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Ataxia

Ataxia refers to the incoordination of volitional movement

- may involve limbs, trunk, gait, speech or ocular motor

- abnormalities of rate, rhythm, and range of movement

- usually attributable to diseases of cerebellum or its connections

Core Clinical Features:

Dyssynergia: trouble coordinating complex movements including contraction of agonist and antagonist muscle pairs; results in jerky decomposed movements

Dysmetria: inaccuracy in reaching target due to premature arrest of movement (hypometria) or overshoot the target (hypermetria) due to delayed activation of antagonists

- often correction to target by series of jerky corrections

- may lead to intention tremor in limbs with finger-to-nose or foot-to-target testing as rhythmic oscillation emerges close to target

Dysdiadochokinesis: trouble with rapid alternating movements such as pronation-supination of arm, with irregularities of force, speed, and rhythm

Gait Ataxia: involvement of vermis or vestibulocerebellum leads to abnormal posture as gait

- wide-based stance with trouble walking in straight line esp with tandem gait maneuver

Asssociated Clinical Features:

Titubation: head or upper trunk tremor (3-4 Hz) usually in AP plane may be seen

Hypotonia: decrease in resistance to passive movement of muscles related to depression of gamma motor neuron activity (usually seen transiently in acute phase of cerebellar lesions)

Rebound: related to poor tone and weak check response, so when tap or displace limb, wider range of movement in return to static position, incl. Holmes phenomenon when suddenly release flexed arm held against resistance - unable to stop flexion and arm strike self (delay in activation of antagonist triceps muscle)

Dysarthria: often scanning type with irregularities in tone, with words broken into syllables; often slow with occasional rapid portions ("explosive speech")

Ocular Motor Abnormalities:

- usually if vestibular connections or flocculonodular lobe affected

- pursuit movements no longer smooth, but saccadic

- may over- or under-shoot target with attempts at fixation (ocular dysmetria)

- in primary position may see saccadic intrusions (such as macro square-wave jerks) or primary nystagmus (incl. vertical, esp up-beat nystagmus) or periodic alternating nystagmus

- rebound nystagmus can occur with contralateral-beating nystagmus on return of eyes to primary position after eccentric gaze evoked nystagmus to one side

Differential Diagnosis:

Symptoms of ataxia and incoordination may be seen with lesions outside of the cerebellum

1. Sensory ataxia:

- with severe sensory neuropathy or ganglionopathy can simulate cerebellar ataxia due to loss of proprioceptive input, as can impairment of dorsal column function in spinal cord

- gait often ataxic and limb movements can also be affected with incoordination in reaching target (often associated with pseudo-athetoid movements of distal limbs due to lack of position sense, and upward drift of arm when eyes closed, arms held out)

- lack of other associated cerebellar features incl. dysarthria or nystagmus

- vision also serves corrective function, so eliminating this (Romberg test) should bring out worsening of imbalance (while minimal worsening of already impaired stance with cerebellar)

2. Vestibular / Vertiginous ataxia:

- due to lesion of vestibular pathways resulting in impairment & imbalance of vestibular inputs

- primarily affects gait but may see past-pointing, and usually rotatory nystagmus

- may or may not be associated with vertigo

3. Thalamic ataxia:

- transient ataxia affecting contralateral limbs after lesion of anterior thalamus

- may see associated motor (pyramidal tract) signs from involvement of internal capsule

- also can result in asterixis in contralateral limbs (hemiasterixis)

History:

1. Duration: acute, subacute vs chronic

2. Rate of Progression: static vs progressive

3. Constant vs Paroxysmal

4. Associated features:

- headache & vomiting suggesting mass lesion with raised ICP

- previous neurological events (similar with ataxia - as in episodic ataxias, or other as in multiple sclerosis or vertebrobasilar TIAs)

5. Medical History:

- recent infection, Hx of malignancy or weight loss, breast mass / tenderness, cough / hemoptysis

- drug use / intoxication, medications, alcohol, smoking, environmental exposures

6. Family History positive or negative (in siblings or cousins but not parents suggesting autosomal recessive or parents and/or sibs suggesting autosomal dominant inheritance)

Examination:

General examination:

- signs of primary neoplasm (with paraneoplastic or metastatic ataxia), vascular disease (stroke), cardiac abnormality (Friedreich's) or Kayser-Fleischer rings (Wilson's)

- short stature and cataracts with mitochondrial disease (Marinesco-Sjogren)

Higher Mental Functions:

- confusion associated with ataxia in Wernicke's, drug or environmental toxicity, prion diseases or any condition obstructing 4th ventricle leading to hydrocephalus with raised ICP

Cranial Nerves:

- ophthalmoplegia seen in Wernicke's, brainstem infarcts, demyelinating lesions, and Miller-Fisher syndrome (MFS)

- nystagmus common in most vestibulocerebellar (or pancerebellar) disorders but prominent if drug toxicity (eg. phenytoin), Wernicke's and multiple sclerosis (also episodic ataxia-2)

