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agate
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 Posted: Tue Sep 26, 2006 11:16 am Post subject: (Abstract & comment)Demyelination & axonal loss |
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From PubMed:
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Brain. 2006 Jun;129(Pt 6):1507-16.
The contribution of demyelination to axonal loss in multiple sclerosis
DeLuca GC, Williams K, Evangelou N, Ebers GC, Esiri MM.
Department of Clinical Neurology, University of Oxford, Oxford, UK.
The traditional notion that multiple sclerosis is a primary demyelinating disease has led to a plaque-centred view of both aetiology and the pathogenesis of disease progression. The presence of axonal loss has received increasing recognition. However, the relative roles of demyelination and axonal loss have not been fully clarified in multiple sclerosis nor have their possible interrelationships been elucidated.
Post-mortem material from the cerebrum, brainstem and spinal cord of 55 multiple sclerosis patients (29 males) with an age range of 25-83 years (mean = 57.5 years) and length of disease history ranging from 2 to 43 years (mean = 17.1 years) was stained for myelin. Plaque load was calculated by summing the relative proportion of plaque area compared with total white matter area of the corticospinal and sensory tracts at each level. This was related to estimates of axonal density and of total axon number in these tracts in the spinal cord.
Our results indicate that plaque load did not correlate with brain weight. Unexpectedly, after adjusting for sex, age and duration of disease, correlations between total plaque load and axonal loss in both the corticospinal tract and sensory tracts were weak or absent at each level investigated.
Since there was little correlation between plaque load and axonal loss, the possibility that demyelination is not the primary determinant of spinal cord axonal loss warrants consideration.
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Journal Watch Neurology for Sept. 19, 2006 contains this summary of the DeLuca article (abstract above) as well as a comment by Thomas Berger, MD:
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Summary and Comment
Axonal Loss Independent of Demyelination in Multiple Sclerosis
Evidence from the corticospinal and sensory tracts suggests that independent axonal loss may occur in at least some CNS regions.
Multiple sclerosis (MS) is considered to be an inflammatory demyelinating disease that leads to plaque formation within CNS white matter. Axonal loss is believed to be caused by inflammatory demyelinating processes within plaques or by Wallerian degeneration.
Researchers examined the relation between plaques and axonal loss in 55 postmortem samples from patients with MS duration of 2 to 43 years. Neuropathologic investigations focused on corticospinal and sensory tracts because of their well-recognized contributions to the chronic clinical progression of MS.
Analyses showed that total plaque loads did not correlate with brain weight or with MS disease duration. Remyelinated plaques were scant. The major finding was that correlations between total plaque load and axonal loss in the spinal tracts were weak or even absent. The authors conclude that at least some axonal loss seems to occur independent of demyelination.
Comment: These findings add to evidence from a series of recent neuropathologic and imaging studies that challenge the "inflammation and demyelination" concept of MS disease progression. Cortical plaques, diffuse alterations of normal-appearing white matter, and axonal loss separate from plaque sites seem to account more for progressive disability than does inflammatory demyelination.
This view is supported by extensive clinical experience showing that MRI plaque load does not correlate well with disease progression and that so-called disease-modifying drugs do not affect disease progression substantially.
However, we should not replace one dogma with another: Inflammation, demyelination, and axonal degeneration may occur at the same time or sequentially, acting dependently or independently.
— Thomas Berger, MD, MSc
Dr. Berger is Professor and Head of the Neuroimmunological and Multiple Sclerosis Clinic & Research Unit and Head of the Neurological Outpatient Clinic, Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
Published in Journal Watch Neurology September 19, 2006
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