Reynaldo B. Sta. Mina, Jr., M.D.

, MMHoA

DISORDERS OF EQUILIBRIUM
MED 7721 (CLINICAL NEUROLOGY)
 CONTENTS
▪ Learning Objectives  Sensory System
▪ Introduction  Reflexes
▪ Vertigo ▪ Investigative Studies
 Peripheral Vertigo  Blood Tests
 Central Vertigo  DNA Testing
 Cerebrospinal Fluid
▪ Ataxia
 CT & MR Imaging
 Vestibular Ataxia
 Evoked Potentials
 Cerebellar Ataxia
 Chest X-Ray & Echocardiography
 Sensory Ataxia
 Audiometry
▪ History  Electronystagmography
 Symptoms & Signs
▪ Peripheral Vestibular Disorders
 Onset & Time Course
 Benign Positional Vertigo
 Medical History
 Pathogenesis
 Family History  Clinical Findings
▪ General Physical Examination  Treatment
▪ Neurologic Examination  Meniere Disease
 Mental Status Examination  Pathogenesis
 Clinical Findings
 Stance & Gait  Treatment
 Cranial Nerves  Acute Peripheral Vestibulopathy
 Motor System  Otosclerosis
  Cerebellopontine Angle Tumor  Alcoholic Cerebellar Degeneration
 Pathogenesis  Toxin-Induced Cerebellar Degeneration
 Pathophysiology  Hypothyroidism
 Clinical Findings  Autoimmune Cerebellar Degeneration
 Differential Diagnosis  Autosomal Dominant Spinocerebellar Ataxia
 Treatment  Dentatorubral-Pallidoluysian Atrophy
 Toxic Vestibulopathies  Ataxia-Telangiectasia
 Alcohol  Fragile X-Associated Tremor/Ataxia Syndrome
 Aminoglycosides  Multiple System Atrophy
 Salicylates  Hepatocerebral Degeneration
 Quinine & Quinidine  Prion Diseases
 Cisplatin  Posterior Fossa Tumors
 Posterior Fossa Malformations
 Vestibulocochlear Neuropathy
▪ Sensory Ataxias
▪ Cerebellar & Central Vestibular Disorders
 Sensory Neuropathy or Neuronopathy
 Acute Disorders
 Drug Intoxication  Myelopathy
 Wernicke Encephalopathy  Combined Lesions
 Vertebrobasilar lschemia & Infarction  Friedreich Ataxia
 Cerebellar Hemorrhage ▪ YouTube Video Links
 Inflammatory Disorders
 Episodic Disorders ▪ Clinical Cases
 Motion Sickness ▪ Main Reference
 Vestibular Migraine ▪ Related Readings
 Autosomal Dominant Episodic Ataxias
 Chronic Disorders
 Multiple Sclerosis
 LEARNING OBJECTIVES

▪ To understand the concept of vertigo and ataxia

▪ To learn how to take history from, perform general physical and

neurologic examination in, and order diagnostic tests for a patient
complaining of symptoms related to vertigo or ataxia

▪ To determine the different disorders that cause vertigo and/or ataxia,

including their pathogenesis, pathophysiology, clinical findings,
differential diagnosis, and treatment
INTRODUCTION
▪ Equilibrium

 Ability to maintain ORIENTATION of the body and its parts in relation

to external space.

 Depends on continuous visual, labyrinthine, and proprioceptive

somatosensory input and its integration in the brainstem and
cerebellum.

 Disorders of equilibrium result from diseases that affect

 VESTIBULAR PATHWAYS (central or peripheral)
 CEREBELLUM
 SENSORY PATHWAYS involved in PROPRIOCEPTION
 Such disorders usually present with:
 Vertigo
 Ataxia
 VERTIGO
▪ ILLUSION OF MOVEMENT of the body or the
environment.

▪ May be associated with:

 IMPULSION (a sensation that the body is being hurled
or pulled in space)
 OSCILLOPSIA (a visual illusion of moving back and
forth)
 NAUSEA
 VOMITING
 GAIT ATAXIA

▪ Must be distinguished from NONVERTIGINOUS

DIZZINESS, which includes sensations of light-
headedness, faintness, or giddiness not
associated with an illusion of movement.
 In contrast to vertigo, these sensations are produced
by conditions that deprive the brain of blood, oxygen,
or glucose (eg, excessive vagal stimulation, orthostatic
hypotension, cardiac arrhythmia, myocardial ischemia,
hypoxia, or hypoglycemia) and may culminate in loss of
consciousness.
 VERTIGO

▪ FIRST STEP in the differential

diagnosis of vertigo is to localize
the pathologic process to the
peripheral or central vestibular
pathways.

▪ Certain characteristics of vertigo,

including the presence of any
associated abnormalities, can
help differentiate between
peripheral and central causes.
VERTIGO
PERIPHERAL VERTIGO

Peripheral vestibular lesions affect the

labyrinth of the inner ear or the vestibular
division of the vestibulocochlear (VIII)
nerve.

Tends to:
▪ Be intermittent
▪ Lasts for shorter periods
▪ Produces more distress than vertigo of central origin.

Nystagmus (rhythmic oscillation of the eyes)

is always present
 Usually unidirectional and never vertical.

Commonly produce additional symptoms:

▪ Hearing loss
▪ Tinnitus (the illusion of hearing a nonexistent sound, such as ringing in the
ears).
CENTRAL VERTIGO

Results from lesions that affect the

brainstem vestibular nuclei or their
connections

Rarely, vertigo is produced by a cerebral cortical lesion, such as when it

occurs as a symptom of focal seizures with impaired awareness
(complex partial seizures).

May occur with or without nystagmus

▪ If nystagmus is present, it can be vertical, unidirectional, or multidirectional and
may differ in character in the two eyes. (Vertical nystagmus is oscillation in a
vertical plane; nystagmus produced by upgaze or downgaze is not necessarily in
the vertical plane.)

May be accompanied by intrinsic brainstem or cerebellar signs, such as

motor or sensory deficits, hyperreflexia, extensor plantar responses,
dysarthria, or limb ataxia.
ATAXIA

▪ Incoordination or clumsiness of
movement that is not the result
of muscle weakness.

▪ Can be caused by vestibular,

cerebellar, or sensory
(proprioceptive) disorders.
 CEREBELLAR ATAXIA
 SENSORY ATAXIA
 VESTIBULAR ATAXIA

▪ Can affect eye movement,

speech (producing dysarthria),
individual limbs, the trunk,
stance, or gait.
VESTIBULAR ATAXIA

▪ The same central and peripheral lesions

that cause peripheral or central vertigo
can also produce vestibular ataxia.

▪ Nystagmus is frequently present and is

typically unilateral and most
pronounced on gaze away from the side
of vestibular involvement.

▪ Dysarthria is not a component of

vestibular ataxia.

▪ Gravity-dependent: Incoordination of
the limbs becomes apparent only when
the patient attempts to stand or walk.
CEREBELLAR ATAXIA

▪ Produced by lesions of the

cerebellum or its afferent or
efferent connections in the
cerebellar peduncles, red
nucleus, pons, or spinal
cord.

▪ Because of the crossed

connection between the
frontal cerebral cortex and
the cerebellum, unilateral
frontal disease can also
occasionally mimic a
disorder of the contralateral
cerebellar hemisphere.
▪ Clinical manifestations consist of
irregularities in the rate, rhythm, amplitude,
and force of voluntary movements.

 HYPOTONIA

 Cerebellar ataxia is commonly associated with

reduced muscle tone (hypotonia), which results
in defective posture maintenance.

 Limbs are easily displaced by a relatively small

force and, when shaken by the examiner, exhibit
an increased range of excursion.

 The range of arm swing during walking may be

similarly increased.

 Tendon reflexes take on a pendular quality, so

that several oscillations of the limb may occur
after the reflex is elicited.

 When muscles are contracted against resistance

that is then removed, the antagonist muscle
fails to check the movement and compensatory
muscular relaxation does not occur promptly.
This results in rebound movement of the limb.
 INCOORDINATION

 Simple movements are

delayed in onset, and their
rates of acceleration and
deceleration are decreased.

 The rate, rhythm,

amplitude, and force of
movements fluctuate, so
they appear jerky.

 Clinical manifestations
include terminal
dysmetria, or “overshoot”
when the limb is directed at
a target, and terminal
intention tremor as the
limb approaches the target.
  More complex movements may be
decomposed into a succession of
individual movements rather than
a single smooth act (ASYNERGIA).

 Movements that involve rapid

changes in direction or greater
physiologic complexity, such as
walking, are most affected.

 EYE MOVEMENT
ABNORMALITIES

 Because the cerebellum has a

prominent role in controlling eye
movements, ocular abnormalities
are common in cerebellar disease.
These include nystagmus and
related ocular oscillations, gaze
paresis, and defective saccadic
and pursuit movements.
 ANATOMIC BASIS OF
CLINICAL SIGNS

 MIDLINE LESIONS

 The middle zone of the

cerebellum [the vermis
and flocculonodular lobe
and their associated
subcortical (fastigial)
nuclei]

 Involved in the control of

axial functions, including
eye movements, head
and trunk posture,
stance, and gait.
 Characterized by nystagmus
and other disorders of
ocular motility, dysarthria,
oscillation of the head and
trunk (titubation),
instability of stance, and
gait ataxia.

 Selective involvement of the

superior cerebellar vermis,
as in alcoholic cerebellar
degeneration, produces
exclusively or primarily gait
ataxia, as predicted by the
somatotopic map of the
cerebellum.
Selective involvement of the superior cerebellar
vermis, as in alcoholic cerebellar degeneration,
produces exclusively or primarily gait ataxia, as
predicted by the somatotopic map of the cerebellum.
 HEMISPHERIC LESIONS

 The lateral cerebellum (cerebellar

hemispheres)

 Helps coordinate movements and

maintain tone in the ipsilateral
limbs.

 Regulate ipsilateral gaze.

 Disorders affecting one cerebellar

hemisphere cause ipsilateral
hemiataxia and limb hypotonia
as well as nystagmus and
transient ipsilateral gaze paresis
(inability to look voluntarily
toward the affected side).

 Involvement of the medial

(paravermian or intermediate)
portion of either cerebellar
hemisphere can also produce
dysarthria.
 DIFFUSE LESIONS

 Many cerebellar
disorders—typically
toxic, metabolic, and
degenerative
conditions—affect the
cerebellum diffusely.

 Clinical picture in such

states combines the
features of midline
and bilateral
hemisphere disease.
SENSORY ATAXIA

▪ Results from disorders

that affect the
proprioceptive pathways
in peripheral sensory
nerves, sensory roots,
posterior columns of the
spinal cord, or medial
lemnisci.

▪ Thalamic and parietal

lobe lesions are rare
causes of contralateral
sensory hemiataxia.
▪ Sensations of joint position and
movement (kinesthesis) originate
in unencapsulated nerve endings
(muscle spindles and Golgi tendon
organs) in joint capsules,
ligaments, muscle, and
periosteum.
▪ These sensations are transmitted
via heavily myelinated A fibers of
primary afferent neurons, which
enter the dorsal horn of the spinal
cord and ascend uncrossed in the
posterior columns.
▪ Proprioceptive information from the legs is
conveyed in the medially located fasciculus gracilis,
and information from the arms is conveyed in the
more laterally situated fasciculus cuneatus.
 These tracts synapse on
second-order sensory
neurons in the nucleus
gracilis and nucleus
cuneatus in the lower
medulla.

