The goal of this proposal is a two-pronged approach to establish interictal high frequency oscillation (HFO) as a spatially localizing biomarker of the epileptogenic zone and as a temporally predictive biomarker of the epileptogenic process in childhood epilepsy. Epilepsy is a common group of disorders in children, a significant portion of whom will continue to have debilitating weekly or daily seizures despite new anticonvulsants and despite surgical resection of epileptogenic cortex. Why seizures continue unabated despite the best current medical and surgical therapy is unclear. Taking advantage of the already existing infrastructure that evaluates children for epilepsy and epilepsy surgery at UCLA, this proposal seeks to establish HFO as a spatially localizing biomarker of the epileptogenic zone (Hypothesis 1). Similarly, with three specialty clinics that follow 3 groups of high-risk pre- epileptic children, the proposal also aims to establish HFO as a temporally predictive marker of the epileptogenic process (Hypothesis 2) of who may go on to have epilepsy, with prospective serial video-EEGs. The results from this proposal will naturally lead to the next set of questions and research aims: 1) to incorporate HFO localization data in surgical decision-making in a clinical trial; 2) to further study the cellular and molecular mechanisms underlying HFO in resected cortical specimens to better understand epileptogenesis and possible antiepileptic drug mechanisms; 3) to enable potential therapeutic intervention in high-risk children, before seizure onset. Studies to help answer these questions are some of the long-term plans.
This proposal aims to establish high frequency oscillation as a spatially localizing biomarker of the epileptogenic zone in childhood epilepsy, and as a temporally predictive biomarker of epileptogenesis in three groups of high-risk pre-epileptic children across different age groups and etiologies.
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