Brain stimulation for the treatment of epilepsy

The treatment of patients with refractory epilepsy has always been challenging. Despite the availability of multiple antiepileptic medications and surgical procedures with which to resect seizure foci, there is a subset of epilepsy patients for whom little can be done. Currently available treatment options for these unfortunate patients include vagus nerve stimulation, the ketogenic diet, and electric stimulation, both direct and indirect, of brain nuclei thought to be involved in epileptogenesis. Studies of electrical stimulation of the brain in epilepsy treatment date back to the early 20th century, beginning with research on cerebellar stimulation. The number of potential targets has increased over the years to include the hippocampus, subthalamic nucleus, caudate nucleus, centromedian nucleus, and anterior nucleus of the thalamus (ANT). Recently the results of a large randomized controlled trial, the electrical Stimulation of the Anterior Nucleus of Thalamus for Epilepsy (SANTE) trial, were published, demonstrating a significant reduction in mean seizure frequency with ANT stimulation. Soon after, in 2011, the results of a second randomized, controlled trial-the NeuroPace RNS trial-were published. The RNS trial examined closed-loop, responsive cortical stimulation of seizure foci in patients with refractory partial epilepsy, again finding significant reduction in seizure frequency. In the present review, the authors examine the modern history of electrical stimulation of the brain for the treatment of epilepsy and discuss the results of 2 important, recently published trials, the SANTE and RNS trials.