Clinico-pathological evidence that axonal loss underlies disability in progressive multiple sclerosis

  title={Clinico-pathological evidence that axonal loss underlies disability in progressive multiple sclerosis},
  author={Emma Clare Tallantyre and Lars B{\o} and O Al-Rawashdeh and Trudy Owens and Chris H. Polman and James S Lowe and Nikos Evangelou},
  journal={Multiple Sclerosis},
  pages={406 - 411}
Growing evidence suggests that axonal degeneration rather than demyelination is the pathological substrate underlying chronic, irreversible disability in multiple sclerosis. However, direct evidence linking clinical disability measured in vivo with corresponding post-mortem measures of axonal pathology is lacking. Our objective in this study was to investigate the relationship between motor disability accumulated by patients with multiple sclerosis during life and the degree of axonal loss… 

Figures and Tables from this paper

Multiple sclerosis: Axonal loss linked to MS disability
  • C. Mcsharry
  • Medicine, Psychology
    Nature Reviews Neurology
  • 2010
Postmortem spinal cord tissue sections from 45 individuals with MS were examined, while using medical records to gain a clear impression of the degree of motor disability that each patient had accumulated before death.
Axonal loss in the multiple sclerosis spinal cord revisited
Over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord, and spinal cord cross sectional area, reduced by about 20%, appears to be a poor predictor of axonaldensity.
Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis
It is indicated that in multiple sclerosis, ongoing demyelination in focal lesions is associated with axonal degeneration in the perilesional white matter, supporting a role for focal pathology in diffuse white matter damage.
Axonal loss in major sensorimotor tracts is associated with impaired motor performance in minimally disabled multiple sclerosis patients
Given that axonal loss is irreversible, the combined use of advanced imaging and kinematic markers could be used to identify patients at risk of more severe motor impairments as they emerge for more aggressive therapeutic interventions.
Chronic Demyelination and Axonal Degeneration in Multiple Sclerosis: Pathogenesis and Therapeutic Implications
The development of therapies to restore lost myelin and protect neurons is a promising avenue of investigation for the benefit of patients with MS.
Slowly Progressive Axonal Degeneration in a Rat Model of Chronic, Nonimmune-Mediated Demyelination
The axonal pathology in the taiep rat provides evidence that CNS axonopathy may, in certain situations, be related to a loss of trophic support normally provided by cells of the oligodendrocyte lineage and/or myelin; this may occur in the absence of significant inflammation.
Cognitive Impairment in Multiple Sclerosis: Clinical, Radiologic and Pathologic Insights
The relative contributions of gray and white matter to MS‐related cognitive impairment will be discussed and the importance of interconnectivity between structures highlighted and the pressing need for longitudinal studies combining standardized neuropsychometric, paraclinical and radiographic outcomes obtained during life with post‐mortem tissue analysis after death is presented.
Myelin Loss Does Not Lead to Axonal Degeneration in a Long-Lived Model of Chronic Demyelination
In vivo evidence is provided that mature glial cells produce various neurotrophic factors that may aid in the survival of axons after chronic demyelination, and there are no signs of axonal degeneration in les rats up to 9 months.
Inflammatory demyelinating diseases of the central nervous system
Sodium accumulation is associated with disability and a progressive course in multiple sclerosis.
Sodium concentration is increased within lesions, normal appearing white matter and cortical and deep grey matter in multiple sclerosis, with higher concentrations seen in secondary-progressive multiple sclerosis and in patients with greater disability.


Greater loss of axons in primary progressive multiple sclerosis plaques compared to secondary progressive disease.
Examining the cervical spinal cord in patients with primary and secondary progressive multiple sclerosis suggests axonal loss is the pathological substrate of progressive disability in both primary progressive and secondarygressive multiple sclerosis with a common plaque-centred mechanism.
Axon Loss in the Spinal Cord Determines Permanent Neurological Disability in an Animal Model of Multiple Sclerosis
Quantitative immunohistochemical methods that correlate inflammation and axonal loss with neurological disability in chronic-relapsing experimental autoimmune encephalomyelitis (EAE) imply a causal relationship between inflammation, axon loss, and irreversible neurological disability for MS.
Axonal transection in the lesions of multiple sclerosis.
Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.
Axonal changes in chronic demyelinated cervical spinal cord plaques.
The results on the cervical cord combined with other observations support the concept of slow axonal degeneration rather than acute damage as a cause of chronic disability in multiple sclerosis.
Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts.
Of the fibres lost in multiple sclerosis, it is found that small fibres seem to be particularly affected, with large fibres remaining relatively preserved in both the corticospinal and sensory tracts.
Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation.
Characterizing the association of axonal injury and histopathological hallmarks of multiple sclerosis such as demyelination, cellular infiltration and expression of inflammatory mediators and quantifying axonal reduction and signs of acute axonal damage in early lesion development of chronic multiple sclerosis found it to be independent of demYelinating activity and inflammation.
Axonal damage in acute multiple sclerosis lesions.
The results show the expression of amyloid precursor protein in damaged axons within acute multiple sclerosis lesions, and in the active borders of less acute lesions, which may have implications for the design and timing of therapeutic intervention.
Neurological disability correlates with spinal cord axonal loss and reduced N‐acetyl aspartate in chronic multiple sclerosis patients
The data support axonal loss as a major cause of irreversible neurological disability in paralyzed MS patients and indicate that reduced NAA as measured by magnetic resonance spectroscopy can reflect axonal Loss and reduced N AA levels in demyelinated and myelinated axons.
Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study.
It is concluded that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to disability.