title: Endothelial Function, Inflammation, Thrombosis, and Basal Ganglia Perivascular Spaces in Patients with Stroke.
abstract: OBJECTIVE
  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.
  
  
  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 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.
  
  
  RESULTS
  In 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).
  
  
  CONCLUSIONS
  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. Quantitative perivascular spaces measurement may increase sensitivity to detect cerebral endothelial dysfunction.
authors: Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh, UK.
authors: Xin
authors: X
authors: Wang
authors: Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh, UK.
authors: Francesca M
authors: FM
authors: Chappell
authors: Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh, UK.
authors: Maria
authors: M
authors: Valdes Hernandez
authors: Institute of Cardiovascular and Medical Sciences, Royal Infirmary, University of Glasgow, Glasgow, UK.
authors: Gordon
authors: G
authors: Lowe
authors: Institute of Cardiovascular and Medical Sciences, Royal Infirmary, University of Glasgow, Glasgow, UK.
authors: Ann
authors: A
authors: Rumley
authors: Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh, UK.
authors: Kirsten
authors: K
authors: Shuler
authors: Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh, UK; NHS Lothian, Edinburgh, UK.
authors: Fergus
authors: F
authors: Doubal
authors: Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh, UK. Electronic address: joanna.wardlaw@ed.ac.uk.
authors: Joanna M
authors: JM
authors: Wardlaw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000098:blood supply* / Q000000981:diagnostic imaging; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D059345:Cerebral Small Vessel Diseases / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D038524:Diffusion Magnetic Resonance Imaging; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D020767:Intracranial Thrombosis / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D014841:von Willebrand Factor
keywords: Endothelial function; perivascular spaces; small vessel disease; stroke