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. 2020 Aug;61(8):1749-1757.
doi: 10.1111/epi.16593. Epub 2020 Jul 13.

Real-world experience with direct brain-responsive neurostimulation for focal onset seizures

Babak Razavi  1 , Vikram R Rao  2 , Christine Lin  1 , Krzysztof A Bujarski  3 , Sanjay E Patra  4 , David E Burdette  4 , Eric B Geller  5 , Mesha-Gay M Brown  6 , Emily A Johnson  7 , Cornelia Drees  6 , Edward F Chang  2 , Janet E Greenwood  8 , Christianne N Heck  8 , Barbara C Jobst  3 , Ryder P Gwinn  9 , Nicole M Warner  9 , Casey H Halpern  1
Affiliations

Real-world experience with direct brain-responsive neurostimulation for focal onset seizures

Babak Razavi et al. Epilepsia. 2020 Aug.

Abstract

Objective: The RNS System is a direct brain-responsive neurostimulation system that is US Food and Drug Administration-approved for adults with medically intractable focal onset seizures based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real-world safety and effectiveness of the RNS System.

Methods: Eight comprehensive epilepsy centers conducted a chart review of patients treated with the RNS System for at least 1 year, in accordance with the indication for use. Data included device-related serious adverse events and the median percent change in disabling seizure frequency from baseline at years 1, 2, and 3 of treatment and at the most recent follow-up.

Results: One hundred fifty patients met the criteria for analysis. The median reduction in seizures was 67% (interquartile range [IQR] = 33%-93%, n = 149) at 1 year, 75% (IQR = 50%-94%, n = 93) at 2 years, 82% (IQR = 50%-96%, n = 38) at ≥3 years, and 74% (IQR = 50%-96%, n = 150) at last follow-up (mean = 2.3 years). Thirty-five percent of patients had a ≥90% seizure frequency reduction, and 18% of patients reported being clinically seizure-free at last follow-up. Seizure frequency reductions were similar regardless of patient age, age at epilepsy onset, duration of epilepsy, seizure onset in mesial temporal or neocortical foci, magnetic resonance imaging findings, prior intracranial monitoring, prior epilepsy surgery, or prior vagus nerve stimulation treatment. The infection rate per procedure was 2.9% (6/150 patients); five of the six patients had an implant site infection, and one had osteomyelitis. Lead revisions were required in 2.7% (4/150), and 2.0% (3/150) of patients had a subdural hemorrhage, none of which had long-lasting neurological consequences.

Significance: In this real-world experience, safety was similar and clinical seizure outcomes exceeded those of the prospective clinical trials, corroborating effectiveness of this therapy and suggesting that clinical experience has informed more effective programming.

Keywords: RNS System; brain-responsive neurostimulation; drug-resistant; medically intractable epilepsy.

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Conflict of interest statement

B.R. has received research support from NeuroPace. V.R.R. has received support from and/or has served as a paid consultant for NeuroPace. S.E.P. has received support from and/or has served as a paid consultant for NeuroPace and Boston Scientific Corporation. D.E.B. has received support from and/or has served as a paid consultant for Greenwich Pharmaceuticals, Eisai Co, Sunovion Pharmaceuticals, NeuroPace, SK Biopharmaceuticals, UCB, and Zogenix. E.B.G. has received support from and/or has served as a paid consultant for NeuroPace, LivaNova, and Xenon Pharmaceuticals. J.E.G. is a prior employee of NeuroPace and has equity ownership/stock options. C.N.H. has received support from and/or has served as a paid consultant for NeuroPace in the form of research sponsorship of the long‐term postmarket outcomes. B.C.J. has received support from and/or has served as a paid consultant for NeuroPace, Medtronic, Eisai Co, Harvard Pilgrim Health Care, National Institutes of Health, Centers for Disease Control and Prevention, National Science Foundation, Defense Advanced Research Projects Agency, and the journals Neurology and Epilepsia. R.P.G. has received support from and/or has served as a paid consultant for NeuroPace's Scientific Advisory Council. C.H.H. has received support from and/or has served as a paid consultant for Boston Scientific Corporation. The remaining authors have no conflicts of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

FIGURE 1
FIGURE 1
Stimulation charge density and current amplitude over time in real‐world and clinical trial populations of patients treated with the RNS System. Changes in charge density (A) and current amplitude (B) are shown as programmed for patients in this real‐world outcome (RWO) study and in patients randomized to the active stimulation arm of the randomized controlled Pivotal (Piv) trial. Time periods represent months since initial placement of the brain‐responsive neurostimulator and leads. The mean values are represented with standard error of the mean (SEM; light gray bars). Although charge density and current amplitude increase over time for both cohorts, the overall values are lower for the patients treated in the RWO study and the initial rate of increase is lower than for the patients in the Piv trial
FIGURE 2
FIGURE 2
Seizure frequency outcomes with RNS System treatment. Outcomes are provided for all patients combined and for patients with seizures of mesial temporal lobe (MTL) and of neocortical onsets. The median percent change in seizure frequency at 1, 2, and 3 or more years is presented with the interquartile ranges (IQRs; light gray lines) for each year of treatment compared to a pretreatment baseline
FIGURE 3
FIGURE 3
Clinician‐determined assessment of change in the patients’ ability to function using the Clinical Global Impressions Scale 10 at most recent follow‐up
See this image and copyright information in PMC

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