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Approximately 30 percent of people with epilepsy have seizures that don't respond to current medications. For these people, vagus nerve stimulation (VNS) has been one therapeutic option, but the evidence supporting its use has been mixed. Now, the American Academy of Neurology (AAN) has released an update to its evidence-based guideline for the use of VNS in people with epilepsy that looks closely at this evidence and makes recommendations on its use. The guideline, which replaces the 1999 guideline on the same topic, has been endorsed by the American Epilepsy Society.
According to the Centers for Disease Control and Prevention, at least 2.2 million Americans are living with some form of epilepsy, which is a neurologic condition that causes seizures in the brain.
In VNS, a device is surgically implanted under the person's chest. Then, a wire is threaded under the skin connecting the device to the vagus nerve, one of 12 pairs of cranial nerves that originate in the brain and help control involuntary body functions such as breathing and digestion. When activated, the device stimulates the vagus nerve, which in turn transmits electrical impulses to the brain.
The U.S. Food and Drug Administration (FDA) has approved VNS as adjunctive (add-on) therapy for people whose seizures have not been helped adequately by antiepileptic drugs (AEDs); people over age 12 with partial epilepsy, which starts in one area of the brain but may spread to other areas (as opposed to generalized epilepsy, in which seizures involve the entire brain from the start); and adults aged 18 and older whose depression is not helped by other treatments.
The AAN's updated evidence-based guideline was established by a comprehensive review of 216 studies published on the procedure, says George Morris III, M.D., Fellow of the AAN, director of the Regional Epilepsy Center at Aurora St. Luke's Medical Center in Milwaukee, WI, and lead author.
The guideline found that weak evidence exists to support VNS for reducing seizures, for preventing seizures before they occur (evidence for this is only with VNS magnet activation at the time of seizure auras), and—as an added benefit—for improving mood in people with epilepsy. (Go to bit.ly/1eB6sXo to read the summary for patients. For a video interview with epilepsy expert Dr. Linda Selwa, go to bit.ly/NbvqJU.) But exactly what does that mean for patients?
According to David Spencer, M.D., a neurologist at the Oregon Health and Science University's Epilepsy Center and Fellow of the AAN, “terms such as ‘weak evidence’ may concern physicians who believe in VNS. However, the language of a guideline is intended not to overreach. It is a reflection of the current data.” Evidence from more studies—and more well-conducted studies—could change the recommendations in the future.
The authors of the updated VNS guideline evaluated all 216 studies based on the strength of their evidence.
“The major role of evidence-based medicine is to identify what we know, what we don't know, and where we have to use our judgment,” says Gary Gronseth, M.D., vice chairman of neurology at the University of Kansas Medical Center in Kansas City and Fellow of the AAN. Dr. Gronseth (who was not involved in the study) has been helping the AAN create evidence-based guidelines since the mid-1990s. Before the rise of evidence-based medicine, neurologists often practiced what Dr. Gronseth calls “eminence-based medicine”: in other words, they adopted the practices recommended by the most respected experts, combined with their own clinical judgment.
“If your professor said, ‘This is what you do,’ then that's often what you did,” Dr. Gronseth says. “We're trying to get beyond that.”
Ideally, the evidence should be based on large studies that include many people. When appropriate, the studies should be “blinded,” which means neither the researchers nor the participants know who is receiving the actual treatment and who is receiving a placebo—as well as “randomized,” which means that participants are assigned randomly (in a sense, by coin toss) to receive either the treatment or a placebo. The effects of the treatment should be clearly measured and not left to interpretation by the researchers. If more than one study produces similar results, the treatment recommendation is considered even more reliable.
However, the fact that no study exists proving that a particular treatment works is not proof that the treatment is useless, according to Dr. Gronseth. “This is one reason why doctors can't rely on evidence alone—good evidence often does not exist,” he notes.
* VNS may be considered as adjunctive treatment for children with partial or generalized epilepsy. (Weak evidence)
* VNS may be considered in patients with Lennox-Gastaut syndrome. (Weak evidence).
* In adult patients receiving VNS for epilepsy, improvement in mood may be an additional benefit. (Weak evidence)
* VNS may be considered progressively effective in patients over multiple years of exposure. (Weak evidence)
* Optimal VNS settings are still unknown, and the evidence is insufficient to support a recommendation for the use of standard stimulation versus rapid stimulation to reduce seizure occurrence. (Insufficient evidence)
* Patients may be counseled that VNS magnet activation may be associated with seizure abortion when used at the time of seizure auras (weak evidence) and that seizure abortion with magnet use may be associated with overall response to VNS treatment. (Weak evidence)
* There is insufficient evidence to determine whether or not new safety concerns have emerged since the last assessment. (Insufficient evidence)
* There is insufficient evidence to determine whether or not adverse effects differ in children from those in adults. (Insufficient evidence)
Guidelines, such as this one, can have implications for patients and physicians because of insurance coverage. Most providers currently cover VNS therapy. With the added evidence beyond the 1999 guideline, the update guideline recommends that physicians carefully document the use of medications and dosages use to treat epilepsy before moving to VNS. The guideline also recommends that physicians get approvals from payers before proceeding with the procedure, especially in children under 12 years of age.
The guideline also cautions against physicians listing depression as the primary reason for performing the procedure. Currently, Medicare (and many other payors) do not reimburse for the treatment of depression with VNS.
“Doing this kind of research is a chance to reflect back on the field's collective experience with a treatment. The process also offers insight into any adverse effects of a treatment or procedure, such as increased risk for infection,” says Dr. Spencer.
The guideline also points to the need for research and studies going forward. Dr. Morris and Dr. Spencer agree that evidence-based guidelines such as this one can point to the need for more evidence, which may change and expand the parameters of care.