Vagus
Nerve Stimulation for Epilepsy Treatment – A Five-Year Review Following
FDA Approval
Vagus nerve
stimulation (VNS), an electrical stimulation therapy currently used
to treat epilepsy, can help reduce seizures in patients while increasing
activity and alertness in the brain. Since its approval by the Food
and Drug Administration (FDA) in July 1997, a number of animal and human
studies have been conducted to determine the various uses and outcomes
of VNS.
In a review article in the
journal Neurology, Thomas Henry, M.D., associate professor of neurology,
Emory University School of Medicine and director of the Emory Epilepsy
Center, examines the different methods, or mechanisms, of VNS tested
and used over the past five years. Because of his expertise in the fields
of epilepsy and vagus nerve stimulation, journal editors selected Dr.
Henry to write the review article, published in the Sept. 23 issue of
the journal.
"The reason for this review
paper is to evaluate the therapeutic mechanisms of vagus nerve stimulation,
how it works, how to maximize its uses and how not to use it in inappropriate
situations," Dr. Henry explains. "Because VNS reduces or stops seizures
through multiple mechanisms and actions, this paper may be beneficial
to physicians and researchers who are looking for the precise treatment
of an individual."
More than two million people
in the U.S. have epilepsy, a chronic medical condition produced by temporary
changes in the electrical function of the brain, causing seizures that
affect awareness, movement, or sensation. Most people don't know why
they have epilepsy. There is no known cause of epilepsy, however the
greatest known cause is head injury followed by infections, tumors and
strokes. Patients who suffer from partial seizures (seizures that affect
only one side of the brain), who do not respond well to antiepileptic
drugs and who cannot undergo brain surgery are all good candidates for
VNS.
Stimulation of the vagus
nerve is thought to affect some of its connections to areas in the brain
that are prone to seizure activity in people with epilepsy. Surgeons
implant a small stimulating device, similar to a cardiac pacemaker,
just under the skin in the left chest area. A connecting wire is run
under the skin from the device to the vagus nerve in the left side of
the neck. Three small leads, or wires, are then carefully attached to
the nerve. Pre-programmed, mild, intermittent electrical pulses are
then delivered 24 hours a day to the nerve, slowing or stopping seizures.
Because the left vagus nerve sends information to both sides of the
brain, researchers only need to stimulate that one side. In 1997, the
FDA approved use of the VNS for patients, 12 years of age and older,
with partial seizures.
"Most of the research in
VNS has been done during the past five years, following the FDAÕs approval,"
says Dr. Henry. "During that time, weÕve found VNS can do more than
just slow or stop seizures. Past studies show VNS can increase activity
of the brain chemical, norepinephrine, which acts as a neurotransmitter
in the brain, and can antagonize seizures in epileptics. Boosting norepinephrine
can also relieve depression, but more studies are needed to determine
if vagus nerve stimulation can be used as a treatment for depression."
Researchers have also found
VNS increases activity in the reticular activating system of the brain,
a network in the brain that controls arousal and alertness. Patients
often report improved alertness during VNS. Several previous studies
have also shown evidence of improved learning and memory during stimulation,
although behavioral effects of VNS have not been completely studied
in animals or humans.
To determine how much the
brain is aroused from thinking and learning before, during and after
VNS, Emory researchers looked at the amount of cerebral blood flow in
the brains of patients with epilepsy. Using position emission tomography
(PET) scans, 10 Emory patients were scanned before receiving a treatment
of VNS and again within 20 hours after treatment was administered (known
as acute VNS). Half received high levels of stimulation, while the other
half received low levels of stimulation.
In both groups, blood flow
changes showed increased synaptic activity in the so-called "sensory
strip" of the brain, the major site for cerebral processing for sensory
activity on the left-side of the body. Widespread blood flow increases
occurred in areas of reticular, autonomic and limbic systems in both
hemispheres, areas important in maintaining alertness, memory and mood,
with more areas of blood flow increases at higher levels of stimulation.
Patients were then scanned
again, following three months of intermittent VNS (known as chronic
VNS). Half received high levels of stimulation and half received low
levels of stimulation. While these scans showed an increase in cerebral
blood flow, they revealed smaller volumes of significant activations
than the previous scans. More studies are needed to determine the difference
in findings between acute and chronic stimulation through PET scans,
but researchers say PET scans may reflect brain adaption to chronic
stimulation of the left vagus nerve.
Like most implantable devices,
there are some complications that may been seen following surgery. Patients
may experience tingling in the neck, hoarseness and a slight cough during
nerve stimulation.
"During the past five years
of VNS research, weÕve determined that various mechanisms of VNS can
help in reducing seizures in those with epilepsy, not just one single
mechanism," says Dr. Henry. "Through these means and as research progresses
in this field, we feel we can help a certain population of patients
with epilepsy obtain manageable seizure control and maintain a good
quality of life."
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