Childhood Status Epilepticus and Epilepsy Determinants of Outcome (SEED)

摘要 癫痫持续状态（SE）是全世界儿童中最常见的严重神经系统急症。在 在撒哈拉以南非洲的低收入和中等收入国家， 死亡率和发病率似乎特别高。然而，儿童SE的表型，临床 SE相关死亡率和SE相关神经发育发病率的预测因子， SE、SE相关死亡率和神经发育发病率的预测因子尚未得到很好的表征 在这个地区。苯二氮卓类耐药SE的临床和基因组预测因子， 导致SE相关死亡率，也没有得到很好的表征，特别是在非洲 孩子在尼日利亚北方，很大一部分患有SE的儿童（约80%）的第一次经历SE 癫痫发作，估计卡诺儿童SE的发病率相对较高。临床上知之甚少。 和基因组风险因素的发展癫痫的非洲儿童谁经历SE作为他们的 第一次发作H3非洲联盟正在深入了解常见人类疾病的基因组因素 并将为SE的全基因组关联研究（GWAS）提供对照。 这个项目，儿童癫痫持续状态和癫痫结果的决定因素（种子），将建立一个 尼日利亚北方卡诺市一个大型SE患儿队列，他们在卡诺市的儿科急诊室就诊。 创新性能力建设将包括将即时脑电图和脑电图视频纳入大规模 卡诺的儿科急诊室，由经过专门培训的社区卫生推广工作者进行 （CHEWs）将接受基本癫痫护理和EEG技术培训。一个专家团队 在Aminu Kano教学医院（AKTH）和范德比尔特大学医学中心（VUMC）， 利用视频检查，EEG视频，详细的历史和大脑MRI对这个大的 SE患儿队列。住院SE相关死亡率的临床风险因素，短期SE- 相关死亡率、长期SE相关死亡率和SE相关神经发育发病率将 下定决心。GWAS将在整个队列中进行，性别匹配的对照来自H3 Africa， 通过AKTH，Bayero University Kano，Sydney Brenner分子生物学研究所 南非的生物科学和VUMC。儿童SE相关死亡率的基因组危险因素， 将确定发病率，以及癫痫发生的临床和基因组风险因素， 首次癫痫发作时发生SE的儿童以及苯二氮卓类药物的临床和基因组风险因素- 抗SE。SEED将为撒哈拉以南非洲的儿童SE提供宝贵的见解。

Abstract Status epilepticus (SE) is the most common serious neurological emergency among children worldwide. In the low- and middle-income countries (LMICs) of sub-Saharan Africa, the burden of childhood SE-associated mortality and morbidity appears to be especially high. However, the phenotypes of childhood SE, clinical predictors of SE-associated mortality and of SE-associated neurodevelopmental morbidity, and genomic predictors of SE, SE-associated mortality and neurodevelopmental morbidity have not been well-characterized in this region. The clinical and genomic predictors of benzodiazepine-resistant SE, which is common and may contribute to SE-associated mortality, have also not been well-characterized, especially among African children. A large percentage of children (~80%) with SE in northern Nigeria experience SE as their first seizure, and the estimated incidence of childhood SE in Kano is relatively high. Little is known of the clinical and genomic risk factors for the development of epilepsy among African children who experience SE as their first seizure. The H3Africa consortium is yielding insights into the genomic factors of common human diseases across the African continent and and will provide controls for genome-wide association studies (GWAS) of SE. This project, Childhood Status Epilepticus and Epilepsy Determinants of Outcome (SEED), will establish a large cohort of children with SE in Kano, northern Nigeria who present to pediatric emergency rooms in Kano. Innovative capacity building will include the incorporation of point-of-care EEG and EEG-video in large pediatric emergency rooms in Kano, performed by specially trained community health extension workers (CHEWs) who will be trained in both basic epilepsy care and EEG technology. A team of specialists working together at Aminu Kano Teaching Hospital (AKTH) and at Vanderbilt University Medical Center (VUMC) will utilize video exams, EEG-video, detailed histories, and brain MRI to perform deep phenotyping on this large cohort of children with SE. Clinical risk factors for in-hospital SE-associated mortality, short-term SE- associated mortality, long-term SE-associated mortality, and SE-associated neurodevelopmental morbidity will be determined. GWAS will be performed on the entire cohort, with gender matched controls from H3Africa, through collaborations between AKTH, Bayero University Kano, the Sydney Brenner Institute for Molecular Bioscience in South Africa, and VUMC. Genomic risk factors for childhood SE-associated mortality and morbidity will be determined, as well as clinical and genomic risk factors for development of epilepsy among children who experience SE as their first seizure and clinical and genomic risk factors for benzodiazepine- resistant SE. SEED will provide valuable insights into childhood SE in sub-Saharan Africa.