Brain, Vol 121, Issue 1 103-113, Copyright © 1998 by Oxford University Press
L Fu, PM Matthews, N De Stefano, KJ Worsley, S Narayanan, GS Francis, JP Antel, C Wolfson and DL Arnold
The current study was designed to determine the relative distribution of
decreases of N-acetylasparate (NAA), a marker of axonal damage, between
lesions and normal-appearing white matter of patients with established
multiple sclerosis and to test for associations between changes in the
ratio of NAA to creatine/phosphocreatine (NAA:Cr) in those compartments and
changes in disability. Data were collected from a 30-month longitudinal
study of 28 patients with either a relapsing course with partial remissons
and no progression between attacks (relapsing/remitting) (11 patients) or a
course of progressively increasing disability, following a period of
relapsing/remitting disease (secondary progressive) (17 patients). Proton
magnetic resonance spectroscopic imaging (MRSI) and conventional MRI
examinations were performed at 6-8-month intervals with concurrent clinical
assessments of disability. General linear models were used to test
associations between MRSI, MRI, lesion volume and clinical data. Analysis
confirmed that the NAA:Cr ratio is lower in lesions than in the
normal-appearing white matter (-15.3% in relapsing/remitting multiple
sclerosis and -8.8% in secondary progressive multiple sclerosis). The lower
NAA:Cr ratio per unit lesion volume previously observed for secondary
progressive relative to relapsing/remitting patients was found to result
from a lower ratio (8.2%, P < 0.01) in the normal-appearing white matter
rather than from any differences within lesions. The importance of changes
in the normal-appearing white matter was emphasized further with the
observation that the NAA:Cr ratio in the normal-appearing white matter
accounted for most of the observed 15.6% (P < 0.001) decrease in the
NAA:Cr ratio in the brains of relapsing/remitting patients over the period
of study. The decrease in the NAA:Cr ratio in normal-appearing white matter
correlated strongly (P < 0.001) with changes in disability in the
relapsing/remitting subgroup. These results add to data suggesting that
axonal damage or loss may be responsible for functional impairments in
multiple sclerosis. The accumulation of secondary axonal damage in the
normal- appearing white matter may be of particular significance for
understanding chronic disability in this disease.
ARTICLES
Imaging axonal damage of normal-appearing white matter in multiple sclerosis
Montreal Neurological Institute, McGill University, Quebec, Canada.
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J. Pelletier, L. Suchet, T. Witjas, M. Habib, C. R. G. Guttmann, G. Salamon, O. Lyon-Caen, and A. A. Cherif A Longitudinal Study of Callosal Atrophy and Interhemispheric Dysfunction in Relapsing-Remitting Multiple Sclerosis Arch Neurol, January 1, 2001; 58(1): 105 - 111. [Abstract] [Full Text] [PDF]
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A. J Thompson Neurological rehabilitation: from mechanisms to management J. Neurol. Neurosurg. Psychiatry, December 1, 2000; 69(6): 718 - 722. [Full Text] [PDF]
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E Fisher, R A Rudick, G Cutter, M Baier, D Miller, B Weinstock-Guttman, M K Mass, D S Dougherty, and N A Simonian Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients Multiple Sclerosis, December 1, 2000; 6(6): 373 - 377. [Abstract] [PDF]
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S. Ropele, S. Strasser-Fuchs, M. Augustin, R. Stollberger, C. Enzinger, H.-P. Hartung, and F. Fazekas A Comparison of Magnetization Transfer Ratio, Magnetization Transfer Rate, and the Native Relaxation Time of Water Protons Related to Relapsing-remitting Multiple Sclerosis AJNR Am. J. Neuroradiol., November 1, 2000; 21(10): 1885 - 1891. [Abstract] [Full Text] [PDF]
