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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.
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
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.
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.
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."
"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 Texas‚Houston 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.
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."
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.
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.
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