Braincounterattack
USC Physicians Approach Stroke-or Brain Attack-From All Angles, Including a Landmark Trial to Evaluate Stroke Prevention
Neurologist Gene Sung, M.D., M.P.H., slides the films from a brain scan onto a light table. One, two, three and then a fourth-all sheets of plastic that, with one flick of a light switch, now glow with images of his patient's cerebellum.
A dozen physicians cluster around the pictures. Arms crossed,
they squint at the images. Some talk and point at a suspicious
area in the scans.
"She's a 30-year-old who presented with headache and ataxia,"
or trouble balancing, explains Sung, associate professor of clinical
neurology at the Keck School of Medicine of USC. "What do
you think?"
And so begins the weekly stroke meeting at USC University Hospital,
where USC physicians from across the landscape of medicine unite
to talk about challenging cases. Neurologists, neurological and
vascular surgeons, neurointerventional radiologists, emergency
physicians and rehabilitation specialists all come together to
decide on the best treatment options for patients whose lives
are threatened by stroke.
The meeting illustrates the physicians' team approach to preventing
stroke in patients both with and without symptoms: screening
patients at high risk for disease before symptoms ever show up,
and brainstorming the best treatment plans for patients showing
symptoms-before a stroke can kill.
"There are so many diagnostic and treatment options available
nowadays that it's very important that we work together to bring
about the best therapies for our patients," Sung says. "That's
the whole point of our stroke program."
Put simply, a stroke or "brain attack" often happens
when brain cells are starved of the nutrients that are delivered
by the blood. When blood cannot get to regions of the brain for
several minutes, the cells in these regions become permanently
damaged and tissues start to die.
Different regions of the brain handle various duties, such as
speaking or walking. So when these regions are harmed, a usually
vibrant and active person may suddenly have difficulty recalling
words, penning a signature or getting up from bed. Rehabilitation
specialists and physical and occupational therapists can help
patients recover, but sometimes setbacks remain stubborn.
Stroke can happen one of two ways: Blood vessels can become clogged
or they may burst. Think of it as a plumbing problem: A blocked
pipe keeps water from flowing where it is needed, while a leak
causes flooding and water damage.
Most strokes-as many as 80 percent-come from clogs. Doctors refer
to these as ischemic strokes.
At the heart of ischemic strokes is atherosclerosis, a gradual
buildup of fatty deposits along interior artery walls. A clot
may form at the clogged, narrowed part of a blood vessel in the
brain, or it might arise somewhere else in the body and flow
to the brain, where it gets stuck in a vessel and blocks blood
flow.
In strokes related to burst blood vessels, or hemorrhagic strokes,
blood suddenly spreads into surrounding brain tissue and compresses
it. A vessel can burst because of an aneurysm-a weakened, ballooned
area in the wall of a vessel-or because of abnormally formed
vessels.
Patients with ischemic problems can suffer mini-strokes, called
transient ischemic attacks. Symptoms such as slurred speech quickly
go away, but provide warning signs that a major stroke probably
will come later.
"These diseases can be totally silent," says Fred A.
Weaver, M.D., professor of surgery and chief of the division
of vascular surgery at the Keck School. "The first sign
at all in 50 percent of these patients is a stroke. And by then,
to some extent, the horse is already out of the barn."
Statistics bear out the disease's impact. Stroke is the third
leading cause of death in the United States after heart disease
and cancer. Each year about 600,000 Americans have a stroke.
Too many people see stroke as an inevitable result of growing
older. "Death by natural causes," shrugs Weaver.
But it does not have to be that way. "USC University Hospital
has been among the leaders in establishing a screening program
for the presence of vascular disease before problems like stroke
can happen," Weaver says. "And now, at the national
level, the American Vascular Association has taken an interest
in it and is moving forward with that screening model."
Susana Perese, technical director of the USC Vascular Laboratory,
has been influential in setting up the American Vascular Association's
free public screening initiative that first started in 2002 under
the leadership of University of Maryland's William R. Flinn,
M.D. This one-day screening held at 17 sites in May detected
potentially lethal or disabling vascular conditions in 13 percent
of all participants even though they had no symptoms (see "Vascular
Screening" below).
"We have Pap tests for cervical cancer and PSA testing for
prostate cancer," says Weaver, who urges better coverage
of preventive testing for stroke. "Why can't we have screenings
for people at high risk for vascular disease?"
He adds: "We want to prevent stroke so people can stay independent.
It's money well-invested, too, because besides the so-cial cost,
the cost of taking care of patients who can't be independent
is huge."
CREST trial
The hunt is on, deep within patient Pearl Hatch's body.
