Brain, Vol 121, Issue 1 3-24, Copyright © 1998 by Oxford University Press
DH Miller, RI Grossman, SC Reingold and HF McFarland
Magnetic resonance (MR) techniques have had a major impact in the last
10-15 years in understanding and managing multiple sclerosis. This review
summarizes the current uses of MR in multiple sclerosis, based on the
proceedings of a recent international workshop, under four headings: (i)
technical issues; (ii) role in diagnosis; (iii) natural history studies in
understanding the disease; (iv) application in clinical trials. The theory
and methodology of relevant technical issues is outlined, in order to
provide a framework with which to understand the potential and limitations
of MR in addressing biological and clinical questions in multiple
sclerosis. The principles underlying signal-to-noise and contrast-to-noise
ratio are discussed, along with the techniques and clinical results for
conventional and fast spin echo T2-weighted imaging, fluid-attenuated
inversion recovery, detection of blood-brain barrier break down and
hypointense lesions on T1-weighted images, magnetization transfer, T2
decay-curve analysis, MR spectroscopy, spinal cord imaging, diffusion
imaging, and quantification of lesion load and atrophy. MRI has an
extremely valuable role in confirming the clinical diagnosis of multiple
sclerosis. T2-weighted brain imaging remains the standard diagnostic tool,
but in some instances it is usefully complemented with gadolinium
enhancement and spinal imaging. The caveat that the diagnosis of multiple
sclerosis remains primarily a clinical one cannot be over- emphasized.
Serial MRI studies have added much to our understanding of the natural
history and pathophysiology of the disease. Blood-brain barrier breakdown
is a consistent early feature of new lesion development in
relapsing-remitting and secondary progressive multiple, sclerosis, and this
usually correlates with active inflammation and myelin breakdown. A number
of the acute MR changes are reversible, but chronic persistent
abnormalities in a number of MR parameters, such as reduced N-acetyl
aspartate, low magnetization transfer ratios, atrophy and T1-hypointensity,
suggest the presence of demyelination and/or axonal degeneration in many
chronic lesions. The presence and extent of T2-weighted MRI abnormalities
at first presentation with a clinically isolated syndrome suggestive of
demyelination strongly predicts the risk of developing clinically definite
multiple sclerosis in the next few years. In established multiple
sclerosis, however, the correlations between T2 abnormalities and
disability are modest. This poor relationship partly relates to the
discrepancy between lesion site and function in attempting to correlate
locomotor disability with brain MRI findings. However, the correlations
between brain lesion load and cognitive dysfunction in multiple sclerosis,
whilst more evident, are still modest. A more important limitation is the
low pathological specificity of abnormalities seen on T2-weighted images.
Stronger correlations have been found between disability and new putative
MR markers for demyelination and/or axonal degeneration. Serial studies
using multiple MR techniques are now needed to further clarify
pathophysiological mechanisms in multiple sclerosis. Serial MR has become
an important tool in monitoring treatment efficacy. It provides data which
can be readily analysed in a blinded fashion and which directly inspects
the pathological evolution; it also enables a rapid and sensitive measure
of treatment outcome in early relapsing-remitting and secondary progressive
disease. Because of the modest clinical correlations it is, however, still
appropriate that the definitive determinant of treatment efficacy remains a
clinical one. Further work is needed to address issues of quality control
in serial studies, statistical calculation of appropriate sample sizes, and
optimization of the nature and frequency of MR outcomes measured.
REVIEWS
The role of magnetic resonance techniques in understanding and managing multiple sclerosis
Institute of Neurology, London, UK.
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J. A. Koziol, S. Wagner, D. F. Sobel, L. S. Slivka, J. S. Romine, J. C. Sipe, and H.-P. Adams Predictive Value of Lesions for Relapses in Relapsing-remitting Multiple Sclerosis AJNR Am. J. Neuroradiol., February 1, 2001; 22(2): 284 - 291. [Abstract] [Full Text] [PDF]
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T. P. Leist, M. I. Gobbini, J. A. Frank, and H. F. McFarland Enhancing Magnetic Resonance Imaging Lesions and Cerebral Atrophy in Patients With Relapsing Multiple Sclerosis Arch Neurol, January 1, 2001; 58(1): 57 - 60. [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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G. R. W. Moore, E. Leung, A. L. MacKay, I. M. Vavasour, K. P. Whittall, K. S. Cover, D. K. B. Li, S. A. Hashimoto, J. Oger, T. J. Sprinkle, et al. A pathology-MRI study of the short-T2 component in formalin-fixed multiple sclerosis brain Neurology, November 28, 2000; 55(10): 1506 - 1510. [Abstract] [Full Text] [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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P. D. Molyneux, L. Kappos, C. Polman, C. Pozzilli, F. Barkhof, M. Filippi, T. Yousry, D. Hahn, K. Wagner, M. Ghazi, et al. The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis Brain, November 1, 2000; 123(11): 2256 - 2263. [Abstract] [Full Text] [PDF]
