White Matter Hyperintensity-Associated Blood-Brain Barrier Disruption and Vascular Risk Factors

Overview

Journal J Stroke Cerebrovasc Dis

Specialties Cardiology & Vascular Diseases
Neurology

Date 2017 Nov 5

PMID 29100854

Citations 16

Authors

Nidhi Gupta

Alexis N Simpkins

Emi Hitomi

Christian Dias

Richard Leigh

Affiliations

Soon will be listed here.

Abstract

Background: White matter hyperintensities (WMH), the hallmark of vascular cognitive impairment, are associated with vascular risk factors (VRF). WMH can also be associated with blood-brain barrier (BBB) disruption. The purpose of this study was to look for associations between VRF and BBB disruption in stroke patients with WMH.

Methods: Magnetic resonance images of stroke patients were reviewed for the presence of WMH. Blood-brain permeability images were retrospectively generated. The degree of BBB permeability was compared with the presence of VRF using logistic regression. Patterns and extent of WMH were classified using Fazekas scores.

Results: Sixty-five patients were included in this study. None of the VRF tested were associated with an increase in BBB disruption. Hypertension was significantly associated with less BBB disruption (P = .04). Nonhypertensive patients in our study had a different pattern of WMH than hypertensive patients, with less involvement of the periventricular white matter.

Conclusions: We found that in stroke patients with WMH, those with hypertension had less BBB disruption and greater involvement of the periventricular white matter when compared with patients who did not have a history of hypertension. Further investigation is needed to determine if the development of WMH in stroke patients with a history of hypertension has a different pathophysiology from patients who develop WMH in the absence of hypertension.

Citing Articles

Asymmetric U-shaped relationship between blood glucose and white matter lesions: results of a cross-sectional study.

Liu D, Li N, Zhu Y, Chen Q, Feng J BMC Neurol. 2025; 25(1):65.

PMID: 39953442 PMC: 11827292. DOI: 10.1186/s12883-025-04077-9.

Convergence of endothelial dysfunction, inflammation and glucocorticoid resistance in depression-related cardiovascular diseases.

Hage Z, Madeira M, Koliatsis D, Tsirka S BMC Immunol. 2024; 25(1):61.

PMID: 39333855 PMC: 11428380. DOI: 10.1186/s12865-024-00653-9.

Carotid artery stenosis is related to cerebral small vessel disease magnetic resonance imaging burden.

Stoisavljevic S, Zdraljevic M, Radojicic A, Pavlovic A, Mijajlovic M Heliyon. 2024; 10(16):e36052.

PMID: 39224254 PMC: 11367513. DOI: 10.1016/j.heliyon.2024.e36052.

Association of pulse pressure and mean blood pressure to frailty, sarcopenia, and cognitive dysfunction in elderly outpatients with history of hypertension.

Ishikawa J, Toba A, Futami S, Saito Y, Tamura Y, Araki A Hypertens Res. 2024; 47(8):2029-2040.

PMID: 38671218 DOI: 10.1038/s41440-024-01684-w.

Nonhypertensive White Matter Hyperintensities in Stroke: Risk Factors, Neuroimaging Characteristics, and Prognosis.

Lim J, Lee K, Kim B, Ryu W, Chung J, Gwak D J Am Heart Assoc. 2023; 12(23):e030515.

PMID: 38014679 PMC: 10727348. DOI: 10.1161/JAHA.123.030515.

References

Simpkins A, Dias C, Leigh R . Identification of Reversible Disruption of the Human Blood-Brain Barrier Following Acute Ischemia. Stroke. 2016; 47(9):2405-8. PMC: 5111547. DOI: 10.1161/STROKEAHA.116.013805. View

Rosenberg G, Bjerke M, Wallin A . Multimodal markers of inflammation in the subcortical ischemic vascular disease type of vascular cognitive impairment. Stroke. 2014; 45(5):1531-8. PMC: 4025998. DOI: 10.1161/STROKEAHA.113.004534. View

de Groot J, de Leeuw F, Oudkerk M, van Gijn J, Hofman A, Jolles J . Periventricular cerebral white matter lesions predict rate of cognitive decline. Ann Neurol. 2002; 52(3):335-41. DOI: 10.1002/ana.10294. View

Kluge A, Lukas M, Toth V, Pyka T, Zimmer C, Preibisch C . Analysis of three leakage-correction methods for DSC-based measurement of relative cerebral blood volume with respect to heterogeneity in human gliomas. Magn Reson Imaging. 2015; 34(4):410-21. DOI: 10.1016/j.mri.2015.12.015. View

