The evolution of blood brain barrier permeability changes after stroke, and its implications on clinical outcome: a systematic review and meta-analysis.

Abstract

Blood-brain barrier permeability (BBBp) is key process involved in ischemic stroke pathophysiology. However, there is a lack of consensus on how BBBp evolves after the ischaemic injury, and its clinical relevance at different time points post stroke. To assess BBBp evolution through stroke phases, and its implications on patient outcomes. We screened PubMed/MEDLINE, EMBASE, Web of Science, Scopus and Cochrane Central Register of Controlled Trials up to December 31, 2021. We included research quantitatively using neuroimaging to assess BBBp in stroke patients. BBBp in the different phases was evaluated by a random effect model based on the standardized mean difference (SMD) between the ipsilateral and contralateral sides of the brain. We performed subgroup analysis on clinical outcome, reperfusion treatment, haemorrhagic transformation and imaging method. We identified 3761 studies of which 22 (1592 patients, 1787 evaluations) were included in our study. Overall, 17 studies reported BBBp for the hyperacute phase, eight for the acute, five for the subacute and two for the chronic phase. All phases were associated with increased BBBp : 0.74 (0.48-0.99), 1.68 (0.94-2.42), 1.98 (0.96-3.00) and 1.00 (0.45-1.55) respectively. An increase in BBBp was associated with hemorrhagic transformation in the hyperacute phase, and with improved functional outcomes in the late subacute phase. BBBp is persistently increased after stroke, peaking in the acute and subacute phases. The degree of BBBp influences patient outcomes depending on stroke phase. Our findings support the clinical relevance of BBBp dynamics in stroke care.