Brain, Vol. 123, No. 2, 308-317,
February 2000
© 2000 Oxford University Press
Axonal changes in chronic demyelinated cervical spinal cord plaques
1 Department of Neurology, `Jahn Ferenc' Teaching Hospital, 2 Department of Comparative Physiology, Eötvös Loránd University of Sciences, 3 National Institute of Psychiatry and Neurology and 4 Laboratory of Neuromorphology, Semmelweis University Medical School, Budapest, Hungary
Correspondence to:
Sámuel Komoly, Department of Neurology, `Jahn Ferenc' Teaching Hospital, Köves u. 2–4, Budapest, H-1203, Hungary E-mail: Komoly{at}mail.matav.hu
Imaging and pathomorphological studies in multiple sclerosis suggest that axonal injury and axonal loss are playing a crucial role in those with persistent disability and long-standing disease. Although the existence of axonal injury in multiple sclerosis is proven, especially in the zone of active inflammation, the effect of chronic inflammation on the axons remains elusive. The aim of this study was to perform a quantitative morphometrical analysis, estimating axonal loss and evaluating axonal degenerative changes in cervical spinal cord samples of patients suffering from secondary progressive multiple sclerosis. Completely demyelinated plaques, normal appearing white matter (NAWM) and control material from anatomically identical regions of the cord have been compared. Neurofilament immunostaining was used for identification of the axons. We observed a significant reduction of axonal density (number of axons/mm2) in multiple sclerosis, both in the plaque and in the NAWM compared with the control cases. Axons under ~3.3 µm diameter seemed to be more affected. The intensity of the immunostaining was significantly reduced in the plaque compared with either NAWM or control. Our 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; multiple sclerosis; spinal cord; neurofilament 200 kDa immunostaining
APP = amyloid precursor protein; Cr = creatine; EDSS = Expanded Disability Status Scale; LC = lateral column; MRS = magnetic resonance spectroscopy; NAA = N-acetyl aspartate; NAWM = normal appearing white matter; NF-H = neurofilament heavy chain; PC = posterior column; RR = relapsing–remitting; SMI-32 = antibody raised against neurofilament protein epitopes known to be expressed in axonal damage; SP = secondary progressive
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]
|
|
|
|
 |
|
 J. M. Anderson, D. W. Hampton, R. Patani, G. Pryce, R. A. Crowther, R. Reynolds, R. J. M. Franklin, G. Giovannoni, D. A. S. Compston, D. Baker, et al. Abnormally phosphorylated tau is associated with neuronal and axonal loss in experimental autoimmune encephalomyelitis and multiple sclerosis Brain, July 1, 2008; 131(7): 1736 - 1748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zivadinov, A.C. Banas, V. Yella, N. Abdelrahman, B. Weinstock-Guttman, and M.G. Dwyer Comparison of Three Different Methods for Measurement of Cervical Cord Atrophy in Multiple Sclerosis AJNR Am. J. Neuroradiol., February 1, 2008; 29(2): 319 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Manconi, M.A. Rocca, L. Ferini-Strambi, P. Tortorella, F. Agosta, G. Comi, and M. Filippi Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage Multiple Sclerosis, January 1, 2008; 14(1): 86 - 93. [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]
|
|
|
|
 |
|
 I. Tsunoda, T. Tanaka, Y. Saijoh, and R. S. Fujinami Targeting Inflammatory Demyelinating Lesions to Sites of Wallerian Degeneration Am. J. Pathol., November 1, 2007; 171(5): 1563 - 1575. [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]
|
|
|
|
 |
|
 R. Dutta and B. D. Trapp Pathogenesis of axonal and neuronal damage in multiple sclerosis Neurology, May 29, 2007; 68(22_suppl_3): S22 - S31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J H Simon Brain atrophy in multiple sclerosis: what we know and would like to know Multiple Sclerosis, November 1, 2006; 12(6): 679 - 687. [Abstract] [PDF]
|
|
|
|
|
|
A Charil, D Caputo, R Cavarretta, M P Sormani, P Ferrante, and M Filippi Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study Multiple Sclerosis, September 1, 2006; 12(5): 662 - 665. [Abstract] [PDF]
|
|
|
|
 |
|
