ABSTRACT
Neuromodulation therapies represent an important treatment arm for patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery. Vagus nerve stimulation (VNS) - the neurostimulation modality in focus in this review - was the first available neuromodulatory therapy for DRE and was followed by anterior thalamic deep brain stimulation (ANT-DBS) and responsive neurostimulation (RNS). Although no comparative trials of these treatments have been performed, published data and clinical experience suggest comparable effectiveness. In VNS, DBS and RNS seizure reduction is delayed and increases over time raising the question of anti-epileptogenic mechanisms of neuromodulation. Considering the long-term effectiveness assumed for neuromodulatory treatments and the chronic nature of drug-resistant epilepsy, study designs allowing for long-term comparative observations would be of great value, but are hindered by the inherent nature of a long-term [surgical] control group and the bias associated with open-label trials. New trial designs using objective endpoints are needed, and may be aided by novel biomarkers of risk and disease severity for specific epilepsy populations.
Subject(s)
Brain/physiology , Epilepsy/therapy , Vagus Nerve Stimulation/methods , Animals , Deep Brain Stimulation , Electroencephalography , Event-Related Potentials, P300/physiology , History, 20th Century , History, 21st Century , Humans , Randomized Controlled Trials as Topic , Vagus Nerve Stimulation/historyABSTRACT
The development of vagus nerve stimulation (VNS) began in the 19th century. Although it did not work well initially, it introduced the idea that led to many VNS-related animal studies for seizure control. In the 1990s, with the success of several early clinical trials, VNS was approved for the treatment of refractory epilepsy, and later for the refractory depression. To date, several novel electrical stimulating devices are being developed. New invasive devices are designed to automate the seizure control and for use in heart failure. Non-invasive transcutaneous devices, which stimulate auricular VN or carotid VN, are also undergoing clinical trials for treatment of epilepsy, pain, headache, and others. Noninvasive VNS (nVNS) exhibits greater safety profiles and seems similarly effective to their invasive counterpart. In this review, we discuss the history and development of VNS, as well as recent progress in invasive and nVNS.
Subject(s)
Headache/therapy , Vagus Nerve Stimulation/methods , Vagus Nerve/physiology , Animals , History, 19th Century , History, 20th Century , Humans , Vagus Nerve/anatomy & histology , Vagus Nerve Stimulation/historyABSTRACT
Early in the last century, neuroscientists initially speculated that it might be possible to influence brain activity and associated behaviours by stimulating the vagus nerve in the neck. Several animal studies pointed to this possibility. In the 1980s, Zabara discovered that vagus nerve stimulation (VNS) could reduce or eliminate seizures in dogs. His discovery led to enhanced methods of direct VNS and the development of an implantable device for human VNS. VNS is now an accepted long-term treatment for epilepsy, used by over 15000 patients worldwide. Many have wondered whether VNS could treat other neuropsychiatric disorders. This paper reviews the neurobiology involved in VNS, highlights the VNS clinical findings to date, and discusses potential VNS research opportunities for both clinical and basic investigators. Comments on the clinical utility of VNS in actual clinical practice are provided.
