title: Blood-brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis.
abstract: OBJECTIVE
  The pathogenesis of cerebral small-vessel disease (SVD) is incompletely understood. Endothelial dysfunction has been implicated and may result in increased blood-brain barrier (BBB) permeability with leakage of blood constituents into the vessel wall and white matter. We used contrast-enhanced MRI to determine whether there was any evidence for BBB permeability in the white matter of patients with SVD, and whether this was present not only in areas of leucoaraiosis (white-matter lesions) but also in normal-appearing white matter (NAWM).
  
  
  METHODS
  Subjects underwent T1 volumetric MRI before and after bolus injection of contrast. Scanning was continued for 30 min postinjection to determine the contrast-enhancement time course. The mean signal intensity change was plotted against time to calculate the area under the curve values, a parameter related to BBB permeability. Automated brain segmentation and regions of interest analysis were performed to determine 'permeability' in different brain compartments.
  
  
  RESULTS
  Compared with controls (n=15), the SVD patient group (n=24) had signal changes consistent with increased BBB permeability in NAWM (p=0.033). Multivariate regression analyses identified leucoaraiosis grade as an independent predictor of these permeability related signal changes in NAWM after adjustment for age, gender, weight, brain volume, area under the curve in the internal carotid arteries and cardiovascular risk factors.
  
  
  CONCLUSIONS
  This study provides evidence for increased BBB permeability in SVD, and this is particularly seen in SVD with leucoaraiosis. Its presence in NAWM would be consistent with it playing a causal role in disease pathophysiology.
authors.affiliation: Centre for Clinical Neuroscience, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: R
authors.initials: R
authors.lastname: Topakian
authors.forename: T R
authors.initials: TR
authors.lastname: Barrick
authors.forename: F A
authors.initials: FA
authors.lastname: Howe
authors.forename: H S
authors.initials: HS
authors.lastname: Markus
mesh_terms: D000368:Aged; D001284:Atrophy / Q000473:pathology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D020520:Brain Infarction / Q000134:cerebrospinal fluid / Q000473:pathology*; D002199:Capillary Permeability / Q000502:physiology*; D002343:Carotid Artery, Internal / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D049292:Leukoaraiosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male