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ORIGINAL RESEARCH article

Front. Stroke
Sec. Mechanisms, Models, and Biomarkers of Stroke
Volume 3 - 2024 | doi: 10.3389/fstro.2024.1510359
This article is part of the Research Topic Post-Stroke Cognitive Decline and Dementia: Unraveling Mechanisms, Models, and Biomarkers View all 3 articles

Blood Brain Barrier Disruption Mediates the Association Between Cerebral Small Vessel Disease and Clinical Outcome after Stroke: A Secondary Analysis of the Lesion Evolution in Stroke and Ischemia on Neuroimaging (LESION) Study

Provisionally accepted
  • 1 University of California, Los Angeles, Los Angeles, California, United States
  • 2 National Institute of Neurological Disorders and Stroke (NIH), Bethesda, Maryland, United States

The final, formatted version of the article will be published soon.

    Introduction: White matter hyperintensities (WMH) in patients presenting with acute ischemic stroke are associated with worse clinical outcomes, but the mechanisms underlying this association are unclear. The purpose of this study was to determine whether blood-brain barrier (BBB) disruption, detected as the hyperintense acute reperfusion marker (HARM) on post-gadolinium follow-up FLAIR MRI, is associated with WMH and mediates the association between WMH and stroke outcomes. Methods: This is a secondary analysis of the LESION study, where patients with suspected acute ischemic stroke who were candidates for acute stroke intervention or had a baseline NIHSS ≥ 4 underwent serial multimodal MRI within 24 hours of last-known-well time, and again at 2 or 24 hours. WMH were visually graded on baseline FLAIR for presence and severity (minor or moderate-severe). HARM was evaluated on post-gadolinium FLAIR for presence and severity (minor, severe focal or severe diffuse). Using binomial and multinomial logistic regression, we tested whether WMH grade was associated with presence or severity of HARM, covarying for demographics, vascular risk factors, and stroke characteristics in sequential models. Finally, we used structural equation models to test the mediation effects of severe HARM on the association between WMH and stroke outcomes, including discharge NIHSS, hemorrhagic transformation, and 90-day modified Rankin scale. Results: For 213 stroke patients (mean age 70 years, 54% female), higher WMH grade was associated with increased risk for severe diffuse HARM (OR:3.37, 95% CI: 1.45-7.81), although not after adjusting for vascular risk factors or stroke characteristics. In our univariate model, severe HARM had a partial mediating effect between WMH and discharge NIHSS, explaining 23% of the association. Discussion: These findings suggest a possible association between severe diffuse HARM and WMH severity. The relationship between WMH severity and early stroke outcome may be mediated by blood-brain barrier disruption.

    Keywords: harm, white matter hyperintensities, Cerebral small vessel disease, ischemic stroke, post-stroke outcome

    Received: 12 Oct 2024; Accepted: 14 Nov 2024.

    Copyright: © 2024 Okine, Kern, Luby, Latour and Gottesman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Rebecca F Gottesman, National Institute of Neurological Disorders and Stroke (NIH), Bethesda, 20892- 9531, Maryland, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.