International Conference on Episodic Ataxia Syndromes

描述（由申请人提供）：发作性共济失调综合征是一种罕见的神经系统疾病，其特征是间歇性的不协调和不平衡，通常伴有进行性共济失调。早发性发作性共济失调的致病基因病变包括神经元电压门控钾钙通道，这些通道广泛分布于神经系统，在小脑特别丰富。遗传定义有助于拓宽发作性共济失调的临床范围，目前已知与癫痫、肌张力障碍、偏瘫性偏头痛、肌无力甚至昏迷有不同的关联。这些离子通道基因的突变如何引起广泛的阵发性神经症状并导致进行性神经变性尚不清楚。此外，即使在具有相同突变的患者中，临床表现和对药物的反应也存在很大差异，这表明其他因素可能调节致病突变的表型表达。发作性共济失调在临床上和遗传学上都是异质的；许多发作性共济失调患者，特别是那些在成年早期发病的患者，需要进一步的基因鉴定和突变鉴定。

DESCRIPTION (provided by applicant): 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.