Endothelial Function, Inflammation, Thrombosis, and Basal Ganglia Perivascular Spaces in Patients with Stroke

Xin Wang,Francesca M Chappell,Maria Valdes Hernandez,Gordon Lowe,Ann Rumley,Kirsten Shuler,Fergus Doubal,Joanna M Wardlaw

doi:10.1016/j.jstrokecerebrovasdis.2016.08.007

Xin Wang, Francesca M Chappell + Show 6 more

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https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.08.007

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Abstract

Background and ObjectiveRecent studies suggest perivascular spaces are a marker of small vessel disease, blood–brain barrier permeability, and inflammation, but little is known about their risk factors and associations with peripheral blood markers.Materials and MethodsIn prospectively recruited patients with recent minor ischemic stroke, we investigated the influence of age, sex, hypertension, diabetes, and smoking on the severity of perivascular spaces in the basal ganglia seen on T2-weighted magnetic resonance imaging. We assessed plasma markers of endothelial function (von Willebrand factor, intracellular adhesion molecule-1), inflammation (interleukin-6, tumor necrosis factor-alpha, C-reactive protein), and thrombosis (fibrinogen, prothrombin fragments 1 + 2, thrombin–antithrombin complex, tissue plasminogen activator, D-dimer). We used a validated semi-automated method to measure basal ganglia perivascular spaces count and volume. We tested uni- and multivariable associations between blood markers and basal ganglia perivascular spaces count and volume.FindingsIn 100 patients (median age: 67 years, range: 37-92), on adjusted analysis, basal ganglia perivascular spaces count was associated with age (r = .117, P = .003) and hypertension (r = 2.225, P = .013). On multivariable linear regression, adjusted for age, sex, hypertension, smoking and diabetes, reduced von Willebrand factor was associated with increased basal ganglia perivascular spaces count (r = −.025, P = .032).ConclusionThe association of increased basal ganglia perivascular spaces count with reduced von Willebrand factor is novel. As von Willebrand factor may promote cerebral endothelial integrity, insufficient von Willebrand factor is consistent with dysfunctional cerebral endothelium and increased basal ganglia perivascular spaces in cerebral small vessel disease. Quantitative perivascular spaces measurement may increase sensitivity to detect cerebral endothelial dysfunction.

Highlights

Perivascular spaces (PVS), or Virchow–Robin spaces, are pial extensions of the subarachnoid space that surround the arteries, arterioles, veins, and venules as they penetrate the brain parenchyma.[1,2] PVS are an important drainage conduit for soluble and insoluble material through the central nervous system.[3]
PVS are associated with other small vessel disease (SVD) features, such as white matter hyperintensities (WMH), atrophy, microbleeds, lacunes, and recent small subcortical infarcts.[10]
Increasing numbers of PVS were associated with increased blood–brain barrier (BBB) permeability in stroke patients,[11] worse cognitive function in older people,[12] and more WMH in older subjects[13] and in patients with stroke.[7,8]

Summary

Introduction

Perivascular spaces (PVS), or Virchow–Robin spaces, are pial extensions of the subarachnoid space that surround the arteries, arterioles, veins, and venules as they penetrate the brain parenchyma.[1,2] PVS are an important drainage conduit for soluble and insoluble material through the central nervous system.[3]. Recent studies suggest perivascular spaces are a marker of small vessel disease, blood–brain barrier permeability, and inflammation, but little is known about their risk factors and associations with peripheral blood markers. Materials and Methods: In prospectively recruited patients with recent minor ischemic stroke, we investigated the influence of age, sex, hypertension, diabetes, and smoking on the severity of perivascular spaces in the basal ganglia seen on T2weighted magnetic resonance imaging. On multivariable linear regression, adjusted for age, sex, hypertension, smoking and diabetes, reduced von Willebrand factor was associated with increased basal ganglia perivascular spaces count (r = −.025, P = .032). Conclusion: The association of increased basal ganglia perivascular spaces count with reduced von Willebrand factor is novel. As von Willebrand factor may promote cerebral endothelial integrity, insufficient von Willebrand factor is consistent with dysfunctional cerebral endothelium and increased basal ganglia perivascular spaces in cerebral small vessel disease.

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