Investigating the Role of Lesion-Network Connectivity in Pediatric Poststroke Epilepsy

Background and ObjectivesEpilepsy is a common and debilitating sequela of pediatric stroke, but it is unclear how poststroke epilepsy risk relates to lesion location. Recent work has identified lesion connectivity networks associated with poststroke epilepsy risk in adults. We aimed to determine whether these risk networks could be directly translated to pediatric stroke. We hypothesized that lesion connectivity with these networks would provide unique information about pediatric poststroke epilepsy outcomes. MethodsWe studied children who were prospectively enrolled in the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with acute arterial ischemic stroke. Acute provoked seizures and epilepsy were identified up to 15 years poststroke through the Seizures and Children's Outcomes after Stroke (SCOUTS) study. Lesion connectivity was estimated using structural and functional epilepsy risk networks derived from adult stroke patients. We compared lesion connectivity between patients with vs without epilepsy, evaluated whether lesion connectivity provided unique information about epilepsy outcomes beyond other risk factors, and evaluated whether effects of lesion connectivity on epilepsy outcomes might be mediated by effects on acute provoked seizures. ResultsData from 328 children were included in the study (median age 8 years, 43% female). Children who developed epilepsy (n = 40, median age 3.1 years, 35% female) showed stronger lesion connectivity to the epilepsy risk networks than children without epilepsy (n = 288, median age 9.0 years, 44% female), enabling robust group discrimination (area under the curve = 0.71, 95% CI = [0.63, 0.78]). The addition of lesion connectivity estimates to logistic regression models that included age at stroke onset, acute provoked seizure occurrence (within 7 days after stroke), and lesion size/total cortical involvement as predictors of epilepsy outcomes improved model performance (likelihood ratio test: χ2[1] = 7.85, pFWE = 0.015). The effect of lesion connectivity on epilepsy risk was partially mediated by acute provoked seizure occurrence (z = 2.65, p = 0.008). DiscussionLesion connectivity uniquely contributes to epilepsy outcomes after pediatric ischemic stroke beyond other known risk factors, in part by modifying the risk of acute provoked seizures. Lesion networks associated with epilepsy risk in adult stroke patients can be translated to predict epilepsy outcomes after pediatric stroke, showing proof-of-concept for translating adult-derived lesion networks to pediatric populations.