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Brain Attack: Cover Story from FDA Magazine Tells Latest
About Strokes
 March
19, 2005 - Learning more about strokes how to reduce the risk and the
latest on treatments is the cover story, Brain Attacks, in the
current FDA Consumer Magazine. Stroke is the third-leading cause of
death and the leading cause of long-term disability in the United
States. About 500,000 new strokes and about 160,000 stroke-related
deaths are reported each year, according to the National Institute of
Neurological Disorders and Stroke (NINDS).
Strokes occur when the blood flow to the brain is
interrupted by either a blockage or rupture of a blood vessel or artery.
A stroke caused by a blood clot that keeps blood from reaching the brain
is called an ischemic stroke. A stroke that occurs when a blood vessel
in the brain ruptures is called a hemorrhagic stroke. About 8 out of 10
strokes reported in the United States annually are ischemic strokes,
writes editor Ray Formanek Jr.
Also called a brain attack, stroke often comes on
suddenly. However, the conditions that make a stroke more likely often
take years to develop. According to the NINDS, the best treatment for
stroke is prevention. High blood pressure, heart disease, smoking,
diabetes, and high cholesterol are among the risk factors that increase
the likelihood of stroke. Experts say that people who quit smoking and
who keep their blood pressure, cholesterol, and diabetes under control
significantly reduce their chances of having a stroke, he adds in his
introduction.
From FDA Magazine
Brain Attack: A
Look at Stroke Prevention and Treatment
By Michelle Meadows
As a physical therapist, Dina Pagnotta, 33, has
helped more than 100 people recovering from stroke. So when she had a
stroke on a May morning in 2002, she had an idea of what was happening.
First, she felt dizzy during a Pilates class in New
York City. One moment, she had been laughing with a friend. Then she
took a sip of water but couldn't swallow. She choked and the water came
right back out of her mouth. Seconds later, she couldn't move her left
leg or arm, the left side of her face went limp, and her speech was
slurred. "It felt like I got a shot of Novocain in the whole left side
of my body," Pagnotta says.
Her friends lowered her to the ground, and someone called 911. "The next
thing I knew, I was in an ambulance with the sirens screaming and a
paramedic calling it in: '30-year-old female, CVA,'" which stands for
cerebrovascular accident, also known as stroke.
A stroke occurs when blood flow to part of the
brain is interrupted, which is why it's sometimes called a "brain
attack." Pagnotta had an ischemic stroke, the most common kind. It
occurs when a blood clot blocks a blood vessel or artery in the brain.
Ischemic strokes account for 80 percent of all strokes. Hemorrhagic
strokes, which account for the other 20 percent, occur when a blood
vessel in the brain ruptures and causes bleeding.
According to the National Institute of Neurological
Disorders and Stroke (NINDS), about 700,000 people have a stroke each
year--500,000 first strokes and 200,000 recurrent strokes. Stroke is the
leading cause of long-term disability and the third-leading cause of
death for Americans after heart disease and cancer.
Time Is Brain
When blood flow to the brain stops, brain cells are
deprived of oxygen and nutrients. "A stroke is a medical emergency
because brain cells start dying quickly," says John R. Marler, M.D., a
neurologist and associate director for clinical trials at the NINDS. And
treatment is most effective when given promptly.
Activase (alteplase), a genetically engineered
version of tissue plasminogen activator (t-PA), is the only drug
approved by the Food and Drug Administration for treating the sudden
onset of ischemic stroke. The drug dissolves blood clots that block
blood flow to the brain, improving the chance for recovery and
decreasing disability. But the drug must be given within three hours
after stroke symptoms begin. It has not been shown to be effective
beyond three hours.
"The longer blood flow is cut off and the longer
treatment is delayed," Marler says, "the more likely it is that the
patient will suffer permanent damage." Stroke experts commonly refer to
the sense of urgency in stroke treatment with this expression: "Time is
brain."
Marler says, "This is why it's so important to
recognize the symptoms of stroke and call 911 right away." The most
common symptoms of stroke are
-
sudden weakness or numbness in the face, arms,
or legs, especially on one side of the body
-
sudden confusion, or difficulty speaking or
understanding speech
-
sudden vision problems, such as blurry vision
or a partial or complete loss of vision in one or both eyes
-
sudden dizziness, trouble walking, or loss of
balance and coordination
-
sudden severe headache with no known cause.
Other symptoms that are less common, but still
important, are sudden nausea, vomiting, brief loss of consciousness, or
decreased consciousness, such as fainting and convulsions.
