical or asymmetrical mild
lower extremities weakness; b) poor rectal tone; d)
absent muscle atrophy.
Reflex changes: a) Achilles reflex absent; b) patellar reflex
normal.

Sphincter dysfunctions: a) present early; b) severe;


c)
absent anal and bulbo-cavernosus reflex.
Sexual dysfunctions: a) impaired erection and ejaculation.
Etiology: the same diseases as in cauda equina syndrome.

VII. BRAIN STEM SYNDROMES

The brain stem is the posterior part of the brain which is located
caudal to the diencephalon, ventral to the cerebellum and rostral
to the spinal cord.
The brain stem provides the main motor and sensory
innervations to the face and neck (via cranial nuclei and
cranial nerves (CN): III, IV,V, VI, VII, VIII, IX, X, XI and XII).
The brain stem includes:
Midbrain (mesencephalon).
Pons (part of metencephalon).
Medulla oblongata (myelencephalon).
Medial structures of brain stem:
Motor pathway.
Medial lemniscus.
Medial longitudinal fasciculus.
Motor nucleus and nerve.
Periaqueductal gray matter.
Central tegmental tract.
Reticular formation.
Lateral structures of brain stem:
Spinocerebellar pathway.
Spinothalamic pathway.
Sensory nucleus of cranial nerve V.
Sympathetic pathway;
Reticular formation.
The brain stem is an extremely important part of the brain
as the nerve connections of the motor and sensory systems of
the main part of the brain to or from the rest of the body
(corticospinal tract, the posterior column-medial lemniscus
pathway, spinothalamic tract and spinocerebellar tract).
The brain stem plays also an important role in:

Regulation of cardiac and respiratory function.


Pain sensitivity control.
Maintaining alertness, awareness and consciousness;
Regulation of the sleep cycles.
The brain stem syndromes general rules:
Pathways and tracts pass through the entire length of the
brain stem and can be linked to meridians of longitude
whereas the various cranial nerves can be regarded as
parallels of latitude.
Establishing of intersect between meridians of longitude
and parallel of latitude it is possible to establish the site of the
lesion.
Lesions of medial structures: a) contralateral weakness; b)
contralateral proprioception/vibration loss; c) ipsilateral
internuclear ophthalmoplegia; d) ipsilateral cranial nerve
function loss.
Lesions of lateral structures: a) ipsilateral ataxia;
b) contralateral pain/temperature loss; c) ipsilateral
pain/temperature loss of face;
d) ipsilateral Horner
syndrome.
Lesions of the four CN of medulla oblongata: a) glossopharingeal (IX) ipsilateral pharyngeal sensory loss;
b)
vagus (X) ipsilateral palatal weakness; c) spinal accessory
(XI) ipsilateral shoulder weakness; d) hypo-glossal (XII)
ipsilateral weakness of tongue.
Lesions of the four CN of pons: a) trigeminal (V) ipsilateral
facial sensory loss; b) abducens (VI) ipsilateral eye
abduction weakness; c) facial (VII) ipsilateral facial
weakness; d) auditory (VIII) ipsilateral deafness.
Lesions of two CN of midbrain: a) oculomotor (III) eye
turned out and down; b) trochlear (IV) eye unable to look
down when looking towards nose.
Alternating syndromes:
Ipsilateral = affected CN.
Contralateral = affected trunk and limbs.
Almost all brain stem syndromes are induced by vascular
lesions (infarcts).
A small part of the brain stem syndromes are of tumoral
nature.
Medulla oblongata syndromes:

Lateral and rostral medullary syndrome (retroolivar


Wallenberg syndrome) = posterior inferior cerebellar
artery syndrome:
Ipsilateral:
Facial hemihypoalgesia and hemithermoanesthesia
syringomyelic dissociation (nucleus and tract
of
CN V).

Palatal, pharyngeal and vocal cord paralysis with


dysphagia, dysarthria and dysphonia (nucleus
ambiguu CN IX, X, XI).
Vestibular syndrome with vertigo, nausea, vomiting
and nystagmus (vestibular nuclei).
Cerebellar hemisyndrome predominant at lower limb
(inferior cerebellar peduncle and spinocerebellar
tract).
Horners syndrome (descending sympathetic fibers).
Contralateral:
Trunk
and
limbs
hemihypoalgesia
and
thermoanesthesia syringomyelic dissociation
(spinothalamic tract).
Medial and caudal medullary syndrome (interolivar
syndrome, Djerine syndrome) = paramedian basilar
artery branches syndrome:
Ipsilateral:
Deviation of the tongue to the ipsilateral side of the
infarct on attempted protrusion caused by muscle
weakness amyotrophy fasciculations of ipsilateral
hemitongue
(nucleus and fibers of CN XII).
Contralateral:
Limbs weakness or hemiplegia (ipsilateral medullary
pyramid).
Loss of discriminative touch, conscious proprioception
and vibration sense tabetic dissociation (medial
lemniscus).
Bilateral
Upbeat nystagmus (medial longitudinal fasciculus
MLF)).
Combined lateral and medial medullary syndrome (hemimedullary syndrome, Babinski-Nageotte syndrome):

Ipsilateral:
Horners syndrome.
Weakness of soft palate, pharynx, larynx and tongue.
Loss of taste of the posterior third of the tongue.
Cerebellar ataxia with nystagmus.
Contralateral:
Hemiparesis.
Hemianesthesia.

Avellis syndrome = tegmentum of the medulla syndrome:


Ipsilateral:
Paralysis of soft palate and vocal cord (nucleus
ambiguu CN IX, X, XI).
Contralateral:
Hemianesthesia.
Schmidt syndrome:
Ipsilateral:
Paresis of muscle of vocal cord, soft palate, trapezius
and
sternocleidomastoid

amyotrophy

fasciculations (nucleus ambiguu CN IX, X, XI +


external part of XI).
Contralateral:
Hemiplegia.
Jackson syndrome:
Ipsilateral:
Paresis of soft palate, trapezius, sternocleidomastoid
and tongue (nucleus ambiguu CN IX, X, XI + external
part of XI + XII).
Contralateral:
Hemiparesis.
Inferior olivary nucleus hypertrophy syndrome:
Controlateral:
Palatal myoclonus.
Pontine syndromes:
Millard-Gubler syndrome (caudal ventral pontine
syndrome):
Ipsilateral:
Diplopia accentuated when the patient looks towards
the lesion (CN VI).
Peripheral facial nerve paralysis and loss of corneal
reflex (CNVII).

Contralateral:
Hemiplegia (corticospinal tract).
Etiology:
Occlusion of paramedian branches and short circumferential arteries of basilar artery.

Inferior Foville syndrome = unilateral lesion in the


dorsal caudal third of the pons:
Ipsilateral:
Peripheral type of facial palsy (nucleus and fibers of
CNVII).
Gaze is away from the lesion (paramedian pontine
reticular formation PPRF or CN VI nucleus).
Controlateral:
Hemiplegia with sparing of face.
Etiology:
Occlusion of paramedian branches and short circumferential arteries of basilar artery.
Locked-in syndrome = ventral pontine syndrome,
cerebro-medullospinal disconnection, de-efferented
state:
Bilateral:
Tetraplegia = quadriplegia (bilateral corticospinal
tract in the basis pontis).
Preserved sensory receptivity.
Patients are conscious and aware with no loss of
cognitive function.
Aphonia (bilateral corticonuclear tract of lower CNs).
Occasionally,
impairment
of
horizontal
eye
movements.
Inability to speak in otherwise cognitively intact
individuals.
May be able to communicate with others through
coded messages by blinking or moving their eyes,
which are often not affected by the paralysis.
Individuals lock coordination between breathing and
voice.
Etiology:
Occlusion of paramedian branches of basilar artery.

Middle Foville syndrome = unilateral lesion in the dorsal


rostral third of the pons:
Ipsilateral:
Gaze is away from the lesion.
Contralateral:
Hemiplegia with central facial paralysis.

Raymond-Cestan syndrome = unilateral lesion in the


ventral rostral medial pons:
Ipsilateral:
Gaze is to the lesion (peduncular or superior Foville
syndrome).
Cerebellar ataxia with rubral tremor (superior
cerebellar peduncle).
Athetosis.
Contralateral:
Hemiparesis (corticospinal tract).
Hemianesthesia (spinothalamic tract and medial
lemniscus).
Etiology:
Occlusion of paramedian branches of basilar artery.
Grenet syndrome = unilateral lesion in the middle third
of ventral caudal of the pons:
Ipsilateral:
Anesthesia of the face and paralysis of chewing
muscles (CN V sensory and motor).
Peripheral facial paralysis (CN VII).
Inferior Foville syndrome.
Ataxia (middle cerebellar peduncle).
Contralateral:
Hemiparesis (corticospinal tract).
Hemianesthesia for pain and temperature (spinothalamic tract).
Etiology:
Occlusion of paramedian branches of basilar artery.
Marie-Foix syndrome = lateral pontine syndrome:
Ipsilateral:
Cerebellar ataxia (middle cerebellar peduncle).
Contralateral:
Hemiparesis (corticospinal tract).

Hemisensory loss pain and temperature (spinothalamic tract).


Etiology:
Occlusion of long circumferential branches of basilar
artery.
Occlusion of anterior inferior cerebellar artery.

Posterior internuclear ophthalmoplegia syndrome:


The ocular axes will be parallel and there is no strabismus
or diplopia at rest.
Fails to abduct the eye normally on attempted horizontal
gaze to the same side with strabismus and uncrossed
diplopia (lateral rectus muscle is paralyzed).
Adduction of contralateral eye is normal (medial rectus
muscle is normal).
Horizontal nystagmus in the abducting eye.
Convergence is preserved.
Etiology:
Unilateral lesion of MLF which interrupt the fiber tract
that connect the pontine center for conjugate
horizontal gaze (PPRF) and the ipsilateral CN VI.
Multiple sclerosis (bilateral).
Brain stem ischemia (unilateral).
One-and-a-half syndrome:
A conjugate horizontal gaze palsy in one direction and an
internuclear ophthalmoplegia in the other.
Limitation of horizontal eye movement to adduction in
one eye with no horizontal movement of the other eye.
Nystagmus is also present when the eye on the opposite
side of the lesion abducted.
Convergence is spared.
Etiology:
Unilateral and ipsilateral lesion of PPRF and of MLF.
Laryngeal, pharyngeal and palatal myoclonus syndrome:
Etiology:
Lesion of central tegmental fasciculus (retroolivary
connections).
Dysarthria-clumsy hand syndrome:

Ipsilateral:
Unilateral central facial weakness (corticospinal tract).
Clumsiness appearing as a cerebellar ataxia.
Dysarthria without dysphasia.
No sensory symptoms or signs.
Etiology:
Lacunar infarction at junction of upper one-third and
lower two-thirds of pons.

Ataxic Hemiparesis syndrome:


Contralateral:
Weakness more prominent in leg than arm.
Ataxia arm and leg.
Etiology:
Lacunar infarction in the basis pontis (small
penetrating arteries of basilar artery).
Midbrain syndromes:
Weber syndrome = ventral medial midbrain syndrome:
Ipsilateral:
Diplopia with drooping eyelid and fixed wide pupil (CN
III).
Contralateral:
Hemiplegia (corticospinal tract).
Etiology:
Occlusion of the paramedian branches of the posterior
cerebral artery or of basilar bifurcation perforating
arteries.
Nothnagel syndrome = dorsal midbrain syndrome:
Ipsilateral:
Oculomotor palsy (CN III).
Contralateral:
Cerebellar ataxia (superior cerebellar peduncle).
Benedikt syndrome = paramedian midbrain syndrome:
Ipsilateral:
Oculomotor paresis with fixed and dilated pupil
(CN III).
Contralateral:
Cerebellar
ataxia
with
tremor
(brachium
conjunctivum).
Involuntary movement resembling parkinsonian.

Rubral tremor, hemichorea and hemiathetosis (red


nucleus).
Hemiparesis (corticospinal tract).
Etiology:
Occlusion of branches of posterior cerebral artery.
Claude syndrome = paramedian midbrain tegmental
syndrome:
Ipsilateral:
Oculomotor paresis with fixed and dilated pupil (CN
III).
Trochlear paresis (CN IV).
Contralateral:
Cerebellar ataxia.
Rubral tremor = present at rest, at posture and with
intention (red nucleus).
Hemianesthesia (spinothalamic tract).
Etiology:
Occlusion of a branch of the posterior cerebral artery.
Anterior internuclear ophthalmoplegia syndrome:
The ocular axes will be parallel and there is no strabismus
or diplopia at rest.
On attempted lateral gaze, the lateral rectus will contract
with failure of contraction of the opposite medial rectus
and strabismus will occur with crossed diplopia.
Horizontal nystagmus in the adducting eye.
Convergence is preserved.
More frequently than posterior internuclear ophthalmoplegia.
Etiology:
Unilateral lesion of MLF which interrupt the fiber tract
that connect the PPRF and contralateral CN III:
Superior Foville syndrome = unilateral lesion at
midbrain level and above, including cerebral
hemisphere:
Ipsilateral:
Gaze is towards the lesion.
Contralateral:
Hemiplegia with central facial paralysis.
Parinaud syndrome = dorsal midbrain syndrome:
Paralysis of upgaze (downward gaze is usually preserved).

Pseudo-Argyll Robertson pupils (accommodative paresis


ensues and pupils become mid-dilated and show lightnear dissociation.
Convergence-retraction syndrome (attempts at upward
gaze often produce this phenomenon).
Collier sign = eyelid retraction.
Conjugate down gaze in the primary position.
Less commonly:
Spasm of accommodation on attempted upward gaze.
Slower movements of the abducting eye than the
adducting eye during horizontal saccades.
See-saw nystagmus.
Ocular motility deficits (e.g.: skew deviation,
oculomotor nerve palsy, trochlear nerve palsy,
internuclear ophthalmoplegia.
Etiology:
Compression, demyelinating disorders or ischemic
damage of mesencephalic tectum, including the
superior colliculus adjacent origin of CN III and
Edinger-Westphal nuclei (e.g.: pinealoma, multiple
sclerosis, stroke of upper brain stem)
Sylvian aqueduct syndrome:
Impairment of vertical gaze.
Retraction nystagmus.
Convergence nystagmus.
Convergence spasm.
Vertical nystagmus.
Extraocular paresis.
Pathologic lid retraction.
Etiology:
Lesions in the mesencephalon involving the periaqueductal gray matter.
Obstructive hydrocephalus.
Tumor.
Top-of- the-basilar syndrome:
Rostral brain stem infarction:
Disorders of vertical gaze one or both eyes may rest
in a downward position.
Disorders of convergence one or both eyes mai rest
in an inward position (convergence spasm,
pseudosixth phenomenon).

Convergence retraction nystagmus.


Elevation and retraction of the upper eyelids.
Skew deviation (ocular divergence in the vertical
plane).
Internuclear ophthalmoplegia or third nerve palsies.
Hypersomnolence.
Pupils are small and the reaction to light is often
transient and of small magnitude.
Peduncular hallucinosis (rare).
Unilateral occipital hemispheric infarction:
Homonymus hemianopsia with awareness of the
visual deficit.
Visual perseverations.
Left occipital infarction: a) anomic aphasia; b) alexia
without agraphia; c) temporary Korsakoff-like
amnestic syndrome.
Right occipital infarction: a) Charcot-Wilbrand
syndrome of defective revisualization, absence of
visual dreaming and prosopagnosia.
Bilateral occipital hemispheric infarction:
Cortical blindness.
Balint syndrome: a) asimultagnosia; b) optical apraxia;
c) apraxia of gaze; d) metamorphosia.
Defects in the acquisition of new information.
Agitated delirium.
Etiology:
Infarction of rostral brain stem, thalamus and part of
the temporal and occipital lobes.
Occlusive vascular disease (e.g.: embolus) of the
rostral basilar artery.

VIII. VESTIBULAR SYSTEM SYNDROMES

Vestibular system (VS) serves three primary purposes in man:


VS plays the dominant role in the subjective sensation of
motion and spatial orientation of the head.
VS adjust muscular activity and body position to maintain
posture.
VS stabilizes in space the fixation point of the eyes when the
head moves, providing a stable image upon the retina.
VS is based on the principle of fusion of bilateral sensors, the
input of which is distributed in a bilaterally organized
neuronal network:
Vestibular ocular motor functions (mediated by the
vestibulo-ocular
reflex
and
vestibulo-cerebellar
connections).
Perceptual functions (operate via pathways that run
through posterolateral vestibular thalamus to a number
of temporoparietal cortex areas).
Postural control of head and body (mediated via the
vestibule-cerebellar connections and vestibulo-spinal
tracts to the cervicothoracic spinal cord);
Vegetative functions (conveyed by pathways from the
vestibular nuclei to the reticular formation nuclei of brain
stem, hippocampus and hypothalamus).
Peripheral vestibular system includes
labyrinth and
vestibular nerve.
Central vestibular system includes vestibular nuclei and all
the connections with the cerebral, cerebellar and spinal cord
structures.

Peripheral vestibular syndromes (harmonious,concordant):


Labyrinthic syndrome (labyrinth):
Sudden, memorable onset.
Vertigo is intense, rotative, paroxystic and underlined by
movement of head.
Nystagmus is dominantly horizontal, spontaneous,
positional or evoked, with the fast eye movement
(saccadic movement) towards the healthy part
(contralateral beating).
Romberg test is positive on affected part (body deviation
after a few seconds).
The arms stretched test (Barany test) tonic deviation in
the arms towards affected part.
Hearing symptoms may be associated (deafness,
hypoacusis, tinnitus).
Pronounced vegetative disorders (nausea, vomiting,
pallor, sweating).
Etiology:
Benign paroxysmal positional vertigo.
Labyrinthitis.
Mnire disease.
Trauma of the ear.
Perilymph fistula.
Retrolabyrinthic syndrome (vestibular nerve):
Mild vertigo.
Nystagmus is horizontal and contralateral beating.
Romberg test is positive on affected part.
Tonic deviation in the arms towards affected part.
Hearing symptoms are minor.
Vegetative disorders are lesser.
Frequently, signs of other affected cranial nerves (CN V,
CN VI and/or CN VII).
Etiology:
Vestibular neuronitis
Cerebral trauma with fracture of petrous bone.
Cerebellopontine angle tumor.
Central vestibular syndrome (disharmonious, nonconcordant):
Mild vertigo, sometimes continuously.
Nystagmus is unsystematic (direction-changing), ample,
vertical, swinging, disjunctive.

Unsystematic tonic deviation of the body and arms.


Vegetative and hearing disorders are missing.
In principle, accompanied by other symptoms of brain
stem lesions.
Etiology:
Multiple sclerosis.
Posterior cerebellar artery occlusion.
Anterior inferior cerebellar artery occlusion.
Auditory artery occlusion.
Pontine hemorrhage.
Brain stem neoplasms.
Arnold-Chiari malformation.
Cerebellopontine angle (CPA) is an area of the lateral
cistern containing CSF, arachnoid tissue, cranial nerves and
their associated vessels.
Borders:
medial lateral surface of brain stem.
lateral petrous bone.
superior middle cerebellar peduncle and cerebellum.
inferior arachnoid tissue of lower cranial nerves.
posterior inferior cerebellar peduncle.
Cerebellopontine angle syndrome:
Ipsilateral:
Tinnitus and deafness.
Retrolabyrinthic syndrome.
Cerebellar syndrome.
Involvement of the trigeminal nerve (common).
Involvement of the facial nerve (less common).
Larger tumor may lead to:
Glossopharingeal and vagus nerves involvement;
Increased intracranial pressure.
Etiology:
Vestibular schwanoma.
Neurofibromatosis.
Meningioma.
Epidermoid cyst.
Paragangliomas.
Metastases.
Vascular malformations.

IX. CEREBELLAR SYNDROMES

Cerebellum:
The largest part of the metencephalon.
Situated with brain stem in the posterior cranial fossa;
Present behind the pons and medulla oblongata.
Separated from pons and medulla oblongata by the cavity of
fourth ventricle
Covered by tentorium cerebelli.
Connected:
To the midbrain by superior peduncle.
To the pons by middle peduncle.
To the medulla oblongata by inferior peduncle.
Cerebellum promotes the synchrony and accuracy of
movement required for purposeful motor activity.
The cerebellar modulation and coordination of muscular
are important in: a) skilled voluntary movement;
b)
movements of posture; c) equilibrium.
Cerebellum receives a tremendous number of inputs from
the spinal cord and from many regions of both the cortical
and subcortical brain.
In this way, the cerebellum receives extensive information
from somesthetic, vestibular, visual and auditory sensory
systems, as well as from motor and nonmotor areas of the
cerebral cortex.
Longitudinally, the cerebellum consists of two large
hemispheres, which are united by midline vermis.
Transversally, the cerebellum is divided in:

Flocculonodular
lobe
(archicerebelum,
vestibulocerebellum);
Anterior lobe (paleocerebellum, spinocerebellum).
Posterior lobe (neocerebellum, cerebrocerebellum).
Vestibulocerebellum (archicerebellum) is phylogenetically
the oldest division of the cerebellum and receives input from
the vestibular system and projects back to the vestibular and
reticular nuclei, which in turn projects to the spinal cord and
oculomotor nuclei.
The vestibulocerebellum is important for equilibrium and
for control of the axial muscles that are used to maintain
balance in face of gravity.
The vestibulocerebellum also controls eye movement and
coordinates movements of the head and eyes.
Spinocerebellum (paleocerebellum) receives extensive
somato-sensory input from the spinal cord, auditory, visual
and vestibular systems.
The vermis projects to the fastigial nucleus and from there
influences cortical and brain stem components of the
medial descending systems (axial and girdle muscles).
The intermediate part of cerebellar hemispheres projects
to the interposed nuclei (globose and emboliform) to
control the lateral descending systems (distal muscles of
extremities).
The spinocerebellum receives a continuous flow of
somatosensory information regarding the status of the
musculo-skeletal system, as well as
concurrent
information from cortical areas about motor commands.
Cerebrocerebellum (neocerebellum), which occupies the
lateral zone of the cerebellar hemispheres, is phylogenetically
late in development and is particularly well represented in
primates.
This region receives, via the pontine nuclei, most of its
input from sensory, motor and premotor areas of cerebral
cortex.
Most of the outputs of the cerebrocerebellum are to the
dentate nucleus, which in turn projects to the cerebral
cortex.
The cerebrocerebellum is thought to function in the
planning and initiation of voluntary movements.

It is necessary for achieving in rapid limb movements,


especially those involving fine dexterity of the distal
extremities and movements at multiple joints.
Although the divisions of the cerebellum that are on
phylogenetic criteria and comparative anatomic studies
correspond reasonably well to by the locus of the termination
of major afferent projections, this congruence is not total.
Considerable overlap exist between the regions defined by
the anatomic sites of afferent terminations.
Moreover, the physiologic effects of activating afferent
sources project far beyond the boundaries ascribed to
these regions.
In addition, it should be recognized that many symptoms of
cerebellar dysfunction simply defy limitation to any one
division of the cerebellum.
For instance, lesions in certain cerebral and brain stem
areas may likewise interrupt the flow of information to or
from the cerebellum, causing gait disturbance similar to
that seen in disease of the cerebellum itself.
Cerebellar syndromes:
Disturbances:
Postural instability.
Delayed initiation and termination of motor.
Inability to perform continuous, repetitive movements.
Errors in smoothness and direction of a movement.
The lock of coordination or synergy of movement,
especially complex movements.
The lock of motor plasticity or learning.
General rules:
If only one side of the cerebellum is affected, the
symptoms are unilateral and ipsilateral to the lesion.
Lesion of the cerebellum produce errors in the planning
and execution of movements, rather than paralysis or
involuntary movements.
If symptoms predominate in the trunk and legs, the lesion
is near the midline.
If symptoms are more obvious in the arms, the lesion is
in the lateral hemispheres.
The most severe disturbances are produced by lesions in
the superior cerebellar peduncle and the deep nuclei.
Many of the symptoms of cerebellar disease improve

gradually with the time if the underlying disease process


does not itself progress.
Almost all patients with cerebellar lesions have some
type of gait disturbance.
Speech disturbances occur only with bilateral damage.
Signs and symptoms similar to those produced by
cerebellar lesions can appear with disorders that affect
structures adjacent to the cerebellum or affect the
afferent or efferent connections of the cerebellum.
Cerebellum is responsible for monitoring both motor and
nonmotor functions.

Ataxia:
Difficulty regulating the force, range, direction, velocity,
duration and rhythm in smooth performance of voluntary
acts.
Defective timing of sequential contraction of agonist/
antagonist muscle.
Usually persists despite visual cues (unlike ataxia due to
posterior column disease affecting the spinal cord).
Gait ataxia:
Unsteady during ambulation.
Waking with broad-based gait.
Lower center of gravity.
Decrease in the normal, free-flowing arm swing.
Walking heel-to-toe or running the heel of one foot
dawn the shin of the other leg while standing or
waking or lying down if difficult.
Limb ataxia:
Dysmetria = difficulty in bringing a limb smoothly and
accurately to a specific target in space (inability to
control range of movement).
Hypermetria = an involved limb may overshoot its
target.
Hypometria = an involved limb may undershoot its
target.
Asynergia = decomposition of movement = lack of
synergy of various muscles while performing complex
movements (because of errors in the timing and
sequencing of their component parts, may deteriorate

into a series of successive simple movement, rather


than one smooth coordinated movement.
Dysdiadochokinesia = inability to perform rapid
alternating movements, such as rapid supination and
pronation of the forearm.
Intention tremor (kinetic tremor) = rhythmic,
alternating, oscillatory movement of a limb as it
approaches a target, with excessive rebound when
an opposed motion is suddenly released.
Truncal ataxia:
Swaying of the trunk.
Staggering gait.
Difficulty in sitting unsupported.

Bulbar ataxia:
Loss of motor coordination caused by a lesion in the
medulla oblongata..
Cerebellar dysarthria = abnormalities in articulation and
prosody: scanning, slurring, staccato, explosive, hesitant,
garbled speech.
Oculomotor dysfunction:
Pendular nystagmus.
Gaze-evoked nystagmus.
Upbeat nystagmus.
Rebound nystagmus.
Optokinetic nystagmus.
Opsoclonus.
Skew deviation.
Occular bobbing.
Muscle hypotonia:
Usually accompanies acute hemispheric lesions and tends
to decrease with time.
More noticeable in upper limbs and proximal muscles.
Refers to a decreased resistance to passive stretch as
might occur with passive limb movement.
In early and severe cases, a distinct flabbiness of muscle
can be palpated and the muscle accommodates greater
stretch without discomfort.
Pendular deep tendon reflex.
Inability to stop a rapidly moving limb.

Although hypotonia is not as conspicuous as ataxia, it can


exacerbate the symptoms produced by ataxia.
Macrography:
Writing may be larger than normal.
Lack of poise:
Inability to carry out motor activities against the force of
gravity.
Particularly evident during rapid changes in body position or
in direction of movement.
Unsteadiness of gait or an inability to sit or stand without
swaying or falling.
Delays in the initiation and termination of movement.
Intentional movements, such as grasping or pointing, may be
slowed in both the buildup and the relaxation of force.
The movement of an affected limb is delayed and slowed.

Nonmotor deficits:
Cerebellar cognitive affective syndrome:
Executive function (impairments of set-shifting,
abstract reasoning, verbal fluency and working
memory.
Spatial cognition (visual-spatial disorganization,
impaired visual-spatial memory).
Language (dysprosodia, agrammatism, mild anomia).
Emotional, personality and behavioral changes:
Disinhibited and inappropriate behavior (anxiety,
hyperactivity, impulsiveness, irritability, dysphoria,
apathy).
Lowering of intellectual function.
Archicerebellar syndrome:
Disorders cause disturbances of locomotion and
equilibrium, with permanent truncal and gait ataxia.
Patients with isolated flocculonodular lesions lose their
ability to stand or to walk without swaying or falling and
trend to fall even when sitting with their eyes open.
When the effects of gravity are reduced by the patient
lying in bed or being physically supported, movements
may be completely normal.
Abnormalities of posture and station (e.g.: head tilt) and
eye movements also occur.

Eye movement disorders (nystagmus, disturbances of


vestibulo-ocular reflexes.
Tremor is not evident and muscle tone remains normal.
Paleocerebellar syndrome:
The cardinal feature is involvement of legs.
The gait is wide-based and ataxic, with small hesitant
steps.
Spinocerebellar ataxia reflects a more general deficit in
the control of the muscles of ambulation, where
vestibule-cerebellar
ataxia reflects a particular
inability to control the leg muscles in the presence of
the force of gravity.
Muscle hypotonia.
Neocerebellar syndrome:
Damage of the lateral cerebellar hemispheres and
dentate nucleus disturbs skilled coordinated
movements and speech.
Errors in direction, deviation from proper course,
dysmetria, dysdiadochokinesia and intention tremor all
may be present, especially in movements of upper
extremities.
The gait may actually be normal, reflecting the relative
sparing of the axial muscles and lower limbs.
Intentional movements, such as grasping or pointing, may
be delayed in their initiation and slowed in both the
buildup an relaxion of intended force.
Stretch reflexes and muscle tone are often diminished,
resulting in flabbiness, lock of check and pendular deep
tendon reflexes.
Dysarthric speech may occur with bilateral involvement
and can be pronounced.
Oculomotor disturbances may also occur.
Pancerebellar syndrome:
Bilateral signs of combination of all cerebellar syndromes.
Etiology:
Although cerebellar disorders as a whole are not very
common, a wide variety of factors, both inherited and
acquired, can adversely affect cerebellar function.
Inherited or idiopathic degenerations:
Spinocerebellar ataxia: (e.g.:Friedriechs ataxia)
Cerebellar ataxia: (e.g.: olivopontocerebellar atrophy).

Developmental disorders:
Arnold-Chiari malformations.
Dandy-Walker malformation.
Congenital cerebellar hypoplasia.
Nutritional disorders:
Vitamin B1 (thiamine) deficiency.
Vitamin B12 (cobalamin) deficiency.
Vitamin E deficiency.
Neoplastic disorders:
Astrocytoma.
Medulloblastoma.
Cerebellar metastasis.
Tumors of the cerebellopontine angle.
Paraneoplastic cerebellar degeneration.
Infections:
Creutzfeldt-Jakob disease.
Cerebellitis with viruses, bacteria, fungi, parasites.
Vascular disorders:
Cerebellar infarction.
Cerebellar hemorrhage.
Intoxications:
Drug-induced cerebellar syndrome.
Recreational or accidental exposure to volatile
solvents.
Poisoning with heavy metals.
Injury due to physical or mechanical trauma:
Trauma of the head, particularly in the area of the
occiput.
Metabolic disorders:
Inherited and acquired disorders of lipids, urea cycle,
pyruvate and lactate metabolism.
Demyelinating disorders:
Multiple sclerosis.

X. THALAMIC SYNDROMES
Thalamus (Th) is a midline paired symmetrical nuclear
structure on the top of brain stem, between midbrain and
forebrain, that form part of the lateral wall of third ventricle.
Th is the largest part of diencephalon.
Th is bordered laterally by the internal capsule, medially by
the third ventricle, inferior by the subthalamus and superiorly
by the lateral ventricle and caudate nucleus.
Th is the primary site of relay for all of the sensory pathways
except olfaction on their way to the cerebral cortex.
Even olfactory signals reach the thalamus via indirect
connections with the cortical regions initially receiving
olfactory pathways. It is a site where sensory inputs can
be modulated.
Th is a site of relay for cerebellar and basal ganglia inputs to
the cerebral cortex.
Limbic pathways also make input to the thalamus.
All thalamic nuclei, with exception of the nonspecific
nuclei, project primarily to the cerebral cortex.
Additionally, each portion of the thalamus receives a
reciprocal and strong connections from the cerebral
cortex.

