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Thrombolysis Proves Effective Outside the 3-Hour Window


Delayed treatment outcomes compare with early CT thrombolysis if diffusion-perfusion mismatch is present

MRI-assisted thrombolysis is as good as and perhaps better than CT-assisted thrombolysis, and it may be particularly valuable for patients treated outside of the prescribed 3-hour treatment window after stroke onset.1 These findings were part of a large multicenter European study reported at the 2007 International Stroke Conference in San Francisco in February by Peter D. Schellinger, MD, PhD, a professor of neurology at the University of Erlangen in Germany.

The study, which compared standard CT-based thrombolysis (within the 3-hour treatment window) with MRI-based thrombolysis within and outside the 3-hour window, included 1210 patients from 5 stroke centers in Germany and Spain. CT-assisted thrombolysis within 3 hours of stroke onset was performed in 714 patients, MRI-assisted thrombolysis within 3 hours after stroke was performed in 322 patients, and MRI-assisted thrombolysis after 3 hours of stroke onset was performed in 174 patients. The mean onset to treatment time was 130, 136, and 279 minutes, respectively.

Despite their significantly longer treatment window and higher baseline National Institutes of Health Stroke Scale scores, patients who received MRI-assisted thrombolysis more than 3 hours after stroke onset fared just as well as or better than patients receiving CT-assisted thrombolysis within 3 hours of stroke onset. Rates of symptomatic intracranial hemorrhage (ICH) for the 3 approaches were 5.3%, 3.1%, and 4.0%, respectively. Mortality rates were 13.7%, 12.4%, and 12.1%, respectively. Favorable outcomes in terms of effectiveness and safety were seen in 35.6%, 35.7%, and 42% of patients, respectively.

Schellinger and coinvestigators from the University of Erlangen and the University of Heidelberg have been looking at the value of MRI-assisted thrombolysis for several years. The study presented at the International Stroke Conference was a recapitulation of a recently published study by Schellinger and coresearchers of 382 patients that specifically looked at the effectiveness and safety of MRI-assisted thrombolysis outside of the 3-hour treatment window after stroke onset.2


The investigators explained in the article that patients are treated at their institutions only if a perfusion-diffusion MRI mismatch (perfusion exceeding diffusion) is apparent. No cutoff for age or stroke severity is applied, but thrombolysis is contraindicated in patients with a diffusion-weighted MRI lesion covering more than 50% of the middle cerebral artery.

Seventy patients received MRI-assisted thrombolysis after 3 hours of stroke onset, 103 received it within 3 hours of stroke onset, and 209 patients received CT-assisted thrombolysis within 3 hours of stroke onset. Incidence of ICH was lower in the MRI-treated groups than in the CT-treated group, although the investigators noted that ICH was more common among older patients (mean age 75 years versus mean age 71 years) and among patients with higher stroke severity scores. Increased age and stroke severity were strong predictors of worse outcomes.

At 90 days, favorable outcomes were seen in 41% of patients receiving MRI-assisted thrombolysis outside of the 3-hour treatment window, 33% receiving MRI-assisted thrombolysis within the treatment window, and 38% receiving CT-assisted thrombolysis. Mortality also was lower among patients treated with MRI compared with those treated with CT.

The investigators came to the same conclusion as the investigators involved in the larger study, that MRI-assisted thrombolysis is at least as good as CT-assisted thrombolysis and of particular value to patients treated outside the prescribed 3-hour window. They added that a good outcome in relation to thrombolytic therapy is more dependent on patient selection than on time to treatment.


  • 1. Schellinger PD, Thomalla G, Fiehler J, et al. MRI-based thrombolysis is at least as safe and effective as standard CT-based treatment: a multicenter study of 1210 patients. Stroke 2007;38:454.

  • 2. Kohrmann M, Juttler E, Fiebach JB, et al. MRI versus CT-based thrombolysis treatment within and beyond the 3 h time window after stroke onset: a cohort study. Lancet Neurol 2006;5:661-667.
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