Sometimes, people experience a transient ischemic
attack (TIA), also called "mini-stroke," which also requires prompt
medical evaluation. When a TIA occurs, stroke symptoms may last only
temporarily and then disappear. Most TIA symptoms disappear within an
hour, but they may persist up to 24 hours.
"About 1 in 4 people who have a TIA go on to have a
bigger stroke within five years," says Ralph L. Sacco, M.D., associate
chairman of neurology and director of the stroke division at New York
Presbyterian Hospital at Columbia University. "Stroke may have been
prevented if the TIA had been detected and appropriately treated," he
says. Doctors may recommend drugs or surgery to reduce the risk of
stroke in people who have had a TIA. "For us, TIA is to stroke what
chest pain is to heart disease. It's a warning sign that shouldn't be
ignored," Sacco says.
The effects of a stroke depend on which area of the
brain is affected and how extensive the damage is. One side of the brain
controls the opposite side of the body. So a blood clot on the right
side of the brain limits function on the left side of the body and vice
versa.
At the hospital, Pagnotta recalls that a doctor
kept lifting up her left arm. "Each time, it flopped back down," she
says. Pagnotta didn't receive treatment with t-PA. Two hours after her
symptoms began, she could move her fingers again, then she could move
her whole arm, and her speech improved. After conducting tests, her
doctors concluded that there had been a blood clot that temporarily
blocked an artery on the right side of her brain, but it dissolved on
its own.
"I was lucky," says Pagnotta, who ran the New York
City Marathon in November 2004. She is among the roughly 10 percent of
stroke survivors who recover almost completely. According to the
National Stroke Association (NSA), 25 percent recover with minor
impairments, 40 percent experience moderate-to-severe impairments that
require special care, 10 percent require care in a nursing home or other
long-term care facility, and 15 percent die shortly after the stroke.
Risk Factors
As Pagnotta discovered, stroke can strike without
warning. After tests done during a six-day hospital stay, her doctors
determined that her stroke likely occurred because of a combination of
factors--she had started taking birth control pills for the first time
three months earlier and she had a heart problem.
Pagnotta found out that she had a hole in her heart
called patent foramen ovale (PFO). She also had an atrial septal
aneurysm, a thinning of the wall between the two chambers of her heart.
She had an embolic stroke, in which a clot travels to the brain. She
says her doctors believe that a blood clot traveled from her heart,
through the PFO, to her brain. A blood clot could move to other areas of
the body and never pose a problem. But compared with other organs, the
brain is much more sensitive to the interruption of blood supply.
A condition called atrial fibrillation also can
increase the risk of having an embolic stroke. Normally, the atrium
pumps blood into the ventricles, which then sends blood to the rest of
the body. In atrial fibrillation, the atrium doesn't pump blood out
properly. This increases the likelihood that blood will pool and clot in
the atrium. If a piece of that clot breaks off, it can then be pumped to
the brain.
Most strokes occur because blood clots develop
directly in the brain. These are known as thrombotic strokes. The most
common cause is atherosclerosis, a process in which fatty deposits form
in the vessel walls of the brain. The process is similar to what happens
in the heart for people with heart disease. This is why stroke and heart
disease share some of the same controllable risk factors: high blood
pressure, cigarette smoking, high cholesterol, diabetes, physical
inactivity, and obesity. These factors raise the risk for plaque
build-up in the arteries, which in turn raises the risk of the formation
of blockages and blood clots. A stroke sometimes occurs because plaque
develops in the carotid artery, the main blood vessel in the neck that
leads to the brain.
Sacco says high blood pressure is perhaps the
biggest risk factor for stroke. "There are too many people with
uncontrolled high blood pressure," he says. "Especially given that it
can be prevented and treated with behavior changes and medications.
"We want people to be aware of their stroke risk
and take steps to address the risk factors they can control. We're all
at risk. But no matter who you are, it is possible to lower your risk
and help prevent a stroke from happening," Sacco says.
Men have a greater stroke rate than women, Sacco
says, but women usually live longer and therefore more women are
disabled or die from stroke each year. Having a family history of stroke
and getting older also raise stroke risk. "African-Americans have twice
the stroke incidence and mortality compared to whites," Sacco says, "and
Hispanics also seem to be at greater risk." In addition, having one
stroke or TIA increases the risk of having another stroke.
Leslie Virgil, 60, of New York City, had a mild
stroke about five years ago with no lasting effects. "So I didn't think
much about it," she says. "But now I see that the first one was like my
body telling me: 'Watch out, because the big one is coming.'
