Preventing Epilepsy After Traumatic Brain Injury With Topiramate

Traumatic brain injury (TBI) causes epilepsy in up to 30% of civilian and 50% of military head injuries, exacerbating chronic neurological disability. There is currently no method for preventing epilepsy after TBI. We hypothesize that the new antiepileptic drug, topiramate (TPM), will (1) reduce acute seizures and prevent the development of epilepsy following TBI and (2) improve neurological recovery. We propose to perform a pilot clinical trial to develop the necessary infrastructure for larger scale randomized clinical trials to test TPM, and, possibly, other new antiepileptic drugs with neuroprotective properties, for their ability to prevent epilepsy after TBI. Subjects with TBI will be randomized within 24 hours to one of three groups: 1) TPM for one week, 2) TPM for three months, or 3) phenytoin for one week. Subjects will be followed for two years for the development of seizures and for neurological outcome. Serial EEGs and MRIs will be performed to explore potential mechanisms for the development of epilepsy after TBI. These new tools for the clinical study of epilepsy prevention, and neuroprotection in general, will be developed that can be applied to a wide variety of studies and which will facilitate future research in this critical area.