Episodic ataxia

Episodic ataxia (EA) presents with paroxysmal truncal ataxia, incoordination, dysarthria, and balance difficulties separated by interictal periods that may be asymptomatic or feature myokymia, nystagmus, or progressive cerebellar signs. Despite clinical classification based on symptomatology and attack features, EAs are conventionally designated as EA1, EA2, and subsequent subtypes according to the order in which their associated loci were identified and described. In total, at least nine episodic ataxia syndromes have been described thus far. While episodic ataxia was the defining feature across all subtypes, each was associated with distinct clinical characteristics. EA1 and EA2 are the most frequently encountered subtypes and best characterized phenotypes. EA1 has short (seconds to minutes) attacks and interictal myokymia, while EA2 has longer attacks (hours to days) and interictal nystagmus in classic cases, and, in over 50% of individuals, chronic progressive ataxia and cerebellar atrophy on imaging. Seizures have been variably reported in association with these genetic conditions, most consistently (but not exclusively) in EA2 and EA6.

The incidence is presumed to be lower than 1 per 100,000; nevertheless, substantial genetic heterogeneity, limited genetic testing, and unresolved molecular diagnoses likely contribute to an underestimation of its true prevalence.

Genes associated with episodic ataxia can be categorized according to their biological function and differ with respect to inheritance patterns, clinical phenotypes, and therapeutic responsiveness. Among these, KCNA1 and CACNA1A are of clinical relevance due to their high prevalence in affected patients. In addition, recently identified disease mechanisms and expanded phenotypic spectra associated with SLC1A3 have further broadened the understanding of EA. Together, these genes exemplify the genetic and clinical heterogeneity of EA and highlight the evolving landscape of classification of paroxysmal movement disorders.

The genetic conditions associated with episodic ataxia so far predominantly follow autosomal dominant inheritance.

• Where episodic ataxia is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members.

• Hasan SM, D’Adamo MC. Episodic ataxia type 1. 2010 Feb 9 [Updated 2018 Nov 1]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from: PMID:20301785.
• Hassan A. Episodic ataxias: primary and secondary etiologies, treatment, and classification approaches. Tremor Other Hyperkinet Mov (N Y). 2023;13:9. doi:10.5334/tohm.747. PMID:; PMCID: PMC10064912.
• de Gusmão CM, Garcia L, Mikati MA, Su S, Silveira-Moriyama L. Paroxysmal genetic movement disorders and epilepsy. Front Neurol. 2021;12:648031. doi:10.3389/fneur.2021.648031. PMID:; PMCID: PMC8021799.
• Harvey S, King MD, Gorman KM. Paroxysmal movement disorders. Front Neurol. 2021;12:659064. doi:10.3389/fneur.2021.659064. PMID:; PMCID: PMC8232056.