Thalamic Stimulation for Epilepsy Study

The purpose of this research is to examine the physiologic underpinnings of deep brain stimulation of the anterior nucleus of the thalamus (ANT), a method reducing seizures in adults diagnosed with medically refractory epilepsy. In this study, the investigator aims to perform cortical stereo electroencephalogram (sEEG) recordings during simultaneous ANT recording and stimulation to better understand the following: 1) how the ANT is involved in various seizure types; 2) which cortical regions are modulated by established ANT stimulation patterns; and 3) how novel ANT stimulation patterns modify epileptogenic cortical activity. Together, this knowledge will advance ANT DBS therapy by providing a physiologic basis for patient selection for ANT DBS, while identifying brain signals and stimulation patterns that can be used to develop novel methods for ANT DBS.

Approximately 3 million people in the United States experience epilepsy. Despite medical therapy, up to 30% of these patients continue to experience recurrent seizures. In this medically refractory population, tissue resection or ablation offer a high likelihood of seizure freedom, if a single epileptogenic focus can be precisely identified. For patients who are not candidates for resection or ablation, or those who continue to have seizures after these treatments, neuromodulation represents an alternative therapeutic option. One such therapy, deep brain stimulation (DBS) has been approved for around 5 years in Europe and was recently approved in the United States as a treatment for medically refractory epilepsy.

A number of potential DBS targets are being investigated, particularly, the ANT, which consists of the anteroventral, anterodorsal, and anteromedial nuclei. The ANT was recognized as a potential target because of its central connectivity to cortical regions where seizures often originate. Several pilot studies and recent trials have demonstrated 5-year efficacy and safety outcomes for ANT DBS. In a large randomized controlled study of ANT stimulation with long-term follow-up, there was a 56% median seizure reduction at the 2 year, and a 69% median and seizure reduction at the 5 year, in patients with drug-resistant focal epilepsy. This study also suggested that patients with temporal lobe epilepsy achieved greater benefit than those with extra-temporal or multifocal seizures. Since these pivotal trials, DBS of the ANT has emerged as a promising therapy for focal drug resistant epilepsy, however, its basic mechanism of action is unclear. One study which examined cortical local field potentials recordings during high-frequency ANT stimulation (130 Hz), has suggested that epileptic network desynchronization is a potential mechanism of DBS of the ANT.