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Avoiding infarction of surrounding tissue is the main goal of reperfusion therapy for ischemic stroke
.
A smaller follow-up infarct volume (FIV), an established measure of treatment effect, is strongly associated with good functional outcomes
stroke vascular thrombosis
Disruption of the blood-brain barrier (BBB) due to tight junction dysfunction and endothelial damage is an important pathophysiological consequence of cerebral ischemia
.
BBB disruption in ischemic tissue is associated with higher clinical severity, more proximal vessel occlusion, longer ischemia time, and inversely proportional to the degree of reperfusion following intravenous thrombolysis
Increased BBB permeability has also been associated with post-stroke complications and worse functional outcomes
.
Hereby, Felix C.
Ng et al.
, Royal Melbourne Hospital, Australia, used post-treatment BBB disruption as a quantitative surrogate marker of ischemic tissue damage to examine the clinical benefit of therapeutic reperfusion versus a reduction in the severity of infarct tissue damage relevant assumptions
.
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, patients with anterior circulation large vessel occlusion were evaluated.
Summary analysis
.
BBB permeability at 24 hours post-treatment was calculated from T1 elevation of extravascular gadolinium on T2* perfusion-weighted imaging and measured in lesions on diffusion-weighted imaging
First, to determine the clinical significance of BBB disruption as a marker of tissue injury severity, they investigated the association between BBB permeability and functional outcome after treatment
.
Second, an exploratory (reperfusion, BBB permeability, functional outcome) mediation analysis was performed to estimate the proportion of the reperfusion-outcome relationship mediated by changes in BBB permeability
The significance of the study is that it found: Among the 238 patients analyzed, the following factors were adjusted for age, baseline NIH Stroke Scale, Premorbid Modified Rankin Scale, infarct topography, lateral orientation, thrombolytic agent, sex , parenchymal hematoma, and subsequent infarct volume, increased BBB permeability measured in the infarct zone at 24 hours was associated with a reduced likelihood of a favorable outcome (90-day modified Rankin scale score ≤2) (adjusted odds ratio, 0.
86 [ 95%CI, 0.
75-0.
98], P=0.
023)
.
Mediation analysis showed that reduced severity of tissue injury (estimated by BBB permeability) accounted for 18.
2% of the association between reperfusion and favorable outcome, as demonstrated by a reduction in the regression coefficient for reperfusion when BBB permeability was added as a covariate
.
The significance of this study lies in the finding that, in patients with ischemic stroke, a reduction in the severity of intra-infarct tissue damage, as determined by assessing BBB integrity, is independently associated with improved functional outcomes
.
In addition to reducing the infarct volume as defined by diffusion-weighted imaging, reperfusion may also improve clinical outcomes by reducing the severity of tissue damage within the infarct
In patients with ischemic stroke, a reduction in the severity of intra-infarct tissue damage, as determined by assessing BBB integrity,
Original source:
Ng FC, Churilov L, Yassi N, et al.
Reduced Severity of Tissue Injury Within the Infarct May Partially Mediate the Benefit of Reperfusion in Ischemic Stroke.
Reduced Severity of Tissue Injury Within the Infarct May Partially Mediate the Benefit of Reperfusion in Ischemic Stroke.
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