Vagus nerve stimulation is an alternative to antiepileptic medications that has specific benefits for many patients. It was approved for general clinical use in Europe in 1994 and in the United States in 1997, and there now have been over 100,000 patients implanted and more than 200,000 patient-years of experience. Along with growing clinical use, research has continued, with much of the focus on vagus nerve stimulation’s optimal use and breadth of indications. In a broad review, the author discusses mechanistic insights, current use, and future directions for vagus nerve stimulation. The treatment of epilepsy continues to evolve to commonly include non-pharmacologic treatments, and vagus nerve stimulation is an important, conventional treatment option.
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• Vagus nerve stimulation is an effective alternative to antiseizure medications, but it rarely produces seizure freedom.
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• Vagus nerve stimulation’s mechanism has been well characterized, and its effect may be maximized through adjustments to the stimulation parameters.
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• Vagus nerve stimulation generally produces minimal adverse effects and can benefit mood.
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• Vagus nerve stimulation may reduce the risk of sudden unexpected death in epilepsy.
Historical note and terminology
Electrical stimulation of the vagus nerve as a treatment for epilepsy has its direct origins in mid 20th century observations that such stimulation may produce EEG changes, but the first clinical application of vagus nerve electrical stimulation for epilepsy dates to the late 19th century (45). In the 1880s, a transcutaneous electrical stimulator was developed to be applied over the carotid artery for prophylactic and abortive treatment of seizures. The basis of this treatment was in late 18th century reports that bilateral carotid artery compression aborts seizures. Such treatments were supported by the belief that seizures were due to excessive blood flow within the brain. With the subsequent development of pharmacologic treatments for epilepsy, these therapies were abandoned.
Vagus nerve stimulation, as it is presently employed, dates back to the 1952 report that states it can prevent interictal spikes in a strychnine model of feline epilepsy (86). Interest in vagus nerve stimulation as a modern treatment for epilepsy was reinforced 30 years later with the demonstration that the antiepileptic effect of vagus nerve stimulation outlasts the electrical stimulus in strychnine and pentylenetetrazol models of canine epilepsy (82). Additional animal studies in rats confirmed this effect, advanced the search for optimal stimulation parameters, and heralded the human trials (81).
Human treatment with vagus nerve stimulation began in 1988 with the first human stimulator implantation and continued over the next 8 years with larger studies and randomized controlled trials. A series of similar stimulators (neurocybernetic prostheses) have been developed for use in clinical trials and subsequent clinical practice. These devices are the only available means to deliver therapeutic vagus nerve stimulation. In the United States, it was approved as a treatment for focal epilepsy in 1997 and as a treatment for treatment-resistant depression in 2005. As of 2018, the neurocybernetic prosthesis has been implanted in more than 100,000 individuals worldwide and used in 70 countries.