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Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space

Owain Howell Orcid Logo, Elena Katharina Schulz-Trieglaff, Daniele Carassiti, Steven M. Gentleman, Richard Nicholas, Federico Roncaroli, Richard Reynolds

Neuropathology and Applied Neurobiology, Volume: 41, Issue: 6, Pages: 798 - 813

Swansea University Author: Owain Howell Orcid Logo

DOI (Published version): 10.1111/nan.12199

Abstract

Multiple Sclerosis (MS) is a progressive inflammatory neurological disease affecting myelin, neurons and glia. Demyelination and neurodegeneration of cortical grey matter contributes to a more severe disease and inflammation of the forebrain meninges associates with pathology of the underlying neoco...

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Published in: Neuropathology and Applied Neurobiology
Published: 2015
URI: https://cronfa.swan.ac.uk/Record/cronfa20148
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spelling 2018-10-26T09:47:31.3646790 v2 20148 2015-02-10 Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space 58c995486fc93a242b987640b692db8c 0000-0003-2157-9157 Owain Howell Owain Howell true false 2015-02-10 BMS Multiple Sclerosis (MS) is a progressive inflammatory neurological disease affecting myelin, neurons and glia. Demyelination and neurodegeneration of cortical grey matter contributes 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.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 to 11 non-neurological controls.Demyelination and meningeal inflammation of the cerebellum was greatest in those cases previously characterised 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, CD4+, CD8+ 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.These data suggest that chronic inflammation is widespread throughout the subarachnoid space and contributes to a more severe subpial demyelinating pathology in the cerebellum. Journal Article Neuropathology and Applied Neurobiology 41 6 798 813 1 10 2015 2015-10-01 10.1111/nan.12199 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2018-10-26T09:47:31.3646790 2015-02-10T08:59:30.4332200 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Owain Howell 0000-0003-2157-9157 1 Elena Katharina Schulz-Trieglaff 2 Daniele Carassiti 3 Steven M. Gentleman 4 Richard Nicholas 5 Federico Roncaroli 6 Richard Reynolds 7 0020148-16082017123351.pdf Howelletal_Cerebellumpathology_onlineearlyedition.pdf 2017-08-16T12:33:51.3370000 Output 1751101 application/pdf Accepted Manuscript true 2017-08-16T00:00:00.0000000 true eng
title Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space
spellingShingle Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space
Owain Howell
title_short Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space
title_full Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space
title_fullStr Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space
title_full_unstemmed Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space
title_sort Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space
author_id_str_mv 58c995486fc93a242b987640b692db8c
author_id_fullname_str_mv 58c995486fc93a242b987640b692db8c_***_Owain Howell
author Owain Howell
author2 Owain Howell
Elena Katharina Schulz-Trieglaff
Daniele Carassiti
Steven M. Gentleman
Richard Nicholas
Federico Roncaroli
Richard Reynolds
format Journal article
container_title Neuropathology and Applied Neurobiology
container_volume 41
container_issue 6
container_start_page 798
publishDate 2015
institution Swansea University
doi_str_mv 10.1111/nan.12199
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description Multiple Sclerosis (MS) is a progressive inflammatory neurological disease affecting myelin, neurons and glia. Demyelination and neurodegeneration of cortical grey matter contributes 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.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 to 11 non-neurological controls.Demyelination and meningeal inflammation of the cerebellum was greatest in those cases previously characterised 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, CD4+, CD8+ 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.These data suggest that chronic inflammation is widespread throughout the subarachnoid space and contributes to a more severe subpial demyelinating pathology in the cerebellum.
published_date 2015-10-01T03:23:45Z
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