This may provide a mechanism for filtering thalamic


inputs to the cerebral cortex.
Th comprises a system of lamellae (made up of myelinated
fibers) separating different thalamic portions: a) lateral;
b) anterior; c) medial.
It is composed of many nuclei, which have motor, sensory
and limbic connections.
Some nuclei are nonspecific in nature with diffuse cortical
connections.
Basic types of thalamic nuclei:
Relay nuclei:
Ventral posterolateral nucleus (VPL) relays medial
lemniscal and spinothalamic connections to the primary
sensory cortex.
Ventral posteromedial nucleus (VPM) receives trigeminothalamic input and relay to the inferior portion of
postcentral gyrus.
Lateral geniculate body (LGB) receives input via optic
tract (contralateral) and projects to the primary visual
cortex via optic radiations.
Medial geniculate body (MGB) receives organized
auditory afferents from the inferior colliculus and projects
to the primary auditory cortex on the superior temporal
gyrus.
Ventral lateral nucleus (VL) receives a larger input from
the cerebellum (mainly from the dentate nucleus) and
smaller input from basal ganglia and projects to the
primary motor area and to the premotor areas (VL is thus
involved in motor feedback from the cerebellum and basal
ganglia to the cerebral cortex).
Ventral anterior nucleus (VA) receives most of its input
from basal ganglia, especially the medial globus pallidus
and substantia nigra reticulata and projects to premotor
cortex including supplementary motor area of the frontal
lobes (involved in planning and initiating movements).
Centromedian nucleus (CM) has reciprocal connections
with globus pallidus and with the premotor cortex
(appears to function as part of the basal ganglia feedback
system).
Associative nuclei:

Pulvinar (P) receives afferent projections from superior


colliculus as well as from the association cortex and
projects to secondary visual areas and to association areas
in the parietotemporal region (contributes to visual
perception and eye movements).
Dorsomedial nucleus (DM) lateral part receives
projections from the superior colliculus, olfactory cortex
and the ventral pallidum and has efferent projections to
the frontal eye fields and to the anterior cingulate cortex
of the frontal lobes (involved in controlling eye
movements and attending to visual stimuli and plays a
role in emotions).
Dorsomedial nucleus (DM) medial part receives inputs
from several brain areas, including hypothalamus, the
solitary nucleus, substantia nigra reticulata, amygdala and
ventral pallidum and projects to limbic areas of the cortex,
including insular cortex, orbital frontal cortex and
subcallosal region (involved in autonomic regulation and
emotions).
Anterior nucleus (A) receives input from the hippocampus
via mammillary bodies and projects to the posterior
cingulate cortex (involved in memory storage and
emotions).
Nonspecific nuclei:
Reticular thalamic nucleus (RT) receives afferents from
the brain stem reticular formation as well as from the
cerebral cortex and thalamus and makes a strongly
inhibitory input to thalamic nuclei (may be important in
sleep-wake cycles and an important regulator of signals
relaying through thalamus).
Intralaminar nuclei (IL) and midline nuclei (ML) have
diffuse projections to the cortex and are probably mostly
involved in arousal and alertness.
Thalamic syndromes:
There are two considerations that must be taken into account
when attempting to diagnose lesions of the thalamus:
Thalamic nuclei are small so that lesions producing highly
specific effects are uncommon.
Thalamus is immediately bounded by the internal capsule
and is in close proximity to the basal ganglia so that
thalamic lesions frequently are accompanied by

symptoms from damage to these structures (most


commonly from cerebral hemorrhage).
Tuberothalamic artery syndrome:
Tuberothalamic artery (polar artery) arises from the
posterior communicating artery and supply the anterior
thalamic region, including the ventral anterior nucleus
and part of the ventral lateral nucleus.
Severe and wide-ranging neuropsychological deficits:
In the early stages of infarction, patients exhibit
fluctuating levels of consciousness.
Persistent personality changes include disorientation
in time and place, euphoria, lock of insight, apathy,
abulia and lock of spontaneity.
Left-sided lesions: a) impairment of recent verbal and
visual memory; b) thalamic aphasia; c) acalculia.
Right-sided lesions: a) impairment of recent visual
memory; b) hemispatial neglect.

Paramedian artery syndrome:


Paramedian arteries (retroromammillary arteries or
thalamo-perforate pedicle) can arise as pair from each P1
segment, but they may equally arise from a common trunk
of P1 segment of the posterior cerebral artery (PCA), thus
supplying thalamus bilaterally.
Unilateral thalamic infarction in the territory of the paramedian artery produces neuropsychological disturbances
predominantly in areas of arousal and memory.
A left-right asymmetry is evident in language versus
visual-spatial deficits.
Impairment of arousal with decreased and fluctuating
level of consciousness is a conspicuous feature in the
early stages, lasting for hours to days.
Confusion, agitation, aggression and apathy may be
persistent features.
Speech and language impairments are characterized
by hypophonia and dysprosody with markedly
reduced verbal fluency and frequent perseveration.
Bilateral infarction may result in an acutely ill and
severely impaired patient.
Disorientation, confusion and hypersomnolence.

Deep coma.
Akinetic mutism (awake unresponsiveness).
Anterograde and retrograde memory deficit and
apathy can be severe and persistent.
In the late stages: a) inappropriate social behaviors; b)
impulsive aggressive outbursts; c) emotional blunting;
d) loss of initiative; e) apraxia; f) dysgraphia.
Thalamic dementia.
Elementary neurological signs: a) asterixis;
b) complete or partial gaze paresis; c) loss of
convergence; d) bilateral internuclear ophthalmoplegia; e) miosis.
Inferolateral artery syndrome:
Inferolateral arteries (thalamogeniculate arteries)
arise from the P2 segment of the PCA.
Djerine-Roussy syndrome (contralateral):
Transient mild hemiparesis.
Hemiataxia.
Choreoathetosis.
Athetiod posture.
Homonymous hemianopsia.
Astereognozia.
Persistent
hemianestesia,
although
superficial
sensation may be more or less spread.
With partial recovery of sensation, the severe,
spontaneous, persistent, distressing and often
intolerable pain is variously described and any
outside stimulus
(e.g.: cold stimuli, emotional
disturbances, loud sound) appears capable of
aggravating it = hypoalgesia with hyperpatia.
Posterior choroidal artery syndrome:
Posterior choroidal arteries arise from the P2 segment of
the cerebral posterior artery and supplies in part the
region of the lateral geniculate body.
There is limited information on clinical manifestations:
Homonymous quadrantanopsia.
Incongruous homonymous hemianoptic scotoma.
Hemisensory loss.
Transcortical aphasia.
Memory deficits.
Delayed complex hyperkinetic motor syndrome.

Spatial neglect is associated with lesions located in the


right side.

XI. EXTRAPYRAMIDAL SYNDROMES

Extrapyramidal system (EPS) is a collateral pathways of motor


system and is composed of nuclei and fibers which do not pass
through the medullary pyramids but which nevertheless is
involved in motor activities.
EPS is difficult to describe, because of the complexity of
pathways, various relays and feedback loops which compose
it.
EPS is a functional, rather than anatomical unit and,
phylogenetically, is older than pyramidal system.
EPS control and coordinate especially the postural, static,
supporting, muscle tone and locomotor mechanisms.
Nerve impulses along EPS pathways follow a complex,
polysynaptic circuits that involves the motor cortex, basal
ganglia, substantia nigra, motor nuclei of thalamus,
subtalamic nucleus, red nucleus, limbic system,
cerebellum, vestibular system, olivary nuclei, reticular
formation and other brain stem nuclei.
If pyramidal pathways may directly innervate motor
neurons of spinal cord ventral horn cells and certain

cranial nerve nuclei, the EPS centers around the


modulation and regulation (indirect control) of motor
neurons from spinal cord and brain stem.
EPS is involved in setting the level of external
responsiveness to stimuli and also in establishing tones
and postures of the body.
Many neurons in the basal ganglia begin to show activity
before movement actually take place.
Projections from diverse cortical areas, including motor,
sensory and association fields, converged within the basal
ganglia and were then funneled back upon precentral
motor areas.
Basal ganglia (BA) along with their connected cortical and
thalamic areas, are viewed as components of parallel circuits
whose functional and morphological segregation is rather
strictly maintained.
Each circuit thought to engage separate regions of the BA
and thalamus and the output of each appears to be centered
on a different type of the frontal lobe.
Each circuit contains a number of highly specialized channels
and sub-channels that permit parallel, multilevel processing
of a vast number of variables to process concurrently.
The BA circuits:
The motor circuit is focuses on the precentral motor fields.
Within this circuit, a well defined somatotopy is
maintained throughout all stages of the circuit, thereby
giving rise to clearly differentiated leg, arm and
orofacial channels.
There is also evidence suggesting further subdivisions
of the motor circuit in terms of the types of behaviors
observed (movement preparation versus execution)
and the maintained segregation of influences from
different cortical areas (e.g.: separate subchannels for
each of precentral motor fields).
Activity within these circuits initiated in the cortex,
although there is an essentially complex temporal
overlap, suggesting that much of the motor processing
produces concurrently a functional integration is
based upon temporally coincidence of processing
within pathways whose functional separation is rather
strict.

The oculomotor circuit = the frontal eye fields and several


other cortical areas project to the body of caudate nucleus
then project back to both the superior colliculus and
frontal eye field, via thalamus.
The circuit is involved in saccadic eye movement.
The dorsolateral orbitofrontal circuit = the dorsolateral
prefrontal cortex and several other areas of association
cortex project to dorsolateral head of caudate nucleus
which in turn project back to the dorsolateral prefrontal
cortex, via the thalamus.
This circuit is probable involved in aspects of memory
concerned with orientation in space.
The lateral orbitofrontal circuit through the ventromedial
caudate nucleus and thalamic medial dorsal nucleus is
thought to be involved in the ability to switch behavioral
set.

The limbic circuit involves the anterior cingulate area


medial orbitofrontal cortex ventral striatum ventral
pallidum thalamic medial dorsal nucleus projections.
This circuit may play some role in emotional and/or
motivational processes.
EPS can be divided into four controlling systems:
a)
cortically originating indirect descending pathways (COIDP);
b) cortically originating extrapyramidal system (COEPS); c)
proprioceptor originating extrapyramidal system (POEPS); d)
auditory-visual-vestibular descending pathways (AVVDP).
COIDP at the same time signals are being transmitted
over the pyramidal system to produce a specific
movement and additional signals relative to the
movement are also relayed to the basal ganglia, red
nucleus and brain stem reticular formation.
The basal ganglia evaluate the command signal sent
down the pyramidal pathway and may contribute to
the establishment of needed background muscle tone
for the movement.
The basal ganglia are able to do this in part by
projecting to the red nucleus, which influence spinal
cord alpha and gamma motor neurons, via rubrospinal
tract.

Similar indirect routing to the spinal cord is achieved


through corticoreticulospinal and corticorubrospinal
pathway.
COEPS feedback are composed of fibers originating in the
motor cortex which synapse in subcortical centers and
after integrating/evaluating the signals, the centers
project fibers back to the cortical source for modification.
Three COEPS loops can be demonstrated:
a) in loop A the signal is tapped off to the striatum
(caudate and putamen), which in turn project to
globus pallidus and then pallidothalamic fibers project
to the thalamus, which completes the loop by
projecting back to the cortical source;

b) in loop B the sample signal is sent to pontine nuclei


for subsequent referral to the cerebellum, were it is
probably compared to propioceptive input coming
from muscle, tendons and joints involved in movement
and following integration of this input, the cerebellum
then projects its output to the thalamus, via
cerebellothalamic tract, which then completes the loop
by sending fibers back to the cortical source through
thalamocortical projections;
c) in loop C the simple signal is sent to the substantia
nigra, which in turn to the striatum and from here the
feedback circuits is identical to the loop A.
POEPS feedback is not directed back toward the cortical
source (as are the COEPS loops), but to the spinal cord
motor neurons instead.
The principal loop involves the relay of muscle, tendon
and joint proprioceptive information to the
cerebellum, via the spinocerebellar tracts.
The signals are integrated in the cerebellum and
probably compared with the intended signals sampled
by corticopontocerebellar pathway. In this way the
cerebellum might compare the intended movement

with the instantaneous performance of that movement


as sampled by the proprioceptors of the
spinocerebellar tracts. It could then direct
modification through its projections to the vestibular,
reticular and rubral nuclei and their respective
descending tracts to the appropriate motor neurons of
the spinal cord.
AVVDP is involved in postural adjustments in response to
auditory, visual and vestibular signals.
AVVDP is an additional way to regulate the activity of
spinal motor neurons.
Auditory and visual input to the tectal nuclei of
midbrain may be responsible for producing reflex
movements of the body in response to a sudden sound
or bright light
Similarly, input from vestibular apparatus to the
vestibular nuclei and cerebellum no doubt plays a role
in reflex postural adjustments through the
vestibulospinal and other tracts.

EPS may be structured on four levels:


Cortical (all neocortical areas).
Subcortical (basal ganglia and thalamus).
Subthalamo-mesencephalic [subthalamic nucleus STN,
red nucleus RN
and substantia nigra SN (pars
compacta SNc and pars reticulata SNr)].
Pontomedullary (reticular formation RF and inferior
olivary nucleus ION).
N.B.: The components of EPS from all the levels are
intraconnected and interconnected.
Cortical level.
Virtually, all neocortical areas (primary and higher order
sensory areas, motor, premotor and prefrontal regions
and limbic cortical areas) projects to the striatum
(caudate nucleus and putamen).
The premotor cortex is most important EPS cortex and is
involved in planning, pattering and initiating movements.
The putamen receives afferents by somatotopically
organized inputs from sensory and motor cortex.

The caudate nucleus, on the other hand, receives fibers


predominantly from association cortex (outside areas of
primary cortex).
There are two described pathways for transmission of
signals through the basal ganglia: a) direct; b) indirect.
Direct pathway is excitatory to motor cortex activity
(movements).
Cortical output to the striatum through direct pathway
would excite by glutamate (GLU) the inhibitory
projection neuron to the medial (internal) globus
pallidus.
This would decrease activity in the tonically active
projection neurons in the medial globus pallidus and in
turn, would decrease the tonic inhibitory pressure on
VA, CM and VL nuclei of the thalamus.
The VA and VL of the thalamus project via excitatory
pathways primarily to the premotor cerebral cortex.
In considering the physiology of direct pathway, note
that the cortical input to the striatum would excite the
inhibitory projection neurons to the medial globus
pallidus.
This would decrease activity in the tonically active
projection neurons in the medial globus pallidus and,
in turn, would decrease the tonic inhibitory pressure
on VA and VL of the thalamus.
This feedback is involved in regulating the tonic level
of excitation in the premotor cortex, an area involved
in planning and initiating the movements. In other
words, this direct pathway results in a net facilitation
of premotor cerebral cortex.
In the case of the premotor cortex, activation of the
direct pathway would increase the ease and initiating
movements.
Indirect pathway is inhibitory to motor cortex activity
(movements).
Excitatory projections (GLU) from the cerebral cortex
facilitates inhibitory projection neurons in the
striatum.
These project to the lateral (external) globus pallidus
where they inhibit the tonic inhibitory output neurons.

This decreases tonic inhibition to the subthalamic


nucleus, resulting in increased excitatory output to the
medial globus pallidus.
This excitatory input to the medial globus pallidus
increases the inhibitory output from medial globus
pallidus to the thalamus, ultimately decreasing the
excitatory feedback to the cerebral cortex.
The indirect pathway has opposite effects on the
medial globus pallidus than does the direct pathway.
Basal ganglia (BG) is the most important central nervous
structure of the EPS (geometric locus).
The BA includes:
Caudate nucleus CN.
Lentiform nucleus (putamen Pt + globus pallidus
GP, internal segment GPi and external segment
GPe).
CN and Pt constitute neostriatum (striatum).
GP (pallidum) constitutes paleostriatum.
Thalamus = only VA, VL and CM nuclei.
Striatum contain three subtypes of neurons:
D1 neurons with gammaaminobutyric acid (GABA) +
substance P which project primarily to the GPi
and
SNr.
D2 neurons with GABA + enkephalin and
project mainly to the GPe.
Interneurons containing acetylcholine (ACH).
N.B.:
GABA is an inhibitory neurotransmitter.
GLU is an excitatory neurotransmitter.
ACH is an excitatory neurotransmitter and it is found
only inside of the striatum.
Efferents:
From the GPi the efferents goes to the thalamus (VA,
VL and CM), while the GPe projects to the STN, which
in turn projects to the SNr.
In addition, the GPe also projects directly to SNr, which
send fibers to the superior colliculus, thalamus and
pedunculopontine nucleus (PPN = midbrain
extrapiramidal area).

The parts of the thalamus that receive fibers from the


GP and SNr project back to different portions of the
frontal lobe.
Dopamine (DA) projections from SNc to the striatum have
complex and opposing effects on activity in the direct and
indirect pathways.
DA acts primarily through dopamine D1 receptors that
participate in the direct pathway, exciting these
neurons.
DA acts on dopamine D2 receptors on the striatal
neurons that are involved in the indirect pathway,
inhibiting these neurons.
DA excites the direct pathway and inhibits the indirect
pathway, with a net effect to increase facilitatory
inputs to the motor regions.
Mesolimbic dopamine reward system is an important
system for the control and reinforcement of behavior.
There is a system that has many similarities to the
direct pathway. It is primarily involved in controlling
emotional tones and responsiveness to the world.
This system has also been termed the ventral striatal
system and begin with projections from the emotional
portions of the cerebral cortex, often termed limbic
cortex, to the ventral striatum.
This is located where the head of the caudate nucleus
and the putamen meet, called the nucleus accumbens.
The nucleus accumbens projects to the ventral
pallidum.
The ventral pallidum projects to the dorsomedial
nucleus of the thalamus, which, in turn, projects to the
limbic areas of the cerebral cortex.
These areas are important for maintaining behavioral
tone and motivation.
Just like the direct pathway, dopamine is important in
increasing activity in striatal neurons. In this case, the
dopamine input derives from the ventral tegmental
area, which is located in ventromedial aspect of
midbrain.
It appears to act primarily on the D3 subtype of
dopamine receptor.

Most outputs from the basal ganglia go through the


thalamus to the cerebral cortex, effecting movement by
influencing motor cortex activity.
The striatum project also to the SNr.
Just like GP, the SNr contains tonically active
GABAergic output neurons.
Efferent projections from SNr project to several
places. These include dorsomedial thalamic nucleus
that feeds back on several cerebral cortical site,
particularly those effecting motivation and mood.
Also, the SNr projects directly to the brain stem
reticular formation (affecting muscle tone) and to the
superior colliculus (affecting eye movements).
Subthalamic nucleus (STN, Luys body) is located ventral to
the thalamus, dorsal to the substantia nigra and medial to the
internal capsule.
STN receives its main GABAergic afferents from the GP,
inhibiting neurons in STN.
Excitatory, GLUergic inputs come from the cortex
(particularly the motor cortex).
STN receives neuromodulary input, notably DA-ergic axon
from the SNc, STN also receives inputs from the thalamus
and PPN.

The two STN communicate via the supramammilloreticular formation.


The efferent axons are GLUergic (excitatory) for both
segments of globus pallidus (GPe and GPi) and for SNr.
Several recent studies have focused on the autonomous
pacemaking ability of STN.
Substantia Nigra (SN) is a pigmented mass of neurons
located in the midbrain, dorsal to the cerebral peduncles.
Humans have two substantiae nigrae, one on each side
of the midline.
SN is divided into two parts:
SN, pars reticulata containing iron compounds (SNr).
SN, pars compacta containing melanin pigment (SNc).
The neurotransmitter in SNc is DA.
SNr are either ACHergic or GABAergic.
SN is an important player in brain function, in particular,
in eye movements, motor planning and reward seeking.

Many of SN effects are mediated through the striatum.


SN afferents:
Striatonigral (GABA).
Corticonigral.
Pallidonigral (GABA).
Subthalamonigral (GLU).
Tegmentonigral (Se Serotonin from raphe nuclei and
ACH from PPN).
SN efferents:
Nigrostriatal (DA from SNc).
Nigrocortical.
Nigropallidal.
Nigrorubral.
Nigrothalamic (GABA).
Nigrotegmental (GABA).
Nigrotectal (GABA).
Nigroamygdaloid (DA).
Collaterals that branch within both SNc and SNr, likely
modulating DAergic activity in the SNc.

SNr.
SNr bears a strong resemblance, both structurally and
functionally, to the GPi.
SNr is an important processing center in basal ganglia.
The neurons in SNr are mainly GABAergic.
The main input to the SNr derives from striatum and
comes by two routes, direct and indirect pathways.
The direct pathway consist of axons from striatum that
project directly to SNr.
The indirect pathway consists of three links: a) a
projection from striatum to the GPe; b) GABAergic
projection from GPe to the STN; c) glutamatergic
projection from STN to SNr.
Striatal activity exerts an excitatory (or rather
disinhibitory) effect on SNr neurons via direct
pathway, but an inhibitory effect via indirect pathway.

GABAergic neurons in SNr convey the final processed


signals of the basal ganglia to the thalamus and
superior colliculus.
SNr inhibits DAergic activity in the SNc via axon
collaterals.
The GABAergic neurons of SNr spontaneously fire
action potentials.
The purpose of these spontaneous action potentials is
to inhibit targets of the basal ganglia and decreases in
inhibition are associated with movement.
SNc.
The most prominent function of the SNc is fine motor
control.
SNc is heavily involved in learned responses to stimuli.
SNc is important in spatial learning, the observations
about ones environment and location in space.
Temporal processing is also an important function of
SNc.
SNc has been suspected of regulating the sleep-wake
cycle (insomnia, REM sleep disturbances).

Basal ganglia-thalamocortical circuits.


Physiological activity in the two striatal output
differentially modulate the GABAergic neurons in SNr.
At rest, striatal output neurons are physiologically
quiescent, whereas nigral GABAergic neurons are tonically
active.
Corticostriatal inputs stimulate activity in striatonigral
neurons which phasically inhibit the tonic activity of
nigral GABAergic neurons, thus desinhibiting the AL
thalamic nucleus and thereby gating or facilitating
cortically
initiated
movements,
via
excitatory
thalamocortical connections.
Cortically driven activity of striatopallidal neurons inhibits
external GABAergic neurons, resulting in the disinhibition
of the subthalamic nucleus, which increases the tonic firing
of nigral GABAergic neurons.

Phasic increases in GPi/SNr discharge increases the


inhibition in the superior colliculus or thalamic target
nuclei.
The execution of a movement requires temporal
coincidence of basal ganglia disinhibition with command
signal from other sources so that the disinhibitory process
is based on gating effect.
The function of the arousing striatal disinhibition is to set
a pattern of readiness in premotor network that will be
further activated for the execution of movement.
Red nucleus (RN), so named because in fresh preparation its
rich vascularity gives it pinkish hue (also have a high iron
content), is a prominent feature of the rostral mesencephalic
tegmentum.
RN receives manly inputs from the contralateral
cerebellar nuclei (dentate, globose, emboliform)
cerebellorubral tract.
RN receives an input from ipsilateral motor cortex
(corticorubral tract).
RN sends efferents axons to the contralateral half of
rhombencephalic reticular formation (rubroreticular
tract) and spinal cord (rubrospinal tract).
RN sends ipsilateral efferents to inferior olivary nucleus
(rubroolivary tract) via the central tegmental tract.
The rubrospinal tract is thought to be involved in the
control of both flexor and extensor muscles.
Rubrospinal tract courses adjacent to the lateral
corticospinal tract and terminates in roughly the same
region of the spinal cord gray matter.
Reticular formation (RF) is comprised of a complex network
of both gray and white matter that is located in the
tegmentum of the mesencephalon to myelencephalon.
There is also reticular nuclei in thalamus.
RF with its network of cell fibers contributes to a variety
of functions within the CNS (ascending and descending
influences):
Regulates cortical activity via Ascending Reticular
Activating System (ARAS).
Contributes to the facilitation and inhibition of motor
activity via Descending Reticular System (DRS).

Controls many autonomic functions (e.g.: respiration,


cardiovascular activity, vomiting, deglutition).
Helps regulate limbic activity in regard to our
emotional response to visceral activity .
Modulates the control of pain.
Afferent connections of RF:
Corticoreticular.
Strioreticular.
Thalamoreticular.
Spinoreticular.
Cerebelloreticular.
From sensory pathways.
Efferent connections of RF:
Reticulocortical.
Reticulospinal.
Reticulocerebellar.
Reticulothalamic.
Reticulohypotalamic.
Reticulosubthalamic.
Reticulonigric.
Reticulorubric.
Reticulotectal.
RF nuclei:
Pedunculopontine nucleus.
Paramedian pontine nucleus.
Precerebellar nuclei.
Raphe nuclei.
Lateral nuclei.
Central nuclei.
Miscellaneous nuclei (area postrema, locus coeruleus,
interpeduncular reticular, peri-hypoglossal and
accessory oculomotor ).
Pedunculopontine nucleus (PPN).
PPN is a columnar structure lying in the dorsolateral part
of the pontomesencephalic tegmentum, caudal to SN,
adjacent to the superior cerebellar peduncle and its main
mass is located at the trochlear nucleus.
PPN has two divisions:
Pars compacta, containing cholinergic neurons.
Pars dissipata, containing mostly glutamatergic
neurons.

Afferents (inhibitory inputs):


GPi-PPN.
SNr-PPN.
Efferents (excitatory outputs):
PPN-GPi.
PPN-STN.
PPN-SNc.
PPN-thalamus.
PPN-cerebellum.
PPN-basal forebrain.
PPN-lower brain stem.
PPN- spinal cord.
PPN-cerebral cortex.
PPN is one of main components of Ascendent reticular
activating system (ARAS).
PPN is involved in:
Arousal.
Attention.
Learning.
Reward.
Voluntary limb movements and locomotion.
Generation and maintenance of REM sleep.
Inferior olivary nucleus (ION) is the largest nucleus
situated in the olivary body, part of the medulla
oblongata.
Afferents of ION ipsilateral RN.
Efferents of ION contralateral cerebellum via the
inferior cerebellar peduncle (restiform body).
Dento-rubro-olivary pathway (Guillain-Mollaret triangle) is
a functional circuit connecting the dentate nucleus of the
cerebellum of one side with the red nucleus and the inferior
olivary nucleus on the other side, via the superior cerebellar
peduncle, the central tegmental tract and the inferior
cerebellar peduncle respectively.
Extrapyramidal pathways to the spinal cord (anterior horn
cells):
Rubrospinal tract is involved in motor-precise of discrete
movements of hands and feet.
Tectospinal tract is involved in reflex head turning
following sudden visual and auditory stimulus.

Vestibulospinal tract is involved in postural reflexes and


control of muscle tone.
Lateral reticulospinal tract is involved in facilitate flexor
reflexes, inhibit extensor reflexes and decrease muscle
tone.
Medial reticulospinal tract facilitate extensor reflexes,
inhibit flexor reflexes and increase muscle tone.
Typical parkinsonian syndrome (PkS) = Parkinsonism.
Idiopathic Parkinsons disease (PD):
Disease onset:
PD is a typically disease of the middle to late years,
beginning at a mean age of 50-60 years and
progressing slowly over 10-20 year period.
Cardinal manifestations: a) rest tremor; b) rigidity;
c) akinesia/ bradykinesia; d) postural instability.
Rest tremor:
Tremor is the first motor manifestation, usually
beginning
unilaterally in the distal limb, in most cases an arm.
Tremor is present at rest and usually abates when the
affected limb performs a motor task or during
voluntary movement.
Oscillations have a characteristic frequency of 3-5
cycles/s.
Tremor often involves rhythmic, alternating
opposition of the forefinger and thumb in the
stereotypic pill-rolling tremor.
Over several years, the tremor may spread proximally
in the affected arm before involving the ipsilateral leg
and finally the contralateral limbs.
It progresses at a slower rate than the other cardinal
manifestations.
Although tremor is bilateral in advanced disease
maintains some asymmetry.
In the later stages an accompanying tremor of the
face, lips or chin is not uncommon.
When the lower limbs are involved, tremor will be
present in the legs when the patient is supine or sitting
but disappears when the patient bears weight.
Tremor often increases in the arms during
walking.

In the curse of a day, tremor will occur intermittently


and vary in intensity.
Tremor disappears in sleep and worsens with stress
or anxiety.
It is important to note that patients often also have a
postural or kinetic component to their tremor.
Rigidity:
The stiffness of PD is caused by an involuntary
increase in muscle tone (an excessive and continuous
contraction of the muscle).
Hypertonia can affect all muscle groups (axial and limb
muscles, flexor as well as extensor muscles).
Rigidity tends to be more prominent in the muscle
than maintain a flexor posture (in the flexor muscles
of trunk and limbs).
Rigidity is noted as increased resistance to passive
movement of a limb segment.
The amount of resistance remains fairly constant
through the entire range of motion, both flexion and
extension.
Rigidity is not greatly influenced by the speed or force
with which the movement is performed.
Rigidity can be either smooth (lead pipe) or rachety
(cogwheel Negros sign).
Both rigidity and cogwheeling can be brought out or
reinforced by voluntary movement in the contralateral
limb.
As with tremor, rigidity frequently begins unilaterally,
may vary during the course of the day and is
influenced by mood, stress and medications.
Akinesia/bradykinesia:
Akinesia means the absence or failure of movement.
Bradykinesia means slowness of movement.
Together they are the terms used to definite the
difficulty PD patients have in initiating and executing a
motor plan.
The nature and severity of akinesia/bradykinesia
worsen over the course of illness.
Early on, hypokinesia (falling short of the mark when
executing a movement) is nearly always present, later

progressing to bradykinesia (slowed movements) and,


finally, to akinesia.
Early signs may be confined to distal muscles
(micrographia,
decreased
dexterity,
impaired
sequential finger movements).
Particularly difficult for patients are sequential actions,
such as alternating pronation-supination of the hand
and complex motor acts, such as buttoning a shirt.
Quick repetitive movements, such as repeated
opposition of the forefinger and thumb, will typically
show a rapid decrease in amplitude and frequency.
In more advanced stages, patients have difficulty rising
from a chair and display a generalized slowing of
voluntary movements.
Inability to perform simultaneous actions.
Difficulty rolling in bed or rising from a seated
position.
Facial and vocal manifestations of bradykinesia
(hypomimia, masked facies, hypophonia, monotonic or
festinating speech, palilalia, dysarthria, dysphagia and
sialorrhea) are often apparent to the clinician before
the formal examination has even begun.
Rapid fatigue with repetitive movements.
Akathisia (an unpleasant desire to move).
Freezing.
Bradykinesia probably plays a greater role than
rigidity in determining a patients degree of disability.
Postural instability:
Postural instability with associated gait disorder is
usually the last of the four cardinal sings to appear.
Postural instability proves to be the most disabling, least
treatable manifestations of PkS.
No single factor is alone responsible for postural
instability and gait disturbances (it stems from a
combination of changes in postural adjustment, the
loss of postural reflexes, rigidity and akinesia).
Loss of postural reflexes often occurs early but is
rarely disabling until years later.
The patients adopt a stooped posture with flexion of
the neck and trunk.

The arms held in an adducted position with elbows


flexed.
Once a patient starts to lose the ability to make rapid
postural corrections, a tendency to fall forward or
backward becomes evident (pull test with
retropulsion).
The earliest sign of gait disturbance is often decreased
arm swing, but over time patients also begin to walk
with short, shuffling, uncertain step.
Gait initiation and turning become particularly
difficult.
Once walking has begun, the loss of postural reflexes
and stooped posture combine to produce a festinating
gait (in effort to retain balance, the patient walks faster
and faster in a shuffling manner, as the legs try to catch
up with the bodys forward momentum).
Although the gait is unsteady, the base is usually
minimally or not at all widened and truncal ataxia is
absent.
Freezing is a phenomenon distinct from other forms of
akinesia because it is during ambulation and it proves
most troublesome.
Patients freeze especially when starting to walk (start
hesitation), attempting to turn or approaching a
narrow or crowded space (doorways, corners, closets,
a sidewalk with heavy traffic).
Sitting en bloc represents a special form of freezing
in which a patients literally falls into a chair.
Kinesia paradoxica (opposite of freezing) is the term
used to describe sudden short periods of relatively
effortless mobility experienced by a few patients.

Cognitive and behavioural disturbances:


Common and often more disabling than motor
disturbances.
Prodromal symptoms of PD can include changes in
mood or personality.

Mental status remains relatively intact in early PD.


