Document Type
Article
Publication Date
5-12-2026
Abstract
BACKGROUND AND OBJECTIVES: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT.
METHODS: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will be conducted at 5 years.
RESULTS: Across 32 US epilepsy centers, 324 patients (mean age 37.1, 59.6% female individuals) were implanted and 271 completed 3 years of follow-up. The median percent reduction in seizure frequency at 6 months was 62% and 82% at 3 years (
DISCUSSION: This prospective real-world study contributes to the body of evidence that adjunctive direct brain-responsive neurostimulation provides significant and sustained reductions in the frequency of focal seizures. Seizure reductions were greater and were achieved faster than in the RCT and long-term treatment trials but were similar to a more recent retrospective multicenter real-world study. As in the preapproval studies, treatment was well-tolerated and safe, and the SUDEP rate was low. The RNS System showed similar safety and improved seizure outcomes in real-world use compared with the RCT. Improvements in efficacy may reflect changes in programming practices. Future research efforts will focus on using the brain data obtained by the device to optimize detection and stimulation paradigms for each patient.
TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov, NCT02403843, submitted March 26, 2015.
CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in adults with refractory focal-onset seizures, direct brain-responsive neurostimulation reduces seizure frequency without serious adverse events up to 3 years.
Recommended Citation
Eliashiv, Dawn; Rao, Vikram R.; Jobst, Barbara C.; Szaflarski, Jerzy P.; Rolston, John D.; Kaye, Lesley C.; Ganguly, Taneeta Mindy; Bullinger, Katie; Dugan, Patricia C.; Burdette, David E.; Peters, Angela Y.; Sheikh, Atif; Haas, Kevin F.; Nair, Dileep R.; Mnatsakanyan, Lilit; Quraishi, Imran H.; Bensalem-Owen, Meriem K.; Doherty, Michael J.; Razavi, Babak; Fisher, Tiffany L.; Skidmore, Christopher T.; Modur, Pradeep N.; Constantino, Tawnya M.; Salanova, Vicenta; Cole, Andrew J.; Taraschenko, Olga; Rivera-Cruz, Angelica; Wheless, James W.; Tandon, Nitin; Balabanov, Antoaneta; Aboumatar, Sami; Fried, Itzhak; Drees, Cornelia; Shin, Hae Won; Jaisani, Zeenat; MacIver, Stephanie E.; Patra, Sanjay E.; Chang, Edward F.; Willie, Jon T.; Gwinn, Ryder; Stoub, Travis; Stern, John M.; Crabtree, Tami; Seale, Cairn G.; McFadden, Sharon C.; Norman, Jacob F.; Johnson, Lise; and Morrell, Martha J., "Postapproval Study for Brain-Responsive Neurostimulation for Drug-Resistant Focal Epilepsy: Three-Year Efficacy and Interim Safety Results" (2026). Department of Neurology Faculty Papers. Paper 398.
https://jdc.jefferson.edu/neurologyfp/398
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
42030518
Language
English
Comments
This article is the author's final published version in Neurology, Volume 106, Issue 9, Article Number e214875.
The published version is available at https://doi.org/10.1212/WNL.0000000000214875. Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.