Pretreatment blood–brain barrier disruption and post-endovascular intracranial hemorrhage

Abstract

Objective: This study sought to confirm the relationship between the degree of blood-brain barrier (BBB) damage and the severity of intracranial hemorrhage (ICH) in a population of patients who received endovascular therapy. Methods:The degree of BBB disruption on pretreatment MRI scans was analyzed, blinded to follow-up data, in the DEFUSE 2 cohort in which patients had endovascular therapy within 12 hours of stroke onset. BBB disruption was compared with ICH grade previously established by the DEFUSE 2 core lab. A prespecified threshold for predicting parenchymal hematoma (PH) was tested.Results: Of the 108 patients in the DEFUSE 2 trial, 100 had adequate imaging and outcome data and were included in this study; 24 developed PH. Increasing amounts of BBB disruption on pretreatment MRIs was associated with increasing severity of ICH grade (p 5 0.004). BBB disruption on the pretreatment scan was associated with PH (p 5 0.020) with an odds ratio for developing PH of 1.69 for each 10% increase in BBB disruption (95% confidence interval 1.09-2.64), although a reliably predictive threshold was not identified. Conclusions:The amount of BBB disruption on pretreatment MRI is associated with the severity of ICH after acute intervention. This relationship has now been identified in patients receiving IV, endovascular, and combined therapies. Further study is needed to determine its role in guiding treatment. Neurology ® 2016;87:263-269 GLOSSARY BBB 5 blood-brain barrier; BBPI 5 blood-brain permeability image; DSC 5 dynamic susceptibility contrast; DWI 5 diffusionweighted imaging; ECASS 5 European Cooperative Acute Stroke Study; GRE 5 gradient echo; HI 5 hemorrhagic infarct; ICH 5 intracranial hemorrhage; PH 5 parenchymal hematoma; PWI 5 perfusion-weighted imaging; ROC 5 receiver operator characteristic; ROI 5 region of interest; tPA 5 tissue plasminogen activator.Recent studies have validated the use of endovascular therapy in the treatment of acute stroke. [1][2][3][4][5] Initial studies that failed to show benefit of endovascular therapy omitted imaging-based selection criteria. 6,7 The first trial to demonstrate that imaging could be used to select a population of patients who would benefit from endovascular therapy was the DEFUSE 2 trial.8 Although the MR RESCUE study subsequently challenged the utility of imaging selection, 9 post hoc comparisons of these 2 trials have identified several limitations to the MR RESCUE trial that likely accounted for its negative results. 10,11The first randomized trial to show benefit simply used large vessel occlusion for imaging selection.1 The absolute benefit of endovascular therapy was greater in subsequent trials that used imaging to exclude patients with large ischemic core or poor collateral blood flow.2,3,5 The DEFUSE 2 trial identified an MRI profile most likely to benefit from endovascular therapy simply using lesion volumes from diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). However, multimodal MRI contains additional information that may be...

Early Blood‐Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke

“…Mild BBB disruption in patients with acute ischemic stroke is reversible after reperfusion treatment. The amount of BBB disruption on pretreatment imaging is associated with the severity of HT after IV thrombolysis or endovascular therapy . Our analysis confirmed that BBB disruption was common after endovascular therapy in patients with acute ischemic stroke.…”

Blood-brain barrier integrity of stroke patients presenting in an extended time window

“…The method for calculating mean permeability derangement (MPD) was the same as was used and described in two prior studies [9,10]. Blood-brain permeability imaging (BBPI) is a method for calculating BBB permeability from the source images of a dynamic susceptibility contrast (DSC) image acquisition.…”

“…Prior studies have identified a MPD cut off of 20% beyond which the risk of developing a PH-2 hemorrhagic transformation increases significantly [9,10]. Thus we dichotomized patients into two groups, those with preserved BBB integrity defined as MPD < 20% and those with BBB rupture defined as MPD > 20%.…”

“…While mild BBB disruption is reversible with reperfusion, severe focal BBB disruption is associated with HT [8]. There is a dose dependency between the severity of BBB disruption within the ischemic lesion and the severity of the HT in patients treated with IV-tPA [9] or endovascular therapy [10], a relationship that has been confirmed using multiple BBB-imaging approaches [11,12]. However, imaging of the BBB has not previously been used for prospective selection of patients in clinical trials of thrombolysis in the extended time window (beyond 4.5 h).…”

Post-Stroke Blood-Brain Barrier Disruption and Poor Functional Outcome in Patients Receiving Thrombolytic Therapy

“…The template atlas was used to segment the left and right hemispheres and remove infratentorial structures. BBB permeability maps were generated from the PWI source images using a method previously described [5][6][7]. BBB permeability of the affected hemisphere was calculated relative to the unaffected hemisphere on a voxel-by-voxel basis, expressed as a percent increase over normal.…”