Chronic major depression or fluctuating dysthymia.
Anxiety.
Obsessive-compulsive behaviors such as craving, binge
eating, hypersexuality, pathological gambling.
Psychotic symptoms are hallucinations or delusions.
Tests of cognitive function demonstrate mild-tomoderate deficits: a) visuospatial impairment;
b)
attentional set-shifting difficulties; c) poor executive
function.
Slowed thinking.
Slowed responses to questions (bradyphrenia) but
usually get the answers right.
Dementia (sucortical type) occurs in 20-30 percent of
PD patients.
Language function is typically spared.
Mild memory impairment.
As PkS progresses, patients often become passive and
apathetic.
Ocular dysfunction:
Some patients will complain of blurred vision or
difficulty reading, which may be a result of weakened
convergence.
Limited upgaze is common in PD patients.
Slow saccades and jerky ocular pursuit are often seen
in PD.
The frequency of spontaneous eye blinking is reduced.
Decreased eye convergence.
Difficulties to open the eye-lids.
Sustained glabellar reflex (persistent eye blinking
when the forehead is repeatedly tapped).
Olfactory dysfunction:
Bilaterally decreased of olfactory functions is an
early sign in PD.

Musculoskeletal deformities:
Deformity of the hands and feet are common in PD.
The parkinsonian hand display ulnar deviation,
flexion
of
metacarpophalangeal
and
distal

interphalangeal joints and extension of the proximal


interphalangeal joints (striatal hand).
The great toe can be tonically extended with
remaining toes curled claw-like.
Coincident with rigidity, mild scoliosis may be seen,
concave contralateral to the affected side.
Later, kyphosis becomes prominent and contributes to
the disabiling postural changes of advanced disease.
Pain and sensory symptoms:
Although peripheral nerve diseases is not associated
with PD, pain and sensory complaints are surprisingly
common.
Pain is often proportional to the degree of motor
dysfunction an may be take the form of muscle cramps,
stiffness, dystonia, radiculopathy or arthralgias.
Paresthesias, numbness, burning or tingling may occur
at any stage of the disease, independent of the degree
of motor manifestations.
Autonomic dysfunction.
Bowel and bladder symptoms:
Urinary difficulties include hesitancy, urgency and
increased frequency.
Constipation.
Sexual dysfunction is a frequent compliant and may
involve both loss of libido and impotence.
Episodic sweating occurs in some patients.
Orthostatic hypotension with dizziness and fainting
is uncommon in PkS.
Dermatologic problems:
Chronic seborrhea leads to greasy skin, particularly on the
face.
Sleep disorders:
Excessive daytime somnolence.
Sleep fragmentation.
Total sleep time is reduced.
Male PD patients have rapid eye movement (REM)
sleep behaviour disorder, in which excessive motor
activity occurs during dreaming.
Pathophysiology of PD.
Bradykinesia and rigidity are result of degeneration of
DA-ergic nigrostriatal tract which leads to the

preponderance of activity in the indirect pathway


(hyperactivity in the indirect pathway and
hypoactivity in the direct pathway) with consecutive
increase of inhibitory basal ganglia output to the
thalamus (increased tonic inhibition of thalamocortical
neurons by excessive output from GPi/SNr may reduce
the responsiveness of cortical mechanisms involved in
motor control).
Tremor is a result of oscillatory activity in motor areas
of the basal ganglia or of the thalamus output nuclei
which lead to rhythmic activity in thalamocortical
cells and in turn may lead to oscillations in
corticospinal projection neurons.
Cognitive and behavioral disturbances
reflect
disruption of nondopaminergic (serotoninergic)
pathways.
Pain and sensory symptoms possible reflects a role for
the basal ganglia in sensory processing (altered
striatal input to sensory centers in the thalamus).
Autonomic dysfunction can be the consequence of the
Lewy body neuropathology described within the
myenteric plexus and partial or complete loss of
autonomic innervations.
Unified Parkinsons Disease Rating Scale (UPDRS):
Contains six sections:
The first is a limited assessment of mentation,
behaviour and mood.
The second is assessment of activities of daily living in
both on and off state, determined by history.
The third is a detailed motor examination based on the
widely used Columbia scale.
The fourth is a questionnaire assessing complications,
focusing principally on fluctuations and dyskinesias.

The fifth is modified Hoehn and Yahr staging.


The sixth is Schwab and England activities of daily
living scale.
Atypical parkinsonian syndrome (Parkinson plus syndrome
PkS+).

Diseases with PkS+ = Disorders of multiple system


degeneration.
Alzheimer-type dementia with parkinsonism (ATD-P).
Corticobasal ganglionic degeneration (CBGD).
Creutzfeldt-Jakob disease (CJD).
Diffuse Lewy body disease (DLBD).
Hallevorden-Spatz disease (HSD).
Hemiparkinsonism-hemiatrophy (HPkSHA).
Hydrocephalic parkinsonism (HP).
Multi-infarct dementia (MID).
Olivopontocerebellar atrophy (OPCA).
Parkinsonism-dementia-amyotrophic lateral sclerosis
complex (PkSDALSC).
Progressive supranuclear palsy (PSP).
Shy-Drager disease (SDD)
Striatonigral degeneration (SND)
Multisistem atrophy (MSA) includes: SND, OPCA, SDD and
PkSDALSC).
Vascular parkinsonism (VP).
Wilsons disease (WD).
Disease onset:
Young onset before age 40 years = Juvenile PD, HSD.
Symmetric onset:
SND, VP, HP.
Orthostatic hypotension:
MSA (particularly SDD).
Tremor:
Minimal or absent tremor: SND, PSP, SDD.
Atypical tremor: CBGD, OPCD,
Predominant postural instability: PSP, MSA (all forms),
HP, VP.
Predominant ataxia: MSA (particularly OPCD).
Pyramidal signs: MSA (particularly SND),CBGD, VP,HP
Neuropathy: MSA (particularly PkSDALSC)

Marked and persistent motor asymmetry: CNGD, HSD,


HPkSHD.
Dystonia: PSP, SND, CBD.
Myoclonus: CBGD, CJD.
Early dementia: DLBD, ATD-P, CJD, MID, PSP.
Focal cortical signs: CBGD, MID.

Oculomotor deficits: PSP, OPCA, CBGD.


Dysautonomia: MSA (particularly SDD).
Other diseases with parkinsonian syndromes:
Infectious and postinfectious parkinsonism.
Toxin-induced parkinsonian syndromes.
Drug-induced parkinsonian syndromes.
Cerebral traumatism with parkinsonian syndrome.
Calcification of basal ganglia with PkS.

XII. INVOLUNTARY MOVEMENTS SYNDROMES

Abnormal involuntary movements (AIM) or dyskinesias are


definite as orofacial, lingual, head, trunk and extremities
movements that can be modified but not abolished by the patient.
AIM can superimpose normal motor activities and can
interfere with coordinated voluntary motor activities and
posture maintenance.
It is important to determine age of onset, rate of progression,
family history, prior medication history, possible toxic
exposure and associated medical, neurological and
psychiatric illnesses.
There are certain characteristics, which help the diagnosis
of AIM:
Topography (distribution).
Symmetry or asymmetry.
Stereotyped or nonstereotyped.
Overflow to other body part.
Velocity: slow, intermediate, fast.
Rhythm: continuous or intermittent.
Relation to general voluntary movement,
Relation to specific tasks.
Relation to posture.
Relation to sleep.
Associated sensory symptoms.
Hypersensibility.
Aggravating factors (e.g.: stress, anxiety).
Precipitating factors (e.g.: stress, fatigue, alcohol, caffeine).
Ameliorating factors (e.g.: sleep, rest, alcohol).
Distractibility and consistency: to distinguish functional
movement disorders.
Tremor:
Physiological tremor:
Physiological tremor (PT) is invisible mechanical
vibration of body part and is present in all normal people.
PT is visible to the naked eye and is symptomatic only
during actions that require extreme precision.
PT is most often caused by anxiety or emotional stress.
Normal elbow tremors have a frequency of 3-5 cycles/s,
wrist tremors 8-12 cycles/s and metacarpophalangeal
joint 17-30 cycles/s.
PT may be a protective measure against unusual limb
posture.

Etiology enhanced PT:


Thyrotoxicosis.
Hypoxia.
Essential tremor (ET):
ET may commence at any age, but its incidence rises with
advancing years.
The onset of ET may be earlier in the familial form, as
compared to the sporadic form.
ET incidence rises with advancing years.
ET appears most frequently in the hands and has both
postural and kinetic character.
The next most frequently affects body is cranial
musculature (e.g.: head, tongue, voice).
In advanced cases, ET is in palate also.
ET is of postural type and is best seen with maintenance of
a fixed posture.
ET may be accentuated with goal-directed movement of
the limbs (kinetic tremor) and, in some instance, may be
present at rest.
The different posture of the arm affected the magnitude of
the tremor.
ET can affect solely or predominantly one body part.
Isolated tremors of the tongue, chin and voice may occur.
ET may occur in a wide range of frequency (4-12
cycles/s),
Inverse relationship between amplitude size and tremor
rate.
ET affecting the hands is primarly writing tremor.
ET is generally considered to be a slowly progressive
disorder.
ET has been described in association with various
disorders and conditions.
The patient with ET may be handicapped by the physical
limitations that the tremor may create (e.g.: writing,
drinking liquids) or by the social embarrassment that it
may cause.
ET has been described in association with various
disorders and conditions (e.g.: significantly higher
incidence of cardio-vascular disorders).

Patients with ET may have deficits on neuropsychological


functioning, particularly those involving prefrontal and
frontal cortex.
ET is probably produced by a central oscillator that can be
enhanced or suppressed by reflex pathways.
Rest tremor (RsT):
RsT occurs in a body part that is not voluntary activated
and is completely supported against gravity.
RsT is produced by the alternate contraction of
antagonistic muscles.
The most common anatomic site for RsT is the distal parts
of the upper limbs.
RsT can also be seen in lower extremities and, less
commonly, in lips, tongue and jaw.
The characteristic upper limb RsT includes pronationsupination of the forearm, flexion-extension of the wrist
or pill-rolling movement of thumb, producing a gliding
movement across the first two or three fingers.
Frequency of RsT is 4-5 cycles/s, varying only by 0.2-0.3
cycles/s from person to person.
The RsT amplitude increases when movement of another
body part is performed, such as walking or under mental
stress.
For the parkinsonism, RsT involves ascending
nigrostriatal dopaminergic pathway, rubrotegmentospinal
fibers and rubroolivodentatorubral loop that normally
modifies the input into the ventrolateral nucleus of the
thalamus.
Etiology:
Parkinson disease (typically).
Progressive supranuclear palsy (rarely).
Multiple system atrophy(rarely).
Diffuse Lewy body disease (rarely).
Brain stem infarction with palatal tremor (rarely).
Cerebellar tremor (CT):
CT is a proximal kinetic tremor and could occur as the
target is reached (ataxic, intention or terminal tremor).
CT is absent when the limbs are inactive and during first
part of a voluntary movement.
As the disease advances, CT may be present during entire
course of finger-to-nose test.

In the early phase, CT can be present in the extremities,


but, as disease advances, it can involve axial structures.
The frequency and amplitude of CT are usual irregular.
In the upper extremities, CT has a frequency of 3-8
cycles/s, whereas in the lower extremities it is around 3
cycles/s.
The truncal CT (titubation), which is a rhythmic partial
sway, usually has a frequency of 2-4 cycles/s.
The tremor and ataxia may seriously interfere with
patients performance of skilled acts.
Head CT can be following bilateral cerebellar lesions.
Damage to the superior cerebellar peduncles or to the
dentate nucleus is definite as the most common site of
focal pathology that leads to severe CT.
The transcerebellar and transcortical loops may explain
CT (e.g.: cerebello-dento-rubro-thalamo-cortical circuit).
Injury of cerebellar cortex itself does not initiate tremor.
Rubral tremor (RT)= midbrain tremor (Holmes tremor):
Rubral tremor (RT) is rest and intention tremor with a
slow frequency of less than 4.5 cycles/s.
RT is sometimes irregular in presentation and often not
rhythmic.
While resting the amplitude of RT may be small, but on
attempting posture, it becomes uncontrollable and on
attempting movement, the amplitude may be at the peak
degree.
During active movement there may be further terminal
acceleration.
The proximal muscles may be affected more than the
distal muscles, unlike in most other forms of tremor.
In addition, there are usually other signs of midbrain
damage, such as hemiparesis and cranial nerve palsy.
RT is a result of interruptions of combination of pathways
in the midbrain tegmentum (rubro-olivocerebellorubral
loop, rubrospinal tract, dopaminergic nigrostriatal fibers
and the serotoninergic brainstem-telencephalic fibers).
Etiology:
Vascular.
Trauma.
Infection.
Multiple sclerosis.

Neoplastic.
Radiation
Asterixis (flapping tremor, negative tremor, negative
myoclonus):
Asterixis consists essentially of arrhythmic lapses of
sustained posture.
Asterixis is by definition only present during active
muscular contraction.
There are two major clinical presentations: a) asterixis;
b) postural lapses.
Asterixis is tremor of the hand when the wrist is extended
(dorsiflexion), sometimes said to resemble a bird flapping
its wings.
It consists of a silence of EMG discharges for a short
period of time (50-200ms), thus producing a brief loss
of anti-gravitational activity and postural control.
Flexion movements of hands may occur once of several
times a minute.
Asterixis is usually multifocal in distribution but may
affect a muscle group in isolation.
Postural lapses consist of a long duration EMG silence
(200-500ms), usually occupying axial and proximal
muscles of the lower limbs, with tendency for repetitive
appearance over a few seconds.
In patients with severe myoclonic encephalopathies,
such as postanoxic myoclonus.
These postural lapses may follow a myoclonic
discharge and may actually lead to greater functional
disability than the myoclonic discharge.
Etiology:
Hepatic encephalopathy.
Postanoxic encephalopathies.
Other metabolic and toxic encephalopathies.
Dystonic tremor (DT):
DT is a tremor in an extremity or body part that is affected
by dystonia.
DT, usually have irregular amplitude and variable
frequency (mainly less than 7 cyles/s).
DT is mainly postural/kinetic and usually not seen during
complete rest.

DT can appear in a body part not affected by dystonia


(upper limb postural tremor in a patient with cervical
dystonia).
Head tremor is common in cervical dystonia.
Etiology:
Wilson disease.
Palatal tremor (PtT) = rhythmic palatal myoclonus,
palatal nystagmus, palatal myorhythmia.
Essential palatal tremor:
Rhythmic activation of the tensor veli palatini
muscles.
Frequency is 26 to 420 cycles/s.
The palatal movement imparts a repetitive audible
click.
Ceases during sleep.
Symptomatic palatal tremor:
Rhythmic movements of soft palate (elevator veli
palatini).
Frequency is 107 to 164 cycles/s.
Often associated with oscillopsia and unilateral or
bilateral brain stem and/or cerebellar signs.
Brain stem reflexes often abnormal.
In some cases, the pharynx as well as the facial,
maseters and extraocular muscles, diaphragm, vocal
cords and even the muscle of the neck and shoulders
partake of a persistent rhythmic movements.
Persists during sleep.
Conspicuous enlargement of the inferior olivary
nucleus, unilaterally or bilaterally.
Primary orthostatic tremor= shaky leg syndrome:
Primary orthostatic tremor is a subjective feeling of
unsteadiness during standing, usually for over 10 seconds.
The age of onset may vary from the third through seventh
decades of life, with the majority of the patients
developing symptoms in the sixth or seventh decades.
Men and women seem to be affected equally.
Standing may induce visible or palpable fine-amplitude
ripping in the leg muscles (gastrocnemians or quadriceps)
with typical 13-18 cyles/s pattern.

Standing involves a wide base, but gait is normal.


Walking, sitting and lying were unaffected.
There are no other abnormal neurological symptoms.
Food-induced tremor :
Coffee, tea, cocoa:
Individual sensitivity to caffeine may vary.
Alcohol:
Alcohol, known to suppress essential tremor and a few
other forms of tremor, can itself induce tremor
through different mechanisms upon withdrawal
following chronic ingestion.
Alcohol withdrawal tremor is postural tremor and
may be a variant of enhanced physiological tremor.
Chronic alcoholism with 3 cycles/s leg tremor and
upper extremity tremor results in cerebellar
degeneration.
Drug-induced tremor:
A tremor is considered to be drug-induced if it occurs in a
reasonable time frame following drug ingestion.
It can have the whole range of clinical presentation of
tremor and there could be presence of additional signs
depending upon the nature of the drug and individual
disposition of the patients.
Tremor secondary to drugs and toxins can take many
forms, including enhanced physiological tremor,
precipitated essential tremor, rest tremor secondary to
parkinsonism, tremor of cerebellar syndrome, or can be
associated with peripheral neuropathy.
Etiology:
Antidepressant drugs.
Antiepileptic drugs.
Cardiac drugs.
Dopamine receptor-blocking drugs.
Immunosuppressant drugs.
Stimulant drugs.
Tranquilizer drugs.
Toxin-induced tremor:
Toxic tremor occurs after intoxication either acutely or
chronically.

There may be other clinical signs of central nervous


system intoxication such as gait disturbance or eye
movement abnormalities.
Etiology:
Heavy metals (e.g.: mercury, manganese, lead).
Insecticides and herbicides.
Solvents.
Peripheral neuropathy-associated tremor:
The tremor seen in peripheral neuropathy is rare and is
described as irregular, rhythmic, proximal or distal.
Frequency ranging from 3-10 cyles/s.
Slowing of nerve conduction would increase the delay in
stretch reflex and this may lead to enhancement of tremor.
Task-specific tremor (TsT):
TsT is a rare form of tremor that involves skilled, highly
learn motor act.
TsT may be a variant of essential tremor.
TsT occurs only when performing a specific repetitive task
unique to each individual.
Frequency of TsT is 5-7 cycles/s.
Generally, no other associated neurological signs and
symptoms are present with the exception of focal
dystonia.
Examples: a) hair-cutting; b) shaving; c) playing a musical
instrument.
Primary writing tremor is the most common form of TsT
that occur predominantly during writing but not during
other hand task (active pronation of hand produces
several beats of pronation-supination tremor).
Vocal tremor (VT):
Synonyms:
Tremulous voice.
Quivering speech.
VT is involuntary, rhythmic, oscillatory movements
that affects vocal musculature in patients with
tremulous disease.
The prime generator of VT is central nervous
disturbance.
The phonatory reflection is typically multifactorial,
involving a combination of the extrinsic and intrinsic
laryngeal muscles, pharyngeal muscles (including that

of the supraglottic structure), diaphragm and


respiratory, intercostal and abdominal muscles.
The frequency of VT may range from 4 to 8 cycles/s, with
amplitudes of oscillations ranging widely.
Etiology:
Parkinson disease.
Cerebellar disease.
Essential vocal tremor.
Focal dystonia.
Trombone tremor:
The tongue projected from the mouth executes to-andfro movements.
Etiology:
Dementia paralytica.
Psychogenic tremor (PsT) hysteric tremor.
Higher incidence in females than males.
Is seldom reported in children.
Abrupt onset and static course.
Spontaneous remissions.
Is generally bilateral with mixture of frequency and
patterns (unclassifiable tremors complex tremors).
PsT has clinical inconsistencies (selective disabilities).
PsT has a changing characteristics.
PsT increases with attention.
PsT lessens with distractibility.
Absence of other neurological signs.
Unresponsiveness to antitremor drugs.
Responsiveness to placebo.
Remission with psychotherapy.
Multiple somatizations.
Presence of unphysiologic weakness or sensory
complaints.
Presence of unwitessed paroxysmal disorders.
Documented functional disturbances in the past.
Chorea:
Chorea (Ch) is a dyskinesia:
Ch consists of irregular, unpredictable brief, jerky
movements that are usually at low amplitude.
The movements are usually distal and range from mild
chorea resembling fidgetiness in children to severe chorea

interfering with speech, swallowing, maintaining posture


and the ability to walk.
The movements eventually occur throughout the body,
including respiratory, pharyngeal and laryngeal
musculature.
Facial grimacing can be present in Ch.
Ch can be associated with hypotonia of the limbs.
The gait may resemble a dance (e.g.: waltz).
Ch can result in a hung-up tendon reflex doe to muscle
contraction immediately after reflex contraction due to
muscle stretch.
In Ch may be seen: a) motor impersistence (e.g.: inability
to protrude the tongue in a sustained manner); b)
milkmaid grip due to contractions alternating with
relaxations of grip.
Although conspicuous and of cosmetics concern, Ch is not
usually disabiling.
Individuals with relatively severe Ch may be able to
function, ambulate and care for themselves surprisingly
well.
In some patients, Ch may appear as severe uncontrollable
failing of extremities or ballism, interfering with the
patients ability to feed, sit in a chair or in bed.
Patients may incorporate choreiform movements into
apparently purposeful gestures, a phenomenon referred
to as parakinesia.
Ch may be the only sign of disease, as in rheumatic chorea
(Sydenhams chorea, chorea minor, acute chorea) or
thyrotoxicosis, or may part of constellation of other sings
as in Huntington disease (chronic chorea) or neuroacanthocytosis.
Huntingtons disease (HD):,
In HD dyskinesias have been reported to occur in sleep
with lowest frequency during slow-wave sleep (stage 3
and 4) but in REM sleep appeared to be a time of relative
activation of Ch.
In HD striatal projection neurons degenerate the
striatal output projecting to GPe are preferentially
affected, leading to reduced inhibition of SNT neurons,
resulting in decreased GPi output, the hallmark of
hyperkinetic disorders.

Sydenhams chorea (SC):


SC may occur 6 months or more after group A streptococcus infection.
In SC, choreatic movements are usually bilateral, but may
be unilateral.
SC may begin either abruptly or insidiously, worsen over
2-4 weeks and usually resolves spontaneously in 3-6
months, although some patients may have residual Ch.
Other choreatic disorders:
Chorea gravidorum.
Systemic lupus erythematosus.
Primary antiphospholipid antibody syndrome.
Hereditary chorea (chorea-acanthocytosis).
Senile chorea.
Vascular chorea.
Hyperthyroidism.
Ballism (Bl):
Bl is rare movement disorder.
Bl and Ch are often interrelated and may occur in the
same patient.
Bl is characterized by proximal large-amplitude, irregular,
flinging, unilateral limb movements.
The onset in Bl is usually sudden, but in some cases it
evolves over several days or weeks.
The movements are often violent and have wide
amplitudes of motion.
The movements are continuous and is common for arms
and legs to move together.
The more a patient is active, the more the movements
increase and with relaxation comes a decrease in
movements.
With time, Bl become less violent and acquire a choreic
quality.
Bl is usually limited to one side of the body (hemiballism).
Rarely, the ballistic movements involve one limb (monoballism) or both sides (biballism).

Bl decreased in Non-REM sleep but continue to be


detectable.
In the majority of cases, Bl results from lesions involving
subthalamic nucleus.
When the subthalamic nucleus stroke is basis of HB, there
is usually a spontaneous recovery.
Lesions of subthalamic nucleus interrupt the indirect
pathway, leaving activity along the direct pathway.
Etiology:
Stroke.
Traumatic brain injury.
HIV infection.
Tardive dyskinesia (TDy):
TDy is defined as AIM appearing after treatment with
antipsychotic neuroleptic drug (that block central dopamine
receptors) for 3 or more months in a patient with no other
identifiable causes for a movement disorder.
Metoclopramide and promethazine, others dopaminergic
receptor blockers, are associated with the same disorder.
Clozapine, a newer atypical antipsychotic has been shown
to have a lower risk to tardive dyskinesia.
Concurrent prophylactic use of a neuroleptic and an
antiparkinsonian drug is useless to avoid early
extrapyramidal side effects and may render the patient
more sensitive to TDy.
A variety of movements occur in TDy.
Most common are rapid unsustained movements
variously described as choreic or stereotypic.
Choreic movements are unpredictable and flow from one
body region to another.
Stereotypic movements are reproducible and regular,
remaining generally restricted in their anatomic
distribution.
Anybody area may be affected, but the mouth is commonly
involved, producing lip-smacking, tongue protrusion or
grimacing.
In addition to facial movements, rapid movements of the
fingers, hands or more proximal arm, nodding or headbobbing, pelvic rocking motions, fine movements of the
toes or a nonrhythmic motion of both legs may develop.

TDy may involve trunk and diaphragm, sometimes leading


to speech disorders or even respiratory distress.
Dystonic movements also occur in TDy, either alone or in
combination with choreic or stereotypic movements.
Tardive akathisia is unpleasant sensation of internal
restlessness that typically involve lower extremities and is
partially relieved by volutional movements.
Tics and myoclonic movements are also within potential
repertoire of TDy.
Pathophysiology:
Dysfunction of indirect striatal outflow may be
consistent with dopaminergic hypothesis of TDy.
A drug-induced overactivity of dopaminergic function,
perhaps via neuroleptic-induced changes in D2
receptors, could cause excessive inhibition of
subthalamic nucleus neurons and functional
disinhibition of pallidothalamic outflow.
Dystonia:
Dystonia is characterized by involuntary twisting and
repetitive movements or abnormal postures resulting from
the sustained co-contraction of agonist and antagonist
muscles.
Dystonia:
Primary (idiopathic) dystonia = idiopathic torsion
dystonia.
Secondary (symptomatic) dystonia.
Different muscle groups can be involved with variable
extent and severity, ranging from intermittent
contractions limited to a single body region to generalized
dystonia involving the axial and limb muscles.
A basal ganglia dysfunction with imbalance between
normal modulation of the direct and indirect pathways is
generally considered the basis for cortical disinhibition
and abnormal motor output in dystonia (both direct and
indirect pathways are overreactive).
Classification of dystonias:
Focal = a single area is involved:
Upper face muscles (blepharospasm).
Lower lace muscle (oromandibular dystonia).
Vocal cords (spasmodic dysphonia, laryngeal
dystonia).

Neck muscles (spasmodic torticollis, cervical


dystonia).
Arm muscles (writers cramp).

Segmental = two or more contiguous areas are affected:


Cranial muscles (face + jaw + tongue + vocal cords).
Cranial, cervical and brachial muscles.
Bilateral brachial muscles (bibrachial dystonia).
Axial muscles (neck and trunk).
Multifocal = two or more noncontiguous body regions are
involved:
Involvement of one or both arms plus one leg.
Cranial muscles involvement (e.g.: blepharospasm plus
leg dystonia).
Hemidystonia.
Generalized = multiple areas including the legs are
involved:
Both legs with or without the trunk and at least one
other region.
One leg and the trunk plus one other region.
Etiology:
Unlike childhood-onset classic idiopathic torsion
dystonia, in which current evidence indicates that the
mode of inheritance is autosomal dominant with
reduced penetrance, the role of hereditary in adultonset cases is not well understood.
Autoimmune diseases.
Dystonia may be precipitated by peripheral factors
such as overuse, misuse or trauma
Blepharospasm (Bsp):
Patients with Bsp have intermittent or sustained bilateral
eyelid closure as a result of involuntary contractions of the
orbicularis oculi muscles.
Mild spasms of the frontalis and the middle and lower
facial muscles also occur frequently.
Bsp affects women more than men and has its onset in
about the sixth decade of life.
Common complaints at onset are excessive blinking, eye
irritation, burning and photophobia.

Patients with Bsp, which may begin in one eye only,


complain of eye discomfort, involuntary eye closure, eye
narrowing or inability to open the eyes.
Bsp patients have variable degrees of difficulty with tasks
such as reading, watching television or driving.

Spasms of eye closure are generally aggravated by stress


and disappear during sleep.
Bsp is worsened by exposure to bright light.
In most patients, dystonia spreads during the initial 5
years of onset of Bsp.
Oromandibular dystonia (OmD):
In OmD spasms occur in the region of jaw, lower face and
mouth.
Involvement of the masticatory muscles frequently
produces spasms of jaw closure associated with
involuntary contractions of the temporalis muscle and the
maseters can produce trismus and bruxism.
Involuntary contractions of the lower facial muscles result
in spasms of lip tightening, involuntary retraction of the
corners of the mouth and lip pursing.
Platysmal contractions are also common.
Lingual dystonia is manifested by lateral or upper
deviation of the tongue, as well as by tongue protrusion.
OmD in isolation is a relatively uncommon form of
dystonia,but is usually very disabiling.
The association of Bsp with OmD is called cranial dystonia
or Meiges syndrome.
Spasmodic dysphonia (SD):
SD occurs between 30 and 50 years of age and affects
more women than men.
Dystonic spasms in SD occur during speech, whereas the
muscles and anatomic structures of the larynx are normal
during rest.
Onset of SD is usually gradual, at times following an upper
respiratory infection and during either occupational or
emotional stress.
The initial complains are increased effort and loss of voice
and pitch control, at times only during stress.
After 1-2 years of progression, the disease tends to
stabilize and become chronic.

Speech can improve briefly after a yawn or a sneeze.


Laughing, coughing or crying do not become affected.
In 20-30% of patients, dystonia occurs elsewhere, usually
in the cranial or cervical region.

Adductor SD is caused by irregular hyperadduction of


vocal cords.
Patients with adductor SD exhibit a choked, strained,
staccato voice quality with abrupt initiation and
termination of vocalization, resulting in short breaks in
phonation.
Abductor SD is caused by irregular contraction of the
posterior cricoarytenoid muscles during of speaking.
Abductor SD is much less frequent.
Patients exhibit a breathy, effortful voice, resulting in
aphonic whispered segments of speech.
Spasmodic torticollis (ST):
ST is a chronic neurological movement disorder causing
the neck to involuntary turn to the left, right, upwards
and/or downwards.
Reported female to male ratios for idiopathic ST are ~2:1.
Mean age at onset is between 38 and 42 years.
Patients with ST experience jerky movements of the head
and intermittent or constant head deviation at rest.
Torticollis is the horizontal turning (rotational collis) of
the head and uses the ipsilateral splenius and
contralateral sternocleidomastoid muscles (chin-toshoulder).
Laterocollis is the tilting of the head from the side to side
and
involves
more
ipsilateral
muscles:
sternocleidomastoid, splenius,
scalene complex,
ipsilateral levator scapule and posterior paravertebrals
(ear-to-shoulder).
Anterocollis is the flexion of the neck (head tilts forwards)
and this movement utilizes the bilateral muscles: scalene
complex, sternocleidomastoid, submental complex (chinto-chest).
Retrocollis is the extension of the neck (head tilts back)
and uses
the following bilateral muscles for the

movement: splenius, upper trapezius, deep posterior


paravertebrals (chin-in-the-air).
Deviation of the head can take any combination of
directions.
Frequently, the shoulder is elevated on the side toward
which the chin is pointing and a mild degree of dystonia
can be detected in the proximal muscles of the limbs on
the same side.
The pain is most frequent in patients with constant head
deviation and it is usually localized in the neck, patients
can develop secondary cervical radiculopathy.
Head tremor is a dystonic tremor.
Sensory tricks used by torticollis patients to reduce the
intensity of spasms include couching of the chin, face or
occiput.
One such trick, called geste antagonistique consist of
correction of the head position when a vary light touch or
pressure is applied to the chin, cheek or elsewhere in the
head contralateral to the direction of the head turn.
The severity of ST tends to progress during the first
months or years of the illness and the dystonic spasms can
later spread to the oromandibular region or arm.
ST is: a) primary (idiopathic); b) secondary
(symptomatic).
Both agonist and
antagonist muscle contract
simultaneously during dystonic movement.
Etiology of secondary ST:
Perinatal cerebral injury.
Kernicterus.
Cerebrovascular disease.
Drug induced.
Central nervous system tumor.
Peripheral or central trauma.
Infectious or postinfectious encephalopathies.
Metabolic or toxins.
Paraneoplastic syndromes.
Central pontine myelinolysis.
Limbs dystonia (LD):
LD is characterized by involuntary contractions of limb
musculature that result in twisting and repetitive
movements of abnormal posture in the extremities.

