PROJECT SUMMARY/ABSTRACT Epilepsy is one of the common problems that can result after ischemic stroke in a child. Children with post- stroke epilepsy have poorer cognitive outcomes, poorer quality of life and worse health measures. A better understanding of the determinants of post-stroke epilepsy is needed. Children who have acute seizures (those that occur within one week of the stroke) are more likely to develop epilepsy later in childhood, with a cumulative epilepsy incidence of 58% by 10 years. Inflammation and infarct location are two potential links between acute seizures and later development of epilepsy after pediatric stroke. Based on studies in animals and prior work, acute seizures worsen the inflammation that occurs after a stroke; in turn, inflammation may be an important mediator of epilepsy. Another possibility is that acute seizures are a marker of an injury to the anatomic brain regions or networks that are epileptogenic. This ancillary study proposal will examine acute seizures and post-stroke epilepsy in children who had a stroke (28 days of life up to 19 years of age at stroke onset) who were enrolled in two separate cohorts. The two independent cohorts will be utilized as a discovery and validation set. One cohort is from the completed VIPS I study of childhood stroke, and the second is from the ongoing VIPS II study of childhood stroke. In Aim 1, the inflammatory signaling pathways activated by acute seizures will be determined using banked blood collected from children after stroke, validating preliminary work from the VIPS I cohort. In Aim 2, changes in inflammatory signaling pathways will be identified in children who later develop epilepsy. Epilepsy outcomes will be ascertained in both cohorts. Banked blood collected at several timepoints after the stroke will be utilized to determine differential expression of analytes in those who develop epilepsy compared to those who do not. In Aim 3, lesion-symptom mapping and lesion-network mapping will identify the brain regions and functional networks associated with post-stroke epilepsy. Machine learning techniques will be used to integrate results from these three aims, creating models that include relevant laboratory data, clinical data and imaging data. The “Seizures and Children's Outcomes after Stroke (SCOUTS)” study is important because it will improve understanding of epilepsy after pediatric stroke. The results will provide evidence for molecular and anatomic pathways associated with seizures and epileptogenesis and will be used in future research of anti-inflammatory therapeutic agents to reduce the risk of post-stroke epilepsy. The SCOUTS study will identify predictors of epilepsy to improve prognostication for families and inform inclusion criteria in future trials. A rich dataset of longitudinal stroke outcomes will also be a legacy of the study. The long-term objectives of this research are to find a treatment that can be given after a child has a stroke to effecti...