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A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis

Roberta Magliozzi, Owain Howell Orcid Logo, Cheryl Reeves, Federico Roncaroli, Richard Nicholas, Barbara Serafini, Francesca Aloisi, Richard Reynolds

Annals of Neurology, Volume: 68, Issue: 4, Pages: 477 - 493

Swansea University Author: Owain Howell Orcid Logo

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DOI (Published version): 10.1002/ana.22230

Abstract

Objective Prominent inflammation with formation of ectopic B-cell follicle-like structures in the meninges in secondary progressive multiple sclerosis (MS) (SPMS) is associated with extensive cortical pathology and an exacerbated disease course. Our objective was to evaluate the cellular substrates...

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Published in: Annals of Neurology
Published: 2010
Online Access: http://www.scopus.com/record/display.url?eid=2-s2.0-78249280011&origin=resultslist&sort=plf-f&src=s&st1=howell&st2=o.w&nlo=1&nlr=20&nls=&sid=942755C5CBB33656BBE96DCBEAC4A9AE.iqs8TDG0Wy6BURhzD3nFA%3a122&sot=anl&sdt=aut&sl=33&s=AU-ID%28%22Howell%2c+O.+W.%22+6602393502%29&relpos=9&relpos=9&searchTerm=AU-ID%28\%26quot%3BHowell%2C+O.+W.\%26quot%3B+6602393502%29
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spelling 2013-12-13T11:24:26.2998329 v2 14215 2013-02-11 A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis 58c995486fc93a242b987640b692db8c 0000-0003-2157-9157 Owain Howell Owain Howell true false 2013-02-11 BMS Objective Prominent inflammation with formation of ectopic B-cell follicle-like structures in the meninges in secondary progressive multiple sclerosis (MS) (SPMS) is associated with extensive cortical pathology and an exacerbated disease course. Our objective was to evaluate the cellular substrates of the cortical damage to understand the role of meningeal inflammation in MS pathology. Methods Using &#62;600 tissue blocks from 37 cases of SPMS and 14 non-neurological controls, we carried out a detailed quantitative analysis of cortical atrophy and layer-specific changes in cell populations in SPMS cases with (F + SPMS) and without (F + SPMS) B-cell follicle-like structures. Results B-cell follicle-like structures were detected in the inflamed meninges of 20 of 37 SPMS cases (54%) and were associated with increased subpial cortical demyelination and cortical atrophy. A clear gradient of neuronal loss was observed in grey matter lesions and normal-appearing grey matter in the motor cortex of F + SPMS cases. The density of pyramidal neurons was significantly reduced in layers III and V of the motor cortex. Neuronal loss was accompanied by glia limitans damage with astrocyte loss and an opposite gradient of increased density of activated microglia. No gradient of neuronal loss was seen in F + SPMS cases. Interpretation We demonstrate substantial cortical neurodegeneration and generalized cell loss in progressive MS in association with meningeal inflammation and lymphoid tissue formation, supporting the hypothesis that cytotoxic factors diffusing from the meningeal compartment contribute to grey matter pathology and the consequent increase in clinical disability. Journal Article Annals of Neurology 68 4 477 493 31 12 2010 2010-12-31 10.1002/ana.22230 http://www.scopus.com/record/display.url?eid=2-s2.0-78249280011&amp;origin=resultslist&amp;sort=plf-f&amp;src=s&amp;st1=howell&amp;st2=o.w&amp;nlo=1&amp;nlr=20&amp;nls=&amp;sid=942755C5CBB33656BBE96DCBEAC4A9AE.iqs8TDG0Wy6BURhzD3nFA%3a122&amp;sot=anl&amp;sdt=aut&amp;sl=33&amp;s=AU-ID%28%22Howell%2c+O.+W.%22+6602393502%29&amp;relpos=9&amp;relpos=9&amp;searchTerm=AU-ID%28\%26quot%3BHowell%2C+O.+W.\%26quot%3B+6602393502%29 I am joint first author COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2013-12-13T11:24:26.2998329 2013-02-11T18:19:51.4897283 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Roberta Magliozzi 1 Owain Howell 0000-0003-2157-9157 2 Cheryl Reeves 3 Federico Roncaroli 4 Richard Nicholas 5 Barbara Serafini 6 Francesca Aloisi 7 Richard Reynolds 8
title A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis
spellingShingle A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis
Owain Howell
title_short A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis
title_full A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis
title_fullStr A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis
title_full_unstemmed A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis
title_sort A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis
author_id_str_mv 58c995486fc93a242b987640b692db8c
author_id_fullname_str_mv 58c995486fc93a242b987640b692db8c_***_Owain Howell
author Owain Howell
author2 Roberta Magliozzi
Owain Howell
Cheryl Reeves
Federico Roncaroli
Richard Nicholas
Barbara Serafini
Francesca Aloisi
Richard Reynolds
format Journal article
container_title Annals of Neurology
container_volume 68
container_issue 4
container_start_page 477
publishDate 2010
institution Swansea University
doi_str_mv 10.1002/ana.22230
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
url http://www.scopus.com/record/display.url?eid=2-s2.0-78249280011&amp;origin=resultslist&amp;sort=plf-f&amp;src=s&amp;st1=howell&amp;st2=o.w&amp;nlo=1&amp;nlr=20&amp;nls=&amp;sid=942755C5CBB33656BBE96DCBEAC4A9AE.iqs8TDG0Wy6BURhzD3nFA%3a122&amp;sot=anl&amp;sdt=aut&amp;sl=33&amp;s=AU-ID%28%22Howell%2c+O.+W.%22+6602393502%29&amp;relpos=9&amp;relpos=9&amp;searchTerm=AU-ID%28\%26quot%3BHowell%2C+O.+W.\%26quot%3B+6602393502%29
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description Objective Prominent inflammation with formation of ectopic B-cell follicle-like structures in the meninges in secondary progressive multiple sclerosis (MS) (SPMS) is associated with extensive cortical pathology and an exacerbated disease course. Our objective was to evaluate the cellular substrates of the cortical damage to understand the role of meningeal inflammation in MS pathology. Methods Using &#62;600 tissue blocks from 37 cases of SPMS and 14 non-neurological controls, we carried out a detailed quantitative analysis of cortical atrophy and layer-specific changes in cell populations in SPMS cases with (F + SPMS) and without (F + SPMS) B-cell follicle-like structures. Results B-cell follicle-like structures were detected in the inflamed meninges of 20 of 37 SPMS cases (54%) and were associated with increased subpial cortical demyelination and cortical atrophy. A clear gradient of neuronal loss was observed in grey matter lesions and normal-appearing grey matter in the motor cortex of F + SPMS cases. The density of pyramidal neurons was significantly reduced in layers III and V of the motor cortex. Neuronal loss was accompanied by glia limitans damage with astrocyte loss and an opposite gradient of increased density of activated microglia. No gradient of neuronal loss was seen in F + SPMS cases. Interpretation We demonstrate substantial cortical neurodegeneration and generalized cell loss in progressive MS in association with meningeal inflammation and lymphoid tissue formation, supporting the hypothesis that cytotoxic factors diffusing from the meningeal compartment contribute to grey matter pathology and the consequent increase in clinical disability.
published_date 2010-12-31T03:16:18Z
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