Neurostimulation in people with drug-resistant epilepsy: Systematic review and meta-analysis from the ILAE Surgical Therapies Commission

Objective: Summarize the current evidence on efficacy and tolerability of vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) through a systematic review and meta-analysis. Methods: We followed the Preferred Reporting Items of Systematic reviews and Meta-Analyses reporting standards and searched Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. We included published randomized controlled trials (RCTs) and their corresponding open-label extension studies, as well as prospective case series, with ≥20 participants (excluding studies limited to children). Our primary outcome was the mean (or median, when unavailable) percentage decrease in frequency, as compared to baseline, of all epileptic seizures at last follow-up. Secondary outcomes included the proportion of treatment responders and proportion with seizure freedom. Results: We identified 30 eligible studies, six of which were RCTs. At long-term follow-up (mean 1.3 years), five observational studies for VNS reported a pooled mean percentage decrease in seizure frequency of 34.7% (95% confidence interval [CI]: −5.1, 74.5). In the open-label extension studies for RNS, the median seizure reduction was 53%, 66%, and 75% at 2, 5, and 9 years of follow-up, respectively. For DBS, the median reduction was 56%, 65%, and 75% at 2, 5, and 7 years, respectively. The proportion of individuals with seizure freedom at last follow-up increased significantly over time for DBS and RNS, whereas a positive trend was observed for VNS. Quality of life was improved in all modalities. The most common complications included hoarseness, and cough and throat pain for VNS and implant site pain, headache, and dysesthesia for DBS and RNS. Significance: Neurostimulation modalities are an effective treatment option for drug-resistant epilepsy, with improving outcomes over time and few major complications. Seizure-reduction rates among the three therapies were similar during the initial blinded phase. Recent long-term follow-up studies are encouraging for RNS and DBS but are lacking for VNS.