Abstracts

Rationale: The RNS System (NeuroPace, Inc.) is an investigational device that includes a cranially implanted programmable responsive neurostimulator connected to depth and/or subdural leads, a physician programmer, a patient remote monitor and a web based interactive database. Long-term seizure frequency and responder rate, as well as safety, were assessed in subjects with medically intractable partial onset seizures participating in the RNS System studies. Methods: Subjects were 18-70 years of age, had > 3 disabling partial seizures/month and had failed > 2 AEDs. After a 3 month baseline, the Neurostimulator and Leads were implanted and the neurostimulator was programmed to detect epileptiform activity. Subjects in a Pivotal study (N=191) were randomized 1:1 to receive active or sham responsive stimulation for 12 weeks, beginning 8 weeks post-operatively. Subjects in a Feasibility study (N=65) were able to receive responsive stimulation for 12 weeks beginning 4 weeks postoperatively, except for 14 subjects randomized to receive sham stimulation in a later blinded protocol. At the end of the evaluation period, all subjects could receive stimulation until 2 years post-implant, and then could transition into an ongoing 5 year, open label, long term treatment trial. Assessment variables included the seizure frequency % change and responder rate (percent of subjects with a 50% or greater reduction in seizures) for each 6-month interval beginning 6 months after implant (when all subjects have the opportunity to receive stimulation). Safety of responsive stimulation was assessed by adverse event reporting. Results: 256 subjects were implanted with the RNS Neurostimulator and Leads. The mean age at enrollment was 34.0 years, mean duration of epilepsy was 19.6 years, mean number of AEDs was 2.9, and median seizure frequency was 10.1 seizures/28 days. The responder rate and the median percent reduction in frequency of total disabling seizures for each 6 month interval is presented in Table 1, with the number of subjects currently reaching that time point. There were no serious unanticipated device-related adverse events during the RNS(TM) System studies, and the overall rate of adverse events did not increase over time. Conclusions: Seizure frequency was reduced across subjects participating in clinical studies of the RNS System. After 2 years post-implant (2 - 2.5 yrs), the median % seizure reduction was >40% and the responder rate was >45%. After 3 years (3 - 3.5 yrs) 53% were responders. These data suggest that the reduction of the seizure frequency is maintained with responsive stimulation, and appears to improve over time. Adverse event rates were stable, supporting the safety of responsive stimulation over time.