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H. Reddy, S. Narayanan, R. Arnoutelis, M. Jenkinson, J. Antel, P. M. Matthews, and D. L. Arnold Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis Brain, November 1, 2000; 123(11): 2314 - 2320. [Abstract] [Full Text] [PDF]
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N. Evangelou, D. Konz, M. M. Esiri, S. Smith, J. Palace, and P. M. Matthews Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis Brain, September 1, 2000; 123(9): 1845 - 1849. [Abstract] [Full Text] [PDF]
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I. Mader, W. Roser, L. Kappos, G. Hagberg, J. Seelig, E. W. Radue, and W. Steinbrich Serial Proton MR Spectroscopy of Contrast-enhancing Multiple Sclerosis Plaques: Absolute Metabolic Values over 2 Years during a Clinical Pharmacological Study AJNR Am. J. Neuroradiol., July 1, 2000; 21(7): 1220 - 1227. [Abstract] [Full Text] [PDF]
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 B. Kornek, M. K. Storch, R. Weissert, E. Wallstroem, A. Stefferl, T. Olsson, C. Linington, M. Schmidbauer, and H. Lassmann Multiple Sclerosis and Chronic Autoimmune Encephalomyelitis : A Comparative Quantitative Study of Axonal Injury in Active, Inactive, and Remyelinated Lesions Am. J. Pathol., July 1, 2000; 157(1): 267 - 276. [Abstract] [Full Text] [PDF]
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J Suhy, W D Rooney, D E Goodkin, A A Capizzano, B J Soher, A A Maudsley, E Waubant, P B Andersson, and M W Weiner 1H MRSI comparison of white matter and lesions in primary progressive and relapsing-remitting MS Multiple Sclerosis, June 1, 2000; 6(3): 148 - 155. [Abstract] [PDF]
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G. Iannucci, C. Tortorella, M. Rovaris, M. P. Sormani, G. Comi, and M. Filippi Prognostic Value of MR and Magnetization Transfer Imaging Findings in Patients withClinically Isolated Syndromes Suggestive ofMultiple Sclerosis at Presentation AJNR Am. J. Neuroradiol., June 1, 2000; 21(6): 1034 - 1038. [Abstract] [Full Text]
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A. O. Nusbaum, C. Y. Tang, T.-C. Wei, M. S. Buchsbaum, and S. W. Atlas Whole-brain diffusion MR histograms differ between MS subtypes Neurology, April 11, 2000; 54(7): 1421 - 1427. [Abstract] [Full Text] [PDF]
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C. Liu and L. D Blumhardt Disability outcome measures in therapeutic trials of relapsing-remitting multiple sclerosis: effects of heterogeneity of disease course in placebo cohorts J. Neurol. Neurosurg. Psychiatry, April 1, 2000; 68(4): 450 - 457. [Abstract] [Full Text] [PDF]
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J. H. Simon, R. P. Kinkel, L. Jacobs, L. Bub, and N. Simonian A Wallerian degeneration pattern in patients at risk for MS Neurology, March 14, 2000; 54(5): 1155 - 1160. [Abstract] [Full Text] [PDF]
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D. B. McGavern, P. D. Murray, C. Rivera-Quinones, J. D. Schmelzer, P. A. Low, and M. Rodriguez Axonal loss results in spinal cord atrophy, electrophysiological abnormalities and neurological deficits following demyelination in a chronic inflammatory model of multiple sclerosis Brain, March 1, 2000; 123(3): 519 - 531. [Abstract] [Full Text] [PDF]
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M Filippi, C Tortorella, M Rovaris, M Bozzali, F Possa, M P Sormani, G Iannucci, and G Comi Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis J. Neurol. Neurosurg. Psychiatry, February 1, 2000; 68(2): 157 - 161. [Abstract] [Full Text] [PDF]
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G. Lovas, N. Szilagyi, K. Majtenyi, M. Palkovits, and S. Komoly Axonal changes in chronic demyelinated cervical spinal cord plaques Brain, February 1, 2000; 123(2): 308 - 317. [Abstract] [Full Text] [PDF]
