title: White matter perivascular spaces: an MRI marker in pathology-proven cerebral amyloid angiopathy?
abstract: OBJECTIVE
  We investigated whether severe, MRI-visible perivascular spaces (PVS) in the cerebral hemisphere white matter (centrum semiovale) are more common in patients with pathology-proven cerebral amyloid angiopathy (CAA) than in those with pathology-proven non-CAA-related intracerebral hemorrhage (ICH).
  
  
  METHODS
  Using a validated 4-point scale on axial T2-weighted MRI, we compared PVS in patients with pathology-proven CAA to PVS in those with spontaneous ICH but no histopathologic evidence of CAA. In a preliminary analysis restricted to patients with T2*-weighted gradient-recalled echo MRI, we also investigated whether including severe centrum semiovale PVS increases the sensitivity of existing diagnostic criteria for probable CAA.
  
  
  RESULTS
  Fourteen patients with CAA and 10 patients with non-CAA-related ICH were included. Eight of the patients with CAA were admitted for symptomatic, spontaneous lobar ICH, 1 because of ischemic stroke, 1 with transient focal neurologic episodes, and 4 due to cognitive decline. Severe (>20) centrum semiovale PVS were more frequent in patients with CAA compared to controls (12/14 [85.7%; 95% confidence interval (CI): 57.2%-98.2%] vs 0/10 [1-sided 95% CI: 0%-30.8%], p < 0.0005); this was robust to adjustment for age. The original Boston criteria for probable CAA showed a sensitivity of 76.9% (95% CI: 46.2%-95%), which increased to 92.3% (95% CI: 64%-99.8%), without loss of specificity, after including severe centrum semiovale PVS.
  
  
  CONCLUSIONS
  Severe centrum semiovale PVS on MRI may be a promising new neuroimaging marker for the in vivo diagnosis of CAA. However, our findings are preliminary and require confirmation and external validation in larger cohorts of pathology-proven CAA.
authors.affiliation: From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
authors.forename: Andreas
authors.initials: A
authors.lastname: Charidimou
authors.forename: Zane
authors.initials: Z
authors.lastname: Jaunmuktane
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Baron
authors.forename: Matthew
authors.initials: M
authors.lastname: Burnell
authors.forename: Pascale
authors.initials: P
authors.lastname: Varlet
authors.forename: Andre
authors.initials: A
authors.lastname: Peeters
authors.forename: John
authors.initials: J
authors.lastname: Xuereb
authors.forename: Rolf
authors.initials: R
authors.lastname: Jäger
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
authors.forename: David J
authors.initials: DJ
authors.lastname: Werring
mesh_terms: D000368:Aged; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology*; D045604:Extracellular Fluid; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D012189:Retrospective Studies