Blood-brain barrier leakage and hemorrhagic transformation: The Reperfusion Injury in Ischemic StroKe (RISK) study

Eur J Neurol. 2021 Sep;28(9):3147-3154. doi: 10.1111/ene.14985. Epub 2021 Jul 8.

Abstract

Background and purpose: In patients with acute ischemic stroke treated with reperfusion therapy we aimed to evaluate whether pretreatment blood-brain barrier (BBB) leakage is associated with subsequent hemorrhagic transformation (HT).

Methods: We prospectively screened patients with acute ischemic stroke treated with intravenous thrombolysis and/or endovascular treatment. Before treatment, each patient received computed tomography (CT), CT angiography, and CT perfusion. We assessed pretreatment BBB leakage within the ischemic area using the volume transfer constant (Ktrans ) value. Our primary outcome was relevant HT, defined as hemorrhagic infarction type 2 or parenchymal hemorrhage type 1 or 2. We evaluated independent associations between BBB leakage and HT using logistic regression, adjusting for age, sex, baseline stroke severity, Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6, treatment type, and onset-to-treatment time.

Results: We enrolled 171 patients with available assessment of BBB leakage. The patients' mean (±SD) age was 75.5 (±11.8) years, 86 (50%) were men, and the median (interquartile range) National Institutes of Health Stroke Scale score was 18 (12-23). A total of 32 patients (18%) received intravenous thrombolysis, 102 (60%) underwent direct endovascular treatment, and 37 (22%) underwent both. Patients with relevant HT (N = 31;18%) had greater mean BBB leakage (Ktrans 0.77 vs. 0.60; p = 0.027). After adjustment in the logistic regression model, we found that BBB leakage was associated both with a more than twofold risk of relevant HT (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.03-6.03 per Ktrans point increase; OR 2.34; 95% CI 1.06-5.17 for Ktrans values > 0.63 [mean BBB leakage value]) and with symptomatic intracerebral hemorrhage (OR 4.30; 95% CI 1.13-13.77 per Ktrans point increase).

Conclusion: Pretreatment BBB leakage before reperfusion therapy was associated with HT, and may help to identify patients at risk of HT.

Keywords: CT perfusion; acute ischemic stroke; blood-brain barrier; hemorrhagic transformation; reperfusion therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood-Brain Barrier
  • Brain Ischemia* / complications
  • Brain Ischemia* / diagnostic imaging
  • Brain Ischemia* / drug therapy
  • Cerebral Hemorrhage / diagnostic imaging
  • Humans
  • Ischemic Stroke*
  • Male
  • Middle Aged
  • Reperfusion Injury*
  • Stroke* / complications
  • Stroke* / diagnostic imaging
  • Stroke* / therapy
  • Thrombolytic Therapy