Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2024 Jan 9;102(1):e207795.
doi: 10.1212/WNL.0000000000207795. Epub 2023 Dec 13.

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

Jonathan G Best  1 , Gareth Ambler  1 , Duncan Wilson  1 , Houwei Du  1 , Keon-Joo Lee  1 , Jae-Sung Lim  1 , Kay Cheong Teo  1 , Henry Mak  1 , Young Dae Kim  1 , Tae-Jin Song  1 , Derya Selcuk Demirelli  1 , Masashi Nishihara  1 , Masaaki Yoshikawa  1 , Marta Kubacka  1 , Annaelle Zietz  1 , Rustam Al-Shahi Salman  1 , Hans Rolf Jäger  1 , Gregory Y H Lip  1 , Leonidas Panos  1 , Martina B Goeldlin  1 , Lee-Anne Slater  1 , Christopher Charles Karayiannis  1 , Thanh G Phan  1 , Maximilian Bellut  1 , Jill Abrigo  1 , Cyrus Cheng  1 , Thomas W Leung  1 , Winnie Chu  1 , Francesca Chappell  1 , Stephen D J Makin  1 , Dianne H K van Dam-Nolen  1 , M Eline Kooi  1 , Sebastian Köhler  1 , Julie Staals  1 , Grégory Kuchcinski  1 , Régis Bordet  1 , Florian Dubost  1 , Joanna M Wardlaw  1 , Yannie O Y Soo  1 , Felix Fluri  1 , Velandai K Srikanth  1 , Simon Jung  1 , Nils Peters  1 , Hideo Hara  1 , Yusuke Yakushiji  1 , Dilek Necioglu Orken  1 , Ji-Hoe Heo  1 , Gary Kui Kai Lau  1 , Hee-Joon Bae  1 , David J Werring  1
Affiliations
Multicenter Study

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

Jonathan G Best et al. Neurology. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

G.Y.H. Lip reports consultant and speaker fee for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo (no fees are received personally); L.D. Panos reports no disclosures relevant to the manuscript; M.B. Goeldlin reports grants from Bangerter-Rhyner-Foundation/Swiss Academy of Medical Sciences, Swiss Stroke Society, European Stroke Organisation, and Mittelbauvereinigung der Universität Bern, Pfizer, outside the submitted work; L.A. Slater reports no disclosures relevant to the manuscript; C. Karayiannis reports no disclosures relevant to the manuscript; T. Phan reports no disclosures relevant to the manuscript; M. Bellut reports no disclosures relevant to the manuscript; J. Abrigo reports no disclosures relevant to the manuscript; C. Cheng reports no disclosures relevant to the manuscript; T. Leung reports no disclosures relevant to the manuscript; W. Chu reports no disclosures relevant to the manuscript; F. Chappell reports no disclosures relevant to the manuscript; S. Makin reports no disclosures relevant to the manuscript; D.H.K. van Dam-Nolen reports no disclosures relevant to the manuscript; M.E. Kooi reports no disclosures relevant to the manuscript; S. Köhler reports no disclosures relevant to the manuscript; J. Staals reports no disclosures relevant to the manuscript; G. Kuchcinski has received funding from the French Society of Neuroradiology (SFNR) and the French Society of Radiology (SFR); R. Bordet reports no disclosures relevant to the manuscript; F. Dubost reports no disclosures relevant to the manuscript; J. Wardlaw is supported by the UK Dementia Research Institute; the MSS2 study was funded by Wellcome Trust and Row Fogo Charitable Trust; D.J. Werring reports personal fees from Bayer, Alnylam, and Portola outside the submitted work; J.G. Best, G. Ambler, D. Wilson, H. Du, K.J. Lee, J.S. Lim, K.C. Teo, H.K.F. Mak, Y.D. Kim, T.J. Song, D.S. Demirelli, M. Nishihara, M. Yoshikawa, M. Kubacka, A. Zietz, R. Al-Shahi Salman, H.R. Jäger;Y. Soo, F. Fluri, V. Srikanth, S. Jung, N. Peters, H. Hara, Y. Yakushiji, D.N. Orken, J.H. Heo, K.K. Lau, H.J. Bae reports no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Study Flowchart
Figure 2
Figure 2. Cumulative Incidence of Ischemic Stroke According to BGPVS Burden
BGPVS = basal ganglia enlarged perivascular spaces.
See this image and copyright information in PMC

References

    1. Wardlaw JM, Smith EE, Biessels GJ, et al. ; STandards for ReportIng Vascular changes on nEuroimaging STRIVE v1. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822-838. doi:10.1016/S1474-4422(13)70124-8 - DOI - PMC - PubMed
    1. Nedergaard M, Goldman SA. Glymphatic failure as a final common pathway to dementia. Science. 2020;370(6512):50-56. doi:10.1126/science.abb8739 - DOI - PMC - PubMed
    1. Rouhl RPW, van Oostenbrugge RJ, Knottnerus ILH, Staals JEA, Lodder J. Virchow-Robin spaces relate to cerebral small vessel disease severity. J Neurol. 2008;255(5):692-696. doi:10.1007/s00415-008-0777-y - DOI - PubMed
    1. Doubal FN, MacLullich AMJ, Ferguson KJ, Dennis MS, Wardlaw JM. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke. 2010;41(3):450-454. doi:10.1161/STROKEAHA.109.564914 - DOI - PubMed
    1. Hurford R, Charidimou A, Fox Z, Cipolotti L, Jager R, Werring DJ. MRI-visible perivascular spaces: relationship to cognition and small vessel disease MRI markers in ischaemic stroke and TIA. J Neurol Neurosurg Psychiatry. 2014;85(5):522-525. doi:10.1136/jnnp-2013-305815 - DOI - PMC - PubMed

Publication types