There are approximately 750,000 stroke patients per year in the United States.  Only 3-5% of these people are treated with intravenous tissue plasminogen activator (IV- tPA), the only FDA-approved medical treatment for acute non-hemorrhagic stroke.  According to current guidelines, IV-tPA must be given within three hours of stroke onset.  Michael Lev of Harvard Medical School, however, suggests that some patients could benefit from IV-tPA even if they were treated beyond the three-hour time window.

The etiology of stroke is due to vascular injury that is either hemorrhagic (15% of cases) or ischemic (85% of cases) in nature. When a patient comes to the hospital suffering from an acute stroke, unenhanced computed tomography (CT) is performed to exclude the possibility of bleeding in the brain.  If there is no evidence of bleeding, then the patient is a candidate for IV-tPA.  Traditionally, doctors have treated stroke patients according to the adage, “Time is brain.”  Lev proposes a more nuanced way of treating patients, and he suggests the adage, “Mismatch is brain.”  He advocates using advanced magnetic resonance imaging (MRI) or CT imaging to determine how much of the brain is already dead at admission and how much of the brain is at risk of dying if there is no reperfusion.  According to these selection criteria, patients with little dead tissue and a lot of at-risk tissue would be candidates to receive IV-tPA reperfusion therapy, even more than three hours after stroke onset.   

The mismatch between dead and dying tissue is being used as a patient selection tool in a Phase Two trial of desmotoplase, a clot-busting drug.  Lev attributes some promising results obtained in this study to the new method of patient selection.   

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