 M Bieniek, D R Altmann, G R Davies, G T Ingle, W Rashid, J Sastre-Garriga, A J Thompson, and D H Miller Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis J. Neurol. Neurosurg. Psychiatry, September 1, 2006; 77(9): 1036 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. DeLuca, K. Williams, N. Evangelou, G. C. Ebers, and M. M. Esiri The contribution of demyelination to axonal loss in multiple sclerosis Brain, June 1, 2006; 129(6): 1507 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M.F. Wong, K. McReelis, and J. A. Sharpe Saccade dynamics in peripheral vs central sixth nerve palsies Neurology, May 9, 2006; 66(9): 1390 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W Rashid, G R Davies, D T Chard, C M Griffin, D R Altmann, R Gordon, A J Thompson, and D H Miller Increasing cord atrophy in early relapsing-remitting multiple sclerosis: a 3 year study J. Neurol. Neurosurg. Psychiatry, January 1, 2006; 77(1): 51 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kutzelnigg, C. F. Lucchinetti, C. Stadelmann, W. Bruck, H. Rauschka, M. Bergmann, M. Schmidbauer, J. E. Parisi, and H. Lassmann Cortical demyelination and diffuse white matter injury in multiple sclerosis Brain, November 1, 2005; 128(11): 2705 - 2712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Caramanos, S. Narayanan, and D. L. Arnold 1H-MRS quantification of tNA and tCr in patients with multiple sclerosis: a meta-analytic review Brain, November 1, 2005; 128(11): 2483 - 2506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tiberio, D. T. Chard, D. R. Altmann, G. Davies, C. M. Griffin, W. Rashid, J. Sastre-Garriga, A. J. Thompson, and D. H. Miller Gray and white matter volume changes in early RRMS: A 2-year longitudinal study Neurology, March 22, 2005; 64(6): 1001 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Agosta, B. Benedetti, M. A. Rocca, P. Valsasina, M. Rovaris, G. Comi, and M. Filippi Quantification of cervical cord pathology in primary progressive MS using diffusion tensor MRI Neurology, February 22, 2005; 64(4): 631 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Kamholz, J. Y. Garbern, O. Gonen, Y. Ge, M. Inglese, and R. I. Grossman Neuronal cell injury precedes brain atrophy in multiple sclerosis Neurology, January 11, 2005; 64(1): 176 - 176. [Full Text] [PDF]
|
|
|
|
|
|
N. Evangelou, G. C. DeLuca, T. Owens, and M. M. Esiri Pathological study of spinal cord atrophy in multiple sclerosis suggests limited role of local lesions Brain, January 1, 2005; 128(1): 29 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. J. Bot, E. L. A. Blezer, W. Kamphorst, G. J. Lycklama a Nijeholt, H. J. Ader, J. A. Castelijns, K. N. Ig, E. Bergers, R. Ravid, C. Polman, et al. The Spinal Cord in Multiple Sclerosis: Relationship of High-Spatial-Resolution Quantitative MR Imaging Findings to Histopathologic Results Radiology, November 1, 2004; 233(2): 531 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lucchinetti and W. Bruck The pathology of primary progressive multiple sclerosis Multiple Sclerosis, June 1, 2004; 10(1_suppl): S23 - S30. [Abstract] [PDF]
|
|
|
|
|
|
R. R. Kreitman and F. Blanchette On the horizon: possible neuroprotective role for glatiramer acetate Multiple Sclerosis, June 1, 2004; 10(1_suppl): S81 - S89. [Abstract] [PDF]
|
|
|
|
 |
|
 M. J. Craner, J. Newcombe, J. A. Black, C. Hartle, M. L. Cuzner, and S. G. Waxman Molecular changes in neurons in multiple sclerosis: Altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger PNAS, May 25, 2004; 101(21): 8168 - 8173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. DeLuca, G. C. Ebers, and M. M. Esiri Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts Brain, May 1, 2004; 127(5): 1009 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lucchinetti and W. Bruck The pathology of primary progressive multiple sclerosis Multiple Sclerosis, May 1, 2004; 10(3_suppl): S23 - S30. [Abstract] [PDF]
|
|
|
|
|
|
R. R. Kreitman and F. Blanchette On the horizon: possible neuroprotective role for glatiramer acetate Multiple Sclerosis, May 1, 2004; 10(3_suppl): S81 - S89. [Abstract] [PDF]
|
|
|
|
|
|
M. J. Craner, B. C. Hains, A. C. Lo, J. A. Black, and S. G. Waxman Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger at sites of axonal injury in the spinal cord in EAE Brain, February 1, 2004; 127(2): 294 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Oleszak, J. R. Chang, H. Friedman, C. D. Katsetos, and C. D. Platsoucas Theiler's Virus Infection: a Model for Multiple Sclerosis Clin. Microbiol. Rev., January 1, 2004; 17(1): 174 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Lo, C. Y. Saab, J. A. Black, and S. G. Waxman Phenytoin Protects Spinal Cord Axons and Preserves Axonal Conduction and Neurological Function in a Model of Neuroinflammation In Vivo J Neurophysiol, November 1, 2003; 90(5): 3566 - 3571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Imitola, E. Y. Snyder, and S. J. Khoury Genetic programs and responses of neural stem/progenitor cells during demyelination: potential insights into repair mechanisms in multiple sclerosis Physiol Genomics, August 15, 2003; 14(3): 171 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Lassmann Axonal injury in multiple sclerosis J. Neurol. Neurosurg. Psychiatry, June 1, 2003; 74(6): 695 - 697. [Full Text] [PDF]
