Two‐year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial

OBJECTIVE: To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. METHODS: Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up. RESULTS: All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was −37.9% in the active and −17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. SIGNIFICANCE: Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

OBJECTIVE: Prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation within 2 year feasibility or randomized controlled trials enrolled into a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL using the quality of life in epilepsy (QOLIE-89) inventory. RESULTS: 230 of 256 patients treated in the initial trials participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p\u3c0.0001; Wilcoxon Signed Rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. 18.4% (47/256) experienced ≥1 year of seizure freedom with 62% (29/47) seizure free at last follow-up and an average seizure-free period of 3.2 years (range: 1.04 - 9.6 years). Overall QOL, epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p\u3c0.05). There were no serious AEs related to stimulation and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p\u3c0.05; one-tailed Chi Square). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated, implant related AEs were typical of other neurostimulation devices, and SUDEP rates were low. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years