title: Blood-brain barrier permeability and long-term clinical and imaging outcomes in cerebral small vessel disease.
abstract: OBJECTIVE
  Increased blood-brain barrier (BBB) permeability occurs in cerebral small vessel disease. It is not known if BBB changes predate progression of small vessel disease.
  
  
  METHODS
  We followed-up patients with nondisabling lacunar or cortical stroke and BBB permeability magnetic resonance imaging after their original stroke. Approximately 3 years later, we assessed functional outcome (Oxford Handicap Score, poor outcome defined as 3-6), recurrent neurological events, and white matter hyperintensity (WMH) progression on magnetic resonance imaging.
  
  
  RESULTS
  Among 70 patients with mean age of 68 (SD ± 11) years, median time to clinical follow-up was 39 months (interquartile range, 30-45) and median Oxford Handicap Score was 2 (interquartile range, 1-3); poor functional outcome was associated with higher baseline WMH score (P<0.001) and increased basal ganglia BBB permeability (P=0.046). Among 48 patients with follow-up magnetic resonance imaging, WMH progression at follow-up was associated with baseline WMH (ANCOVA P<0.0001) and age (ANCOVA P=0.032).
  
  
  CONCLUSIONS
  Further long-term studies to evaluate the role of BBB dysfunction in progression of small vessel disease are required in studies that are large enough to account for key prognostic influences such as baseline WMH and age.
authors.affiliation: Brain Research Imaging Center, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, United Kingdom. Joanna.wardlaw@ed.ac.uk
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.forename: Fergus N
authors.initials: FN
authors.lastname: Doubal
authors.forename: Maria
authors.initials: M
authors.lastname: Valdes-Hernandez
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Chappell
authors.forename: Kirsten
authors.initials: K
authors.lastname: Shuler
authors.forename: Paul A
authors.initials: PA
authors.lastname: Armitage
authors.forename: Trevor C
authors.initials: TC
authors.lastname: Carpenter
authors.forename: Martin S
authors.initials: MS
authors.lastname: Dennis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology*; D059345:Cerebral Small Vessel Diseases / Q000175:diagnosis* / Q000503:physiopathology* / Q000628:therapy; D038524:Diffusion Magnetic Resonance Imaging / Q000639:trends*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome