Childhood Status Epilepticus and Epilepsy Determinants of Outcome (SEED)

儿童期癫痫持续状态和癫痫结果决定因素 (SEED)

• 批准号: 10222800
• 负责人: Michele Michele Ramsay
• 金额: $ 70.76万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10222800
• 关键词: Academic Medical Centers; Accident and Emergency department; Address; Africa; Africa South of the Sahara; African; Age; Asia; Awareness; Benzodiazepines; Biological Sciences; Blood; Brain; Brain imaging; Candidate Disease Gene; Caring; Central Nervous System Infections; Cessation of life; Child; Childhood; Cities; Clinical; Cohort Studies; Collaborations; Collection; Community Health; Country; DNA; Data; Data Coordinating Center; Development; EEG-based imaging; Electroencephalography; Emergency Situation; Enrollment; Epilepsy; Europe; Family; Frequencies; Funding; Future; Gender; Genetic; Genomics; Grant; Hospitals; Human; Hypoglycemia; Incidence; Income; Infant; Institutes; Laboratories; Lead; Life; Magnetic Resonance Imaging; Medical History; Medical Records; Molecular; Morbidity - disease rate; Neurologic; Neurological emergencies; Neurology; Nigeria; North America; Outcome; Pharmaceutical Preparations; Phenotype; Physicians; Population Control; Prevention; Publishing; Randomized Controlled Trials; Recording of previous events; Recurrence; Research; Resistance; Rest; Risk Factors; Seizures; Site; South Africa; Specialist; Standardization; Status Epilepticus; Survivors; System; Teaching Hospitals; Technology; Testing; Training; Treatment Protocols; United States National Institutes of Health; Universities; Variant; Wit; base; clinical predictors; clinical risk; cohort; disability; disability risk; experience; genome wide association study; genomic data; genomic predictors; global health; high risk; human disease; improved; innovation; insight; low and middle-income countries; modifiable risk; mortality; mortality risk; pediatric emergency; phenotypic data; point of care; screening; treatment strategy

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.

摘要 癫痫持续状态(SE)是世界范围内儿童最常见的严重神经急症。在 撒哈拉以南非洲的低收入和中等收入国家(LMIC)儿童的负担与SE相关 死亡率和发病率似乎特别高。然而，儿童SE的临床表型 SE相关死亡率、SE相关神经发育发病率和基因组的预测因素 SE、SE相关死亡率和神经发育发病率的预测因素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素 导致SE相关死亡的因素也没有得到很好的描述，特别是在非洲 孩子们。尼日利亚北部患有SE的儿童中有很大比例(约80%)第一次经历SE 据估计，卡诺儿童癫痫的发病率相对较高。临床上对此知之甚少。 和基因组危险因素在经历SE的非洲儿童中发展为癫痫 第一次癫痫发作。H3非洲联盟正在对常见人类疾病的基因组因素进行深入研究 整个非洲大陆，并将为SE的全基因组关联研究(GWAS)提供控制。 该项目，儿童癫痫状态和癫痫结局决定因素(SEED)，将建立一个 尼日利亚北部卡诺的一大批患有SE的儿童来到卡诺的儿科急诊室就诊。 创新能力建设将包括纳入护理地点EEG和EEG-视频 卡诺的儿科急诊室，由受过专门培训的社区卫生推广人员执行 他们将接受基本的癫痫护理和脑电技术方面的培训。一组专家在工作 在Aminu Kano教学医院(AKTH)和范德比尔特大学医学中心(VUMC)将一起 利用视频检查、脑电视频、详细的病史和脑MRI对这一大型病例进行深度表型分析 患有自闭症的儿童队列。住院SE相关死亡率、短期SE相关死亡的临床危险因素 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 要下定决心。将在整个队列中进行GWAS，并使用来自H3非洲的性别匹配对照， 通过AKTH、巴耶罗大学卡诺、悉尼布伦纳分子研究所 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和 将确定发病率，以及癫痫发生的临床和基因组危险因素 首次癫痫发作的儿童与苯二氮类药物的临床和基因组危险因素 抗性SE。SEED将为撒哈拉以南非洲的儿童SE提供有价值的见解。