Please use this identifier to cite or link to this item: https://repository.southwesthealthcare.com.au/swhealthcarejspui/handle/1/3849
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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