LD can affect the leg or the arm and can be focal as in


writers cramp or segmental, as when involving the arm
and the neck (brachial) or leg and trunk (crural).
LD is always present in patients with generalized dystonia
and in hemidystonia.
Idiopathic LDs are frequently action dystonias, superimposed on voluntary movements such writing, using
eating utensils or walking.
As the disease progresses, the dystonic postures become
more sustained and fixed, even more so when they occur
in the legs.
When occurring in the upper extremities, distal
involvement is more common in the form of wrist flexion,
ulnar deviation and supination (however, elevation,
internal rotation of the arm can occur also).
In some patients the arm pulls behind the patients
back spontaneously.
Many upper LDs are task-specific dystonia (TsD) : they
occur exclusively or primarly when the patient
performs a specific task.
The most frequent TsD of arm is writers cramp.
Others TsD: a) musicians (e.g.: guitarists, trumpet
players, string players); b) sportsmen (e.g.: golfers,
snooker players, dart throwers).
Dystonia occurring in the lower extremities usually affects
distal joints, principally the ankle, with plantar flexion and
inversion of the foot.
The sole of the foot can also cup and the toes can flex.
Initially, the foot dystonia occurs only when one is
walking, being absent with the limb at rest.
Frequently, running, walking in tandem or walking
backwards fails to trigger the abnormal posture.
The initial equinovarus posture that occurs when the
patient is walking may evolve into a fixed dystonic
posture, commonly causing plantar flexion, extension
of the knee and extension, internal rotation and
abduction of the hip.
When lower LD occurs in childhood, it usually
heralds the onset of early generalized dystonia.
Truncal dystonia (TD):

Continuous or repetitive spasm cause flexion, extension or


torsion of the trunk.
At onset, TD may occur only when walking or standing,
eventually can be present even when the patient is lying
down.
In some patients, spasms are rapid enough to resemble
myoclonus and this has been referred to as woodpecker
dystonia.
Extension to adjacent regions can occur, such as
retrocollis, involving of proximal limb muscles or pelvic
involvement copulatory dystonia).
Writers cramp (WCr):
WCr is a most common task-specific dystonia.
WCr is classified:
Simple dystonia occurs only when writing.
Dystonic the spasms appear with other hand task,
such as using a screwdriver or shaving.
WCr may evolve from simple to dystonic.
Symptoms of WCr appear as the pen is picked up or after a
few words of writing.
WCr usually presents as a forceful exaggeration of the
usual grip of the pen, but in other instances
hyperextension of the fingers may prevent the pen from
being held in the hand.
The wrist can show hyperextension or flexion or forced
supination or pronation.
Writing is jerky, shaky and laborious and it may be
accompanied by a sensation of tension and discomfort in
the forearm.
Frequently, writing becomes impossible after few words.
Extension of dystonia to other adjacent or more distant
body regions can occur over months to years after onset of
symptoms.
Tremor occurs and can be postural symmetrical hand
tremor or a tremor triggered by writing.
Secondary (symptomatic) dystonia:
Secondary dystonia is considered to: a) be often
accompanied by other neurological disorders; b)
begins suddenly at rest and occur at rest from the
onset; c) be associated with different known
hereditary and environmental causes.

Secondary dystonia due to chemical or therapeutic


agents can be: a) acute; b) persistent.
Anatomoclinical correlation:
Putaminal lesions hemidystonia or limb
dystonia.
Thalamic lesions hand dystonia.
Brain stem lesions blepharospasm, Meiges
syndrome.
Dystonia in neurodegenerative disorders:
Parkinson disease.
Progressive supranuclear palsy.
Corticobasal degeneration.
Multiple system atrophy.
Huntington disease.
Neuroacanthocytosis.
Dentorubropallidoluysian atrophy.
Wilson disease.
Hallervorden-Spatz disease.
Calcification of the basal ganglia.
Progressive pallidal degenerations.
Segawa disease (dopamine-responsive dystonia).
Rett syndrome.
Xeroderma pigmentosum.
Dystonia in hereditary ataxias:
Machado-Joseph disease.
Ataxia telangiectasia.
Dystonia in metabolic disorders:
GM1 gangliosidosis.
GM2 gangliosidosis.
Niemann-Pick disease.
Metachromatic leucodystrophy.
Ceroid lipofuscinosis.
Palizaeus-Merzbacher disease.
Disorders of energy production:
Mitochondrial encephalomyopathies.
Leighs syndrome.
Disorders of organic and amino acid metabolism:
Glutaric aciduria type I.
Methylmalonic aciduria.
Fumarase defiency.

Hartnup disease.
Abnormalities of purine metabolism:
Lesch-Nyhan syndrome.
Dystonia due to physical agents:
Head trauma.
Dystonia due to therapeutic agents:
Dopamine receptor blockers.
Antihistaminics + dopamine receptor blocking
properties.
Catecholamine stimulating agents.
Serotonin stimulating agents.
Acetylcholine stimulators or inhibitors.
Anxiolytics.
Antiepileptic drugs.
Other: a) anesthetics; b) disulfiram; c) flecainide;
d) ranitidine; e) cimetidine; f) sumatriptan;
g)
meperidine; h) flunarizine; i) cinnarizine; j) lithium; k)
betahistine.
Dystonia due to neurotoxic chemicals:
Minerals: a) manganese; b) copper: c) mercury.
Organic compounds: a) methyl alcohol; b) cyanide;
c) carbon monoxide; d) carbon disulfide.
Plant derivates and pesticide: a) ergotmycotoxin;
b) fenthion.
Psychogenic dystonia:
Munchausens syndrome is characterized by a chronic
factitious disorder consistent with clinical symptoms
that are under patients voluntary control and depend
on the medical knowledge of the subject.
Athetosis:
Athetosis is an involuntary movement disorder:
Irregular, forceful, slow, writhing movements generally of
the extremities, very often with finger movements and
with co-contraction of agonists and antagonists.
Athetosis can be characterized
by unbalanced,
involuntary movements of muscle tone and a difficulty
maintaining posture.
Athetosis can vary from mild to severe motor dysfunction.
Athetosis can be restricted to a part of body or present
through the body.

Athetosis is caused by lesions in several brain areas such


as the hippocampus, motor thalamus and corpus striatum.
Pseudoathetosis is a movement disorder, very similar to
athetosis, in which the symptoms are not differentiable
from those of actual athetosis, but is caused by the loss of
proprioception.
Athetosis can use to describe distal, slow writhing forms
of dystonia.

Restless legs syndrome (RLS):


RLS is a neurological disorder.
RLS may start at any age, including childhood and is a
progressive disease for some, while the symptoms may
remit in others.
Mean age of onset is between 27 and 41 years.
RLS is slightly more common in women.
Positive family histories are in ~50% of patients with RLS.
Distressing and irresistible urge to move the legs
(akathisia), usually accompanied by disagreeable leg
sensations.
It most commonly affects the legs, but can affect the arms,
torso and even phantom limbs.
RLS sensations can most closely be compared to an itching
in the muscle, like pins and needles, crawling sensation
an itch you cant scratch or unpleasant tickle that wont
stop and even as a deep-seated fullness in the calves.
The sensations typically begin or intensify during quiet
wakefulness, such as when relaxing, reading, studying or
trying to sleep.
The sensations and need to move may return after ceasing
movement or at a later time.
Most individuals with RLS have limb jerking during sleep
(periodic leg movements in sleep), which is an objective
physiologic marker of disorder and is associated with
sleep disruption.
NIH criteria of RLS:
An urge to move the limbs with or without sensations.

Improvement with activity (in more severe RLS the


relief of symptoms not to be complete or the
symptoms may reappear when the movement ceases).
Worsening at rest (an increased level of mental
awareness may help reduce these symptoms).
Worsening in the evening or night (RLS show a clear
circadian rhythm).

Myoclonus:
Myoclonus (Mc) is a movement disorder:
Mc is a brief jerk caused by neuronal discharges.
A myoclonic jerk consist of a single muscle discharge but
can be repetitive, giving rise to a salvo of muscle activity.
Myoclonic jerks mai occur alone or in sequence, in a
pattern or without pattern.
Mc is caused by rapid contraction (positive Mc) and
relaxation (negative Mc) of the muscle.
Both forms often share the same etiology, coincide in the
same patients and can even affect the same muscle group.
It is important to realize that different patterns of Mc are
often combined in the same subject.
Mc can be classified from various point of view:
Clinical presentation:
Spontaneous.
Action.
Reflex.
Clinical distribution:
Generalized.
Multifocal.
Segmental.
Focal.
Neurophysiological origin:
Cortical.
Brain stem (reticular).
Spinal cord.
Epileptic myoclonus:
Cortical reflex Mc.

Reticular reflex Mc.


Primary generalized epileptic Mc.
Photic cortical reflex Mc.
Juvenile myoclonic epilepsy.
Progressive myoclonic epilepsy.
Etiology:
Physiological.
Essential.
Symptomatic (associated with epilepsy or associated with
other causes).

Normal Mc:
Hiccups: Mc of the diaphragm.
Hypnic jerks: involuntary myoclonic twitch during
hypnagogia just as a person is beginning to fall asleep
or during the non-REM sleep, often causing awaken
suddenly.
Essential Mc:
Essential Mc occurs in the absence of the epilepsy or
other apparent abnormalities in the brain or nerves.
The EEG should be normal.
Familial cases as well as sporadic cases are seen.
The Mc is generalized, appears to occur seldom at rest
and is clearly induced by action.
Reflex Mc:
Somesthetic,
visual
and
auditory
stimuli,
independently and in combination may trigger Mc.
Such Mc is focal or generalized in distribution.
Action Mc:
Action Mc occurs during active muscular contraction
and affects both posturally acting muscles and prime
action.
Action Mc may be focal or segmental, but the most
common distribution is multifocal or generalized.
Negative Mc (astreixis):
Negative Mc is present only during active muscular
contraction and in fact is almost always combined with
positive action Mc.
Negative Mc are two major clinical presentation:
a)
asterixis; b) postural lapses.

Spontaneous Mc:
Spontaneous Mc may be focal, multifocal or
generalized.
It may be sporadic and occur unpredictably or coincide
with specific movements, such as in normal people
with nocturnal myoclonus or in patients with early
morning myoclonic epilepsy.
In other instances, it may be almost continuously
present,
as
in
patients
with
metabolic
encephalopathies or Creutzfeldt-Jakob disease.

Rhythmic Mc(platal myoclonus):


Rhythmic Mc is always spontaneous in presentation,
with a focal or segmental distribution.
The myoclonic discharge may persist during sleep and
is little affected by sensory stimulation.
Cortical Mc = epileptic Mc:
Cortical reflex Mc results from abnormal activity
arising in the sensorimotor cortex and spreading down
via corticospinal pathway.
Cortical reflex Mc is a fragment of focal or partial
epilepsy.
Each myoclonic jerks involves only a few adjacent
muscles, but larger jerks with more muscles involved
can be seen.
The disorder is commonly multifocal and is
accentuated by action and sensory stimulation.
The EEG reveals a focal positive-negative event over
the sensorimotor cortex contralateral to the jerk
preceding both spontaneous and reflex-induced
myoclonic jerks.
Reticular Mc = epileptic Mc:
Reticular reflex Mc is a fragment of a type of
generalized epilepsy.
The muscle jerks are usually generalized, with
predominance that is proximal more than distal and
flexor more than extensor.
Voluntary action and sensory stimulation increase
jerking.

Etiology: a) postanoxic myoclonus; b) toxic-metabolic


encephalopathies (uremia).
Primary generalized epileptic myoclonus (PGEM):
PGEM is a fragment of primary generalized epilepsy.
The most common clinical manifestation is small, focal
jerks, involving only the fingers (minipolymyoclonus
of central origin).
The second clinical presentation of PGEM consists of
generalized, synchronized whole-body jerks not unlike
seen with reticular reflex Mc.
The EEG correlation is a slow, bilateral frontocentrally
predominant negativity similar to the wave of primary
generalized paroxysm.
Photic cortical reflex Mc = epileptic Mc:
Photic cortical reflex Mc has an origin in a
hyperexcitable motor cortex and is driven by an
occipital response of normal appearance.
Juvenile myoclonic epilepsy:
Myoclonic seizures usually involve the neck, shoulders
and upper arms.
These seizure typically shortly occurs after waking up.
Progressive myoclonic epilepsy:
Progressive myoclonic epilepsy includes both
myoclonic and tonic-clonic seizures.
Epileptic myoclonus has been recognized in several
disease state not conventionally conceived of as part
of the myoclonic syndromes (e.g.: Lennox-Gastaut
syndrome, corticobasal degeneration, olivopontocerebellar atrophy, progressive supranuclear palsy.
Spinal Mc:
Spinal Mc is secondary to abnormal
neuronal
discharge originating in the spinal cord.
It is frequently rhythmical and only exceptionally
stimuli-sensitive.
The most frequent clinical presentation consists of
spontaneous, repetitive jerks of one limb, sometimes
spreading to the adjacent neck and trunk muscles.
The frequency of the Mc is variable from 10 to 50/min.
The spinal Mc persists during sleep.

Propriospinal Mc, in which spontaneous and


stimuli-sensitive (tapping) jerks involve mainly the
trunk and abdominal muscles (nonrhythmic,
repetitive axial flexion).
Etiology: a) cervical myelopathy (posttraumatic),
tumors, multiple sclerosis and infections.
Axial Mc:
Axial Mc consists in segmental and rhythmical My
of the neck and trunk.
Etiology: a) brain stem lesions; b) Arnold-Chiari
malformation; c) upper cervical cord damage.
Minipolymyoclonus of peripheral origin refers to small
jerks seen in patients with peripheral motor neuron
disease.
Minipolymyoclonus has progressive muscle
weakness and denervation.
Tics:
Tics (Tc) are
brief, rapid, repetitive and seemingly
purposeless stereotyped actions that involve a single muscle
or multiple muscle groups.
Tc typically present in childhood or adolescence and may
be transient or last a lifetime.
With aging, most Tc tends to reach a stable plateau or
disappear altogether.
Tc are:
Motor or vocal.
Simple or complex.
Motor Tc:
Motor Tc have a wide spectrum of severity, ranging
from the barely detectable to the complex, emotionally
laden gestures.
Motor Tc can affect any part of the body but they
typically begin in the eyelids or face and, over time,
involve other muscle groups, spreading to the neck,
shoulders, trunk, legs and feet with apparent
rostrocaudal migration.
Motor Tc may be fast or clonic, slower or dystonic Tc.
Clonic Tc include repetitive and persisting blinking,
nose twitching, blepharospasm, grimacing, jaw
opening shoulder shrugging and head jerking.

Distonic Tc are characterized by sustained twisting,


pulling or squeezing, producing a grief maintained
body posture.
Vocal Tc:
Vocal Tc can range from throat clearing or sniffing
sounds, to other simple sounds or words, to the
sometimes offensive utterances found in a minority of
patients (barking, growling, coughing, moaning,
humming, panting, belching, stuttering, echolalia,
palilalia).
Etiology:
Sydenhams chorea (infectious, parainfectious or
immo-logic disorders).
Toxic (e.g.: carbon monoxide poisoning).
Vascular (e.g.: lacunar states or systemic vasculitides
involving basal ganglia).
Drug-induced (e.g.: drugs that may cause excitation
and anxiety, psychostimulants).
Tourette syndrome (TS):
TS onset is before 15 years (between the ages of 2 and 15,
with mean age at onset being 7 years).
The initial tics ( motor) usually occur in the upper body.
Both multiple motor and one or more vocal tics have been
present at the same time during the illness, although not
necessarily concurrently.
The tics occur many times a day (usually in bouts) nearly
every day or intermittently throughout a period of more
than 1 year and during this period there was never a ticfree period of more than 3 consecutive months.
Complex motor tics consist of more coordinated and
complicated movements that may appear purposeful as if
performing a voluntary motor act (e.g.: touching, smelling,
jumping, obscene gesture and mimicking movements
performed by others.
Complex vocal tics have linguistic meaning and consistent
of full or truncated words, such as echolalia (repeating the
words of others), palilalia (repeating the individuals own
words) and coprolalia (obscene words).
The tic disorder of TS represents a wide spectrum of
involuntary movements and noises, some of which

may appear bizarre (e.g.: throwing objects, pulling


down pants).
The motor and vocal tics in TS characteristically
follow a waxing and waning pattern.
The patient often experiences an irresistible urge to
tic.
Behavioral features: a) obsessive-compulsive disorder;
b) attention deficit; c) hyperactivity disorder.
Distinctive personality: a) argumentativeness;
b)
defen-siveness; b) negativism; c) impulsiveness.
Neurobiology:
Striatal dopamine receptor supersensitivity, at least
partially, underlies the tic disorder.
Stiff-person syndrome (SPS):
SPS is a rare neurologic disorder characterized by severe axial
and proximal limb rigidity due to continuous motor unit activity.
SPS is sporadic, affecting individuals of both sexes
(~2/1
male/female).
The common signs of SPS found during assessment are
hypertonia, hyperreflexia and rigidity of muscles.
Symptoms usually start slowly and insidiously (patients
often complaining of episodic aching and tightness of the
axial musculature neck, paraspinal and abdominal
muscles.
Muscle tightness, stiffness and rigidity become constant
within several weeks or months.
Involvement is usually symmetrical, spreading on to
include proximal muscle groups in all four limbs.
The patients adopt a typical hyperlordotic lumbar posture.
The hyperlordosis persist even when lying down on their
back.
An additional incapacitating symptoms is the occurrence
of intermittent severe spasm in affected muscles.
Spasms are precipitated by wide range of triggering
factors (e.g.: sudden noise, an unexpected movement, a
simple touch, emotional stimuli, passive stretching of the
muscle).
Spasms are short-lasting (minutes) and gradually
disappear if the triggering stimulus is removed and are
typically relieved by sleep.
Muscle spasms are often associated with pain.

Etiology:
In the GAD (glutamic acid decarboxylase) antibody
positive form of SPS there is a strong association with
other autoimmune diseases such as diabetes,
hyperthyroidism, pernicious anemia and vitiligo.
Neuromyotonia (Nmt):
Nmt is a form of peripheral nerve hyperexcitability that
causes spontaneous muscular activity resulting from
repetitive motor unit action potentials of peripheral origin.
As result of muscular hyperactivity patients with Nmt may
present:
Muscle cramps.
Stiffness.
Myotonia-like symptoms (delyed muscle relaxion after
voluntary contraction).
Hyperhidrosis.
Myokymia (quivering of muscle).
Fasciculations.
Fatigue.
Exercise intolerance.
The symptoms (especially the stiffness and fasciculations)
are most prominent in the calves, legs, trunk and
sometimes the face and neck, but can also affect other
body parts.
Symptoms range from mere inconvenience to debilitating
(rare).
Etiology:
Autoimmune Nmt is typically caused by antibodies
that bind to potassium channels on the motor nerve
resulting in continuous hyperexcitability.
Fasciculations (Fsc):
Fsc are visible spontaneous twitches of muscle caused by
sporadic discharges of motor unit.
Fsc arise as a result of spontaneous depolarization of a
lower motor neuron leading to the synchronous
contraction of all of skeletal muscle fibers within a single
motor unit.
Fsc can happen in any skeletal muscle in the body.
Fsc indicate denervation of muscle caused by a lesion
of the lower motor neuron at any site from the
anterior horn cell to the terminal motor axon.

Fsc is most striking in anterior horn cell disease.


Fsc may occur as a benign phenomenon without
accompanying denervation in thyrotoxicosis and are
seen in normal subjects during muscle fatigue.
Etiology:
Diseases of the lower motor neuron.
Neuromyotonia.
Organophosphate poisoning.
Acetylcholinesterase inhibitors.
Benzodiazepine withdrawal.
Magnesium deficiency.
Myalgic encephalomyelitis.
Rabies.
Fibrillations (Fib):
Fib refers to the spontaneous discharge of single muscle
fibers, recorded electromyographically.
The resulting muscle twitches are too small to by visible in
skeletal muscles but may be seen in the tongue.

Fib reflect denervation of muscle fibers as a result of


lower motor neuron damage and axonal degeneration, but
may also be found in inflammatory myopathies as the
result of intramuscular nerve damage.
Myokymia (Mk):
Mk is defined clinically as an involuntary, spontaneous,
localized quivering, undulating, wavelike, vermicular ripping
of muscles bundles within a muscle.
Mks are insufficient to move a joint.
Superior oblique Mk:
Typically involving the lower eyelid or less often the
upper eyelid.
It occurs in normal individuals and typically starts and
disappears spontaneously.
Facial Mk:
It is a fine ripping of muscles on one side of the face
and may reflect: a) an underlying tumor in the brain
stem (typically a glioma); b) multiple sclerosis
Mk in otherwise unrelated body:
Neuromyotonia.
Recovery stage of Guillain-Barr syndrome.

Inflammatory polyneuropathy.
Radiation plexopathies.
Chronic radiculopathies.
Focal compressive neuropathies.

XIII. CEREBRAL LOBES SYNDROMES

Cerebral cortex CC (pallium) is the layer of gray matter


covering the entire surface of cerebral hemispheres.
CC varies in thickness from 2 to 4 mm, being thinnest in the
primary sensory areas and thickest in the motor and
association areas.
CC contains ~14 billion neurons and ~50 billion glial cells.
Total surface area is 2200 cm2 (~1/3 surface area and 2/3
hidden in the sulci).
The weight of CC is 600 gm (~40% of total brain weight).
Laminar organization of CC:
The different cortical layers contain a characteristic
distribution of neuronal cell types and connections with
other cortical and subcortical regions.

Phylogenetically, old elements, including paleocortex of


uncus (concerned with olphalction) and archicortex of
hippocampus in the medial temporal lobe (concerned with
memory) are made up of three cellular laminae, whereas
six laminae are seen in the neocortex covering the
remaining 90% of the cortex.
Cellular laminae of the neocortex:
I. The molecular layer contains the tips of the apical
dendrites of pyramidal neurons and the most distal
branches of axons projecting to the cortex from
Intralaminar nuclei of the thalamus (the layer is the
main target of interemisferic corticocortical afferents).
II. The outer (external) granular layer contains small
pyramidal and stellate cells.
III. The outer (external) pyramidal layer contains
medium-sized pyramidal neurons and non-pyramidal
neurons with vertically-oriented intracortical axons.
The layer is the main target of interemisferic
corticocortical afferents and the principal source of
corticocortical efferents.

IV. The inner (internal) granular layer contains


different types of stellate and pyramidal neurons and
is the main target of thalamocortical afferents. Stellate
cells are especially numerous in the primary sensory
cortex, primary visual cortex and primary auditory
cortex. In contrast, the primary motor cortex, contains
relatively few stellate cells in lamina IV and is called
agranular cortex.
V. The inner (internal) pyramidal layer contains large
pyramidal neurons (such as Betz cells in the primary
motor cortex). The layer is the principal source of
subcortical efferents (the large pyramidal cells give
rise to leaving cortex and running down through the
basal ganglia, the brain stem and the spinal cord).

VI. The polymorphic (multiform, fusiform) layer


contains few large pyramidal neurons and many small
spindle-like pyramidal and multiform neurons. The
layer sends efferent fibers to the thalamus,
establishing a very precise reciprocal interconnection
between the cortex and thalamus. These connections
are both excitatory and inhibitory.
Columnar organization of cerebral cortex:
The cortical layers are not simply stacked one over the
other.
There exist characteristic connections between different
layers and neuronal types, which span all the thickness of
the cortex.
These cortical microcircuits are grouped into cortical
columns and minicolumns.
Within each column, all of cells are modality-specific.
Subsequent research has shown that cell columns
comprising several hundred neurons are the functional
units or modules of the cortex.
Some modules are activated by specific thalamocortical
inputs, others by corticocortical inputs from the same
hemisphere, others again by inputs from opposite
hemisphere.
The vast majority of connections (~99%) are from one
area of the cortex to another, rather than to subcortical
areas.
Aggregates of modules create a cortical mosaic.

Classification of cerebral cortex:


Neocortex (isocortex, homogenetic cortex, newest
cortex), the part of the mature cerebral cortex with six
distinct layers (homotypic cortex), or that passes through
a six-layered stage during development to have more or
less than six layers (heterotypic cortex) in the mature
brain.
Examples of heterotypic isocortex are agranular area 4
Brodmann and striate area 17 Brodmann.
Paleocortex is a layer of cerebral cortex intermediate
phylogenetically between the neocortex and the
archicortex (it contains 3-5 layers).

It includes the anterior olfactory nucleus, anterior


perforated substance, prepyriform area and periamygdalar area.
Archicortex (allocortex, hererogenic cortex, oldest
cortex) is the part of cerebral cortex with less than six
layers (a thinner three layered cortex)
Examples of allocortex are the olfactory cortex and
hippocampus.
Auxiliary classes:
Mesocortex (between isocortex and allocortex) where
layers 2, 3 and 4 are merged.
Proisocortex (transitional area between the true
isocortex and periallocortex). It is found in cingulate
cortex (areas 24, 25, 30 and 32 Brodmann), insula and
parahippocampal gyrus.
Periallocortex (transition zone between paleocortex
and allocortex), comprising cortical areas adjacent to
allocortex.
Brodmann areas for human cortex:
Brodmann areas are the most widely known and
frequently cited cytoarchitectural organization of human
cortex.
Areas 3, 1 & 2 primary somatosensory cortex.
Area 4 primary motor cortex.
Area 5 associatiative somatosensory cortex.
Area 6 premotor cortex and supplementary
motor cortex.
Area 7 associatiative somatosensory cortex.
Area 8 frontal eye fields.
Area 9 dorsolateral prefrontal cortex.
Area 10 anterior prefrontal cortex.
Area 11 orbitofrontal area.
Area 12 orbitofrontal area.
Area 13 insular cortex.
Area 17 primary visual cortex (V1).
Area 18 secondary visual cortex (V2).
Area 19 associative visual cortex (V3, V4, V5).
Area 20 inferior temporal gyrus.
Area 21 middle temporal gyrus.
Area 22 superior temporal gyrus (the caudal part is
usually considered to contain the Wernicke area).

Area 23 ventral posterior cingulate cortex.


Area 24 ventral anterior cingulate cortex.
Area 25 subgenual cortex (part of the ventromedial
pre-frontal cortex).
Area 26 ectosplenial portion of the retrosplenial
region of the cerebral cortex.
Area 27 pyriform cortex.
Area 28 posterior entorhinal cortex.
Area 29 retrosplenial cingulate cortex.
Area 30 part of cingulate cortex.
Area 31 dorsal posterior cingulate cortex.
Area 32 dorsal anterior cingulate cortex.
Area 33 part of anterior cingulate cortex.
Area 34 anterior entorhinal cortex (on the parahippocampal gyrus).
Area 35 perirhinal cortex (on the para-hippocampal
gyrus).
Area 36 para-hippocampal cortex (on the parahippocampal gyrus).
Area 37 fusiform gyrus.
Area 38 temporopolar area (most rostral part of the
superior and middle temporal gyri).
Area 39 angular gyrus (considered by some to be
part of Wernicke area).
Area 40 supramarginal gyrus (considered by some to
be part of Wernicke area).
Areas 41 & 42 primary and associative auditory
cortex.
Area 43 primary gustatory cortex.
Area 44 pars opercularis (part of Broca area)
Area 45 pars triangularis (Broca area).
Area 46 dorsolateral prefrontal cortex.
Area 47 inferior prefrontal gyrus.
Area 48 retrosubicular area (a small part of the
medial surface of the temporal lobe).
Area 52 parainsular area (at the junction of the
temporal and the insula).
N.B.: areas 14, 15, 16, 49, 50 & 51 only found in nonhuman primates.
The parts of cerebral cortex:
Sensory areas:

The sensory areas receive and process information


from the sense.
Parts of the cortex that receive sensory inputs from
thalamus are called primary sensory areas.
The senses of vision, audition and touch are served by
primary visual cortex, primary auditory cortex and
primary somatosensory cortex.
In general, the two hemispheres receive information
from opposite (contralateral) sides of the body.
Motor areas:
The motor areas are very closely related to the control
of voluntary movements.
Primary motor cortex executes voluntary movements.
Supplementary motor areas and premotor cortex
select voluntary movements.
Association areas:
Association areas function to produce a meaningful
perceptual experience of the world, enable us to
interact effectively and support abstract thinking and
language.
The parietal, temporal and occipital lobes all located
in the posterior part of the cortex organize sensory
information into a coherent perceptual model of our
environment centered of our body image.
The frontal lobe or prefrontal association complex is
involved in planning actions and movement, as well as
abstract thought.
Language abilities are localized in the major
hemisphere in areas 44 and 45 Brodmann (Brocas
area), for expression and area 22 Brodmann
(Wernickes area), for language reception.
N.B.: the processes of language expression and
reception occur in areas other just the perisylvian
structures .
Cortical afferents:
Corticocortical (afferent/efferent): a) association
fibers; b) commissural fibers.
Thalamocortical : a) specific fibers; b) non-specific
fibers.
Extrathalamic subcortical: a) cholinergic fibers (Ach
basal nucleus of Meynert); b) mesolimbic

dopaminergic fibers (DA ventral tegmental area); c)


serotoninergic fibers (SE raphe nuclei); d) norepinephrinergic fibers (NA nucleus locus coeruleus).
Cortical efferents:
Corticofugal fibers (projection fibers): a) corticostriate; b) corticothalamic; c) corticorubral; d) corticotectal; e) corticopontine; f) corticoolivary; g) corticobulbar; h) corticospinal.
Opercular cortex, covers the insula and includes:
Frontal operculum formed by posterior part of the inferior
frontal gyrus (pars- triangularis, pars-opercularis and
even by the caudal portion of pars-orbitaris area 47
Brodmann).
Frontoparietal opercula formed by the lowermost part of
precentral and postcentral lobule (parts of areas 40 & 43
Brodmann).
Temporal operculum formed by the superior temporal
gyrus (parts of areas 41, 42 & 22 Brodmann).
Parietotempooccipital (PTO) junction is an association
area located in the cerebral cortex of the human brain
(parietal part of area 40 + temporal part of area 37 +
occipital part of area 19 Brodmann).
Cerebral cortex is divided into four distinct areas called
lobes with specific responsibilities: a) frontal; b) parietal;
c) temporal; d) occipital.
Frontal lobe (FL):
FL is a part in the human brain located at the front of each
cerebral hemisphere.
FL is positioned anterior to the parietal lobe and
superoanterior to the temporal lobe.
FL is separated from parietal lobe by the central sulcus
(Rolando fissure) and from temporal lobe by the lateral
sulcus (Sylvian fissure).
FL is the largest and likely most complex structure in the
brain.
FL contains most of the dopamine-sensitive neurons in the
cerebral cortex.
There are three main division:
Prefrontal cortex is responsible for personality expression
and the planning of complex cognitive behaviors.
Premotor cortex.

Motor cortex.
Motor area and premotor area receive information from
various cerebral structures and control the execution of
voluntary muscle movement.
Prefrontal cortex is extremely well developed in humans
(~30% of cortical volume).
There are three main portions of the prefrontal cortex:
a) dorsolateral; b) dorsomedial; c) orbitofrontal.
Dorsolateral prefrontal cortex :
It is roughly equivalent to areas 9 and 46 and consists
of lateral portions of areas 9-12, of areas 45, 46 and
superior part of area 47 Brodmann.
Connections: temporal, parietal, thalamus, caudate GP,
substantia nigra, cingulate.
Primarily involved in executive functions: a) working
memory; b) judgment; c) motor initiating and
planning;
d) sequencing of activity (maintaining,
alternating or stopping); e) abstract reasoning and
dividing attention; f) monitoring behavior.
Dorsomedial prefrontal cortex:
It consist of medial portions of Brodmann areas 9-12
and of Brodmann areas 32, 33.
Connections: motor/sensory convergence areas,
thalamus, GP, caudate, SN.
Functions: monitors and adjusts behavior using
working memory

Orbitofrontal cortex:
Especially areas 10, 11, 12 and 47 Brodmann.
It has extensive connections with other association
cortices, primary motor, primary sensory, olfaction,
gustatory, visual streams, striatum and other
subcortical areas
It is involved in: emotional impulse control, arousal,
personality, reactivity to the surroundings and mood.

