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)

基本信息

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
项目类别：
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

项目摘要

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.

抽象的癫痫持续状态（SE）是全世界儿童中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)，与 SE 相关的儿童负担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素以及基因组 SE、SE 相关死亡率和神经发育发病率的预测因素尚未得到充分表征在这个地区。苯二氮卓类耐药 SE 的临床和基因组预测因素，这种情况很常见，可能导致 SE 相关死亡率的因素也尚未得到充分表征，特别是在非洲孩子们。在尼日利亚北部，很大一部分患有 SE 的儿童 (~80%) 将 SE 作为他们的第一次经历癫痫发作，并且卡诺儿童癫痫发作的估计发病率相对较高。临床上知之甚少以及以 SE 为经历的非洲儿童中发生癫痫的基因组危险因素第一次癫痫发作。 H3Africa 联盟正在深入了解人类常见疾病的基因组因素整个非洲大陆，并将为 SE 的全基因组关联研究 (GWAS) 提供对照。该项目名为“儿童癫痫持续状态和癫痫结果决定因素 (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将床旁脑电图和脑电图视频纳入大型医疗中心卡诺的儿科急诊室，由经过专门培训的社区卫生推广人员执行 (CHEW) 将接受基础癫痫护理和脑电图技术方面的培训。专家团队在工作阿米努卡诺教学医院 (AKTH) 和范德比尔特大学医学中心 (VUMC) 共同将利用视频检查、脑电图视频、详细病史和脑部 MRI 对这一大样本进行深度表型分析患有 SE 的儿童队列。院内 SE 相关死亡率、短期 SE 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被确定。 GWAS 将对整个队列进行，其中性别匹配的对照来自 H3Africa，通过 AKTH、卡诺巴耶罗大学、悉尼布伦纳分子研究所之间的合作南非生物科学和 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经历 SE 作为首次癫痫发作以及苯二氮卓类药物临床和基因组危险因素的儿童抗SE。 SEED 将为撒哈拉以南非洲地区的儿童 SEED 提供宝贵的见解。