VAGUS NERVE-STIMULATION THERAPY FOR PARTIAL-ONSET SEIZURES - A RANDOMIZED ACTIVE-CONTROL TRIAL

Objective: The purpose of this multicenter, add-on, double-blind, rand omized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimul ation has been shown in animal models and in preliminary clinical tria ls to suppress the occurrence of seizures, Methods: Patients had at le ast six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs we re unaltered. After a 3-month baseline, patients were surgically impla nted with stimulating leads coiled around the left vagus nerve and con nected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-u p period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in tot al seizure frequency compared with baseline. Results: Patients receivi ng high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0 .04). The high-stimulation group also had greater improvements on glob al evaluation scores, as rated by a blinded interviewer and the patien t. High stimulation was associated with more voice alteration and dysp nea. No changes in physiologic indicators of gastric, cardiac, or pulm onary functions occurred. Conclusions: Vagus nerve stimulation is an e ffective and safe adjunctive treatment for patients with refractory pa rtial-onset seizures. It represents the advent of a new, nonpharmacolo gic treatment for epilepsy.