Perspective:

In patients with acute ischemic stroke, there is a core of irreversibly damaged tissue surrounded by an ischemic penumbra. As time from the stroke onset progresses, the penumbra shrinks and the core grows. A multitude of factors predict the ratio of core to penumbra and the rate of core growth. An infarct with a large core and small penumbra cannot be distinguished clinically from an infarct with small core and large penumbra, but the later is more amenable to thrombolysis as there is salvageable tissue. Until recently, accurate quantification of the mismatch between core and penumbra was challenging and time was used as a surrogate to identify patients who can safely be treated with IV thrombolysis.

This meta-analysis shows that in patients who receive perfusion imaging, IV alteplase improved functional outcome, even though treatment was administered outside standard time windows. These results are exciting, as they suggest that more stroke patients could be eligible for thrombolysis. Caution is warranted before incorporating these findings into clinical practice, as two of the three trials included in the meta-analysis were stopped early and the overall number of patients in the analyses is small, which may contribute to bias. Additionally, the studies included in the meta-analysis were performed before trials showing that some patients with large-vessel occlusion can be treated with endovascular treatment up to 24 hours from stroke onset. About two-thirds of the patients included in the meta-analysis had a large-vessel occlusion and would likely receive endovascular treatment, limiting the generalizability of the results. A practical limitation is that the perfusion imaging used in these studies is not widely available outside large medical centers and the study does not address what type of perfusion imaging (CT vs. MRI) should be used for patient selection.