Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy
Dileep Nair, Kenneth D. Laxer, Peter Weber, Anthony M. Murro, Yong D. Park, Gregory L. Barkley, Brien Smith, Ryder P. Gwinn, Michael J. Doherty, Katherine H. Noe, Richard S. Zimmerman, Gregory K. Bergey, William S. Anderson, Christianne Heck, Charles Y. Liu, Ricky W. Lee, Toni Sadler, Robert B. Duckrow, Lawrence J. Hirsch, Robert E. Wharen, William O. Tatum, Shraddha Srinivasan, Guy M. McKhann, Mark Agostini, Andreas V. Alexopoulos, Barbara C. Jobst, David W. Roberts, Vicenta Salanova, Thomas C. Witt, Sydney S. Cash, Andrew J. Cole, Gregory A. Worrell, Brian N. Lundstrom, Jonathan Edwards, Jonathan J. Halford, David Spencer, Lia Ernst, Christopher Skidmore, Michael R. Sperling, Ian Miller, Eric B. Geller, Michel J. Berg, A. James Fessler, Paul Rutecki, Alica M. Goldman, Eli M. Mizrahi, Robert E. Gross, Donald C. Shields, Theodore H. Schwartz, Douglas Labar, Nathan B. Fountain, W. Jeff Elias, Piotr W. Olejniczak, Nicole R. Villemarette-Pittman, Stephan Eisenschenk, Steven N. Roper, Jane Boggs, Tracy A. Courtney, Felice T. Sun, Cairn G. Seale, Kathy L. Miller, Tara L. Skarpaas, Martha J. Morrell, on behalf of the RNS System LTT Study
Abstract
ObjectiveTo prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. MethodsAdults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in 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 with the Quality of Life in Epilepsy (QOLIE-89) inventory. ResultsOf 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04–9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). ConclusionsAdjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. Classification of evidenceThis study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.