Cerebral perivascular spaces as an important diagnostic marker of cerebral small vessel disease and brain pathology

S. P. Moskovko, S. R. Bartiuk

DOI: http://dx.doi.org/10.12775/JEHS.2020.10.05.020


Objective. To assess the association of enlarged perivascular spaces (EPVS) with cerebral small vessel disease (CSVD), some basic metabolic tests, brain atrophy and clinical outcome after territorial stroke.

Methods. 90 patients with acute stroke (<24 hours of onset) were recruited. Modified Rankin scale and Bartel index where used to assess stroke outcome. Cerebral MRI was performed to assess white matter lesions (WML), lacunes, cerebral atrophy and EPVS in basal ganglia and cortical-subcortical area with a validated four-point visual rating scale. Total CSVD burden was calculated with summation of lacunes, WML and EPVS with a validated scale. Spearmen correlation and logistic regression were used to identified association between EPVS, total CSVD burden, CSVD features and some basic metabolic tests (creatinine, urea, cholesterol, bilirubin, fibrinogen, erythrocyte sedimentation rate).

Results. There was a very strong correlation between EPVS and total CSVD burden (r = 0.9, p <0.000) and with Fazekas score scale (r = 0.9, p <0.000). A strong correlation was found between EPVS and global cortical atrophy (r = 0.7, p <0.000), and a moderate correlation with presence of lacunes (r = 0.4, p <0.05). EPVS in basal ganglia had a significant correlation with the degree of extracranial carotid stenosis (r = 0.4, p <0.05). The severity of EPVS was associated with a more severe neurological deficit on the NIHSS scale (r = 0.5, p <0.05) and an increased degree of disability by Bartel's index (r = 0.5, p <0.05) in patients on discharge. Creatinine was associated with CSVD features.

Conclusions. EPVS is highly associated with total CSVD burden and others its features as well as with stroke outcome. EPVS in different brain regions may lead to the distinguish of two main type of CSVD – hypertensive arteriolosclerosis and beta-amyloid angiopathy.


perivascular spaces; cerebral small vessel disease; stroke; MRI

Full Text:



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; 41:450–4.

Ohba H, Pearce LA, Potter GM, Benavente OR. Enlarged perivascular spaces in lacunar stroke patients. The Secondary Prevention of Small Subcortical Strokes (SPS3) Trial. Stroke 2012; 43:A151.

Gutierrez J, Elkind MS, Cheung K, et al. Pulsatile and steady components of blood pressure and subclinical cerebrovascular disease: the Northern Manhattan Study. J Hypertens. 2015.

Mestre H, Kostrikov S, Mehta RI, Nedergaard M. Perivascular spaces, glymphatic dysfunction, and small vessel disease. Clin Sci 2017;131:2257–2274.

Kwee RM, Kwee TC. Virchow-Robin spaces at MR imaging. Radiographics 2007;27: 1071–1086.

Bucchieri F, Farina F, Zummo G, Cappello F. Lymphatic vessels of the dura mater: a new discovery? J Anat 2015;227:702–703.

Sweeney MD, Sagare AP, Zlokovic BV. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 2018;14:133–150.

Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med 2012;4:147ra111.

Bakker EN, Bacskai BJ, Arbel-Ornath M, Aldea R, Bedussi B, Morris AW, Weller RO, Carare RO. Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases. Cell Mol Neurobiol 2016;36:181–194.

Abbott NJ. Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem int 2004;45:545–52.

Kapasi A, DeCarli C, Schneider JA. Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathol 2017;134:171–186.

Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010;9:689–701.

Berezuk C, Ramirez J, Gao F, Scott CJ, Huroy M, Swartz RH, Murray BJ, Black SE, Boulos MI. Virchow-Robin spaces: correlations with polysomnography-derived sleep parameters. Sleep 2015;38:853–858.

Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013;12:483–497.

