Vagus nerve stimulation (VNS) was approved by the US FDA in 1997 as an adjunctive treatment for medically refractory epilepsy. It is considered for use in patients who are poor candidates for resection or those in whom resection has failed. However, disagreement regarding the utility of VNS in epilepsy continues because of the variability in benefit reported across clinical studies. Moreover, although VNS was approved only for adults and adolescents with partial epilepsy, its efficacy in children and in patients with generalized epilepsy remains unclear. The authors performed the first meta-analysis of VNS efficacy in epilepsy, identifying 74 clinical studies with 3321 patients suffering from intractable epilepsy. These studies included 3 blinded, randomized controlled trials (Class I evidence); 2 nonblinded, randomized controlled trials (Class II evidence); 10 prospective studies (Class III evidence); and numerous retrospective studies. After VNS, seizure frequency was reduced by an average of 45%, with a 36% reduction in seizures at 3-12 months after surgery and a 51% reduction after > 1 year of therapy. At the last follow-up, seizures were reduced by 50% or more in approximately 50% of the patients, and VNS predicted a ≥ 50% reduction in seizures with a main effects OR of 1.83 (95% CI 1.80-1.86). Patients with generalized epilepsy and children benefited significantly from VNS despite their exclusion from initial approval of the device. Furthermore, posttraumatic epilepsy and tuberous sclerosis were positive predictors of a favorable outcome. In conclusion, VNS is an effective and relatively safe adjunctive therapy in patients with medically refractory epilepsy not amenable to resection. However, it is important to recognize that complete seizure freedom is rarely achieved using VNS and that a quarter of patients do not receive any benefit from therapy.

BACKGROUND Neuromodulation–based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuro–modulation do not achieve complete seizure freedom, and, therefore, previous studies of vagus nerve stimulation (VNS) therapy have focused instead on reduction of seizure frequency as a measure of treatment response. OBJECTIVE To elucidate rates and predictors of seizure freedom with VNS. METHODS We examined 5554 patients from the VNS therapy Patient Outcome Registry, and also performed a systematic review of the literature including 2869 patients across 78 studies. RESULTS Registry data revealed a progressive increase over time in seizure freedom after VNS therapy. Overall, 49% of patients responded to VNS therapy 0 to 4 months after implantation (≥50% reduction seizure frequency), with 5.1% of patients becoming seizure–free, while 63% of patients were responders at 24 to 48 months, with 8.2% achieving seizure freedom. On multivariate analysis, seizure freedom was predicted by age of epilepsy onset >12 years (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.38–2.58), and predominantly generalized seizure type (OR, 1.36; 95% CI, 1.01–1.82), while overall response to VNS was predicted by nonlesional epilepsy (OR, 1.38; 95% CI, 1.06–1.81). Systematic literature review results were consistent with the registry analysis: At 0 to 4 months, 40.0% of patients had responded to VNS, with 2.6% becoming seizure–free, while at last follow–up, 60.1% of individuals were responders, with 8.0% achieving seizure freedom. CONCLUSION Response and seizure freedom rates increase over time with VNS therapy, although complete seizure freedom is achieved in a small percentage of patients.