Fighting Back Against
Used with Permission from:
MGH 1996 A Magazine for the
Massachusetts General Hospital Community
Spring 1996

The warning symptoms may be subtle and last only a few minutes — weakness in an arm or leg, dizziness, double vision, difficulty speaking. But such experiences never should be ignored because they could be signaling the approach or even the beginning of what could be a catastrophic event: a stroke.

A stroke always has been a medical emergency. The sudden loss of blood supply to part of the brain, caused by blockage or rupture of a blood vessel, puts in jeopardy an individual’s ability to walk, to speak, even to think. New diagnostic and treatment methods, many pioneered at the MGH, now have the potential to save lives and prevent some of the most devastating consequences of stroke, making it more important than ever to seek medical attention at the first sign of a possible stroke.

These new methods, however, have a catch. They must be used within a few hours of a stroke’s onset or they may be ineffective or even do more harm than good.To emphasize the urgency of a stroke and the need for rapid treatment, specialists at the MGH and around the country have begun using the term “brain attack.”

“Americans know very well that heart attacks need immediate attention. We hope to convey this same sense of urgency by calling strokes brain attacks,” says Walter Koroshetz, MD, who leads the Acute Stroke Treatment Team in the MGH Stroke Service. “In some ways, strokes can be even more damaging than heart attacks. If part of your heart muscle is permanently damaged, you may be able to continue living a fairly normal life. But if you lose a crucial portion of your brain, you’re a different person.”

The MGH Stroke Service concentrates its research efforts in two primary areas: stroke prevention and acute stroke treatment. Philip Kistler, MD, director of the service, explains that both areas follow the service’s longtime philosophy: to identify the exact physical problem that causes a patient’s stroke or risk of stroke and direct prevention and treatment efforts toward that condition. Another area of study is investigating treatments to help patients recover from stroke with less long-term disability.

The vast majority of strokes result from a blood clot blocking a vessel supplying the brain. Most of these ischemic (loss of blood supply) strokes have one of three causes: blood clots that form in the heart or major arteries and travel to the brain, blockage of tiny vessels deep within the brain or the buildup of atherosclerotic plaques in major arteries supplying the brain.

Small-vessel blockages usually are associated with chronic high blood pressure or diabetes, control of which can effectively prevent a stroke. To prevent strokes related to plaque buildup, the plaques in major arteries may need to be removed surgically. If plaques are identified early enough, their size may be limited by making lifestyle changes — stopping smoking, reducing fat in the diet and increasing exercise — and taking cholesterol-lowering medications.

Prevention of strokes caused by blood clots, which account for 60 percent of ischemic strokes, took a major step forward when an MGH research team led by Kistler showed that the blood-thinning drug warfarin prevents strokes in patients with a rapid, irregular heartbeat called atrial fibrillation. This condition causes clots to form in the upper chambers of the heart. The clots can break off and travel to the brain. The researchers estimate that appropriate use of warfarin could prevent more than 50,000 strokes each year in the United States.

Kistler and his colleagues now are conducting several studies to further investigate how factors in a patient’s blood may interact with how well the heart functions to produce stroke-causing clots not associated with fibrillation.

“All of our stroke prevention efforts rely on very close cooperation with colleagues in internal medicine, cardiology, hypertension, vascular surgery and neurosurgery here at the MGH,” Kistler says. “We’ve also set up collaborations with internists and specialists at Brigham and Women’s Hospital, elsewhere in the Partners network and at other local health care institutions.” The collaborations will include joint clinical research projects and sharing clinical experiences with both preventive therapies and exciting new approaches to acute stroke treatment.

One approach generating a lot of attention lately is to dissolve stroke-causing clots with the same kind of thrombolytic or “clot-busting” drugs that have revolutionized treatment of heart attacks. Last December a National Institutes of Health-sponsored study reported that injections of a drug called tissue plasminogen activator (TPA) reduced long-term disability in a carefully selected group of stroke patients.