Awad IA, Johnson PC, Spetzler RF, et al. Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. II. Postmortem pathological correlations. Stroke. 1986; 17:1090– 1097.

Aribisala BS, Wiseman S, Morris Z, Valdes-Hernandez MC, Royle NA, Maniega SM, Gow AJ, Corley J, Bastin ME, Starr J, Deary IJ, Wardlaw JM. Circulating inflammatory markers are associated with magnetic resonance imaging-visible perivascular spaces but not directly with white matter hyperintensities. Stroke 2014;45:605–607.

Abbott NJ. Inflammatory mediators and modulation of blood-brain barrier perme- ability. Cell Mol Neurobiol 2000;20:131–147.

Kress BT, Iliff JJ, Xia M, Wang M, Wei HS, Zeppenfeld D, Xie L, Kang H, Xu Q, Liew JA, Plog BA, Ding F, Deane R, Nedergaard M. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol 2014;76:845–861.

Potter GM, Chappell FM, Morris Z, Wardlaw JM. Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability. Cerebrovasc Dis. (2015) 39:224– 31.

Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. (2013) 12:822–38.

Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol. (1987) 149:351–6.

Klarenbeek P, van Oostenbrugge RJ, Rouhl RP, Knottnerus IL, Staals J. Ambulatory blood pressure in patients with lacunar stroke: association with total MRI burden of cerebral small vessel disease. Stroke. (2013) 44:2995– 9.

Scheltens P, Launer L, Barkhof F et-al. Visual assessment of medial temporal lobe atrophy on magnetic resonance imaging: Interobserver reliability. J Neurol. 1995;242 (9): 557-560.

Lau KK, Li L, Schulz U, Simoni M, Chan KH, Ho SL, et al. Total small vessel disease score and risk of recurrent stroke: validation in 2 large cohorts. Neurology. (2017) 88:2260–7.

Staals J, Makin SD, Doubal FN, Dennis MS, Wardlaw JM. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology. (2014) 83:1228–34.

Liang Y, Chen YK, Deng M, Mok VCT, Wang DF, Ungvari GS, et al. Association of cerebral small vessel disease burden and health-related quality of life after acute ischemic stroke. Front Aging Neurosci. (2017) 9:372.

Song TJ, Kim J, Song D, Yoo J, Lee HS, Kim YJ, et al. Total cerebral small-vessel disease score is associated with mortality during follow-up after acute ischemic stroke. J Clin Neurol. (2017) 13:187– 95.

Vinoo Jacob, A.S. Krishna Kumar. “CT Assessment of Brain Ventricular Size Based On Age And Sex: A Study of 112 Cases”. Journal of Evolution of Medical And Dental Sciences 2013; Vol2, Issue 50, December 16; Page: 9842-9855.

Ambarki K, Israelsson H, Wåhlin A, Birgander R, Eklund A, Malm J. Brain ventricular size in healthy elderly: Comparison between Evans index and volume measurement. Neurosurgery. 2010;67:94–9.

Alexandra M. Nicholson and Adriana Ferreira. Cholesterol and Neuronal Susceptibility to Beta- Amyloid Toxicity. Cogn Sci (Hauppauge). 2010 July 1; 5(1): 35–56.

Wuerfel J, Haertle M, Waiczies H, Tysiak E, Bechmann I, Wernecke KD, Zipp F, Paul F. Perivascular spaces–MRI marker of inflammatory activity in the brain? Brain 2008;131:2332–2340.

Kazunori Toyoda. Cerebral Small Vessel Disease and Chronic Kidney Disease. J Stroke. 2015;17(1):31–37.

Ott BR, Jones RN, Daiello LA, de la Monte SM, Stopa EG, Johanson CE, Denby C and Grammas P (2018) Blood-Cerebrospinal Fluid Barrier Gradients in Mild Cognitive Impairment and Alzheimer’s Disease: Relationship to Inflammatory Cytokines and Chemokines. Front. Aging Neurosci. 10:245.

