What’s new in the field of epilepsy? On November 14, 2013, the U.S. Food and Drug Administration (FDA) approved the NeuroPace RNS? system for the adjunctive treatment of adults with partial epilepsy who have no more than 2 epileptogenic foci and are refractory to 2 or more antiepileptic drugs. November also saw the approval of eslicarbazepine (Aptiom?), a once-daily antiepileptic drug, for International Epilepsy Month. The FDA’s approval of these two new approaches was the most important event of “2013 Changing Practice. The new world of therapeutic instruments Antiepileptic drugs are an important pillar of epilepsy treatment, but many patients need additional treatment options. The NeuroPace RNS (reactive neurostimulator) system was the first new device to be used in the treatment of patients with refractory partial epilepsy since the FDA approved the vagus nerve stimulator (VNS) in 1997. To date, the VNS has been implanted in tens of thousands of patients suffering from various epilepsy types. Other devices under development in refractory epilepsy include: stimulation of the anterior thalamic nucleus, which has been approved in Europe (and not in the United States), and trigeminal nerve stimulation, which has not yet shown convincing antiepileptic benefit. How does the NeuroPace RNS system work? There are a number of important differences between the VNS and NeuroPace RNS systems. First, the VNS stimulates the vagus nerve in the neck, while the NeuroPace RNS system is implanted intracranially and pre-stimulates cortical epileptic foci in the brain. Then depending on the epileptic focus (or foci) 1 or 2 can be surgically implanted as well as the depth of stimulation or the subdural cortical band that has been previously identified by detailed electroencephalographic (EEG) testing of the epileptic foci. Although the VNS can be stimulated according to a conventional schedule, the NeuroPace RNS system automatically detects abnormal EEG activity and responds by delivering electrical shocks. This constitutes a “closed-loop” system, rather than an “open-loop” VNS. Whether the RNS system is more effective than VNS is unclear, as comparative studies have not yet been completed. Data from a clinical trial of the NeuroPace RNS system Morrell and colleagues published a multicenter, double-blind, randomized, controlled trial of 191 adults with medically refractory partial epilepsy who had been implanted with a reactive neurostimulator. These patients underwent a blinded, sham treatment trial for 12 weeks, followed by 84 weeks of open-label treatment. Seizure frequency was reduced by a mean of 37.9% in the treatment group (n = 97) and by 17.3% in the sham treatment group (n = 94; P = 0.012). In any case, response rates (defined as at least a 50% reduction in seizures) were comparable in the treatment group (29%) and the sham treatment group (27%). Adverse events were similar in both groups. This year, the American Epilepsy Society meeting reported long-term data on 256 patients (191 from the pivotal study and 65 from the feasibility study) revealing a median percent reduction in epilepsy of 38.9% at 1 year and 51.1% at 2 years, and 20% of patients were seizure-free for at least 6 months. A prospective, open-label, 7-year treatment study is ongoing. Tolerability In the pivotal study, none of the tested neuropsychological tests deteriorated. In contrast, language function, visuospatial ability, and memory improved significantly (P < 0.05) at the end of 1 and 2 years. Quality of life also improved (P < 0 .02). Adverse events included intracranial hemorrhage in 9 of 191 patients (4.7%), 6 of whom developed postoperatively (3 epidural hematomas, 2 parenchymal hemorrhages, and 1 subdural hematoma). In addition, three patients with subdural hematomas were due to seizure-related brain injury. These hemorrhagic patients had no permanent neurological sequelae. 10 patients had soft tissue values or incision site infections. 4 patients required isolation of the device. Six patients died during the study period (four of them died unexpectedly and suddenly during a seizure [SUDEP], one had lymphoma, and one committed suicide). A leap forward in epilepsy treatment The NeuroPace RNS system is the second medical device that has been approved for the treatment of refractory epilepsy and represents a huge breakthrough over VNS. This new device will be indicated for patients who are considered unsuitable for epilepsy surgery for some reason (patients with many epileptic foci or epileptic foci in areas of speech function are preferred). Although six patients died during the study period, these deaths were not related to the device. The fact that four patient deaths were classified as SUDEP and may have been caused by refractory epilepsy further emphasizes the urgency of aggressive epilepsy control. There are data showing that the NeuroPace RNS system has durable antiepileptic activity and even brings further improvement over time.FDA approval of the NeuroPace RNS system provides an important new option for the treatment of refractory partial epilepsy. It remains to be seen how well this closed-loop response cortical stimulation works in the "real world" of epilepsy patients.