title: Extensive hippocampal demyelination in multiple sclerosis.
abstract: Memory impairment is especially prominent within the spectrum of cognitive deficits in multiple sclerosis (MS), and a crucial role for hippocampal pathology may therefore be expected in this disease. This study is the first to systematically assess hippocampal demyelination in MS. Hippocampal tissue samples of 19 chronic MS cases and 7 controls with non-neurologic disease were stained immunohistochemically for myelin proteolipid protein. Subsequently, number, location, and size of demyelinated lesions were assessed. Furthermore, the specimens were stained for HLA-DR to investigate microglia/macrophage activity. An unexpectedly high number of lesions (n = 37) was found in 15 of the 19 MS cases. Mixed intrahippocampal-perihippocampal lesions, which were more often found in cases with cognitive decline, were large and did not respect anatomical borders. Moderate microglial activation was frequently observed at the edges of these mixed lesions. Isolated intrahippocampal lesions were also frequently found. These were smaller than the mixed lesions and had a specific anatomical predilection: the cornu ammonis 2 subregion and the hilus of the dentate gyrus were consistently spared. Microglial activation was rare in isolated intrahippocampal lesions. Our results indicate that hippocampal demyelination is frequent and extensive in MS and that anatomical localization, size, and inflammatory activity vary for different lesion types.
authors.affiliation: Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands. j.geurts@vumc.nl
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
authors.forename: Lars
authors.initials: L
authors.lastname: Bö
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Roosendaal
authors.forename: Thierry
authors.initials: T
authors.lastname: Hazes
authors.forename: Richard
authors.initials: R
authors.lastname: Daniëls
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Menno P
authors.initials: MP
authors.lastname: Witter
authors.forename: Inge
authors.initials: I
authors.lastname: Huitinga
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002102:Cadaver; D003072:Cognition Disorders / Q000209:etiology; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000473:pathology; D008297:Male; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology* / Q000523:psychology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology* / Q000523:psychology; D009186:Myelin Sheath / Q000473:pathology*