EEG markers predictive of epilepsy risk in pediatric cerebral malaria - A feasibility study

Objective: Cerebral malaria (CM) affects 500,000 million children annually, 10% whom develop epilepsy within two years. Acute identification of biomarkers for post-CM epilepsy would allow for follow-up of the highest risk populations in resource-limited regions. We investigated the utility of electroencephalogram (EEG) and clinical metrics obtained during acute CM infection for predicting epilepsy.

Methods: We analyzed 70 EEGs recorded within 24 h of admission for CM hospitalization obtained during the Blantyre Malaria Project Epilepsy Study (2005-2007), a prospective cohort study of pediatric CM survivors. While all studies underwent spectral analyses for comparisons of mean power band frequencies, a subset of EEGs from the 10 subjects who developed epilepsy and 10 age- and sex-matched controls underwent conventional visual analysis. Findings were tested for relationships to epilepsy outcomes.

Results: Ten of the 70 subjects developed epilepsy. There were no significant differences between groups that were analyzed via visual EEG review; however, spectral EEG analyses revealed a significantly higher gamma-delta power ratio in CM survivors who developed epilepsy (0.23 ± 0.10) than in those who did not (0.16 ± 0.06), p = 0.003. Excluding potential confounders, multivariable logistic-regression analyses found relative gamma power (p = 0.003) and maximum temperature during admission (p = 0.03) significant and independent predictors of post-CM epilepsy, with area under receiver operating characteristics (AUROC) curve of 0.854.

Conclusions: We found that clinical and EEG metrics acquired during acute CM presentation confer risk of post-CM epilepsy. Further studies are required to investigate the utility of gamma activity as a potential biomarker of epileptogenesis and study this process over time. Additionally, resource limitations currently prevent follow-up of all CM cases to surveil for epilepsy, and identification of acute biomarkers in this population would offer the opportunity to allocate resources more efficiently.