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Clot-busting Treatment and New MRI Analysis Determine Which Stroke Patients will be Helped or Harmed

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Researchers from the John Hopkins University have reported that they have recently developed a predictive method that can determine, with 95 percent accuracy, which stroke victims will serve to benefit from intravenous clot-busting drugs and which serve to suffer dangerously, with potential fatal bleeding in the brain.

Reporting in the online journal Stroke, the Johns Hopkins team note that these predictions were made possible by incorporating a novel technique they developed that utilizes conventional magnetic resonance imaging (MRI) scans to measure and determine damage to the blood-brain barrier that shields the brain from drug exposure.

If further testing verifies their new technique's accuracy, then it could result in the basis of expanded and more precise use of intravenous tPA, a drug that is presently restricted to patients who are within 4.5 hours of a stroke onset, in order to have the best opportunity of dissolving the blood clot causing the stroke without risking any further damage.

"If doctors had a safe, reliable tool to determine which patients could still be safely treated outside that window, more patients could be helped," said the John Hopkins team.

"If we are able to replicate our findings in more patients, it will indicate we are able to identify which people are likely to have bad outcomes, improving the drug's safety and also potentially allowing us to give the drug to patients who currently go untreated," said study leader and an assistant professor of neurology and radiology at the Johns Hopkins University School of Medicine, Richard Leigh, M.D.

Leigh's technique uses a computer program that allows physicians to view how much gadolinium, the contrast material injected into a patient's vein during an MRI scan, has leaked into the brain tissue from neighboring blood vessels. By calculating this damage in 75 stroke patients, Leigh recognized a threshold for measuring how much leakage was hazardous. Then, he and his team implemented this threshold to those 75 records in order to determine how well it would predict who had suffered a brain hemorrhage and who had not. The new test accurately predicted the results with a 95 percent accuracy rate.

The blood-brain barrier is a unique guard of blood vessels which restricts the passage of molecules from the bloodstream into the brain. Without it, the brain becomes open to infection, inflammation, and hemorrhage. Therefore, ischemic stroke patients are at risk of bleeding into the brain when the barrier is damaged.

In an ischemic stroke, a blood clot is caught in a vessel, cutting off blood flow to a region of the brain, which will begin to die the longer the clot is in place. When patients come to the hospital within a few hours of suffering an ischemic stroke, physicians hastily move to give intravenous tPA, in the hopes that it will dissolve the clot without leading to any further damage.

In approximately 30 percent of patients, receiving tPA in a timely fashion offers great benefit. In some individuals, around 6 percent of stroke patients, there is already too much damage taken by the blood-brain barrier, and as a result the drug only exacerbates bleeding in the brain, leading to severe injury, and sometimes death.mri stroke

"But doctors haven't known with any precision which patients are likely to suffer a drug-related bleed and which are not. In these situations, if physicians knew the extent of the damage to the blood-brain barrier, they would be able to more safely administer treatment. Most stroke patients, don't get to a hospital within the window for optimal tPA use, so physicians don't give them tPA, fearing dangerous complications. Sometimes, more aggressive treatment can be attempted, such as pulling the clot out mechanically via a catheter threaded from the groin area or by directly injecting tPA into the brain," said Leigh.

Usually, physicians perform a CT scan of a stroke victim to see if they have visible bleeding prior to administering tPA. Leigh notes that his computer program, which operates with an MRI scan, can identify slight changes to the blood-brain barrier that are otherwise impossible to see. If his findings are indeed confirmed, Leigh says, "We should probably be doing MRI scans in every stroke patient before we give tPA."

"The biggest obstacle in successful stroke treatment has always been time. The longer it takes for a patient to be treated, the less chance of a full recovery. An MRI scan does take longer to conduct in most institutions than a CT scan. But if the benefits of getting tPA into the right people and most importantly, protecting the wrong people from getting it outweigh the harms of waiting a little longer to get MRI results, doctors should consider changing their practice. If we could eliminate all intracranial hemorrhages, it would be worth it," he said.

At present time, Leigh is analyzing data from patients who received other treatments for stroke outside the usual time window, in some cases many hours following the FDA-approved cutoff for tPA.

"It's possible that some people who come to the hospital many hours after a stroke can still benefit from tPA, the only FDA-approved treatment for ischemic stroke," he said.

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