Electrographic seizures on responsive neurostimulation: An early and objective measure of response to cenobamate

Responsive neurostimulation (RNS) electrocorticographic (ECoG) data may have a role in objectively assessing the efficacy of add-on antiseizure medications (ASMs). This retrospective, multicenter, observational, 24-week study is the first to report the effects of cenobamate on RNS-detected events (RDE).

Patients included adults (≥18 years) with a history of recurrent focal seizures and implanted RNS who initiated adjunctive cenobamate ≥ 3 months after RNS implant between 4/1/20-12/15/23 and who received ≥ 2 weeks of cenobamate (≥50 mg/day). RDE ("long episodes," "long episodes with saturation," and "saturation") obtained from the NeuroPace Patient Data Management System were reviewed to select only electrographic seizures (ESs) based on electrographic ictal patterns. RDEs and ESs were counted during the 8-week baseline period, every 2 weeks for 12 weeks after starting cenobamate, and at study end. The main outcome was percent change from baseline to the end of the 16-week treatment period (12 + weeks) for overall ESs, ESs ≥ 50 seconds, and ESs < 50 seconds. Patient-reported clinical seizure frequency was recorded when available.

Thirty-seven patients (mean age 36.7 years) were included. Median cenobamate dose was 150 mg/day (range, 50-250 mg/day). There was a significant median percent reduction from baseline to the end of cenobamate treatment in ESs (94.4 %; p < 0.0001), ESs ≥ 50 s (100.0 %; p < 0.0001), and ESs < 50 s (100.0 %; p < 0.0001). Among patients with available seizure data (n = 24), median percent reduction in clinical seizures per 28 days from baseline to end of treatment was 72.2 % (p < 0.0001). Adverse events were reported in 27 % (10/37) of patients; dizziness, fatigue, and sleepiness were most reported.

Patients with uncontrolled seizures after RNS had a significant reduction in ESs and clinically reported seizures during adjunctive cenobamate treatment. Results from this analysis support the potential use of RNS ECoG data as an objective measure to supplement clinical data when determining cenobamate efficacy and may provide a strategy for monitoring responses to ASMs more generally in this population.

The data for the analyses described in this paper are available by request from the corresponding author or from SK Life Science, Inc., the company sponsoring the clinical development of cenobamate for the treatment of focal epilepsy.