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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

Citation(s):

DeLuca GC et al. The contribution of demyelination to axonal loss in multiple sclerosis. Brain 2006 Jun; 129:1507-16.

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