DESCRIPTION

• Ataxia refers to incoordination of movement out of proportion to weakness.
• Can be caused by dysfunction of cerebellum, proprioception, or vestibular system
• Careful history of timing of onset and antecedent events key in framing differential: acute, subacute, chronic/progressive, episodic

EPIDEMIOLOGY

• Acute cerebellar ataxia (ACA) was previously seen in 1 per 5,000 cases of varicella, accounting for 25% of total cases. The risk following varicella-zoster virus (VZV) vaccination is 1.5 per 1,000,000 doses.
• Most cases of ACA are still postviral, followed by ingestions, then Guillain-Barré syndrome (GBS) (combined account for 80% of total).
• Dominantly inherited spinocerebellar ataxias (SCAs) are 1 to 5 per 100,000 but tend to have a later age of onset.
• More likely to see autosomal recessive (AR) ataxias in childhood; most common is Friedreich ataxia (FRDA) at 1 in 30,000 to 50,000.

PATHOPHYSIOLOGY

• The cerebellum does not generate motor commands; instead, it modifies them to make them accurate and adaptive.
• The cerebellum receives input from the vestibular apparatus, spinal cord, and the cerebral cortex (via the pons).
• Both input and output is ipsilateral (i.e., right-sided cerebellar lesions cause right-sided ataxia).
• Midline cerebellum (vermis) controls gait, head and trunk stability, eye movements; lesions of vermis result in wide-based (“drunken sailor”) gait, truncal sway, and head titubation (bobbling movements).
• Cerebellar hemispheres control limb tone and coordination, motor learning, speech, eye movements; lesions of the cerebellar hemispheres cause limb dysmetria (trouble with finger-nose-finger testing).
• Function can be impaired by chemicals, autoimmune processes, genetic mutations; typical pathologic finding is loss of Purkinje cells and injury to their elaborate dendritic arbor.

ETIOLOGY

• Acute onset
  • Ingestions/intoxications: alcohol, anticonvulsants including phenytoin, benzodiazepines, antihistamines, heavy metals, carbon monoxide
  • Infections (e.g., Bartonella, Mycoplasma, Epstein-Barr virus)
  • Postinfectious
  • Postvaccination
  • Demyelinating events: multiple sclerosis, acute disseminated encephalomyelitis (ADEM) (can be associated with altered mental status and seizure), Miller Fisher variant of GBS (triad of ataxia, ophthalmoplegia, areflexia; look for eye movement abnormalities and areflexia)
  • Initial presentation of recurrent ataxia
• Subacute onset
  • Cerebellar hemorrhage
  • Ischemic stroke
  • Encephalitis or cerebellitis
  • Acute labyrinthitis/vestibular neuronitis (often prominent nausea/vomiting, hearing affected)
  • Posterior fossa tumors (e.g., medulloblastoma)
  • Paraneoplastic syndromes (opsoclonus-myoclonus syndrome, with multidirectional chaotic eye movements; evaluate for neuroblastoma)
• Chronic or progressive
  • Developmental defects: Dandy-Walker syndrome, cerebellar agenesis, rhombencephalosynapsis, Chiari I malformation
  • Ataxic cerebral palsy
  • Tumors
  • Paraneoplastic
  • Metabolic/degenerative
    • With pathologic accumulation: hexosaminidase deficiency, Niemann-Pick type C, metachromatic leukodystrophy, Wilson disease
    • Hypomyelinating leukodystrophies (e.g., Pelizaeus-Merzbacher disease)
    • SCAs
    • AR ataxias including FRDA (associated pes cavus, cardiomyopathy, diabetes, polyneuropathy), ataxia telangiectasia (frequent infections, increased susceptibility to leukemia/lymphoma; telangiectasias are a late finding)
• Recurrent
  • Migraine (Vestibular migraine can present with ataxia and vertigo without headache.)
  • Episodic ataxia (EA1 and EA2 best characterized, at least six loci identified)
  • Metabolic disorders: mitochondrial disorders, Hartnup disease, urea cycle defects, intermittent forms of maple syrup urine disease

