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Cited by 255Multiple Sclerosis Research StudiesPeripheral Neuropathies and DisordersAdvanced Neuroimaging Techniques and Applications

Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts

DeLuca, G. C.·2004·Brain
DOI 10.1093/brain/awh118
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Abstract

Clinical, imaging, and pathological studies in multiple sclerosis have generally emphasized the relative preservation of axons in comparison with myelin. Recent evidence, however, demonstrates that axonal loss is also significant, affects long tracts such as the corticospinal and sensory tracts and relates closely to functional disability. Accordingly, the distribution and extent of this axonal loss is the focus of the current investigation. Post-mortem material of 55 multiple sclerosis patients and 32 matched controls was used to examine quantitatively the population of axons in the corticospinal tracts from the medulla to the lumbar spinal cord and the sensory tracts from the lumbar to the upper cervical spinal cord. Myelin- and axon-stained sections have been prepared to estimate the notional area and axon density, respectively of both tracts. Our results indicate that in the corticospinal tracts there is a significant reduction of the area and axon density at all levels investigated in multiple sclerosis cases when compared with controls. In contrast, the sensory tracts in multiple sclerosis cases showed a significant reduction in area and axon density only in the upper regions of the spinal cord. As has been found with MRI plaque load and T2 burden, correlations of axonal loss with duration of disease were not strong. Of the fibres lost in multiple sclerosis, we have found that small fibres (<3 microm2) seem to be particularly affected, with large fibres remaining relatively preserved in both the corticospinal and sensory tracts. In multiple sclerosis, axonal loss is widespread, and its extent is tract specific and size selective.

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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 [6]

    The Introduction (page not provided) describes inflammatory demyelination and axonal loss in multiple sclerosis, and says cumulative axonal loss seems likely to contribute to progressive neurological disability. The Discussion (page not provided) describes substantial spinal-cord tract axon loss but notes that limited clinical information prevented relating this study’s findings to established disability scales. The cited passages do not establish synaptic or neuronal loss as cardinal characteristics, or show that spinal-cord pathology determines permanent disability. (LLM, conf=0.88)

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  • Neurofilament antigenicity can be negatively affected by formalin fixation.

    “Regarding the NSF maps, neurofilament antigenicity can be negatively affected by formalin fixation,6 which may be at least in part responsible for some of the heterogeneity shown in our neurofilament immunolabeling.”

    From Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology? (2017) · cites this paper as [6]

    Materials and methods describes formalin-fixed tissue, and Validation of Palmgren stain to demonstrate axons reports that neurofilament immunostaining demonstrated axons less consistently than the Palmgren stain. The paper does not say that formalin fixation caused this difference or that it reduced neurofilament antigenicity; no page numbers are available in our copy. (LLM, conf=0.74)

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2 of the 30 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. Bjartmar C, Kidd G, Mork S, Rudick R, Trapp BD. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 2000; 48: 793±901.
  2. Charcot M. Histologie de la sclerose en plaques. Gaz Hop (Paris) 1868; 141: 554±8.
  3. Evangelou N, Esiri MM, Smith S, Palace J, Matthews PM. Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 2000a; 47: 391±5.
  4. Scherer S. Axonal pathology in demyelinating diseases. Ann Neurol 1999; 45: 6±7.

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Authors
DeLuca, G. C.
Affiliations
University of Oxford (GB)
Corresponding author
DeLuca, G. C.
ORCID
DeLuca, G. C.
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2004-02-26
Volume
127
Issue
5
Pages
1009-1018
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awh118
OpenAlex
W1999110803
Cited by
255
References
30
Citations by year
2026: 5 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 8 · 2020: 14 · 2019: 12 · 2018: 13 · 2017: 10 · 2016: 10 · 2015: 16 · 2014: 14 · 2013: 12 · 2012: 12
FWCI
11.90
Type
journal article
Language
en
Open access
closed
Locations
  • Brain (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Multiple Sclerosis Society of Canada
  • Multiple Sclerosis Society
  • University of Oxford
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
Keywords
multiple sclerosis, axonal loss, corticospinal tract, axon density, myelin, spinal cord, disease duration, functional disability, postmortem pathology
MeSH terms
Adult, Aged, Aged, 80 and over, Axons, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Multiple Sclerosis, Pyramidal Tracts, Spinal Cord, Staining and Labeling, Case-Control Studies, Ganglia, Sensory

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