Brain, Vol. 121, No. 8, 1469-1477,
August 1, 1998
© 1998 Oxford University Press
Axonal damage correlates with disability in patients with relapsing- remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study
AbstractIt has been difficult to establish a strong correlation between total brain T2-weighted lesion volume on MRI and clinical disability in multiple sclerosis, in part because of the lack of pathological specificity of T2-weighted MRI signal changes. Proton magnetic resonance spectroscopy studies have shown that measurements of the resonance intensity of N-acetylaspartate (which is localized exclusively in neurons and neuronal processes in the mature brain) can provide a specific index of axonal damage or dysfunction. Here we report a 30-month longitudinal study of 29 patients with multiple sclerosis who had either a relapsing or a secondary progressive clinical course. Conventional brain MRI and single-voxel proton magnetic resonance spectroscopy examinations were obtained at intervals of 6-8 months with concurrent clinical evaluation. At the onset of the study, the brain N-acetylaspartate:creatine resonance intensity ratio was abnormally low for the whole group of patients (control mean = 2.93 +/- 0.2, patient mean = 2.56 +/- 0.4, P < 0.005). There were no significant differences between the relapsing and secondary progressive subgroups. Over the follow-up period, there was a trend towards a decrease (8%) in the brain N-acetylaspartate:creatine ratio for the 11 relapsing patients and a significant (P < 0.001) correlation between changes in the brain N-acetylaspartate:creatine ratio and expanded disability scale scores for the patients in this group. This correlation was even more evident for the patients who had clinically relevant relapses during the 30 months of follow-up (seven of 11 patients). Increases in T2-weighted lesion volumes (35% in 30 months for the group as a whole, P < 0.0001, without differences between the subgroups) did not correlate with disability either in the group of patients as a whole or in the different subgroups. We conclude that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to disability. Total T2-weighted lesion volumes, although more sensitive to changes with time than brain N-acetylaspartate, may be less relevant to understanding the progression of disability.
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N. De Stefano, M. T. Dotti, M. Mortilla, and A. Federico Magnetic resonance imaging and spectroscopic changes in brains of patients with cerebrotendinous xanthomatosis Brain, January 1, 2001; 124(1): 121 - 131. [Abstract] [Full Text] [PDF]
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M. K. Racke, K. Hawker, and E. M. Frohman Multiple Sclerosis and Magnetic Resonance Imaging: Advancement in Linking the Pictures With the Progression Arch Neurol, January 1, 2001; 58(1): 35 - 36. [Full Text] [PDF]
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N. De Stefano, S. Narayanan, G. S. Francis, R. Arnaoutelis, M. C. Tartaglia, J. P. Antel, P. M. Matthews, and D. L. Arnold Evidence of Axonal Damage in the Early Stages of Multiple Sclerosis and Its Relevance to Disability Arch Neurol, January 1, 2001; 58(1): 65 - 70. [Abstract] [Full Text] [PDF]
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M. R. Garnett, A. M. Blamire, R. G. Corkill, T. A. D. Cadoux-Hudson, B. Rajagopalan, and P. Styles Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury Brain, October 1, 2000; 123(10): 2046 - 2054. [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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M. R. Garnett, A. M. Blamire, B. Rajagopalan, P. Styles, and T. A. D. Cadoux-Hudson Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: A magnetic resonance spectroscopy study Brain, July 1, 2000; 123(7): 1403 - 1409. [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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A. Bitsch, J. Schuchardt, S. Bunkowski, T. Kuhlmann, and W. Bruck Acute axonal injury in multiple sclerosis: Correlation with demyelination and inflammation Brain, June 1, 2000; 123(6): 1174 - 1183. [Abstract] [Full Text] [PDF]
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R. W. Haley, W. W. Marshall, G. G. McDonald, M. A. Daugherty, F. Petty, and J. L. Fleckenstein Brain Abnormalities in Gulf War Syndrome: Evaluation with Radiology, June 1, 2000; 215(3): 807 - 817. [Abstract] [Full Text]
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M. ESIRI;, G V MCDONNELL, and S A HAWKINS Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors J. Neurol. Neurosurg. Psychiatry, March 1, 2000; 68(3): 396 - 396. [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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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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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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A. Tourbah, J. L. Stievenart, O. Gout, B. Fontaine, R. Liblau, C. Lubetzki, E. A. Cabanis, and O. Lyon-Caen Localized proton magnetic resonance spectroscopy in relapsing remitting versus secondary progressive multiple sclerosis Neurology, September 1, 1999; 53(5): 1091 - 1091. [Abstract] [Full Text]
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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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G. Mastronardo, M. A. Rocca, G. Iannucci, C. Pereira, and M. Filippi A Longitudinal MR Study of the Presymptomatic Phase in a Patient with Clinically Definite Multiple Sclerosis AJNR Am. J. Neuroradiol., August 1, 1999; 20(7): 1268 - 1272. [Abstract] [Full Text]
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G. Pike, de Stefano, Narayanan, G. Francis, J. Antel, and D. Arnold Combined Magnetization Transfer and Proton Spectroscopic Imaging in the Assessment of Pathologic Brain Lesions in Multiple AJNR Am. J. Neuroradiol., May 1, 1999; 20(5): 829 - 837. [Abstract] [Full Text]
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