 The second-order neurons

decussate as internal
arcuate fibers and ascend
in the contralateral medial
lemniscus.

 They terminate in the

ventral posterior nucleus
of the thalamus, from
which third-order sensory
neurons project to the
parietal cortex.
▪ Sensory ataxia from
polyneuropathy or
posterior column lesions
typically affects the gait and
legs in symmetric fashion;
the arms are involved to a
lesser extent or are spared
entirely.

▪ Examination reveals
impaired sensation of joint
position in the affected
limbs, and vibration sense is
also commonly disturbed.

▪ Vertigo, nystagmus, and

dysarthria are
characteristically absent.
HISTORY
SYMPTOMS & SIGNS

▪ Vertigo

 True vertigo must be distinguished from a light-headed or

presyncopal sensation.

 Vertigo is typically described as spinning, rotating, or

moving.

 When the description is vague, the patient should be asked

specifically if the symptom is associated with a sense of
movement, of either the patient or the environment.
 The circumstances under which
symptoms occur may also be
diagnostically helpful.

 Vertigo is often brought on by

changes in head position.

 In contrast, symptoms that occur

upon arising after prolonged
recumbency suggest orthostatic
hypotension, and may be
relieved immediately by sitting
or lying down.
 Orthostatic hypotension and
other cerebral hypoperfusion
states can also lead to loss of
consciousness, which is rarely
associated with true vertigo.
 Symptoms associated with
vertigo may help to localize
the site of the causal lesion.

 Hearing loss or tinnitus

strongly suggests a disorder
of the peripheral vestibular
apparatus (labyrinth or
vestibulocochlear [VIII] nerve).

 Dysarthria, dysphagia,
diplopia, or focal weakness
or sensory loss affecting the
face or limbs points to a likely
central (brainstem) lesion.
▪ Ataxia

 Ataxia associated with vertigo

suggests a VESTIBULAR
DISORDER, whereas ataxia with
numbness or tingling in the legs is
common in patients with SENSORY
ATAXIA.

 Because proprioceptive deficits may

be partly compensated for by other
sensory cues, patients with sensory
ataxia may report that their balance
is improved by watching their feet
when they walk or by using a cane
or the arm of a companion for
support. Thus, they may be less
steady in the dark and have more
difficulty descending than
ascending stairs.
ONSET & TIME COURSE

▪ Sudden
 Sudden onset of disequilibrium, without a prior history of such events,
occurs with infarcts and hemorrhages in the brainstem or cerebellum
(eg, lateral medullary syndrome, cerebellar hemorrhage or infarction).
▪ Episodic
 Episodic disequilibrium of acute onset suggests transient ischemic
attacks in the basilar artery distribution, benign positional vertigo,
Meniere disease, or vestibular migraine.
 Disequilibrium from transient ischemic attacks is usually accompanied
by cranial nerve deficits, neurologic signs in the limbs, or both. Meniere
disease is usually associated with progressive hearing loss and tinnitus as
well as vertigo.
 Vestibular migraine produces headache or other migrainous symptoms.
▪ Chronic & Progressive
 Chronic, progressive disequilibrium evolving over weeks to months is
most suggestive of a toxic, nutritional, immune-mediated, or neoplastic
disorder.
 Evolution over months to years is characteristic of an inherited
spinocerebellar degeneration.
MEDICAL HISTORY
▪ Scrutinized for diseases that affect the sensory pathways
(vitamin B12 deficiency, syphilis), cerebellum (hypothyroidism),
or both (multiple sclerosis, tumors, paraneoplastic syndromes)
and for drugs that impair vestibular or cerebellar function
(ethanol, sedative drugs, phenytoin, aminoglycoside antibiotics,
quinine, salicylates).

FAMILY HISTORY
▪ A hereditary degenerative disorder may be the cause of chronic,
progressive cerebellar ataxia.
▪ Such disorders include spinocerebellar degenerations, Friedreich
ataxia, ataxia-telangiectasia, and Wilson disease.
 GENERAL PHYSICAL EXAMINATION
1. Orthostatic hypotension is
associated with tabes dorsalis,
polyneuropathies, and
spinocerebellar degenerations.

2. Skin may show oculocutaneous

telangiectasia (ataxia-
telangiectasia), or it may be dry
with brittle hair (hypothyroidism) or
have a lemon-yellow coloration
(vitamin B12 deficiency).
3. Pigmented corneal (Kayser–
Fleischer) rings are seen in
Wilson disease.

4. Skeletal abnormalities include

kyphoscoliosis in Friedreich
ataxia, hypertrophic or
hyperextensible joints in tabes
dorsalis, and pes cavus in certain
hereditary neuropathies.

Abnormalities at the
craniocervical junction may be
associated with Arnold–Chiari
malformation or other congenital
anomalies involving the posterior
fossa.
NEUROLOGIC EXAMINATION
MENTAL STATUS EXAMINATION

▪ Acute confusional state with ataxia

suggests ethanol or sedative drug
intoxication or Wernicke encephalopathy.

▪ Dementia with cerebellar ataxia is seen in Wilson disease, prion diseases

(Creutzfeldt–Jakob disease and Gerstmann–Straussler-Scheinker
syndrome), hypothyroidism, paraneoplastic syndromes, and some
spinocerebellar degenerations.

▪ Dementia with sensory ataxia suggests syphilitic taboparesis or vitamin

B12 deficiency.

▪ Amnesia and cerebellar ataxia are associated with chronic alcoholism

(Korsakoff amnestic syndrome).
STANCE & GAIT

▪ Observation of stance and gait is helpful for

distinguishing among vestibular, cerebellar, and
sensory ataxia.

▪ Ataxia from any cause can produce a wide-based

and unsteady stance and gait, often associated
with reeling or lurching movements.

▪ Stance
 An ataxic patient asked to stand with the feet together may be reluctant or unable to
do so. With urging, the patient may gradually move the feet closer together but will
typically leave some space between them.

 1. Patients with sensory ataxia and some with vestibular ataxia may be able to
stand with the feet together and eyes open, using vision to compensate for the loss
of proprioceptive or labyrinthine input. When the eyes are closed, eliminating visual
cues, there is increased unsteadiness and sometimes falling (Romberg sign). With a
vestibular lesion, the tendency is to fall toward the side of the lesion.

 2. Patients with cerebellar ataxia cannot compensate for their deficit using visual
input, and are unstable on their feet whether the eyes are open or closed.
▪ Gait
 1. The gait in CEREBELLAR ATAXIA is wide-based, often with a staggering
quality that can suggest drunkenness. Oscillation of the head or trunk
(titubation) may be present. With a unilateral cerebellar hemisphere lesion,
there is a tendency to deviate toward the side of the lesion when the patient
tries to walk in a straight line or circle or marches in place with eyes closed.
Tandem (heel-to-toe) gait, which requires walking with an especially
narrow base, is always impaired in cerebellar ataxia.

 2. In SENSORY ATAXIA, the gait is also wide-based, and tandem gait is

poor. In addition, the feet are typically lifted high off the ground and slapped
down heavily (steppage gait) to enhance proprioceptive input. Stability
may be dramatically improved by letting the patient use a cane or lightly rest a
hand on the examiner’s arm for support. If the patient attempts to walk in the
dark or with eyes closed, gait is much more impaired.

 3. Gait ataxia may also be a manifestation of conversion

disorder or malingering. The most helpful observation in
identifying factitious gait ataxia is that such patients may
exhibit wildly reeling or lurching movements from which
they are able to recover without falling, whereas recovery
from such awkward positions actually requires excellent
equilibrium.
CRANIAL NERVES
▪ Abnormalities of extraocular (III, IV, and VI) and vestibulocochlear
(VIII) nerve function are typically present with vestibular disease
and often present with lesions of the cerebellum.

▪ Eye Movements
 1. The eyes are examined in the primary position of gaze (looking
directly forward) to detect misalignment in the horizontal or vertical
plane.

 2. The patient is asked to turn the eyes in each of the cardinal directions
of gaze to detect ocular nerve palsy or gaze paresis (inability to move
the two eyes coordinately in any of the cardinal directions of gaze).

 3. Nystagmus—an involuntary oscillation of the eyes—is characterized

in terms of the positions of gaze in which it occurs (gaze-evoked
nystagmus), its amplitude, and the direction of its fast phase. Pendular
nystagmus, usually due to visual impairment beginning in infancy, has
the same velocity in both directions, whereas jerk nystagmus has fast
(vestibular-induced) and slow (cortical) phases. The direction of jerk
nystagmus is defined by the direction of the fast component.
 4. Fast voluntary eye movements (saccades) are elicited by
having the patient rapidly shift gaze between targets in different
regions of the visual field. Slow voluntary eye movements
(pursuits) are assessed by having the patient track a slowly
moving target such as the examiner’s finger.

 5. Peripheral vestibular disorders produce unidirectional

horizontal jerk nystagmus that is maximal on gaze away from
the involved side.

 6. Central vestibular disorders can cause unidirectional or

bidirectional horizontal nystagmus, vertical nystagmus, or
gaze paresis.

 7. Cerebellar lesions are associated with a wide range of ocular

abnormalities, including gaze paresis, defective saccades or
pursuits, nystagmus in any or all directions, and ocular
dysmetria (overshoot of visual targets during saccadic eye
movement).
▪ Hearing
 Preliminary examination of the vestibulocochlear (VIII)
nerve should include otoscopic inspection of the auditory
canals and tympanic membranes, assessment of auditory
acuity in each ear, and Weber and Rinne tests performed
with a 256-Hz tuning fork.

 1. In the Weber test, unilateral sensorineural hearing loss

(from lesions of the cochlea or vestibulocochlear nerve)
causes the patient to perceive the sound produced by a
vibrating tuning fork placed at the vertex of the skull as
coming from the normal ear. With a conductive (external
or middle ear) disorder, sound is localized to the abnormal
ear.

 2. The Rinne test may also distinguish between

sensorineural and conductive defects in the affected ear.
Air conduction (tested by holding the vibrating tuning fork
next to the external auditory canal) normally produces a
louder sound than does bone conduction (tested by
placing the base of the tuning fork over the mastoid bone).
This also occurs with sensorineural hearing loss due to
vestibulocochlear nerve lesions but is reversed in
conductive hearing loss.
▪ Positional Vertigo Testing

 When vertigo occurs with a change in position, the Nylen–Barany

or Dix–Hallpike maneuver is used to try to reproduce the
precipitating circumstance. The head is rapidly lowered 30-45
degrees below horizontal and the eyes are observed for
nystagmus, while the patient is asked to note the onset, severity,
and cessation of vertigo. This is repeated with the head and eyes
turned first to the right and then to the left.

 Positional nystagmus and vertigo are usually associated with

peripheral vestibular lesions and are most often a feature of
benign positional vertigo. This is typically characterized by
severe distress, a latency of several seconds between
assumption of the position and the onset of vertigo and
nystagmus, a tendency for the response to remit spontaneously
(fatigue) as the position is maintained, and attenuation of the
response (habituation) as the offending position is repeatedly
assumed.

 Positional vertigo can also occur with central vestibular disease.

Nylen–Barany or
Dix–Hallpike maneuver
▪ Caloric Testing
 Should be preceded by careful otoscopic
examination and should not be undertaken if the
tympanic membrane is perforated.

