Brain Advance Access originally published online on April 5, 2006
Brain 2006 129(6):1507-1516; doi:10.1093/brain/awl074
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The contribution of demyelination to axonal loss in multiple sclerosis
1 Department of Clinical Neurology, University of Oxford Oxford, UK 2 Department of Neuropathology, Oxford Radcliffe NHS Trust Oxford, UK 3 Department of Neurology, Queen's Medical Centre, University Hospital NHS Trust Nottingham, UK
Correspondence to: Prof. M. M. Esiri, Neuropathology Department, Radcliffe Infirmary, Oxford OX2 6HE, UK E-mail: margaret.esiri{at}clneuro.ox.ac.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.
Key Words: demyelination; axon; axonal degeneration; multiple sclerosis; neuropathology
Abbreviations: NAWM, normal appearing white matter
Received September 19, 2005. Revised February 24, 2006. Accepted March 3, 2006.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A Wilkins and N Scolding Protecting axons in multiple sclerosis Multiple Sclerosis, September 1, 2008; 14(8): 1013 - 1025. [Abstract] [PDF]
|
|
|
|
|
|
I. Kezele, D. Arnold, and D. Collins Atrophy in white matter fiber tracts in multiple sclerosis is not dependent on tract length or local white matter lesions Multiple Sclerosis, July 1, 2008; 14(6): 779 - 785. [Abstract] [PDF]
|
|
|
|
 |
|
 A. P. D. Henderson, S. A. Trip, P. G. Schlottmann, D. R. Altmann, D. F. Garway-Heath, G. T. Plant, and D. H. Miller An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography Brain, January 1, 2008; 131(1): 277 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Qi, L. Sun, A. S. Lewin, W. W. Hauswirth, and J. Guy Long-term Suppression of Neurodegeneration in Chronic Experimental Optic Neuritis: Antioxidant Gene Therapy Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5360 - 5370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Mathey, T. Derfuss, M. K. Storch, K. R. Williams, K. Hales, D. R. Woolley, A. Al-Hayani, S. N. Davies, M. N. Rasband, T. Olsson, et al. Neurofascin as a novel target for autoantibody-mediated axonal injury J. Exp. Med., October 1, 2007; 204(10): 2363 - 2372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Agosta, M. Absinta, M. P. Sormani, A. Ghezzi, A. Bertolotto, E. Montanari, G. Comi, and M. Filippi In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study Brain, August 1, 2007; 130(8): 2211 - 2219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Birnbaum, T. P. Leist, and F. D. Lublin Commentary I: Pathophysiologic construct for neuronal degeneration/regeneration in multiple sclerosis Neurology, May 29, 2007; 68(22_suppl_3): S2 - S4. [Full Text] [PDF]
|
|
|
|
|
|
R. P. Lisak Neurodegeneration in multiple sclerosis: Defining the problem Neurology, May 29, 2007; 68(22_suppl_3): S5 - S12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Axonal Loss Independent of Demyelination in Multiple Sclerosis Journal Watch Neurology, September 19, 2006; 2006(919): 1 - 1. [Full Text]
|
|