Wake-up Strokes

Strokes continue to be the leading cause of long term disability. One of the primary reasons for this is a short time window acutely where patients are eligible for IV thrombolysis. Endovascular intervention increases the time window. Large proportions of patients with stroke do not make it to the hospital within this treatment window. When evaluating patients with stroke, one important fact to establish is last seen normal (LSN). This is important if the stroke onset was unwitnessed and the patient is unable to provide history. About a fourth of stroke patients suffer from “wake-up strokes”, or strokes with unclear time of onset. A wake-up stroke happens when a patient wakes up with stroke symptoms. In this scenario, the time of onset is not clear, and we base our treatment decision on LSN. Based on current treatment guidelines, vast majority of these patients are not eligible for thrombolysis.
Why do people have wake up strokes
The pathophysiology of a wake-up strokes is not entirely clear, but circadian changes in cerebral blood flow, coagulability, serum catecholamine level, and autonomic tone all seem to play a role in this.
Role of Imaging in wake-up strokes
Imaging has a paramount role in this scenario. This is one way to identify what damage has already occurred, and what’s potentially salvageable (aka tissue at risk). This can be performed with simple non-contrasted CT using the ASPECT score. On the other hand, this can be achieved by obtaining multimodal imaging with CT angiography/CT perfusion, or MRI brain with MR angiography and perfusion. The study mentioned below shows how imaging data can be used in treatment decision making.
This was a Phase II open label non-randomized trial to see if treatment with tPA in wake-up stroke patients is safe while using MRI to guide the therapy. In this study1, if the FLAIR sequence on MRI was negative at the time of imaging, it was deemed that the stroke is early enough to be treated with IV tPA. 80 patients were enrolled and this study was presented at International Stroke Conference in 2016 in Los Angeles, Calif. Primary outcome was rate of symptomatic ICH (sICH). Out of 80 patients, there was only one sICH.  Primary outcomes of the trial were met and the investigators plan to go ahead with Phase III trial by the name of I-WITNESS.
Future directions
In addition to the above-mentioned study, there are several ongoing studies around the world looking at this question. Some of the ongoing trials include EXTEND, WAKE-UP, DAWN & POSITIVE. In future, we will be treating wake-up strokes regardless of the LSN based on imaging characteristics of individual patients.


Muhammad Alvi, MD
Assistant Professor Neurology, West Virginia University, Morgantown, WV 

Mud Alvi is an Assistant Professor of Neurology at West Virginia University. His research interest includes Cerebral Small Vessel Disease and its association with Stroke and Dementia. He tweets @wvstrokedoc

1-  IV Altephase in MR-Selected Patients With Stroke of Unknown Onset and Feasible: Results of the Multicenter MR WITNESS Trial (NCT01282242), Lee H. Schwamm, MD, Stroke Service, Massachusetts General Hospital, Harvard Medical School

Posted by Muhammad ALVI on Feb 1, 2017 2:52 PM America/Chicago