 The patient is placed supine with the head elevated

30 degrees to bring the superficially situated lateral
semicircular canal into the upright position. Each ear
canal is irrigated in turn with cold (~33°C) or warm
(~44°C) water for 40 seconds, with at least 5 minutes
between tests. Warm water tends to produce less
discomfort than cold.

 1. In the normal, awake patient, cold-water caloric

stimulation produces nystagmus with the slow
phase toward and the fast phase away from the
irrigated ear. Warm water irrigation produces the
opposite response and is generally better tolerated.

 2. In patients with unilateral labyrinthine,

vestibulocochlear (VIII) nerve, or vestibular nuclear
dysfunction, irrigation of the affected side fails to
cause nystagmus or elicits nystagmus that is later in
onset or briefer in duration than on the normal side.
▪ Other Cranial Nerves

 Papilledema associated with disequilibrium

suggests an intracranial mass lesion,
usually in the posterior fossa, causing
increased intracranial pressure.

 Optic atrophy may be present in multiple

sclerosis, neurosyphilis, or vitamin B12
deficiency.

 A depressed corneal reflex or facial palsy
ipsilateral to the lesion (and the ataxia) can
accompany cerebellopontine angle tumor.

 Weakness of the tongue or palate,

hoarseness, or dysphagia results from
lower brainstem disease.
MOTOR SYSTEM
▪ Examination of motor function in a patient with a disorder of
equilibrium should disclose the pattern and severity of ataxia and
any associated pyramidal, extrapyramidal, or lower motor
neuron involvement that might suggest a cause.

▪ Muscle Tone

 1. Hypotonia is characteristic of cerebellar disorders; with unilateral

cerebellar hemispheric lesions, the ipsilateral limbs are hypotonic.

 2. Extrapyramidal hypertonia (rigidity) may occur in disorders that

affect both the cerebellum and basal ganglia (eg, Wilson disease,
acquired hepatocerebral degeneration, and some spinocerebellar
ataxias).

 3. Ataxia with spasticity may be seen in conditions that affect both the
cerebellum and upper motor neuron pathways (eg, multiple sclerosis,
posterior fossa tumors or congenital anomalies, vertebrobasilar
infarction, some spinocerebellar ataxias, Friedreich ataxia, and vitamin
B12 deficiency).
▪ Coordination

 1. Truncal stability is assessed by examining gait (discussed

earlier) and by observing the seated, unsupported patient.
In addition to gait ataxia, patients may show oscillation of
the head or trunk (titubation) and truncal ataxia while
seated, causing a tendency to fall (toward the affected
side with a lateralized cerebellar lesion).

 2. Movement of the arm is observed as the patient’s finger

tracks back and forth between his or her own nose or chin
and the examiner’s finger (FINGER-TO-NOSE TEST). With
cerebellar ataxia, an intention tremor characteristically
appears near the beginning and end of each such
movement, and the patient may overshoot the target.
 .
 3. When the patient is asked to raise the arms rapidly to a given height—or
when the extended and outstretched arms are displaced by a sudden
force—there may be overshoot (rebound). Impaired ability to check the
force of muscle contractions can also be demonstrated by having the
patient flex the arm at the elbow against resistance, and then suddenly
removing the resistance. If the limb is ataxic, continued contraction
without resistance may cause the hand to strike the patient (whose head
should be turned to the side to avoid being hit in the face).

 4. Ataxia of the legs is demonstrated by the supine patient’s inability to

run the heel of the foot smoothly up and down the opposite shin (HEEL-
TO-SHIN TEST).

 5. Ataxia of any limb is reflected by irregularity in the rate, rhythm,

amplitude, and force of rapid successive tapping movements.
▪ Weakness

 1. Pure vestibular, cerebellar, or sensory disorders do not

cause weakness, but weakness may occur in disorders that
also affect motor pathways.

 2. Distal weakness can be seen in disorders that produce

sensory ataxia, such as polyneuropathies and Friedreich
ataxia.

 3. Paraparesis may be superimposed on ataxia in vitamin

B12 deficiency, multiple sclerosis, foramen magnum
lesions, or spinal cord tumors.

 4. Ataxic quadriparesis, hemiataxia with contralateral

hemiparesis, or ataxic hemiparesis suggests a brainstem
lesion.
▪ Abnormal Involuntary Movements

 1. Chorea or parkinsonism may accompany cerebellar signs in

multiple system atrophy, Wilson disease, acquired
hepatocerebral degeneration, certain autosomal dominant
spinocerebellar ataxias (eg, SCA3 or Machado–Joseph disease),
dentatorubral-pallidoluysian atrophy, and ataxia-
telangiectasia.

 2. Myoclonus is a prominent manifestation of Creutzfeldt–

Jakob disease and dentatorubral-pallidoluysian atrophy, both
of which may also produce ataxia.
SENSORY SYSTEM

▪ Joint Position Sense

 In sensory ataxia, joint position sense is always impaired in the legs and may be
defective in the arms. Joint position sense is tested by asking the patient to
detect passive movement of the joints, beginning distally and moving
proximally, to establish the upper level of any deficit in each limb. With normal
joint position sense, it should be possible to detect even the smallest
displacement of a joint by the examiner. Abnormal position sense also can be
demonstrated by positioning a limb and having the patient, with eyes closed,
place the opposite limb in the same position.

▪ Vibration Sense
 Vibration sense is also frequently impaired in sensory ataxia. The patient is
asked to detect vibration of a 128-Hz tuning fork placed on a bony prominence.
Successively more proximal sites are tested to determine the upper level of the
deficit in each limb. The patient’s threshold for detecting vibration is compared
with the examiner’s ability to detect it in the hand that holds the tuning fork.
REFLEXES

▪ 1. Tendon reflexes are typically hypoactive, with a pendular

quality, in cerebellar disorders; unilateral cerebellar lesions
produce ipsilateral hyporeflexia.

▪ 2. Hyporeflexia of the legs is a prominent manifestation of

Friedreich ataxia, tabes dorsalis, and polyneuropathies that cause
sensory ataxia.

▪ 3. Hyperactive reflexes and extensor plantar responses may

accompany ataxia caused by multiple sclerosis, vitamin B12
deficiency, focal brainstem lesions, and certain autosomal
dominant spinocerebellar ataxias.
INVESTIGATIVE STUDIES
BLOOD TESTS
▪ Blood studies may disclose low vitamin B12 levels and hematologic
abnormalities (macrocytic anemia, leukopenia with hypersegmented
neutrophils, thrombocytopenia with giant platelets) in vitamin B12
deficiency, decreased levels of thyroid hormones in hypothyroidism,
elevated hepatic enzymes and low ceruloplasmin and copper
concentrations in Wilson disease, immunoglobulin deficiency and
elevated α-fetoprotein in ataxia-telangiectasia, or autoantibodies in
autoimmune (including paraneoplastic) cerebellar degenerations.

DNA TESTING
▪ Blood, saliva, and other sources can be tested for gene defects
associated with a variety of disorders that cause disorders of
equilibrium. These include certain autosomal dominant spinocerebellar
ataxias, dentatorubral-pallidoluysian atrophy, ataxia-telangiectasia,
fragile X-associated tremor/ataxia syndrome, and Friedreich ataxia.
CEREBROSPINAL FLUID
▪ The cerebrospinal fluid (CSF) shows elevated protein with cerebellopontine
angle, brainstem, or spinal cord tumors; hypothyroidism; and some
polyneuropathies.
▪ Increased protein concentration with pleocytosis is found in infectious or
parainfectious encephalitis, paraneoplastic cerebellar degeneration, and
neurosyphilis.
▪ Elevated pressure and bloody CSF characterize cerebellar hemorrhage, but
lumbar puncture is contraindicated if cerebellar hemorrhage is suspected.
▪ CSF VDRL is reactive in tabes dorsalis, and oligoclonal immunoglobulin G (IgG)
bands may be present in multiple sclerosis or other inflammatory disorders.

CT & MR IMAGING
▪ Computed tomography (CT) can demonstrate posterior fossa tumors or
malformations, cerebellar infarction or hemorrhage, and cerebellar or brainstem
atrophy associated with degenerative disorders (eg, spinocerebellar ataxias).
▪ Magnetic resonance imaging (MRI) provides better visualization of posterior
fossa lesions, including cerebellopontine angle tumors, and is superior to CT for
detecting lesions of multiple sclerosis. MRI can also detect endolymphatic
hydrops in the inner ear in Meniere disease.
EVOKED POTENTIALS
▪ Visual evoked potentials may be helpful in evaluating patients with suspected
multiple sclerosis. Brainstem auditory evoked potentials can localize disease to
peripheral vestibular pathways and help identify cerebellopontine angle tumors.
CHEST X-RAY & ECHOCARDIOGRAPHY
▪ The chest X-ray may reveal a lung tumor in paraneoplastic cerebellar
degeneration, and the chest X-ray or echocardiogram may provide evidence of
cardiomyopathy associated with Friedreich ataxia.
AUDIOMETRY
▪ This is useful in vestibular disorders associated with auditory impairment and
can distinguish conductive, labyrinthine, vestibulocochlear (VIII) nerve, and
brainstem disease. Tests of pure tone hearing are abnormal when sounds are
transmitted through air with conductive hearing loss and when transmitted
through either air or bone with labyrinthine or vestibulocochlear (VIII) nerve
disorders.
▪ Speech discrimination is markedly impaired with vestibulocochlear (VIII) nerve
lesions, less impaired in labyrinthine disorders, and normal with conductive
hearing loss or brainstem disease.
ELECTRONYSTAGMOGRAPHY
▪ This can detect and characterize nystagmus, including that elicited by caloric
stimulation.
PERIPHERAL VESTIBULAR DISORDERS
 BENIGN POSITIONAL VERTIGO
Positional vertigo is vertigo that occurs upon
changing head position. It is usually associated with
peripheral vestibular lesions, but also may be due to
central (brainstem or cerebellar) disease.

PATHOGENESIS
▪ Benign positional vertigo is the most common cause of vertigo of
peripheral origin. It results from canalolithiasis, in which debris
(otoconia) floating in the endolymph stimulates a semicircular canal,
most often the posterior canal.
▪ Benign positional vertigo may follow head trauma, but in most
instances, no precipitating factor can be determined.
▪ When head trauma is the cause, the labyrinth is the usual site of
injury. However, fractures of the petrosal bone may lacerate the
vestibulocochlear (VIII) nerve, producing vertigo and hearing loss;
hemotympanum or CSF otorrhea suggests such a fracture.
CLINICAL FINDINGS
▪ The syndrome is characterized by brief (seconds to minutes) episodes of severe
vertigo and nystagmus, which may be accompanied by nausea and vomiting.
▪ Symptoms may occur with any change in head position but are usually most severe
in the lateral decubitus position with the affected ear down.
▪ Episodic vertigo typically continues for several weeks and then resolves
spontaneously; in some cases, it is recurrent.
▪ Hearing loss is not a feature.
▪ Peripheral and central causes of positional vertigo usually can be distinguished by the
Nylen–Barany or Dix–Hallpike maneuver.
▪ Vertigo evoked by this maneuver is always accompanied by positional nystagmus
when the underlying cause is peripheral, and is typically unidirectional, rotatory, and
delayed in onset by several seconds after assumption of the precipitating head
position. If the position is maintained, nystagmus and vertigo resolve within seconds
to minutes. If the maneuver is repeated, the response is attenuated.
▪ In contrast, positional vertigo of central origin tends to be less severe, and positional
nystagmus may be absent. In contrast, there is no latency, fatigue, or habituation in
central positional vertigo.
▪ When benign positional vertigo is documented in this manner, no additional
diagnostic investigation (eg, auditory or vestibular testing or imaging) is required.
TREATMENT
▪ The mainstay of treatment is repositioning (Epley) maneuvers,
which use gravity to move endolymphatic debris out of the
semicircular canal and into the vestibule, where it can be
reabsorbed. In one such maneuver, the head is turned 45 degrees
in the direction of the affected ear (determined clinically, as
described earlier), and the patient reclines to a supine position,
with the head (still turned 45 degrees) hanging down over the
end of the examining table. The head, still hanging down, is then
turned 90 degrees in the opposite direction, to 45 degrees
toward the opposite ear. Next, the patient rolls to a lateral
decubitus position with the affected ear up, and the head still
turned 45 degrees toward the unaffected ear and hanging down.
Finally, the patient turns to a prone position and sits up.
▪ Vestibulo-suppressant drugs may also be useful in the acute
period.
▪ Vestibular rehabilitation, which promotes compensation for
vestibular dysfunction through the recruitment of other sensory
modalities, may also be helpful.
Repositioning treatment for benign positional
vertigo resulting from canalolithiasis.

