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Ann Neurol. 2018 May;83(5):980-993. doi: 10.1002/ana.25235. Epub 2018 Apr 27.

Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results.

Author information

1
Department of Neurology, Massachusetts General Hospital, Boston, MA.
2
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA.
3
Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA.
4
Acute Cerebrovascular Diagnostics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
5
Department of Neurology, Washington University School of Medicine, St Louis, MO.
6
Comprehensive Stroke Center, MedStar Washington Hospital Center, Washington, DC.
7
Massachusetts General Hospital Biostatistics Center, Boston, MA.
8
Harvard T. H. Chan School of Public Health, Boston, MA.
9
Neuroendovascular Service, Texas Stroke Institute, Plano, TX.
10
Department of Radiology, Massachusetts General Hospital, Boston, MA.
11
Department of Neuroradiology, Paris Descartes University, Saint Anne Hospital Center, Paris, France.
12
Dell Medical School, University of Texas at Austin, Austin, TX.

Abstract

OBJECTIVE:

Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242).

METHODS:

Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS).

RESULTS:

Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5-13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0-1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions.

INTERPRETATION:

Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980-993.

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