TY - JOUR
T1 - DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4·5 h of symptom onset (PRE-FLAIR)
T2 - A multicentre observational study
AU - Thomalla, Götz
AU - Cheng, Bastian
AU - Ebinger, Martin
AU - Hao, Qing
AU - Tourdias, Thomas
AU - Wu, Ona
AU - Kim, Jong S.
AU - Breuer, Lorenz
AU - Singer, Oliver C.
AU - Warach, Steven
AU - Christensen, Soren
AU - Treszl, Andras
AU - Forkert, Nils D.
AU - Galinovic, Ivana
AU - Rosenkranz, Michael
AU - Engelhorn, Tobias
AU - Köhrmann, Martin
AU - Endres, Matthias
AU - Kang, Dong Wha
AU - Dousset, Vincent
AU - Sorensen, A. Gregory
AU - Liebeskind, David S.
AU - Fiebach, Jochen B.
AU - Fiehler, Jens
AU - Gerloff, Christian
N1 - Funding Information:
PRE-FLAIR received funding from the Else Kröner-Fresenius-Stiftung (2009_A36). Funding was provided for central data collection and analysis; there was no funding for inclusion of patients. We thank the EPITHET (Echoplanar Imaging Thrombolysis Evaluation Trial) investigators, the University of California, Los Angeles Stroke investigators, all co-investigators of VIRAGE, and all our colleagues from the Departments of Neurology and Neuroradiology, and medical and technical staff in the participating centres for their support. In Berlin, data were collected within the 1000+ study, which has received funding from the Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin (01 EO 0801) . This work was further supported by the European Union Seventh Framework Programme grant agreement No 202213 and No 223153 (European Stroke Network), the Volkswagen Foundation, and the Deutsche Forschungsgemeinschaft. EPITHET was funded by the National Health and Medical Research Council (Australia), the National Stroke Foundation (Australia), and the Heart Foundation of Australia. VIRAGE is supported by French national grant PHRC.
Funding Information:
VD has received a national grant from the French Government. MEn has received grant support from Astra Zeneca and Sanofi-Aventis, has participated in advisory board meetings of Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Sanofi-Aventis, and has received honoraria from Novartis, Pfizer, Bayer, Astra Zeneca, Boehringer Ingelheim, Sanofi-Aventis, Trommsdorff, Berlin-Chemie, GlaxoSmithKline, and Bristol-Myers Squibb. JBF has received fees as a board member, consultant, or lecturer from Boehringer Ingelheim, Lundbeck, Siemens, Syngis, and Synard. CG has received fees as a consultant or lecture fees from Bayer Vital, Boehringer Ingelheim, EBS Technologies, GlaxoSmithKline, Lundbeck, Pfizer, Sanofi-Aventis, Silk Road Medical, and Union Chimique Belge. DSL has received fees as a consultant for CoAxia and Concentric Medical. AGS was supported by grants from the National Institutes of Health, has received fees as a board member, consultant, or lecturer from the American College of Radiology Imaging Network, Biogen, Genzyme, Mitsubishi, and has received royalties from General Electrics and Olea. GT has received a research grant from the Else Kröner-Fresenius-Stiftung. TT has received a national grant from the French Government (PHRC). OW was supported in part by grants from the National Institutes of Health. LB, BC, SC, MEb, TE, JF, NDF, IG, QH, D-WK, JSK, MK, MR, OCS, AT, and SW declare that they have no conflicts of interest.
