Environmental Triggers of Eating Seizures in Nodding Syndrome

描述(申请人提供)：点头综合症是一种脑部癫痫，在撒哈拉以南非洲的热点地区发现，包括南苏丹的西赤道省蒙德里县，拟议的流行病学研究的背景。儿童通常在开始吃当地食物后不久就会出现一种无法控制的、有节奏的点头现象，这种现象被称为“进食性癫痫发作/癫痫”。随着时间的推移，点头可能会进展为强直阵挛发作、虚弱和认知障碍，最终导致致命后果。初步研究表明，点头综合征与皮肤感染螺旋体线虫有关，这是盘尾丝虫病(河盲症)的原因，但其他当地环境因素必须参与其中，因为在非洲其他地区，盘尾丝虫病与癫痫有不同的联系，很少与点头综合征有关。我们假设，食物中的植物和/或真菌毒素，在存在或不存在特定营养缺乏的情况下，有助于引发点头综合征儿童的进食性癫痫。我们将在1000名符合条件的受试者(男性和女性，5-21岁)中检验这一假设，我们将从其中选择50名患有点头综合症的受试者(病例)和100名没有头部点头或其他癫痫类型(失神、癫痫发作)的受试者(对照组)。我们将开展这个嵌套病例：点头综合征对照研究，以检验暴露于与癫痫和其他惊厥障碍相关的环境因素的相对贡献。这些包括感染源(螺旋螺)、营养状况(维生素B6、锌)、植物毒素(氰化物)和真菌毒素(海藻毒素、麦角菌)。这些因素将在从病例和对照中收集的食物、血液和尿液中进行分析，并针对点头综合征进行分析。结果将与家庭、社区和卫生当局分享。将就食物的准备和储存提出建议，以最大限度地减少对植物和真菌制剂的接触，这些物质可能会引发癫痫发作，从而加剧大脑损伤。发现植物/真菌毒素可促进癫痫易发个体的癫痫发作，将对全世界癫痫障碍的预防和治疗具有现实意义。

DESCRIPTION (provided by applicant): Nodding Syndrome is a brain seizure disorder found in hotspots in sub-Saharan Africa, including Mundri County, Western Equatoria Province, South Sudan, the setting of the proposed epidemiological study. Children typically develop an uncontrollable, rhythmic nodding of the head shortly after beginning to eat their local diet, a phenomenon termed "eating seizures/epilepsy". With time, head nodding may advance to tonic-clonic seizures, wasting, and cognitive deficits, eventually with a fatal outcome. Preliminary studies show that Nodding Syndrome is associated with skin infection with the nematode worm Onchocerca volvulus, the cause of onchocerciasis (River Blindness), but additional local environmental factors must participate because, in other parts of Africa, onchocerciasis is variably associated with epilepsy and rarely with Nodding Syndrome. We hypothesize that plant and/or fungal toxins in food, in the presence or absence of specific nutritional deficiencies, contribute in triggering eating epilepsy in children with Nodding Syndrome. We will test this hypothesis in a cohort of 1000 eligible subjects (males and females, aged 5-21 years), from which we will select 50 subjects with Nodding Syndrome (Cases) and 100 subjects with no history of head nodding or other seizure types (absence, grand mal) (Controls). We will carry out this nested Case:Control study of Nodding Syndrome to examine the relative contributions of exposure to environmental factors associated with epilepsy and other convulsive disorders. These include infectious agents (Onchocerca volvulus), nutritional status (vitamin B6, zinc), plant toxins (cyanogens) and fungal toxins (tremorgens, ergot). These factors will be analyzed in food, blood and urine collected from Cases and Controls and analyzed with respect to Nodding Syndrome. The results will be shared with families, community and health authorities. Recommendations will be made on food preparation and storage to minimize exposure to plant and fungal agents that may trigger seizure activity and thereby advance brain damage. Discovery that plant/fungal toxins can promote seizures in individuals prone to epileptic attacks would have relevance in the prevention and treatment of epileptic disorders worldwide.