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New
Treatments for Epilepsy Chelsea
Henrie first knew something was wrong when, at age 16, she poured
cereal into her shoe. “I
also stuck my hand in the toaster once,” recalls Henrie, now 20
and a student at the University of New Mexico in Albuquerque.
“That was the worst thing that happened.” Like
2.8 million other Americans, Chelsea Henrie has epilepsy, a
disorder characterized by seizures, or sudden electrical storms,
in the brain. Though rarely fatal unless a seizure occurs while a
person is swimming or driving or the seizure is severe and
prolonged, epilepsy can be a life-wrecker. But
today, Henrie is seizure-free, thanks to a promising kind of brain
surgery that some epilepsy specialists believe should be a
treatment of first, not last, resort. Last
week at a meeting of the American Epilepsy Society in Boston,
researchers discussed a number of new approaches to treating
epilepsy, from the kind of surgery Henrie had to a device called a
Vagus Nerve Stimulator that shocks a nerve to the brain and an
increasingly broad array of drugs. In children, a small study
shows that the very high fat, low carbohydrate Atkins diet can
reduce the need for epilepsy medications. Another approach in the
pipeline is a device that may spot and abort seizures before they
start. The
kind of surgery Henrie had is the focus of a $30 million study at
19 medical centers funded by the National Institute of
Neurological Disorders and Stroke, part of the National Institutes
of Health. The goal of the ERSET study, which is still enrolling
new patients, is to see whether early surgical intervention to
remove a small piece of the temporal lobe in the brain is better
than aggressive treatment with drugs. The underlying causes of
seizures are well-documented: head trauma, infections, genetic
defects and problems that occur as a child’s brain grows. In
women, seizures often strike just before menstruation. Sleep
deprivation can provoke seizures, too, notes
Dr. Gregory L. Barkley, an epilepsy specialist at Henry
Ford Medical Center in Detroit. “Every year, at the end of the
semester, I have a high school or college student who has a
seizure,” says Barkley. In
partial seizures, the electrical storm begins in one part of the
brain and spreads; in generalized seizures, the abnormal activity
bursts out all over the brain at once. Some
partial seizures are so mild a person may merely twitch and not
lose consciousness. Even in generalized seizures, patients
sometimes just stare for a few minutes, a state once called
“petit mal” and now called “absence” (pronounced the
French way). In more
severe cases, once called “grand mal” and now called
“tonic-clonic” seizures, the body stiffens and jerks
rhythmically for several minutes.
As
seen on an EEG, or electroencephalogram, the brain’s electrical
activity changes dramatically during a seizure. Unlike the heart,
whose electrical activity normally appears simple and coordinated,
the brain “normally appears to be chaotic ,” says Dr. John
Stern, co-director of the UCLA Seizure Disorder Center. “But
during a seizure, this apparently disorganized activity becomes
more regular and with this change, brain function becomes
impaired.” Surgeons
have known for years that a hemispherectomy, removing half of the
brain, can reduce seizures, and a study published in October in
the journal Neurology confirmed this. Led by Dr. Eric Kossoff, an
epileptologist at Johns Hopkins Hospital, the study found that 86
percent of 111 children who had hemispherectomies between 1975 and
2001 became either seizure-free or vastly improved. But
removing half the brain “is pretty radical,” says Kossoff. So
in cases where seizures are confined to a smaller region of the
brain, the idea is to remove less brain tissue. A pivotal,
randomized study of 80 patients with temporal lobe epilepsy in
Canada published in 2001 showed that the 40 who had surgery to
remove an ice-cube sized portion of the brain were more likely to
be seizure-free than the 40 patients assigned to drug therapy.
The surgery was effective 60 percent of the time. That
raised an obvious question: If surgery is so much more effective
than drugs, why wait to do it? “Most
people wait 18 to 22 years to have surgery, partly out of the
understandable fear of having part of their brains removed and
partly because doctors feel it is an intervention of last
resort,” says Dr. Daniel Hoch, an epileptologist at
Massachusetts General Hospital. During that time, they “are not
driving, they may not hold a job and they may have dropped out of
a lot of life.” Hence
the ERSET study (www.erset.org
or www.erset.net ), run by
neurologist Dr. Jerome Engle, Jr. at UCLA, in which patients will
be randomized to get drugs or surgery to remove part of one mesial
temporal lobe. ((The temporal lobes, one on each side of the
brain, lie just above the ear. Deep inside each is a structure
called the hippocampus, which is vital to memory. People seeking
the surgery must be tested beforehand to make sure the remaining
hippocampus on the “good” side can process memory
sufficiently.) A
less invasive surgical approach is implanting a “pacemaker”
under the skin on the chest. Wires from the pacemaker are
threaded, under the skin, to the vagus nerve in the neck. The
Vagus Nerve Stimulator, which is made by Cyberonics, Inc. and
costs $15,000, is programmed to fire for 30 seconds every five
minutes or so. When
it fires, it stimulates the vagus nerve, which transmits the
signal to the brain. The device, which has been used in 22,000
patients worldwide, yields good seizure control in more than one
third of cases, some control in another third and none in the
rest, says Dr. Edward Bromfield, an epilepsy specialist at Brigham
and Women’s Hospital in Boston. Vagus nerve stimulation studies
were the focus of more than two dozen reports at last week’s
epilepsy meeting. Scientists
are also working on a device being developed by NeuroPace, Inc.
that would be implanted into the skull with electrodes placed on
the surface of the brain. The idea, says Kossoff of Johns Hopkins,
is to detect abnormal brain activity before it becomes a seizure,zonegran
then stimulate the brain to abort the seizure. A
lower tech approach is the ketogenic (or low carbohydrate, high
fat) diet, which creates “ketone
bodies,” substances produced when the body burns fat instead of
carbohydrates. The
diet induces a state of semi-starvation, which makes it tough to
adhere to. But it can be quite effective, especially in children.
A tiny study by Hopkins researchers presented at last week’s
meeting showed the Atkins diet allowed some children to reduce
their medications. Increasingly
sophisticated medications can also help. In recent years,
dual-mechanism drugs such as Zonegran, Topamax, Lamictal and
Keppra have come on the market. They can simultaneously decrease
excitation in the brain and boost the brain’s own inhibitory, or
dampening, signals. Older anti-epileptic drugs like Dilantin and
Tegretol just dampen
brain excitation, while
others like phenobarbitol, Valium, Depakote and Neurontin, just
boost the inhibitory system. But
for many people, the ultimate answer may be surgery, sooner rather
than later. John Davies, 60, an accountant who lives in Salem, MA
endured decades of seizures before having brain surgery a year and
a half ago. “I haven’t had an attack since,” he says.
“I’m back doing things I couldn’t do before.”
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