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Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space
Author(s) -
Howell Owain W.,
SchulzTrieglaff Elena Katharina,
Carassiti Daniele,
Gentleman Steven M.,
Nicholas Richard,
Roncaroli Federico,
Reynolds Richard
Publication year - 2015
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12199
Subject(s) - grey matter , pathology , meninges , cerebellum , inflammation , multiple sclerosis , microglia , forebrain , subarachnoid space , medicine , white matter , neuroscience , biology , central nervous system , cerebrospinal fluid , immunology , magnetic resonance imaging , radiology
Aims Multiple sclerosis ( MS ) is a progressive inflammatory neurological disease affecting myelin, neurons and glia. Demyelination and neurodegeneration of cortical grey matter contribute to a more severe disease, and inflammation of the forebrain meninges associates with pathology of the underlying neocortical grey matter, particularly in deep sulci. We assessed the extent of meningeal inflammation of the cerebellum, another structure with a deeply folded anatomy, to better understand the association between subarachnoid inflammation and grey matter pathology in progressive MS . Methods We examined demyelinating and neuronal pathology in the context of meningeal inflammation in cerebellar tissue blocks from a cohort of 27 progressive MS cases previously characterized on the basis of the absence/presence of lymphoid‐like aggregates in the forebrain meninges, in comparison with 11 non‐neurological controls. Results Demyelination and meningeal inflammation of the cerebellum was greatest in those cases previously characterized as harbouring lymphoid‐like structures in the forebrain regions. Meningeal inflammation was mild to moderate in cerebellar tissue blocks, and no lymphoid‐like structures were seen. Quantification of meningeal macrophages, CD 4+, CD 8+ T lymphocytes, B cells and plasma cells revealed that the density of meningeal macrophages associated with microglial activation in the grey matter, and the extent of grey matter demyelination correlated with the density of macrophages and plasma cells in the overlying meninges, and activated microglia of the parenchyma. Conclusions These data suggest that chronic inflammation is widespread throughout the subarachnoid space and contributes to a more severe subpial demyelinating pathology in the cerebellum.