Orbitofrontal circuit connects the frontal monitoring


systems to the limbic system
A particular area Anterior cingulate gyrus (areas 24
and 25 Brodmann) appears to be most associated with
mood (particularly depression and mania).
Premotor cortex (supplemental motor area, secondary
motor cortex, area 6 Brodmann):
It is immediately anterior to the motor cortex.
It has many of the same connections as motor cortex.
Its output is to motor cortex, with a smaller output to the
brain stem and spinal cord.
This region receives input from sensory association cortex
as well as feedback from the basal ganglia via the VA and
VL of the thalamus.
Frontal eye field (inferior area 8 Brodmann):
It is located just inferior and rostral to the premotor
cortex.
Its activity in this region results in conjugate horizontal
gaze of the eyes away from the stimulus.
This receives input from the medial dorsal nucleus of the
thalamus as well as other areas of the cerebral cortex.
It makes output to the superior colliculus and the paramedian pontine reticular formation (PPRF).
Broca area:
Broca area has two executive language regions.
The first and main executive region is found on the
inferior third frontal gyrus (opercular and triangular
portions of inferior frontal gyrus areas 44 and 45
Brodmann).
Localized in the dominant hemisphere is involved in
the coordination or programming of motor
movements for the production of speech sounds (does
not directly cause movement to occur).
In the nondominant hemisphere, Broca area is
involved in the ability to generate inflections of voice.
Visually perceived words are given expression in writing
through a second executive language area.
Motor area (precentral gyrus, primary motor cortex,
Brodmann area 4):

It is in the precentral gyrus and is the origin of most of the


corticospinal tract and a large number of corticobulbar
fibers.
There is a very-defined somatotopic organization of motor
cortex.
Cortical motor homunculus is a visual representation of
the concept of the body within the brain.
The homunculus is like an upside-down motor map of
contralateral side of the body.
The resulting image is a grotesquely disfigured human
with disproportionately huge hands, lips and face in
comparison to the rest of the body.
Because of the fine skills harvest found in these
particular parts of the body, they are represented as
being larger on the homunculus.
Specific movements tend to be represented (such as
elbow flexion) rather than specific muscle.
Motor area has projections to the thalamus and basal
ganglia.
Thalamus (VL nucleus) makes significant input to the
motor cortex.
The precentral gyrus receives significant input from
sensory cortical areas as well as from the premotor cortex.
Frontal lobe syndromes:
Effects of frontal lobe disease may be summarized as
follows:
Effects of unilateral frontal lobe disease, either left or
right:
Contralateral spastic hemiplegia.
Slight elevation of mood.
Increased talkativeness.
Tendency to joke.
Lock of tact.
Difficulty in adaption.
Loss of initiative.
If entirely prefrontal: a) no hemiparesis; b) grasp and
suck reflexes or instinctive grasping may be released.
Anomia with involvement of orbital parts.
Effects of dominant frontal lobe disease:
Motor speech disorder with agraphia, with or without
apraxia of lips and tongue.

Apraxia of left hand.


Loss of verbal associative fluency.
Perseveration.
Changes seen in first section of frontal lobe disease.
Effects of bifrontal disease:
Bilateral hemiplegia.
Spastic pseudobulbar palsy.
If entirely bilateral prefrontal: a) abulia; b) akinetic
mutism; c) lack of ability to sustain attention and solve
complex problems; d) rigidity of thinking; e) bland
affect; f) social ineptitude; g) behavioral disinhibition;
h) inability to anticipate; i) labile mood; j) varying
combinations of grasping, sucking, decomposition of
gait and sphincteric incontinence.
Motor cortex syndromes:
Contralateral hemiparesis.
Hemiparesis is with faciobrachial prevalence.
Rarely, hemiparesis is with lower limb prevalence.
Hemiparesis is frequently associated with other cortical
signs (aphasia in the dominant hemisphere, apraxia,
agnosia, jacksonian epileptic seizures).
Broca aphasia = expressive aphasia = motor aphasia =
non-fluent aphasia = anterior aphasia.
Lesion in frontal suprasylvian region (44 & 45
Brodmann areas) in dominant hemisphere.
Speech is telegraphic, meaning that articles,
conjunctions, prepositions, auxiliary verbs (function
words) and morpho-logical inflexions ( e.g.: plurals,
past tense), are omitted.
Speech output (sentences) is severely reduced and
limited to short utterances of less than four words and
restricted to noun-verb combinations.
Syntax and morphology are affected
Speech is laborious and clumsy.
Comprehension relatively preserved (the person may
understand speech relatively well and be able to read or
write beyond an elementary level).
Repetition is impaired.
Associated signs: right arm and face weakness.
Pure word mutism (aphemia, pure motor aphasia of
Djrine):

The patient looses all capacity to speak while retaining


perfectly the ability to write, to understand spoken
words, to read silently with comprehension and to
repeat spoken words.
Facial and brachial paresis may be associated.
Lesion is anterior and superior to Broca area.
Transcortical motor aphasia:
The patient is unable to initiate conversational speech,
producing only a few grunts or syllables.
Comprehension is relatively preserved, but repetition is
strikingly intact.
This type of aphasia occurs in two clinical context:
In a mild or partially recovered Broca aphasia in which
repetition remains superior to conversational speech.
In states of abulia and akinetic mutism with frontal
lobe damage.
Several cases have resulted from infarctions in the
watershed zone between the anterior and middle cerebral
arteries.
In the nondominant hemisphere, lesions of the regions of
the brain that are analogous to Broca area affect to
generate inflexion of voice (aprosodia).
Apraxia.
Left frontal lesions, especially near supplementary motor
and premotor cortices, can cause limb apraxia without
loosing knowledge or understanding of the movement.
There is often a concomitant apaxia of speech (buccofacial
apraxia).
Callosal apraxia also may occur with anterior cerebral
artery stroke, causing unilateral left-limb apraxia.
Constructional apraxia localizes to the right hemisphere
or to the frontal lobes.

Dorsolateral prefrontal cortex syndrome:


Apathy, personality changes, indifference, abulia, lock of
ability to plan or to sequence actions or tasks.
These patients have poor working memory for verbal or
spatial information.

Psychomotor retardation.
Loss of self.
Discrepant motor and verbal behavior
Motor programming deficits.
Poor word list generation.
Poor abstraction approach to visuospatial analysis.
Compromised learning and poor spontaneous recall are
the primary memory disturbances.
Poor strategies for copying tasks.
Compromised attention.
Environmental dependency.
Depressive symptoms.
Paucity of spontaneous movements and gestures.
Sparse verbal output (repetition may be preserved).
Lower extremity weakness and loss of sensation.
When frontal eye field is affected unilaterally, the patients
has ipsilateral gaze deviation or gaze preference directed
toward the side of the lesion.
Prefrontal lesions can also produce contralateral neglect,
usually manifested by lock of action directed into the
neglected space (hemi-intention).
Gait impairment:
A relatively upright posture in the setting of shortstride.
Hesitant, lightly widened-base gait are characteristic
to frontal lobe disorders (common in Alzheimer
disease, vascular dementia and normal pressure
hydro-cephalus.
Frontal release responses, including suck, grasp, snout
and groping reflexes, may by present.
Alien hand syndrome occurs when a patients hand
assumes complex position that are not under the patients
volitional control.
Incontinence: dysfunction of the posterior superior frontal
gyri and anterior part of the cingulate gyrus can lead to
incontinence of urine and stool.
Orbitofrontal syndrome:
The orbitofrontal syndrome is the most dramatic of all
frontal lobe disorders.

The predominant behavioral change is social disinhibition


(personality change):
Ignore social conventions and exhibit undue
familiarity, talking to strangers and touching or
fondling others without permission.
The patients are tactless in conversation and may
make uncivil or lewd remarks.
The patients are impulsive, responding immediately
and unpredictably
to changing
environmental
circumstances.
The patients lack empathy and are unsympathetic to
the needs of others.
The patients lock conscientiousness and fail to
complete assigned tasks.
The patients are unconcerned about the consequences
of their behavior and may engage in activities that
endanger themselves or others.
Risk assessment is poor.
Mood alterations accompany the orbitofrontal syndrome.
Lability and irritability are the most common changes
(patients rapidly shift from happiness to anger or
sadness).
Anger can often be relieved by redirecting the patients
attention to some new activity.
Hypomania or mania may accompany orbitofrontal
dysfunction, characteristic if the lesion affects the right
hemisphere.
Involvement of orbitofrontal cortex (OFC) is often
implicated in addictive behavior in addition to nucleus
accumbens and amygdala.
Addicted individuals show deficits in orbitofrontal, striatal
and thalamic regions.
Conscious and unconscious components are hypothesized
to serve as mechanisms responsible for maintenance drug
addiction.
In addition, hypoactivity in the OFC in the alcoholics is
further supported by blunted metabolism in the OFC to
response to both serotoninergic and GABA-ergic agents.
Patients with inferior mesial lesion tend to manifest
anterograde and retrograde amnesia and confabulation.
Frontomedial syndrome (anterior cingulate syndrome):

The frontomedial syndrome:


Marked by apathy.
Emotionally, the apathetic individuals is unmotivated
to initiate new tasks and there is a disinterest in
establishing or accomplishing goals.
Cognitively, the apathetic individuals fails to formulate
or implement plans and activities.
N.B.: The patient with a left unilateral lesion may have
transcortical motor aphasia characterized by transient
mutism recovering to a nonfluent verbal output with
preserved repletion and comprehension.
Motorically, apathetic individuals have reduced
activity (they may sit for a long periods without
participating in conversation or activities).
The grasp reflex is commonly present; a) contact
grasp; b) traction grasp; c) magnetic grasp.
In the most extreme form of apathy (bilateral lesions of
anterior cingulate):
Permanent akinetic mutism:
Wakeful state;
Prominent apathy;
Indifference to pain, thirst or hunger;
Lock of motor and psychic initiative;
Spontaneous movements;
Verbalization and respond to commands;
Such individuals will eat if fed;
The patients are not paralyzed;
The patient may be incontinent.
A severe but less enduring defect in retentive memory
has been observed with infarction of septal gray matter, a
cluster of midline nuclei at the base of frontal lobe, just
below the interventricular septum and including the
septal nucleus (connected with the hippocampus and
amygdala), nucleus accumbens and paraventricular
hypothalamic gray matter.
The amnesic syndrome that follows ruptured anterior
communicating aneurysm is due to a lesion involving
these nuclei.
N.B.: The frontomedial syndrome must by distinguished
from locked-in syndrome or catatonia.

Opercular syndrome (anterior opercular syndrome, FoixChavany-Marie syndrome):


Rare disorder due to bilateral lesions of opercular cortex
surrounding the insula.
Loss of voluntary control of facial, pharyngeal, lingual,
masticatory and sometimes ocular muscle activity.
Decreased gag reflex.
Absence of emotionalism.
Frontal lobe epilepsies (FLE):
FLE are a focal type of epilepsy originating from an
epileptic focus anywhere within the frontal lobe.
Complex and varied patters in the spread of seizure
discharges explain the variability in the clinical and EEG
manifestations of FLE.
General characteristics:
Generally short seizures.
Complex partial seizures arising from frontal lobe,
often with minimal or no postictale confusion.
Rapid secondary generalization (more common in
seizures of frontal lobe than of temporal lobe
epilepsies).
Prominent motor manifestations which are tonic or
postural.
Complex gestural automatisms frequent at onset.
Frequent falling when the discharge is bilateral.
Seizures from the motor cortex:
Simple focal motor-clonic or tonic-clonic seizures with
or without jaksonian march and their localization
depend on the side and topography of area involved.
In cases of lower prerolandic area there may be speech
arrest, vocalization or dysphasia, tonic-clonic
movements of the face on contralateral side or
swallowing.
Generalization of the seizure frequently occurs.
In the rolandic area, partial motor seizures without
march or jaksonian seizures occur, particularly
beginning in the contralateral upper extremities.

In the case of seizures involving the paracentral lobule,


tonic movements of ipsilateral foot may occur as well
as the expected contralateral leg movements.
Post ictal (Todd paralysis) is frequent.
Seizures from the supplementary motor area:
Hyper motor seizures (sudden and explosive) of
bizarre bilateral, asymmetric tonic posturing and
movements.
Complex gestural automatisms.
Extreme motor restlessness.
Complex motor automatisms and agitation.
Frenetic complex motor automatisms of both arms and
legs.
Intensity affective vocal and facial expression
associated with powerful bimanal-bipedal and axial
activity..
Repetitive rhythmical and postural movements
accompa-nied by bizarre vocalization.
Complex motor automatisms with kicking and
thrashing.
Complex and global gesticulations.
Anterior frontopolar region:
Forced thinking.
Initial of contact and adversive movements of head
and eyes.
Contraversive movements.
Axial clonic jerks and fall.
Autonomic signs.
Dorsolateral region:
Tonic or, less commonly, clonic movements.
Versive eye and head movements.
Speech arrest.
Orbitofrontal region:
One of complex partial seizures.
Initial motor and gestural automatism.
Olfactory hallucinations and illusions.
Autonomic signs.
Opercular region:
Mastication,
salivation,
swallowing,
laryngeal
symptoms, speech arrest, epigastric aura, fear,
gustatory hallucinations and autonomic phenomena.

Simple partial seizures, particularly partial clonic facial


seizures, are common and may be ipsilateral.
Cingulate region:
Complex partial seizures with complex motor gestural
automatisms at onset.
Autonomic signs are common, as are changes in mood
and affect.
Other types of frontal lobe seizures:
Epilepsia partialis continua Kozhevnikov
Frontal absences.
forced thinking and forced acts.
Gelastic seizures
Lesions of frontal lobes:
Degenerative:
Pick disease.
Alzheimer disease.
Dementia with Lewy bodies.
Frontotemporal dementia.
Amyotrophic lateral syndrome with dementia.
Vascular:
Anterior cerebral artery occlusion medial frontal
syndrome.
Anterior cerebral artery/communicating anterior
artery aneurysm rupture orbitofrontal syndrome.
N.B.: some patients develop infarctions in the basal
forebrain.
In addition to the akinesia and personality changes,
patients may develop a striking confabulatory amnesia
that is severe and permanent and that resembles
Wernicke-Korsakoff syndrome.
Mild anomia may be present.
Finally, a syndrome of affective depression may occur
after strokes affecting predominantly the left frontal
lobe.
Bilateral cerebral artery infarct is associated with a
syndrome of quadriparesis (legs worse than arms) and
akinetic mutism.
Occlusion of the artery of Heubner may cause
infarction of the head of the caudate nucleus and may
result in an agitated confusional state that evolves to

akinesia, abulia and mutism, along with personality


changes.
Infarction of the anterior branches of the upper
division of the middle cerebral artery which supply
parts of the lateral prefrontal cortex may be
characterized by planning deficits, impairment of
working memories and apathy.
Borderzone infarctions between the distribution of
the anterior and middle cerebral arteries are
characterized by the man-in the barrel syndrome
with proximal weakness at the shoulder and hip.
Traumatic:
Closed head injury orbitofrontal contusion,
diffuse axonal injury to white matter fibers.
Middle cerebral artery occlusion lateral
convexity.
Binswanger disease hemispheric white matter.
Demyelinating:
Multiple sclerosis white matter (especially periventricular).
Metachromatic leucodystrophy white matter
(begins frontally).
Marchiafava-Bignami disease corpus callosum
(anteriorly).
Neoplastic:
Meningioma subfrontal orbitofrontal.
Meningioma convexity lateral convexity.
Meningioma falcine medial frontal.
Glioblastoma, oligodendroglioma, metastasis local with
diffuse edema.
Infectious:
Creutzfeldt-Jakob disease focal onset with rapid spread.
Syphilis prefrontal.
Herpes encephalitis orbitofrontal and temporal.
Inflammatory:
Systemic lupus erythematosus or other inflammatory
disorders diffuse.

Parietal lobe:
Parietal lobe extends from the central sulcus (Rolando
fissure) anteriorly to the imaginary parietal-occipital fissure
posteriorly, above temporal lobe (Sylvian fissure).
There is a parietal lobe in each hemisphere and one is not
completely a mirror image of the other, especially in the
functional level.
Each lobe shows three parts: a) the postcentral gyrus; b)
the superior parietal lobule; c) the inferior parietal lobule.
The inferior lobule includes the angular and
supramarginal gyri.
From the medial aspect, the parietal lobe contains:
The postcentral gyrus part of paracentral lobule.
Part of cingulate gyrus.
Precuneus.
Primary sensory strip (postcentral gyrus) = Brodmann
areas 3, 1 & 2.
Secondary sensory area (superior parietal lobule, sensory
associated areas) = 5 &7 Brodmann areas.
Supramarginal gyrus = 40 Brodmann area.
Angular gyrus = 39 Brodmann area.
Afferents:
Ventral posterior nucleus of thalamus.
Commissural fibers from the opposite somatic sensory
cortex through the corpus callosum.
Short association fibers from the adjacent primary
motor cortex (collaterals of corticospinal fibers).
Efferents:
Association fibers pass to the ipsilateral motor cortex
and to area 5 and area 40 Brodmann.
Commissural fibers pass to the contralateral
somesthetic cortex.
Projection fibers descend to the ventral posterior
nucleus of the thalamus of the same side and the
posterior column and spinal posterior gray horn of the
opposite side.
The first function of the parietal lobes is to integrate
sensory information to form a single perception
(cognition).

The dominant lobe is particularly important for:


Perception, interpretation of sensory information.
Formation of idea of a complex meaningful motor
responses to the stimuli.
Language, mathematical operations, body image
(supra-marginal gyrus and angular gyrus).
The nondominant lobe is especially important for visualspatial functions.
The posterior parietal cortex receives somatosensory
and/or visual input, which then, through motor
signals, control movement of the arm, hand, as well as
eye movements.
The parietal-temporal-occipital (PTO) junction is an association area located in the cortex of human brain, which
includes portions of parietal lobe
(Brodmann areas
39 angular and 40 supramarginal), temporal lobe
(Brodmann area 37 fusiform) and occipital lobe
(Brodmann area 19 peristriate).
This association area one of three in the cortex is
responsible for the assembly of auditory, visual and
somatosensory information system.
Meaning is assigned to stimuli in PTO, which outputs
to numerous other areas of the brain. Notably the
limbic and prefrontal areas, which are involved in
memory.
In the dominant hemisphere, the PTO is involved in
language recognition (reading, listening and writing).
In the nondominant hemisphere, the PTO identifies
the spatial characteristics of objects and is involved
in spatial awareness.
Parietal lobe syndromes:
Either hemisphere:
Hemianesthesia (pseudo-thalamic syndrome).
Tactile inattention.
Unilateral muscular atrophy.
Hemiataxia.
Homonymous incongruent hemianopsia.
Unilateral visual inattention and disorientation.
Neglect of one half of body and extrapersonal space.

Constructional apraxia.

Dominant hemisphere:
Bilateral idiomotor apraxia (motor apraxia, kinesthetic
apraxia limb-kinetic apraxia):
Loss of ability to carry out, on command, a complex or
skilled movement, though the purpose thereof is clear
to the patient.
Bilateral ideational apraxia:
Loss of ability to conceptualize, plan and execute the
complex sequence of motor actions involving the use
of tools or objects in everyday life.
The patient has lost the perception of the objects
purpose.
Disturbance in the idea of sequential organization of
voluntary actions.
Cannot perform a series of acts although able to
perform individual components of the series.
Loss of conceptual knowledge associated with objects
and overall goal of the activity sequence.
Disorder of language.
Tactile agnosia (bimanual asteriognosis).
Visual autotopagnosia.
Dyslexic types of aphasia (conduction aphasia, lesions in
supramarginal gyrus):
Severely defective repetition.
Paraphasia in repletion and in spontaneous speech.
Normal comprehension.
Impaired writing spontaneous and to dictation.
Errors in spelling, word choice and syntax.
Pain asymboly.
Gerstman syndrome (angular syndrome):
Dysgraphia/agraphia (deficiency in the ability to
write).
Dyscalculia/acalculia (difficulty in learning or comprehending mathematics).
Finger agnosia (inability to distinguish the finger on
the hand).

Left-right disorientation (inability to distinguish right


from left).

Nondominant hemisphere:
Topographic disorientation.
Topographic memory loss.
Dressing apraxia ( lesions in inferior parietal lobule).
Constructional apraxia ( lesions in inferior parietal
lobule).
Hemiinattention.
Contralateral neglect a part of the body.
Anton-Babinski syndrome:
Asomatognosia (inability to recognize part of ones
body).
Anosodiaphoria (indifference to illness).
Anosognosia (denial of illness).
Spatial neglect.
Apraxia of eye opening.
The individual typically has difficulty putting together
puzzle.
Bilateral parietal lobe:
Blint syndrome:
Bilateral damage to the posterior superior watershed
area of parietooccipital junction (Brodmann areas 7 &
19).
Paralysis of visual fixation.
Optic ataxia (the inability to guide the hand toward an
object using visual information).
Ocular apraxia (inability to voluntarily control gaze
and inability to carry out familiar movements when
asked to do so).
Spatial disorientation
Inability to execute voluntary movement in response
to visual stimuli.
Despite normal field of view and normal acuity, the
patients perceives only one object, from which he can

hardly move his eyes, while all other objects are not
recognized.
Simultanagnosia inability to perceive the visual field
as a whole (inability to perceive simultaneous events
or objects in ones visual field (difficulty integrating
components of visual scene).
Pure cases are extremely rare, often associated with
alexia, prosopagnosia, visual field deficits.

Agraphias:
Pure agraphia:
Aphasic agraphia:
Spelling and grammatical errors abound.
Special forms of agraphia caused by abnormalities of
spatial perception and praxis.
Constructional agraphia:
Words are formed clearly enough but are wrongly
arranged on the page.
Words may be superimposed, reversed, written
diagonally or haphazard arrangement, or from right to
left.
With right parietal lesions, only the right of the page is
used.
Usually one finds other constructional difficulties as
well, such as inability to copy geometric figures or to
make drawings of clocks, flowers, or maps.
Apraxic agraphia:
Language formation is correct and the spatial
arrangements of words are respected, but the hand
has lost its skill in forming letters and words.
Handwriting becomes a scrawl, losing all personal
characters.
Apraxias:
An inability to use body parts successfully.
An inability to carry out learned skilled, purposeful
movements to command or in imitation, despite intact
motor and sensory systems, good comprehension, normal
volition normal cognition and full cooperation.
The subject cannot produce the correct movement in
response to verbal command, nor imitate correctly a

movement performed by the examiner, nor perform a


movement correctly in response to a scene or object,
nor handle an object correctly.
Apraxias result from disconnections of the posterior
speech area from the association areas lying anterior to
the primary motor cortex, and from disconnections of the
visual association areas from these motor association
areas.

Idiomotor apraxia (idiokinetic apraxia):


An impairment in the timing, sequencing and spatial
organization of gestural movements (temporal and
spatial errors).
Transitive movements are more affected than
intransitive ones, when patients pantomime in
response to command and patients usually do better
on imitation than when responses are elicited through
verbal commands.
N.B.: a) transitive movements are those that are being
as a goal-directed movement, like reaching for an
object and grasping it; b) intransitive movements are
those that are frivolous and are done without the
motivation of explicit goal.
An inability on both arms to perform a motor act on
command which can be performed spontaneously.
The movements are incorrectly produced, but the goal
of the action can usually be recognized.
In the right-handed subjects, it is associated with lesions
of left parietal region (Brodmann areas 5 and 7) and thus
is a common finding in patients with aphasia.
N.B.: Gait apraxia (Burns ataxia) and gaze apraxia no
relationship to idiomotor apraxia
Ideational apraxia (conceptual apraxia):
A deficit in the conception of a single movement or of
sequence of them, so that the patient does not know
what to do.
An inability to perform the coordinated sequence of
actions that constitute goal-directed activity despite

the patients ability to perform the individual


components of the actions in isolation.
An inability to select and use objects as a result of
disruption of the normal of the normal integration of
systems subserving the functional knowledge of
actions and those involved in object knowledge.
Buccofacial apraxia (orofacial apraxia):
Impairment in performing mouth or face actions on
verbal command or imitation.
Probably the most common of all apraxias.
May be associated with apraxia of limbs.
It may occur with lesions that undercut the left
supramarginal gyrus or the left association cortex.
Dressing apraxia:
Usually associated with right parietal lesions and is a
part of a neglect syndrome.
Constructional apraxia:
Inability to copy 2-dimensional (2D) drawings or 3D
assemblies may be associated with the right or left
parietal areas and is a part of neglect syndrome.
Parietal lobe epilepsies (PLE):
Seizures arising from the parietal lobe have following
features:
Seizures are predominantly sensory with many
characteristics.
Positive phenomena consist of tingling, thermal,
burning, pricking, creeping, tight and a feeling of
electricity, which may be confined or may spread in a
jacksonian manner.
Negative phenomena include numbness, a feeling that
a body part is absent and a loss of awareness of a half
part of the body (disturbance of body image
somatoagnosia) in the nondominant hemisphere
involvement.
There may be a desire to move a body part or a
sensation as if a part were being moved.
The parts most frequently involved are those with the
largest cortical representation (e.g.: hand, arm, face).
There may be tongue sensations of crawling, stiffness
or coldness.
Facial sensory phenomena may occur bilaterally.

Occasionally, an intraabdominal sensation of striking,


choking or nausea may occur, particularly in cases of
inferior and lateral parietal lobe involvement.
Rarely, there may be pain, which may take the form of
a superficial burning dysesthesia or a very severe
painful sensation.
Muscle tone may be lost.
Parietal lobe visual
phenomena may occur as
hallucinations metamorphopsia with distorsions,
shortenings and elongations (more frequently
observed in case of nondominant hemisphere lesions).
Severe vertigo or disorientation in space may be
indicative of inferior parietal lobe seizures.
Seizures in the dominant parietal lobe result in a
variety of receptive or conductive language
disturbances.
Paracentral involvement may induce same well
lateralized genital sensations.
Some rotatory or postural motor phenomena may
occur.
Seizures of paracentral lobule have a tendency to
become secondary generalized.
Simple focal seizures often spread to extraparietal
regions producing different types of epilepsy.
Lesions of parietal lobe:
Tumor.
Posttraumatic.
Encephalitis.
Tuberus sclerosis.
Vascular malformation.
Vascular ischemia.
Temporal lobe:
Temporal lobe represent ~17% of volume of the human
cerebral cortex.
On the lateral surface, the stem and posterior ramus of
lateral sulcus (sylvian fissure) mark the separation of the
temporal lobe from the frontal and parietal lobes.
The temporal lobe is separated from occipital lobe by an
imaginary line rather than any natural boundary.
The lateral surface of temporal lobe is indented by
superior and inferior temporal sulci, thus delineating:

Superior temporal gyrus ( Brodmann area 38 & 22


Wernicke area).
Middle temporal gyrus (Brodmann area 21).
Inferior temporal gyrus (Brodmann area 20).
The superior surface of the temporal lobe, which forms
the floor of sylvian fissure, is continuous with superior
temporal gyrus.
It is marked by two obliquely oriented ridges, the
transverse temporal gyri, which constitute the primary
auditory cortex (Heschl gyrus = Brodmann areas 41
& 42).
The inferior temporal gyrus curves around onto the
inferior surface of the brain and extends posteriorly into
the occipital lobe (occipitotemporal gyrus).
The occipitotemporal sulcus separates the medial border
of inferior temporal gyrus from the lateral border of the
fusiform (medial occipitotemporal gyrus, Brodmann
area 37).
Medial to the fusiform gyrus is collateral sulcus and
medial to the collateral sulcus, the parahippocampal gyrus
forms the medial border of inferior surface of the
temporal lobe.
The posterior part of temporal lobe bleds into the parietal
lobe above and occipital lobe behind.
The limits of the lobes are arbitrary straight lines
connecting anatomical landmarks.
The prominent part of the anterior end of temporal lobe is
the temporal pole (area 38).
Cytoarchitecturally, it is bounded caudally by the
inferior temporal Brodmann area 20, the middle
temporal Brodmann area 21, the superior temporal
Brodmann area 22 and entorhinal Brodmann area
36.
The medial (mesial) temporal lobe is comprised of
multiple structures including the hippocampal
formation (the dentate nucleus, Cornu Ammonis CA
fields and subiculum), the amygdala, entorhinal cortex
and surrounding perirhinal and parahippocampal
cortices, including uncus (Brodmann areas 27, 28, 34,
35 & 36).
Functions of temporal lobe:

The primary auditory cortex (Brodmann areas


41
& 42) performs basic of hearing pitch and volume.
Neurons in the primary auditory cortex are
organized according to the frequency of sound
to which they respond best (tonotopically
organized).
The secondary auditory cortex has been indicated in the
processing of harmonic, melodic and rhythmic patterns.
The tertiary auditory cortex an association areas that
integrates everything into overall experience of music.
The three areas a concentrically organized such that
primary auditory cortex is in center.
The frontotemporal system underlying perception allows
to distinguish sound as speech, music or noise.
The middle and inferior temporal gyri (Brodmann areas
21 & 37) receive massive contingent of fibers from visual
cortex (Brodmann area 17) and parastriate visual
association areas (Brodmann areas 18, & 19).
The temporal Brodmann areas 21 & 37 make
abundant connections with the medial limbic,
rhinencephalic (olfactory brain), orbitofrontal, parietal
and occipital cortices.
Here the cortices subserving vision and hearing are
intimately interconnected.
It is postulate four main language areas, situated
perisylvian in the dominant cerebral hemisphere.
Two areas are receptive (Wernicke zone) in the
temporal lobe.
Two areas are executive (Broca zone) in the frontal
lobe.
One receptive area, subserving the perception of
spoken language, occupies the posterosuperior
temporal area (the posterior portion of Brodmann
area 22 Wernicke area)) and Heschl gyri (Brodmann
areas 41& 42).
A second receptive area, subserving the perception of
written language, occupies the angular gyrus
(Brodmann area 39) in the inferior parietal lobule.
The supramarginal gyrus and the inferior temporal
region are probably part of central language zone as
well.

On the left side of the brain the area 22 helps


generation and understanding of individual words
(active in processing language).
On the right side of brain, the Brodmann area 22 helps
tell the difference between melody, pitch and sound
intensity, that is prosody.
Right temporal lobe is mainly involved in visual memory.
Left temporal lobe is mainly involved in verbal memory.
The most important role of hippocampus and other
structure of the hippocampal formation (dentate gyrus,
subiculum, entorhinal cortex and parahippocampal gyrus)
is in learning and memory functions.
There is an abundance of connections between the medial
temporal lobe and the entire limbic system (visceral
brain or emotional brain).
A massive fiber system projects from the striate and
parastriate zones of the occipital lobe to the inferior and
medial parts of temporal lobe.
The temporal lobes are connected to one another through
the anterior commisure and middle part of the corpus
callosum.
The inferior (uncinate) fasciculus connects the anterior
temporal and orbital frontal regions.
The arcuate fasciculus connects the posterosuperior
temporal lobe to the motor cortex and Broca area.
The temporal lobe is the great integrator of sensations,
emotions and behavior.
The temporal lobe seems to be the site where sensory
modalities are integrated into ultimate self-awareness
(the cartesian view of consciousness of ones self as a
person with mind).
In the superior and posterior part of the temporal lobe
(posterior to the primary auditory cortex), there is an area
that responds to vestibular stimulation (cortical vestibular
area).
Temporal lobe syndromes:
Visual disorders:
Homonymous qudrantanopia, usually not perfect
congruent.
Quadrantanopia from dominant lesion is often combined
with aphasia.

Bilateral lesions induce psychically blind.


Visual hallucinations of complex form, including ones of
the patient himself (autoscopy), appear during temporal
lobe epilepsy.
Some visual hallucinations have an auditory component.
Temporal lobe abnormalities may also distort visual
perception:
Seen objects may appear too large (macropsia) or too
small (micropsia).
Seen objects may appear too close, far away or unreal.

Auditory disorders:
Cortical deafness appears in bilateral lesions of Heschl
gyri.
Lesions of the secondary (unimodal association) zones of
auditory cortex Brodmann area 21 and part of
Brodmann area 22 have no effect on the perception of
sounds and pure tones.
However, the perception of complex combinations of
sounds is severely impaired (auditory agnosia).
Amusia is a form of the auditory agnosia and appears
in lesions of nondominant hemisphere.
Nondominant
hemisphere is important for
recognition of harmony and melody (in the absence of
words), but that the naming of musical scores and all
the semantic (writing and reading) aspects of music
require integrity of dominant temporal and probably
the frontal lobes as well.
Auditory illusions (paracusias) :
Sounds or words may seem strange or disagreeable.
Sounds or words may seem to be repeated, a kind of
sensory perseveration.
Auditory hallucinations:
Elementary (e.g.: murmurs, blowing, sound of running
water or motors, whistles, clangs, sirens).
Complex (e.g.: musical themes, choruses, voices).
Hearing may fade before or during hallucinations.

In temporal lobe epilepsy, the hallucinations may


occur alone or in combination with visual or gustatory
hallucinations, visual distortions, dizziness and
aphasia.
Vestibular disturbances:
If the cortical vestibular area is destroyed on one side, the
only clinical effect may be subtle change in eye
movements on optokinetic stimulation (mere often a
result of parietal damage).
Epileptic activation of this area may occur vertigo or
sense of disequilibrium.
Pure vertiginous epilepsy does occur but is a rarity.

