What Is the Role of the Vagus Nerve Stimulator in the Treatment of Epilepsy?
| Response from Andrew Wilner, MD
Neurohospitalist, Department of Neurology, Lawrence and Memorial Hospital, New London, Connecticut
Vagus Nerve Stimulation: Introduction
The vagus nerve stimulator (VNS) is a pacemaker-like device implanted in the chest that delivers intermittent electrical signals to the brain via an electrode wrapped around the left vagus nerve. The VNS received US Food and Drug Administration (FDA) approval in 1997 for the adjunctive treatment of partial seizures in patients 12 years and older. In addition, VNS was approved in 2005 for chronic or recurrent refractory depression. The device is manufactured by Cyberonics.
History, MOA, and Efficacy
At this year's American Epilepsy Society meeting in San Antonio, Texas, Elinor Ben-Menachem, MD, an experienced VNS investigator and Professor of Neurology and Epilepsy at the Institute for Clinical Neurosciences and Physiology, Gothenborg University, Gothenborg, Sweden, reviewed the history of VNS therapy for epilepsy. The first human implant was performed in 1988 by legendary epileptologists Kiffen Penry, BJ Wilder, and Gene Ramsay. To date, more than 60,000 patients have been implanted.
Dr. Menachem described VNS as "peripheral stimulation" to the brain. As early as 1938, it was observed that VNS affects EEG synchrony in cats. The exact mechanism of action of VNS responsible for seizure control remains unknown. Possible mechanisms include: arousal of reticular formation, stimulation of the locus coeruleus and noradrenaline pathways, peripheral sensory stimulation, changes in neurotransmitter, amino acid, or neuropeptide concentrations, long-term learning through synaptic structural changes, and indirect thalamic stimulation. Functional MRI during VNS stimulation has shown changes in blood oxygenation levels reflecting changes in neuronal activity in multiple brain areas, including orbitofrontal, parieto-occipital cortex bilaterally, left temporal cortex, left amygdala, thalamus, and hypothalamus.
Only about 2.5% of patients with pharmacoresistant seizures become seizure free with VNS, but about 42% have > 50% and 20% have > 75% seizure reduction. Partial seizures appear more likely to respond than other types. Common side effects include cough, hoarseness, or shortness of breath. After the device is implanted by a neurosurgeon, stimulation parameters of frequency, duration, and amperage are tailored for each patient by a neurologist to optimize efficacy and tolerability. Seizure control may improve with time. According to Dr. Ben-Menachem, patients should wait 18-24 months before concluding whether the device is effective.
VNS Candidates and New Advances
VNS should be considered for patients who have failed 2-3 appropriate antiepileptic drugs and are not candidates for resective epilepsy surgery (patients who are good surgical candidates should pursue that route first, as complete seizure control is much more likely with resective surgery than with VNS). VNS may also be considered in patients who have failed epilepsy surgery. VNS lacks adverse cognitive side effects, which may prove an advantage in patients who are already receiving 1 or more antiepileptic drugs.
Future Neurostimulation Devices
Several other types of neurostimulation are currently under investigation for the control of epilepsy. These include anterior thalamic stimulation, responsive neurostimulation, and trigeminal neurostimulation. At present, none of these are FDA approved.
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