As many as a quarter of all stroke victims suffer a stroke in their sleep and are therefore unaware of the exact time of the incidence, however, knowing the exact timing is crucial for treatment because it determines whether or not patients can receive thrombolytic treatment, a therapy that breaks down blood clots, but which is ineffective and potentially harmful if administered too late after the incident.
According to an article published online first in The Lancet Neurology, researchers now discovered that patients with an acute ischemic lesion detected with diffusion-weighted imaging (DWI) but not with fluid-attenuated inversion recovery (FLAIR) imaging are likely to be within the 4 ½ h time-window for which thrombolysis is safe and effective.
During a small study researchers observed that lesions visible on DWI but not yet on FLAIR imaging indicate that the stroke has occurred during the 4 ½ hour ‘safety-window’ and therefore enables thrombolysis treatment. Götz Thomalla from the Universitätsklinikum (University Medical Center) in Hamburg-Eppendorf, Hamburg, Germany and his team decided to extend this study and retrospectively evaluated FLAIR and DWI scans from 543 patients with an average age of 66 years that were taken within 12 hours of ischemic stroke symptom onset.
They discovered that DWI revealed acute ischemic lesions in 95% (516) patients compared with FLAIR, which showed 50% (271) respectively.
Based on DWI-FLAIR mismatch, 78% of patients within the 4-½ hour window of symptom onset were identified with high specificity and 83% with a positive predictive value, while sensitivity and negative predictive values were lower with 62% and 54% respectively. The positive predictive value was even higher with 87% in the subgroup of patients that had suffered from a middle cerebral artery stroke and a relevant neurological deficit, the typical target population for thrombolysis.
“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 recanalization treatment…Intravenous thrombolysis is effective and is recommended up to 4 ½ hours 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,” write the authors, saying that the next step will be “to test DWI-FLAIR mismatch in a randomized controlled trial of thrombolysis in patients with unknown time of symptom onset.”
Michael D Hill and Richard Frayne at the University of Calgary, Canada write in a comment:
“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. This study sets the stage for optimization and validation of the FLAIR-DWI mismatch biomarker. Validation would allow this biomarker to be used as a participant selection method for randomized 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.”
Written by Petra Rattue