Long-term treatment with responsive brain stimulation in adults with refractory partial seizures

Abstract

Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures.

Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy.

Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%).

Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures.

Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

Figure 1. Implanted RNS neurostimulator and NeuroPace cortical strip and depth leads

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Figure 2. RNS System studies: Participant accountability

^a Six participants discontinued before completing the study; 2 participants completed the study, but elected not to enroll in the Long-Term Treatment (LTT) Study. ^b Fourteen participants discontinued prior to completing the study; 4 participants completed the study, but elected not to enroll in the LTT Study. ^c Discontinuation reasons: to pursue other treatments (9); insufficient efficacy (5); participant chose not to replace neurostimulator after expected battery depletion (5) or after resolution of infection (4); noncompliance (3); elective explant (1); ongoing suicidality/noncompliance (1). ^d Study ongoing; data as of November 1, 2013.