Childhood Status Epilepticus and Epilepsy Determinants of Outcome (seed): A Cohort Protocol

Childhood Status Epilepticus and Epilepsy Determinants of Outcome (SEED): A cohort protocol

Objective: To perform deep phenotyping of childhood status epilepticus (SE) and determine the clinical and genomic predictors of outcome in a large cohort study. Methods: We will enroll up to ~1800 children, ages 30 days to < 15 years, with SE from three hospitals in Kano, Nigeria over 24 months. SE diagnosis and treatment will be based upon a standardized protocol implemented at the three participating hospitals. Epileptologists will phenotype SE, using standardized criteria, including point-of-care EEG-video, MRI, and detailed medical and family history, and standard laboratory tests. Blood for DNA extraction will be obtained upon enrollment. Genomic risk factors for SE-associated mortality, morbidity, benzodiazepine-resistant SE, and development of epilepsy will be studied via genome-wide association studies (GWAS). GWAS, identifying SNPs associated with poor outcomes, and candidate gene analyses will be performed using the H3Africa Illumina array of ~2.3 million SNPs, enriched for common African variants, with PCA-matched population controls from H3Africa collaborators. Results: The outcomes measures will include the clinical and genomic predictors of (1) short-term SE-associated mortality, (2) benzodiazepine-resistant SE, (3) long-term SE-associated mortality and morbidity, (4) recurrent SE, and (5) development of epilepsy after surviving first seizure as SE. Others are detailed EEG-video and MRI findings associated with SE.

Conclusions: SEED will provide the most detailed-to-date characterization of childhood SE in sub-Saharan Africa, as well as significant insights into the clinical and genomic predictors of SE-associated outcomes, including the development of epilepsy. Funding: NIH1R01 NS118483