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Journal Title: | Microvascular Dysfunction in Blood-Brain Barrier Disruption and Hypoperfusion Within the Infarct Posttreatment Are Associated With Cerebral Edema |
Authors: | Ng, Felix C. Churilov, Leonid Yassi, Nawaf Kleinig, Timothy J. Thijs, Vincent Wu, Teddy Y. Shah, Darshan G.. Dewey, Helen M. Sharma, Gagan Desmond, Patricia M. Yan, Bernard Parsons, Mark W. Donnan, Geoffrey A. Davis, Stephen M. Mitchell, Peter J. Leigh, Richard Campbell, Bruce C. V. Part, EXTEND-IA TNK Investigators |
Keywords: | Blood-Brain Barrier Brain Edema Brain Ischemia Cerebral Infarction Cerebrovascular Circulation Humans Blood-Brain Barrier Hematoma Magnetic Resonance Imaging Perfusion Permeability |
Issue Date: | May-2022 |
Date Accessioned: | 2023-04-24T02:44:21Z |
Date Available: | 2023-04-24T02:44:21Z |
Accession Number: | 34937423 |
Url: | https://www.ncbi.nlm.nih.gov/pubmed/34937423 |
Description Affiliation: | Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Australia (F.C.N., L.C., N.Y., G.S., B.Y., M.W.P., G.A.D., S.M.D., B.C.V.C.). The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia (F.C.N., V.T.). Department of Neurology, Austin Hospital, Austin Health, Heidelberg, Australia (L.C., V.T., B.C.V.C.). Melbourne Medical School, The University of Melbourne, Heidelberg, Australia (L.C.). Population Health and Immunity Division. The Walter and Eliza Hall Institute of Medical Research. Parkville, Australia (N.Y.). Department of Neurology, Royal Adelaide Hospital, Australia (T.J.K.). Department of Neurology, Christchurch Hospital, New Zealand (T.Y.W.). Department of Neurology, Princess Alexandra Hospital, Brisbane, Australia (D.G.S.). Eastern Health and Eastern Health Clinical School, Department of Neurosciences, Monash University, Clayton, Australia (H.M.D.). Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia (P.M.D., B.Y., P.J.M.). Department of Neurology, John Hopkins University, Baltimore, MD (R.L.). |
Format Startpage: | 1597-1605 |
Source Volume: | 53 |
Issue Number: | 5 |
Notes: | Meta-Analysis |
DOI: | 10.1161/STROKEAHA.121.036104 |
Date: | May 2022 |
Abstract: | BACKGROUND: Factors contributing to cerebral edema in the post-hyperacute period of ischemic stroke (first 24-72 hours) are poorly understood. Blood-brain barrier (BBB) disruption and postischemic hyperperfusion reflect microvascular dysfunction and are associated with hemorrhagic transformation. We investigated the relationships between BBB integrity, cerebral blood flow, and space-occupying cerebral edema in patients who received acute reperfusion therapy. METHODS: We performed a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK and EXTEND-IA TNK part 2 trials who had MRI with dynamic susceptibility contrast-enhanced perfusion-weighted imaging 24 hours after treatment. We investigated the associations between BBB disruption and cerebral blood flow within the infarct with cerebral edema assessed using 2 metrics: first midline shift (MLS) trichotomized as an ordinal scale of negligible (<1 mm), mild (>/=1 to <5 mm), or severe (>/=5 mm), and second relative hemispheric volume (rHV), defined as the ratio of the 3-dimensional volume of the ischemic hemisphere relative to the contralateral hemisphere. RESULTS: Of 238 patients analyzed, 133 (55.9%) had negligible, 93 (39.1%) mild, and 12 (5.0%) severe MLS at 24 hours. The associated median rHV was 1.01 (IQR, 1.00-1.028), 1.03 (IQR, 1.01-1.077), and 1.15 (IQR, 1.08-1.22), respectively. MLS and rHV were associated with poor functional outcome at 90 days (P<0.002). Increased BBB permeability was independently associated with more edema after adjusting for age, occlusion location, reperfusion, parenchymal hematoma, and thrombolytic agent used (MLS cOR, 1.12 [95% CI, 1.03-1.20], P=0.005; rHV beta, 0.39 [95% CI, 0.24-0.55], P<0.0001), as was reduced cerebral blood flow (MLS cOR, 0.25 [95% CI, 0.10-0.58], P=0.001; rHV beta, -2.95 [95% CI, -4.61 to -11.29], P=0.0006). In subgroup analysis of patients with successful reperfusion (extended Treatment in Cerebral Ischemia 2b-3, n=200), reduced cerebral blood flow remained significantly associated with edema (MLS cOR, 0.37 [95% CI, 0.14-0.98], P=0.045; rHV beta, -2.59 [95% CI, -4.32 to -0.86], P=0.004). CONCLUSIONS: BBB disruption and persistent hypoperfusion in the infarct after reperfusion treatment is associated with space-occupying cerebral edema. Further studies evaluating microvascular dysfunction during the post-hyperacute period as biomarkers of poststroke edema and potential therapeutic targets are warranted. |
URI: | https://repository.southwesthealthcare.com.au/swhealthcarejspui/handle/1/3849 |
Journal Title: | Stroke |
Type: | Journal Article |
Appears in Collections: | SWH Data Contributions |
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