Episodic ataxia syndromes are rare neurological conditions characterized by spells of incoordination and imbalance, often with associated progressive ataxia. The causative gene lesions for episodic ataxia of early onset include neuronal voltage-gated potassium and calcium channels that are widely distributed in the nervous system with special abundance in the cerebellum. Genetic definition has helped broaden the clinical spectrum of episodic ataxia, now known to be variably associated with epilepsy, dystonia, hemiplegic migraine, myasthenia, and even coma. How mutations in these ion channel genes cause a broad spectrum of paroxysmal neurological symptoms and lead to progressive neurodegeneration is not understood. Furthermore, there is much variation regarding clinical manifestations and response to medications even among patients with the same mutations, suggesting that other factors may modulate the phenotypic expression of disease-causing mutations. Episodic ataxia is clinically and genetically heterogeneous; many patients with episodic ataxia, especially those with onset after early adulthood, await further genetic characterization and mutation identification. This grant requests support for a 2-day meeting to be held in Santa Monica, CA that will bring together clinicians, basic researchers, and representatives of lay organizations with a research focus on episodic ataxia. ORD/NINDS has funded a multicenter project to recruit patients to define the natural course of neurological channelopathies (CINCH, for clinical investigation of neurological channelopathies) including episodic ataxia and to develop treatment strategies for episodic ataxia and other related neurological disorders. This proposed meeting is the second in a sequence of 3 international meetings proposed as a key aspect of achieving the goals of CINCH. The meeting's goals will be 1) to review clinical studies and animal models to summarize current understanding concerning the pathogenesis of episodic ataxia, 2) to evaluate the rationale for various treatment strategies and to discuss the feasibility of clinical trials to validate various treatment options, and 3) to consider shared mechanisms underlying episodic ataxia and other far more prevalent paroxysmal conditions such as epilepsy and migraine.
