Patients with an acute ischaemic lesion detected with diffusion-weighted imaging (DWI) but not with fluid-attenuated inversion recovery (FLAIR) imaging are likely to be within the 4•5 h time-window for which thrombolysis (treatment that breaks down blood clots) is safe and effective, say authors in an article published Online First in The Lancet Neurology. Pinpointing the time at which patients have had a stroke is important because as many as a quarter of people have a stroke while sleeping and so are unaware of the exact time of onset. Yet knowing when symptoms started determines whether or not they can have thrombolytic treatment—late treatment is ineffective and potentially harmful.
If a lesion is visible on DWI but not yet on FLAIR imaging, it suggests that the stroke has been recent enough that thrombolysis could work. This has already been shown in a small study, but to extend this work, Götz Thomalla, Universitätsklinikum (University Medical Center) Hamburg-Eppendorf, Hamburg, Germany, and colleagues retrospectively analysed FLAIR and DWI scans done within 12 h of ischemic stroke symptom onset in 543 patients (with an average age of 66 years).
They identified acute ischaemic lesions on DWI in 516 patients (95%) and on FLAIR in 271 patients (50%). On the basis of DWI-FLAIR mismatch, patients within 4•5 h of symptom onset were identified with high specificity (78%) and positive predictive value (83%), while sensitivity (62%) and the negative predictive value (54%) were lower. In the subgroup of patients with middle cerebral artery stroke and a relevant neurological deficit (ie the typical target population for thrombolysis) the positive predictive value was even higher (87%).
The authors say: "The clinical use of DWI-FLAIR mismatch as a surrogate marker of lesion age could enable the extension of thrombolysis to a new population of patients who are likely to benefit from recanalisation treatment…Intravenous thrombolysis is effective and is recommended up to 4•5 h after symptom onset. Furthermore, combined analyses of acute stroke thrombolysis trials suggest a beneficial effect or at least no net harm from thrombolysis up to 6 h after symptom onset." The next step, they say, will be to test DWI-FLAIR mismatch in a randomised controlled trial of thrombolysis in patients with unknown time of symptom onset.
In a Comment on the paper, Michael D Hill and Richard Frayne at the University of Calgary, Canada, say that "the key features of interest in this study are the use and validation of imaging as a biomarker, the simplicity of the use of FLAIR-DWI mismatch, and the obvious implication for planned large trials of thrombolysis in patients with stroke on awakening."
They add: "This study sets the stage for optimisation and validation of the FLAIR-DWI mismatch biomarker. Validation would allow this biomarker to be used as a participant selection method for randomised trials of thrombolytic stroke therapy in patients with stroke on awakening or with unwitnessed stroke onset. Such trials are on the drawing board and it will be these kinds of imaging biomarkers—which are simple, practical, and easily implementable at many sites—that will allow relevant candidates to be selected for enrolment in these trials."
Götz Thomalla, Universitätsklinikum (University Medical Center) Hamburg-Eppendorf, Hamburg, Germany. E) thomalla@uke.uni-hamburg.de T) +49 40 7410 53770
Michael D Hill, Hotchkiss Brain Institute, Departments of Clinical Neurosciences, Radiology, Medicine and Community Health Sciences, University of Calgary, Alberta, Canada. E) hillmd@ucalgary.ca T) +1 403 944 8065
Journal
The Lancet Neurology