In the example shown, repositioning maneuvers

are used to move endolymphatic debris out of the
posterior semicircular canal (PSC) of the right
ear and into the utricle (UT), the larger of two
membranous sacs in the vestibule of the
labyrinth, where this debris can be reabsorbed.

The numbers (1-6) refer to both the position of

the patient and the corresponding location of
debris within the labyrinth.
The patient is seated, and the head is turned 45
degrees to the right (1).

The head is lowered rapidly to below the

horizontal (2); the examiner shifts position
(3); and the head is rotated rapidly 90 degrees
in the opposite direction, so it now points 45
degrees to the left, where it remains for 30
seconds (4).

The patient then rolls onto the left side

without turning the head in relation to the body
and maintains this position for another 30
seconds (5) before sitting up (6).

This maneuver may need to be repeated until

nystagmus is abolished.

The patient must then avoid the supine position

for at least 2 days.
MENIERE’S DISEASE
Meniere disease is characterized by repeated episodes of vertigo lasting
from ~20 minutes to ~12 hours, accompanied by tinnitus and
progressive, low- to medium frequency sensorineural hearing loss.
It is thought to be the second most common peripheral cause of vertigo,
after benign positional vertigo.

PATHOGENESIS
▪ Most cases are sporadic, but up to ~10% cluster in families.
▪ Onset is usually between ages 20 and 50 years, and men are affected
more often than women.
▪ Symptoms are thought to result from an increase
in the volume of labyrinthine endolymph
(endolymphatic hydrops), which results in distension
of the endolymphatic space and its encroachment on
the perilymphatic space.
▪ The cochlear duct and saccule are affected most often.
▪ The cause of endolymphatic hydrops is unknown,
but immune mechanisms may be involved.
CLINICAL FINDINGS
▪ At the time of the first acute attack, patients already may have noted
the insidious onset of tinnitus, hearing loss, and a sensation of fullness in
the ear. Acute attacks are characterized by vertigo, nausea, and
vomiting and recur at intervals ranging from weeks to years.
▪ Hearing deteriorates in a stepwise fashion, with bilateral involvement in
~15% to ~50% of patients.
▪ As hearing loss increases, vertigo tends to become less severe.
▪ Physical examination during an acute episode shows spontaneous
horizontal or rotatory nystagmus (or both) that may change direction.
▪ Although spontaneous nystagmus is characteristically absent between
attacks, caloric testing usually reveals impaired vestibular function.
▪ Hearing deficit is not always sufficiently advanced to be detectable at
the bedside.
▪ Audiometry shows low-frequency pure-tone hearing loss that fluctuates
in severity, impaired speech discrimination, and increased sensitivity to
loud sounds.
▪ Endolymphatic hydrops can be demonstrated
by MRI.
TREATMENT

▪ Between episodes, patients may be treated with a low-salt

diet and diuretics, such as hydrochlorothiazide (50 mg
orally daily) plus triamterene (25 mg orally daily), or with
the histamine H3 receptor antagonist betahistine (16-48
mg orally three times daily).
▪ In persistent, disabling cases, vestibular ablation by
intratympanic gentamicin, vestibular (VIII) nerve section,
or labyrinthectomy may be beneficial.
ACUTE PERIPHERAL
VESTIBULOPATHY

▪ This term is used to describe a spontaneous attack of vertigo of

inapparent cause that resolves spontaneously and is not
accompanied by hearing loss or central nervous system
dysfunction.
▪ It includes disorders diagnosed as acute labyrinthitis or
vestibular neuronitis and may follow a febrile illness.
▪ May result from viral infection (eg, reactivation of latent herpes
simplex virus in vestibular ganglia), but this association has never
been proven.
▪ Considered the third most common cause of peripheral vertigo,
after benign positional vertigo and Meniere disease.
▪ The disorder is characterized by the acute onset of vertigo,
nausea, and vomiting, typically lasting up to 2 weeks.
▪ Symptoms may recur, and some degree of vestibular
dysfunction may be permanent.
▪ During an attack, the patient appears acutely ill, typically
lies on one side with the affected ear upward, and is
reluctant to move the head.
▪ Nystagmus with the fast phase away from the affected ear
is always present.
▪ The vestibular response to caloric testing is defective in one
or both ears but auditory acuity is normal.
▪ Acute peripheral vestibulopathy must be distinguished
from central causes of acute vertigo; the latter are
suggested by vertical nystagmus, altered consciousness,
motor or sensory deficit, or dysarthria.
▪ Treatment of acute peripheral vestibulopathy is with a 10-
to 14-day course of prednisone (20 mg orally twice daily),
the drugs listed in the Table below, or both.
OTOSCLEROSIS

▪ Otosclerosis is caused by immobility of the stapes.

▪ Its most distinctive feature is bilateral conductive
hearing loss, but sensorineural hearing loss and
recurrent episodic vertigo may also occur, whereas
tinnitus is infrequent.
▪ Auditory symptoms usually begin before 30 years of
age, and familial occurrence is common.
▪ Imaging studies may be diagnostically useful.
▪ Sodium fluoride, vitamin D, intratympanic
dexamethasone, and surgical stapedectomy are
recognized treatments.
CEREBELLOPONTINE ANGLE TUMOR
PATHOGENESIS
▪ The most common tumor in the cerebellopontine angle—a triangular
region in the posterior fossa bordered by the cerebellum, lateral pons,
and petrous ridge—is the histologically benign acoustic neuroma.
▪ Also termed neurilemoma, neurinoma, or schwannoma, it typically
arises from the neurilemmal sheath of the vestibular portion of the
vestibulocochlear (VIII) nerve in the internal auditory canal.
▪ Less common tumors at this site include meningiomas, epidermoid
tumors, and lipomas.
▪ Acoustic neuromas usually occur as isolated lesions in patients 30 to 60
years old, but may also be a manifestation of neurofibromatosis.
▪ Neurofibromatosis 1 (von Recklinghausen disease) is a
common autosomal dominant disorder arising from mutations in
the gene for neurofibromin 1 (NF1). Characterized by unilateral
acoustic neuromas, neurofibromatosis 1 is associated with cafe-
au-lait spots on the skin, cutaneous neurofibromas, axillary or
inguinal freckles, optic gliomas, iris hamartomas, and dysplastic
bony lesions.

▪ Neurofibromatosis 2 is a rare autosomal dominant disorder

caused by mutations in the gene for merlin (NF2). Its hallmark is
bilateral acoustic neuromas, which may be accompanied by other
central or peripheral nervous system tumors, including
neurofibromas, meningiomas, gliomas, and schwannomas.

PATHOPHYSIOLOGY
▪ Cerebellopontine angle tumors produce symptoms by
compressing or displacing the cranial nerves, brainstem, and
cerebellum and by obstructing CSF flow.
▪ Because of their anatomic relationship to the vestibulocochlear
(VIII) nerve, the trigeminal (V) and facial (VII) nerves are often
affected.
CLINICAL FINDINGS

▪ Symptoms & Signs

 Insidious hearing loss is usually the initial symptom. Less often, patients present
with headache, vertigo, gait ataxia, facial pain, tinnitus, a sensation of fullness in
the ear, or facial weakness.
 Vertigo ultimately develops in 20% to 30% of patients, but nonspecific
unsteadiness is more common.
 Symptoms may be stable or progress over months or years.
 Unilateral sensorineural hearing loss is the most common finding on examination.
 Other frequent findings are ipsilateral facial palsy, depressed or absent corneal
reflex, and sensory loss over the face. Ataxia, spontaneous nystagmus, other
lower cranial nerve palsies, and signs of increased intracranial pressure are less
common.
 Unilateral vestibular dysfunction can usually be demonstrated with caloric
testing.
▪ Laboratory Findings
 Audiometry shows a sensorineural deficit with high-frequency pure-tone hearing
loss, poor speech discrimination, and marked tone decay.
 CSF protein is elevated in approximately 70% of patients, usually in the range of
50 to 200 mg/dL.
 The most useful imaging study is MRI of the cerebellopontine angle.
 Acoustic neuromas may cause abnormal brainstem auditory evoked potentials.
DIFFERENTIAL DIAGNOSIS
▪ Meningioma should be considered in patients who present
with more than isolated vestibulocochlear (VIII) nerve
disease.
▪ Cholesteatoma is suggested by conductive hearing loss,
early facial weakness, or facial twitching, with normal CSF
protein.
▪ Metastatic carcinoma may also present as a lesion in the
cerebellopontine angle.