Disturbance of time perception:


In a temporal lobe seizure, time may seem to stand still or
to pass with great speed.
On recovery from a seizure, the patient, having lost all
sense of time, may repeatedly look at the clock.
The impairment of time sense occurred after left
temporal stroke tat also produced cortical deafness.
Disturbances of smell and taste.
The seizure foci in medial part of temporal lobe (in the
region of the uncus) may evoke olfactory hallucinations
(uncinate fit).
Hallucinations of taste are rare.
There are cases in which a lesion of medial temporal lobe
caused both gustatory and olfactory hallucinations.
Disturbances of memory.
The anatomic structures of particular importance in
memory function are:
The diencephalon (specially the medial portions of the
dorsomedial
and adjacent middle nuclei
of
thalamus).
The hippocampal formations (dentate nucleus, hippocampus, parahippocampal gyrus, subiculum and
entorhinal cortex).

Discrete bilateral lesions in these regions derange


memory and learning out of all proportion to other
cognitive functions.
Unilateral lesion of these structures, especially of the
dominant hemisphere can produce a lesser degree of
same effect.
Lesion in the inferolateral area of temporal lobe of
dominant lobe induce a defect in retrieval of words =
amnesic dysnomia.
Wernicke aphasia = receptive aphasia = sensory aphasia
= fluent aphasia = posterior aphasia.
Disturbance of comprehension of spoken language.
Disturbance of comprehension of written language
(alexia).
Agraphia.
Speech may be hesitant, in which case the block tends to
occur in part of the phrase that contains the central
communicative (predictive) item, such as a key noun, verb
or descriptive phrase.
Fluent paraphasic speech.
Fluent
paraphasic
speech
may
be
entirely
incomprehensible (jargon aphasia).
The patient talks volubly, gestures freely and appears
strangely unaware of his deficit.
Speech is produced without effort.
The phrases and sentences appear to be of normal lengh
and are properly intoned and articulated.
Normal prosody.
The patient produces many nonsubstantive words and the
words themselves are often malformed or inappropriate
(literal paraphasia, verbal paraphasia, semantic
substitution).
Neologisms may also appear.
Hemi - or quadrantanopia.
No paresis.
As a rule, the lesion lies in the posterior perisylvian
region.
Total aphasia = global aphasia.
This syndrome is due to destruction of a large part of
language zone, embracing Broca and Wernicke areas and
much of the territory between them.

All aspects of speech and language are affected.


The patients can say only a few words, usually come clich
or habitual phrase and they can imitate single sounds or
can only emit a syllable.
The patients are not mute.
The patients may understand a few words and phrases,
but because of rapid fatigue and verbal and motor perseveration, they characteristically fail to carry out a series
of simple commands of a name, a series of objects.
The patients cannot read or write or repeat what is said to
them.
The patients may participate in common gestures of
greeting, show modesty and avoidance reactions and
engage in self-help activities.
With the passage of time, some degree of comprehension
of language may return and the clinical picture that is then
most likely to emerge is close to that of a severe Broca
aphasia.

Varying degrees of right hemiplegia, hemianesthesia and


homonymous hemianopia almost invariably accompany
global aphasia of vascular origin (e.g.: occlusion of the left
internal carotid artery or left middle cerebral artery,
hemorrhage in left hemisphere).
Klver-Bucy syndrome:
A rare and complicated neurobehavioral syndrome
resulting from damage of bilateral anterior temporal
portion (bilateral temporal lobectomy), especially the
amygdala.
Hyperorality (a strong tendency to examine all objects
orally, putting objects into mouth, licking, biting,
chewing,touching with lips).
Hyperphagia (eating inappropriate objects and/or
overeating).
Placidity (exhibiting diminished or loss of normal fear
and anger responses or reacting with unusually low
aggression).
Indiscriminate hypersexuality.
Visual agnosia ( psychic blindness of inability to
recognize objects without a loss of gross visual
discrimination).

Lock of emotional response.


Memory loss.
Hypermetamorphosis (an irresistible impulse to notice
and react to everything within sight).
Disconnection (dissociative) syndrome:
is severely affected both for single words and for
nonwords in the face of relatively This term refers to
certain disorders of language that result not from lesions
of the cortical language areas themselves but from an
apparent interruption of association pathways joining the
primary receptive areas to the language areas.
Conduction aphasia:
Repetition preserved comprehension.
The features of conduction aphasia resemble those of
Wernicke aphasia.

The lesion has been localized in the cortex and


subcortical white matter in the upper bank of the left
sylvian
fissure,
sometimes
involving
the
supramarginal gyrus and occasionally the most
posterior part of the superior temporal region.
Pure word deafness:
An impairment of auditory comprehension and
repetition and an inability to dictation.
Self-initiated utterance are usually correctly phrased
but sometimes paraphasic.
Spontaneous writing and ability to comprehend
written language are preserved, thus distinguishing
this disorder from classic Wernicke aphasia.
The lesions have been bilateral, in the middle third of
superior temporal gyri, in position to interrupt the
connections between the primary auditory cortex in
the transverse gyri of Heschl and association areas of
the superioposterior cortex of the temporal lobe.
Pure word blindness (alexia without agraphia, visual
verbal agnosia).

Literate person loses the ability to read aloud, to


understand written script and often to name colors
(visual verbal color anomia).
Understanding spoken language, repetition of what is
heard, writing spontaneously and to dictation and
conversation are all intact.
The ability to copy words is impaired but is better
preserved than reading.
In some cases, the patient manages to read single
letters but not to join them together (asyllabia).
A rare variant of this syndrome take the form of alexia
without agraphia and without hemianopia.
Autopsies of such cases have usually demonstrated a
lesion that destroys the left visual cortex and
underlying
white
mater,
particularly
the
geniculocalcarine tract, as well as the connections of
the right visual cortex with the intact language areas of
the dominant hemisphere.

Anomic (amnestic, nominal ) aphasia:


Some degree of word-finding difficulty is probably part
of every type of language disorder.
When the world-finding difficulty is the most notable
aspect of language is the term anomic aphasia.
In this condition, the patient loses only ability to name
people and objects.
The patient may simply fail to name a shown object, in
contrast to the usual aphasic patient, who produces a
paraphasic error.
The lesion has been deep in the basal portion of the
posterior temporal lobe or in middle temporal
convolution, in position to interrupt connections
between sensory language areas and hippocampal
regions concerned with learning and memory.
Transcortical sensory aphasia:

The patient suffers a deficit of auditory and visual


word comprehension and writing and reading are
impossible.
Speech remains fluent, with marked paraphasia,
anomia and empty circumlocutions.
Repetition is remarkably preserved.
Facility in repetition, in extreme degree, takes the form
of echoing, parrot-like, word phrases and songs that
are heard (echolalia).
Lesion in the posterior parietooccipital region.
Agraphia is a specific difficulty in transforming
phonologic information, acquired through the auditory
sense, into orthographic forms.
Lesion of the posterior perisylvian area (in or
near the angular gyrus).
Temporal lobe epilepsies (TLE):
TLE comprise a heterogeneous group of disorders sharing
the same topographical seizure onset.
Anatomically, TLE are broadly divided into those
originating from the lateral or mesial regions of temporal
lobe.
Mesial temporal lobe epilepsies (MTLE) with hippocampal sclerosis is far more common (2/3 of cases) than
lateral temporal epilepsies (LTLE).

TLE manifests with:


Simple focal seizures.
Complex focal seizures.
Secondary generalized clonic seizures.
Focal non-convulsive status epilepticus (limbic or neocortical).
Secondary convulsive status epilepticus.
Subjective ictal clinical manifestations:
Ascending epigastric aura or visceral aura (mainly
characterize MTLE).
Experiential (mental, intellectual or psychic)
hallucinations: a) dreamy state; b) ideational
aberration; c) dysmnesia; d) emotional impairment;
e) impairment of perception and/or cognition (are
common in both MTLE and LTLE).

Fear and panic (mainly characterize MTLE).


dj vu, dj entendu or dj veu (MTLE + LTLE).
jamais vu, jamais entendu or jamais veu, dreamy
state (MTLE + LTLE) .
Mental aberrations: a) impairment of thoughts
(ideational); b) impairment of memory (dysmnesic);
c) emotional impairment (affective); d) impairment of
perception (dyscognitive).
Auditory hallucinations and illusions (mainly
characterize LTLE).
Olfactory and gustatory hallucinations (MTLE).
Visual hallucinations and illusions (originate from PTO
junction).
Urinary urge (from the insula in the nondominant
temporal lobe).
Objective ictal symptoms:
Simple/complex automatisms : a) oroalimentary
(characteristic of MTLE); b) verbal; c) gestural;
d)
ambulatory; e) behavioural aberrations .
Autonomic disturbances (tachycardia, bradycardia,
asystole, arrhythmias, hypertension, brief respiratory
arrest, hyperpnea, hypopnea, mydriasis, miosis, hippus
papillae, penile erection and even ejaculation, ictus
emeticus).
Speech disturbances (speech arrest, inability to speak
and ictal aphasia in dominant temporal lobe).
Head and eye deviation.
Unilateral tonic or dystonic postures (in MTLE).
Motor arrest with staring + loss of consciousness =
temporal lobe absence.
Unilateral ictal paresis (contralateral to the origin of
the seizure).
Unilateral eyelid blinking (ipsilateral to the origin of
the seizure).
Gelastic seizures (has been attributed mainly to rightand less to left-sided extramesial seizures).
Other TLE symptoms:
Amnestic seizures (inability to retain in memory what
occurs during the seizure and other cognitive

functions are preserved and patients interact normally


with their physical and social environment).
Catamenial TLE.
Postictal symptoms:
Postictal symptoms are common, often characteristic
and might be of value in lateralising TLE.
Postictal symptoms are common, often characteristic
and may be of value in lateralizing TLE.
Postictal symptoms include: a) mental and physical
fatigue; b) drowsiness; c) headache; d) language
aberrations; e) inability to concentrate; f) confusion to
varying degree that is often severe and associated with
automatic behaviour of which the patient may be
amnestic.
Occipital lobe:
Occipital lobe is the processing center of the mammalian
brain containing most of the anatomical region of the visual
cortex.
The two occipital lobes are the smallest of four paired
lobes in the human cerebral cortex.
At the front edge of the occipital lobe are several
lateral gyri, which are separated by lateral occipital
sulcus.
The occipital aspects along the inside face of each
hemisphere are divided by the calcarine sulcus.
Above the media Y-shaped sulcus lies the cuneus and
the area below the sulcus is the lingual gyrus.
The primary visual cortex is coniocortex (V1, striate
cortex, Brodmann area 17) is located in and around the
calcarine fissure in the occipital lobe.
Extrastriate (visual association area) cortical areas (V2,
V3, V4 and V5) consist on Brodmann area 18 (parastriate)
and Brodmann 19 (peristriate).
The left hemisphere visual cortex receives signals from
right visual field and right visual cortex from left visual
field.
The upper retinal quadrant (lower field of view)
projects to the superior lip of calcarine fissure.
The lower retinal quadrant (superior field of view)
projects to the inferior lip of the calcarine fissure.

Macula fibers terminate in the caudal third of calcarine


fissure.
Functions of occipital lobe:
Each V1 area transmits information to two primary
pathways: a) dorsal stream; b) ventral stream.
Area V1 has a very well-defined map of the spatial
information in vision.
The visual information relayed to V1 is not coded in terms
of spatial imagery, but rather as the local contrast.
The dorsal stream begins with V1, goes through V2, then
to V5 and to the posterior parietal cortex.
The dorsal stream is associated with motion, representation of objects locations and control of eyes and
arms, especially when visual information is used to
guide saccades or reaching.
The ventral stream begins within V1, goes through V2,
then through V4 to inferior temporal cortex.
The ventral stream is associated with form
recognition, object representation and with storage of
long-term memory.
Area V2 (prestriate cortex) is second major area in the
visual cortex and the first region within the visual
association area.
It receives strong feedforward
and feedback
connections to V1 and sends strong connections to V3,
V4 and V5.
V2 is important for visual short-term and long-term
memories.
Area V3:
Dorsal V3 (anatomically located in Brodmann area 19)
is normally considered to be part of the dorsal stream,
receiving inputs from V2, may play a role in the
processing of global motion.
Ventral V3 has much weaker connections from the V1
and stronger connections with the inferior temporal
cortex.
Area V4:
It is the third cortical area in the ventral stream,
receiving strong feedforward input from V2 and
sending strong connections to the posterior

inferotemporal area and has weaker connections to


V5.
It is the first area in the ventral stream to show strong
attentional modulation.
Like V1, V4 is tuned for orientation, spatial frequency
and color.
Unlike V1, V4 is tuned for object features of
intermediate complexity (simple geometric shapes).
V4 is not tuned for complex objects such as faces, as
areas in the inferotemporal cortex are.
Area V5, also known as visual area middle temporal (MT),
is a region of extrastriate visual cortex that is thought to
play a major role in the perception of motion, the
integration of local motion signal into global percepts and
guidance to some eye movements.
Occipital lobe syndrome:
Clinical effects of occipital lobe lesions:
Visual field defects:
Homonymous hemianopsia = loss of vision in
corresponding halves of visual fields:
a) if the field defects in the two eyes are identical
(congruous), the lesion is likely to be in the calcarine
cortex and subcortical white matter of the occipital
lobe;
b) if the field defects are incongruous, the visual fibers
in the optic tract or in parietal or temporal lobe are
more likely to be implicated;

c) extensive destruction abolishes all vision in the


corresponding half of each visual field;
d) if the lesion that eventually involves the entire
striate region, the field defect may extend from the
periphery toward the center and loss of color vision
(hemiachromatopsia) precedes loss of black and white.
A lesion confined to the pole of the occipital lobe results
in a central hemianoptic defect that splits the macula and
leaves peripheral fields intact (half of each macula is
unilaterally represented).

Bilateral lesions of the occipital lobe result in bilateral


central hemianopias.
The cortex below the fissure is the terminus of fibers from
the lower half of the retina and field defect is in upper
quadrant and vice versa.
Cortical blindness = bilateral lesions of occipital lobes
(destruction of Brodmann area 17 of both hemispheres)
induce a loss of sight and loss of reflex closure of the
eyelids to a bright light.
The papillary light reflexes are preserved, since they
depend upon visual fibers that terminate in the
midbrain.
Less complete lesions leave the patient with varying
degrees of visual perception.
Visual anosognosia (Anton syndrome) = denial of
blindness by a patient who obviously cannot see.
The lesions extend beyond the striate cortex to involve
the visual association areas.
Visual illusions (metamorphopsias) = distortions of form,
size, movement or color.
More frequently due to shared occipitoparietal or
occipito-temporal lesions.
The right hemisphere appears to be involved more
frequently than the left.
Visual field defects are present in many of the cases.
Visual hallucinations :
Elementary (unformed) hallucinations include flashes
of light, colors, luminous points, stars, multiple lights
and geometric forms: a) they may be stationary or
moving (zigzag, oscillations, vibration or pulsations);
b) lesions in the calcarine cortex.
Complex (formed) hallucinations include objects,
persons or animals: a) they are indicative of lesions in
the visual association areas or their connections with
temporal lobes; b) they may be of natural size,
lilliputian or grossly enlarged; c) with hemianopia,
they may appear in defective field or move from the
intact field toward the hemianoptic one; d) the patient
may realize that hallucinations are false experiences or
may be convinced of their reality.

Visual agnosias = failure to name and indicate the use of a


seen object by spoken or written word or by gesture.
Visual acuity is intact, the mind is clear and the patient
is not aphasic.
Visual object agnosia is usually associated with alexia
(visual verbal agnosia) and homonymous hemianopia.
Prosopagnosia (the inability to identify faces) is also
present in most cases.
The underlying lesions are usually bilateral.
Balint syndrome:
Simultanagnosia = an inability to perceive
simultaneous events or objects in ones visual field.
Ocular apraxia = psychic paralysis of fixation of gaze
(an inability to project gaze voluntarily into the
peripheral field and to scan it despite the fact that eye
movements are full).
Optic ataxia = a failure to precisely grasp or touch an
object under visual guidance, as though hand and eye
were not coordinated.
Visual inattention mainly to the periphery of the visual
field, attention to other sensory stimuli being intact.
In all reported cases of Balint syndrome, the lesions
have been bilateral, often in the vascular border zones
(areas 10 and 7) of parietooccipital regions.
Prosopagnosia = a type of visual defect in which the
patient cannot identify a familiar face, by looking at either
the person or a picture, even though he knows that face is
a face and can point out the features.
Such patients cannot learn to recognize new faces.
They may also be unable to interpret the meaning of
facial expressions or to judge the ages or distinguish
the gender of faces.
Other agnosias are present in such cases (color
agnosia, simultanagnosia) and there may be
topographic disorientation, disturbances of body
schema, environ-mental agnosia (the patient is unable
to recognize familiar places), constructional or
dressing apraxia.
It is associated with bilateral lesions of the
ventromesial occipitotemporal regions.

Pure word blindness (visual verbal agnosia, alexia without


agraphia) = literate person loses the ability to read aloud,
to understand written script and often to name color.
The patient is blind in the right half of each visual field
by virtute of the left occipital lesion.
Autopsies of such cases have usually demonstrated a
lesion that destroys the left visual cortex,
geniculocalcarine tract, as well as connections of the
right visual cortex with the intact language areas of the
dominant hemisphere (disconnection occurred in the
posterior part splenium of the corpus callosum,
wherein lie the connections between the visual
association areas of the two hemispheres.
Color agnosia (central achromatopsia) = loss of correct
perception (indentification) of colors.
Color anomia = the patients with color agnosia have
difficulty with color perception, but they cannot name
them or point out colors in response to their names.
Occipital lobe epilepsies (OLE):
OLE are usually characterized by simple partial and
secondary generalized seizures.
Complex partial seizures may occur with spread beyond
the occipital lobe.
Clinical manifestations:
Visual illusions = misinterpretations or false percepts of
real external images:
Metamorphopsia (changes in size, dimension,
proportions, position, colour and movement, alone or
in combination);
Micropsia (percepts being smaller than real);
Macropsia (percepts being larger than real);
Objects may be distorted in shape, pulled, compressed
or rotated;
Achromatopsia (object may appear in black and
white);
Monochromatopsia (hazy and dark or highly
illuminated and bright);
Palinopsia (persistence or recurrence of visual images
after exciting stimulus has been removed).
Elementary visual hallucinations:
Most common, characteristic and well-defined OLE;

Bright, multicolored and circular;


The location at onset is usually unilateral, mainly in
the temporal visual hemifield;
The components usually multiply and become larger;
The side is contralateral to the epileptogenic focus;
Develop rapidly within seconds and they are usually
brief (few seconds to 1-3 minutes).
Complex visual hallucinations:
Often follow elementary visual hallucinations;
May take the form of persons, animals, objects, figures
or scenes;
Heauscopy (viewing his own image); d) do not have
the emotional character of TLE.
Ictal blindness (ictal amaurosis) may follow the visual
hallucinations and is usually longer (3-5 minutes) than
visual hallucinations.
Tonic deviation of the eyes, oculoclonic seizures and
epileptic nystagmus.
Repetitive eyelid, eyelid fluttering and eyelid blinking.
Consciousness is not impaired during the elementary and
complex visual hallucinations, blindness, but may be
disturbed or lost in the course of seizure.
Seizures may spread from the occipital to other
more anterior regions:
Infracalcarine occipital foci will propagate to the
temporal lobe causing complex focal seizures;
Supracalcarine foci tend to propagate to the parietal
and frontal areas giving rise to predominantly motor
seizures.

Insular lobe.
Insular lobe (insula, insular cortex) is a portion of the
cerebral cortex folded deep within the lateral sulcus between
the temporal lobe and the frontal lobe.

The cortical area overlying it towards the lateral surface of


the brain is the operculum (formed from parts of the
enclosing frontal, temporal and parietal lobes)
Operculum is believed to be involved in consciousness.
The insular cortex is divided into two parts:
The larger anterior insula receives: a) a direct
projection from the basal part of ventral medial
nucleus of the thalamus; b) a particularly large input
from the central nucleus of amygdala.
The anterior insula is interconnected to regions in the
temporal and occipital lobes, opercular and
orbitofrontal cortex.
The smaller posterior insula connects reciprocally
with the secondary somatosensory cortex and receives
input from spinothalamically activated posterior
inferior thalamic nuclei.
Left insular cortex has a relationship with cerebellar
system.
Functions of insular lobe:
The insular cortex:
Aids interoceptive awareness of body states, such as
the ability to time one own heart beat.
Correlates with increased accuracy in the subjective
sense of the inner body and with negative emotional
experience.
Involved in the control of blood pressure, particularly
during and after exercise.
Is where sensation of pain is judged as to its degree.
Processing vestibular sensations.
Noninteroceptive perceptions include: a) passive
listening to music; b) laughter and crying; c) empathy
and compassion.
It contributes to hand and eye motor movement,
swallowing, gastric mobility and speech articulation.

It controls autonomic functions though the regulation


of the sympathetic and parasympathetic systems.
It has a role in regulating the immune system.
Insular cortex is activated when drug abusers are
exposed to environmental cues that trigger cravings.

The insula is believed to process convergent information


to produce an emotionally relevant context for sensory
experience.
The anterior insula is related more to olfactory,
gustatory, viscera-autonomic and limbic functions.
The posterior insula is related more to auditorysomesthetic-skeletomotor functions.
Insular cortex integrates cognitive, affective, sensory and
autonomic information to create a consciously perceived
feeling state
Lesions of insular cortex.
Somatosensory deficits (central pain with transient
pseudothalamic sensory syndrome).
Gustatory disorders.
Vestibular-like syndrome (dizziness, gait instability and
tendency to fall, but no nystagmus).
Cardiovascular disturbances (hypertensive episodes).
Neuropsychological disorders, including aphasia and
dysartria.
Neglect in multisensory modalities.
Insular seizures (including visceral, motor and
somatosensory symptoms) may mimic temporal, parietal
or frontal lobes seizures and may coexist with seizures
from other lobes.
Limbic system.
Limbic system a set of brain structures that forms the inner
border of the cortex:
Limbic lobe:
Cingulate cortex (Brodmann areas 23, 24, 26, 29, 31 &
32): a) anterior cingulate cortex (Brodmann areas 24,
32 & 33); b) posterior cingulate cortex (Brodmann
area 23).
Parahippocampal gyrus (a grey matter cortical region
of the brain that surrounds the hippocampus).
Dentate gyrus (part of hippocampal formation).

Hippocampus and associated structures:


Hippocampus
Amygdala.
Fornix.

Mammillary body.
Septal nuclei (located anterior to the interventricular
septum).
Cingulum (white matter fibers projecting from cingulate
cortex to the entorhinal cortex).
In addition:
Entorhinal cortex.
Pyriform cortex.
Nucleus accumbens.
Orbitofrontal cortex.
Functions of limbic system:
Parahippocampal gyrus plays a role in formation of spatial
memory.
Cingulate cortex:
Autonomic function regulating heart rate and blood
pressure.
Cognitive and attentional processing.
Dentate gyrus thought to contribute to new memories.
Hippocampus:
Required for the formation of long-term memories.
Implicated in maintenance of cognitive maps for
navigation.
Amygdala is involved in signaling the cortex of
motivationally significant stimuli as those related to
reward and fear in addition to social functions such as
mating.
Fornix carries signals from the hippocampus to the
mammillary bodies and septal nuclei.
Mammillary body is important for the formation of
memory.
Septal nuclei provide critical interconnections.
Entorhinal cortex is important in memory and associative
components.
Pyriform cortex relates to the olfactory system.
Nucleus accumbens is involved in reward, pleasure and
addiction.
Orbitofrontal cortex is required for decision making.
Anterior cingulate cortex appears to play a crucial role in
initiation, motivation and goal-directed behaviors.
Papez circuit (PC):
PC:

One of major pathways of the limbic system.


Involved in the cortical control of emotion.
Plays a role in storing memory.
Initial loop:
Hippocampal formation (subiculum) fornix
mammillary bodies.
Mammillary bodies mammillothalamic tract
anterior thalamic nucleus.
Anterior thalamic nucleus genu of the internal
capsule cingulate gyrus.
Cingulate gyrus cingulum parahippocampal gyrus.
Parahippocampal gyrus entorhinal cortex
perforant pathway hippocampus.
Larger loop:
Initial loop also includes the prefrontal cortex,
amygdala and septal nuclei among other areas.
Limbic dysfunction:
Memory deficits.
Sleep disturbance.
Delusions.
Hallucinations.
Disinhibition of emotional expression:
Emotional lability.
Fear.
Pathologic laughing and crying.
Depression.
Euphoria.
Anxiety.
Panic disorders.
Rage reactions and aggressivity:
Anger.
Agitation.
Violence.
Apathy and placidity.

Altered sexuality:
Hypersexuality.
Hyposexuality.
Etiology:

Encephalitis (autoimmunity).
Cerebrovascular diseases.
Tumor.
Corpus callosum
There are three structures that interconnect the cerebral
hemispheres:
The anterior commisure, a structure that interconnects
the olfactory system and part of the limbic system.
The posterior commisure (hippocampal), a structure that
interconnects parts of the limbic system.
The corpus callosum, a large structure that mediates
interconnection between a large number of cortical
processing areas.
Corpus callosum (CC):
CC is a wide, flat bundle of neural fibers beneath the
cortex in the human brain at the longitudinal fissure.
CC connect the left and right cerebral hemispheres and
facilitates interhemispheric communication.
CC is consisting of 200-250 millions contralateral axonal
projections.
The posterior portion of corpus callosum is called the
splenium.
The anterior is called the genu (knee).
Between anterior and posterior portions is the truncus
(body) of the corpus callosum.
The part between the body and splenium is often
markedly thinned and thus referred to as the isthmus.
The rostum is part of corpus callosum that projects
posteriorly and inferiorly from the anterior most genu.
Thinner axons in the genu connect the prefrontal cortex
between the two hemispheres.
Thicker axons in the midbody of the corpus callosum and
the splenium interconnect areas of the premotor,
supplementary motor regions and motor cortex, with
proportionally more corpus callosum dedicated to
supplementary motor regions.
The posterior body of corpus callosum communicates
somatosensory information between the two halves of the
parietal lobe and visual center at the occipital lobe.
Callosal disconnection syndromes

Alien hand:
The actions of each side of the body are independently
controlled by the contralateral hemisphere.
The patients hand often act is if they were independently
motivated.
This is most apparent when the left hand behaves
inconsistent with what the patient say he is doing.
Sometimes patients will notice the aberrant actions of the
left hand and comment on the behaviour as if the hand did
not belong of the body.
Verbal anosmia:
Patients are unable to name smells presented only to the
right nostril.
Double hemianopsia:
Patients cannot indicate the onset of visual stimulus in
the left or right visual field with the contralateral hand.
Processing of verbal information:
Patients will have a complete right ear advantage for
verbal information.
Verbal information is very poorly perceived by the left
ear.
Unilateral apraxia of the left hand:
The patient cannot perform an action with left hand to
verbal command that is easily performed by the right
hand.
Unilateral agraphia of the left hand:
The patient has an inability to write with left hand.
The right hand writes fluently.
Unilateral anomia:
Patients cannot name objects placed in the left hand when
blindfolded.
Patients can easily name objects placed in the right hand.
Unilateral constructional apraxia:
The patient has a poor performance by the right hand on
tasks that require spatial processing (e.g.: copying
geometric forms).

XIV. ISCHEMIC CEREBROVASCULAR


SYNDROMES

Ischemic cerebrovascular syndromes (ICVS):


ICVS are acute onset of neurologic dysfunction of any severity
consistent with focal brain ischemia and imaging/laboratory
confirmation of a vascular ischemic territory.
ICVS can be embolic or trombotic:
Embolic ICVS characteristically occurs suddenly and the
deficit reaches its peak almost at once.
Thrombotic ICVS may have a similarly abrupt onset, but
many of them evolve somewhat more slowly over a period
of several minutes or hours and occasionally days (in this
later case, the ICVS usually progresses in a salutatory
fashion, in series of steps rather than smoothly).
Temporal profile of ICVS:
Temporal profile is an important aspect in the arrest and
then regression of neurologic deficit in all except the fatal
ICVS.
Not infrequently, an extensive deficit from embolism
reverses itself dramatically within a few hours or days.
More often and this is the case in the most thrombotic
ICVS, improvement occurs gradually over weeks and
months and the residual disability is considerable.
Some ICVS are clinically silent or course disorders of
function so mild as to concern the patient little if at all.
Spatial profile of ICVS:
The neurologic deficit reflects both the location and size of
the ICVS.
Imaging techniques for the demonstration of both the
cerebral lesion and the affected blood vessel continue to
enhance the clinical study of ICVS.
Focal ischemia differs from global ischemia.
In global ischemia, if absolute, there is no collateral flow
and irreversible destruction of neurons occurs within 4 to
8 minutes at normal body temperature.

In focal ischemia there is nearly always some degree of


circulation (via collateral vessels), permitting to a varying
extent the delivery of oxygenated blood and glucose.
The effects of arterial occlusion on brain tissue vary
depending upon the location of the occlusion in
relation to available collateral and anastomotic
channels.
If the occlusion lies proximal to the Circle of Willis
(toward the heart), the anterior and posterior
communicating arteries of circle are often adequate to
prevent ICVS.
If the occlusion is distal to the Circle of Willis, a series
of meningeal interarterial anastomosis may carry
sufficient blood into the compromised territory to
lessen (rarely to prevent) ischemic damage.
There is also a capillary anastomotic system between
adjacent arterial branches and although it may reduce
the size of the ischemic field, particularly of the
penetrating arteries, it is usually not significant in
preventing ICVS.
In the event of occlusion of major arterial trunk, the
extent of ICVS ranges from minimal zone to the entire
vascular territory of that vessel (between these two
extremes are all degrees of variation in extent of
infarction and its degree of completeness.
Circle of Willis (CW).
CW is formed by an arterial polygon as the internal artery
and vertebrobasilar system anastomose around the optic
chiasm and infundibulum of pituitary stalk that supply blood
to the brain.
CW is a potential collateral pathway through which adequate
distribution of cerebral blood flow can be maintained in case
of impaired or decreased flow through one or more of its
proximal feeding vessels.
Its ability to redistribute blood flow depends on the presence
and size of the component vessels.
Components of CW:
Left and right internal carotid arteries.
Left and right anterior cerebral arteries (segments A1)
Anterior communicating artery.
Left and right posterior communicating arteries.

Left and right posterior cerebral arteries (segments P1).


Origin of arteries:
The left and right internal carotid arteries arise from the
left and right common carotid arteries and usually
terminates by bifurcating into the anterior and middle
cerebral arteries.
The left and right posterior cerebral arteries typically
arise from the basilar artery, which is formed by the left
and right vertebral arteries (vertebral arteries arise from
subclavian arteries).
The anterior communicating artery (ACoA) connects the
two anterior cerebral arteries and could be said to arise
from either the left or right side.
The posterior communicating artery (PCoA) is given off as
branch of the internal carotid artery just before it divides
into terminal branches (the anterior and middle cerebral
arteries).
The anterior cerebral artery forms the anterolateral
portion of the CW.
The middle cerebral artery does not contribute to the CW.
The internal carotid arteries, anterior cerebral arteries
and anterior communicating artery form the anterior
circulation.
The basilar artery, posterior cerebral arteries and
posterior communicating arteries are termed the
posterior circulation.
Anatomic variation of CW:
Considerable anatomic variation exist in CW.
In one common variation the proximal part of the
posterior cerebral artery is narrow and its ipsilateral
posterior communicating artery is large, so the internal
carotid artery supplies the posterior cerebrum (fetal
variant of posterior CW).
In another variation, the anterior communicating artery is
a large vessel, such that a single internal carotid supplies
both anterior cerebral arteries.
Internal carotid artery (ICA):
The two ICA (anterior cerebral circulation) provide about
80% of the brain blood supply.
ICA arises from the common carotid artery, which bifurcate
into internal and external carotid arteries.

ICA has 6 segments:


Cervical segment (C1) extends from the carotid
bifurcation until it enters the carotid canal in the skull
anterior to the jugular foramen.
During this part of its course, it lies in front of
transverse processes upper three cervical vertebrae.
Unlike the external carotid artery, ICA normally has no
branches in the neck.
At the base of the skull the IX, X, XI and XII cranial
nerves lie between the ICA and jugular vein.
Intrapetrosal segment (C2) is inside the petrous part of
temporal bone.
The intrapetrosal
portion classically has three
sections: a) ascending (vertical); b) genu (bend);
c)
horizontal.
Intracavernous segment (C3) begins at the petrolingual
ligament and extends to the proximal dural ring.
ICA is surrounded by the cavernous sinus.
The curve of ICA in the cavernous segment is called the
carotid siphon.
Supraclinoid segment (C4) is a short portion of the ICA
that begins after the artery exits the cavernous sinus at
the proximal dural ring and extends distally to the distal
dural ring, after which the ICA is considered intradural
and has entered the subarachnoid space.
Ophthalmic segment (C5) extends from the distal dural
ring to the origin of the posterior communicating artery.
The C5 segment courses roughly horizontally, parallel
to the optic nerve, which runs supero-medially to the
ICA at this point.
From this segment arises the ophthalmic artery.
Communicating segment (C6) or terminal segment
passes between the optic and oculomotor nerves to the
anterior perforated substance at the medial extremity
of lateral cerebral fissure.
From this segment arises the anterior choroidal
artery (AChA).

