Investigating the correlation between short-term effectiveness of VNS Therapy in reducing the severity of seizures and long-term responsiveness

VNS (Vagus Nerve Stimulation) Therapy^® is an adjunctive therapy for patients with medically refractory epilepsy. The primary metric used to assess response to any treatment for epilepsy is seizure frequency reduction as measured using seizure diaries. In addition to seizure frequency, reduction in seizure severity is clinically meaningful to patients and can be measured objectively. Analysis of electro-encephalographic (EEG) signals has revealed that seizures are accompanied by spatial synchronization of EEG electrodes that may persist for several minutes after the seizure. A quantitative feature was obtained from EEG data around ictal events collected during a 3-5day epilepsy monitoring unit (EMU) visit prior to VNS implantation and following one month after VNS implant. This feature was obtained from 15 patients who underwent implantation of the closed-loop AspireSR^® VNS Therapy System. We used this feature to first evaluate if automated delivery of VNS at the time of seizure onset reduces the severity of seizures in patients by reducing EEG spatial synchronization. We then explored the correlation between the effectiveness of VNS in reducing the severity of seizures and long-term (12 month follow-up) responsiveness using clinical metrics of seizure frequency reduction. Results of application of this methodology to 103 pre-VNS and 102 post-VNS seizures revealed that automatic delivery of VNS Therapy reduces ictal spatial synchronization (EEG-based quantitative feature) in patients who responded (≥50% reduction in seizure frequency) to VNS Therapy. This feature may be used as potential biomarker for predicting long-term response to VNS Therapy.