Vagus nerve stimulation for drug‐resistant epilepsy: A European long‐term study up to 24 months in 347 children

Abstract

SUMMARYObjective: To gain insight into the long-term impact of vagus nerve stimulation (with VNS Therapy) in children with drug-resistant epilepsy, we conducted the largest retrospective multicenter study to date over an extended follow-up period of up to 24 months. Methods: The primary objective was to assess change in seizure frequency of the predominant seizure type (defined as the most disabling seizure) following VNS device implantation. Treating physicians collected data from patient records from baseline to 6, 12, and 24 months of follow-up. Results: The analysis population included 347 children (aged 6 months to 17.9 years at the time of implant). At 6, 12, and 24 months after implantation, 32.5%, 37.6%, and 43.8%, respectively, of patients had ≥50% reduction in baseline seizure frequency of the predominant seizure type. The responder rate was higher in a subgroup of patients who had no change in antiepileptic drugs (AEDs) during the study. Favorable results were also evident for all secondary outcome measures including changes in seizure duration, ictal severity, postictal severity, quality of life, clinical global impression of improvement, and safety. Post hoc analyses demonstrated a statistically significant correlation between VNS total charge delivered per day and an increase in response rate. VNS Therapy is indicated as adjunctive therapy in children with focal, structural epilepsies, who for any reason are not good candidates for surgical treatment following the trial of two or more AEDs. Children with predominantly generalized seizures from genetic, structural epilepsies, like Dravet syndrome or Lennox-Gastaut syndrome, could also benefit from VNS Therapy.Significance: The results demonstrate that adjunctive VNS Therapy in children with drug-resistant epilepsy reduces seizure frequency and is well tolerated over a 2-year follow-up period. No new safety issues were identified. A post hoc analysis revealed a dose-response correlation for VNS in patients with epilepsy.

The role of vagus nerve stimulation in refractory epilepsy

“…Similarly, VNS also played a relevant role in the management of refractory epilepsy in children, as observed in one of the major retrospective multicenter studies, which analyzed 347 children and found that 32.5% were responsive patients after six months, 37.6% after 12 months and 43.8% after 24 months 8 . When comparing patients younger and older than 12 years, no significant difference in efficacy or complication rate was demonstrated after five years of follow-up in 141 patients 39 , although some reported increased infection rates in children 40 .…”

“…These were followed by double-blind, randomized studies, which were extremely relevant for the establishment of vagus nerve stimulation as an option for refractory epilepsy treatment and were also considered evidence for therapy approval by regulatory agencies in Europe and in the United States. Vagus nerve stimulation therapy was approved by the European community in 1994 and by the American community in 1997 and, nowadays, more than 70,000 patients have had implants for the treatment of epilepsy or depression 8 .…”

Interfacing with the nervous system: a review of current bioelectric technologies

“…The cuff electrode is routinely used in the clinical setting for vagus nerve stimulation (VNS), which has been shown to be effective in the management of epilepsy [31,104], resistant depression [127], blood pressure control [110], as well as prevention of heart failure in patients with reduced ejection fractions [32,43,113]. Additionally, the Inspire® hypoglossal nerve stimulator, a Food and Drug Administration (FDA)- Fig.…”

A Review of Neuromodulation in the Neurorehabilitation

“…Management of patients who have recurrent seizures and did not respond to medication or surgery is challenging. A number of double-blind randomized controlled trials have confirmed the therapeutic effects of Vagus Nerve Stimulation [VNS] for epilepsy [66][67][68][69]. A recent European long-term study [n=347] showed a 50% reduction in seizure frequency for up to 43.8% of patients [66].…”

“…A number of double-blind randomized controlled trials have confirmed the therapeutic effects of Vagus Nerve Stimulation [VNS] for epilepsy [66][67][68][69]. A recent European long-term study [n=347] showed a 50% reduction in seizure frequency for up to 43.8% of patients [66]. Greater treatment effect has been observed with higher VNS settings [66].…”