β° Wake-Up Stroke Eligibility Guide
When the clock started while you slept.
Stroke is an emergency. Call emergency services immediately for any suspected stroke; do not use this page to decide about treatment.
Eligibility screen
For informational purposes only, not medical advice.
Wake-up strokes, discovered on awakening with unknown onset, were historically excluded from thrombolysis for lack of a clock. The WAKE-UP trial changed that: an MRI pattern of DWI positive but FLAIR negative identifies brain tissue likely injured within the last 4.5 hours, making such patients eligible for alteplase. In screening terms: unknown onset plus mismatch present plus no exclusions reads as Potentially eligible: DWI-FLAIR mismatch suggests onset within 4.5h.
About one in five strokes is discovered on waking. Before imaging-based selection, those patients simply missed treatment. The mismatch concept gave them a clock made of tissue rather than time.
How This Guide Works
Answer the three screening questions. The tool applies the WAKE-UP logic and tells you what the finding means, while the actual treatment decision stays with the emergency stroke team.
Note the timing: truly unknown (woke with symptoms), known under 4.5 hours, or known beyond it.
Enter the MRI result if available: DWI positive with FLAIR negative is the mismatch pattern.
Note any standard thrombolysis exclusion. Read the screening result and get emergency evaluation regardless.
The DWI-FLAIR Mismatch Idea
Diffusion-weighted imaging lights up within minutes of ischemia; FLAIR takes hours to show the same lesion. A lesion visible on DWI but not yet on FLAIR is therefore young, very likely under 4.5 hours old. The WAKE-UP trial randomized such patients to alteplase or placebo and found better functional outcomes with treatment, at the cost of the expected bleeding risk.
CT-based alternatives exist for centers without emergency MRI, using perfusion imaging to find salvageable tissue, but the DWI-FLAIR mismatch remains the cleanest validated criterion for the wake-up scenario.
Worked Example
A patient wakes at 7 am with right-sided weakness and aphasia, last known well at 11 pm: unknown onset, roughly 8 hours by the clock. Emergency MRI shows a left MCA lesion bright on DWI and invisible on FLAIR, with no hemorrhage and no exclusions. Screening: Potentially eligible: DWI-FLAIR mismatch suggests onset within 4.5h.
The stroke team would then run the full eligibility protocol and, if it passes, give alteplase per the standard 0.9 mg/kg regimen (see our tPA dose reference). Without the mismatch, the same patient at 8 hours would not receive thrombolysis. The MRI finding is the entire difference.
Reading Your Result
| Screening result | Meaning |
|---|---|
| Standard window | Onset known under 4.5h: routine thrombolysis evaluation. |
| Potentially eligible | Mismatch suggests young lesion: full stroke-team workup for thrombolysis. |
| Mismatch absent | Lesion likely older than 4.5h: WAKE-UP criteria do not support lysis. |
| Needs emergency MRI | Cannot apply criteria without imaging: evaluate emergently. |
My take: the biggest real-world barrier is not the criteria but the MRI at 3 am. Centers that built wake-up MRI pathways treat these patients; centers without them still cannot. If your local hospital advertises stroke care, this is worth asking about before you need it.
Limits
This is a screening explainer, not a treatment pathway. MRI interpretation needs neuroradiology expertise, many wake-up patients have exclusions anyway, and thrombectomy candidacy follows separate imaging rules. Most nothing here should slow emergency activation: call first, screen later.
Related Tools
See the tPA dose reference for the standard regimen, and the blood pressure checker for the pressure management that frames acute stroke care.
For informational purposes only, not medical advice. Consult a healthcare professional.
Frequently Asked Questions
What is a wake-up stroke?
A stroke discovered on awakening, with symptoms not present at sleep onset, so the exact onset time is unknown. About 20% of strokes present this way, historically excluding patients from time-based thrombolysis.
Can wake-up strokes get tPA?
Yes, in selected patients. The WAKE-UP trial showed that MRI DWI-FLAIR mismatch identifies lesions likely under 4.5 hours old, and alteplase improved outcomes in that group. Emergency MRI and stroke-team judgment are required.
What is DWI-FLAIR mismatch?
A lesion visible on diffusion-weighted MRI (appears within minutes of ischemia) but not yet on FLAIR imaging (takes hours). The mismatch indicates a young lesion, likely within the thrombolysis window despite unknown clock time.
What did the WAKE-UP trial show?
Published in NEJM 2018: alteplase in DWI-FLAIR mismatch patients with unknown onset improved functional outcome versus placebo, with more intracranial hemorrhage but lower mortality. It established imaging-based selection for unknown-onset stroke.
What is last known well?
The last time the patient was seen normal, which anchors all stroke timing when exact onset is unknown. For wake-up strokes it is typically bedtime the night before.
Do all hospitals offer wake-up stroke MRI?
No. Emergency MRI availability varies, which is the main practical limit. Some centers use CT perfusion alternatives. Comprehensive stroke centers are most likely to have wake-up pathways.
What about thrombectomy for wake-up strokes?
Mechanical thrombectomy for large vessel occlusion uses perfusion imaging selection up to 24 hours and follows separate criteria from thrombolysis. Many wake-up patients are evaluated for both.
What are standard tPA exclusions?
Intracranial hemorrhage, recent brain or spinal surgery, head trauma, active bleeding, very high blood pressure, abnormal clotting labs, and very mild symptoms, among others. The full checklist runs at the bedside.
Should I wait to see if symptoms improve?
No. Call emergency services immediately for any suspected stroke. Time lost is brain lost, and improvement can be temporary. Evaluation, not waiting, is always the right move.
Does this page decide treatment?
Never. It explains the eligibility concept for education. Thrombolysis decisions belong to emergency stroke teams with imaging, labs, and the patient in front of them.