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Title: Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow).
Austin Authors: Ng, Felix C ;Churilov, Leonid ;Yassi, Nawaf;Kleinig, Timothy John;Thijs, Vincent N ;Wu, Teddy;Shah, Darshan;Dewey, Helen;Sharma, Gagan;Desmond, Patricia;Yan, Bernard;Parsons, Mark;Donnan, Geoffrey A ;Davis, Stephen;Mitchell, Peter;Campbell, Bruce
Affiliation: Medicine (University of Melbourne)..
The Florey Institute of Neuroscience and Mental Health..
Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Australia..
Department of Radiology, the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia..
Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia..
Department of Neurology, Christchurch Hospital, Christchurch, New Zealand..
Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland, Australia..
Eastern Health and Eastern Health Clinical School, Department of Neurosciences, Monash University, Clayton, Victoria, Australia..
Population Health and Immunity Division. The Walter and Eliza Hall Institute of Medical Research. Parkville, Australia..
Issue Date: 22-Feb-2022
Date: 2021-12-14
Publication information: Neurology 2022; 98(8): e790-e801
Abstract: BackgroundThe relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiological features of this phenomenon, and its associations with outcomes in three international randomized controlled thrombectomy trials with pre-specified follow-up perfusion imaging.MethodsIn a pooled analysis of the EXTEND-IA ( number NCT01492725), EXTEND-IA TNK (NCT02388061) and EXTEND-IA TNK Part-two (NCT03340493) trials, patients undergoing thrombectomy with final angiographic extended Thrombolysis In Cerebral Ischemia 2c-3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative Cerebral Blood Volume or Flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homologue in the absence of carotid stenosis or re-occlusion.ResultsRegions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (Interquartile range 47.8-70.7%) of the infarct volume, and involved both subcortical (n=26/33,78.8%) and cortical (n=10/33,30.3%) regions. Patients with no-reflow had a median 25.2% ([Interquartile range 16.4-32.2%],p<0.00001) relative Cerebral Blood Volume interside reduction and 19.1% (Interquartile range 3.9-28.3%,p=0.00011) relative Cerebral Blood Flow reduction but similar mean-transit-time (median -3.3%, Interquartile range -11.9-24.4%,p=0.24) within the infarcted region. Baseline characteristics were similar between patients with and without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (aOR=1.79,95%CI2.32-15.57,p=0.0002), greater infarct growth (ß=11.00,95%CI5.22-16.78,p=0.00027), reduced National Institutes of Health Stroke Score improvement at 24-hours (ß=-4.06,95%CI-6.78--1.34,p=0.004) and being dependent or dead at 90-day as assessed on the modified Rankin Scale (aOR=3.72,95%CI1.35-10.20,p=0.011) in multivariable analysis.ConclusionCerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with post-treatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted.Classification of evidenceThis study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24-hours is associated with post-treatment complications and poor 3-month functional outcome.
DOI: 10.1212/WNL.0000000000013210
ORCID: 0000-0001-6973-8677
Journal: Neurology
PubMed URL: 34906976
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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