Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches

source extracted confidence: high 2026-04-09
#humans #ataxia #cerebellar-ataxia #acetazolamide #mutation

Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches

Hassan et al., 2023 | Tremor Other Hyperkinet Mov (N Y) | Systematic Review

Citation

Hassan Anhar. Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches. Tremor Other Hyperkinet Mov (N Y). 2023;13:9. doi:10.5334/tohm.747

Abstract

BACKGROUND: Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in KCNA1 and CACNA1A. EA3-8 are reported in rare families. Advances in genetic testing have broadened the KCNA1 and CACNA1A phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists. METHODS: A systematic literature review was performed in October 2022 for 'episodic ataxia' and 'paroxysmal ataxia', restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized. RESULTS: EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (SCA-14, SCA-27, SCA-42, AOA2, CAPOS), epilepsy syndromes (KCNA2, SCN2A, PRRT2), GLUT-1, mitochondrial disorders (PDHA1, PDHX, ACO2), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause. DISCUSSION: EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and treatment pathways. For atypical phenotypes, next generation genetic testing can aid diagnosis and guide treatment. Updated classification systems for EA are discussed which may assist diagnosis and management.

Key Findings

EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (SCA-14, SCA-27, SCA-42, AOA2, CAPOS), epilepsy syndromes (KCNA2, SCN2A, PRRT2), GLUT-1, mitochondrial disorde

Outcomes Measured

  • anxiety
  • inflammatory markers

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition anxiety

MeSH Terms

  • Humans
  • Ataxia
  • Cerebellar Ataxia
  • Acetazolamide
  • Mutation

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Systematic Review, Case Reports, Journal Article
  • Vertical: biotin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09