Joanna H Cox, Stefano Seri, Andrea E Cavanna

About one third of patients with epilepsy are refractory to medical treatment. For these patients, alternative treatment options include implantable neurostimulation devices such as vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation systems (RNS). We conducted a systematic literature review to assess the available evidence on the clinical efficacy of these devices in patients with refractory epilepsy across their lifespan. VNS has the largest evidence base, and numerous randomized controlled trials and open-label studies support its use in the treatment of refractory epilepsy. It was approved by the US Food and Drug Administration in 1997 for treatment of partial seizures, but has also shown significant benefit in the treatment of generalized seizures. Results in adult populations have been more encouraging than in pediatric populations, where more studies are required. VNS is considered a safe and well-tolerated treatment, and serious side effects are rare. DBS is a well-established treatment for several movement disorders, and has a small evidence base for treatment of refractory epilepsy. Stimulation of the anterior nucleus of the thalamus has shown the most encouraging results, where significant decreases in seizure frequency were reported. Other potential targets include the centromedian thalamic nucleus, hippocampus, cerebellum, and basal ganglia structures. Preliminary results on RNS, new-generation implantable neurostimulation devices which stimulate brain structures only when epileptic activity is detected, are encouraging. Overall, implantable neurostimulation devices appear to be a safe and beneficial treatment option for patients in whom medical treatment has failed to adequately control their epilepsy. Further large-scale randomized controlled trials are required to provide a sufficient evidence base for the inclusion of DBS and RNS in clinical guidelines.