ICA then divides to form the anterior cerebral artery (ACA)


and middle cerebral artery (MCA).

ICA ischemic syndromes:


Transient ischemic attacks (TIA):
Temporary, focal neurological deficits of ischemic etiology
generally lasting less than 24 hours (usually last a few
seconds to a few minutes and most symptoms disappear
within 60 minutes)
At least half of carotid artery stroke patients have one or
more TIAs before permanent infarction occurs.
Up to a third of patients with carotid TIAs do not
ultimately go on to infarction.
About one-third of patients with TIAs ultimately go on to
have infarction.
Overall, the relationship between antecedent TIA and
carotid territory infarctions is much stronger than with
infarctions in other vascular territories since there is only
about a 10% incidence of TIA with all stroke types taken
as a whole.
Transient monocular blindness (amaurosis fugax):
Is an important carotid TIA syndrome;
Has a duration usually less than 5 minutes and rarely
exceeds 30 minutes;
May be a marker for the presence of carotidbifurcation atherothrombotic disease (artery-to-artery
embolism).
Transient hemispheric attack:
Is another important carotid TIA syndrome;
Has a duration generally less than 10 minutes;
Is characterized by symptoms reflecting temporary
ischemia within a part of cerebrum supplied by the
anterior, middle or posterior choroidal arteries severe
enough to produce dysfunction;
When lasts hours at a time, the suggested mechanism may
be intracranial branch occlusion by an embolic source
more proximal than the carotid, such as the ascending
aorta or the heart.
Hemispheric border-zone infarct:

Appears when carotid and collateral occlusive disease is


severe enough to compromise flow to the distal-most
fields of the major cerebral arteries.

When fully manifest, the damage extends as a band from


the frontal pole posteriorly to the occipitoparietal region,
sparing the parasagital, lateral and primary occipital
aspects of the hemisphere.
Clinical syndrome can be distinctive and includes
weakness and sensory disturbance of the contralateral
shoulder usually with notable absence of severity
disturbed language, vision or lower limb function.
Hemispheric arterial infarction:
The clinical features are often catastrophic (malign
infarction), producing major motor and sensory deficits
of the contralateral limbs and severe language and
cognitive dysfunction, especially when the dominant
hemisphere is involved.
The deficits depend in large part on the caliber, location
and duration of occlusion of the intracranial vessel
involved by thromoembolism.
The signs and symptoms noted at presentation often
change over the hours following onset.
There are some recognizable syndromes, when emboli
lodge in the stems of middle and anterior cerebral
arteries.
Etiology:
Atherothrombosis of the ICA.
Artery-to-artery embolism.
Anterograde propagation of thrombus up the ICA to the
CW and even into the proximal anterior cerebral and/or
middle cerebral arteries.
ICA dissection:
Young patients.
ICA syndromes.
Horner syndrome.
Middle cerebral artery (MCA).
MCA is the most commonly affected artery in ICVS and is the
largest of major branches of internal carotid artery.

MCA is one of the three major paired arteries that supply


blood to cerebrum.
MCA is a continuation or the main branch of the ICA.

MCA arises from the internal carotid and continues into


lateral sulcus where gives branches and projects to many
parts of the lateral cerebral cortex, anterior temporal lobes
and insular cortices.
The size of the MCA and territory that it supplies is larger
than those of ACA and posterior cerebral artery (PCA).
MCAs are not considered part of the CW.
The segmental approach analyzes branches of MCA in
relation to brain landmarks, dividing the artery into 4 main
segments:
M1 (sphenoidal) is the portion most proximal to the origin
of the vessel:
From first portion of M1, the lateral lenticulostriate
arteries (15-17 small arteries) arise and supply the
lentiform nucleus (putamen and the upper part of the
globus pallidus), internal capsule, caudate nucleus (the
posterior portion of the head and all of the body),
extreme capsule, claustrum, corona radiata.
The second portion of M1 describes the 2 brances that
result from bifurcation of the MCA and enter the
sylvian sulcus.
M2 (insular) is the segment that runs along the insula: a)
the MCA may bifurcate into trunks (superior and inferior
divisions), which then extend into branches that terminate
towards the cortex
M3 (opercular) follows the operculum superior to the
insula.
M4 (terminal, cortical) perfuse nearly the entire cortex
surface of the cerebral hemisphere.
The cortical branches of MCA can be described by the areas
that they irrigate:
Frontal lobe:
Orbitofrontal;
Prefrontal;

Prerolandic;
Rolandic.
Parietal lobe:
Anterior parietal.
Posterior parietal.
Angular.
Temporal occipital.
Temporal lobe:
Temporopolar.
Anterior temporal:
Middle temporal.
Posterior temporal.
Areas supplied:
The bulk of the lateral surface of the hemisphere
except for the superior inch of the frontal and parietal
lobes ( supplies by ACA) and the inferior part of the
temporal lobes (supplies by PCA).
Superior division supplies rolandic and prerolandic
areas (location of Brocas area).
Inferior division supplies lateral temporal and inferior
parietal lobes (location of Wernickes area).
The penetrating branches of MCA supply:
Putamen.
Part of the head and body of caudate nucleus.
Outer globus pallidus. Posterior limb of the internal
capsule.
Corona radiata.
MCA ischemic syndromes:
Occlusion of MCA by a thrombus is relatively infrequent.
Most MCA occlusions are embolic.
Main trunk occlusion of either side yields:
Contralateral hemiplegia.
Eye and head deviation toward the MCA infarct.
Contralateral hemianopia.
Contralateral hemianesthesia.
Loss of consciousness may occur.
Main trunk occlusion involving dominant hemisphere:
Global aphasia.
Idiomotor apraxia.
Agraphia

Main trunk occlusion involving nondominant hemisphere:


Anosognosia.
Superior division of MCA (more frequent) infarct lead to:
Contralateral deficit with significant involvement of the
upper extremity and face, sparing partially of the
contralateral leg and foot.
Broca aphasia (dominant insula and operculum).

Inferior division of MCA (less frequent) infarct leads to:


Wernicke aphasia (dominant posterior temporal, inferior
parietal and lateral temporo-occipital regions).
Superior quadranopsia or homonymous hemianopsia,
depending on extent of infarction (either side).
Visual neglect (right inferior branch).
Agitated and confused state (temporal lobe damage).
Etiology:
Embolism.
Cardiac arrhythmia.
Arterial hypotension.
Significant internal carotid stenosis.
Atherosclerosis/thrombotic occlusion of the MCA.
Anterior cerebral artery (ACA).
ACA is one of the pair of arteries on the brain that supplies
blood to most medial portions of the frontal lobes and
superior medial parietal lobes.
The two ACAs arise from the ICA lateral to the optic chiasm
and are part of the CW.
The left and right ACAs are connected by the anterior
communicating artery(ACoA).
The ACA is classified into 3 segments:
A1 originates from the ICA and extends to the ACoA.
The medial lenticulostriate arteries arise from this
segment as well as the ACoA and irrigate caudate
nucleus and the anterior limb of the internal capsule.
A2 extend from the ACoA to the bifurcation forming the
pericallosal and callosomarginal arteries.
The recurrent artery of Heubner (distal medial striate
artery), which irrigate the anterior limb and genu of
the internal capsule and parts of the head of the
caudate, rostral putamen and globus pallidus, usually
arises at the beginning of A2 near the ACoA.

Orbitofrontal artery arises first from A2 at small


distance away from ACoA.
Frontopolar artery arises after the orbitofrontal artery
close to when A2 curves posteriorly over the corpus
callosum.

A3 (pericallosal artery) is one of (or the only) the main


terminal branches of the ACA.
The pericallosal artery extends posteriorly in the pericallosal sulcus.
Callosomarginal artery is a commonly present
terminal branch of the ACA, which bifurcates from
pericallosal artery.
A3 may form an anastomosis with posterior cerebral
artery.
Areas supplied by ACA:
Orbital gyri and medial surface of frontal lobe and part of
the septal area.
Most of the pole of the frontal lobe.
Precuneus gyrus of the parietal lobe.
The anterior four-fifths of the corpus callosum.
Anterior portions of the basal ganglia and internal capsule.
Olfactory bulb and olfactory tract.
ACA ischemic syndromes:
Occlusion of the stem of ACA distal to the ACoA (beyond a
point that would allow for potential collateral blood supply
from the contralateral ICA) causes:
Hemiparesis or hemiplegia contralaterally, involving
primarly the lower limb.
Sensory deficits contralaterally, involving primarly the leg
and perineum.
Apraxia of affected side.
Disconnection syndrome (due to callosal branches).
Anosmia (due to branches of olfactory bulb and olfactory
tract).
Urinary incontinence (usually occurs with bilateral
damage in acute phase).
Abulia (inability to make decisions or voluntary acts).

Grasp reflex or sucking reflex contralaterally (if CW is


compromised).
Mental status impairment:
Confusion;
Amnesia;
Perseveration;
Cognitive change (short attention span, slowness);
Deterioration of intellectual function.
Blockades to the proximal portion (A1) of ACA produce only
minor deficits (due to the collateral blood flow from opposite
ICA via ACoA.
In some individuals both ACAs arise from a single stem and
if this stem is occluded the resulting bilateral infarction
produces:
Marked spastic paraplegia.
Behavioral syndromes:
Urinary incontinence.
Apathy.
Distractibility.
Slowness of thought.
Paucity of insight and movement.
Sometimes mutism (akinetic mutism).
Anterior choroidal artery (AChA).
AChA is a long, narrow artery that arises from the ICA, just
above the origin of PCoA.
AChA supplies:
Choroid plexus of the lateral ventricle and third
ventricle.
Optic chiasm and optic tract.
Posterior limb of the internal capsule.
Internal segment of the globus pallidus.
Tail of the caudate nucleus.
Hippocampus.
Amygdala.
Substantia nigra.
Red nucleus.
Lateral geniculate body.
Anastomoses with posterior choroidal artery.
AChA ischemic syndromes:
AChA infarction of either side yields:
Contralateral:

hemiplegia.
hemihyposthesia.
homonymous hemianopia.
Right AChA infarction:
Spatial hemineglect.
Left AChA infarction:
Mild language disorders.

Bilateral AChA infarctions:


Pseudobulbar mutism.
Vertebrobasilar system (VBS):
VBS (posterior cerebral circulation) is constitute from:
Two vertebral arteries.
Basilar artery.
Two posterior cerebral arteries.
N.B.: The VBS provide about 20% of the brain blood
supply.
Vertebral artery (VA):
VA arises as the first branch of the subclavian arteries.
The first part of the VA enter the foramen transversaria of
fifth or sixth cervical vertebra.
The second part of the VA ascend through more rostral
transverse foramena to exit at second cervical vertebral level.
The third part of the VA loop posterolaterally, circling the
posterior arch of the first cervical vertebra and enter the
cranium between the atlas and occiput.
The fourth part of the VA pierces the dura mater (the
foramen magnum is traversed), inclines medialward to the
front of medulla oblongata and at the level of pontomedullary
junction it unites with VA of opposite side to form basilar
artery (BA).
The relative size of the VAs vary considerably and in ~10%
of cases, one artery is so small that the other is essentially for
BA.
The posteroinferior cerebellar artery (PICA) is the largest
branch of the VA and one of the three main arterial blood
supplies for the cerebellum.
VAs are the chief arteries of the medulla and each supplies:
Lower three-fourth of the pyramid.
The medial lemniscus.

All or nearly all of the retro-olivary (lateral medullary)


region.
The restiform body (inferior cerebellar peduncle).
Posteroinferior part of the cerebellar hemisphere.

VA ischemic syndromes:
The results of VA occlusion are quite variable.
When there are two good-sized arteries, occlusion of one
may cause no recognizable symptoms and signs.
If the subclavian artery is blocked proximal to the origin of
left VA, exercise of the arm on that side may draw blood
from the right VA and BA, down the VA and into the distal
left subclavian artery sometimes resulting in the
symptoms of vertebrobasilar insufficiency (subclavian
steal syndrome).
Subclavian steal syndrome (a demand for blood flow to
the arm is met by siphoning effect on the blood within the
ipsilateral VA causing it to flow in retrograde fashion):
Vertebrobasilar insufficiency: a) moderate posterior
headache; b) dizziness or vertigo; c) syncope;
d)
ataxia; e) motor deficits; f) visual disturbances.
Symptoms and signs in the left arm: a) diminished or
absent radial pulse; b) transient weakness on exercise;
c) claudication; c) paresthesias;
d) coldness; e)
pain.
Initiation or exacerbation of symptoms by physical
exercise.
If the occlusion of the VA is so situated as to block the
branches suppying the lateral medulla (PICA) a
characteristic syndrome may result (lateral medullary
syndrome Wallenberg syndrome).
When the vertebral branch to the anterior spinal artery is
blocked, flow from the other (corresponding) branch is
usually sufficient to prevent infarction of cervical cord.
Rarely, occlusion of the VA or one of its medial branches
produces a medial medullary syndrome.

Occlusion of a VA low in the neck is usually compensated


by the anastomotic flow to the upper part of the artery via
the thyrocervical, deep cervical and occipital arteries or
reflux from the circle of Willis.
Basilar artery (BA):
BA is formed by the two VAs joining each other in the midline.
It ascends along the ventral aspect of the pons.
It ends at pontomidbrain junction where it divides into
two posterior cerebral arteries.
The branches of the BA may by grouped as follows:
Paramedian 7 to 10 in number, supplying a wedge of
pons on either side of the midline.
Short circumferential 5 to 7 in number, supplying the
lateral two-thirds of the pons and the middle and
superior cerebellar peduncles.
Long circumferential 2 on each side (anteroinferior
cerebellar artery AICA and superior cerebellar
artery SCA), which run laterally around the pons to
reach the cerebellar hemispheres.
Interpeduncular at the bifurcation of the BA supplying
the high midbrain and medial subthalamic regions.
N.B.: the internal auditory (labyrinthine) artery arises
from the BA in about 20% of the population whereas
in the remainder it arises from the AICA.
BA ischemic syndromes:
The syndrome of BA occlusion reflects the involvement of a
large number of structures:
Corticospinal tract.
Corticobulbar tract.
Cerebellum.
Middle and superior cerebellar peduncles.
Medial and lateral lemnisci.
Spinothalamic tract.
Medial longitudinal fascicule.
Pontine nuclei.
Vestibular and cochlear nuclei.
Descending hypothalamospinal sympathetic fibers.
Third to eighth cranial nerves (the nuclei and their
segments within the brainstem).
Complete basilar syndrome:

Patients with BA thrombosis typically have a waxing and


waning course of symptoms, with as many as 50% of
patients experiencing transient ischemic attacks for
several days to weeks prior to the occlusion.
In contrast, embolic events are sudden, without prodome
or warning, with acute and dramatic presentation.

Commonly reported symptoms associated with basilar


occlusion include the following:
Vertigo.
Nausea and vomiting.
Headache.
Abnormalities of alerting, arousal and sleep
(compromise parts of reticular activating system).
Behavioral disturbances including confabulation with
or without memory disturbance may be present.
Peduncular hallucinosis.
Transient or persistent movement disorders: a) hemiballism; b) hemichorea.
Abnormal oculomotor signs: a) nystagmus; b) lateral
gaze paresis/paralysis; c) diplopia; d) papillary
changes.
Ipsilateral cranial nerve weakness: a) dysartria;
b)
dysphonia; c) facial paresis/paralysis; e) tongue
paresis/ paralysis.
Sensory loss.
Ataxia.
Motor weakness (contralateral hemiparesis or
quadriparesis.
Pain and temperature loss.
Visual field defects.
Incontinence.
Presence of central pain.
Abnormal swelling.
Sweating in the face or extremities.
A variety of specific neurologic syndromes have been
described in BA occlusion.

Cerebellar infarctions.
Locked-in syndrome.
Top-of-basilar syndrome.
Internuclear ophthalmoplegia.
One-and-a-half syndrome.
Ventral pontine (Millard-Gubler) syndrome.
Upper dorsal pontine (Raymond-Cestan) syndrome.
Lower dorsal pontine (Foville) syndrome.
Ventral midbrain (Weber) syndrome.
Dorsal midbrain (Benedikt) syndrome.
Posterior cerebral artery syndromes.

Transient global amnesia (TGA).


TGA is a sudden, temporary episode of memory loss that
cant be attributed to a more common neurological
condition, such as epilepsy or stroke.
Sudden onset of recent memory loss (anterograde
amnesia), verified by a witness.
Temporary disorientation in time and sometimes in
space.
Inability to retain newly presented material during the
attack.
Retention of personal identity despite memory loss.
Normal cognition, such as an ability to recognize and
name familiar objects and follow simple directions.
Absence of signs indicating damage to a particular area
of the brain, such as limb paralysis, involuntary
movements or impaired word recognition.
Duration of no more than 24 hours.
Gradual return of memory.
No evidence of seizures during the period of amnesia.
No history of active epilepsy or recent head injury.
TGA is a transient perturbation of hippocampal function,
especially of CA1 field of the cornu ammonis.
SCA ischemic syndrome:
Ipsilateral cerebellar ataxia.
Nausea and vomiting.
Slurred speech.
Loss of pain and thermal sensation over the opposite side
of the body (spinothalamic tract).
Partial deafness.

Static tremor of the ipsilateral upper extremity.


Ipsilateral Horner syndrome.
Palatal myoclonus.
AICA ischemic syndrome:
N.B.: The extent of the infarct is extremely variable, since
the size of this artery and the territory supplied vary
inversely with the size and territory of supply of the PICA.
Vertigo.
Nausea.
Vomiting.
Nystagmus.
Tinnitus and sometimes unilateral deafness.

Facial weakness.
Ipsilateral cerebellar ataxia.
Ipsilateral Horner syndrome.
Paresis of conjugate lateral gaze.
Contralateral loss of pain and temperature sense of arm,
trunk and leg (lateral spinothalamic tract).
If the AICA occlusion is close to the origin of the artery, the
corticospinal fibers may also be involved, producing a
contralateral hemiplegia.
If the AICA occlusion is distal, there may be cochlear and
labyrinthine infarction.
Posterior cerebral artery (PCA):
PCAs are paired vessels, usually arising from the top of the BA
and curving laterally, posteriorly and superiorly around the
midbrain.
In about 70% of persons, both PCAs are formed by the
bifurcation of BA and only thin PCoAs join this system to
the ICAs.
In 20 to 25% of the persons one PCA arises from the BA in
the usual way, but the other arises from the ICA.
In the remainder (5 to 10%) both PCAs arise from
corresponding ICA.
The PCA is divided into P1 and P2 segments by the PCoA.
Penetrating branches to the mesencephalon, subthalamic,
basal structures and thalamus arise primarly from the P1
segment and PCoA.
The P2 segment bifurcate into posterior temporal artery
and internal occipital artery.

The interpeduncular branches of the PCA arise just above


the BA bifurcation and supply: a) the red nuclei; b) the
substantia nigra bilaterally; c) medial parts of the cerebral
peduncles; d) oculomotor and trochlear nuclei; e)
reticular formation of the upper brainstem;
f)
decussation of the brachia conjunctivae (superior
cerebellar peduncles); g) medial longitudinal fasciculi;
h) medial lemnisci.
The thalamoperforate branches (paramedian thalamic
arteries) of the PCA arise more distally, near the junction
of the PCA and PCoA and supply the inferior, medial and
anterior parts of the thalamus.
The thalamogeniculate branches of the PCA arise still
more distally and supply: a) geniculate body; b) the
central and posterior parts of thalamus.
The medial branches of the PCA supply: a) lateral part of
the cerebral peduncle; b) lateral tegmentum and corpora
quadrigemina; c) pineal gland.
Posterior choroidal branches of the PCA run to:
a)
postero-superior thalamus; b) choroid plexus;
c)
posterior parts of the hippocampus.
Cortical branches of PCA supply: a) inferomedial part of
the temporal lobe; b) medial occipital lobe, including
cuneus, precuneus and visual Brodmann areas 17, 18 and
19.
PCA ischemic syndromes:
Occlusion of the PCA:
Can produce a greater variety of clinical effects than
occlusion of other artery, because both the upper
brainstem, which is crowded with important structures
and the inferomedial parts of temporal and occipital lobes
lie within its domain.
Obviously the site of the occlusion and the arrangement of
the Circle of Willis will in large measure determine the
location and extend of the resulting infarct.
Occlusion proximal to the PCoA may by asymptomatic or
have only transitory effects if the collateral flow is
adequate.
Even distal to the PCoA, an occlusion may cause relatively
little damage if the collateral flow through border-zone
from anterior and middle cerebral arteries is sufficient.

PCA ischemic syndromes can be classified in: a) central and


peripheral territory of PCA; b) anterior-proximal, cortical and
bilateral cortical.
Central territory PCA syndromes:
Thalamic syndrome (contralateral).
Thalamoperforate syndrome (crossed cerebellar ataxia
with ipsilateral third nerve palsy).
Weber syndrome.
Paresis or paralysis of vertical eye movement.

Contralateral:
Ataxic tremor.
Postural tremor.
Intention tremor.
Chorea.
Hemiballismus.
Decerebrate attacks.
Peripheral territory PCA syndromes:
Contralateral homonymous hemianopsia.
Bilateral occipital lobe lesion, possibly with involvement
of parieto-occipial region:
Bilateral homonymous hemianopia.
Achromatopsia.
Failure to see to-and-from movements.
Inability to perceive objects not centrally located.
Apraxia of ocular movements.
Inability to count or enumerate objects.
Memory defects.
Topographic disorientation.
Prosopagnosia.
Simultagnosia.
Unformed visual hallucinations.
Metamorphopsia.
Teleopsia.
Illusory visual spread.
Palinopsia.
Distortion of outlines.

Anterior-proximal PCA syndromes:


In these syndromes are involved:
Interpeduncular branches.
Thalamoperforate branches.
Thalamogeniculate branches.
Thalamic syndrome (Djerine-Roussy) = thalamogeniculate arteries syndrome.
Central midbrain and subthalamic syndromes = interpeduncular arteries syndromes:
Weber Syndrome.
Paresis of vertical gaze.
Stupor or coma.
Contralateral ataxic tremor.
Movement disorders.
Anteromedial inferior thalamic syndromes = thalamoperforate syndromes:
Extrapyramidal movement disorders (hemiballismus
or hemichoreoathetosis).
Deep sensory loss.
Hemiataxia or tremor may be added in various
combina-tions.
Vascular amnesia
is induces by occlusion of
paramedian thalamic branches.
Cortical PCA syndrome:
Homonymous hemianopsia (macular or central vision
may be spared because of collateralization of occipital
pole from distal branches).
Visual hallucinations in the blind parts of visual fields.
Metamorphopsia and palinopsia.
Alexia with or without agraphia.
Anomia (amnestic aphasia).
Visual agnosia.
Color dysnomia.
Bilateral cortical PCA syndromes:
These may occur as a result of successive infarctions or
from a single embolic occlusion of the upper BA, especially
if the PCoAs are unusually small.
Extensive lesions:
Total blindness of cortical type.
Bilateral homonymous hemianopsia.
Unformed visual hallucinations.

The papillary reflexes are preserved.


Optic disc appears normal.
Prosopagnosia (bilateral mesiotemoporo-occipital
lesions).
Anton syndrome = the patient is unaware of being
blind and may deny it even when it is pointed out to
him.
Balint syndrome (bilateral occipitoparietal borderzone lesions).
Korsakoff amnestic-like syndrome (bilateral lesions
that involve inferomedial portions of temporal lobes).

Lacunar ischemic syndromes (LIS):


LIS (lacunar infarcts) are caused by occlusion of a single small
deep penetrating artery that arises directly from the
constituents of the cerebral arteries, cerebellar arteries and
basilar artery.
Most symptomatic lacunar infarctions are due to the
occlusion of penetrating arteries of 200-800m in
diameter.
Lacunes may be defined as small subcortical infarcts (<15
mm in diameter).
LIS constitute up to 25% of all acute ischemic cerebrovascular diseases.
The corresponding lesions occur in the deep structures of
the brain: a) putamen 37%; b) pons 16%; c) thalamus
14%; d) caudate 10%; internal capsule 10%.
Silent lacunar infarction is one type of silent lacunae
which usually shows no identifiable outward symptoms.
Etiology:
Small arteries occlusion.
Cardioembolism.
Large arteries atherosclerosis.
Classical LIS:
Pure motor hemiparesis (PMH).
Location of infarct is: a) posterior limb of the internal
capsule; b) basis pontis; c) medullary pyramids.

PMH affects the face, arm or leg one side


(contralateral).
Dysartria, dysphagia and transient sensory symptoms
may also be present.
Ataxic hemiparesis (AH).
Location of infarct is: a) posterior limb of the internal
capsule; b) basis pontis; c) corona radiata.
AH displays a combination of cerebellar and motor
symptoms, including weakness and clumsiness on the
ipsilateral side of the body.
The face is not usually involved.
Ataxia is a much more bothersome symptom than
weakness.
AH usually affects the leg more than it does the arm
(homolateral ataxia and crural paresis).
The onset of symptoms is often over hours or days.
Dysartria clumsy-hand (DCH).
Location of infarct is in the anterior portion of the
internal capsule.
The main symptoms are dysartria and clumsiness of
the hand, which often are most prominent when the
patient is writing.
Pure sensory .
Location of infarct is contralateral thalamus (VPL).
Persistent or transient numbness, tingling, pain
burning or another unpleasant sensation on one side
of the body.
Mixed sensorimotor.
Location of infarct is thalamus and adjacent posterior
internal capsule.
Hemiparesis/hemiplegia with sensory impairment on
the same side of the body.
Reversible posterior leucoencephalopathy syndrome (RPLS)
RPLS is a specific form of hypertensive encephalopathy that is
strongly associated with renal disease, vasculitis, eclampsia
and immunosuppressive treatment.
Acute or subacute onset.
Neurological symptoms:
Headache.
Altered mental status (e.g.: confusion. drowsiness).

Visual disturbance: a) hemianopsia; b) visual neglect;


c) cortical blindness; d) Anton syndrome.
Seizures:
Usually multiple seizures.
Often precede other symptoms.
Usually generalized tonic-clonic.
May be preceded by visual aura/hallucinations.
Systemic signs:
Hypertensive encephalopathy.
Eclampsia.
Pregnancy.
Puerperium.
Renal failure with hypertension.

Therapy with immunosuppressive agents and cytotoxic


drugs:
Cyclosporin A.
Tacrolimus.
INF-.
Cisplatin.
Cytarabine.
Intravenous immunoglobulins.
Erythropoietin.

XV. MENINGEAL SYNDROME

Meningeal syndrome (meningism) is a clinical condition


induced by irritation of the meninges.
The meningism is the term used when the clinical triad
(nuchal rigidity, photophobia and headache) is present
without actual infections or inflammation (e.g.: meningitis).
The meninges are a group of membranes that envelops
central nervous system (CNS brain and spinal cord).
The meninges are made up of three layers: a) the pia
mater; b) the arachnoid mater; c) the dura mater.
Between the arachnoid mater and pia mater there is the
subarachnoid space.
Functions of meninges:
Protect the CNS.
Responsible for nourishing the brain.
Provide cushioning effect for the CNS.
Support the large venous channels carrying blood from
the brain toward the heart.
The pia mater:
Delicate innermost layer of the meninges.
It is the meningeal envelope which firmly adheres to
the brain and spinal cord, following the brains minor
contours (cerebral gyri and cerebellar laminae).
Pia mater is only absent at the natural opening
between the ventricles, the foramen Majendie and the
foramina Luschka.

It is a very thin membrane composed of fibrous tissue


covered on its outer surface by a sheet of flat cells
thought to be impermeable to fluid.
This allows the pia mater to enclose cerebrospinal
fluid (CSF).
It is pierced by blood vessels which travel to the brain
and spinal cord and its capillaries are responsible for
nourishing the brain.
Pia mater allows for the formation of perivascular
spaces that help serve as the brains lymphatic system.
The cranial pia mater is anchored to the brain by the
processes of astrocytes.
The spinal pia mater attaches to the dura mater through
21 pairs of denticulate ligaments that pass through the
arachnoid mater.
In conjunction with the other meningeal membranes, pia
mater functions are: a) to cover and protect the CNS; b)
to protect the blood vessels; c) to enclose the venous
sinuses near the CNS; d) to contain CSF; e) to form
partitions with skull.
The arachnoid mater:
It is one of the three meninges.
It is interposed between the two other meninges, the more
superficial and much thicker dura mater and the deeper
pia mater, from which it is separated by the subarachnoid
space.
The delicate arachnoid layer is attached to the inside of
the dura and surrounds the brain and spinal cord.
It does not line the brain down into sulci (folds), as does
the pia mater, exception of the longitudinal fissure, which
divides the left and right cerebral hemispheres.
The arachnoid mater makes arachnoid vili (act as one-way
valves), small protrusions through the dura mater into the
venous sinuses of the brain which allow CSF to exit
subarachnoid space and enter the blood stream.
The fine spider web-like appearance of the delicate fibres
of the arachnoid which extend down through the
subarachnoid space and attach to the pia mater
The arachnoid and pia mater are sometimes considered as
a single structure leptomeninge.
The dura mater:

The dura mater is the outmost of the three layers of the


meninges surrounding the CNS.
The dura mater is a sac that envelops the arachnoid mater.
It surrounds and supports the dural sinuses (cerebral
sinuses, cranial sinuses).
The dura mater has two layers: a) the superficial layer,
which serves as the skulls inner periostium; b) the deep
layer, the actual dura mater.
The two layers of dura mater run together throughout
most of the scull.
Where the two layers separate, the gap between them
is called a dural venous sinus, which drain blood and
CSF from the brain and empty into the internal jugular
vein.
There are two main dural reflections: a) the tentorium
cerebelli exists between and separates the cerebellum
and brain stem from the occipital lobes of cerebrum;
b) the falx cerebri, which separates the two
hemispheres of the brain and is located in the
longitudinal cerebral fissure.
Other two dural infoldings include: a) the falx cerebelli,
which partially separates the cerebellar hemispheres;
b) the sellar diaphragm is the smallest dural infolding
and is circular sheet of dura that is suspended between
the clinoid processes, forming a partial roof over the
hypophysial fossa (the sellar diaphragm covers the
pituitary gland in this fossa and has an aperture for
passage of infundibulum pituitary stalk and
hypophysial veins).
The subarachnoid space:
The subarachnoid space is a cavity between the
arachnoid mater and pia mater.
It is occupied by spongy tissue consisting of:
a) trabeculae (delicate connective filaments that
extend from the arachnoid mater and blend into the
pia mater);
b) intercommunicating channels in
which the CSF is contained.
The cavity is small on the surface of the hemispheres
of the brain.

At certain parts of base of the brain, the arachnoid is


separated from the pia mater by wide intervals, which
communicate freely with each other = subarachnoid
cistern (in these the subarachnoid tissue is less
abundant).
Blood-Brain Barrier (BBB).
CNS is tightly sealed from the changeable milieu of blood
by the BBB (localized at the level of the endothelial cells
within CNS and blood-CSF barrier (established by choroid
plexus epithelial cells) .

BBB is a complex anatomophysiological system which


impedes and regulates passage of molecules in and out of
brain.
BBB is essential for normal function of CNS.
BBB protects brain from foreign substances in the
blood that may injure the brain.
BBB protects the brain from hormones and neurotransmitters in the rest of the body.
Maintains a constant environment for the brain.
N.B.: BBB restricts the entry from blood of watersoluble drugs which are used to treat brain tumors or
infections (to use drugs that open the BBB).
BBB is formed by: a) microvascular endothelial cells
(MVEC) with tight junctions; b) astrocyte end feet;
c)
pericytes.
Difference between MVEC and normal endothelial cells:
Structural: a) absence of fenestrations; b) more
extensive tight junctions.
Functional: a) impermeable to most substance; b) no
gap junctions, only tight junctions; c) sparse pinocyric
vesicular transport; d) increased expression of
transport and carrier proteins = receptor mediated
endocytosis; limited paracellular and transcellular
transport.
Tight junctions:
Are present between the cerebral endothelial cells,
form a diffusion barrier, which selectively excludes
most blood-borne substances from entering the brain.
Astrocyte end feet:
Provides biochemical support for MVEC.

