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Thrombolysis in patients with WAKE-UP or unknown time of stroke onset: ready for prime time?
  1. Ashutosh P Jadhav1,2,
  2. Shashvat M Desai1,
  3. Joshua A Hirsch3
  1. 1 Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
  2. 2 Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
  3. 3 NeuroInterventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Ashutosh P Jadhav, University of Pittsburgh, Stroke Institute, Pittsburgh, PA 15213, USA; jadhavap{at}upmc.edu

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Endovascular therapy for emergent large vessel occlusion has proven benefit in the treatment of patients with acute ischemic stroke.1–3 This benefit is time dependent, with higher rates of good outcomes in patients treated earlier after symptom onset. The efficacy of chemical or mechanical recanalization disappears after 4.5 hours4 or 7.3 hours5 in unselected patients. Results of the recently published trials Diffusion Weighted Imaging or Computerized Tomography Perfusion Assessment with Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE-3)6 7 demonstrated superior outcomes in selected patients presenting beyond 6 hours of symptoms.8–11 Advanced imaging was applied to measure baseline core infarct on MRI head (diffusion weighted imaging (DWI)) or CT perfusion to identify patients with clinical or perfusion mismatch in the presence of a proximal anterior circulation large vessel occlusion. Similar efforts to identify thrombolysis candidates beyond conventional time windows have focused on the use of perfusion and/or core imaging to identify tissue at risk.12 13 No studies to date have shown the benefit of intravenous thrombolysis over medical therapy using this method14 although further efforts are ongoing.

An alternative approach using MRI relies on the observation that patients demonstrating ischemic lesions on DWI, in the absence of fluid attenuated inversion recovery (FLAIR) hyperintense signal, are likely within 4.5 hours of stroke onset. Utilizing this DWI-FLAIR mismatch to identify patients that fell within this time frame, investigators in the WAKE-UP trial then treated stroke patients with either alteplase or placebo.15 The investigators reasoned that the WAKE-UP MRI signature allows reclassification of patients presenting with ‘wake-up’ strokes or unwitnessed strokes as actually early time window (<4.5 hours) patients. The WAKE-UP trial was a multicenter, …

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