Reassessment: Vagus nerve stimulation for epilepsy

A July 1997 assessment of the American Academy of Neurology (AAN) Therapeutics and Technology Subcommittee reviewed vagus nerve stimulation (VNS) for epilepsy, and concluded that it was promising, but not yet established.1 Subsequent to that review, a second multicenter, randomized, controlled clinical trial has shown safety and efficacy of VNS for treatment of intractable partial seizures. Given the importance of this novel therapy for epilepsy, and the new information provided by a second major study, the Therapeutics and Technology Subcommittee requested an update on VNS. Use of VNS in epilepsy has recently been reviewed.2-4 VNS uses intermittent stimulation of the left vagus nerve in the neck to reduce the frequency and intensity of seizures. Mechanism of action of VNS remains uncertain, but stimulation does not induce grossly visible alterations in the human EEG.5 Recent studies suggest that metabolic activation of certain thalamic, brainstem, and limbic structures may be important in mediating the effect of VNS.6,7 Depletion of norepinephrine in the locus coeruleus attenuates the antiseizure affect of VNS.8 After open-label studies,9,10 sponsors of VNS engaged in a multicenter randomized study, named E03,11 details of which were reviewed in the previous assessment.1 Results of this trial were positive, and the technology was considered promising, but the number of patients receiving VNS was insufficient to achieve Food and Drug Administration approval. Therefore, a second randomized, controlled, multicenter clinical trial, called E05, was undertaken.12 The E05 study12 of VNS evaluated 254 patients, ages 13 to 60 years, with intractable partial seizures. To be eligible, subjects had to have at least six complex partial, visible partial motor, or secondarily generalized seizures in the month before entry, and to be free from other complicating neurologic, psychiatric, or medical conditions. …