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.