What is the recommended management of a patient who wakes up with new neurological deficits suggestive of an acute ischemic stroke (wake‑up stroke)?

Management of Wake-Up Stroke

For patients who wake up with stroke symptoms and have unknown onset time, proceed with acute stroke imaging and treatment protocols using advanced neuroimaging to guide therapy decisions, rather than automatically excluding them from reperfusion therapy. 1

Initial Assessment and Time Determination

• Define "last known well" as the time the patient was last awake and symptom-free, which becomes the reference point for treatment decisions 1, 2
• Use creative questioning to establish time anchors: check cell phone call timestamps, television programming times, or bathroom/kitchen visits during the night 1
• Implement stroke pathways and notify the stroke team immediately, treating wake-up stroke with the same urgency as known-onset stroke 2

Imaging Protocol for Wake-Up Stroke

For Patients Presenting 0-6 Hours from Awakening

• Obtain non-contrast CT immediately to exclude hemorrhage and assess ASPECTS score 1, 2
• Follow with multiphase CT angiography to detect large vessel occlusion and assess collateral flow 1
• Do not delay IV alteplase administration for additional perfusion imaging if the patient otherwise meets eligibility criteria within the standard time window 1

For Patients Presenting 6-24 Hours from Last Known Well

• Obtain CT perfusion or diffusion-weighted MRI to identify salvageable tissue and guide mechanical thrombectomy decisions 1
• The 2018 AHA/ASA guidelines specifically recommend obtaining CTP, DW-MRI, or MRI perfusion for patients with large vessel occlusion in the 6-24 hour window 1
• Apply DAWN or DEFUSE-3 eligibility criteria strictly when selecting patients for mechanical thrombectomy in this extended window 1

Treatment Decisions

Intravenous Alteplase

The 2018 AHA/ASA guidelines state that using imaging criteria to select wake-up stroke patients for IV alteplase is NOT recommended outside a clinical trial (Class III: No Benefit) 1. However, this represents a critical area of controversy:

• The guideline recommendation reflects the evidence available at the time of publication 1
• More recent expert opinion suggests that MRI-based selection (DWI/FLAIR mismatch) may benefit wake-up stroke patients, and some centers now offer alteplase to these patients with favorable imaging 1
• Research demonstrates that wake-up stroke patients have similar rates of CT perfusion mismatch and intracranial occlusions compared to known-onset strokes, suggesting potential treatment benefit 3, 4

Clinical approach: If your institution participates in clinical trials or has established protocols for MRI-based selection in wake-up stroke, this may be reasonable. Otherwise, focus on mechanical thrombectomy for eligible patients with large vessel occlusion 1.

Mechanical Thrombectomy

For wake-up stroke patients with large vessel occlusion presenting 6-24 hours from last known well, mechanical thrombectomy is strongly recommended when DAWN or DEFUSE-3 criteria are met 1:

• DAWN criteria: Clinical-imaging mismatch using NIHSS and CTP or DW-MRI showing small core 1
• DEFUSE-3 criteria: Perfusion-core mismatch with maximum core size limits 1
• These trials demonstrated dramatic benefit (mRS 0-2: 49% vs 13% in DAWN; 44.6% vs 16.7% in DEFUSE-3) 1

Do not use mechanical thrombectomy outside these specific criteria for late-window patients, as only DAWN and DEFUSE-3 have proven benefit beyond 6 hours 1

Critical Pitfalls to Avoid

• Never assume wake-up stroke patients are "too late" for treatment without proper imaging evaluation 5, 3
• Approximately 25-33% of all ischemic strokes are wake-up strokes, representing a substantial population that deserves acute evaluation 5, 3
• Do not delay mechanical thrombectomy to obtain perfusion imaging in patients presenting within 6 hours who have large vessel occlusion on CTA 1
• Multimodal imaging should never delay IV alteplase administration when indicated 1
• Wake-up stroke patients have similar baseline characteristics, etiology, and imaging findings compared to known-onset strokes, suggesting they should not be systematically excluded from therapy 3, 6

Practical Algorithm

1. Patient wakes with stroke symptoms → Activate stroke code immediately 2
2. Determine last known well time (when last awake and normal) 1, 2
3. Obtain non-contrast CT → Exclude hemorrhage, assess ASPECTS 1, 2
4. Obtain CT angiography → Identify large vessel occlusion 1
5. If <6 hours from awakening + no LVO → Consider standard stroke care (alteplase generally not recommended per guidelines unless in trial) 1
6. If <6 hours from awakening + LVO present → Proceed to mechanical thrombectomy 1
7. If 6-24 hours from last known well + LVO → Obtain CTP or DW-MRI, apply DAWN/DEFUSE-3 criteria for thrombectomy 1

The key principle: Wake-up stroke should trigger the same urgent evaluation as known-onset stroke, with imaging-guided decisions replacing time-based exclusions for mechanical thrombectomy in the extended window. 1, 5