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REASONS FOR HOPE:Vampire bats // cell-suicide preventers // free-radical scavengers // neuron revivers // improved logistics for better care faster.

Why Strokes Still Kill

By Cathryn Delude // Fall 2005
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Stroke patients

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C onsidering the plight of most people in her situation, Becky Hemingway was faring well. Her right side had gone numb, and she couldn’t speak. But her family had immediately suspected a stroke, and emergency room physicians at a hospital in South-bridge, Mass., not only made the diagnosis but also rushed the 31-year-old new mother to a regional stroke center in Boston, two hours to the east, where she could receive specialized care.

In contrast, the average stroke victim doesn’t get treated for almost a day, though the only approved current drug therapy must begin within three hours. Nine out of 10 strokes are ischemic, resulting from blood clots that cut off the oxygen supply to brain tissue, and the drug—tissue plasminogen activator, or TPA—dissolves clots. Given too late, however, TPA can further weaken blood vessels in the brain, increasing the risk of a potentially fatal hemorrhage. What’s worse, medical researchers have recently concluded that TPA itself might be toxic to some brain cells. Because of such risks, most physicians are reluctant to administer TPA even within the three-hour window. And the 3% of patients who receive the drug on time have a less than even chance of a positive outcome.

So stroke remains a prodigious killer, taking 165,000 lives annually in the U.S. (Only heart attacks and cancer are deadlier.) Another 535,000 stroke victims survive each year, but many have lifelong disabilities—ranging from complete paralysis and cognitive dysfunction to impaired speech. That makes stroke one of the nation’s most expensive diseases, costing an estimated $57 billion a year.

With a large clot obstructing her middle cerebral artery, Hemingway risked landing on the wrong side of the statistical divide. Yet after her ambulance arrived at the Massachusetts General Hospital and she was rushed to the neurology unit for a CAT scan, the images of her brain gave neurologist Lee Schwamm hope. Though the tissue adjacent to the clot was already dead, the surrounding area might still be saved if blood flow could be quickly restored, a process known as reperfusion.

Normally, stroke patients receive high doses of TPA intravenously. But in Hemingway’s case, a chest X-ray suggested that her heart was enlarged and possibly surrounded by fluid, and TPA, coursing through her bloodstream, could cause fatal bleeding. Moreover, her blood clot was so large that it might not respond to conventional intravenous TPA treatment. “Intravenous TPA is good at dissolving small clots in smaller arteries but not so good with clots in major arteries, which can be centimeters long,” says Schwamm, the head of the hospital’s Acute Stroke Service.

Schwamm recommended an experimental procedure intended to deliver TPA directly into the blocked artery, thereby reducing the amount of the drug needed as well as the risk of hemorrhage. The hospital’s interventional neuroradiology team inched a catheter through an artery in Hemingway’s groin, using real-time X-ray images to guide the threadlike wire into the middle cerebral artery. When the catheter tip reached the clot, the endovascular team squirted the TPA. The massive blockage melted away under the direct hit.

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Stroke by the Numbers

The particulars of treating stroke with the drug TPA.

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1. “Mechanisms, Challenges, and Opportunities in Stroke, ” by Eng H. Lo, Turgay Dalkara and Michael A. Moskowitz, Nature Reviews: Neuroscience, May 2003. A well-illustrated historical overview of the understanding of stroke biology, brain imaging, treatments and new research directions.

2. “Exciting, Radical, Suicidal: How Brain Cells Die After Stroke,” by Eng H. Lo, Michael A. Moskowitz and Thomas P. Jacobs, Stroke, Feb. 2005. A helpful summary of recent research about cell death and the neurovascular unit.

3. “Recommendations for the Establishment of Stroke Systems of Care,” by Lee H. Schwamm et al, Stroke, March 2005. Influential recommendations from the American Stroke Association’s task force for establishing a network of stroke centers, as well as education for prevention, emergency response, treatment and rehabilitation.

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