Abstracts

Rationale: The RNS™ System (NeuroPace, Inc.) is an investigational device being evaluated for safety and efficacy in adults with medically intractable partial onset seizures. The RNS™ System 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 data repository. Based on the favorable safety results of a two year Feasibility Investigation, a Pivotal Investigation commenced in December 2005. Methods: Eligible subjects were 18 to 70 years of age, had an average of 3 disabling partial seizures a month, had failed 2 or more antiepileptic medications (AEDs) and had seizure foci localized to one or 2 regions. Subjects completed a 3 month baseline to determine eligibility based on seizure frequency and were then given the option to have the RNS System Neurostimulator and Leads implanted. The Neurostimulator was programmed to acquire data on seizure detection. One month post-operatively, subjects were randomized 1:1 to receive sham or active responsive stimulation. In order to maintain the blind, physicians responsible for acquiring data for the primary and secondary safety and efficacy outcomes were blinded to the randomization status. Programming and other device management was the responsibility of a non-blinded treatment physician. Seizure frequency was considered over the 84 days beginning 2 months after implantation. At completion of this blinded efficacy evaluation period (BEP), all subjects were able to receive stimulation until 2 years post-implant, then could transition into a 5 year open label long term treatment trial. Results: As of May 28, 2009, 191 subjects had been implanted with the RNS System Neurostimulator and Leads across 29 sites. Mean age was 36 years (range 18-67) and 48% were female. The mean age of seizure onset was 14 years (range 0-54). Subjects were taking 2.8 AEDs (range 0-8). 34% had been previously treated with a VNS and 33% with epilepsy surgery; 16% had been treated with both VNS and surgery. 60% of subjects had prior intracranial monitoring for localization of the epileptic focus. 46% had ictal onset in mesial temporal structures only, and 82% of these subjects had bilateral mesial temporal ictal onsets. The results of a safety and efficacy analysis for the BEP will be available after the final subject completes in August 2009. Conclusions: The RNS™ System is a cranially implanted responsive neurostimulator being evaluated as an adjunctive treatment for adults with intractable partial-onset epilepsy. A multicenter double blind randomized controlled pivotal investigation of the RNS System collected efficacy and safety data on 191 adults with medically intractable partial onset seizures. These subjects had severe epilepsy and many had failed multiple epilepsy treatments. Nearly half of these subjects had seizures originating in mesial temporal structures, most with bilateral onsets. Efficacy and safety results will be presented for the blinded efficacy evaluation period.