"I had high blood pressure, diabetes, and high
cholesterol, but I didn't make any changes. My mother had a stroke and
so did my mother's brother."
Virgil experienced a second, major stroke in
November 2004. Due to a blood clot on the left side of her brain, she
lost function in her right leg. Her speech is still slurred. And she has
difficulty concentrating and finding the right words to communicate
sometimes.
Virgil entered the Rusk Institute of Rehabilitation
Medicine, part of New York University Medical Center, in December 2004.
She is working with a team of specialists to regain her strength. "My
goal is to walk out of here," she says.
Now she takes medication to control blood pressure,
cholesterol, and diabetes, and she has switched to a diet that's low in
fat, cholesterol, and salt. "This stroke knocked some sense into me,"
Virgil says.
Small Window of Opportunity
When the FDA approved Activase (t-PA) in 1996, it
was the first drug approved to treat acute ischemic stroke. Made by
Genentech of South San Francisco, Calif., the drug is given
intravenously to dissolve the clot or clots that are keeping blood from
flowing to the brain. It improves the chance of recovery by up to 30
percent when used correctly. But there is a major limitation--the need
to begin the treatment within three hours.
"The fraction of people who get treated with t-PA
is very, very low, just a few percent of all stroke patients," says Marc
Walton, M.D., Ph.D., director of the FDA's Division of Therapeutic
Biological Internal Medicine Products. "The three-hour time window is
very limiting. There is also a risk of causing intracranial bleeding.
Research shows that for safety reasons, doctors are selecting patients
carefully."
When someone suffers a stroke, doctors have to run
tests to figure out which kind of stroke has occurred and whether the
patient is a candidate for t-PA. Meanwhile, time is ticking away.
"Hospitals are getting better at evaluating and treating patients with
stroke symptoms quickly," Sacco says. "But we also need people to
recognize the warning symptoms and get to the hospital sooner."
Most people don't go to the emergency room until
more than 24 hours after they experience stroke symptoms, according to
the NSA.
James Grotta, M.D., a professor of neurology and
stroke program director at the University of Texas Medical School in
Houston, says there is a host of reasons for the delay.
"Some people don't know the signs of stroke,"
Grotta says. "Other people call their doctor's office or a family member
when they should call 911. Some people are embarrassed to call 911 or
they go to bed and hope the symptoms will go away. Stroke symptoms also
usually don't hurt, which is why some people try to ignore it. And there
are geographical challenges when people are far away from a stroke
center."
It's a good idea to talk with your doctor about
what hospital you should go to if you are at high risk for a stroke,
Grotta says. "Consumers should demand good stroke care." The Joint
Commission on Accreditation of Healthcare Organizations has recently
moved to certify primary stroke centers by requiring them to meet
certain criteria. One requirement is that doctors consider administering
t-PA.
"It's also important that family members know about
stroke symptoms because the stroke victim's thinking may not be clear
and the person may not be able to call for help," Grotta says. Les
Bissell, 40, who was treated with t-PA after having a stroke in January
2002, credits his girlfriend at the time for getting emergency help so
quickly.
Following a vacation, Bissell got up to look at his
mail in his Washington, D.C., apartment. Then he walked across the
living room and collapsed, breaking a table on the way down. "My legs
wouldn't work; they were like jelly," Bissell says.
He tried to get up and came crashing down again,
this time taking the TV and stereo with him. His girlfriend had a friend
who suffered a stroke a couple of years before and she recognized the
signs. After asking him basic questions that he couldn't answer, like
his name and where he was, she called 911. "I will always be thankful
for her quick action," he says. "If I had been alone, I probably would
have just stayed there on the floor and fallen asleep."
The morning after the stroke, a doctor jingled some
keys in front of Bissell and asked him what they were. He had no idea.
He was unable to walk or speak. "I could only cry out of fear and
frustration," he says. "The alphabet was a complete mystery, although it
did look vaguely familiar."
Slowly, Bissell recalled letters, words, and names.
He got out of the hospital a few days later, and underwent months of
speech therapy and physical therapy. He was treated for depression and
attended support groups.
He has a slight speech impediment, gets exhausted
easily, and has trouble with comprehension. He also has a whole new
outlook. Now he lives on a 28-foot boat named HOPE and is sailing around
the world to raise awareness about stroke. His voyage began in
Annapolis, Md., in April 2004 and he expects to be sailing for three
years.