Ezekiel F, Chao L, Kornak J, et al. Comparisons between global and focal brain atrophy rates in normal aging and Alzheimer disease: Boundary Shift Integral versus tracing of the entorhinal cortex and hippocampus. Alzheimer Disease and Associated Disorders. 2004 Oct-Dec;18(4):196-201.

Kandel BM, Avants BB, Gee JC, et al. White matter hyperintensities are more highly associated with preclinical Alzheimer's disease than imaging and cognitive markers of neurodegeneration. Alzheimers Dement (Amst). 2016;4:18–27. Published 2016 Apr 7.

Steven Sourbron, Michael Ingrisch, Axel Siefert, Maximilian Reiser, Karin Herrmann. Quantification of cerebral blood flow, cerebral blood volume, and blood–brain‐barrier leakage with DCE‐MRI. Magnetic Resonance in Medicine 62:205–217 (2009).

Adams, H. P., Bendixen, B. H., Kappelle, L. J., Biller, J., Love, B. B., rd Gordon, D. L. & Marsh, E. E. 3. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24:35–41.

Meyer BC, Lyden PD. The modified National Institutes of Health Stroke Scale: its time has come. Int J Stroke. 2009;4(4):267–273.

Monroe T, Carter M. Using the Folstein Mini Mental State Exam (MMSE) to explore methodological issues in cognitive aging research. Eur J Ageing. 2012;9(3):265–274. Published 2012 Jun 15.

Broderick JP, Adeoye O, Elm J. Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials. Stroke. 2017;48(7):2007–2012.

Rhodius-Meester HFM, Benedictus MR, Wattjes MP, et al. MRI Visual Ratings of Brain Atrophy and White Matter Hyperintensities across the Spectrum of Cognitive Decline Are Differently Affected by Age and Diagnosis. Front Aging Neurosci. 2017;9:117. Published 2017 May 9.

Zhang ET, Inman CB, Weller RO. Interrelationships of the pia mater and the perivascular (Virchow- Robin) spaces in the human cerebrum. J Anat. 1990; 170:111–123.

Fleury J, Gherardi R, Poirier J. The perivascular spaces of the central nervous system. Histophysiological data. Ann Pathol. 1984; 4:245– 247.

Pollock H, Hutchings M, Weller RO, et al. Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes. J Anat.

Lesage SR, Mosley TH, Wong TY, Szklo M, Knopman D, Catellier DJ, et al. Retinal microvascular abnormalities and cognitive decline: the ARIC 14-year follow-up study. Neurology 2009;73: 862-868.

Yaffe K, Ackerson L, Hoang TD, Go AS, Maguire MG, Ying GS, et al. Retinopathy and cognitive impairment in adults with CKD. Am J Kidney Dis 2013;61:219-227.

Nagaoka T, Yoshida A. Relationship between retinal blood flow and renal function in patients with type 2 diabetes and chronic kidney disease. Diabetes Care 2013;36:957-961.

Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014


POL-index 2011 - 2014


BASE 2011 - 2014




Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska, EuroPub database, NLM Catalog Result - NCBI, BASE, Russian Sciences Index, Arianta.



US NLM = 101679844

101679844 - NLM Catalog Result - NCBI


Find a library that holds this journal: http://worldcat.org/issn/23918306


PBN Poland






Redaction, Publisher and Editorial Office

Publisher and Editorial Office
Department of Physical Culture,
Faculty of Earth Sciences and Spatial Management,
Nicolaus Copernicus University in Toruń, Poland
Address: Str. Lwowska 1, 87-100 Toruń, Poland

  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at https://dbh.nsd.uib.no/publiseringskanaler/erihplus/periodical/info?id=485984

Indexed in Index Copernicus Journals Master List.


ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48


Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (https://pbn.nauka.gov.pl/journals/36616)

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ) http://elibrary.ru/contents.asp?titleid=37467

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski


Partnerzy platformy czasopism