Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy

Abstract

Background: Neuromodulation-based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuromodulation 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.

Abbreviations: AED, antiepileptic drugVNS, vagus nerve stimulation.

FIGURE 1.

Seizure freedom, response to treatment, and median seizure reduction from the VNS therapy registry. Across all patients together (A), a progressive increase in seizure freedom was observed after device implantation, paralleling increases in the rate of response to therapy (defined as patients with ≥50% seizure frequency reduction) and the median reduction of seizure frequency. When comparing patients with partial seizures (B) vs generalized seizures (C) as the predominant seizure type, seizure freedom was significantly more likely in patients with generalized seizures at 0 to 4 months (P < .01, Pearson χ²) and at 4 to 12 months of follow-up, although this difference was not significant at 12 to 24 months or 24 to 48 months (P > .5). Responder rate and median seizure reduction did not differ significantly between patients with primarily partial vs generalized seizures. N = 12 319 visits among 5554 patients, including 4666, 3277, and 3182, and 1194 patients at each follow-up period, respectively. VNS, vagus nerve stimulation.

FIGURE 2.

Seizure freedom rates by age of epilepsy onset and implantation. A, patients who achieve seizure freedom had significantly later onset of epilepsy than those with persistent seizures at 0 to 4 (P < .001, Wilcoxon sum rank test) 4 to 12 (P < .001), 12 to 24 (P < .001), and 24 to 48 (P < .05) months. B, no significant difference in age of implantation was observed between patients with or without seizure freedom (P > .2 at each time point, Wilcoxon sum rank test). C, patients who achieved seizure freedom showed shorter onset-to-implant intervals than those with persistent seizures, but this difference was not significant (P range 0.07-0.26 at each time point, Wilcoxon sum rank test). N = 12 319 visits among 5554 patients, including 4666, 3277, and 3182, and 1194 patients at each follow-up period, respectively.

FIGURE 3.

Seizure freedom and response rate with VNS from systematic literature review. Data compiled from 2869 patients across 78 studies in the systematic review show progressive increase in both seizure freedom and response rate over time, resembling findings from the registry (Figure 1). At latest follow-up, 60% of patients responded to VNS (≥50% reduction in seizures), and 8% were seizure free. N = 650, 405, 1503, 876, and 326 patients at each follow-up period, respectively. VNS, vagus nerve stimulation.