He exchanges e-mails with other stroke survivors
and spreads the word about prevention and treatment. "Don't let it beat
you," Bissell says. "Seek help fast."
Expanding the Options
"The biggest impediment to designing therapy for
acute stroke is that the brain is extremely vulnerable," Grotta says.
"Brain tissue dies rapidly. The brain is also hard to access. The blood
vessels are delicate and tiny, and it's hard to get to the brain with a
catheter." One big area of research, he says, involves trying to improve
on t-PA.
According to a study published in the Nov. 18,
2004, issue of The New England Journal of Medicine, patients who get a
combination of t-PA and ultrasound may be able to leave the hospital
with a greater chance of recovery. This preliminary study suggests that
larger studies to assess the effects on the patient's functional
abilities and stroke recovery are worth pursuing.
"Ultrasound causes vibrations that work with t-PA
to break up clots," says Grotta, who was part of the international
research team that conducted the study. The team was led by Andrei
Alexandrov, M.D., at the University of TexasHouston School of Medicine.
Grotta says, "This may help the drug get to the clot and open up blood
vessels faster."
Joseph Broderick, M.D., chairman of the neurology
department at the University of Cincinnati, says, "We know that t-PA,
while a great advance, doesn't really open up the clots fast enough in
people with big strokes. We want to find out whether we can do better."
Broderick and his colleagues are studying an
approach that combines t-PA with additional treatment through a catheter
at the site of the brain clot. Broderick says, "Patients who have
already received intravenous t-PA within three hours of onset are taken
immediately for intra-arterial angiography, a procedure in which a
catheter is inserted into the groin and threaded up to the arteries in
the brain." Additional t-PA is put directly into the clot and the
catheter is also used to help break up the clot.
"In another NINDS-funded study, we are also
comparing t-PA with GP2B3A inhibitors, which are already approved for
cardiac use, to see if this combination can open up arteries earlier,"
Broderick says. GP2B3A inhibitors are agents that prevent platelets in
the blood from clumping together.
Researchers are also looking for novel approaches
for treating acute ischemic stroke that could be used in addition to
t-PA or instead of it. For example, neuroprotective agents protect the
ischemic cells from damage or death until blood flow is restored. These
agents hold promise, and many have worked in a lab, but none have proven
effective in clinical trials.
Hypothermia is another neuroprotective approach
under study. This involves cooling the body to lower body temperature
and slow down brain damage due to stroke. Hypothermia can be achieved by
inserting cold saline into the body intravenously to cool the body to a
certain temperature. The more common method involves external cooling
through the skin, such as with "cooling" blankets. "This has been
effective in cardiac arrest patients with brain damage," Grotta says.
"It's proof that neuroprotection could work."
Stroke experts say there is also great interest in
treatment that could be started much earlier. Jeffrey Saver, M.D., is
leading a study at the UCLA School of Medicine that involves treating
stroke patients in the ambulance. Paramedics give the potentially
neuroprotective agent magnesium sulfate in an attempt to increase blood
flow to the brain and prevent buildup of damaging calcium in injured
nerve cells. This experimental treatment is being studied in an NINDS-funded
clinical trial.
Preventing Another Stroke
According to the NINDS, about 25 percent of people
who recover from a first stroke will have another within five years, and
the chance of death and disability increases with each stroke. The good
news is that there is a lot people can do to prevent a recurrence.
Besides lowering stroke risk through lifestyle
changes and medication that lowers blood pressure and cholesterol,
surgery may be beneficial. In a procedure called carotid endarterectomy,
surgeons open up the carotid artery in the neck and scrape out plaque.
This is sometimes done for acute stroke, but the procedure has more of a
role in preventing recurrent strokes, experts say.
Surgeons also may open up a clogged carotid artery
with a small balloon and insert a small tube called a stent to keep the
artery open. In August 2004, the FDA approved the Acculink Carotid Stent
System made by Guidant Corp. of Santa Clara, Calif. The stent is
intended to prevent stroke by opening a blocked artery. The Acculink is
inserted during angioplasty, a procedure in which the stent is threaded
up to the neck artery via a catheter inserted in the groin.
The device helps prevent stroke in people who have
had a TIA or stroke and who have at least 50 percent blockage of a
carotid artery. It also may be used in those who have had no previous
stroke but have a carotid artery that's at least 80 percent blocked and
who are not good candidates for the surgical alternative. The FDA is
requiring Guidant to conduct post-approval studies to confirm the
stent's performance in more patients and to assess its long-term safety
and effectiveness.
