Skip to content
Evevident
Original paper
2018NEJMNeurology

WAKE-UP

MRI-guided thrombolysis for stroke with unknown time of onset

RCTAcute ischemic stroke

On this page

Overview

MRI-selected alteplase improved functional outcome in stroke with unknown onset time.

Clinical takeaway

WAKE-UP extended thrombolysis thinking beyond the clock by using DWI-FLAIR mismatch to select patients likely within a treatable window.

Key result

Favorable functional outcome at 90 days was higher with alteplase than placebo.

Practice impact

Advanced imaging can identify selected unknown-onset stroke patients for thrombolysis.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

503

Follow-up

90 days.

Geography

Europe

Clinical question

Does MRI-guided alteplase improve outcomes in ischemic stroke with unknown time of onset?

Population

  • Patients with acute ischemic stroke of unknown onset time and MRI DWI-positive/FLAIR-negative mismatch.

Intervention

Intravenous alteplase.

Comparator

Placebo.

Primary outcome

Favorable functional outcome at 90 days, defined by modified Rankin Scale score 0 or 1.

MRI-guided alteplase improved favorable functional outcome in unknown-onset ischemic stroke.

Adjusted odds ratio / 1.61 / CI 95% CI 1.09-2.36 / p=0.02

Key results

  • Favorable functional outcome was more common with alteplase.
  • Symptomatic intracranial hemorrhage was numerically higher with alteplase.
  • Trial was stopped early because funding ended.

Harms

  • Symptomatic intracranial hemorrhage risk remains the major thrombolysis concern.

Clinical Use

When to cite

  • When evaluating unknown-onset stroke for thrombolysis using MRI mismatch.

Practice impact

  • Supported imaging-selected thrombolysis for wake-up or unknown-onset ischemic stroke.

Applicability

  • Patients with disabling ischemic stroke symptoms, unknown onset, no contraindications, and appropriate MRI mismatch.

Limitations

  • Requires rapid MRI access and expertise.
  • Stopped early; estimates are less precise.

Common misinterpretations

  • Do not give alteplase to all wake-up strokes; imaging selection is the point.

Related evidence

NINDS tPA - ContextDAWN - Context

Citation

Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018;379(7):611-622. doi:10.1056/NEJMoa1804355