Factors released by astrocytes involved in postnatal


maturation of BBB.
Co-regulate function by secretion of soluble cytokines.
Pericytes:
Cells of microvessels including capillaries, venules and
arterioles that wrap around endothelial cells.
Provide structural support and vasodynamic capacity
to microvasculature.
Role in structural stability of vessel wall.
Endothelial cells associated with pericytes are more
resistance to apoptosis than isolated endothelial cells.
Phagocytic activity.
Regions of brain not enclosed by BBB = need to respond to
factors present in systemic circulation.
Pineal body = secrets melatonin and neuroactive
peptides associated with circadian rhythms.
Area postrema (vomiting center) = when a toxic
substance enters the bloodstream it will get to the area
postrema and may cause the humans to throw up.
Median eminence = regulates anterior pituitary
through release of neurohormones.
Neurohypophysis (posterior pituitary) = releases
neuro-hormones like oxytocin and vasopressin in the
blood.
Subfornical organ = important for the regulation of
body fluids.
Lamina terminalis (vascular organ) = a chemosensory
area that detects peptides and other molecules.
Normal BBB transport:
Diffusion: a) phospholipid bilayer; b) movement of
substance down diffusion gradient; c) transfer of
lipophilic substances (e.g.: alcohol, nicotine, oxygen,
carbon dioxide, barbiturate drugs).
Facilitated transport by carrier system.
Receptor mediated endocytosis.
Paracellular transfer more common than transcellular
transfer.
Large molecules do not pass through the normal BBB
easily.
Molecule that have a high electrical charge are slowed.

The BBB can be broken down and causing brain to swell


(cerebral edema) by:
High blood pressure.
Hyperosmolitity (high concentration of a substance in
the blood).
Microwaves (exposure to microwaves).
Radiation (exposure to radiation).
Epilepsy.
Alzheimers disease.
Infections
(meningitis,
encephalitis,
meningoencephalitis).
Inflammation (multiple sclerosis, neuromyelitis optica,
progressive multifocal leukoencephalopathy).
Cerebral trauma.
Cerebral hemorrhage.
Cerebral ischemia.
Cerebrospinal fluid (CSF).
CSF is clear, colorless, bodily fluid, that occupies the brain
and spinal cord subarachnoid space (cisterns and sulci),
the ventricular system, as well the central canal of the
spinal cord.
CSF is produced from arterial blood by the choroid
plexuses (50-70%) of the lateral and fourth ventricles and
remainder is formed around blood vessels and along
ventricular walls, by a combined process of diffusion,
pinocytosis and active transfer.
Choroid plexus consists of tufts of capillaries with thin
fenestrated endothelial cells.
CSF circulation.
CSF circulates from the lateral ventricles to the
foramen Monro (interventricular foramen) third
ventricle, aqueduct of Sylvius (cerebral aqueduct),
fourth ventricle, foramen of Magendie (median
aperture) and foramina of Luschka (lateral apertures),
subarachnoid space over the brain and spinal cord.
CSF moves in a pulsatile manner throughout the CSF
system with nearly zero net flow.
CSF is reabsorbed into venous sinus blood via
arachnoid granulations (vili).
CSF amount and constitution.

The total volume of CSF in the adult ranges from 140


to 270 ml (the volume of ventricles is about 25 ml).
The CSF is produced at a rate of 0.2 0.7 ml per
minute or 600 700 ml per day.
The CSF pressure, as measured by lumbar puncture is
10 18 cm H2O (8 15 mm Hg) with the patient lying
on the side and 20 30 cm H2O (16 24 mm Hg) with
patient sitting up.
The CSF from the lumbar region contains 15 45
mg/dl protein (protein concentration in cisternal and
ventricular CSF is lower).
The CSF from the lumbar region contains 50 80
mg/dl glucose (two-third of blood glucose).
The normal CSF contains 0 5 mononuclear
cells.
The IgG index of CSF is a measure of the
immunoglobulin G content and is defined as: IgG index
=
(IgGCSF/IgGserum) / (albuminCSF/albuminserum) = 0.73
(normal value), with a higher value indicating
presence of multiple sclerosis.
CSF functions.
Bouyancy: The actual mass of the human brain is about
1400 grams; however, the net weight of the brain
suspended in the CSF is equivalent to a mass of 25
grams (the brain therefore exists in neutral buoyancy,
which allows the brain to maintain its density without
being impaired by its own weight).
Protection: CSF protects the brain tissue from injury
when jolted or hit (in certain situation such as auto
accidents or spots injuries, the CSF cannot protect the
brain from forced contact).
Chemical stability: CSF flows throughout the inner
ventricular system in the brain and its absorbed back
into the bloodstream, rinsing the metabolic waste from
CNS through blood-brain barrier.
Symptoms of meningism (MN).
The triad of MN: a) nuchal rigidity; b) photophobia;
c) headache.
Nuchal rigidity (neck stiffness) is the inability to flex the
head forward due to rigidity of the neck muscles induced

by muscles contraction (if flexion of the neck is painful but


range of motion is present, nuchal rigidity is absent).
Kernigs sign: a) is assessed with the patient lying
supine, with the hip and knee flexed to 90 degrees; b)
in a patient with a positive Kernigs sign, pain limits
passive extension of the knee (leading to resistance);
c) resistance due to involuntary hamstring contraction
suggests irritation of the L5 and S1, two roots.
Brudzinskis sign consists in the flexion of the hips and
knees (sometimes with extension of the hallus and
fanning of the toes) in response to passive neck
flexion.

Types of Brudzinskis signs: a) passive flexion of one


knee into abdomen leads to involuntary flexion in the
opposite leg and stretching of a limb that was flexed
leads to contralateral extension: b) contralateral leg
sign = the involuntary flexion or extension of one leg in
response to forceful passive flexion of other leg at the
hip (straight leg
raising); c) the reciprocal
contralateral leg sign is seen when one leg is flexed at
the hip and the other is extended (when the flexed
limb is lowered to bed, the other limb flexes); d) cheek
sign = flexion of the elbows with upward jerking of
both arms in response to pressure on the cheeks,
below the zygoma; e) symphysis sign = flexion of the
legs in response to suprapubic pressure.
Patients may also show opisthotonus spasm of the
whole body that leads legs and head bent back and
body bowed backwards.
Photophobia is abnormal intolerance to visual perception
of light with discomfort or pain to the eyes and is
consequence of optic nerves irritation.
Headache is, in general, intense and diffuse but sometimes
is localized occipital or frontal and can by exacerbated by
active or passive movements of the head.
Additional signs:
Rachialgia and radiculalgia.
Projectile vomiting.

Seizures.
Papilledema.
Dilated, nonreactive pupil or pupils.
Unilateral or bilateral cranial nerve VI palsies.
Altered level of consciousness.
Fever (in meningitis or in meningoencephalitis).
Cushing reflex bradycardia, hypertension and
irregular respirations; i) decerebrate posturing.
Psychical disturbances (irritability, aggressiveness,
hallucinations, delirium).

Etiology:
Subarachnoid hemorrhage.
Bacterial meningitis (including tuberculosis
meningitis).
Viral meningitis.
Meningoencephalitis.
Parasitic meningitis.
Aseptic meningitis.
Neoplastic meningitis

XVI. INTRACRANIAL HYPERTENSION.


Intracranial pressure (ICP).
ICP is the pressure inside the skull and thus in the brain
tissue and cerebrospinal fluid (CSF).
The body has various mechanisms by which it keeps the
ICP stable, with CSF pressure varying by about 1 mmHg in
normal adults through shifts in production and adaption
of CSF.
CSF pressure has been shown to be influenced by abrupt
changes in intrathoracic pressure during:
Coughing (intra-abdominal pressure).
Valsalva maneuver (attempted exhalation against a
closed airway).
Oueckenstedt maneuver ( exert pressure on both
external jugular veins).
Communication with vasculature (venous and arterial
systems).
ICP is measured in millimeters of mercury (mmHg).
At rest ICP is normally 5-15 mmHg (60-180 mmH2O)
for spine adult
In the vertical position ICP becomes negative
(averaging 10 mmHg).

Changes in ICP are attributed to volume changes in one or


more of constituents contained in the cranium.
Intracranial hypertension (ICH).
ICH is elevation of the pressure in the cranium.
In general, the seriosity of the case depends on:
Site of lesion.
Time length of the expansion.
Character of the causative agent.
ICH has 4 evolutive stages:
Total compensation.
Partial compensation.
Decompensation.
Vasomotor paralysis.
At 20-25 mmHg, the upper limit of normal ICP, treatment
to reduce ICP may be needed.
ICH is very likely to cause severe harm if it rises to high.
Very high ICH is usually fatal if prolonged.
Children can tolerate higher pressure for longer periods
because their cranial sutures have not closed and
fontanels have not fused.
An increase in pressures most commonly due to head
injury:
Intracranial tumors.
Intracranial hematoma.
Intracranial malign infarct.
Brain trauma.
Cerebral edema.
ICH:
Induces crush brain tissue.
Induces shift brain structures.
Contributes to hydrocephalus.
Causes the brain to herniate (usually uncal or tonsilar).
Restricts blood supply to the brain (brain ischemia by
decreasing cerebral perfusion pressure).
It is a cause of reflex bradycardia.
Signs and symptoms:
Onset of ICH:
Headache (constant, increasing, aggravated by
movement or straining, frontal or occipital).
Vomiting without nausea (recurrent and projectile, not
related to meals).

Ocular palsies (abducens nerve is anatomically most


vulnerable).
Altered level of consciousness.
Papilledema.
If papilledema is protracted, it may lead to visual disturbances, optic atrophy and eventually blindness.
If mass effect is present with resulting displacement of
brain tissue, additional signs may include:
Any changes in pupillary size (especially dilatation),
shape or reactivity.
Nuchal rigidity.
Abducens palsies.
Lateralizing signs: a) help localize lesion to one side of
brain; b) may herald herniation (emergency!).
Seizure activity (common in intracranial tumor).
Cushing triad: a) increased systolic blood pressure;
b) bradycardia; c) abnormal respiratory pattern.
Decreased motor ability: a) decortication (internal
rotation and flexion of upper extremities, plantar
flexion of feet, extension and internal rotation of lower
extremities; b) decerebrate (extension and outward
rotation of upper extremities, plantar flexion and
extension of lower extremities; c) flaccidity with loss
of reflexes.
In children, a slow heart rate is especially suggestive of
high ICH.
Irregular respiration occur when injury to part of the
brain interfere with respiratory drive.
Cheyne-Stokes respiration, in which breathing is rapid
for a period and then absent for a period, occurs
because of injury to the cerebral hemispheres or
diencephalon.
Hyperventilation can occur when the brainstem or
tegmentum is damaged.
Only when ICP exceeds 40-50 mmHg do cerebral
perfusion pressure decreases to a level that results in loss
consciousness and further elevations will lead to brain
infarction and brain death.
Etiology:
Mass effect (tend to deform the adjacent grain):
Brain tumor.

Metastasis.
Intracerebral hematoma.
Cerebral infarction with edema.
Contusions.
Subdural or epidural hematoma.
Abscesses.
Generalized brain swelling (tend to decreases the cerebral
perfusion pressure, but with minimal tissue shifts:
Ischemic-anoxia states.
Acute liver failure.
Hypertensive encephalopathy.
Pseudotumor cerebri.
Hypercarbia.
Reye hepatocerebral syndrome.
Increase in venous pressure:
Cerebral venous thrombosis.
Heart failure.
Obstruction of superior mediastinal or jugular veins.
Obstruction to CSF flow and/or absorption:
Hydrocephalus
(blockade
in
ventricles
or
subarachnoid space al base of brain, e.g.: Arnold-Chiari
malformation).
Extensive meningeal diseases (e.g.: infection,
carcinoma, granuloma, hemorrhage).
Obstruction in cerebral convexities and superior
sagital sinus (decreased absorption).
Increased CSF production:
Meningitis.
Choroid plexus tumor.
Idiopathic intracranial hypertension (IIH).
IIH is a neurological disorder that is characterized by
increased intracranial pressure around the brain in absence
of tumor or other disease.
The term idiopathic means existence without any
underlying cause.
This is why the condition is diagnosed only in absence of
any alternative explanation for manifestations or
symptoms.
Signs and symptoms:

The most common symptoms is headache and it is


characteristically worse in the morning, generalized
in character and throbbing in nature.
The headache can be worse by any activity that
further increases the ICP, such as coughing and
sneezing.
The pain may also be experienced in the neck and
shoulders.
Headache may be associated with nausea and
vomiting.
Many patients have pulsatile tinnitus, a whooshing
sensation in one or both ears and this sound is
synchronous with pulse.
More rarely: a) numbness of extremities;
b)
generalized weakness; c) los of smell;
d)
incoordination.

The increased pressure leads to compression and


traction of cranial nerves:
The abducens nerve palsy is most commonly
involved.
The oculomotor nerve and trochlear nerve are more
rarely affected.
The facial nerve is affected occasionally.
The increased pressure leads to papilledema, sometimes
with transient visual obscurations.
Long-term untreated papilledema leads to visual loss,
initially in the periphery but progressively towards the
center of visual field.
Modified Dandy criteria for IIH diagnosis:
Symptoms of raised intracranial pressure.
No localizing signs with the exception of abducens
nerve.
The patient is awake and alert.
Normal CT/MRI findings without evidence of
thrombosis.
Lumbar puncture opening pressure of >15 mm Hg.

Normal biochemical and cytological composition of


CSF.
No other explanation for the raised intracranial
pressure.
Etiology:
Long-term tetracycline treatment.
Hormonal contraceptives.
Reaction to vitamin A derivates.
Sleep apnea.
Chronic kidney diseases.
Systemic lupus erythematosus.
Young women, especially those with obesity.

XVII. COMA
Consciousness is a set of neural process that allow an individual
to perceive, comprehend and act on internal and external
environments.
Consciousness is envisioned in two parts: a) arousal;
b) awareness.
Arousal describes the degree of which the individual appears
to be able to interact with these environments (the contrast
between waking and sleeping is common example of two
different states of arousal.
Awareness:
Reflects the depth and content of aroused state and
awareness is dependent on arousal.
Does not imply any specificity for the modality of
stimulation (external auditory or internal thirst).
Attention depends on awareness and implies the ability to
respond to particular types of stimuli (modality-specific).
Gradations of consciousness:

Stupor refers to a condition in which the patients is less


alert than usual but can be stimulated into responding.
Obnubilation is clouding of consciousness.
Obtunadation is a condition of mild to moderately reduced
consciousness, the subject being rousable with verbal or
slightly painful stimuli but tending to slip back into sleep
after the stimuli cease (this eyes-closed state is not
electro-encephalographic EEG sleep).
Stuporous and obtunded patients respond to noxious
stimuli by attempting to deflect or avoid the stimuli.
The comatose patient lies with eyes closed and does not
make an attempt to avoid noxious stimuli (such person
may display various form of reflex posturing).
After a period of coma, some patients may enter a
vegetative state, in which :
The patients eyes open and close.
The patient may appear to track objects about the
room.
The patient may chew and swallow food placed in the
mouth.

The patient does not respond to auditory stimuli.


The patient does not appear to sense pain, hunger or
other stimuli.
This is the state in which there is arousal but not
awareness.
Anatomophysiology of arousal.
Arousal requires the interplay of both the reticular
formation (RF) and cerebral cortex (CC).
The RF necessary for arousal reside in the midbrain and
diencephalon (the pontine RF is not necessary for
arousal).
The midbrain may be viewed as a driving center for the
higher structures.
Loss of midbrain RF produces a state in which the CC
appears to be waiting for the command or ability to
function (this is manifested EEG as alpha coma, in which
the resting electrical activity of the CC appears relatively

normal but cannot be altered by external or internal


stimuli).
Ascending reticular activating system (ARAS) from
midbrain extends upward into the hypothalamus to the
thalamus.
ARAS receives collaterals from and is stimulated by
every major somatic and sensory pathway directly or
indirectly.
This system is best regarded as a physiological rather
than a precise anatomical entity.
Three principle paths projects out of the midbrain: a)
to the thalamic reticular nuclei (midline and
intralaminar nuclei) and other nuclei of the thalamus
and via these structures to the CC; b) to the
hypothalamus and then on to the basal forebrain and
limbic system; c) to the brain stem median raphe and
locus coeruleus with consequent diffuse cortical
projections.
ARAS is an alerting or arousal system that also
indirectly influences sensory processing in the CC.
The thalamic reticular nuclei act predominantly to
inhibit the CC via outflow tracts that transverse
numerous other thalamic nuclei.
By increasing or decreasing thalamic inhibitory
mecha- nisms on the CC, the ARAS from the midbrain
provides a gating mechanism to enhance or diminish
neural activation.
Because of the diffuse anatomical substrate of the arousal
little is known of the specific neurochemistry involved in
the maintenance of arousal.
The cholinergic nuclei , such as the basal forebrain
nuclei, the pedunculopontine nucleus and laterodorsal
nucleus tegmental nuclei, play a role in alertness and
arousal (acetylcholine is probably an important
neurotransmitter of memory function).
The noradrenergic locus coeruleus assists in
responding to sudden contrasting or adverse stimuli
and the locus coeruleus projection to the forebrain and
visual cortex is involved in attention.

The majority of the cell bodies of dopaminergic system


are in ventral brain stem tegmentum and are involved
in motor function and cognition (the dopaminergic
nigrostriatal projection is also involved in motor
function and attention).
The serotoninergic system of the midline raphe nuclei
of tegmentum, largely inhibitory in nature, has a
stabilizing effect on information processing, is
involved in sleep and modulates the sleep-wake cycle.
The -amino butyric acid (GABA) inhibitory neurons
are widely dispersed throughout the central nervous
system and are involved with the selection of sensory
information,
Glutamate and aspartate are the excitatory neurotransmitters that play a key role in cortical interplay
(essential for consciousness).
Many other peptides and receptors are also involved in
cortical function and consciousness.
Two primary types of lesions depress the level of arousal:
a) direct brain stem diencephalic dysfunction involving
RF; b) bilateral cortical dysfunction (unilateral cortical
lesions should not impair arousal function).

Anatomophysiology of awareness.
Awareness implies that the individual is not only alert but
is cognizant of self and surroundings.
Interaction of the CC and RF is required for the individual
to be awake.
Anatomophysiology of attention.
Attention to specific aspects of the perceived universe
depends on both awareness as a general property and on
the specific anatomical structures that mediate the
sensory phenomena involved.
In order to attend to a particular stimulus, the pathways
required for its perception must be functional.
Each primary sensory modality has one or more principal
cortical regions the must function in order to attend to a
stimulus.

Attention enables an awake and alert individual to select


a task or a stimulus to process from a number of
alternatives to select a cognitive strategy to carry it out
(the ARAS is thought to facilitate this process by
enhancing the perception of differences between
competing stimuli).
Coma.
Coma is a state of unconsciousness, lasting more than six
hours in which a person:
Inability to be aroused.
Cannot be awaked.
Fails to respond normally to painful stimuli, light and
sound.
Lock a normal sleep-wake cycle.
Does not initiative voluntary actions.
A person in a state of coma is described as being comatose.
Etiology nonstructural or structural causes:
Nonstructural causes.
Metabolic and endocrine derangements:
Hypothermia and hyperthermia.
Hypoglycemia.
Diabetic ketoacidosis.
Hyperosmolar nonketotic coma.
Renal failure uremia.
Reyes syndrome.
Hyponatremia/ hypernatremia.
Panhypopituitarism.
Myxedema.
Adrenal cortical failure (addisonian crisis).
Porphyria.
Hypertensive encephalopathy.
Nutritional.
Wernickes encephalopathy (thiamine deficiency).
Vitamin B12 deficiency.
Burn encephalopathy.
Septicemic/toxic shock.
Hypoxic brain injury:
Asphyxiation.
Drowning.
Anoxemic anoxia (cardiac arrest).
Anemic anoxia (hemorrhagic shock).

Toxic brain damage:


Alcohol.
Carbon monoxide.
Cyclosporine.
Drug overdose.
Opiates.
Barbiturates.
Benzodiazepine.
Inflammatory/infectious processes:
Meningitis.
Encephalitis.
Postinfectious encephalomyelitis.
Vasculitis:
Cerebral lupus
Neurosarcoidosis.
Neoplastic:
Leptomeningeal carcinomatosis.
End stage of dementing processes ( persistent vegetative
state is more usual).
Epilepsy:
Convulsive status epilepticus.
Nonconvulsive status epilepticus.
Postictal state.
Structural causes:
Traumatic brain injury:
Diffuse brain injury
Epidural hematoma.
Subdural hematoma.
Intracerebral hematoma.
Penetrating brain injury.
Intracranial hemorrhage.
Subarachnoid hemorrhage.
Spontaneous subarachnoid hemorrhage.
Aneurysm rupture.
Arteriovenous malformation rupture.
Tumor hemorrhage.
Spontaneous hemorrhage.
Intracerebral.
Cerebellar.
Brain stem.
Infarction.

Cerebral.
Cerebellar.
Brain stem.
Intracranial infection.
Subdural empyema.
Focal encephalitis (herpes simplex).
Cerebral abscess.
Brain tumor.
Primary neoplasm.
Secondary neoplasm.
Hydrocephalus.
Obstructive.
Communicating.
Pathophysiology.
Diffuse lesion of both cerebral hemispheres (cortical gray
matter and subcortical white matter).
Bilateral diencephalic damage (especially to the
paramedian dorsal thalamus).
Damage to the paramedian gray matter anywhere from
the posterior hypothalamus to the tegmentum of the
lower pons.
When the respiratory centers in the lower medulla are
damage, apnea ensues.
The irreversible destruction of critical brain stem areas
usually follows catastrophic supratentorial events that
cause brain herniation and subsequent compression and
ischemia of the brain stem.

The sequence of cardiovascular changes resulting from


progressive mechanical compression and/or ischemia of
the brain stem (autonomic storm) begins with vagal
stimulation, which causes decreases in heart rate, mean
arterial pressure and cardiac output.
As pons becomes ischemic, sympathetic stimulation
occurs, which results in hypertension with persistence of
the bradycardia (Cushings reflex).
As the medulla becomes ischemic, there is unopposed
sympathetic stimulation with tachycardia, increased
arterial pressure and increased cardiac output.
Overview of neurological examination.

The examination of the patient with altered consciousness


begins by ensuring that the patients vital signs and basic
biochemistry are adequate to support brain function.
It is essential to ensure that blood pressure, pulse,
respiration, core temperature, state of hydration and
oxygen saturation are adequate and that the patient is not
hypoglycemic or thiamine deficient before proceeding
with the examination outlined later.
Glasgow Coma Scale (GCS).
GCS was devised to provide a simple, reliable and
reproducible method of assessment of conscious state.
GCS has become a universally accepted scale for
neurological observation, prognostication and grading
severity.
GCS comprise three tests: eye, verbal and motor
responses.
The three values separately as well as their sum are
considered.
The lowest possible GCS (the sum) is 3 (deep coma).
The highest is 15 (fully awake).
Severe brain injury = 8.
Moderate brain injury = 9-12.
Minor brain injury = 13.
Many clinicians regard a maximum GCS of 8 as cutoff
for coma.

GCS (adult): 15 points.


_____________________________________________
Response
_____________________________________________

Score

Eye opening
Spontaneous open with blinking at baseline..4
Opens to verbal command....3
Opens to pain, not applied to face..2
None.... 1

Best verbal response


Oriented...5
Confused conversation, able to answer question.4
Inappropriate words, words discernible..3
Incomprehensible speech.2
None.1
Best motor response
Obeys commands for movement.6
Localizes painful stimuli5
Flexion/withdrawal to painful stimuli..4
Abnormal (spastic) flexion decorticate response...3
Abnormal (rigid) extension decerebrate response.2
None.1
Maximum Score..15

Respiratory pattern.
Normal pattern.
Cheyne-Stokes: periodic increase and decrease of rate and
depth, followed by an expiratory pause and then a
repeated pattern seen with diencephalic pathology and
bilateral hemisphere dysfunction (nonspecific).
Hyperventilation: raises suspicion of hypoxia or metabolic
coma with acidosis, such as with ethylene glycol,
methanol, salicylates and lactic acidosis (central
neurogenic hyperventilation may occur with midbrain
damage).
Cluster breathing: periods of rapid irregular breathing
separated by periods of apnea it is similar to CheyneStokes respiration but without the crescendo/
decrescendo pattern or regularity of the latter (this is seen
with high medullary or low pontine lesions.
Apneustic breathing: deep inspiration followed by breath
holding, then long slow expiration at a rate of 6 breath per
minute (implies pontine damage basilar artery
occlusion).

Ataxic (Biots) breathing: irregular and disorganized


breathing (occur with medullary dysfunction and is
usually preterminal).
Pupil examination.
Pupillary size, shape and reaction are integral components
of the assessment of conscious state.
Equal-sized and reactive pupils in a comatose patient
indicate a metabolic or toxic cause, with exception of
anoxia, anticholinergics, glutethimide and botulinum
toxin, which cause fixed, dilated pupils (narcotics cause
small pupils that react sluggishly).
Unequal-sized pupils:
Imply a structural lesion of the brain or cranial nerves.
One caveat is that direct ocular trauma may produce
mydriasis.
A pupil that dilates after a cerebral insult is indicative
of changing intracranial pathology with increasing
tension on the ipsilateral oculomotor nerve resulting
from uncal herniation through the tentorial hiatus.
Dilated nonreactive pupils from the time of an injury
imply irreparable brain damage or bilateral optic
nerve injury.
The Horners syndrome implies disruption of the
sympathetic nervous system input to the pupil an may
follow carotid occlusion or dissection, among other
causes.
Bilateral pinpoint pupils occur with pontine lesions that
leave the parasympathetic nerves unopposed.
Bilateral fixed and dilated pupils (7 to 10 mm) occurs with
medullary injury, with post-tonsilar or central herniation,
after anoxia or with hypothermia (< 32o C).

Bilateral nonreactive pupils at the mid position (4 to 6


mm) occurs with an extensive midbrain lesion.
Deviation of the ocular axes.
Bilateral conjugate deviation:
Frontal lobe lesion (frontal center for contralateral
gaze) = the eyes look toward the side of the lesion.
Pontine lesion = the eyes look away from the side of
the lesion.

Medial thalamic lesion = the eyes look away from the


side of the lesion.
Downward deviation = thalamic or midbrain pretectal
lesions, metabolic cause (especially barbiturate).
Unilateral outward deviation with dilated pupil =
nerve III palsy.
Unilateral inward deviation = nerve VI palsy.
Skew deviation = nerve III or IV nuclear or nerve injury or
an infratentorial lesion, especially of the dorsal midbrain.
Spontaneous eye movement.
Ocular bobbing with rapid downward movement of the
eyes and a slow return occurs with pontine lesions.
Random conjugate eye movements are nonspecific for
lesion location.
In the uncommon periodic alternating gaze (ping-pong
gaze) the deviate side to side with frequency of 3 to 5 per
second and a pause of 2 to 3 seconds in each direction =
bilateral cerebral dysfunction.
Internuclear ophthalmoplegia.
Internuclear ophthalmoplegia is caused by a lesion of the
medial longitudinal fasciculus = the eye on the side of the
lesion does not adduct on spontaneous or reflex-induced
eye movement.
Reflex eye movement.
Oculocephalic reflex (dolls eye reflex):
In the awake patient, the eyes follow the movement of
the head or, if the movement is performed slowly,
there is contraversive conjugate eye movement if the
eyes fixate on stationary target.

In the comatose patient with intact brain stem and


cranial nerves, the reflex is preserved and the eyes
move in the opposite direction when the head is
turned laterally or the neck flexed and extended (the
conjugate eye movement is contraversive).
When the brain stem is damaged, the reflex is lost and
the eyes follow the head movement.

N.B.: Cervical spine injury should be ruled out before


this test is performed.
Decorticate posturing.
Decorticate posturing is abnormal flexion of the upper
limbs (adduction of the arm and slow flexion of the elbow,
wrist and fingers) and extensor posturing of the lower
limbs (extension, internal rotation and plantar flexion).
It occurs with large cortical or subcortical lesions.
The corticospinal tract is interrupted above the level of
midbrain.
Decerebrate posturing.
Decerebrate posturing occurs with brain stem injury at
the level of midbrain or below.
There is said to be disinhibition of the vestibulospinal
tract and pontine reticular formation by removal of
inhibition of the medullary reticular formation (e.g.: the
transection is at the intercollicular level between the red
nuclei and vestibular nuclei in the classical lesion.
There is abnormal extension of upper and lower limbs
with internally rotated legs, plantar-flexed and inverted
feet. plantar-flexed toes, variability clenched teeth and
opistho-tonus.

SELECTIVE REFERENCES
Afifi AK, Bergman RA. Functional Neuroanatomy, McGrawHill,NewYork, 1998, pg. 105-233.
Aminoff MJ, Greenberg DA, Simon RP. Clinical Neurology,
Lange Medical Books/ McGraw-Hill, New York, 2005, pg.: 69-262.
Blaa R. Nervii cranieni, University Press, Trgu Mure, 2010,
pg.: 3-245.
Blaa R, Pascu I. Sindroame neurologice majore. University
Press,Trgu Mure, 2006, pg.:1-204.
Bradley WG, Daroff RB, Fenichel GH, et al (Eds). Neurology in
Clinical Practice, Butterworth Heinemann, Philadelphia, 2004, pg.:
1-456.
Brandt T, Caplan LR, Dichgans, et al (Eds). Neurological
Disorders, Academic Press-Elsevier, Amsterdam, 2003, pg.: 59-75;
115-183; 245-302, 327-347.
Brazis PW, Masdeu JC, Biller J. Localization in Clinical
Neurology, Lippincott Williams &Wilkins, Philadelphia, 2001, pg.:
127-370.
Clarke C, Howard R, Rossor M, et al (Eds). Neurology:
A Queen Square Textbook, Willey-Blackwell, Oxford, 2009. Pg.:
75-244.
Goetz GG (Ed). Textbook of Clinical Neurology, SaundersElsevier, Philadelphia, 2003, pg.: 3-424.
Hauser SL (Ed). Harrisons Neurology in Clinical Medicine,
McGraw-Hill, New York, 2006, pg.: 39-152; 187-348.
Jankovic J, Tolosa E. (Eds). Parkinsons Disease & Movement
Disorders, Lippincott Williams & Wilkins, Philadelphia, 2007, pg.:132; 67-92; 213-245; 298-386.
Miller NR, Newman NJ, Biousse Valrie, et al. Walsh and
Hoyts Clinical Neuro-Ophthalmolohy: The essentials. Lippincott
Williams &Wilkins, Philadelphia, 2008, pg. 98-330.
Mohr JP, Choi DW, Grotta JC, et al. Stroke, Pathophysiology
and Management. Churchill Livingstone, Philadelphia, 2004, pg.:
75-274.
Panayiotopoulos CP. The Epilepsies, Bladon Medical Publishing,
Oxfordshire, 2005, pg.: 361-429.
251

Pryse Phillips W. Companion to Clinical Neurology.


Oxford University Press, Oxford, 2009, pg.: 1-89; 262-319; 688739;
762-903.
Royden Jones H, Jr (Ed). Netters Neurology, Icon Learning
System,Terboro, 2005, pg.: 64- 176; 195-217.
Shapira AH, Byrne E, DiMauro S, et al (Eds). Neurology and
Clinical Neuroscience, Mosby-Elsevier, Philadelphia, 2007, pg.:
31-95; 155-177; 396-485.
Victor M, Ropper AH. Adams and Victors Principles of
Neurology, McGraw-Hill, New York, 2001, pg.: 45-521.
Waxman SG. Clinical Neuroanatomy. Lange Medical
Books/McGraw-Hill, New York, 2003, pg.: 35-327.
Weiner WJ, Goetz CG, Shin RK, et al (Eds). Neurology for
Non-Neurologist, Lippincott Williams & Wilkins, Philadelphia,
2010, pg.: 20-32; 105-286.