Abstracts

Rationale: The RNS® System (NeuroPace, Inc.) is a brain-responsive neurostimulation system that is FDA-approved as an adjunctive treatment for adults with partial onset seizures. This study reports the complete follow up experience of 33 epilepsy centers who participated in a 7 year prospective open-label long-term treatment (LTT) study, following a 2 year randomized, double-blinded controlled pivotal study, or a prior 2 year feasibility study. Methods: 256 adults with medically intractable partial onset seizures localized to 1 or 2 seizure foci were treated in the randomized controlled pivotal (N=191) or feasibility (N=65) studies and 230 transitioned into the LTT study. Efficacy assessments included median % change in seizure frequency as well as responder rate (RR, % of subjects with = 50% seizure reduction). Safety was assessed by reporting of adverse events. Results: At enrollment, mean age was 34.0 years, mean epilepsy duration was 19.6 years, mean number of AEDs was 2.9, and median seizure frequency was 10.2 seizures/month. The follow-up was 9 years with 1895 patient implant years. The median % seizure reduction and RR for each year beginning year 3 are presented in Figure 1. The median % reduction reached 75% at the end of year 9 (n=168). In addition, 30% of subjects experienced at least one period of = 6-months without seizures and 19% experienced =12 months without seizures. To control for decreases in sample size over time, a last observation carried forward analysis was performed for all subjects with at least 3 months of data in the open-label period (n=247). This showed a median % reduction of 67.2% (IQR: 23 to 94.5%) with 33% of patients having a 90% or greater reduction in seizures in their most recent 3 months of follow-up. There were no unanticipated device-related serious adverse events (SAEs). Six of the 256 patients had SAEs related to intracranial hemorrhage that were not attributed to seizure related head trauma. One patient experienced persistent mild right hand weakness, one patient had headache and others were asymptomatic. The risk for infection was 3.7% per procedure (initial implant, replacement, explant or lead revision), and all but one infection was soft tissue only. There were 16 deaths; 2 due to suicide, 1 each due to status epilepticus, herpes encephalitis, sepsis, lung/colon cancer, and lymphoma, and 4 due to definite SUDEP, 1 due to probable SUDEP, 2 due to possible SUDEP and 2 awaiting adjudication by the independent SUDEP committee. Conclusions: Patients treated with the RNS System experienced sustained reductions in seizures that reached 75% at 9 years of prospective follow-up, with a third of patients having a 90% or greater reduction in their seizures during their last 3 months of follow-up. In addition, 19% had at least one period of 1 year or more without seizures. Treatment remained safe over time. The study is the largest multicenter prospective study in the field of neuromodulation with 9-year follow-up data, and supports the long-term effectiveness and safety of treatment of medically intractable focal seizures with the RNS System. Funding: None