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Cited by 93Multiple Sclerosis Research StudiesPeripheral Neuropathies and DisordersParkinson's Disease Mechanisms and Treatments

Greater loss of axons in primary progressive multiple sclerosis plaques compared to secondary progressive disease

Tallantyre, E. C., Bo, L., Al-Rawashdeh, O., Owens, T., Polman, C. H., Lowe, J., Evangelou, N.·2009·Brain
DOI 10.1093/brain/awp106
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Abstract

The pathological substrate of progressive disability in multiple sclerosis is hypothesized to be axonal loss. Differences in the demographic, pathological and radiological features of patients with primary progressive compared with secondary progressive multiple sclerosis raise the question as to whether they actually represent separate clinical entities. So far, large pathological studies comparing axonal damage between primary progressive and secondary progressive multiple sclerosis have not been reported. In this clinico-pathological study we examined the cervical spinal cord in patients with primary and secondary progressive multiple sclerosis. Human cervical spinal cord was derived at autopsy from 54 patients (17 primary progressive, 30 secondary progressive and 7 controls). Tissue was stained immunohistochemically and examined to determine: (i) the number of surviving corticospinal tract axons; (ii) the extent of grey and white matter demyelination; (iii) the degree of inflammation inside and outside of lesions; and (iv) the relationship between demyelination and axonal loss. Associated clinical data was used to calculate expanded disability status scale for each patient preceding death. Motor disability in the primary progressive and secondary progressive groups was similar preceding death. Secondary progressive multiple sclerosis patients showed considerably more extensive demyelination of both the white and grey matter of the cervical spinal cord. The total number of corticospinal axons was equally low in primary progressive and secondary progressive multiple sclerosis groups versus controls. The reduction of axonal density in demyelinated regions compared to normal appearing white matter was significantly more extensive in primary progressive versus secondary progressive patients (33% reduction versus 16% reduction, P < 0.001). These findings suggest axonal loss is the pathological substrate of progressive disability in both primary progressive and secondary progressive multiple sclerosis with a common plaque-centred mechanism. More extensive axonal loss within areas of demyelination in primary progressive multiple sclerosis could explain high levels of axonal loss observed in these patients despite low levels of demyelination.

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  • Spinal cord pathology is an important determinant of permanent neurological disability in multiple sclerosis, with cardinal characteristics being inflammatory demyelination, synaptic, neuronal and axonal loss.

    “Spinal cord pathology is an important determinant of permanent neurological disability with cardinal characteristics being inflammatory demyelination, synaptic, neuronal and axonal loss.6, 7, 8, 9, 10, 11”

    From Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology? (2017) · cites this paper as [8]

    The Introduction (page not provided) links inflammatory demyelination to relapse disability and describes neuro-axonal pathology as a hypothesized explanation for progressive disability. The study examines cervical spinal cord demyelination, inflammation and axonal loss, but our copy does not establish synaptic or neuronal loss as cardinal characteristics, and it hedges rather than establishes the cause of permanent disability. (LLM, conf=0.86)

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Research works printed but not linked: 38

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Sorted by citations

Authors
Tallantyre, E. C., Bo, L., Al-Rawashdeh, O., Owens, T., Polman, C. H., Lowe, J., & Evangelou, N.
Affiliations
  • University of Nottingham (GB)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Nottingham University Hospitals NHS Trust (GB)
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2009-05-01
Volume
132
Issue
5
Pages
1190-1199
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awp106
OpenAlex
W2126802540
Cited by
93
References
2
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 7 · 2021: 7 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 8 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 9 · 2012: 10
FWCI
7.07
Type
journal article
Language
en
Open access
closed
Locations
  • Brain (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • Multiple Sclerosis Society
  • Research Councils UK
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
primary progressive multiple sclerosis, secondary progressive multiple sclerosis, axonal loss, demyelination, corticospinal tract, cervical spinal cord, multiple sclerosis plaques, white matter demyelination, inflammation, disability progression, Expanded Disability Status Scale
MeSH terms
Aged, Aged, 80 and over, Axons, Cell Count, Disability Evaluation, Female, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Degeneration, Spinal Cord, Staining and Labeling, Chi-Square Distribution, Case-Control Studies, Statistics, Nonparametric, Multiple Sclerosis, Chronic Progressive

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