HISTORY

• Focus on the time course of onset.
• Elicit possible ingestions, access to medications at homes of friends, family
• Antecedent infections or vaccinations (fever, especially upper respiratory infection [URI] and GI symptoms)
• Recent trauma (concussion, possible vertebral artery dissection)
• Past medical history: similar episodes, migraines, congenital heart defect, multiple organ system involvement suggestive of metabolic/mitochondrial disease, unusual susceptibility to infection
• Family history: recurrent or progressive ataxias, migraines
• Symptoms to elicit: altered mental status, headache, diplopia, vertigo (illusion of movement or dizziness), history of seizure, nausea/vomiting, diminished hearing, or tinnitus

PHYSICAL-EXAM

• Vital signs: presence of fever
• General exam: presence of meningismus; otoscopic examination for otitis; assess for pharyngitis, lymphadenopathy, splenomegaly, rash, skin and eyes for telangiectasias
• Neurologic exam
  • Mental status: altered with ingestions, CNS infections, ADEM
  • Cranial nerves: funduscopic exam for papilledema, eye movement abnormalities, presence of nystagmus, head impulse (thrust) test for vestibular function, hearing with tuning fork (Weber and Rinne tests), dysarthria or scanning speech
  • Motor: presence of hypotonia or tremor, exclude weakness as cause of incoordination
  • Reflexes: absence suggestive of GBS
  • Sensory: Assess for sensory ataxia due to lack of proprioceptive input.
  • Coordination: presence of head titubation, truncal ataxia, intention tremor; limb dysmetria with finger-nose-finger, overshoot with finger chase; dysdiadochokinesia with rapid alternating movements, and heel to shin test
  • Gait: ability to tandem walk, sway with Romberg test (either cerebellar or proprioceptive defect)

DIFF-DIAGNOSIS

• Movement disorders: Tremor, chorea, athetosis may be mistaken for ataxia.
• Weakness: incoordination in proportion to weakness (myasthenia gravis, GBS)
• Conversion disorder: variability, distractibility, lack of associated cerebellar signs, astasia-abasia (exaggerated factitious inability to walk or stand)
• Epileptic ataxia (pseudoataxia): episodic, associated alteration of awareness
• Optic ataxia: difficulty reaching for target due to lesions in posterior parietal lobe resulting in impaired visual input to cerebellum

TESTS

PROGNOSIS

• Most acute ataxias are ingestions and postviral and have a good prognosis. If recovery from a presumed postviral ataxia is delayed (>2 weeks), evaluation for neuroblastoma should be undertaken.
• Recovery from GBS is generally good but can be incomplete.
• Specific diagnosis of an inherited cerebellar ataxia is helpful in predicting clinical course (time to wheelchair, potential for cognitive decline, death).

COMPLICATIONS

• Risk of injury due to falls
• Risk of aspiration due to swallow dysfunction
• Autonomic instability can be associated with GBS.
• With inherited cerebellar ataxias: Some patients also develop neuropathy, spasticity, and cognitive decline.
• Risk of depression and cognitive impairment given increasingly recognized role of cerebellum in cognition and emotion

ICD9

• 781.3 Lack of coordination
• 334.3 Other cerebellar ataxia
• 334 Friedreich’s ataxia
• 334.4 Cerebellar ataxia in diseases classified elsewhere
• 334.1 Hereditary spastic paraplegia

ICD10

• R27.0 Ataxia, unspecified
• G11.9 Hereditary ataxia, unspecified
• G11.1 Early-onset cerebellar ataxia
• G11.8 Other hereditary ataxias
• R26.0 Ataxic gait
• G11.0 Congenital nonprogressive ataxia
• G11.2 Late-onset cerebellar ataxia
• R27.8 Other lack of coordination

SNOMED

• 20262006 Ataxia (finding)
• 129609000 Spinocerebellar ataxia
• 10394003 Friedreich's ataxia (disorder)
• 230227009 Early onset cerebellar ataxia (disorder)
• 192874000 cerebellar ataxia associated with another disorder (disorder)
• 230232005 Late onset cerebellar ataxia (disorder)