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

Gregory K Bergey, Martha J Morrell, Eli M Mizrahi, Alica Goldman, David King-Stephens, Dileep Nair, Shraddha Srinivasan, Barbara Jobst, Robert E Gross, Donald C Shields, Gregory Barkley, Vicenta Salanova, Piotr Olejniczak, Andrew Cole, Sydney S Cash, Katherine Noe, Robert Wharen, Gregory Worrell, Anthony M Murro, Jonathan Edwards, Michael Duchowny, David Spencer, Michael Smith, Eric Geller, Ryder Gwinn, Christopher Skidmore, Stephan Eisenschenk, Michel Berg, Christianne Heck, Paul Van Ness, Nathan Fountain, Paul Rutecki, Andrew Massey, Cormac O'Donovan, Douglas Labar, Robert B Duckrow, Lawrence J Hirsch, Tracy Courtney, Felice T Sun, Cairn G Seale, Gregory K Bergey, Martha J Morrell, Eli M Mizrahi, Alica Goldman, David King-Stephens, Dileep Nair, Shraddha Srinivasan, Barbara Jobst, Robert E Gross, Donald C Shields, Gregory Barkley, Vicenta Salanova, Piotr Olejniczak, Andrew Cole, Sydney S Cash, Katherine Noe, Robert Wharen, Gregory Worrell, Anthony M Murro, Jonathan Edwards, Michael Duchowny, David Spencer, Michael Smith, Eric Geller, Ryder Gwinn, Christopher Skidmore, Stephan Eisenschenk, Michel Berg, Christianne Heck, Paul Van Ness, Nathan Fountain, Paul Rutecki, Andrew Massey, Cormac O'Donovan, Douglas Labar, Robert B Duckrow, Lawrence J Hirsch, Tracy Courtney, Felice T Sun, Cairn G Seale

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.

© 2015 American Academy of Neurology.

Figures

Figure 1. Implanted RNS neurostimulator and NeuroPace…
Figure 1. Implanted RNS neurostimulator and NeuroPace cortical strip and depth leads
Copyright owned by NeuroPace, Inc; no permissions for use are required.
Figure 2. RNS System studies: Participant accountability
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.

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Source: PubMed

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