Baseline characteristics and predictors for early implantation of vagus nerve stimulation therapy in people with drug-resistant epilepsy: Observations from an international prospective outcomes registry (CORE-VNS).

Objective: Vagus nerve stimulation (VNS) Therapy is routinely indicated for people with drug-resistant epilepsy (DRE). We analyzed the baseline characteristics of individuals receiving the recently released VNS models and identified factors associated with early or late implantation.

Methods: The Comprehensive Outcomes Registry of subjects with Epilepsy (CORE-VNS), a prospective observational study evaluating the clinical and psychosocial outcomes of VNS Therapy®, is following participants for up to 60 months after VNS implantation. In this analysis, we used Cox proportional hazards model to identify baseline characteristics associated with the time from diagnosis to first implantation.

Results: Of the 819 enrolled, 792 (96.7%) participants implanted with a VNS device were evaluated. 529 (64.6%) underwent the first implantation and 263 (32.1%) a re-implantation. Participants' median age at first implant was 24 years; 492 (62.1%) were ≥18 years old and 166 (20.3%) were < 12 years old. The average number of failed ASMs prior to VNS implantation was 7.1, and 145 (17.7%) had undergone previous epilepsy-related surgery. Epilepsy was classified as focal in 47.7% of participants, generalized in 16.1% and combined focal and generalized in 34.2%. Many of the participants (40.9%) had epilepsy of unknown etiology. The median time from diagnosis to first implantation was 10.33 years and was significantly shorter in participants with combined focal and generalized epilepsy compared to those with focal epilepsy alone, and in participants with genetic and immune epilepsy compared to those with unknown etiologies.

Significance: In people with DRE, VNS Therapy is provided after multiple failures of ASMs and after failure of epilepsy surgery in one in six individuals. Time from diagnosis to first implantation is associated with epilepsy type and etiology, likely reflecting variable treatment pathways. Clearer guidelines on when and how non-drug therapies should be deployed in people with DRE related to different epilepsy factors are needed.

Plain Language Summary: Neuromodulation can be a very helpful treatment in people who have seizures that do not respond to medications. The most widely utilized neuromodulation therapy is vagus nerve stimulation (VNS). We present data from a large, global study to show that people use an average of seven anti-seizure medications before attempting VNS Therapy and that it takes about 10 years for people to get their first VNS implant. We advocate for clearer treatment guidelines on how and when to consider VNS Therapy in people with seizures that are resistant to medication.