Journal article 1173 views 224 downloads
Meningeal inflammation and cortical demyelination in acute multiple sclerosis
Ryan J. Bevan,
Rhian Evans,
Lauren Griffiths,
Lewis M. Watkins,
Mark Rees,
Roberta Magliozzi,
Ingrid Allen,
Gavin McDonnell,
Rachel Kee,
Michelle Naughton,
Denise C. Fitzgerald,
Richard Reynolds,
James W. Neal,
Owain Howell
Annals of Neurology
Swansea University Authors: Mark Rees, Owain Howell
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DOI (Published version): 10.1002/ana.25365
Abstract
Cortical grey matter (GM) pathology, involving demyelination and neurodegeneration, associated with meningeal inflammation, could be important in determining disability progression in multiple sclerosis (MS). However, we need to know more about how cortical demyelination, neurodegeneration and menin...
Published in: | Annals of Neurology |
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ISSN: | 03645134 |
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2018
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URI: | https://cronfa.swan.ac.uk/Record/cronfa45060 |
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2020-07-01T16:16:05.3549426 v2 45060 2018-10-23 Meningeal inflammation and cortical demyelination in acute multiple sclerosis 10f39a4e9c2ee00d453cd84c10667ac8 Mark Rees Mark Rees true false 58c995486fc93a242b987640b692db8c 0000-0003-2157-9157 Owain Howell Owain Howell true false 2018-10-23 Cortical grey matter (GM) pathology, involving demyelination and neurodegeneration, associated with meningeal inflammation, could be important in determining disability progression in multiple sclerosis (MS). However, we need to know more about how cortical demyelination, neurodegeneration and meningeal inflammation contribute to pathology in early stages of MS to better predict long-term outcome. Tissue blocks from short disease duration MS (n=12, median disease duration 2 years), progressive MS (n=21, disease duration 25 years), non-diseased controls (n=11) and other neurological inflammatory disease controls (n=6), were quantitatively analysed by immunohistochemistry, immunofluorescence and in situ hybridisation.Cortical GM demyelination was extensive in some cases of acute MS (range 1– 48% of total cortical GM) and subpial lesions were the most common type (62%). The numbers of activated (CD68+) microglia/ macrophages were increased in cases with subpial lesions and the density of neurons was significantly reduced in acute MS normal appearing and lesion GM, compared to controls (p<0.005). Significant meningeal inflammation and lymphoid-like structures were seen in 4 of 12 acute MS cases. The extent of meningeal inflammation correlated with microglial/ macrophage activation (p<0.05), but not the area of cortical demyelination, reflecting the finding that lymphoid-like structures were seen adjacent to GM lesions as well as areas of partially demyelinated/remyelinated, cortical GM. Our findings demonstrate that cortical demyelination, neuronal loss and meningeal inflammation are notable pathological hallmarks of acute MS and support the need to identify early biomarkers of this pathology to better predict outcome. Journal Article Annals of Neurology 03645134 B-cells; follicles; pathology 25 10 2018 2018-10-25 10.1002/ana.25365 COLLEGE NANME COLLEGE CODE Swansea University 2020-07-01T16:16:05.3549426 2018-10-23T09:19:58.9280862 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Ryan J. Bevan 1 Rhian Evans 2 Lauren Griffiths 3 Lewis M. Watkins 4 Mark Rees 5 Roberta Magliozzi 6 Ingrid Allen 7 Gavin McDonnell 8 Rachel Kee 9 Michelle Naughton 10 Denise C. Fitzgerald 11 Richard Reynolds 12 James W. Neal 13 Owain Howell 0000-0003-2157-9157 14 0045060-27112018141220.pdf 45060.pdf 2018-11-27T14:12:20.2500000 Output 1521873 application/pdf Accepted Manuscript true 2019-10-25T00:00:00.0000000 true eng |
title |
Meningeal inflammation and cortical demyelination in acute multiple sclerosis |
spellingShingle |
Meningeal inflammation and cortical demyelination in acute multiple sclerosis Mark Rees Owain Howell |
title_short |
Meningeal inflammation and cortical demyelination in acute multiple sclerosis |
title_full |
Meningeal inflammation and cortical demyelination in acute multiple sclerosis |
title_fullStr |
Meningeal inflammation and cortical demyelination in acute multiple sclerosis |
title_full_unstemmed |
Meningeal inflammation and cortical demyelination in acute multiple sclerosis |
title_sort |
Meningeal inflammation and cortical demyelination in acute multiple sclerosis |
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10f39a4e9c2ee00d453cd84c10667ac8 58c995486fc93a242b987640b692db8c |
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10f39a4e9c2ee00d453cd84c10667ac8_***_Mark Rees 58c995486fc93a242b987640b692db8c_***_Owain Howell |
author |
Mark Rees Owain Howell |
author2 |
Ryan J. Bevan Rhian Evans Lauren Griffiths Lewis M. Watkins Mark Rees Roberta Magliozzi Ingrid Allen Gavin McDonnell Rachel Kee Michelle Naughton Denise C. Fitzgerald Richard Reynolds James W. Neal Owain Howell |
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Annals of Neurology |
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03645134 |
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10.1002/ana.25365 |
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Faculty of Medicine, Health and Life Sciences |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine |
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description |
Cortical grey matter (GM) pathology, involving demyelination and neurodegeneration, associated with meningeal inflammation, could be important in determining disability progression in multiple sclerosis (MS). However, we need to know more about how cortical demyelination, neurodegeneration and meningeal inflammation contribute to pathology in early stages of MS to better predict long-term outcome. Tissue blocks from short disease duration MS (n=12, median disease duration 2 years), progressive MS (n=21, disease duration 25 years), non-diseased controls (n=11) and other neurological inflammatory disease controls (n=6), were quantitatively analysed by immunohistochemistry, immunofluorescence and in situ hybridisation.Cortical GM demyelination was extensive in some cases of acute MS (range 1– 48% of total cortical GM) and subpial lesions were the most common type (62%). The numbers of activated (CD68+) microglia/ macrophages were increased in cases with subpial lesions and the density of neurons was significantly reduced in acute MS normal appearing and lesion GM, compared to controls (p<0.005). Significant meningeal inflammation and lymphoid-like structures were seen in 4 of 12 acute MS cases. The extent of meningeal inflammation correlated with microglial/ macrophage activation (p<0.05), but not the area of cortical demyelination, reflecting the finding that lymphoid-like structures were seen adjacent to GM lesions as well as areas of partially demyelinated/remyelinated, cortical GM. Our findings demonstrate that cortical demyelination, neuronal loss and meningeal inflammation are notable pathological hallmarks of acute MS and support the need to identify early biomarkers of this pathology to better predict outcome. |
published_date |
2018-10-25T07:36:20Z |
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11.047783 |