“The NIH study provided the first hard evidence supporting what we have contended for years: Getting patients to the hospital quickly gives us the best chance of minimizing brain damage caused by a stroke,” says Koroshetz. He explains that any clot-dissolving treatment must be applied quickly for two reasons. The faster blood flow is restored, the less brain tissue will be damaged. But if the blood supply is restored after too much damage has occurred, the patient will suffer a dangerous hemorrhage in the brain.

“When the blood supply is cut off to an area of the brain, tissues go through a series of stages before they die. Eventually the walls of the blood vessels in dying areas begin to break down,” he explains. “If you restore blood flow to an area where the vessels have been damaged, you’ll have a hemorrhage. This is almost invariably fatal.”

Because of this danger, doctors considering thrombolytic treatment must carefully weigh the risk of hemorrhage against the benefits of treatment. The judgment leads to what was until recently an unanswerable question: How much of a patient’s brain will be affected by the stroke? New brain imaging techniques are able to answer this question soon enough to help make that crucial decision.

Traditional brain-imaging technology — CT scans and standard MRI examinations — cannot confirm the presence and location of a stroke until eight or more hours after its onset. But a new form of MRI largely developed by researchers, led by Bruce Rosen, MD, in the MGH Radiology Department can diagnose a stroke almost immediately. Furthermore, refinements of the technique, called functional MRI, show not only where the stroke has already damaged brain tissue but also where further damage is likely to occur if a vessel-blocking clot is not removed.

“Sometimes a patient’s stroke is very small and not going to spread to other areas of the brain,” Koroshetz says. “For someone like that, you wouldn’t want to risk a hemorrhage. But some patients are in the first stages of what could be a huge stroke, and now we can see just how large an area of tissue would be damaged if blood flow is not restored. The consequences of such a stroke would be so devastating that it’s worth using a risky treatment. The patient has little to lose.”

Two years ago Gilberto Gonzalez, MD, and Gregory Sorensen, MD, MGH neuroradiologists, expanded the hospital’s MRI capacity, allowing use of the most advanced functional MRI techniques to diagnose any patient with a suspected stroke. The MGH was the first and remains one of a handful of hospitals with such a capability. In collaboration with the Interventional Neuroradiology group, led by In Sup Choi, MD, Koroshetz and Ferdinando Buonanno, MD, of the Stroke Service are offering an experimental clot-dissolving treatment to those patients most likely to benefit.

The MGH approach differs from that of the NIH investigation. Instead of injecting TPA into a vein, which carries it throughout the body, the radiologist passes a catheter directly into the artery where the clot has lodged and delivers a clot-dissolving drug called urokinase directly to the clot.

“Our success rate in dissolving the clot is much higher with this intra-arterial approach, 90 percent versus the less than 40 percent reported with the intravenous technique,” Koroshetz says. “But intra-arterial is more invasive, complex and difficult. You need the ability to locate and dissolve the clot quickly, and you need sophisticated equipment and neuroradiologists with the expertise to carry out a very delicate procedure.”

Koroshetz believes that there is a place for both approaches. Intravenous injection will be a first-line therapy applied as soon as patients arrive in the MGH Emergency Department and a stroke diagnosis is confirmed. Intra-arterial treatment, probably available only at tertiary centers like the MGH, would be a second option if the intravenous therapy is not successful.

Koroshetz and his colleagues also are investigating drugs that have the potential to protect brain cells against toxic molecules released when tissue is injured by lack of blood supply. Protective substances called growth factors that may be able to reduce stroke injury and aid brain recovery also are being investigated by Seth Finkelstein, MD, and Koroshetz. And colleagues at Spaulding Rehabilitation Hospital are studying how patients recover from stroke. Taken together, these new approaches may revolutionize the outlook for what is still the number three cause of death in this country.

Kistler says: “The whole stroke community is now gearing up toward this more aggressive approach of getting people in quickly to determine whether a stroke is occurring and what its cause is. With that knowledge, physicians can apply appropriate treatment to prevent further damage or recurrence. At the MGH we’ve always espoused this approach, but because treatment options were limited, many physicians believed that all you could do in stroke was comfort the patients and family members.

“Now we know we can make a difference. When members of our Acute Stroke Treatment Team are successful in safely breaking up the clot, the patient gets better right before their eyes. That is unbelievably gratifying.”