Anne Sophie Grosch1, Anna Kufner1,2,3, Florent Boutitie4,5,6, Bastian Cheng7, Martin Ebinger1,8, Matthias Endres1,2,3,9,10,11, Jochen B Fiebach1, Jens Fiehler12, Alina Königsberg7, Robin Lemmens13,14,15, Keith W Muir16, Norbert Nighoghossian17, Salvador Pedraza18, Claus Z Siemonsen19, Vincent Thijs20,21, Anke Wouters13,14,15, Christian Gerloff7, Götz Thomalla7, Ivana Galinovic1. 1. Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany. 2. Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Berlin, Germany. 3. Berlin Institute of Health (BIH), Berlin, Germany. 4. Hospices Civils de Lyon, Service de Biostatistique, Lyon, France. 5. Université Lyon 1, Villeurbanne, France. 6. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France. 7. Department of Neurology, Head and Neurocenter, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 8. Department of Neurology, Medical Park Berlin Humboldtmühle, Berlin, Germany. 9. German Centre for Cardiovascular Research (DZHK), Berlin, Germany. 10. German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany. 11. Excellence Cluster NeuroCure, Charite-Universitätsmedizin Berlin, Berlin, Germany. 12. Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 13. Department of Neurology, University Hospitals Leuven, Leuven, Belgium. 14. Department of Neurosciences, Experimental Neurology, Katholieke Universiteit Leuven-University of Leuven, Leuven, Belgium. 15. Laboratory of Neurobiology, Center for Brain & Disease Research, Flanders Institute for Biotechnology, Leuven, Belgium. 16. Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, United Kingdom. 17. Department of Stroke Medicine, Claude Bernard University Lyon 1, CREATIS National Center for Scientific Research Mixed Unit of Research 5220-National Institute of Health and Medical Research U1206, National Institute of Applied Sciences of Lyon, Lyon Civil Hospices, Lyon, France. 18. Department of Radiology, Girona Institute of Biomedical Research, Institute of Diagnostic Imaging, Dr. Josep Trueta Hospital, Girona, Spain. 19. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. 20. Stroke Theme, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, VIC, Australia. 21. Department of Neurology, Austin Health, Heidelberg, VIC, Australia.
Abstract
Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial. Methods:One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30). Results: Here, 85% of all patients (n = 140) and 95% of middle cerebral artery (MCA) occlusion patients (n = 127) showed FHVs at baseline. Between MCA occlusion patients with few and extensive FHVs, no differences were identified in relative lesion growth (p = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; p = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) <2 at 90 days poststroke; p = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96-3.36; p = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2-24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3-3.8), p-value for interaction was 0.11. Conclusion: While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis. Clinical Trial Registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012.
RCT Entities:
Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial. Methods: One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30). Results: Here, 85% of all patients (n = 140) and 95% of middle cerebral artery (MCA) occlusionpatients (n = 127) showed FHVs at baseline. Between MCA occlusionpatients with few and extensive FHVs, no differences were identified in relative lesion growth (p = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; p = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) <2 at 90 days poststroke; p = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96-3.36; p = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2-24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3-3.8), p-value for interaction was 0.11. Conclusion: While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis. Clinical Trial Registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012.