- associated brainstem (cranial nerve) dysfunction if concomitant involvement of brainstem or compression of it by mass effect from cerebellum

- hearing loss or tinnitus with lesions of the cerebellopontine angle (eg. vestibular schwannoma or meningioma)

Motor:

- weakness associated with ataxia is uncommon but can be seen ipsilaterally with infarcts (or other lesions) of the basis pontis or internal capsule (ataxic hemiparesis syndrome)

- also seen in MFS (with concomitant demyelinating polyneuropathy), cord dysfunction (in paraneoplastic syndromes or demyelinating multifocal disease)

- tremor associated either as intention tremor of cerebellar origin or postural tremor in FXTAS (Fragile X), multiple sclerosis, Wilson's disease

- myoclonus in prion disorders with cerebellar involvement

- parkinsonism with ataxia in multiple systems atrophy (also dystonia and chorea if DRPLA)

Etiology of Cerebellar Ataxia:

By Duration:

1. Acute:

a. Infectious

- Viral cerebellitis (often due to VZV but also rubella, HIV)

- Post-infectious (inflammatory)

b. Toxic:

- Acute intoxication with lithium, ethyl alcohol, barbiturates, phenytoin

- Wernicke's encephalopathy (triad of ataxia, ophthalmoplegia, and confusion)

- Environmental exposure to mercury, toluene (glue sniffing, spray painting)

- Childhood hyperammonemias

c. Paroxysmal (recurrent):

- Episodic ataxias (inherited, acetazolamide-responsive) - types 1 and 2

- simulated by demyelinating events in MS, vertebrobasilar TIAs, foramen magnum compression (eg. Chiari malformation) or toxic ingestions

d. Vascular

- infarction, usually arterial involving portion of cerebellum or cerebellar peduncles

- cerebellar hemorrhage (usually hypertensive, but also AVMs)

e. Demyelinating:

- acute plaque of multiple sclerosis or cerebellar involvement in ADEM

- cerebellar involvement in inflammatory demyelinating polyneuropathy (AIDP) specifically in Miller-Fisher variant with anti-GQ1b antibodies

2. Subacute: (over weeks to months)

a. Neoplastic:

- Primary cerebellar or other posterior fossa tumors incl. medulloblastoma, astrocytoma (esp pilocytic) in children, hemangioblastoma, astrocytoma, and esp metastasis in adults; as well as cerebellopontine angle lesions including vestibular schwannoma, meningioma, epidermoid, cholesteatoma, glomus tumor, aneurysm or dolichoectatic basilar artery

- also cerebellar abscess or other mass lesion as well as hydrocephalus

b. Nutritional:

- Alcoholic cerebellar degeneration (gait primarily involved)

c. Paraneoplastic:

- associated with various tumors including gynecological (anti-Yo), testicular (anti-Ta), small-cell lung cancer (anti-Hu, usually with encephalomyelitis and/or sensory neuronopathy), Hodgkin's lymphoma (anti-Tr) and breast (anti-Ri)

d. Slow infections:

- Prion diseases including Creutzfeld-Jakob disease (CJD) and familial (Gerstmann-Straussler-Sheinker or GSS)

3. Chronic Progressive (over months to years)

a Inherited

- Autosomal dominant cerebellar ataxia (ADCA); or spinocerebellar ataxias (SCAs) as well as rarely (usually in Japan) DRPLA (dentato-rubro-pallido-luysian atrophy)

- Autosomal recessive ataxias esp. Friedreich's ataxia, as well as in children, ataxia-telangiectasia, vitamin E deficiency states (AVED and abetalipoproteinemia), Marinesco-Sjogren syndrome (with mental retardation, bilateral cataracts and short stature), and Ramsay-Hunt syndrome (ataxia with myoclonus, usually associated with mitochondrial mutations such as MERRF)

- also Wilson's disease, leukodystrophies (metachromatic, Krabbe's, adrenoleukodystrophy)

- Hartnup disease

- Multiple Carboxylase deficiency and biotinidase deficiency

b. Degenerative:

- Multiple systems atrophy (incl. olivopontocerebellar atrophy, now MSA-c)

- FXTAS (Fragile X Tremor-Ataxia Syndrome)

4. Chronic Static:

- Congenital ataxia incl. ataxic cerebral palsy of various etiologies

Investigations:

- MRI to rule-out mass lesions, infarcts, white matter disease

for chronic ataxias:

- Wilson's disease screen (24-hr urinary copper, ceruloplasmin, slit-lamp examination)

- Vitamin E level

- Genetic testing for SCAs (esp SCA1, 2, and 3), Friedreich's ataxia (FRDA gene), DRPLA, and MERRF if appropriate family history or clinical presentation

References:

Last update: January 2005

Reviewed by: pending review

Neurological Medicine Pocketbook

http://www.uwo.ca/cns/resident

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