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M Filippi Enhanced magnetic resonance imaging in multiple sclerosis Multiple Sclerosis, October 1, 2000; 6(5): 320 - 326. [Abstract] [PDF]
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V. Janardhan and R. Bakshi Quality of Life and Its Relationship to Brain Lesions and Atrophy on Magnetic Resonance Images in 60 Patients With Multiple Sclerosis Arch Neurol, October 1, 2000; 57(10): 1485 - 1491. [Abstract] [Full Text] [PDF]
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A. O. Nusbaum, D. Lu, C. Y. Tang, and S. W. Atlas Quantitative Diffusion Measurements in Focal Multiple Sclerosis Lesions: Correlations with Appearance on TI-Weighted MR Images Am. J. Roentgenol., September 1, 2000; 175(3): 821 - 825. [Abstract] [Full Text] [PDF]
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F. Fazekas, S. Strasser-Fuchs, H. Schmidt, C. Enzinger, S. Ropele, A. Lechner, E. Flooh, R. Schmidt, and H.-P. Hartung Apolipoprotein E genotype related differences in brain lesions of multiple sclerosis J. Neurol. Neurosurg. Psychiatry, July 1, 2000; 69(1): 25 - 28. [Abstract] [Full Text] [PDF]
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V L Stevenson, D H Miller, S M Leary, M Rovaris, F Barkhof, B Brochet, V Dousset, V Dousset, M Filippi, R Hintzen, et al. One year follow up study of primary and transitional progressive multiple sclerosis J. Neurol. Neurosurg. Psychiatry, June 1, 2000; 68(6): 713 - 718. [Abstract] [Full Text] [PDF]
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I L. Tan, R. A. van Schijndel, P. J. W. Pouwels, M. A. A. van Walderveen, J. R. Reichenbach, R. A. Manoliu, and F. Barkhof MR Venography of Multiple Sclerosis AJNR Am. J. Neuroradiol., June 1, 2000; 21(6): 1039 - 1042. [Abstract] [Full Text]
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G. B. Pike, N. De Stefano, S. Narayanan, K. J. Worsley, D. Pelletier, G. S. Francis, J. P. Antel, and D. L. Arnold Multiple Sclerosis: Magnetization Transfer MR Imaging of White Matter before Lesion Appearance on T2-weighted Images Radiology, June 1, 2000; 215(3): 824 - 830. [Abstract] [Full Text]
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M. H. Lev Diffusion-weighted MR imaging of multiple sclerosis: added clinical value or "just another pretty face?". AJNR Am. J. Neuroradiol., May 1, 2000; 21(5): 805 - 808. [Full Text]
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A. C. Scanderbeg, F. Tomaiuolo, U. Sabatini, U. Nocentini, M. G. Grasso, and C. Caltagirone Demyelinating Plaques in Relapsing-remitting and Secondary-progressive Multiple Sclerosis: Assessment with Diffusion MR Imaging AJNR Am. J. Neuroradiol., May 1, 2000; 21(5): 862 - 868. [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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I. Elovaara, M. Ukkonen, M. Leppakynnas, T. Lehtimaki, M. Luomala, J. Peltola, and P. Dastidar Adhesion Molecules in Multiple Sclerosis: Relation to Subtypes of Disease and Methylprednisolone Therapy Arch Neurol, April 1, 2000; 57(4): 546 - 551. [Abstract] [Full Text] [PDF]
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N. C. Fox, R. Jenkins, S. M. Leary, V. L. Stevenson, N. A. Losseff, W. R. Crum, R. J. Harvey, M. N. Rossor, D. H. Miller, and A. J. Thompson Progressive cerebral atrophy in MS: A serial study using registered, volumetric MRI Neurology, February 22, 2000; 54(4): 807 - 812. [Abstract] [Full Text] [PDF]
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C. Gasperini, C. Pozzilli, S. Bastianello, E. Giugni, M. A Horsfield, T. Koudriavtseva, S. Galgani, A. Paolillo, S. Haggiag, E. Millefiorini, et al. Interferon-beta -1a in relapsing-remitting multiple sclerosis: effect on hypointense lesion volume on T1 weighted images J. Neurol. Neurosurg. Psychiatry, November 1, 1999; 67(5): 579 - 584. [Abstract] [Full Text]
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H. F. McFarland Correlation between MR and Clinical Findings of Disease Activity in Multiple Sclerosis AJNR Am. J. Neuroradiol., November 1, 1999; 20(10): 1777 - 1778. [Full Text]
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A. Rovira, J. Alonso, G. Cucurella, C. Nos, M. Tintoré, S. Pedraza, J. Rio, and X. Montalban Evolution of Multiple Sclerosis Lesions on Serial Contrast-Enhanced T1-Weighted and Magnetization-Transfer MR Images AJNR Am. J. Neuroradiol., November 1, 1999; 20(10): 1939 - 1945. [Abstract] [Full Text]
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D. B. Hackney MR Studies of the Spinal Cord in Patients with Multiple Sclerosis: What Should We Do? AJNR Am. J. Neuroradiol., October 1, 1999; 20(9): 1581 - 1583. [Full Text]
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A. Bitsch, H. Bruhn, V. Vougioukas, A. Stringaris, H. Lassmann, J. Frahm, and W. Brück Inflammatory CNS Demyelination: Histopathologic Correlation with In Vivo Quantitative Proton MR Spectroscopy AJNR Am. J. Neuroradiol., October 1, 1999; 20(9): 1619 - 1627. [Abstract] [Full Text]
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A. Paolillo, A. J. Coles, P. D. Molyneux, M. Gawne-Cain, D. MacManus, G. J. Barker, D. A. S. Compston, and D. H. Miller Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H Neurology, September 1, 1999; 53(4): 751 - 751. [Abstract] [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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