Epilepsy Surgery in the Era with New Antiepileptic Drugs : Introduction of Neuromodulation Surgery in Epilepsy

Abstract

  Many new-generation anti-epileptic drugs (AEDs) have been approved in Japan since 2000. While the AEDs may decrease side effects, they have not significantly decreased the incidence of drug-resistant epilepsy. From 30% to 40% of epilepsy patients are drug resistant and should be considered for epilepsy surgery. Resective epilepsy surgery is the only established curative treatment. For various reasons, however, many patients are ruled out as candidates for resection.

  Neuromodulation surgery is an alternative palliative treatment option for drug-resistant epilepsy patients contraindicated for resection. Three neuromodulation systems have been approved for refractory epilepsy treatment in the United States : vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and responsive neurostimulation (RNS). VNS primarily works by stimulating the left vagus nerve according to a fixed schedule. In addition, a new mode of closed-loop VNS that detects heart rate variability has recently been developed. VNS achieves 50% seizure reduction in 60% of patients and seizure freedom in 5-10% of patients. The effectiveness of VNS, moreover, increases year by year. ANT-DBS is another option for patients with drug-resistant epilepsy. The 50% responder rate has reached about 75% in ANT-DBS patients. The most important complications associated with ANT stimulation may be psychiatric problems arising from the procedure. RNS is a closed-loop neuromodulation system that continuously monitors neural electroencephalography activity via electrodes placed over the possible seizure onset zone and responds with electrical stimulation when a pre-defined epileptic activity is detected. Controlled clinical trials have revealed a continuous improvement in seizure reduction rates reaching 75% over 9 years of treatment.

  These neuromodulation systems will be promising palliative options for patients with drug-resistant epilepsy. The prompt introduction of ANT-DBS and RNS in Japan is urgently desired.