- 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
- 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.
- 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.
- Acute onset
- Ingestions/intoxications: alcohol, anticonvulsants including phenytoin, benzodiazepines, antihistamines, heavy metals, carbon monoxide
- Infections (e.g., Bartonella, Mycoplasma, Epstein-Barr virus)
- 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
- With pathologic accumulation: hexosaminidase deficiency, Niemann-Pick type C, metachromatic leukodystrophy, Wilson disease
- Hypomyelinating leukodystrophies (e.g., Pelizaeus-Merzbacher disease)
- AR ataxias including FRDA (associated pes cavus, cardiomyopathy, diabetes, polyneuropathy), ataxia telangiectasia (frequent infections, increased susceptibility to leukemia/lymphoma; telangiectasias are a late finding)
- 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
- 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
- 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)
- 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
- Initial ER screening labs for acute presentation:
- CBC, comprehensive metabolic panel (CMP)
- Lactate, ammonia
- Toxicology screen and drug levels for specific intoxications
- Additional investigations for chronic/progressive ataxias:
- Rule out reversible/potentially treatable causes:
- Exposures: heavy metals, zinc (chelated copper)
- Autoimmune: celiac, anti-glutamic acid decarboxylase (GAD), paraneoplastic panel, urine homovanillic acid/vanillylmandelic acid (HVA/VMA) for neuroblastoma
- Metabolic: TSH, vitamin E, coenzyme Q, vitamin B12 and B1 levels, copper, ceruloplasmin, lactate, ammonia, plasma amino acids, urine organic acids, urine amino acids (for Hartnup disease), very-long-chain fatty acid (VLCFA) with phytanic acid (Refsum), paired CSF and serum glucose levels or SLC2A1 sequencing for GLUT1 deficiency, cholestanol (cerebrotendinous xanthomatosis), lysosomal enzymes
- Other potential screening laboratories: lipid panel, IgA levels
- Serum α-fetoprotein (AFP) level is sensitive screening lab after 1 year of age for AT
- Ataxia panels for inherited cerebellar ataxias (e.g., SCAs); most not clinically distinguishable in early stages
- Rule out reversible/potentially treatable causes:
- Head CT in the acute setting for altered mental status or concern for hemorrhage
- MRI of brain more sensitive in assessing posterior fossa pathology; consider administration of contrast if concern for infection/demyelination; MRA of brain and neck if concern for stroke/dissection
- Lumbar puncture
- For infection or ADEM: cell counts, protein, glucose, bacterial culture and viral polymerase chain reactions (PCRs), IgG index, oligoclonal bands
- For suspected metabolic disorders: glucose, protein, cell counts, lactate, pyruvate, 5-methyltetrahydrofolate (5-MTHF), amino acids; pair with serum glucose and amino acids
- Metaiodobenzylguanidine (MIBG) scan and body CT for potential neuroblastoma
- Nerve conduction studies: suspected GBS
- Electronystagmography (ENG) for potential vestibular involvement
- EEG for consideration of epileptic ataxia
- Treatment of many of the acute ataxias (ingestions, postviral) is supportive.
- Specific therapies
- ADEM: corticosteroids
- GBS: intravenous immunoglobulin (IVIG), plasmapheresis
- Paraneoplastic: treatment of malignancy, immunosuppression
- Migraine: avoidance of food triggers, preventive medications (e.g., calcium channel blockers, tricyclic antidepressants [TCAs])
- Episodic ataxias: acetazolamide
- Inherited ataxias: some evidence for use of medications such as amantadine, riluzole, varenicline
- Possible role for treatment with specific vitamins and cofactors (carnitine, coenzyme Q, vitamin E, riboflavin, folinic acid) for mitochondrial disorders
- 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).
- 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
- Blaser SI, Steinlin M, Al-Maawali A, et al. The pediatric cerebellum in inherited neurodegenerative disorders: a pattern-recognition approach. Neuroimaging Clin N Am. 2016;26(3):373–416. [PMID:27423800]
- Caffarelli M, Kimia AA, Torres AR. Acute ataxia in children: a review of the differential diagnosis and evaluation in the emergency department. Pediatr Neurol. 2016;65:14–30. [PMID:27789117]
- National Ataxia Foundation: www.ataxia.org [PMID:23683541]
- Neuromuscular Disease Center of Washington University: http://neuromuscular.wustl.edu/ataxia/aindex.html
- Paulson HL, Shakkottai VG, Clark HB, et al. Polyglutamine spinocerebellar ataxias—from genes to potential treatments. Nat Rev Neurosci. 2017;18(10):613–626. [PMID:28855740]
- 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
- 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
- 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)
- Q: Which ingestions are most likely to cause ataxia?
- A: Alcohol, anticonvulsants, antihistamines, benzodiazepines, TCAs
- Q: What is the typical time course of postinfectious ataxia?
- A: Typically, it will be maximal in onset in the first day or two, then improve within 2 weeks. Ataxia persisting beyond 2 weeks should prompt evaluation for neuroblastoma.
- Q: What is the role of physical therapy for cerebellar ataxia?
- A: Studies have demonstrated that intensive coordination training improves motor performance in progressive cerebellar disorders and translates into improved activities of daily living.
- Q: What is the risk of transmitting a hereditary cerebellar ataxia?
- A: It depends on the mode of inheritance: AR (25%), autosomal dominant (50%, with risk of anticipation for disorders with polyglutamine expansion), maternal (mitochondrial and X-linked disorders).
Kristin W. Barañano, MD, PhD
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