TREATMENT
▪ Treatment is complete surgical excision.
▪ Patients with acoustic neuroma and neurofibromatosis 2
may benefit from bevacizumab, a monoclonal antibody
against vascular endothelial growth factor (VEGFA).
▪ In untreated cases, severe complications can result from
brainstem compression or hydrocephalus.
TOXIC VESTIBULOPATHIES
ALCOHOL
▪ Alcohol can cause acute positional vertigo beginning as early as
~30 minutes after ingesting amounts sufficient to produce blood
levels ≥40 mg/dL.
▪ Alcohol diffuses into the cupula, then into the endolymph, leaves
the cupula, and finally leaves the endolymph. Because alcohol is
less dense than endolymph, this renders the peripheral vestibular
system gravity-sensitive, resulting in two phases of vertigo that
together last up to ~12 hours.
▪ During the first phase, the cupula is lighter than endolymph, and
vertigo is accompanied by nystagmus that beats toward the
lower ear with the patient in the lateral recumbent position.
About 3.5-5 hours after this phase resolves, as endolymph
becomes heavier than the cupula, vertigo returns, with
nystagmus that beats toward the upper ear in lateral
recumbency.
AMINOGLYCOSIDES
▪ Aminoglycoside antibiotics are widely recognized ototoxins that can
produce both vestibular and auditory symptoms.
▪ Streptomycin, gentamicin, and tobramycin are the agents most likely to
cause vestibular toxicity, and amikacin, kanamycin, and tobramycin are
associated with hearing loss.
▪ Aminoglycosides concentrate in the perilymph and endolymph and
exert their ototoxic effects by destroying sensory hair cells.
▪ The risk of toxicity is related to drug dosage, plasma concentration,
duration of therapy, conditions—such as renal failure—that impair drug
clearance, preexisting vestibular or cochlear dysfunction, and
concomitant administration of other ototoxic agents.
▪ Symptoms of vertigo, nausea, vomiting, and gait ataxia may begin
acutely; physical findings include spontaneous nystagmus and the
Romberg sign.
▪ The acute phase typically lasts 1 to 2 weeks and is followed by gradual
improvement.
▪ Prolonged or repeated aminoglycoside therapy may be associated with
chronic, progressive vestibular dysfunction.
SALICYLATES
▪ Salicylates, when used chronically and in high doses, can cause vertigo, tinnitus, and sensorineural
hearing loss—all usually reversible when the drug is discontinued.
▪ Symptoms result from cochlear and vestibular end-organ damage.
▪ Salicylism is characterized by headache, tinnitus, hearing loss, vertigo, nausea, vomiting, thirst,
hyperventilation, and sometimes a confusional state.
▪ Severe intoxication may be associated with fever, skin rash, hemorrhage, dehydration, seizures,
psychosis, or coma.
▪ Laboratory findings include a high plasma salicylate level (≥0.35 mg/mL) and combined metabolic
acidosis and respiratory alkalosis.
▪ Treatments include gastric lavage, activated charcoal, forced diuresis, peritoneal dialysis or
hemodialysis, and hemoperfusion.
QUININE & QUINIDINE
▪ Quinine and quinidine can produce cinchonism, which resembles salicylate intoxication in many
respects.
▪ Manifestations include tinnitus, impaired hearing, vertigo, visual deficits (including disordered
color vision), nausea, vomiting, abdominal pain, hot flushed skin, and sweating.
▪ Fever, encephalopathy, coma, and death can occur.
▪ Symptoms usually result from overdosage, but can also be due to idiosyncratic reactions to
therapeutic doses.
CISPLATIN
▪ Cisplatin is an antineoplastic drug used to treat solid tumors of the ovary, testis, uterine cervix,
lung, head and neck, bladder, and other tissues. It causes ototoxicity, which is commonly bilateral
and irreversible, in a high percentage of patients.
▪ Tinnitus, hearing loss, and vestibular dysfunction may all occur.
VESTIBULOCOCCHLEAR
NEUROPATHY
▪ Involvement of the vestibulocochlear (VIII) nerve by
systemic disease is an uncommon cause of vertigo.
▪
▪ Basilar meningitis from bacterial, syphilitic, or tuberculous
infection or sarcoidosis can compress the vestibulocochlear
and other cranial nerves, but hearing loss is a more
common consequence than vertigo.

▪ Metabolic disorders associated with vestibulocochlear

neuropathy include hypothyroidism, diabetes, and Paget
disease.
CEREBELLAR & CENTRAL
VESTIBULAR DISORDERS
▪ Many disorders can
produce acute or chronic
cerebellar dysfunction.

▪ Some of these may also

involve central vestibular
pathways (eg, Wernicke
encephalopathy,
vertebrobasilar ischemia or
infarction, multiple
sclerosis, and posterior
fossa tumors).

▪ For this reason, cerebellar

and central vestibular
disorders are considered
together here.
ACUTE DISORDERS
DRUG INTOXICATION

▪ PANCEREBELLAR DYSFUNCTION — manifested by

nystagmus, dysarthria, and limb and gait ataxia—is a
prominent feature of intoxication with ethanol, sedative-
hypnotics, anticonvulsants, and some hallucinogens.

▪ The severity of symptoms is dose-related; therapeutic

doses of sedatives or anticonvulsants commonly produce
nystagmus, but other cerebellar signs imply toxicity.

▪ Drug-induced cerebellar ataxia is often associated with

altered consciousness.
WERNICKE ENCEPHALOPATHY

▪ Pathogenesis
 Wernicke encephalopathy is an acute disorder comprising the clinical triad of
ataxia, ophthalmoplegia, and confusion.
 It is caused by thiamine (vitamin B1) deficiency and is most common in chronic
alcoholics, but may occur as a consequence of malnutrition from any cause.
▪ Clinical Findings
 Cerebellar and vestibular involvement both contribute to ataxia, which affects
gait primarily or exclusively; the legs are ataxic in only about 20% of patients, and
the arms in 10%.
 Dysarthria is rare.
 Other findings include an amnestic syndrome or global confusional state,
horizontal or combined horizontal and vertical nystagmus, bilateral lateral rectus
palsy, and absent ankle reflexes.
 Caloric testing shows bilateral or unilateral vestibular dysfunction.
 Conjugate gaze palsy, pupillary abnormalities, and hypothermia can occur.
▪ Diagnosis & Treatment
 The diagnosis should be suspected in alcoholic and other malnourished patients
and is confirmed by the clinical response to thiamine.
 Ocular palsies improve within hours and ataxia, nystagmus, and confusion within
a few days.
 Horizontal nystagmus may persist.
 Ataxia is fully reversible in only approximately 40% of patients, in whom recovery
takes weeks to months.
VERTEBROBASILAR ISCHEMIA &
INFARCTION

▪ Transient ischemic attacks and

strokes in the vertebrobasilar system
are often associated with ataxia or
vertigo.

Internal Auditory Artery Occlusion

 The internal auditory (labyrinthine)
artery originates from the anterior
inferior cerebellar (or, less commonly,
basilar) artery and supplies the
vestibulocochlear (VIII) nerve.

 Isolated occlusion of the labyrinthine

artery causes vertigo and nystagmus,
with the fast phase directed away from
the involved side, and unilateral
sensorineural hearing loss.
Principal arteries of the posterior fossa.
Lateral Medullary Infarction

 Lateral medullary infarction, which is caused by

occlusion of the proximal vertebral artery and, less
often, the posterior inferior cerebellar artery,
produces Wallenberg syndrome.

 Clinical manifestations vary, but the most common

are listed here, together with their likely anatomic
correlates.

 1. Vertigo, nausea, vomiting, and nystagmus

(vestibular nucleus)
 2. Loss of pain and temperature sense over the
contralateral limbs and trunk (lateral
spinothalamic tract)
 3. Loss of pain and temperature sense over the
ipsilateral face (spinal trigeminal nucleus and tract)
 4. Truncal and gait ataxia (vestibular nucleus and
inferior cerebellar peduncle)
 5. Ipsilateral limb ataxia (inferior cerebellar
peduncle)
 6. Ipsilateral Horner syndrome (descending
sympathetic tract)
 7. Dysphagia, dysarthria, hoarseness, and
ipsilateral palatal paralysis (nucleus ambiguus)
Lateral medullary infarction (Wallenberg syndrome) showing
the area of infarction (blue) and anatomic structures
affected.
Cerebellar Infarction

 The cerebellum is supplied by the

superior cerebellar, anterior inferior
cerebellar, and posterior inferior
cerebellar arteries.
 The territory supplied by each of these
vessels is highly variable, but the
superior, middle, and inferior
cerebellar peduncles are typically
supplied by the superior, anterior
inferior, and posterior inferior
cerebellar arteries, respectively.
 Signs of cerebellar infarction include
ipsilateral limb ataxia, lateropulsion
(falling toward or, less commonly,
away from the side of the lesion), and
hypotonia.
 Headache, nausea, vomiting, vertigo,
nystagmus, dysarthria, ocular or gaze
palsies, facial weakness or sensory
loss, and contralateral hemiparesis or
hemisensory deficit may also occur.
 Occlusions of the superior
cerebellar, anterior inferior
cerebellar, and posterior inferior
cerebellar arteries may be
clinically indistinguishable, but
associated brainstem findings can
help in this regard. Thus,
midbrain, pontine, and medullary
signs may suggest infarction in
the superior cerebellar, anterior
inferior cerebellar, and posterior
inferior cerebellar territories,
respectively. Brainstem infarction
or compression by cerebellar
edema can result in coma and
death.
 Diagnosis is by CT or MRI, which
differentiates between infarction
and hemorrhage and should be
obtained promptly.
 Brainstem compression is an
indication for surgical
decompression and resection of
infarcted tissue, which can be
lifesaving.
Paramedian Midbrain Infarction

 Caused by occlusion of the

paramedian penetrating
branches of the basilar artery,
affects the oculomotor (III)
nerve root fibers and red
nucleus.

 Benedikt syndrome
 Ipsilateral oculomotor (III)
nerve involvement (producing
medial rectus palsy with a fixed
dilated pupil) and contralateral
limb ataxia (typically affecting
only the arm).
 Cerebellar signs result from
involvement of the RED
NUCLEUS, which receives a
crossed projection from the
cerebellum in the ascending
limb of the superior cerebellar
peduncle.
Paramedian midbrain infarction (Benedikt syndrome). The
area of infarction is indicated in blue.
CEREBELLAR HEMORRHAGE

▪ Pathogenesis

 Cerebellar hemorrhage is usually due to

hypertensive vascular disease; less common
causes include anticoagulation,
arteriovenous malformation, blood
dyscrasia, tumor, and trauma.
 Hypertensive cerebellar hemorrhages are
usually located in the deep white matter of
the cerebellum and commonly extend into
the fourth ventricle.

▪ Clinical Findings
 Hypertensive cerebellar hemorrhage causes
the sudden onset of headache, which may
be accompanied by nausea, vomiting, and
vertigo, followed by gait ataxia and
impaired consciousness, usually evolving
over hours.
 At presentation, patients can be
fully alert, confused, or comatose.
 The blood pressure is typically
elevated, and nuchal rigidity may be
present.
 The pupils are often small and
sluggishly reactive.
 Ipsilateral gaze palsy (with gaze
preference away from the side of
hemorrhage) and ipsilateral
peripheral facial palsy are common.
The gaze palsy cannot be overcome
by cold-water caloric stimulation.
Nystagmus may be present, and the
ipsilateral corneal reflex may be
depressed.
 The patient, if alert, exhibits ataxia
of stance and gait; limb ataxia is less
common.
 In the late stage of brainstem
compression, there is spasticity in
the legs and extensor plantar
responses.
▪ Diagnosis & Treatment

 The diagnosis of cerebellar

hemorrhage can be missed or
delayed, and death results, if
gait is not tested promptly in
every patient with hypertension
and either acute headache or
depressed consciousness. This
is because gait ataxia is often
the earliest neurologic sign in
this condition.
 The CSF is frequently bloody,
but lumbar puncture should be
avoided if cerebellar
hemorrhage is suspected,
because it may lead to brain
herniation.
 Diagnosis is by CT.
 Treatment consists of surgical
evacuation of the hematoma,
which can be life-saving.
INFLAMMATORY DISORDERS

▪ Viral Infection

 Cerebellar ataxia can result from cerebellitis

due to a variety of viral infections.
 Varicella-zoster is most common in children,
and reactivation of varicella-zoster or
Epstein–Barr virus is most common in adults.
 Less frequent causes include coxsackie virus,
echo virus, influenza virus, and parvovirus
B19.
 Truncal ataxia is usually the most prominent
sign of cerebellar involvement and may be
accompanied by headache, nausea, vomiting,
and altered consciousness.
 Viral cerebellitis is usually self-limited and
recovery is good, especially in children.
 JC polyoma virus, which causes progressive
multifocal leukoencephalopathy, can infect
the cerebellum of immunocompromised
patients.
▪ Bacterial Infection

