Vagus nerve stimulation

Historical note and nomenclature
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By John M Stern MD

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 (Lanska 2000). 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 to the 1952 report that such stimulation can prevent interictal spikes in a strychnine model of feline epilepsy (Zanchetti et al 1952). 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 (Zabara 1985). Additional animal studies in rats confirmed this effect, advanced the search for optimal stimulation parameters, and heralded the human trials (Woodbury and Woodbury 1990).

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 2011, the neurocybernetic prosthesis has been implanted in more than 60,000 individuals worldwide and used in 70 countries.