Journal article 1489 views
Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis
O. W Howell,
C. A Reeves,
R Nicholas,
D Carassiti,
B Radotra,
S. M Gentleman,
B Serafini,
F Aloisi,
F Roncaroli,
R Magliozzi,
R Reynolds,
Owain Howell 
Brain, Volume: 134, Issue: 9, Pages: 2755 - 2771
Swansea University Author:
Owain Howell
Full text not available from this repository: check for access using links below.
DOI (Published version): 10.1093/brain/awr182
Abstract
Meningeal inflammation in the form of ectopic lymphoid-like structures has been suggested to play a prominent role in the development of cerebral cortical grey matter pathology in multiple sclerosis. The aim of this study was to analyse the incidence and distribution of B cell follicle-like structur...
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The aim of this study was to analyse the incidence and distribution of B cell follicle-like structures in an extensive collection of cases with secondary progressive multiple sclerosis with a wide age range and to determine their relationship to diffuse meningeal inflammation, white matter perivascular infiltrates and microglial activation. One hundred and twenty three cases with secondary progressive multiple sclerosis were examined for the presence of meningeal and perivascular immune cell infiltrates in tissue blocks and/or whole coronal macrosections encompassing a wide array of brain areas. Large, dense, B cell-rich lymphocytic aggregates were screened for the presence of follicular dendritic cells, proliferating B cells and plasma cells. Ectopic B cell follicle-like structures were found, with variable frequency, in 49 cases (40) and were distributed throughout the forebrain, where they were most frequently located in the deep sulci of the temporal, cingulate, insula and frontal cortex. Subpial grey matter demyelinated lesions were located both adjacent to, and some distance from such structures. The presence of B cell follicle-like structures was associated with an accompanying quantitative increase in diffuse meningeal inflammation that correlated with the degree of microglial activation and grey matter cortical demyelination. The median age of disease onset, time to disease progression, time to wheelchair dependence and age at death all differed significantly in these cases when compared with those without B cell follicle-like structures. 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2013-12-13T11:22:36.0592717 v2 14214 2013-02-11 Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis 58c995486fc93a242b987640b692db8c 0000-0003-2157-9157 Owain Howell Owain Howell true false 2013-02-11 BMS Meningeal inflammation in the form of ectopic lymphoid-like structures has been suggested to play a prominent role in the development of cerebral cortical grey matter pathology in multiple sclerosis. The aim of this study was to analyse the incidence and distribution of B cell follicle-like structures in an extensive collection of cases with secondary progressive multiple sclerosis with a wide age range and to determine their relationship to diffuse meningeal inflammation, white matter perivascular infiltrates and microglial activation. One hundred and twenty three cases with secondary progressive multiple sclerosis were examined for the presence of meningeal and perivascular immune cell infiltrates in tissue blocks and/or whole coronal macrosections encompassing a wide array of brain areas. Large, dense, B cell-rich lymphocytic aggregates were screened for the presence of follicular dendritic cells, proliferating B cells and plasma cells. Ectopic B cell follicle-like structures were found, with variable frequency, in 49 cases (40) and were distributed throughout the forebrain, where they were most frequently located in the deep sulci of the temporal, cingulate, insula and frontal cortex. Subpial grey matter demyelinated lesions were located both adjacent to, and some distance from such structures. The presence of B cell follicle-like structures was associated with an accompanying quantitative increase in diffuse meningeal inflammation that correlated with the degree of microglial activation and grey matter cortical demyelination. The median age of disease onset, time to disease progression, time to wheelchair dependence and age at death all differed significantly in these cases when compared with those without B cell follicle-like structures. Our findings suggest that meningeal infiltrates may play a contributory role in the underlying subpial grey matter pathology and accelerated clinical course, which is exacerbated in a significant proportion of cases by the presence of B cell follicle-like structures. Journal Article Brain 134 9 2755 2771 31 12 2011 2011-12-31 10.1093/brain/awr182 http://www.scopus.com/record/display.url?eid=2-s2.0-80052927697&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=3&relpos=3&searchTerm=AU-ID%28\%26quot%3BHowell%2C+O.+W.\%26quot%3B+6602393502%29 First author COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2013-12-13T11:22:36.0592717 2013-02-11T18:15:43.5231755 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine O. W Howell 1 C. A Reeves 2 R Nicholas 3 D Carassiti 4 B Radotra 5 S. M Gentleman 6 B Serafini 7 F Aloisi 8 F Roncaroli 9 R Magliozzi 10 R Reynolds 11 Owain Howell 0000-0003-2157-9157 12 |
| title |
Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis |
| spellingShingle |
Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis Owain Howell |
| title_short |
Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis |
| title_full |
Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis |
| title_fullStr |
Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis |
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Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis |
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Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis |
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58c995486fc93a242b987640b692db8c_***_Owain Howell |
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Owain Howell |
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O. W Howell C. A Reeves R Nicholas D Carassiti B Radotra S. M Gentleman B Serafini F Aloisi F Roncaroli R Magliozzi R Reynolds Owain Howell |
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Meningeal inflammation in the form of ectopic lymphoid-like structures has been suggested to play a prominent role in the development of cerebral cortical grey matter pathology in multiple sclerosis. The aim of this study was to analyse the incidence and distribution of B cell follicle-like structures in an extensive collection of cases with secondary progressive multiple sclerosis with a wide age range and to determine their relationship to diffuse meningeal inflammation, white matter perivascular infiltrates and microglial activation. One hundred and twenty three cases with secondary progressive multiple sclerosis were examined for the presence of meningeal and perivascular immune cell infiltrates in tissue blocks and/or whole coronal macrosections encompassing a wide array of brain areas. Large, dense, B cell-rich lymphocytic aggregates were screened for the presence of follicular dendritic cells, proliferating B cells and plasma cells. Ectopic B cell follicle-like structures were found, with variable frequency, in 49 cases (40) and were distributed throughout the forebrain, where they were most frequently located in the deep sulci of the temporal, cingulate, insula and frontal cortex. Subpial grey matter demyelinated lesions were located both adjacent to, and some distance from such structures. The presence of B cell follicle-like structures was associated with an accompanying quantitative increase in diffuse meningeal inflammation that correlated with the degree of microglial activation and grey matter cortical demyelination. The median age of disease onset, time to disease progression, time to wheelchair dependence and age at death all differed significantly in these cases when compared with those without B cell follicle-like structures. Our findings suggest that meningeal infiltrates may play a contributory role in the underlying subpial grey matter pathology and accelerated clinical course, which is exacerbated in a significant proportion of cases by the presence of B cell follicle-like structures. |
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2011-12-31T03:16:18Z |
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