Ataxia

Basics

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

Diagnosis

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

INITIAL-TESTS

  • 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
  • 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

DIAG-PROCED-SURGERY

  • 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

  • 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

Ongoing Care

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

Additional Reading

  1. 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]
  2. 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]
  3. National Ataxia Foundation: www.ataxia.org [PMID:23683541]
  4. Neuromuscular Disease Center of Washington University: http://neuromuscular.wustl.edu/ataxia/aindex.html
  5. 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]

Codes

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)

FAQ

  • 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).

Authors

Kristin W. Barañano, MD, PhD


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