Abstract
Introduction: Hemorrhagic transformation (HT) is a complication of reperfusion therapy for acute ischemic stroke. Blood–brain barrier (BBB) disruption is a crucial step toward HT; however, in clinical studies, there is still uncertainty about this relation. Hence, we conducted a systematic review and meta-analysis to summarize the current evidence.Methods: We performed systematic review and meta-analysis of observational studies from January 1990 to March 2020 about the relation between BBB disruption and HT in patients with acute ischemic stroke with both computed tomography (CT) and magnetic resonance (MR) assessment of BBB. The outcome of interest was HT at follow-up imaging evaluation (within 48 h from symptom onset). We pooled data from available univariate odds ratios (ORs) in random-effects models with DerSimonian–Laird weights and extracted cumulative ORs.Results: We included 30 eligible studies (14 with CT and 16 with MR), N = 2,609 patients, with 88% and 70% of patients included in CT and MR studies treated with acute stroke therapy, respectively. The majority of studies were retrospective and had high or unclear risk of bias. BBB disruption was measured with consistent methodology in CT studies, whereas in MR studies, there was more variability. All CT studies provided a BBB disruption cutoff predictive of HT. Four CT and 10 MR studies were included in the quantitative analysis. We found that BBB disruption was associated with HT with both CT (OR = 3.42; 95%CI = 1.62–7.23) and MR (OR = 9.34; 95%CI = 3.16–27.59). There was a likely publication bias particularly for MR studies.Conclusion: Our results confirm that BBB disruption is associated with HT in both CT and MR studies. Compared with MR, CT has been more uniformly applied in the literature and has resulted in more consistent results. However, more efforts are needed for harmonization of protocols and methodology for implementation of BBB disruption as a neuroradiological marker in clinical practice.
Highlights
Hemorrhagic transformation (HT) is a complication of reperfusion therapy for acute ischemic stroke
Data for the quantitative analysis were available for 1,298 (50%) patients, from 4/14 studies with computed tomography (CT) (794 patients, 53% of patients included in CT studies) and 9/16 magnetic resonance (MR) studies (504 patients, 45% of patients included in MR studies)
Among studies included in the meta-analysis, only three [36, 39, 42] out of 10 MR studies had quantitative assessment of blood–brain barrier (BBB) disruption; MR studies had smaller sample size compared with CT studies, as reflected by the wider confidence intervals in the pooled MR analysis
Summary
Hemorrhagic transformation (HT) is a complication of reperfusion therapy for acute ischemic stroke. Acute treatments aiming to recanalize the occluded vessel demonstrated efficacy in reducing the functional burden of the disease; reperfusion of the ischemic tissue brings some risk, with the most feared being hemorrhagic transformation (HT). In vitro and in vivo models suggested failure of endothelial integrity and loss of neurovascular homeostasis as the cellular mechanisms underlying blood extravasation [3, 4] and, from a structural point of view, disruption of the blood–brain barrier (BBB) as the pathophysiological step that leads to HT [5, 6]. In vivo visualization and measurement of BBB disruption in the acute stroke setting before reperfusion therapy may represent a useful marker to identify patients more prone to develop HT. BBB disruption can be investigated using different algorithms that mainly measure contrast extravasation through microcirculation, with either qualitative or quantitative methods [7]
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