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Cited by 175Multiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration MechanismsPsoriasis: Treatment and Pathogenesis

Mechanisms underlying progression in multiple sclerosis

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Absinta, Martina, Lassmann, Hans, Trapp, Bruce D.·2020·Current Opinion in Neurology
DOI 10.1097/wco.0000000000000818PMC PMC7337978
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Abstract

Purpose of review: In multiple sclerosis, currently approved disease-modifying treatments are effective in modulating peripheral immunity, and coherently, in reducing clinical/radiological relapses, but still, they perform poorly in preventing disease progression and overall disability accrual. This review provides an up-to-date overview of the neuropathology of progressive multiple sclerosis, including a summary of the main mechanisms of disease progression. Recent findings: Clinical progression in multiple sclerosis is likely related to the accumulation of neuro-axonal loss in a lifelong inflammatory CNS environment (both adaptive and innate) and relative un-balance between damage, repair and brain functional reserve. A critical driver appears to be the T-cell and B-cell-mediated compartmentalized inflammation within the leptomeninges and within the parenchyma. Recent perspective highlighted also the role of the glial response to such lifelong inflammatory injury as the critical player for both pathological and clinical outcomes. Summary: The neuropathological and biological understanding of disease progression in multiple sclerosis have progressed in the last few years. As a consequence, new therapeutic approaches are emerging outside the modulation of T-cell activity and/or the depletion of B cells.

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  • Focal lesions such as those in the brainstem result in axonal loss, and cortical demyelination is associated with selective neuronal loss; both are prominent determinants of progression.

    “It is well established that focal lesions such as those in the brainstem result in axonal loss, and that cortical demyelination, which occurs independently of white matter lesions, is associated with selective neuronal loss18; both these degenerative features are prominent determinants of progression18,19.”

    From Locus for severity implicates CNS resilience in progression of multiple sclerosis (2023) · cites this paper as [19]

    The Neuropathology of progressive MS section (page unavailable) says subpial cortical demyelination can develop independently of white-matter lesions and identifies cortical lesions as a major substrate of disability. The Final pathways section (page unavailable) reports significant cortical neuronal loss, but says neuronal loss was not correlated with cortical demyelination in the myelocortical patients discussed. It describes axonal injury in white matter, not specifically brainstem lesions, and does not establish the claimed association with selective neuronal loss. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Homozygous rs10191329 risk allele carriers demonstrated more severe MS-specific brainstem and cortical pathology, which result in axonal and neuronal degeneration respectively and drive progression.

    “Besides these clinical differences, homozygous rs10191329 risk allele carriers also demonstrated more severe MS-specific brainstem and cortical pathology, which result in axonal and neuronal degeneration respectively and drive progression18,19.”

    From Locus for severity implicates CNS resilience in progression of multiple sclerosis (2023) · cites this paper as [19]

    The 'Neuropathology of progressive MS' section links cortical lesions to disability, and 'Final pathways of neuro-axonal dysfunction and death' discusses axonal degeneration and cortical neuronal loss (page numbers unavailable). But the paper does not report that homozygous rs10191329 risk-allele carriers have more severe brainstem or cortical pathology, nor does it link brainstem pathology specifically to their axonal degeneration. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Absinta, M., Lassmann, H., & Trapp, B. D.
Affiliations
  • Johns Hopkins University (US)
  • Medical University of Vienna (AT)
  • Cleveland Clinic (US)
Corresponding author
Absinta, Martina
ORCID
Venue
Current Opinion in Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2020-06
Volume
33
Issue
3
Pages
277-285
ISSN
  • 1350-7540 (ISSN-L)
  • 1473-6551
DOI
10.1097/wco.0000000000000818
PMC
PMC7337978
OpenAlex
W3018930382
Cited by
175
References
19
Citations by year
2026: 26 · 2025: 29 · 2024: 37 · 2023: 34 · 2022: 25 · 2021: 22 · 2020: 2
FWCI
3.22
Type
journal article
Language
en
Open access
Locations
  • Current Opinion in Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R35NS097303)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
multiple sclerosis, disease progression, neuropathology, T cell-mediated inflammation, leptomeningeal inflammation, glial response, brain repair, disease-modifying therapy, neuroinflammation
MeSH terms
Humans, Immunologic Factors, Inflammation, Recurrence, Disease Progression, Multiple Sclerosis, Chronic Progressive

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