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Ataxia, Pediatric

Basics

Description

- 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, 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, check alpha fetoprotein [AFP] level, sensitive after 1 year of age)

- 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, and limb dysmetria with finger-nose-finger, overshoot with finger-chase, dysdiadochokinesia with rapid alternating movements, heel to shin test - Gait: ability to tandem walk, sway with Romberg test (either cerebellar or proprioceptive defect)

- 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 (MTHF), amino acids; pair with serum glucose and amino acids

- Treatment of many of the acute ataxias (ingestions, postviral) is supportive. - Specific therapies - ADEM: steroids - 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

  • 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-Barr © syndrome (GBS) (combined account for 80% of total).
  • Dominantly inherited spinocerebellar ataxias (SCAs) are 1-5 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 (FRDA) at 1 in 30,000-50,000

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 onsetIngestions/intoxications: alcohol, anticonvulsants including phenytoin, benzodiazepines, antihistamines, heavy metals, carbon monoxideInfections (e.g., Bartonella, Mycoplasma, Epstein-Barr virus)PostinfectiousPostvaccinationDemyelinating 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 onsetCerebellar hemorrhageIschemic strokeEncephalitis or cerebellitisAcute 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 progressiveDevelopmental defects: Dandy Walker, cerebellar agenesis, rhombencephalosynapsis, Chiari I malformationAtaxic cerebral palsyTumorsParaneoplasticMetabolic/degenerativeWith pathologic accumulation: hexosaminidase deficiency, Niemann-Pick type C, metachromatic leukodystrophy, Wilson diseaseHypomyelinating leukodystrophies (e.g., Pelizaeus-Merzbacher disease)SCAsAR ataxias including FRDA (associated pes cavus, cardiomyopathy, diabetes, polyneuropathy), ataxia telangiectasia (frequent infections, increased susceptibility to leukemia/lymphoma; telangiectasias are a late finding, check alpha fetoprotein [AFP] level, sensitive after 1 year of age)
  • RecurrentMigraine (vestibular migraine can present with ataxia and vertigo without headache)Episodic ataxia (EA1 and EA2 best characterized, at least 6 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 examMental status: altered with ingestions, CNS infections, ADEMCranial 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 speechMotor: presence of hypotonia or tremor, exclude weakness as cause of incoordinationReflexes: absence suggestive of GBSSensory: assess for sensory ataxia due to lack of proprioceptive inputCoordination: presence of head titubation, truncal ataxia, intention tremor, and limb dysmetria with finger-nose-finger, overshoot with finger-chase, dysdiadochokinesia with rapid alternating movements, heel to shin testGait: ability to tandem walk, sway with Romberg test (either cerebellar or proprioceptive defect)

Diagnostic Tests & Interpretation

Lab

  • Initial ER screening labs for acute presentation:CBC, comprehensive metabolic panel (CMP)Lactate, ammoniaToxicology screen and drug levels for specific intoxications
  • Additional investigations for chronic/progressive ataxias:Rule out reversible/potentially treatable causes:Exposures: heavy metals, zinc (chelates copper)Autoimmune: celiac, anti-glutamic acid decarboxylase (GAD), paraneoplastic panel, urine homovanillic acid/vanillylmandelic acid (HVA/VMA) for neuroblastomaMetabolic: TSH, vitamin E, coenzyme Q, 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 enzymesOther potential screening laboratories: lipid panel, IgA levels, AFPAtaxia panels for inherited cerebellar ataxias (e.g., SCAs); most not clinically distinguishable in early stages

Imaging

  • 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.

Diagnostic Procedures/Other

  • Lumbar punctureFor infection or ADEM: cell counts, protein, glucose, bacterial culture and viral polymerase chain reactions (PCRs), IgG index, oligoclonal bandsFor suspected metabolic disorders: glucose, protein, cell counts, lactate, pyruvate, 5-methyltetrahydrofolate (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

Differential 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

Treatment

  • Treatment of many of the acute ataxias (ingestions, postviral) is supportive.
  • Specific therapiesADEM: steroidsGBS: intravenous immunoglobulin (IVIG), plasmapheresisParaneoplastic: treatment of malignancy, immunosuppressionMigraine: avoidance of food triggers, preventive medications (e.g., calcium channel blockers, tricyclic antidepressants [TCAs])Episodic ataxias: acetazolamideInherited ataxias: some evidence for use of medications such as amantadine, riluzole, vareniclinePossible 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 (more than 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

  • Poretti A, Benson JE, Huisman TA, et al. Acute ataxia in children: approach to clinical presentation and role of additional investigations. Neuropediatrics. 2013;44(3):127-141. [View Abstract]
  • Vedolin L, Gonzalez G, Souza CF, et al. Inherited cerebellar ataxia in childhood: a pattern-recognition approach using brain MRI. AJNR Am J Neuroradiol. 2013;34(5):925-934. [View Abstract]
  • Whelan HT, Verma S, Guo Y, et al. Evaluation of the child with acute ataxia: a systematic review. Pediatr Neurol. 2013;49(1):15-24. [View Abstract]
  • National Ataxia Foundation: www.ataxia.org
  • Neuromuscular Disease Center of Washington University: http://neuromuscular.wustl.edu/ataxia/aindex.html

Codes

ICD09

  • 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 Friedreichs 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 of the mode of inheritance: AR (25%), autosomal dominant (50%, with risk of anticipation for disorders with polyglutamine expansion), maternal (mitochondrial and X-linked disorders).