The Effect of Cenobamate on Responsive Neurostimulation Epileptiform Events
Sami Aboumatar1, Jay Gavvala2, Zeenat Jaisani3, Ruben Kuzniecky4, Michael Privitera5, Madeline Ring5, Eric Heidel6, William Rosenfeld7, Jacob Pellinen8
1Austin Epilepsy Care Center, 2McGovern Medical School UTHealth Houston, 3University of Alabama at Birmingham Heersink School of Medicine, 4Hofstra Zucker School of Medicine/Northwell Health, 5University of Cincinnati College of Medicine, 6Scalë, LLC, 7Comprehensive Epilepsy Care Center for Children and Adults, 8University of Colorado School of Medicine
Objective:
To assess cenobamate’s effect on the number of electrocorticographic (ECoG) events recorded by responsive neurostimulation (RNS).
Background:
RNS ECoG data have been used as a potential method to assess efficacy following new add-on antiseizure medications (ASMs).
Design/Methods:
This retrospective, multicenter, observational, 24-week study included adults (≥18 years) with a history of recurrent focal seizures and implanted RNS who initiated adjunctive cenobamate ≥3 months after RNS implant between 4/1/2020-12/15/2023. Patients who received ≥2 weeks of cenobamate treatment at a minimum dose of 50 mg/day were enrolled. RNS-detected events (RDE) obtained from NeuroPace PDMS were reviewed to select only epileptiform events (EEs) based on electrographic ictal patterns. RDEs and EEs were counted during the 8-week baseline period, every 2 weeks for 12 weeks after starting cenobamate, and at study end. The primary outcome was the change in the number of EEs from baseline to the last treatment period observation (12+ weeks). Patient-reported clinical seizure frequency was recorded when available.
Results:
Thirty-seven patients (mean age 36.7 years) were included. Median cenobamate (range) dose was 150 (50-250) mg/day. EE numbers were significantly reduced from baseline (mean 15.7 per 28 days) to last observation (mean 2.5 per 28 days; P<0.001). Likewise, EE numbers >50 seconds (P<0.001) were significantly reduced. Among 25 patients with clinical seizure data, median clinical seizure frequency per 28 days decreased from 2.5 to 0.75 post-treatment. Dizziness and lethargy were the most commonly reported adverse events during cenobamate treatment; these resolved with slower titration and/or reductions in concomitant ASMs.
Conclusions:
Patients with uncontrolled seizures after RNS had a significant reduction in EEs (including EEs >50 seconds) and a numerical reduction in clinically reported seizures during adjunctive cenobamate treatment. Results from this analysis support the potential use of RNS ECoG data as an objective measure to assess the efficacy of cenobamate and possibly other adjuvant ASMs.
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