Leigh R, Jen S, Varma D, Hillis A, Barker P . Arrival time correction for dynamic susceptibility contrast MR permeability imaging in stroke patients. PLoS One. 2013; 7(12):e52656. PMC: 3527589. DOI: 10.1371/journal.pone.0052656. View

Fazekas F, Chawluk J, Alavi A, Hurtig H, Zimmerman R . MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol. 1987; 149(2):351-6. DOI: 10.2214/ajr.149.2.351. View

Leigh R, Christensen S, Campbell B, Marks M, Albers G, Lansberg M . Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology. 2016; 87(3):263-9. PMC: 4955280. DOI: 10.1212/WNL.0000000000002862. View

Spilt A, Goekoop R, Westendorp R, Blauw G, de Craen A, van Buchem M . Not all age-related white matter hyperintensities are the same: a magnetization transfer imaging study. AJNR Am J Neuroradiol. 2006; 27(9):1964-8. PMC: 7977888. View

Gottesman R, Coresh J, Catellier D, Sharrett A, Rose K, Coker L . Blood pressure and white-matter disease progression in a biethnic cohort: Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2009; 41(1):3-8. PMC: 2803313. DOI: 10.1161/STROKEAHA.109.566992. View

10.

Lechner H, Schmidt R, Bertha G, Justich E, Offenbacher H, Schneider G . Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals. Stroke. 1988; 19(2):263-5. DOI: 10.1161/01.str.19.2.263. View

11.

Duering M, Csanadi E, Gesierich B, Jouvent E, Herve D, Seiler S . Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease. Brain. 2013; 136(Pt 9):2717-26. DOI: 10.1093/brain/awt184. View

12.

Schulz U, Gruter B, Briley D, Rothwell P . Leukoaraiosis and increased cerebral susceptibility to ischemia: lack of confounding by carotid disease. J Am Heart Assoc. 2013; 2(4):e000261. PMC: 3828783. DOI: 10.1161/JAHA.113.000261. View

13.

Wardlaw J, Doubal F, Armitage P, Chappell F, Carpenter T, Munoz Maniega S . Lacunar stroke is associated with diffuse blood-brain barrier dysfunction. Ann Neurol. 2009; 65(2):194-202. DOI: 10.1002/ana.21549. View

14.

Wardlaw J, Allerhand M, Doubal F, Hernandez M, Morris Z, Gow A . Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities. Neurology. 2014; 82(15):1331-8. PMC: 4001185. DOI: 10.1212/WNL.0000000000000312. View

15.

Wardlaw J, Doubal F, Valdes-Hernandez M, Wang X, Chappell F, Shuler K . Blood-brain barrier permeability and long-term clinical and imaging outcomes in cerebral small vessel disease. Stroke. 2012; 44(2):525-7. PMC: 3843346. DOI: 10.1161/STROKEAHA.112.669994. View

16.

Farrall A, Wardlaw J . Blood-brain barrier: ageing and microvascular disease--systematic review and meta-analysis. Neurobiol Aging. 2007; 30(3):337-52. DOI: 10.1016/j.neurobiolaging.2007.07.015. View

17.

Rosenberg G, Wallin A, Wardlaw J, Markus H, Montaner J, Wolfson L . Consensus statement for diagnosis of subcortical small vessel disease. J Cereb Blood Flow Metab. 2015; 36(1):6-25. PMC: 4758552. DOI: 10.1038/jcbfm.2015.172. View

18.

Topakian R, Barrick T, Howe F, Markus H . Blood-brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis. J Neurol Neurosurg Psychiatry. 2009; 81(2):192-7. DOI: 10.1136/jnnp.2009.172072. View

19.

Schmidt R, Fazekas F, Reinhart B, Kapeller P, Fazekas G, Offenbacher H . Estrogen replacement therapy in older women: a neuropsychological and brain MRI study. J Am Geriatr Soc. 1996; 44(11):1307-13. DOI: 10.1111/j.1532-5415.1996.tb01400.x. View

20.

Arba F, Leigh R, Inzitari D, Warach S, Luby M, Lees K . Blood-brain barrier leakage increases with small vessel disease in acute ischemic stroke. Neurology. 2017; 89(21):2143-2150. PMC: 5696647. DOI: 10.1212/WNL.0000000000004677. View