 Bacterial infection is an uncommon

cause of cerebellar ataxia, but 10% to
20% of brain abscesses are located in
the cerebellum, and ataxia may be a
feature of encephalitis due to Listeria
monocytogenes.
 Listeria typically affects healthy adults
who consume tainted foods, such as
cheese, meat, or fruit. A prodromal flu-
like illness is followed by a neurologic
disorder that involves the brainstem
and cerebellum. Signs include ataxia,
cranial nerve (especially V, VI, VII, IX,
and X) palsies, hemiparesis, altered
consciousness, and meningismus.
 MRI shows diffuse and focal, abscess-
like lesions and CSF shows pleocytosis.
 Treatment is with ampicillin (2 g IV
every 4 hours), often together with
gentamicin (1.5 mg/kg IV loading
followed by 1-2 mg/kg IV every 8
hours).
▪ Fungal Infection
 Fungal infection of the cerebellum is rare
but may occur in immunocompromised
patients or following neurosurgical
procedures or epidural injections.
 Organisms involved include Aspergillus.
▪ Prion Infection
 Prion diseases (Creutzfeldt–Jakob and
Gerstmann–Straussler–Scheinker
syndrome) can produce cerebellar ataxia
associated with dementia.
▪ Acute Postinfectious Cerebellar Ataxia
of Childhood
 Acute postinfectious cerebellar ataxia of
childhood is the most common cause of
acute ataxia in children.
 It usually affects children aged 1-6 years and
follows a viral illness or vaccination.
 Gait ataxia is the most prominent clinical
feature.
 MRI is typically normal; CSF may show mild
pleocytosis.
 Most patients recover completely within
one month.
▪ Acute Disseminated Encephalomyelitis
 Acute disseminated encephalomyelitis, a monophasic
illness caused by immune-mediated demyelination of
CNS white matter, may affect the cerebellum, producing
ataxia.
 Other common features include impaired consciousness,
seizures, focal neurologic signs, and myelopathy.
▪ Miller-Fisher Variant of Guillain–Barré Syndrome
 ATAXIA, OPHTHALMOPLEGIA, and AREFLEXIA
characterize this variant of Guillain–Barre syndrome.
 Incomplete forms of the Fisher variant and forms that
overlap with classic Guillain–Barre syndrome also occur.
 Symptoms develop over days and are thought to be
caused by autoantibodies against GQ1b ganglioside
located on ocular motor and dorsal root ganglion nerves.
 Ataxia primarily affects the gait and trunk, with lesser
involvement of the individual limbs; dysarthria is
uncommon.
 Ophthalmoplegia can involve the pupils as well as
extraocular muscles.
 CSF protein may be elevated and anti-GQ1b antibodies
may be detected in the blood.
 Respiratory insufficiency is rare, and the usual course is a
gradual and often complete recovery over weeks to
months.
 EPISODIC DISORDERS
MOTION SICKNESS
▪ Motion sickness affects up to 30% of the general
population, with susceptibility influenced by
genetics, age (peak ~9 years), and concurrent
disorders (eg, migraine).
▪ Symptoms are triggered by real or perceived
movement of the affected individual or of his or
her environment, as occurs during vehicular travel,
watching 3D movies, or using virtual reality
devices.
▪ Features include nausea, vomiting, vertigo,
headache, pallor, sweating, salivation, anorexia,
osmophobia, and a sensation of warmth.
▪ Motion sickness may be prevented by lying supine
or viewing the horizon while traveling, and
habituation therapy may be effective in the long
term. Muscarinic anticholinergic drugs (eg,
scopolamine, 1.5 mg transdermally) and H1
antihistamines (eg, dimenhydrinate, 50 mg orally)
are useful for acute attacks, but dopamine D2 and
serotonin 5-HT3 receptor antagonist anti-emetics
are not.
VESTIBULAR MIGRAINE

▪ Vestibular migraine is
characterized by episodic
vertigo accompanied by
other features of migraine
attacks, such as headache,
photophobia,
phonophobia, or visual
aura.
▪ Treatment includes
vestibular rehabilitation
training and drugs used for
other forms of migraine.
AUTOSOMAL DOMINANT EPISODIC ATAXIAS
▪ Episodic ataxias are autosomal dominant disorders characterized by transient
attacks of cerebellar ataxia that may be precipitated by physical or emotional
stress.
▪ Episodic ataxia 1 (EA1) results from mutations in KCNA1, which codes for the
Kv1.1 voltage-gated potassium channel.
▪ Attacks last from seconds to minutes and may occur many times per day;
myokymia—a quivering, involuntary movement of muscle—commonly occurs
between episodes.
▪ EA2 is caused by mutations in CACNA1A, which codes for the α1A subunit of
the P/Q-type voltage-gated calcium channel; this gene is also affected in
spinocerebellar ataxia 6 and familial hemiplegic migraine.
▪ Attacks are more prolonged than in EA1, typically lasting for hours, and
nystagmus and slowly progressive ataxia persist between acute episodes.
▪ ACETAZOLAMIDE (500 mg orally four times daily) can often prevent or
relieve acute symptoms in EA2.
▪ EA5 likewise affects voltage-gated calcium channels, but in this case the
mutation is in CACNB4, which encodes the β subunit.
▪ EA6 is due to mutations in SLC1A3, which encodes the EAAT1 glial glutamate
transporter. Glutamate uptake is reduced, leading to enhanced excitatory
input onto cerebellar Purkinje cells.
▪ EA1 and EA6 are thought to impair channel function through dominant
negative effects, whereas EA2 involves haploinsufficiency; the mechanism in
EA5 is uncertain.
CHRONIC DISORDERS
MULTIPLE SCLEROSIS*
▪ Pathogenesis
 Multiple sclerosis is characterized clinically
by remitting and relapsing neurologic
dysfunction at multiple sites in the central
nervous system.
 Because these include vestibular, cerebellar,
and sensory pathways, multiple sclerosis can
produce disorders of equilibrium.
 Symptoms and signs are associated with
demyelination and axonal loss, which
primarily affect white matter.
▪ Clinical Findings
 Cerebellar signs are present in approximately
one-third of patients on initial examination
and ultimately develop in twice that number.
 Nystagmus, dysarthria, and limb ataxia are
common, but vertigo is less so.
 Gait ataxia is a presenting complaint in 10-
15% of patients and is usually due to
cerebellar involvement.
▪ Diagnosis
 The diagnosis relies on a history of multiple
episodes of neurologic dysfunction
separated in both time and space.
 Subclinical lesions may be evident from
physical findings such as optic neuritis,
internuclear ophthalmoplegia, or pyramidal
signs, or from laboratory investigations.
 CSF analysis may reveal oligoclonal bands,
elevated IgG, increased protein, or a mild
lymphocytic pleocytosis.
 Visual, auditory, or somatosensory evoked
response recording can also document
subclinical sites of involvement.
 CT or MRI shows demyelination.

