Following Severe Pediatric Malaria, Epilepsy Screening Is Needed Even Among Children Without Coma: Findings From a Prospective Cohort Study

Background: Severe pediatric malaria with neurological presentation has a spectrum of severity, from frank coma (Cerebral Malaria (CM)) to impaired consciousness and/or complex seizures without coma (malaria with central nervous system signs, CNS-M). Approximately 9-16% of pediatric CM survivors develop post-malaria epilepsy (PME), but rates after CNS-M are understudied. Objective: Determine PME rates following severe pediatric malaria with neurologic signs, with and without coma (CM and CNS-M). Design: Prospective cohort study. Methods: Children 6 months-11 years who presented to a district level hospital in Zambia with CM or CNS-M between Nov 2021-June 2024 were enrolled. Children were excluded for pre-existing epilepsy or alternative explanation for acute neurologic symptoms. Primary outcome was PME at 1 year. Important covariates included coma, age, pre-illness neurodevelopment, acute hospitalization data, acute and follow-up EEG, and 1-year neurodevelopmental outcomes. Acute, 1-, 6-, and 12-month data were collected. EEGs were analyzed with conventional and quantitative methods. PME was determined by standardized screening and physician review using ILAE criteria. Results: 141 children met inclusion criteria, 48 had CM, 93 CNS-M. CNS-M children were younger (mean 40.8 vs. 54.3 months, p=0.005) and male predominant (64.8% vs. 43.8%, p=0.006). 18.4% of the cohort developed PME, with no significant incidence difference between CNS-M (20.4%) and CM (14.6%) groups, p=0.495. Focal epilepsy was more common in CNS-M 78.9% vs. CM 28.6% (p=0.028). There were no differences in qualitative EEG findings. Quantitative EEG measures demonstrated more severe and prolonged cortical dysfunction in CM (p<0.01). Conclusions: CNS-M presentation was twice as frequent as CM at this district hospital. Quantitative EEG supports CM as a more severe acute illness, but PME developed in 15-20% of children within one year regardless of malarial coma. These findings suggest that severe malaria with neurologic involvement-regardless of coma during acute presentation-has significant secondary epilepsy risk.