174 Convection-Enhanced Delivery of Muscimol to the Epileptic Focus: Preclinical and Clinical Research

Surgically remediable medically intractable epilepsy usually arises from mesial temporal sclerosis. Standard treatment requires surgical removal of the affected hippocampus, which eliminates seizures in 2/3 patients. Less invasive therapies have been advocated. We are developing therapy using muscimol, a GABA-A agonist, to focally suppress the epileptic focus.

A five-day muscimol infusion to the hippocampus via convection-enhanced delivery (CED) was conducted in six nonhuman primates (NHPs) to assess muscimol distribution and neurologic and neurophysiologic effects. After the animal study a clinical protocol was initiated under an IND. Three human subjects underwent CED of vehicle (artificial CSF) and muscimol into the seizure focus (cortex in one patient; hippocampus in two patients) using a cross-over design. To improve monitoring of muscimol delivery, we subsequently performed experiments in NHPs comparing relative distributions of 3H-muscimol and gadolinium-DTPA after co-infusion by CED. NHPs underwent serial MR-imaging during...