▪ Treatment
 This involves immunomodulating or
disease-modifying drugs, steroids or plasma
exchange.
ALCOHOLIC CEREBELLAR DEGENERATION
▪ Pathogenesis
 A characteristic cerebellar syndrome may develop
in chronic alcoholics, probably as a result of
nutritional deficiency.
 Degenerative changes in the cerebellum are largely
restricted to the superior vermis, which is also the
site of involvement in Wernicke encephalopathy.
▪ Clinical Features
 Alcoholic cerebellar degeneration is most common in
men between ages 40 and 60 years.
 Patients typically have a history of daily or binge drinking
lasting 10 or more years with associated dietary
inadequacy.
 Most have experienced other medical complications of
alcoholism, such as liver disease, delirium tremens,
Wernicke encephalopathy, or polyneuropathy.
 Cerebellar degeneration usually has an insidious onset
and progresses gradually over weeks to months,
eventually reaching a plateau of dysfunction.
 In occasional cases, ataxia appears abruptly.
ALCOHOLIC CEREBELLAR
DEGENERATION
▪ Pathogenesis
 A characteristic cerebellar syndrome may
develop in chronic alcoholics, probably as a result
of nutritional deficiency.
 Degenerative changes in the cerebellum are
largely restricted to the superior vermis, which is
also the site of involvement in Wernicke
encephalopathy.
▪ Clinical Features
 Alcoholic cerebellar degeneration is most common in
men between ages 40 and 60 years.
 Patients typically have a history of daily or binge
drinking lasting 10 or more years with associated
dietary inadequacy.
 Most have experienced other medical complications of
alcoholism, such as liver disease, delirium tremens,
Wernicke encephalopathy, or polyneuropathy.
 Cerebellar degeneration usually has an insidious onset
and progresses gradually over weeks to months,
eventually reaching a plateau of dysfunction.
 In occasional cases, ataxia appears abruptly.
  Gait ataxia is universal and almost
always the problem that brings the
patient to medical attention.
 The legs are ataxic on heel-knee-shin
testing in approximately 80% of
patients.
 Common associated findings include
distal sensory deficits in the feet and
absent ankle reflexes, which result
from polyneuropathy.
 Ataxia of the arms, nystagmus,
dysarthria, hypotonia, and truncal
instability are less frequent.
 CT or MRI may show cerebellar
atrophy.
▪ Treatment
 Patients should receive thiamine
because of the likely role of thiamine
deficiency in pathogenesis.
 Abstinence from alcohol and adequate
nutrition may help prevent progression.
CT scan in alcoholic cerebellar degeneration, showing
marked atrophy of the midline cerebellar vermis with
relative sparing of the cerebellar hemispheres.
TOXIN-INDUCED CEREBELLAR
DEGENERATION
▪ Purkinje cells and granule cells of
the cerebellum are selectively
vulnerable to a variety of toxins.
These may cause cerebellar
degeneration associated with
nystagmus, dysarthria, and ataxia
affecting the limbs, trunk, and
gait.
▪ Can be produced by phenytoin,
lithium, amiodarone, fluorouracil,
cytarabine, toluene, lead,
mercury, and thallium.
▪ Treatment is discontinuation of
the offending agents and, for
fluorouracil, administration of
thiamine (vitamin B1), but toxin-
induced cerebellar syndromes
may be irreversible.
HYPOTHYROIDISM
▪ Hypothyroidism can cause a subacute or
chronically progressive cerebellar
syndrome, which is most common in
middle-aged and elderly women.
▪ Symptoms evolve over months to years.
▪ Systemic symptoms (eg, myxedema)
usually precede the cerebellar disorder.
▪ Gait ataxia is universal and is the most
prominent finding.
▪ Limb ataxia is also common and may be
asymmetric.
▪ Dysarthria and nystagmus occur less
frequently.
▪ Other neurologic disorders related to
hypothyroidism may coexist with
cerebellar involvement, including
sensorineural hearing loss, carpal tunnel
syndrome, neuropathy, or myopathy.
AUTOIMMUNE CEREBELLAR DEGENERATION
▪ Paraneoplastic Cerebellar Degeneration
 Autoimmune cerebellar degeneration can occur as a remote
(paraneoplastic) effect of systemic cancer.
 Lung cancer (especially small-cell), ovarian cancer, Hodgkin
disease, and breast cancer are the most commonly associated
neoplasms.
 Paraneoplastic degeneration affects the cerebellar vermis and
hemispheres diffusely.
 The cause appears to be autoimmunity involving antineural
antibodies, which are directed against either neuronal nuclear
antigens or antigens expressed more specifically in the cell
membranes or cytoplasm of cerebellar Purkinje cells.
 Cerebellar symptoms can appear either before or after the
diagnosis of cancer and typically evolve over months.
 Gait and limb ataxia are prominent, and may be asymmetric.
 Dysarthria is common but nystagmus is rare.
 Involvement of additional regions besides the cerebellum may
produce dysphagia, dementia, memory disturbance, pyramidal
signs, or neuropathy.
 Onconeural antibodies can sometimes be detected in the blood, and the
CSF may show a mild lymphocytic pleocytosis or elevated protein.
 Diagnosis may be difficult when neurologic symptoms precede the
discovery of cancer.
 Dysarthria, dysphagia, and ataxia of the arms help distinguish
paraneoplastic cerebellar degeneration from syndromes produced by
chronic alcoholism or hypothyroidism. However, Wernicke
encephalopathy should always be considered because patients with
cancer may suffer from malnutrition.
 Treatment is of the underlying tumor, supplemented in some cases by
immunotherapy with immunoglobulin G, corticosteroids,
cyclophosphamide, tacrolimus, rituximab, mycophenolate, or plasma
exchange.
 The disorder usually progresses steadily, but may stabilize or remit with
treatment.
▪ Other Autoimmune Cerebellar
Degenerations
 Autoimmune cerebellar degeneration also occurs in patients without
cancer who produce autoantibodies against transglutaminase,
glutamic acid decarboxylase, or thyroid antigens.
 Gluten ataxia is manifested by gait ataxia, lower limb ataxia, and
nystagmus. It appears to result from autoantibodies against gluten
proteins (gliadins) that cross react with transglutaminases in the
small intestine (TG2) and brain (TG6). Symptoms of gluten
enteropathy (celiac disease) are typically absent, but intestinal
biopsy may show immune deposits. MRI may show cerebellar
atrophy, and anti-transglutaminase antibodies are commonly
present in the blood. The mainstay of treatment is a gluten-free diet.
 Anti-glutamic acid decarboxylase (GAD) cerebellar ataxia is associated
with autoantibodies against the enzyme (GAD) that synthesizes γ–
aminobutyric acid (GABA), the brain’s principal inhibitory
neurotransmitter. Gait ataxia is the most consistent clinical feature, but
limb ataxia, dysarthria, and nystagmus can also occur. Intravenous
immunoglobulin and corticosteroids may be beneficial. Anti-GAD
antibodies are also implicated in stiff-person syndrome.
 Hashimoto encephalopathy is a steroid-responsive encephalopathy
associated with autoimmune thyroiditis. In addition to ataxia,
confusional states, seizures, and myoclonus may occur. Patients are
typically euthyroid when ataxia is first diagnosed, and MRI shows little or
no cerebellar atrophy. Antibodies against thyroid antigens and α-enolase
may be detected in the blood. Treatment is with corticosteroids.
AUTOSOMAL DOMINANT SPINOCEREBELLAR
ATAXIA
▪ Autosomal dominant spinocerebellar ataxia (SCA) encompasses a
group of over 40 genetically and clinically heterogeneous disorders.
▪ Genetics
 Several types of mutations can produce autosomal dominant
SCA, including expansion of CAG trinucleotide repeats coding
for polyglutamine (polyQ) tracts, expansion of tri- or
pentanucleotide repeats in noncoding regions, and point
mutations. Of these, the polyQ disorders are the most common
and best characterized. They affect a wide range of proteins,
including ion channels, receptors, enzymes, and cytoskeletal
proteins.
 A striking feature of polyQ disorders is that the underlying
trinucleotide expansion is unstable and tends to enlarge with
time. This leads to anticipation, in which the age at onset
decreases, the disease severity increases, or both, in successive
generations.
 In addition to SCAs, polyQ disorders include spinal bulbar
muscular atrophy (Kennedy disease) and Huntington disease.
▪ Pathogenesis
 PolyQ expansions confer a toxic gain of function on the target protein.
 The abnormally long polyQ tract predisposes the protein to
conformational changes, misfolding, and proteolytic cleavage. As a
consequence, protein fragments are generated that are prone to
aggregate and, in some cases, translocate from the cytoplasm to the
nucleus. Neuronal dysfunction and death are thought to result from
some combination of direct toxicity of abnormal proteins or their
cytoplasmic or nuclear aggregates; impaired proteasomal function,
axonal transport, or nuclear function; and protein-protein interactions.
Proposed mechanisms of polyQ protein processing and toxicity.
In polyQ diseases including several autosomal dominant spinocerebellar ataxias, a gene containing a CAG
trinucleotide repeat (CAG ) undergoes mutation by expansion of the repeat. The resulting abnormal protein (Q
QQQQ) contains an abnormally long polyQ tract, which induces conformational changes that promote misfolding.
The misfolded protein is subject to proteolytic cleavage, which generates abnormal and possibly toxic
fragments, which may also have an increased tendency to be translocated from the cytoplasm to the nucleus,
to aggregate, or both. As a result of these events, neuronal function is impaired, and neurons may
eventually die. How neurotoxicity and neuronal death ultimately occur is unknown, but there may be multiple
mechanisms, and these may differ across polyQ diseases. Possible contributing factors include direct
toxicity of misfolded and cleaved protein monomers or oligomers, or of cytoplasmic or nuclear aggregates
(red in figure); impaired proteasomal degradation, axonal transport, or nuclear function; and interactions
between polyQ proteins and other cellular proteins.
▪ Clinical Findings
 The autosomal dominant SCAs show considerable clinical variability, even within
a given family.
 In general, they are associated with an adult-onset, slowly progressive cerebellar
syndrome in which gait ataxia is an early and prominent feature.
 Other manifestations are dysarthria, diplopia, and limb ataxia.
 Extracerebellar findings are common, including cognitive, pyramidal,
extrapyramidal, motor neuron, peripheral nerve, or macular involvement.
 The most common SCAs are 1, 2, 3, 6, and 7. SCA1 produces gait ataxia, limb
ataxia, and dysarthria, with brainstem involvement but little cognitive
abnormality.
 SCA2 is notable for the association of ataxia and dysarthria with slow saccadic eye
movements and polyneuropathy.
 SCA3 (Machado–Joseph disease) is especially common in patients of Portuguese
ancestry; ataxia is accompanied by eyelid retraction, reduced blinking, external
ophthalmoplegia, dysarthria, dysphagia, and sometimes parkinsonism or
peripheral neuropathy.
 SCA6 is comparatively less severe, progresses more slowly, and is more limited to
cerebellar involvement than other SCAs.
 SCA7 is distinguished by retinal degeneration leading to blindness, in addition to
ataxia.
 Atrophy of the cerebellum and sometimes also of the brainstem may be apparent
on CT or MRI.
 Definitive diagnosis is by genetic testing.
 There is no specific treatment, but occupational and physical therapy and devices
to assist ambulation may be helpful, and genetic counseling may be indicated.
DENTATORUBRAL-PALLIDOLUYSIAN
ATROPHY
▪ Dentatorubral-pallidoluysian atrophy (DRPLA) is a dominantly
inherited disorder that results from a polyglutamine expansion in
the ATN1 gene coding for the protein atrophin 1.
▪ DRPLA causes ataxia, chorea, dementia, seizures, and
myoclonus.
ATAXIA-TELANGIECTASIA
▪ Pathogenesis
 Ataxia-telangiectasia (also known as Louis–Bar syndrome) is an
inherited autosomal recessive disorder with onset in infancy.
 It results from loss-of-function mutations in the ataxia-telangiectasia
mutated (ATM) gene, which codes for a serine/threonine protein
kinase related to phosphatidylinositol 3-kinase.
 Deletions, insertions, and substitutions all have been described.
 A defect in the repair of DNA double strand breaks is thought to be
involved in pathogenesis.
▪ Clinical Findings
 Ataxia-telangiectasia is characterized by progressive cerebellar ataxia,
oculocutaneous telangiectasia, sinopulmonary infections, and
lymphoid tumors.
 Patients typically suffer from progressive pancerebellar degeneration
characterized by nystagmus, dysarthria, and gait, limb, and trunk ataxia.
 Choreoathetosis, loss of vibration and position sense in the legs,
areflexia, and disorders of voluntary eye movement are almost universal
findings.
 Mental deficiency is commonly observed in the second decade.
 Oculocutaneous telangiectasia usually appears in the teen years.
 The bulbar conjunctivae are typically affected first, followed by sun-
exposed areas of the skin, including the ears, nose, face, and antecubital
and popliteal fossae.
 The vascular lesions, which rarely bleed, spare the central nervous
system.
 Immunologic impairment usually becomes evident later in childhood,
with recurrent sinopulmonary infections in more than 80% of patients.
 Malignancies occur in approximately one-third of patients and include
non-Hodgkin lymphoma, leukemia, and Hodgkin disease.
 Other common clinical findings are progeric changes of the skin
and hair, hypogonadism, and insulin-resistant diabetes mellitus.
 The characteristic laboratory abnormalities include decreased
circulating levels of IgG2, IgA, and IgE and elevation of α-
fetoprotein and carcinoembryonic antigen levels.
 Atypical phenotypes may be associated with later (including
adult) onset, slower progression, absence of telangiectasia, and
movement disorders rather than ataxia as the primary neurologic
manifestation.
 Because the vascular and immunologic manifestations of ataxia-
telangiectasia occur later than the neurologic symptoms, the
condition may be confused with Friedreich ataxia, which also
manifests in childhood.
 Ataxia-telangiectasia can be distinguished by its earlier onset
(before age 4 years), associated choreoathetosis, and the
absence of kyphoscoliosis.
 There is no specific treatment for ataxia-telangiectasia, but
antibiotics are useful in the management of infections.
 X-rays should be avoided because of the hypersensitivity to
ionizing radiation present in this disorder.
FRAGILE X-ASSOCIATED TREMOR/ATAXIA
SYNDROME
▪ Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-
linked disorder caused by gain-of-function mutations (CGG
expansions) in the 5′ untranslated region of the fragile X mental
retardation 1 (FMR1) gene.
▪ White matter tracts, including the middle cerebellar peduncles,
are prominently involved.
▪ FXTAS affects males primarily and presents at an average age of
60 years, with features that include intention tremor and
cerebellar ataxia.
▪ Diagnosis is by DNA testing.
MULTIPLE SYSTEM ATROPHY
▪ Multiple system atrophy is a neurodegenerative proteinopathy
associated with deposition of α-synuclein in affected neurons.
▪ It produces autonomic dysfunction and either parkinsonism or ataxia.
HEPATOCEREBRAL DEGENERATION
▪ Hepatocerebral degeneration refers to diseases that impair the
function of both the liver and brain, including acquired (non-
Wilsonian) hepatocerebral degeneration (eg, that due to liver
cirrhosis with portosystemic shunting) and hereditary disorders.
Ataxia may be a feature in both cases.
▪ Wilson disease, a disorder of copper metabolism characterized
by copper deposition in a variety of tissues, is an important cause
of hereditary hepatocerebral degeneration. It is an autosomal
recessive disorder that results from mutations in the ATP7B gene,
which codes for the β polypeptide of a copper-transporting
ATPase. Extrapyramidal features are usually the most prominent
neurologic manifestations.
PRION DISEASES

