Vagus nerve stimulation for treatment of seizures?

Abstract

V AGUS NERVE stimulation (VNS) is a new treatment available for patients with refractory epilepsy. The first implant was performed in 1988, and since then more than 900 patients have received this therapy. There has been skepticism among epileptologists concerning VNS. Many have questioned the efficacy of this treatment, referring frequently to the disappointing results of early cerebellar and thalamus stimulation attempts. Vagus nerve stimulation has erroneously been compared with epilepsy resective surgery, and many have the opinion that VNS proponents promote using VNS rather than traditional surgery when it is indicated. Some neurosurgeons have insinuated that clinicians who use VNS are depriving their patients of the possibility of resective surgery and have not even bothered to evaluate them properly. Because of these misconceptions and heated debates, I want to make clear the distinction between resective surgery, which is a successful and superior method of treating selected patients who are deemed appropriate candidates, and VNS, which is best compared with the efficacy and adverse effects of the new antiepileptic drugs (AEDs). All patients entering into VNS protocols are usually extensively evaluated for epilepsy surgery and are not implanted with the VNS device haphazardly. Unfortunately, the majority of patients with refractory cases are not epilepsy surgery candidates, so the development of other techniques, such as new drugs and VNS, are, of course, necessary. The VNS generator (NeuroCybernetic Prosthesis System, Cyberonics Inc, Webster, Tex) is implanted in the upper left area of the chest, with the stimulating lead attached to the left vagus nerve in the neck. The generator is then programmed externally with a programming wand attached to a personal computer. Frequency, output current, pulse width, signal-on time, signal-off time, and magnet parameters are adjusted by the physician using the programming system. The most commonly studied stimulation paradigm has been a 20to 30-Hz, 1.0to 2.0-mA, 500-microsecond pulse width, with 3 seconds–on time and 5 minutes off, 24 hours a day regardless of seizure activity. There is a magnet provided that can restart the VNS generator at its own parameters for a brief time to try to abort an emerging seizure. Magnet parameters may be programmed to their own settings by the same method as for the continual intermittent stimulation parameter settings. Vagus nerve stimulation is approved in Europe and other countries; therefore, this procedure is now used in regular clinical practice. Two double-blind studies comparing high stimulation (30 seconds on and 5 minutes off) with low stimulation (30 seconds on and 90 minutes off) have been completed. The first study (EO-3) was conducted in the United States, Germany, the Netherlands, and Sweden. The most recent study (EO-5) was conducted in the United States (Cyberonics Inc, unpublished data, August 1997). All patients in these trials had at least 6 partial seizures monthly despite the use of multiple AEDs at entry. Some were considered epilepsy surgery failures or not appropriate candidates for resective surgery. Other study protocols that have included 500 patients have been open-label trials. Efficacy results of the doubleblind trials at the end of 3 months of VNS treatment were remarkably similar, with a median of 24% (EO-3) and 27% (EO-5) reduction of seizure frequency, and 30% and 23%, respectively, with greater than 50% reduction in seizures for the patients receiving high stimulation. After 2 years of VNS therapy, 71 of 87 evaluable patients from the EO-3 study were still receiving VNS and 43% had experienced a greater than 50% reduction in seizures (Cyberonics Inc, unpublished data, June 1997). Besides delivering continual intermittent stimulation, the VNS generator allows patients the option of using a magnet to activate the device (“therapy on demand”) when experiencing an aura or a simple partial seizure. In many cases, this effectively prevents spreading of seizure activity and can give the patient a method to exert some type of control over his or her seizures. The safety profile of VNS is very favorable and the adverse effects are completely different from those seen with the use of AEDs. Cognitive and sedative adverse effects are not generally reported. In fact, many actually report an increase in awareness. Adverse effects of VNS have been restricted to local irritation, hoarseness, coughing, and, in a few cases, swallowing difficulties when the stimulator was on. All were immediately reversible with reduction of the stimulation parameters or when the generator was turned off. Vagus nerve stimulation does not interfere negatively with concomitant AED use or with any other drug given for other disorders. Surgery morbidity is very low, with infections causing the most problems (2%). SECTION EDITOR: VLADIMIR HACHINSKI, MD, FRCPC, DSCMED