Authors :
Presenting Author: Ryan Verner, PhD – LivaNova USA Inc.
Ryan Verner, PhD – LivaNova USA Inc.; Ana Suller-Marti, MD PhD – Western University; Gaia Giannicola, PhD – Sorin Group Italia S.r.l; Mark Keezer, MD PhD – Université de Montréal; Andrea Andrade, MD – Western University; Martin Veilleux, MD – Montreal Neurological Institute and Hospital; Kenneth Myers, MD PhD – Research Institute of the McGill University Medical Center; Jorge Burneo, MD – Western University
Rationale:
Generalized tonic-clonic seizures (GTCS) are highly debilitating seizures with significant health risk, including sudden unexpected death in epilepsy. For patients resistant to antiseizure medications (ASMs), and especially those for whom surgery is undesirable or not feasible, off-label use of device-based therapies like vagus nerve stimulation (VNS) is common.
We aim to examine the real-world impact of VNS on the frequency of GTCS.
Methods:
Patients were enrolled into a prospective, multicenter observational registry called CORE-VNS (NCT03529045). We selected patients with primary GTCS, and excluded patients who had focal seizures at baseline or GTCS in the context of Lennox-Gastaut Syndrome. These participants completed a three month retrospective baseline period, where seizure information and other patient-reported outcomes measures were collected prior to VNS implantation. After the implant, participants were followed for up to 36 months. For purposes of analysis, we identified a subpopulation of patients implanted within five years of original epilepsy diagnosis as compared to those implanted greater than five years from diagnosis.
At 3, 6, 12, and 24 months, seizure diary information and adverse events were collected.
Results:
We identified a total of 59 participants who fulfilled the criteria and who received an initial VNS implant for the study. Twelve (12) subjects were implanted within less than five years of their initial epilepsy diagnosis, and 47 were implanted later than five years from their initial epilepsy diagnosis. Patients implanted earlier tended to be younger (9.7 vs 25.9 years old, median) and nearly all were pediatric (11/12 participants). Participants had failed several previous ASMs (6 median, range 2 to 20) and there was no significant difference between the early and late implant groups. For the entire cohort, the responder rate (≥50% reduction from baseline) for GTCS at 12 months was 59.6% (95% CI: 47.3% to 71.1%) and the median seizure frequency change was -66.3% (95% CI: -93.3% to -25%). At 24 months, the responder rate for GTCS was 65.4% (95% CI: 53.1% to 76.3%) and the median seizure frequency change was -69.0% (95% CI: -100% to -50.0%). Patients with GTCS implanted earlier were slightly less likely to be responders at 12 months (55.6% vs 60.5%) and had a lower median seizure frequency change (-50% vs -73.3%), but these trends were non-significant. By 12 months, 35.6% (n=21) of participants experienced at least one adverse event and the most frequent side effects associated with VNS stimulation were dysphonia (11.9%,n=7), dyspnea (5.1%, n=3), cough (3.4%, n=2), and implant site pain (3.4%,n=2).
Conclusions:
In this prospective study, VNS was well tolerated and effective in reducing the frequency of GTCS.
Other than demographic differences between the populations, there were no relevant differences in seizure outcomes between GTCS response in patients implanted less than five years versus greater than five years from initial epilepsy diagnosis.
Funding:
This work was funded by LivaNova USA Inc.