Editors' note: Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window

The timely meta-analysis by Tsivgoulis et al.(1)is an illustration of the transformative shift in hyperacute stroke management that has characterized the last several years. Focus has appropriately expanded beyond the classic mantra, "time is brain," to view time as a necessary, but no longer sufficient, surrogate for predicting functional outcome and to recognize that, perhaps, now "penumbra is key." Ultimately, this is an extraordinary advance for the more than 13 million people having new stroke each year(2)and the first-line health care professionals who help treat them. The summation of these studies prompted the American Heart Association to update recommendations about thrombolysis in an extended time window. 2019 Guidelines now provide a Class IIa recommendation, supporting IV alteplase administration in select patients with unclear time of onset and MRI diffusion-positive FLAIR-negative lesions who have symptom recognition within 4.5 hours.(3)