It is estimated that up to 1% of the general population suffers from epilepsy. For 15 to 20% of these people, medications provide poor to no control over their seizures. Up to four million people in the United States suffer from treatment-resistant depression. These groups of patients now have a new treatment option available to them in the form of vagal nerve stimulation.
Vagal nerve stimulation as a treatment for epilepsy was first conceived by Jacob Zabara, a neurophysiologist at Temple University. He observed a common finding from historical animal studies in that stimulation of the vagus nerve at different intensities produced different effects on the EEGs (electroencephalogram) of animals. He then hypothesized that properly timed direct stimulation of the vagus nerve might be useful in disrupting or preventing seizures.
In 1988 the first human subject was implanted with a vagal nerve stimulator. Since then over 1,000 patients have participated in at least seven clinical trials throughout 26 countries. These studies have shown that vagal nerve stimulation decreases the frequency of seizures, decreases seizure duration, and decreases seizure intensity in many patients who were previously poorly controlled on anticonvulsive medications. The studies also revealed that the severity and duration of postictal symptoms were decreased by stimulating the vagus nerve and that the overall seizure frequency continues to decrease with time.
On July 16, 1997, the FDA approved the first medical device for the treatment of epilepsy. The vagal nerve stimulator is a generator attached to leads on the vagus nerve which stimulates the vagus nerve periodically whether or not the patient experiences a seizure. In addition, the stimulator can be activated by running a magnet across its surface. Stimulating the vagus nerve near the time of the seizure can effectively abort several types of seizures and is nearly imperceptible to the patient.
The surgical procedure involves placing a generator in a subcutaneous pocket over the left chest between the subcutaneous tissues and the pectoralis fascia. A second incision is made on the left side of the neck approximately midway between the mastoid process and the clavicle. A subcutaneous tunnel is then created connecting the neck incision to the subcutaneous pocket over the left chest and the vagus nerve stimulator leads are passed through the subcutaneous tunnel connecting the leads to the generator. The vagus nerve is then isolated and the helical platinum leads are placed very gently on the vagus nerve. The device is tested in the operating room, the wounds are then closed, and the patient is generally sent home on the day of surgery.
Stimulating either the right or left vagus nerve is equally effective in seizure reduction. Stimulating both vagus nerves provides no greater effect than unilateral stimulation. Ninety percent of the fibers in the vagus nerve are afferent; the efferent innervation of the right and left vagus nerves is asymmetric. The right vagus nerve innervates the sinoatrial node while the left vagus nerve preferentially innervates the atrioventricular node. Stimulation of the right vagus nerve is more likely to cause greater cardiac slowing than stimulating the left vagus nerve. For this reason the left vagus nerve is chosen as the nerve to stimulate.
Follow-up studies reveal that 33% of patients experienced a greater than 50% decrease in seizures at one year, 38% of patients experienced a greater than 50% seizure reduction at two years, and 37% of patients experienced a greater than 50% reduction in seizures at three years. In long-term followup, it was found that these patients also seemed to have less frequent migraine headaches, and depression seemed to be improved as well. This prompted independent studies of patients with depression undergoing vagal nerve stimulation, and studies have shown improvement in resistant depression in patients who have undergone vagal nerve stimulation. The FDA has just recently approved vagal nerve stimulation as a treatment for otherwise treatment-resistant depression.
There are different hypotheses of how the vagal nerve stimulator works in reducing seizures, treating depression, and possibly improving migraine headaches; however, the mechanism of action for vagal nerve stimulation is unknown at this time. Advantages of the vagal nerve stimulator are that, if the patient is not happy with the device, it can be removed. The procedure is a relatively simple outpatient procedure. Toxicity that has been associated with anticonvulsants does not exist. The effectiveness of vagal nerve stimulation does not decrease with time. Side effects, which include hoarseness at approximately 7.8%, headache at 4.5%, and shortness of breath at 3.8%, have been minimal and generally decrease with time.
Lastly, intermittent stimulation of the vagus nerve in the neck is a novel adjunct in the treatment of medication refractory seizures and treatment-resistant depression. Preclinical studies of animal models and large randomized trials in humans support its feasibility, tolerance, safety, and potential efficacy.