Predicting epilepsy in cerebral malaria: working toward identifying biomarkers of epileptogenesis in children

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PROJECT SUMMARY/ABSTRACT Over half a million children suffer from cerebral malaria annually, with up to 10-16% of this population developing epilepsy within two years. Thus, cerebral malaria contributes significantly to the global epilepsy burden. As in many acquired epilepsies, there remains an important gap in knowledge on how to identify which children after cerebral malaria infection will be at risk for epilepsy development. Identification of biomarkers heralding epilepsy risk would improve timely identification of who would most benefit from closer clinical monitoring- a critical consideration for improved allocation of the limited available resources in regions where this disease is most prevalent. Identification of the specific clinical and electroencephalographic (EEG) metrics which confer risk of post- malaria epilepsy will also importantly help understand epilepsy development in this disease. Studying these processes in acquired epilepsies has proven difficult to date due to the varied nature of etiologies and timing of epilepsy development after brain insult. Cerebral malaria has potential to be a unique model for identification of epileptogenesis biomarkers, as it is a single disease state with a high rate of post-epilepsy development within a relatively short time frame. This proposal will address key gaps in knowledge regarding the utility of clinical and EEG metrics readily available in resource-limited settings for predictive ability to prognosticate epilepsy risk in children with cerebral malaria. The findings have the potential to lay the foundation for future research of targeted interventions directed toward reducing post-cerebral malaria epilepsy development. This Mentored Patient-Oriented Career Development Award application aligns with two of the benchmarks set by the National Institute of Neurological Disorders and Stroke and American Epilepsy Society, including Area II- understanding epileptogenesis, and Area III- identify biomarkers. This proposal is also designed to provide important opportunities for the training and career development of the candidate. Dr. Patel has experience in global neurology research and clinical neurophysiology; this award will allow her to gain further experience in clinical research methodology and specific training in computational analysis of EEG. These skills will lay a foundation for further study of this condition and potentially in anti-epileptogenesis trials of the post-cerebral malaria epilepsy model. Ultimately, this research proposal and the accompanying training will provide a strong foundation for a successful independent research career devoted to the understanding of epileptogenesis and reducing the risk of acquired epilepsies in children globally.