Rolston, John D

Background Deep brain stimulation (DBS) has been investigated for patients with drug-resistant epilepsy who are not candidates for resective surgery. Because different types of epilepsy involve distinct brain networks, numerous DBS targets have been explored, yet a comprehensive synthesis is lacking. Methods To provide a comprehensive overview of this expanding literature, we conducted a systematic review of studies for DBS in epilepsy, including case series, prospective and retrospective studies. We collected data on surgical targets, individual disease characteristics, outcomes and precise electrode placements. DBS electrode coordinates were gathered into a common template space and related to clinical outcomes. Results We included 124 studies, corresponding to 1210 patients and 20 distinct surgical targets. While the anterior (ANT) and centromedian (CM) nuclei of the thalamus remain the most studied, we also review less commonly used targets that show promise for specific forms of epilepsy and may warrant further investigation. Substantial variability in targeting strategies and electrode placement was observed within each of the target regions. Importantly, significant relationships between stimulation location and outcomes were identified for ANT-DBS and CM-DBS. For ANT-DBS, shorter distance to the mammillothalamic tract junction was associated with greater seizure reduction on both study-level and patient-level analyses (r=−0.55, p<0.001 and r=−0.51, p<0.001, respectively). For CM-DBS, localisation effects may be dependent on the form of epilepsy, with stimulation of the parvocellular CM being associated with better outcomes in generalised epilepsy. Conclusions Our results emphasise the importance of accurate targeting in DBS for epilepsy. Our database and atlas of DBS targets are made publicly available, potentially serving further meta-analytical work. PROSPERO registration number CRD420250649304.

AbstractObjectiveSummarize 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.MethodsWe 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.ResultsWe 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.SignificanceNeurostimulation 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.