Brain Infusion of Muscimol to Treat Epilepsy

Objectives: The objectives of this study are to test the hypotheses that direct infusion of the brain (convection enhanced delivery) with neurotransmitter receptor agonists is 1) safe and 2) can be used to study the basic pathophysiology of the epileptic focus in human subjects. The approach described may be a new approach for precise localization of a seizure focus. It may also prove to indicate the distribution of suppression (in space) required for elimination of seizure activity in individual patients and, by doing so, may more accurately define the minimum treatment area that is required for success. Finally, the data obtained may support the treatment of patients with medically intractable epilepsy with neurotransmitter-specific agents infused directly into the epileptic focus. Study Population: The study population will include adult patients with medically intractable epilepsy who are candidates for surgical resection of their epileptic region. Design: Adult patients who are candidates for standard surgical care for medically intractable epilepsy will undergo standard noninvasive evaluation to identify the location of the seizure focus. After surface EEG confirms the side and approximate location of the seizure focus, a depth electrode with a central lumen will be placed in the seizure focus for the purpose of this research study. The lumen in the depth electrode will be used to deliver vehicle (artificial cerebrospinal fluid) or muscimol, a neurotransmitter (gamma-aminobutyric acid, GABA) receptor agonist that suppresses neuronal activity. During the infusion trials, patients will be monitored by neurologic examination and by video-EEG. Following the trials, the epileptic focus will be resected, which is standard care for medically intractable epilepsy, and the surgical specimen will be examined for any histological changes caused by the infusions. Outcome Measures: Basic pathophysiology of the epileptic focus will be examined by assessing the effect of the infusion on seizure frequency (the primary end point), EEG recordings, motor function, and visual object naming. Safety will be assessed by neurologic examination and by pathologic examination (gross and microscopic) of the resected surgical specimen (presence or absence of infusion-induced injury).