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C. Tortorella, B. Viti, M. Bozzali, M. P. Sormani, G. Rizzo, M. F. Gilardi, G. Comi, and M. Filippi A magnetization transfer histogram study of normal-appearing brain tissue in MS Neurology, January 11, 2000; 54(1): 186 - 186. [Abstract] [Full Text] [PDF]
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M. Filippi, M. Bozzali, M. A. Horsfield, M. A. Rocca, M. P. Sormani, G. Iannucci, B. Colombo, and G. Comi A conventional and magnetization transfer MRI study of the cervical cord in patients with MS Neurology, January 11, 2000; 54(1): 207 - 207. [Abstract] [Full Text] [PDF]
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M. A. Lee, A. M. Blamire, S. Pendlebury, K.-H. Ho, K. R. Mills, P. Styles, J. Palace, and P. M. Matthews Axonal Injury or Loss in the Internal Capsule and Motor Impairment in Multiple Sclerosis Arch Neurol, January 1, 2000; 57(1): 65 - 70. [Abstract] [Full Text] [PDF]
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C A Davie, N C Silver, G J Barker, P S Tofts, A J Thompson, W I McDonald, and D H Miller Does the extent of axonal loss and demyelination from chronic lesions in multiple sclerosis correlate with the clinical subgroup? J. Neurol. Neurosurg. Psychiatry, December 1, 1999; 67(6): 710 - 715. [Abstract] [Full Text] [PDF]
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 J. W Prichard and J. R Alger The NMR revolution in brain imaging BMJ, November 13, 1999; 319(7220): 1302 - 1302. [Full Text]
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M. Bozzali, M. A. Rocca, G. Iannucci, C. Pereira, G. Comi, and M. Filippi Magnetization-Transfer Histogram Analysis of the Cervical Cord in Patients with Multiple Sclerosis AJNR Am. J. Neuroradiol., November 1, 1999; 20(10): 1803 - 1808. [Abstract] [Full Text]
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M. Filippi, M. A. Rocca, L. Moiola, V. Martinelli, A. Ghezzi, R. Capra, F. Salvi, and G. Comi MRI and magnetization transfer imaging changes in the brain and cervical cord of patients with Devic's neuromyelitis optica Neurology, November 1, 1999; 53(8): 1705 - 1705. [Abstract] [Full Text] [PDF]
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S M Leary, N C Silver, V L Stevenson, G J Barker, D H Miller, and A J Thompson Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis Multiple Sclerosis, October 1, 1999; 5(5): 313 - 316. [Abstract] [PDF]
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N. De Stefano, S. Narayanan, P. M. Matthews, G. S. Francis, J. P. Antel, and D. L. Arnold In vivo evidence for axonal dysfunction remote from focal cerebral demyelination of the type seen in multiple sclerosis Brain, October 1, 1999; 122(10): 1933 - 1939. [Abstract] [Full Text] [PDF]
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J. Garbern, F. Cambi, M. Shy, and J. Kamholz The Molecular Pathogenesis of Pelizaeus-Merzbacher Disease Arch Neurol, October 1, 1999; 56(10): 1210 - 1214. [Full Text] [PDF]
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A J THOMPSON Benign multiple sclerosis J. Neurol. Neurosurg. Psychiatry, August 1, 1999; 67(2): 138 - 138. [Full Text] [PDF]
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V L Stevenson and D H Miller Magnetic resonance imaging in the monitoring of disease progression in multiple sclerosis Multiple Sclerosis, August 1, 1999; 5(4): 268 - 272. [Abstract] [PDF]
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M. Filippi, C. Tortorella, and M. Bozzali Normal-appearing white matter changes in multiple sclerosis: the contribution of magnetic resonance techniques Multiple Sclerosis, August 1, 1999; 5(4): 273 - 282. [Abstract] [PDF]
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