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Title: Microvascular Dysfunction in Blood-Brain Barrier Disruption and Hypoperfusion Within the Infarct Posttreatment Are Associated With Cerebral Edema.
Austin Authors: Ng, Felix C ;Churilov, Leonid ;Yassi, Nawaf;Kleinig, Timothy J;Thijs, Vincent N ;Wu, Teddy Y;Shah, Darshan G;Dewey, Helen M;Sharma, Gargan;Desmond, Patricia M;Yan, Bernard;Parsons, Mark W;Donnan, Geoffrey A ;Davis, Stephen M;Mitchell, Peter J;Leigh, Richard;Campbell, Bruce C V
Affiliation: Neurology..
The Florey Institute of Neuroscience and Mental Health..
Medicine (University of Melbourne)..
Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Australia..
Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia..
Department of Neurology, Royal Adelaide Hospital, Australia..
Department of Neurology, Christchurch Hospital, New Zealand..
Department of Neurology, Princess Alexandra Hospital, Brisbane, Australia..
Eastern Health and Eastern Health Clinical School, Department of Neurosciences, Monash University, Clayton, Australia..
Department of Neurology, John Hopkins University, Baltimore, MD..
Population Health and Immunity Division. The Walter and Eliza Hall Institute of Medical Research. Parkville, Australia..
Issue Date: May-2022
Date: 2021-12-23
Publication information: Stroke 2022; 53(5): 1597-1605.
Abstract: 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. 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. 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 β, 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 β, -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 β, -2.59 [95% CI, -4.32 to -0.86], P=0.004). 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.
DOI: 10.1161/STROKEAHA.121.036104
ORCID: 0000-0001-6973-8677
Journal: Stroke
PubMed URL: 34937423
PubMed URL:
Type: Journal Article
Subjects: blood-brain barrier
magnetic resonance imaging
Appears in Collections:Journal articles

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