title: Blood-brain barrier alterations in both focal and diffuse abnormalities on postmortem MRI in multiple sclerosis.
abstract: Postmortem MRI-guided tissue sampling significantly enhances the yield of MS lesions in autopsy material, but so far it is unknown whether abnormalities concur with blood-brain barrier alterations. Here we sampled MS lesions with focal and diffuse abnormalities (diffusely abnormal white matter; DAWM) on MRI; both were coupled to the presence of MS lesions upon neuropathological examination. Extravascular distribution of fibrinogen, indicating BBB disturbance, was observed in so-called (p)reactive lesions that reflect discrete areas of microglial activation without demyelination within an otherwise normal appearing white matter. Leakage became more extensive in active demyelinating MS lesions to chronic inactive lesions. An enlargement of the perivascular (Virchow-Robin) space containing infiltrated leukocytes was associated with both DAWM and focal abnormalities on postmortem MRI. This study shows for the first time that in MS brain changes in the vasculature take place not only in focal lesions but also in DAWM as detected by postmortem MRI.
authors.affiliation: Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Catharina M P
authors.initials: CM
authors.lastname: Vos
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
authors.forename: Lisette
authors.initials: L
authors.lastname: Montagne
authors.forename: Elise S
authors.initials: ES
authors.lastname: van Haastert
authors.forename: Lars
authors.initials: L
authors.lastname: Bö
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000098:blood supply* / Q000473:pathology* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000473:pathology* / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007962:Leukocytes / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011180:Postmortem Changes
chemical_list: D005340:Fibrinogen