Childhood Status Epilepticus and Epilepsy Determinants of Outcome (SEED)

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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.