Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

Jonathan G. Best, Gareth Ambler, Duncan Wilson, Houwei Du, Keon Joo Lee, Jae Sung Lim, Kay Cheong Teo, Henry Mak, Young Dae Kim, Tae Jin Song, Derya Selcuk Demirelli, Masashi Nishihara, Masaaki Yoshikawa, Marta Kubacka, Annaelle Zietz, Rustam Al-Shahi Salman, Hans Rolf Jäger, Gregory Y.H. Lip, Leonidas Panos, Martina B. GoeldlinLee Anne Slater, Christopher Charles Karayiannis, Thanh G. Phan, Maximilian Bellut, Jill Abrigo, Cyrus Cheng, Thomas W. Leung, Winnie Chu, Francesca Chappell, Stephen D.J. Makin, Dianne H.K. Van Dam-Nolen, M. Eline Kooi, Sebastian Köhler, Julie Staals, Grégory Kuchcinski, Régis Bordet, Florian Dubost, Joanna M. Wardlaw, Yannie O.Y. Soo, Felix Fluri, Velandai K. Srikanth, Simon Jung, Nils Peters, Hideo Hara, Yusuke Yakushiji, Dilek Necioglu Orken, Ji Hoe Heo, Gary Kui Kai Lau, Hee Joon Bae, David J. Werring

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Background and Objectives: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. Methods: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. Results: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. Discussion: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

Original languageEnglish
Article numbere207795
Issue number1
StatePublished - 9 Jan 2024

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© 2023 American Academy of Neurology.


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