Dr. Jeffrey Farkas

Mrs. Vitiello was taken to University Hospital, where a stroke team evaluated her condition. She was indeed having a stroke; on the positive side, test results showed she was a good candidate for tPA treatment. Dr. Jeffrey Farkas, the hospital's chief of interventional neuroradiology and an assistant professor of radiology at New Jersey Medical School, performed the procedure that delivered tPA directly to the blood clot in Mrs. Vitiello's brain. Today, Mrs. Vitiello is recovering from a stroke that, because of early intervention, caused a relatively minimal amount of disability. She's at home instead of being in a nursing home.

"People generally have a fatalistic attitude toward stroke. They believe that it's just something you have to cope with," says Dr. Patrick Pullicino, chairman of the Department of Neurosciences at New Jersey Medical School. "Now, we have a proven way to reduce the disability caused by stroke. The brain is very important, and we have to protect every bit of it that we can. TPA enables us to do exactly that."

Dr. Patrick Pullicino

TPA has already dramatically changed how neurologists think about stroke. For the first time, they have a weapon in their arsenal to use against the third leading cause of death in America and the top cause of disability in adults. "Before tPA, we had nothing to 'cure' stroke," says Dr. Andrea Hidalgo, director of University Hospital's Stroke Program and assistant professor of neurosciences at New Jersey Medical School. "Now something can be done, and medical personnel from EMS to the nurses and physicians in the Emergency Department know that time is of the essence. Stroke is treated as a true medical emergency now."

TPA occurs naturally in the body-it's an enzyme made by cells in blood vessel walls. Scientists have been able to genetically engineer tPA, using it first to dissolve blood clots in the heart; then testing it on how well it worked in the brain. One landmark study showed that patients given tPA within three hours of experiencing stroke symptoms were less impaired three months later than patients who received a placebo. In 1996, the Food and Drug Administration (FDA) approved the use of tPA to treat acute ischemic stroke, the type caused by a blood clot.

Here's how tPA works: When blood flow to the brain is blocked, oxygen-starved brain cells begin to die. That causes a decrease in brain function, and if the cells do die, permanent damage to that area of the brain. Given early on, tPA can dissolve the clot and restore the blood flow-and oxygen supply- to the brain.

Bleeding strokes are Different

It's important to remember that not all strokes are the same.  Ischemic strokes, the most common form, are caused by a blockage in an artery in the brain that tPA may be able to reverse.  However, if the stroke is hemorrhagic-caused by bleeding in the brain-then tPA is not used. Hemorrhagic strokes are less common than acute ischemic strokes, accounting for about 20 percent of all strokes. However, they are more deadly. In the case of intracerebral hemorrhage, about 30 percent to 60 percent of the patients die. This type of stroke often occurs because of high blood pressure or use of illegal drugs such as cocaine. Intracerebral hemorrhage generally is treated by administering drugs to lower blood pressure, discontinuing any blood-thinning medicine the patient is taking, and sometimes giving Vitamin K to help the blood clot.

Subarachnoid hemorrhage refers to bleeding within tissues near the base of the brain and is often caused by a ruptured blood vessel, or aneurysm. If the patient is a candidate for surgery, the most standard procedure is to clip the aneurysm to stop the bleeding. Still, most patients with a ruptured aneurysm die either before reaching the hospital or within one month of the occurrence. Although researchers are working on other treatments for hemorrhagic stroke, there is currently nothing that has the same life-saving effect that tPA has on acute ischemic stroke.

	Dr. Andrea Hidalgo

A Matter of Time

There are two ways to administer tPA-through an IV or directly at the clot site in the artery, although only the intravenous route has received FDA approval. "The use of intra-arterial tPA has advantages," says Dr. Hidalgo. "Rather than injecting in into an IV, tPA is given under direct visualization during angiography, so the doctor can see the clot. That allows the doctor to place the tip of the catheter into the clot, injecting the tPA directly into it. This way, the amount of tPA needed may be very small and the doctor can see when the clot is successfully dissolved. All this may enhance the success rate of clot removal," says Dr. Hidalgo.

University Hospital is one of less than 150 hospitals in the nation, and is believed to be the only facility in New Jersey, offering this procedure and the specialized CT scans that go along with it. In addition, the stroke team is on-call 24 hours a day, 7 days a week. This high level of staffing is difficult to duplicate in a community hospital and is only found in a handful of the nation's academic medical centers.

"Our doctors can even read the scans from their homes, thanks to some new technology," says Dr. Farkas. "It's really a remarkable program and a huge time saver."  An accurate diagnosis of the cause and extent of the stroke is absolutely vital as administration of tPA could be seriously damaging, and even cause death, if given to a patient who is not an appropriate candidate.

Time matters in both cases of tPA treatment. Intravenous tPA needs to be given no later than three hours after a patient begins to experience stroke symptoms. With intraarterial tPA, there's a little more time-up to six hours.

