Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response

A review

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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.

Abbreviations used in this paper: HSD = honestly significant difference; LSD = least significant difference; VNS = vagus nerve stimulation.

Article Information

Address correspondence to: Dario J. Englot, M.D., Ph.D., Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, Box 0112, San Francisco, California 94143-0112. email:

Please include this information when citing this paper: published online August 12, 2011; DOI: 10.3171/2011.7.JNS11977.

© AANS, except where prohibited by US copyright law.



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    Forest plots depicting effect size in each study. Effect size for each study is represented as the OR of attaining ≥ 50% reduction in seizure frequency as compared with the preoperative baseline. Error bars represent the 95% CI, while the size of each point estimates proportional study weight. Dashed lines indicate an OR = 1, and diamonds represent the mean effect size (OR 1.83, 95% CI 1.80–1.86).

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    Bar graph depicting the decrease in seizure frequency after VNS by seizure type. The mean decrease in seizure frequency after VNS was greater in patients with generalized epilepsy than in those with partial epilepsy or other/mixed seizure types (p < 0.001, 1-way ANOVA). *p < 0.001, Tukey HSD and Fisher LSD post hoc tests, comparing patients with generalized (gen.) versus partial epilepsy. Number of patients = 507 (partial), 111 (generalized), and 169 (mixed).

  • View in gallery

    Bar graph demonstrating the decrease in seizure frequency after VNS by epilepsy etiology. The mean decrease in seizure frequency after VNS varied between 47.8% ± 1.9% and 78.6% ± 8.7%, depending on the etiology attributed to a patient's epilepsy syndrome (p < 0.001, 1-way ANOVA). *Significantly greater decrease in seizure freedom versus patients with unknown epilepsy etiology (p < 0.02, Tukey HSD and Fisher LSD post hoc tests). Number of patients = 93 (Lennox-Gastaut syndrome [LGS]), 58 (unknown/idiopathic), 27 (tuberous sclerosis [scl.]), 16 (infection), 13 (disorders of neuronal migration [migr.] or genetics [genet.] or metabolism), 11 (trauma), 5 (ischemia), and 4 (tumor).



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