Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis.
Open accessAbstract
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.
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While ectopic lymphoid follicles (ELFs) are only present in ~40% of secondary progressive multiple sclerosis (SPMS) cases, diffuse meningeal inflammation plays a role in the pathology of primary progressive MS and the remaining 60% of SPMS.
“While ELFs are only present in ~ 40% of SPMS cases, diffuse meningeal inflammation plays a role in the pathology of PPMS and the remaining 60% of SPMS [70, 72].”
From Insights and challenges on animal models for progressive multiple sclerosis (2026) · cites this paper as [72]
The presentation of MS induced leptomeningeal inflammation can be variable, ranging from disorganized collections of immune cells to organized ectopic lymphoid follicle-like structures, and these ectopic lymph structures are potentiated by leptomeningeal fibroblasts which form a reticular cell network consisting of activated fibroblasts in a scaffold-like structure that might be driven by a subset
“The presentation of MS induced leptomeningeal inflammation can be variable, ranging from disorganized collections of immune cells to organized ectopic lymphoid follicle-like structures”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Choi et al., 2012
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- Authors
- Choi, S. R., Howell, O. W., Carassiti, D., Magliozzi, R., Gveric, D., Muraro, P. A., Nicholas, R., Roncaroli, F., & Reynolds, R.
- Affiliations
- Hammersmith Hospital (GB)
- Istituto Superiore di Sanità (IT)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-08-18
- Volume
- 135
- Issue
- 10
- Pages
- 2925-2937
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2131288952
- Cited by
- 386
- References
- 39
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 35 · 2023: 33 · 2022: 27 · 2021: 37 · 2020: 28 · 2019: 35 · 2018: 32 · 2017: 22 · 2016: 24 · 2015: 27 · 2014: 29 · 2013: 28 · 2012: 4
- FWCI
- 20.26
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Funders
- Parkinson's UK (G0909)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- primary progressive multiple sclerosis, meningeal inflammation, perivascular inflammation, demyelination, microglial activation, neuronal loss, disease progression, postmortem brain
- MeSH terms
- Adult, Aged, Aged, 80 and over, Demyelinating Diseases, Humans, Inflammation, Male, Meninges, Middle Aged, Time Factors, Disease Progression, Multiple Sclerosis, Chronic Progressive
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