As Hatch lies on an operating table in USC University Hospital,
neurointerventional radiologist and professor of neurological
surgery George Teitelbaum, M.D., carefully threads a slender
wire through an artery above her leg until its tip reaches the
carotid arteries in her neck. His remote target: a narrowed blood
ves-sel that is cheating her brain of needed nourishment, wielding
eye pain and in-termittently stealing her sight.
If Teitelbaum and his fellow physicians, nurses and technologists
succeed with the angioplasty, they will reopen the artery and
significantly improve the 85-year-old patient's quality of life.
But this time they are not just helping a single patient: The
team also is contributing to the medical world's knowledge about
the best ways to intervene and prevent strokes before they can
happen.
The USC team is participating in the landmark Carotid Revascularization
End-arterectomy-Stenting Trial, or CREST, which compares two
ways of reopening narrowed blood vessels in the neck that lead
to the brain. They are one of only three teams in California
currently enrolling patients for the trial, which is backed by
the National Institute of Neurological Disorders and Stroke.
It will grow to 2,500 patients at 50 sites nationwide.
"This trial is here because of our surgical skills and results,
our neurointerventional talent and our excellent neurologists,"
says Weaver, CREST's principal investigator at USC. "We
all work as a group."
Sung and Glenn M. Fischberg, M.D., assistant professor of neurology,
assess patients who may be eligible for the trial.
CREST focuses on patients who have a narrowing in the carotid
arteries, a condition known as stenosis. The carotid arteries
on either side of the neck carry blood up to the brain. Fatty
atherosclerotic deposits can gather along artery walls where
the arteries fork, causing stenosis.
Initial trial patients may have symptoms from stenosis-vision
problems, weakness and clumsiness, for example-or may have no
symptoms. Later, only symptomatic patients will be eligible.
In the early 1990s, a national trial showed that for patients
with symptoms, surgery is twice as effective in preventing future
stroke than taking medication alone. In this surgery, called
endarterectomy, a surgeon makes an incision in the neck to reach
the carotid artery and its branches. After placing a shunt to
make sure the brain continues getting blood, the surgeon focuses
on the area of stenosis.
"We go into the artery and core out the area with the lesion,"
Weaver says. "Then we close the artery back up, put a patch
around it and reestablish blood flow."
The endarterectomy is considered the gold standard for surgical
treatment today. In more than 300 cases at USC over the past
10 years, the risk of a stroke or death following the procedure
is less than 1.5 percent, Weaver says.
But over the last five to six years, another type of procedure
has become available in a few American medical centers, including
USC University Hospital: angioplasty with stenting.
The CREST trial seeks to find out how well angioplasty compares
with endarterectomy. Vascular surgeons Weaver and Douglas B.
Hood, M.D., assistant professor of surgery, Steven L. Giannotta,
M.D., professor of neurological surgery, and neurointerventional
radiologists Teitelbaum and Donald W. Larsen, M.D., associate
professor of neurological surgery and radiology, perform the
procedures.
The angioplasty part of the trial uses investigational devices
made by Guidant Inc. In Hatch's angioplasty-the first in the
CREST trial at USC-Teitelbaum threaded a guidewire through a
catheter in the femoral artery just above the leg and guided
it toward the head, watching its progress through roadmap-like
X-ray images on a monitor. Once he reached the carotid, he installed
a tiny filter just beyond the area of stenosis and popped it
open like an umbrella so it could catch any dangerous clots that
might flow through the blood during the procedure.
Images showed the artery was nearly 90 percent blocked. Teitelbaum
threaded another wire to the area of blockage, and this time,
the wire held a minuscule balloon on its tip. The balloon swiftly
inflated and deflated, compressing the fatty plaque against the
artery wall and reopening the artery.
But that was not all. Teitelbaum maneuvered another device to
the area of the lesion, and when he removed the sheath covering
the device, a cuff made of a special mesh sprung open and clung
to the artery wall. The cuff, called a stent, remained in the
artery as scaffolding.
After the procedure, Hatch was soon up and doing well.
The perceived benefits of carotid stenting include avoiding an
incision and scar on the neck, possibly shorter procedure time,
and the chance of fewer complications in certain patients. But
answers on complications and longer-term health will not be known
until the trial ends in about five years.
"We'd like to know: Is it better to have one procedure than
the other? Are there any patients that would do better with one
than the other?" explains Larsen.
Adds Sung: "CREST is very interesting because we're all
concerned about what to do about carotid artery stenosis. It
has been proven that surgery is best under certain circumstances,
but with the advent of interventional devices, the decision becomes
more complicated. Hopefully this will help determine the best
treatments for individual patients."
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