PY - 2011/11
Y1 - 2011/11
N2 - Background: Many patients with stroke are precluded from thrombolysis treatment because the time from onset of their symptoms is unknown. We aimed to test whether a mismatch in visibility of an acute ischaemic lesion between diffusion-weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI (DWI-FLAIR mismatch) can be used to detect patients within the recommended time window for thrombolysis. Methods: In this multicentre observational study, we analysed clinical and MRI data from patients presenting between Jan 1, 2001, and May 31, 2009, with acute stroke for whom DWI and FLAIR were done within 12 h of observed symptom onset. Two neurologists masked to clinical data judged the visibility of acute ischaemic lesions on DWI and FLAIR imaging, and DWI-FLAIR mismatch was diagnosed by consensus. We calculated predictive values of DWI-FLAIR mismatch for the identification of patients with symptom onset within 4·5 h and within 6 h and did multivariate regression analysis to identify potential confounding covariates. This study is registered with ClinicalTrials.gov, number NCT01021319. Findings: The final analysis included 543 patients. Mean age was 66·0 years (95% CI 64·7-67·3) and median National Institutes of Health Stroke Scale score was 8 (IQR 4-15). Acute ischaemic lesions were identified on DWI in 516 patients (95%) and on FLAIR in 271 patients (50%). Interobserver agreement for acute ischaemic lesion visibility on FLAIR imaging was moderate (κ=0·569, 95% CI 0·504-0·634). DWI-FLAIR mismatch identified patients within 4·5 h of symptom onset with 62% (95% CI 57-67) sensitivity, 78% (72-84) specificity, 83% (79-88) positive predictive value, and 54% (48-60) negative predictive value. Multivariate regression analysis identified a longer time to MRI (p<0·0001), a lower age (p=0·0009), and a larger DWI lesion volume (p=0·0226) as independent predictors of lesion visibility on FLAIR imaging. Interpretation: Patients with an acute ischaemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomised trial of thrombolysis in patients with unknown time of symptom onset. Funding: Else Kröner-Fresenius-Stiftung, National Institutes of Health.
AB - Background: Many patients with stroke are precluded from thrombolysis treatment because the time from onset of their symptoms is unknown. We aimed to test whether a mismatch in visibility of an acute ischaemic lesion between diffusion-weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI (DWI-FLAIR mismatch) can be used to detect patients within the recommended time window for thrombolysis. Methods: In this multicentre observational study, we analysed clinical and MRI data from patients presenting between Jan 1, 2001, and May 31, 2009, with acute stroke for whom DWI and FLAIR were done within 12 h of observed symptom onset. Two neurologists masked to clinical data judged the visibility of acute ischaemic lesions on DWI and FLAIR imaging, and DWI-FLAIR mismatch was diagnosed by consensus. We calculated predictive values of DWI-FLAIR mismatch for the identification of patients with symptom onset within 4·5 h and within 6 h and did multivariate regression analysis to identify potential confounding covariates. This study is registered with ClinicalTrials.gov, number NCT01021319. Findings: The final analysis included 543 patients. Mean age was 66·0 years (95% CI 64·7-67·3) and median National Institutes of Health Stroke Scale score was 8 (IQR 4-15). Acute ischaemic lesions were identified on DWI in 516 patients (95%) and on FLAIR in 271 patients (50%). Interobserver agreement for acute ischaemic lesion visibility on FLAIR imaging was moderate (κ=0·569, 95% CI 0·504-0·634). DWI-FLAIR mismatch identified patients within 4·5 h of symptom onset with 62% (95% CI 57-67) sensitivity, 78% (72-84) specificity, 83% (79-88) positive predictive value, and 54% (48-60) negative predictive value. Multivariate regression analysis identified a longer time to MRI (p<0·0001), a lower age (p=0·0009), and a larger DWI lesion volume (p=0·0226) as independent predictors of lesion visibility on FLAIR imaging. Interpretation: Patients with an acute ischaemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomised trial of thrombolysis in patients with unknown time of symptom onset. Funding: Else Kröner-Fresenius-Stiftung, National Institutes of Health.
UR - http://www.scopus.com/inward/record.url?scp=80054767683&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054767683&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(11)70192-2
DO - 10.1016/S1474-4422(11)70192-2
M3 - Article
C2 - 21978972
AN - SCOPUS:80054767683
SN - 1474-4422
VL - 10
SP - 978
EP - 986
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 11
ER -