Austin Health

Title
Reduced Severity of Tissue Injury Within the Infarct May Partially Mediate the Benefit of Reperfusion in Ischemic Stroke.
Publication Date
2022-06
Author(s)
Ng, Felix C
Churilov, Leonid
Yassi, Nawaf
Kleinig, Timothy J
Thijs, Vincent N
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
Subject
blood-brain barrier
infarction
ischemic stroke
reperfusion
thrombectomy
Type of document
Journal Article
OrcId
0000-0001-6973-8677
0000-0002-9807-6606
0000-0002-0685-0060
0000-0003-4430-3276
0000-0002-6614-8417
0000-0003-1845-1769
0000-0002-5254-219X
0000-0001-9484-2070
0000-0002-4803-6323
0000-0001-8802-9606
0000-0001-8874-2487
0000-0001-6324-3403
0000-0003-0962-2300
0000-0002-8337-7529
0000-0002-8285-1815
0000-0003-3632-9433
DOI
10.1161/STROKEAHA.121.036670
Abstract
Emerging data suggest tissue within the infarct lesion is not homogenously damaged following ischemic stroke but has a gradient of injury. Using blood-brain-barrier (BBB) disruption as a marker of tissue injury, we tested whether therapeutic reperfusion improves clinical outcome by reducing the severity of tissue injury within the infarct in patients with ischemic stroke. In a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) and EXTEND-IA part-2 (Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke) trials, post-treatment BBB permeability at 24 hours was calculated based on the extent of T1-brightening by extravascular gadolinium on T2* perfusion-weighted imaging and measured within the diffusion-weighted-imaging lesion. First, to determine the clinical significance of BBB disruption as a marker of severity of tissue injury, we examined the association between post-treatment BBB permeability and functional outcome. Second, we performed an exploratory (reperfusion, BBB permeability, functional outcome) mediation analysis to estimate the proportion of the reperfusion-outcome relationship that is mediated by change in BBB permeability. In the 238 patients analyzed, an increased BBB permeability measured within the infarct at 24 hours was associated with a reduced likelihood of favorable outcome (90-day modified Rankin Scale score of ≤2) after adjusting for age, baseline National Institutes of Health Stroke Scale, premorbid modified Rankin Scale, infarct topography, laterality, thrombolytic agent, sex, parenchymal hematoma, and follow-up infarct volume (adjusted odds ratio, 0.86 [95% CI, 0.75-0.98], P=0.023). Mediation analysis suggested reducing the severity of tissue injury (as estimated by BBB permeability) accounts for 18.2% of the association between reperfusion and favorable outcome, as indicated by a reduction in the regression coefficient of reperfusion after addition of BBB permeability as a covariate. In patients with ischemic stroke, reduced severity of tissue injury within the infarct, as determined by assessing the integrity of the BBB, is independently associated with improved functional outcome. In addition to reducing diffusion-weighted imaging-defined infarct volume, reperfusion may also improve clinical outcome by reducing tissue injury severity within the infarct.
Link
Citation
Stroke 2022; 53(6): 1915-1923
Jornal Title
Stroke

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