Based on these results, the 2019 guidelines from American Heart Association/American Stroke Association (AHA/ASA) gave a class IIa recommendation to consider the AIS patients with unclear time of onset or who wake-up with stroke symptoms, in whom MRI show a mismatch between DWI and FLAIR signals, no signs of intracranial hemorrhage or the lesions not larger than 1/3rd of the territory of the middle cerebral artery, and the NIHSS score of <25, for tPA administration within 4.5 h from the stroke symptom recognition (41). This evidence concerns the gene PLAT and Stroke.