There are two main types of drugs approved by the
FDA to prevent a recurrent ischemic stroke. Antiplatelet drugs, such as
aspirin, Plavix (clopidogrel), Ticlid (ticlopidine), and Aggrenox
(aspirin and dipyridamole), prevent clotting by decreasing activity of
the platelets--the blood cells that make blood clot. These drugs are
used to prevent recurrent thrombotic strokes.
Anticoagulants, such as Coumadin (warfarin) and
heparin, thin the blood to prevent it from clotting and also prevent
existing clots from growing. These drugs are particularly useful in
preventing the formation of clots in people with atrial fibrillation.
Pagnotta takes Coumadin every day. She says she
bruises easily, which is a side effect of the treatment. She also has to
be careful to prevent cuts and other accidents because anticoagulants
increase the risk of bleeding. She must have her blood levels checked
regularly to monitor her risk of clotting and bleeding.
Pagnotta says, "The scary part is that I worry
every time I have a headache or feel tingling or numbness. I'm wondering
is this another stroke?" But this concern has lessened over time.
She is anxiously awaiting the results of a study
comparing blood thinners to having her heart condition surgically
corrected. "For now," she says, "I'm happy to be alive."
Blocked or Ruptured Arteries
Ischemic strokes occur because a blood clot blocks
an artery or vessel in the brain. Hemorrhagic stokes occur because a
blood vessel in the brain ruptures and causes bleeding in the
surrounding brain tissue. With ischemic stroke, doctors want to open the
artery up and dissolve the clot. With hemorrhagic stroke, they want to
clot the blood and stop the bleeding.
Hemorrhagic strokes can be caused by an aneurysm, a
thin or weak spot in an artery that bulges and can burst. Other causes
include a group of abnormal blood vessels called arteriovenous
malformation or leakage from a vessel wall that was weakened by high
blood pressure.
One drug, Nimotop (nimodipine), is approved by the
Food and Drug Administration for subarachnoid hemorrhage due to
aneurysm. Subarachnoid hemorrhage occurs when a blood vessel ruptures
and bleeds into the space between the brain and the skull.
Hemorrhagic stroke is also sometimes treated with
surgery that removes abnormal blood vessels or places a clip at the base
of an aneurysm. Aneurysms are increasingly being treated by using
catheters to place wire coils inside the aneurysm to abolish it.
There is no currently FDA-approved treatment for
intracerebral hemorrhage, which is when a vessel leaks blood into the
brain itself. Joseph Broderick, M.D., chairman of the neurology
department at the University of Cincinnati, says this type of stroke
kills up to 40 percent of people within about a month after the stroke
occurs.
One therapy under investigation is called NovoSeven,
which is made by Denmark-based Novo Nordisk. The drug is approved by the
FDA for treating bleeding in people with hemophilia, a condition in
which a person's blood doesn't clot normally.
In a clinical trial led by Stephan Mayer, M.D.,
director of the neurological intensive care unit at New York
Presbyterian Hospital at Columbia University, NovoSeven has shown
promise for stopping early bleeding and improving outcomes in people
with intracerebral hemorrhage.
The MERCI Retriever
In August 2004, the Food and Drug Administration
cleared the first device to remove blood clots in the brain in people
with ischemic stroke. The MERCI Retriever--Mechanical Embolus Removal
for Cerebral Ischemia--is made by Concentric Medical Inc. of Mountain
View, Calif.
"The device is a catheter with a coiled tip that
grasps the clot and allows it to be removed by the physician," says
Miriam Provost, deputy director of the FDA's Division of General,
Restorative and Neurological Devices. "It may provide an option for some
patients who aren't eligible for t-PA."
The risks of the MERCI Retriever include bleeding
and vessel punctures. The National Institute of Neurological Disorders
and Stroke is funding a clinical trial that continues to study the
device. The MERCI Retriever is intended for use by interventional
radiologists, doctors who are specially trained to use imaging
techniques to view the inside of the body while they guide small
instruments through blood vessels to the site of the problem.
For More Information
Contents of current FDA Magazine:
http://www.fda.gov/fdac/205_toc.html
Home Page for FDA Magazines:
http://www.fda.gov/fdac/
American Stroke Association
7272 Greenville Ave.
Dallas, TX 75231
(888) 4-STROKE (478-7653)
National Stroke Association
9707 E. Easter Lane
Englewood, CO 80112-3747
(800) STROKES (787-6537)
National Institute of Neurological Disorders and Stroke
PO Box 5801
Bethesda, MD 20824
(800) 352-9424
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