Brain, Vol. 119, No. 6, 2009-2019, 1996
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research-article |
Progressive cerebral atrophy in multiple sclerosis A serial MRI study
1 NMR Research Unit, Institute of Neurology 2 Department of Medical Physics and Bio-Engineering, University College London UK
Correspondence to:
Correspondence to: Dr A. J. Thompson, NMR Research Unit, Institute of Neurology, Queen Square, London WC1N 3BG, UK
Summary Recent studies of the spinal cord and cerebellum have highlighted the importance of atrophy in the development of neurological impairment in multiple sclerosis. We have therefore developed a technique to quantify the volume of another area commonly involved pathologically in multiple sclerosis: the cerebral white matter. The technique we describe extracts the brain from the skull on four contiguous 5 mm periventricular slices using an algorithm integrated in an image analysis package, and quantifies their volume. Intra-observer scan-rescan reproducibility was 0.56%. We have applied this technique serially to 29 patients with multiple sclerosis selected for an 18-month treatment trial with a monoclonal antibody against CD4+ lymphocytes (deemed clinically ineffective). A decrease in volume beyond the 95% confidence limits for measurement variation was seen in 16 patients by the end of the 18-month period. The rate of development of atrophy was significantly higher in those who had a sustained deterioration in their Kurtzke expanded disability status scale (EDSS) score compared with those who did not (respective means: –6.4 ml year–1 and –1.8 ml year–1, P < 0.05) but in both groups these changes differed significantly from baseline (P < 0.05). Baseline T2 lesion load, change in T2 lesion load over 18 months and the volume of new gadolinium enhancing lesions on monthly scans for the first 10 months showed no correlation with the development of atrophy. This study demonstrates that progressive cerebral atrophy can be detected in individual patients with multiple sclerosis, correlates with worsening disability and gives additional information to that obtained with conventional MRI. The effect of putative therapies aimed at preventing disability could be objectively assessed by this measure.
multiple sclerosis; MRI; disability; cerebral atrophy; gadolinium enhancement; lesion load; clinical measurement.
Received April 16, 1996. Revised July 29, 1996. Accepted August 5, 1996.
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C Gasperini, M Rovaris, M P Sormani, S Bastianello, C Pozzilli, G Comi, and M Filippi Intra-observer, inter-observer and inter-scanner variations in brain MRI volume measurements in multiple sclerosis Multiple Sclerosis, February 1, 2001; 7(1): 27 - 31. [Abstract] [PDF]
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J. S Wolinsky, P. A Narayana, K. P Johnson, and Copolymer 1 Multiple Sclerosis Study Group and the United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates Multiple Sclerosis, February 1, 2001; 7(1): 33 - 41. [Abstract] [PDF]
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J. T. Phillips Rethinking Multiple Sclerosis Arch Neurol, January 1, 2001; 58(1): 30 - 32. [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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M. A. A. van Walderveen, G. J. Lycklama a Nijeholt, H. J. Ader, P. J. H. Jongen, C. H. Polman, J. A. Castelijns, and F. Barkhof Hypointense Lesions on T1-Weighted Spin-Echo Magnetic Resonance Imaging: Relation to Clinical Characteristics in Subgroups of Patients With Multiple Sclerosis Arch Neurol, January 1, 2001; 58(1): 76 - 81. [Abstract] [Full Text] [PDF]
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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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M. Filippi, M. Rovaris, G. Iannucci, S. Mennea, M. P. Sormani, and G. Comi Whole brain volume changes in patients with progressive MS treated with cladribine Neurology, December 12, 2000; 55(11): 1714 - 1718. [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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R. A Rudick, E. Fisher, J.-C. Lee, J. T Duda, and J. Simon Brain atrophy in relapsing multiple sclerosis: relationship to relapses, EDSS, and treatment with interferon {beta}-1a Multiple Sclerosis, December 1, 2000; 6(6): 365 - 372. [Abstract] [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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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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J. H. Noseworthy, P. C. O'Brien, B. G. Weinshenker, J. A. Weis, T. M. Petterson, B. J. Erickson, A. J. Windebank, J. P. Whisnant, K. A. Stolp-Smith, C. M. Harper Jr., et al. IV immunoglobulin does not reverse established weakness in MS: A double-blind, placebo-controlled trial Neurology, October 24, 2000; 55(8): 1135 - 1143. [Abstract] [Full Text] [PDF]
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H.-P. Adams, J. A. Koziol, N. C. Fox, D. H. Miller, and A. J. Thompson Progressive cerebral atrophy in MS: A serial study using registered, volumetric MRI Neurology, October 24, 2000; 55(8): 1242 - 1243. [Full Text] [PDF]
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T L Luks, D E Goodkin, S J Nelson, S Majumdar, P Bacchetti, D Portnoy, and R Sloan A longitudinal study of ventricular volume in early relapsing-remitting multiple sclerosis Multiple Sclerosis, October 1, 2000; 6(5): 332 - 337. [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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P. D Molyneux, P. A Brex, C. Fogg, S. Lewis, C. Middleditch, F. Barkhof, M. P Sormani, M. Filippi, and D. H Miller The precision of T1 hypointense lesion volume quantification in multiple sclerosis treatment trials: a multicenter study Multiple Sclerosis, August 1, 2000; 6(4): 237 - 240. [Abstract] [PDF]
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J. H. Simon, J. Lull, L. D. Jacobs, R. A. Rudick, D. L. Cookfair, R. M. Herndon, J. R. Richert, A. M. Salazar, J. Sheeder, D. Miller, et al. A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon {beta}-1a Neurology, July 25, 2000; 55(2): 185 - 192. [Abstract] [Full Text] [PDF]
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A. M. Saindane, Y. Ge, J. K. Udupa, J. S. Babb, L. J. Mannon, and R. I. Grossman The effect of gadolinium-enhancing lesions on whole brain atrophy in relapsing-remitting MS Neurology, July 12, 2000; 55(1): 61 - 65. [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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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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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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P. A. Brex, R. Jenkins, N. C. Fox, W. R. Crum, J. I. O'Riordan, G. T. Plant, and D. H. Miller Detection of ventricular enlargement in patients at the earliest clinical stage of MS Neurology, April 25, 2000; 54(8): 1689 - 1691. [Abstract] [Full Text] [PDF]
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Y. Ge, R. I. Grossman, J. K. Udupa, L. Wei, L. J. Mannon, M. Polansky, and D. L. Kolson Brain Atrophy in Relapsing-Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis: Longitudinal Quantitative Analysis Radiology, March 1, 2000; 214(3): 665 - 670. [Abstract] [Full Text]
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W. J. Jagust and J. H. Noseworthy Brain atrophy as a surrogate marker in MS: Faster, simpler, better? Neurology, February 22, 2000; 54(4): 782 - 783. [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. L. A. Mann, M. B. Davies, M. D. Boggild, J. Alldersea, A. A. Fryer, P. W. Jones, C. Ko Ko, C. Young, R. C. Strange, and C. P. Hawkins Glutathione S-transferase polymorphisms in MS: Their relationship to disability Neurology, February 8, 2000; 54(3): 552 - 552. [Abstract] [Full Text] [PDF]
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M. Blinkenberg, K. Rune, C. V. Jensen, M. Ravnborg, S. Kyllingsbak, S. Holm, O. B. Paulson, and P. S. Sorensen Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS Neurology, February 8, 2000; 54(3): 558 - 558. [Abstract] [Full Text] [PDF]
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