Neurology 1999;53:139
© 1999 American Academy of Neurology
Articles
A longitudinal study of brain atrophy in relapsing multiple sclerosis
J. H. Simon, MD, PhD,
L. D. Jacobs, MD,
M. K. Campion, MS,
R. A. Rudick, MD,
D. L. Cookfair, PhD,
R. M. Herndon, MD,
J. R. Richert, MD,
A. M. Salazar, MD,
J. S. Fischer, PhD,
D. E. Goodkin, MD,
N. Simonian, MD,
M. Lajaunie, MD,
D. E. Miller, PhD,
K. Wende, PhD,
A. Martens-Davidson, MS,
R. P. Kinkel, MD,
F. E. Munschauer, III, MD,
C. M. Brownscheidle, PhD and
The Multiple Sclerosis Collaborative Research Group (MSCRG)*
From the William C. Baird Multiple Sclerosis Research Center (Drs. Jacobs, Munschauer, and Brownscheidle), Millard Fillmore Health System, and the Department of Neurology, The Buffalo General Hospital, Buffalo, NY; MSCRG Data Management and Statistical Center (Drs. Cookfair and Wende, A. Martens-Davidson), Department of Neurology, The Buffalo General Hospital, Buffalo, NY; Mellen Center for Multiple Sclerosis Treatment and Research (Drs. Rudick, Fischer, and Kinkel), Cleveland Clinic Foundation, Cleveland, OH; Department of Neurology (Dr. Herndon), Good Samaritan Hospital and Medical Center, Portland, OR; Department of Neurology (Dr. Richert), Georgetown University Medical Center, Washington, DC; Department of Neurology (Dr. Salazar), Walter Reed Army Medical Center, Washington, DC; UCSF/Mount Zion Multiple Sclerosis Center (Dr. Goodkin), San Francisco, CA; Department of Radiology–MRI (Drs. Simon, Lajaunie, and Miller), University of Colorado Health Sciences Center, Denver, CO; and Biogen, Inc. (Dr. Simonian, M.K. Campion), Cambridge, MA.
Address correspondence and reprint requests to Dr. J.H. Simon, Department of Radiology–MRI, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Box A-034, Denver, CO 80262.
OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon ß-1a (Avonex).
METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area.
RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement.
CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.
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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;
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[Abstract]
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M. Filippi, M. Rovaris, G. Iannucci, S. Mennea, M. P. Sormani, and G. Comi
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Neurology,
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[Abstract]
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A. J Thompson
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J. Neurol. Neurosurg. Psychiatry,
December 1, 2000;
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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):
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[Abstract]
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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;
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373 - 377.
[Abstract]
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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,
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123(11):
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[Abstract]
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M Filippi
Enhanced magnetic resonance imaging in multiple sclerosis
Multiple Sclerosis,
October 1, 2000;
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[Abstract]
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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;
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[Abstract]
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S. Sathornsumetee, D. B. McGavern, D. R. Ure, and M. Rodriguez
Quantitative Ultrastructural Analysis of a Single Spinal Cord Demyelinated Lesion Predicts Total Lesion Load, Axonal Loss, and Neurological Dysfunction in a Murine Model of Multiple Sclerosis
Am. J. Pathol.,
October 1, 2000;
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[Abstract]
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D. Berg, M. Maurer, M. Warmuth-Metz, P. Rieckmann, and G. Becker
The Correlation Between Ventricular Diameter Measured by Transcranial Sonography and Clinical Disability and Cognitive Dysfunction in Patients With Multiple Sclerosis
Arch Neurol,
September 1, 2000;
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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.
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Neurology,
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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
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July 12, 2000;
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J. H. Simon, R. P. Kinkel, L. Jacobs, L. Bub, and N. Simonian
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Neurology,
March 14, 2000;
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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;
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R. A. Rudick, E. Fisher, J.-C. Lee, J. Simon, and L. Jacobs
Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS
Neurology,
November 1, 1999;
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R. A. Rudick
Disease-Modifying Drugs for Relapsing-Remitting Multiple Sclerosis and Future Directions for Multiple Sclerosis Therapeutics
Arch Neurol,
September 1, 1999;
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R. A. Rudick
A 29-Year-Old Man With Multiple Sclerosis
JAMA,
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