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Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis

S. R Choi, O. W Howell, D Carassiti, R Magliozzi, D Gveric, P. A Muraro, R Nicholas, F Roncaroli, R Reynolds, Owain Howell Orcid Logo

Brain, Volume: 135, Issue: 10, Pages: 2925 - 2937

Swansea University Author: Owain Howell Orcid Logo

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DOI (Published version): 10.1093/brain/aws189

Abstract

The primary progressive form of multiple sclerosis is characterized by accrual of neurological dysfunction from disease onset without remission and it is still a matter of debate whether this disease course results from different pathogenetic mechanisms compared with secondary progressive multiple s...

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Published in: Brain
Published: 2012
Online Access: http://www.scopus.com/record/display.url?eid=2-s2.0-84867707040&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=2&relpos=2&searchTerm=AU-ID%28\%26quot%3BHowell%2C+O.+W.\%26quot%3B+6602393502%29
URI: https://cronfa.swan.ac.uk/Record/cronfa14213
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spelling 2013-12-13T11:21:35.9026649 v2 14213 2013-02-11 Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis 58c995486fc93a242b987640b692db8c 0000-0003-2157-9157 Owain Howell Owain Howell true false 2013-02-11 BMS The primary progressive form of multiple sclerosis is characterized by accrual of neurological dysfunction from disease onset without remission and it is still a matter of debate whether this disease course results from different pathogenetic mechanisms compared with secondary progressive multiple sclerosis. Inflammation in the leptomeninges has been identified as a key feature of secondary progressive multiple sclerosis and may contribute to the extensive cortical pathology that accompanies progressive disease. Our aim was to investigate the extent of perivascular and meningeal inflammation in primary progressive multiple sclerosis in order to understand their contribution to the pathogenetic mechanisms associated with cortical pathology. A comprehensive immunohistochemical analysis was performed on post-mortem brain tissue from 26 cases with primary progressive multiple sclerosis. A variable extent of meningeal immune cell infiltration was detected and more extensive demyelination and neurite loss in the cortical grey matter was found in cases exhibiting an increased level of meningeal inflammation. However, no tertiary lymphoid-like structures were found. Profound microglial activation and reduction in neuronal density was observed in both the lesions and normal appearing grey matter compared with control cortex. Furthermore, cases with primary progressive multiple sclerosis with extensive meningeal immune cell infiltration exhibited a more severe clinical course, including a shorter disease duration and younger age at death. Our data suggest that generalized diffuse meningeal inflammation and the associated inflammatory milieu in the subarachnoid compartment plays a role in the pathogenesis of cortical grey matter lesions and an increased rate of clinical progression in primary progressive multiple sclerosis. Journal Article Brain 135 10 2925 2937 31 12 2012 2012-12-31 10.1093/brain/aws189 http://www.scopus.com/record/display.url?eid=2-s2.0-84867707040&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=2&amp;relpos=2&amp;searchTerm=AU-ID%28\%26quot%3BHowell%2C+O.+W.\%26quot%3B+6602393502%29 I am a joint first author COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2013-12-13T11:21:35.9026649 2013-02-11T18:12:21.3640457 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine S. R Choi 1 O. W Howell 2 D Carassiti 3 R Magliozzi 4 D Gveric 5 P. A Muraro 6 R Nicholas 7 F Roncaroli 8 R Reynolds 9 Owain Howell 0000-0003-2157-9157 10
title Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis
spellingShingle Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis
Owain Howell
title_short Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis
title_full Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis
title_fullStr Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis
title_full_unstemmed Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis
title_sort Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis
author_id_str_mv 58c995486fc93a242b987640b692db8c
author_id_fullname_str_mv 58c995486fc93a242b987640b692db8c_***_Owain Howell
author Owain Howell
author2 S. R Choi
O. W Howell
D Carassiti
R Magliozzi
D Gveric
P. A Muraro
R Nicholas
F Roncaroli
R Reynolds
Owain Howell
format Journal article
container_title Brain
container_volume 135
container_issue 10
container_start_page 2925
publishDate 2012
institution Swansea University
doi_str_mv 10.1093/brain/aws189
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-s2.0-84867707040&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=2&amp;relpos=2&amp;searchTerm=AU-ID%28\%26quot%3BHowell%2C+O.+W.\%26quot%3B+6602393502%29
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description The primary progressive form of multiple sclerosis is characterized by accrual of neurological dysfunction from disease onset without remission and it is still a matter of debate whether this disease course results from different pathogenetic mechanisms compared with secondary progressive multiple sclerosis. Inflammation in the leptomeninges has been identified as a key feature of secondary progressive multiple sclerosis and may contribute to the extensive cortical pathology that accompanies progressive disease. Our aim was to investigate the extent of perivascular and meningeal inflammation in primary progressive multiple sclerosis in order to understand their contribution to the pathogenetic mechanisms associated with cortical pathology. A comprehensive immunohistochemical analysis was performed on post-mortem brain tissue from 26 cases with primary progressive multiple sclerosis. A variable extent of meningeal immune cell infiltration was detected and more extensive demyelination and neurite loss in the cortical grey matter was found in cases exhibiting an increased level of meningeal inflammation. However, no tertiary lymphoid-like structures were found. Profound microglial activation and reduction in neuronal density was observed in both the lesions and normal appearing grey matter compared with control cortex. Furthermore, cases with primary progressive multiple sclerosis with extensive meningeal immune cell infiltration exhibited a more severe clinical course, including a shorter disease duration and younger age at death. Our data suggest that generalized diffuse meningeal inflammation and the associated inflammatory milieu in the subarachnoid compartment plays a role in the pathogenesis of cortical grey matter lesions and an increased rate of clinical progression in primary progressive multiple sclerosis.
published_date 2012-12-31T03:16:18Z
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