Related Experiment Video
Updated: Apr 26, 2026
A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy
Published on: November 13, 2016
Postapproval Study for Brain-Responsive Neurostimulation for Drug-Resistant Focal Epilepsy: Three-Year Efficacy and
Dawn Eliashiv1, Vikram R Rao2,3, Barbara C Jobst4
1Neurology, David Geffen School of Medicine at University of California, Los Angeles.
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 (p < 0.0001; Wilcoxon signed-rank test); 41% had a ≥90% reduction in seizure frequency at 3 years, 42.5% of participants had at least 1 seizure-free period of 6 months or more, and 22.0% experienced seizure freedom for 12 months or more. Observed effectiveness was similar across patients with 1 or 2 seizure onsets and across onset locations (mesial temporal, neocortical, or both mesial temporal and neocortical). No serious stimulation-related adverse events were reported. Combining data from all RNS System trials (n = 645), the sudden unexplained death in epilepsy (SUDEP) rate was 2.3/1,000 patient years, which was significantly lower than predefined comparators (p < 0.05; 1-tailed χ2).
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.