The time factor is crucial, yet patients who are unaware that an intervention therapy is available often delay seeking medical help. Some people don't realize that they are having a stroke, and others, dismissing the early symptoms, don't go for help until it's too late to reap tPA's benefits. The National Institute of Neurological Disorders and Stroke estimates that only about 10 percent of eligible stroke patients receive tPA, and it says that time is a leading reason why.

Emergency medical service personnel notify University Hospital when they are transporting a possible stroke patient so that the stroke team can be called to the emergency room. The patient is examined and tests-such as blood work and a CT scan-are begun. If the stroke is caused by bleeding in the brain, not a blood clot, then tPA is not used. One risk of using tPA is that it can cause bleeding in the brain. Some factors other than time and hemorrhagic stroke eliminate some people from receiving tPA, including recent major surgery or if the patient is taking coumadin, a blood thinner.

If a patient is a candidate for tPA, his or her specific condition will determine how the therapy is given-by IV or within the artery. Before undergoing tPA therapy patients go through a special CT scan, " To capture the clearest, most detailed images of the brain, Dr. Farkas uses a multislice CT scanner. This sophisticated machine can take up to four images in a half-second. When combined with an intravenous contrast injection three-dimensional images of the brain blood vessels are made and the exact site of the blockage is identified. This procedure takes 5 minutes and the information that this special scan provides is invaluable. It tells us who to treat and whether to give the tPA in the IV or directly into the blood clot intraarterially. To Dr. Farkas, intraarterial tPA has some advantages. "There's more time to administer intraarterial tPA-up to six hours after symptoms begin rather than three. Because the drug is being delivered at the clot site a much lower dose of tPA is necessary," he says. "Since we can see the blockage on the angiogram we only give small doses of tPA and watch to see the artery open. If we see that the medicine is not working we can physically destroy the clot by crushing it using a balloon inserted into the artery.

When deciding whether to use IV or intraarterial tPA, the doctor's goal is to choose the option that potentially offers the patient the best outcome. The recommendation is based on a host of factors, from the clot's location to the patient's overall health. "Interestingly, advanced age is not necessarily a contraindication to tPA treatment. Some older patients do very well. I treated a woman in her late 80s with tPA, and she went home from the hospital a week later," says Dr. Farkas. "When all is said and done, we want to give stroke patients their lives back, not send them to a nursing home."

This is a CT Angiogram of a 78 year old woman. The green arrow demonstrates a blocked cerebral artery at the base of the brain.	The same patient after intra-arterial stroke therapy. Notice how the vessel flow has been restored to normal. This patient recovered completely and no stroke was seen on the CT scans even days later.
A green arrow points to the initial angiogram picture confirming there is a complete blockage of the left Middle Cerebral Artery.	After Intrarterial thrombolysis the vessel is once again supplying blood to the left side of the brain.

Other Tools Against Stroke

There are other exciting avenues being explored in the area of stroke treatment and prevention. Neurovascular stenting, which has been done at University Hospital in carefully selected patients, is one of them.

A stent is a small flexible tube-shaped metal device that when placed inside a narrowing artery acts as a gate to push the artery open and to keep it open.   Just as stents are used to open blocked vessels in the heart, they can sometimes be used for the same purpose in the brain.

"While cardiologists have been placing stents for years, it's an emerging concept as applied to neurology-and a very exciting one," says Dr. Farkas. "New types of stents are being developed: those that are more flexible, as well as those that are coated with medicine to prevent irritation in the artery in which they are placed. Down the road, neurovascular stenting may be the gold standard."

Neuroprotective drugs are another area that holds promise, although it may be far off. "While these drugs would not prevent stroke, they could help brain cells survive a reduced blood supply during stroke," says Dr. Hidalgo. "In theory, neuroprotective drugs could stabilize cells and serve a protective function."

There are stroke prevention measures virtually anyone can follow (see "Strike First Against Stroke"). But people who have had a stroke-and thus, are at risk for another-often are given further medication. One important medication is aspirin. Many studies have shown that stroke patients given aspirin have a lower risk of having another stroke," says Dr. Hidalgo. "Aspirin is easy to take, and it's inexpensive. But there's no proven benefit to people without a history of stroke taking aspirin." Coumadin sometimes is prescribed for patients whose stroke was caused by a clot that traveled from the heart to the brain.

Centralized care

The hours and days immediately following a stroke are critical, and there's been a great amount of research indicating the patients who are cared for in a designated stroke unit have better outcomes.

"The staff of these units-from nurses to therapists-are specially trained to care for stroke patients, who receive the close monitoring and other benefits of a dedicated team," says Dr. Pullicino. "When University Hospital opens its four-bed stroke center this November, it will mean improved care for stroke patients. It's well known that stroke units save lives."

If you think you are having a stroke, call 911. If you would like more information about stroke prevention and treatment, call the Stroke Service at (973) 972-0571.