|
|
|
|
|
|
A. Castriota-Scanderbeg, F. Fasano, G. Hagberg, U. Nocentini, M. Filippi, and C. Caltagirone Coefficient Dav Is More Sensitive Than Fractional Anisotropy in Monitoring Progression of Irreversible Tissue Damage in Focal Nonactive Multiple Sclerosis Lesions AJNR Am. J. Neuroradiol., April 1, 2003; 24(4): 663 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Tsunoda, L.-Q. Kuang, J. E. Libbey, and R. S. Fujinami Axonal Injury Heralds Virus-Induced Demyelination Am. J. Pathol., April 1, 2003; 162(4): 1259 - 1269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M. Medana and M. M. Esiri Axonal damage: a key predictor of outcome in human CNS diseases Brain, March 1, 2003; 126(3): 515 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bergers, J.C.J. Bot, C.J.A. De Groot, C.H. Polman, G.J. Lycklama a Nijeholt, J.A. Castelijns, P. van der Valk, and F. Barkhof Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions Neurology, December 10, 2002; 59(11): 1766 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kuhlmann, G. Lingfeld, A. Bitsch, J. Schuchardt, and W. Bruck Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time Brain, October 1, 2002; 125(10): 2202 - 2212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Charles, R. Reynolds, D. Seilhean, G. Rougon, M. S. Aigrot, A. Niezgoda, B. Zalc, and C. Lubetzki Re-expression of PSA-NCAM by demyelinated axons: an inhibitor of remyelination in multiple sclerosis? Brain, September 1, 2002; 125(9): 1972 - 1979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Miller, F. Barkhof, J. A. Frank, G. J. M. Parker, and A. J. Thompson Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance Brain, August 1, 2002; 125(8): 1676 - 1695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rovaris, M. Bozzali, G. Santuccio, A. Ghezzi, D. Caputo, E. Montanari, A. Bertolotto, R. Bergamaschi, R. Capra, G. Mancardi, et al. In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis Brain, December 1, 2001; 124(12): 2540 - 2549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bjartmar, R. P. Kinkel, G. Kidd, R. A. Rudick, and B. D. Trapp Axonal loss in normal-appearing white matter in a patient with acute MS Neurology, October 9, 2001; 57(7): 1248 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. F. Kalkers, E. Bergers, J. A. Castelijns, M. A. A. van Walderveen, J. C. J. Bot, H. J. Ader, C. H. Polman, and F. Barkhof Optimizing the association between disability and biological markers in MS Neurology, October 9, 2001; 57(7): 1253 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Meyer, R. Weissert, R. Diem, M. K. Storch, K. L. de Graaf, B. Kramer, and M. Bahr Acute Neuronal Apoptosis in a Rat Model of Multiple Sclerosis J. Neurosci., August 15, 2001; 21(16): 6214 - 6220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kornek, M. K. Storch, J. Bauer, A. Djamshidian, R. Weissert, E. Wallstroem, A. Stefferl, F. Zimprich, T. Olsson, C. Linington, et al. Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis Brain, June 1, 2001; 124(6): 1114 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. L. a Nijeholt, E. Bergers, W. Kamphorst, J. Bot, K. Nicolay, J. A. Castelijns, J. H. T. M. van Waesberghe, R. Ravid, C. H. Polman, and F. Barkhof Post-mortem high-resolution MRI of the spinal cord in multiple sclerosis: A correlative study with conventional MRI, histopathology and clinical phenotype Brain, January 1, 2001; 124(1): 154 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Phillips Rethinking Multiple Sclerosis Arch Neurol, January 1, 2001; 58(1): 30 - 32. [Full Text] [PDF]
|
|
|
|
|
|
L. Jasmin, G. Janni, T. M. Moallem, D. A. Lappi, and P. T. Ohara Schwann Cells Are Removed from the Spinal Cord after Effecting Recovery from Paraplegia J. Neurosci., December 15, 2000; 20(24): 9215 - 9223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rovaris, M. Bozzali, G. Santuccio, G. Iannucci, M. P. Sormani, B. Colombo, G. Comi, and M. Filippi Relative contributions of brain and cervical cord pathology to multiple sclerosis disability: a study with magnetisation transfer ratio histogram analysis J. Neurol. Neurosurg. Psychiatry, December 1, 2000; 69(6): 723 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Revesz Axonal lesions in multiple sclerosis: an old story revisited Brain, February 1, 2000; 123(2): 203 - 204. [Full Text] [PDF]
|
|