Authors :
Presenting Author: Kathryn Nichol, PhD – LivaNova USA Inc.
Kathryn Nichol, PhD – LivaNova USA Inc.; Arjune Sen, MD PhD – John Radcliffe Hospital; Rhys Thomas, MD PhD – Royal Victoria Infirmary; Menaka Paranathala, MD – Royal Victoria Infirmary; Patrick Kwan, MD PhD – University of Melbourne; Ryan Verner, PhD – LivaNova USA Inc.
Rationale:
People with drug-resistant epilepsy (DRE) must navigate a care journey that involves trials of multiple pharmaceutical, dietary, surgical interventions. Often, these individuals will advance from managing their seizures with the help of a primary care physician to more advanced care offered at secondary or tertiary centers (e.g. Comprehensive Epilepsy Centers). Delayed referral to these centers can result in delayed access to advanced epilepsy management techniques including surgery or neuromodulation which have been proven effective in reducing the severity of epilepsy symptoms.
Methods:
Patients were invited into a prospective, multicenter observational registry called CORE-VNS (NCT03529045). This all-comers registry aimed to collect a wide range of outcomes data on people with epilepsy treated with VNS Therapy. The study enrolled both patients seeking initial implantation with VNS and those seeking reimplantation due to battery replacement. The study is ongoing, and participants will be followed for up to 36 months as both seizure and non-seizure outcomes of therapy are collected. Participants were grouped into subpopulations: all individuals undergoing initial implant, first implant < 5 years from epilepsy diagnosis, and first implant >5 years from epilepsy diagnosis.
Results:
CORE-VNS enrolled 529 participants seeking initial implant with VNS. Participants were geographically and ethnically diverse, with 42.7% European, 30.1% from the Americas, and 22.9% from the Western Pacific. These people were largely adults (54.6% vs 45.4%), with a median age at implant of 24.43 years (range 1.0-71.5) and median age of epilepsy diagnosis of six years (range 0.5-62). Of participants receiving their first VNS device as part of the CORE-VNS registry, 115 were implanted less than five years from epilepsy diagnosis (414 implanted later). A total of 84.1% (n=445) had no prior brain surgery, likely indicating these participants were not candidates for, or were unwilling to undergo, more invasive surgical options. Patients who waited longer for VNS were more likely to have had epilepsy surgery prior to VNS (18.6% (n=77/414) vs 6.1% (n=7/115)). At enrollment, participants had failed a median six anti-seizure medications (range 2-20), and there was little difference between participants implanted shortly after diagnosis (< 5 years: mean 6.6) versus later ( >5 years: mean 6.9). Notably, nearly seven in ten participants had some level of cognitive impairment. At the most recent follow-up of the full cohort data (12 months data), 65.7% of all first implanted patients were responsive to therapy (≥50% reduction in seizure frequency) and had reduced their anti-seizure medication load by an average of 10.99%. There was a marginally greater likelihood to respond to therapy when implanted earlier (71.3% vs 64.1%).
Conclusions:
VNS is effective in highly refractory patients, with nearly two in three patients experiencing meaningful reduction in seizure frequency by 12 months. While further study will be needed to confirm the increased likelihood of favorable outcomes following earlier implantation, interim data suggest care for people with DRE may be improved by more efficient referral.
Funding:
This work was funded by LivaNova USA Inc.