▪ Creutzfeldt–Jakob disease and Gerstmann–Straüssler–Scheinker syndrome (a rare,

autosomal dominant disorder) are prion diseases that can produce ataxia.
▪ Cerebellar signs are present in approximately 60% of patients with Creutzfeldt–Jakob
disease, and patients present with ataxia in approximately 10% of cases.
▪ Cerebellar involvement is diffuse, but the vermis is often most severely affected.
▪ In contrast to most other cerebellar disorders, depletion of granule cells is frequently
more striking than Purkinje cell loss.
▪ Patients with cerebellar manifestations of Creutzfeldt–Jakob disease typically
complain first of gait ataxia.
▪ Dementia is usually evident at this time, and cognitive dysfunction always develops
eventually.
▪ Nystagmus, dysarthria, truncal ataxia, and limb ataxia are all present initially in
approximately one-half of patients with the ataxic form of Creutzfeldt–Jakob disease.
▪ The course is characterized by rapidly progressive dementia, myoclonus, and
extrapyramidal and pyramidal dysfunction.
▪ Death typically occurs within 1 year after onset.
POSTERIOR FOSSA TUMORS
▪ Tumors of the posterior fossa cause cerebellar symptoms when they
arise in the cerebellum or compress it from without.
▪ Common posterior fossa tumors in children include medulloblastoma,
cystic astrocytoma, ependymoma, and brainstem glioma, whereas
hemangioblastoma, choroid plexus papilloma, meningioma, and
metastases from outside the nervous system (especially the lung and
breast) predominate in adults.
▪ Clinical Findings
 Patients with cerebellar tumors usually present with headache from increased
intracranial pressure or with ataxia.
 Nausea, vomiting, vertigo, cranial nerve palsies, and hydrocephalus are common.
 The nature of the clinical findings varies with the location of the tumor.
 Most metastases are located in the cerebellar hemispheres, causing asymmetric
cerebellar signs.
 Medulloblastomas and ependymomas, on the other hand, tend to arise in the
midline, with early involvement of the vermis and hydrocephalus.
 Hemangioblastoma may occur as one feature of von Hippel–Lindau disease,
which results from a dominant mutation in the VHL tumor suppressor gene, and
may also cause retinal hemangioblastoma, renal or pancreatic cysts, and
polycythemia.
 Ependymomas commonly arise in the fourth ventricle, which predisposes to
seeding through the ventricular system and hydrocephalus.
▪ Diagnosis & Treatment
 CT scan or MRI is useful for diagnosis, but biopsy may be required for
histologic characterization.
 Methods of treatment include surgical resection, irradiation, and
chemotherapy.
 Corticosteroids are useful in controlling tumor-associated edema.
 Total resection may be curative for cystic astrocytoma of the cerebellum
and meningioma.
 Medulloblastoma shows wide variation in prognosis based on molecular
subgrouping.
POSTERIOR FOSSA MALFORMATIONS
▪ Congenital anomalies affecting the cerebellum and brainstem include malformations of
the hindbrain (cerebellar agenesis, Dandy–Walker malformation, arachnoid cyst) or
cranial vault (Arnold–Chiari malformation).
▪ Vestibular or cerebellar symptoms presenting in adulthood are most common in type I
Arnold–Chiari malformation, which consists of downward displacement of the
cerebellar tonsils through the foramen magnum.
▪ Clinical manifestations are related to cerebellar involvement, obstructive
hydrocephalus, brainstem compression, and syringomyelia (a cyst or syrinx in the
spinal cord).
▪ Type II Arnold–Chiari malformation is associated with meningomyelocele (protrusion of
the spinal cord, nerve roots, and meninges through a fusion defect in the vertebral
column) and has its onset in childhood.
▪ Type III Arnold–Chiari malformation is accompanied by encephalocele (herniation of
posterior fossa contents through an occipital or cervical bony defect).
▪ Cerebellar ataxia in the type I malformation usually affects the gait and is bilateral;
in some cases, it is asymmetric.
▪ Hydrocephalus leads to headache and vomiting.
▪ Compression of the brainstem by herniated cerebellar tissue may be associated
with vertigo, nystagmus, and lower cranial nerve palsies.
▪ Syringomyelia typically produces a cape-like distribution of defective pain and
temperature sensation.
▪ Arnold–Chiari malformation can be diagnosed by CT or MRI studies that
demonstrate cerebellar tonsillar herniation.
▪ Patients with headache, neck pain, hydrocephalus, or other symptoms related to
compression of the cerebellum or brainstem may benefit from surgical
decompression of the foramen magnum.
▪ Neuropathic pain may respond to antidepressants or anticonvulsants.
SENSORY ATAXIAS
SENSORY ATAXIA
Result of impaired proprioceptive
sensation due to lesions of the
▪ peripheral sensory nerves
(sensory neuropathy)
▪ dorsal root ganglia (sensory
neuronopathy)
▪ posterior columns of the spinal
cord (myelopathy).

CLINICAL FINDINGS include

▪ Defective joint position and
vibration sense in the legs and
sometimes the arms
▪ unstable stance with Romberg
sign
▪ gait of slapping or steppage
quality.
CAUSES OF SENSORY ATAXIA

▪ Sensory neuropathy or
neuronopathy
▪ Myelopathy
▪ Combined lesions
SENSORY NEUROPATHY OR
NEURONOPATHY

▪ Polyneuropathies that affect large myelinated

sensory fibers and sensory neuronopathies
(which target dorsal root ganglia) may present
with ataxia.

▪ Prominent examples include the Hu antibody-

positive sensory neuronopathy associated with
small-cell lung cancer, sensory neuronopathy
from consumption of high doses of pyridoxine,
and the Miller-Fisher variant of the Guillain–
Barre syndrome.
MYELOPATHY

▪ Myelopathies that affect the posterior columns can also cause ataxia.

▪ A common cause of this syndrome is multiple sclerosis.

COMBINED LESIONS
▪ Several diseases can affect both peripheral and central sensory pathways.

▪ Examples include neurosyphilis (tabes dorsalis) and combined systems

disease from vitamin B12 deficiency.

▪ Another example is Friedreich ataxia.

 FRIEDREICH ATAXIA
▪ An autosomal recessive disorder with onset
usually in childhood, is the most common
cause of hereditary ataxia.

▪ It results from an expanded GAA

trinucleotide repeat in a noncoding region
of the FXN gene, which causes loss-of-
function of a mitochondrial protein,
FRATAXIN.

▪ The key pathologic findings are degeneration

of the dorsal root ganglia, large myelinated
axons of peripheral sensory nerves,
corticospinal tracts, and dentate nuclei of the
cerebellum, with secondary involvement of
the spinocerebellar tracts, posterior columns,
and dorsal nucleus of Clarke.
▪ CLINICAL FINDINGS

 The average age at onset is

approximately 13 years, with longer
GAA repeats correlating with earlier
onset.
 The INITIAL SYMPTOM is usually
progressive gait ataxia, followed by
limb ataxia, dysarthria, and sensory
gait ataxia.
 NEUROLOGIC EXAMINATION shows
knee and ankle areflexia, impaired
joint position and vibration sense in
the legs, leg (and sometimes arm)
weakness, and extensor plantar
responses.
 PES CAVUS (high-arched feet with
clawing of the toes caused by
weakness and wasting of the
intrinsic foot muscles) is often
present, but can also occur in other
neurologic disorders (eg, Charcot–
Marie–Tooth disease).
 Severe progressive
KYPHOSCOLIOSIS may lead to
chronic restrictive lung disease.
 CARDIOMYOPATHY may result in
congestive heart failure, arrhythmia,
and death.
 Other abnormalities include visual
impairment from OPTIC ATROPHY
and DIABETES MELLITUS.
 Atypical phenotypes may be seen with
smaller GAA expansions and include
late (>25 years) or very late (>40 years)
onset and preserved reflexes. These
syndromes are characterized by slow
progression and a paucity of non-
neurologic features.
 Friedreich ataxia can usually be
differentiated from other cerebellar
and spinocerebellar degenerations by
its early onset and the presence of
prominent sensory impairment,
areflexia, skeletal abnormalities, and
cardiomyopathy.
 Definitive diagnosis is by GENETIC
TESTING
▪ Treatment & Prognosis
 There is no current treatment
for the neurologic
manifestations of Friedreich
ataxia.
 Orthopedic procedures or
devices may improve
kyphoscoliosis and gait
disorder.
 The average duration of
symptomatic illness is
approximately 25 years, with
death occurring at a mean age
of approximately 40 years.
 Cardiomyopathy and infection
are the usual causes of death.
YouTube Video Links

Vertigo and Its Causes

▪ https://www.youtube.com/watch?v=YMWZRwWIHZ4
▪ https://www.youtube.com/watch?v=kx4mQB0QzvQ
Ataxia
▪ https://www.youtube.com/watch?v=Ri5iUR4Pi_0
Sensory Ataxia
▪ https://www.youtube.com/watch?v=uZlrDVoQub0
CLINICAL CASES
▪ A 63-year-old man presents with a 3-month history of dizziness. His
dizziness comes and goes, but usually lasts for about 10 to 15 seconds. He
notices that his dizziness is worse when he rolls over in bed or when he gets
out of bed. This gives him imbalance and difficulty walking
One time, he became very dizzy while trying to reach for an object on a
high shelf. He does not have any nausea or vomiting associated with it.
When it occurs, it is very strong, and he has tried to avoid sleeping on his left
side. He does not have any hearing loss or tinnitus. He denies aural pressure
and headache.
His past medical history is otherwise unremarkable. He is not on any
medications.
On physical examination, he is a healthy appearing 63-year-old man. His
temperature is 37.1°C; pulse, 64 beats/min; and blood pressure, 124/74
mmHg. There are no lesions or masses on his face or head. His voice is
normal, and his speech is fluent. His facial nerve function is normal. His ear
canals and tympanic membranes are normal appearing. His remaining head
and neck examination is normal. The cranial nerve examination is
normal. The remaining physical examination is normal.
 Question 1: What is the likely diagnosis?
 Question 2: What is the neuroanatomic localization? Explain.
 Question 3: How do you explain the patient’s signs and symptoms?
 Question 4: What is the next logical step to do?
 Question 5: How is this condition managed?
▪ A 57-year-old man of Portuguese descent noticed that he had difficulty
marching in line as a soldier. From age 20 until the age of 40 he had a
slow progression of symptoms. Since then he experienced a rapidly
progressing gait disturbance, diplopia, dyssynergia, and paraesthesia in
the limbs. At age 45 he was confined to a wheelchair.
On examination, he was intellectually normal but had severe dysarthria
and constant drooling. He had bulging eyes, slow saccades, and
impaired voluntary up- and down-gaze but no nystagmus. He had
fasciculations and dyscoordination of the tongue but no facial
fasciculations.
A general moderate muscle weakness and atrophy were revealed, but
muscle tone was normal. Tendon reflexes were absent, but there were
bilateral Babinski signs. Deep senses were impaired, and coordination
was impaired by severe ataxia, dysmetria, and dysdiadochokinesia. A
constant static tremor was seen in the hands.
His mother and paternal grandfather as well as his sister and her son also
had problems with gait, which were progressive and began during
adulthood.
MRI of the brain revealed cerebellar folial atrophy.
 Question 1: What is the likely diagnosis?
 Question 2: What is the neuroanatomic localization? Explain.
 Question 3: How do you explain the patient’s signs and symptoms?
 Question 4: What is the next logical step to do?
 Question 5: How is this condition managed?
 Question 6: What is the prognosis?
MAIN REFERENCE

▪ Clinical Neurology, 10ed, Roger P. Simon et

al, Chapter 8, pp 190-248
RELATED READINGS

▪ Hankey’s Clinical Neurology, 2ed, Philip B.

Gorelick et al
▪ Current Diagnosis & Treatment Neurology,
3ed, John C.M. Brust
▪ Netter’s Neurology, 3ed, H. Royden Jones, Jr.
▪ Case Files Neurology, 1ed, Eugene C. Toy et al
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