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High Levels of Perivascular Inflammation and Active Demyelinating Lesions at Time of Death Associated with Rapidly Progressive Multiple Sclerosis Disease Course: A Retrospective Postmortem Cohort Study
Richard Nicholas 
,
Roberta Magliozzi ,
Damiano Marastoni,
Owain Howell ,
Federico Roncaroli,
Paolo Muraro,
Richard Reynolds,
Tim Friede
,
Roberta Magliozzi ,
Damiano Marastoni,
Owain Howell ,
Federico Roncaroli,
Paolo Muraro,
Richard Reynolds,
Tim Friede
Annals of Neurology
Swansea University Author:
Owain Howell
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DOI (Published version): 10.1002/ana.26870
Abstract
Objective:Analysis of postmortem multiple sclerosis (MS) tissues combined with in vivo disease milestones suggeststhat whereas perivascular white matter infiltrates are associated with demyelinating activity in the initial stages,leptomeningeal immune cell infiltration, enriched in B cells, and asso...
| Published in: | Annals of Neurology |
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| ISSN: | 0364-5134 1531-8249 |
| Published: |
Wiley
2024
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa65421 |
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| Abstract: |
Objective:Analysis of postmortem multiple sclerosis (MS) tissues combined with in vivo disease milestones suggeststhat whereas perivascular white matter infiltrates are associated with demyelinating activity in the initial stages,leptomeningeal immune cell infiltration, enriched in B cells, and associated cortical lesions contribute to disease pro-gression. We systematically examine the association of inflammatory features and white matter demyelination at post-mortem with clinical milestones.Methods:In 269 MS brains, 20 sites were examined using immunohistochemistry for active lesions (ALs) and perivenularinflammation (PVI). In a subset of 22, a detailed count of CD20+B cells and CD3+T cells in PVIs was performed.Results:ALs were detected in 22%, whereas high levels of PVI were detected in 52% of cases. ALs were present in35% of cases with high levels of PVI. Shorter time from onset of progression to death was associated with increasedprevalence and higher levels of PVI (bothp< 0.0001). Shorter time from onset of progression to wheelchair use wasassociated with higher prevalence of ALs (odds ratio [OR]=0.921, 95% confidence interval [CI]=0.858–0.989,p=0.0230) and higher level of PVI (OR=0.932, 95% CI=0.886–0.981,p=0.0071). High levels of PVI were associ-ated with meningeal inflammation and increased cortical demyelination and significantly higher levels of B lymphocyteswithin the PVI.Interpretation:ALs, a feature of early disease stage, persist up to death in a subgroup with high levels of PVI. Thesefeatures link to a rapid progressive phase and higher levels of meningeal inflammation and B-cell infiltrates, supportingthe hypothesis that chronic inflammation drives progression in MS. |
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| Item Description: |
Data Availability:Data used for this article are available upon reasonablerequest. |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
This study was supported by the Laboratory of Neuropa-thology at University Laboratory of Medical Research andthe Excellence Project 2023–2027 (funded by ItalianMinistry of University and Research) of the Departmentof Neuroscience, Biomedicine, and Movement Sciences,University of Verona; and the National MS Society (grantRFA-2305-41332). Work undertaken at Imperial CollegeHealthcare NHS Trust and Imperial College receivedfunding from the Department of Health’s NIHR Biomed-ical Research Centres funding scheme.We thank the UK MS Society Tissue Bank at Impe-rial College and Dr D. Gveric (funding from the MS Soci-ety of Great Britain, grant 007/14 to R.R. and R.N.) forthe supply of postmortem MS samples. |