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From the Dutch MR Centre for MS Research (Drs. Truyen, van Waesberghe, Van Walderveen, Polman, and Barkhof) and Department of Neurology (Drs. Truyen, Van Oosten, and Polman), Free University Hospital, Amsterdam, The Netherlands; the Department of Neurology (Dr. Hommes), University Hospital St. Radboud, Nijmegen, The Netherlands; and the Department of Epidemiology and Biostatistics (Dr. Ader), Free University Amsterdam, The Netherlands.
Supported in part by a grant from the Dutch MS society ("Stichting Vrienden MS Research").
Received February 29, 1996. Accepted in final form April 11, 1996.
Address correspondence and reprint requests to Dr. F. Barkhof, Radiology Department, Free University Hospital Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
MRI findings are increasingly used as outcome measures in therapeutic trials in MS.The discrepancy between the extent of the lesions on conventional T2 images and the clinical condition of the patient is one of the problems encountered in such studies. This clinical-radiological paradox prevents the use of MRI data as surrogate markers of disability in MS. A recent pilot study suggested a relationship between hypointense lesions on T1 MRI and disability. To assess in more detail the correlation of changes in hypointense lesion load on T1-weighted spin-echo MR images ("black holes") with changes in disability in MS, we studied 46 patients with clinically definite MS at baseline and after a median follow-up of 40 months. There was a significant correlation between baseline disability and hypointense lesion load (Spearman rank correlation coefficient [SRCC] = 0.46, p = 0.001). In secondary progressive patients, the rate of accumulation of these "black holes" was significantly related to progression rate (SRCC = 0.81, p < 0.0001). We speculate that the appearance of hypointense lesions is the MRI equivalent of a failure of remission. Overall, T1 lesion load measurements correlated better with clinical assessments than T2 lesion load measurements. Quantification of hypointense lesion load on T (1-weighted) spin-echo MRI helps to resolve the clinical-radiological paradox between disability and MRI and has the potential to be a surrogate marker of disability in MS.
NEUROLOGY 1996;47: 1469-1476
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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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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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M. Rovaris, M. Filippi, L. Minicucci, G. Iannucci, G. Santuccio, F. Possa and, and G. Comi Cortical/Subcortical Disease Burden and Cognitive Impairment in Patients with Multiple Sclerosis AJNR Am. J. Neuroradiol., February 1, 2000; 21(2): 402 - 408. [Abstract] [Full Text]
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M Rovaris, B Viti, G Ciboddo, S Gerevini, R Capra, G Iannucci, G Comi, and M Filippi Brain involvement in systemic immune mediated diseases: magnetic resonance and magnetisation transfer imaging study J. Neurol. Neurosurg. Psychiatry, February 1, 2000; 68(2): 170 - 177. [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. 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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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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P. A. Brex, J. I. O'Riordan, K. A. Miszkiel, I. F. Moseley, A. J. Thompson, G. T. Plant, and D. H. Miller Multisequence MRI in clinically isolated syndromes and the early development of MS Neurology, October 1, 1999; 53(6): 1184 - 1184. [Abstract] [Full Text] [PDF]
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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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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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F. Barkhof MRI in multiple sclerosis: correlation with expanded disability status scale (EDSS) Multiple Sclerosis, August 1, 1999; 5(4): 283 - 286. [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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J. H. Simon, L. D. Jacobs, M. K. Campion, R. A. Rudick, D. L. Cookfair, R. M. Herndon, J. R. Richert, A. M. Salazar, J. S. Fischer, D. E. Goodkin, et al. A longitudinal study of brain atrophy in relapsing multiple sclerosis Neurology, July 1, 1999; 53(1): 139 - 139. [Abstract] [Full Text]
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E. K. Jordan, H. I. McFarland, B. K. Lewis, N. Tresser, M. A. Gates, M. Johnson, M. Lenardo, L. A. Matis, H. F. McFarland, and J. A. Frank Serial MR Imaging of Experimental Autoimmune Encephalomyelitis Induced by Human White Matter or by Chimeric Myelin-Basic and Proteolipid Protein in the Common Marmoset AJNR Am. J. Neuroradiol., June 1, 1999; 20(6): 965 - 976. [Abstract] [Full Text]
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Rovaris, Comi, M. Rocca, Cercignani, Colombo, Santuccio, and Filippi Relevance of Hypointense Lesions on Fast Fluid-Attenuated Inversion Recovery MR Images as a Marker of Disease Severity in Cases of Multiple AJNR Am. J. Neuroradiol., May 1, 1999; 20(5): 813 - 820. [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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M. A. A. van Walderveen, L. Truyen, B. W. van Oosten, J. A. Castelijns, G. J. Lycklama a Nijeholt, J. H. T. M. van Waesberghe, C. Polman, and F. Barkhof Development of Hypointense Lesions on T1-Weighted Spin-Echo Magnetic Resonance Images in Multiple Sclerosis: Relation to Inflammatory Activity Arch Neurol, March 1, 1999; 56(3): 345 - 351. [Abstract] [Full Text] [PDF]
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M. Filippi, G. Iannucci, C. Tortorella, L. Minicucci, M. A. Horsfield, B. Colombo, M. P. Sormani, and G. Comi Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI Neurology, February 1, 1999; 52(3): 588 - 588. [Abstract] [Full Text] [PDF]
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J I O'Riordan, M G. Cain, A Coles, L Wang, D A. Compston, P Tofts, and D H Miller T1 hypointense lesion load in secondary progressive multiple sclerosis: a comparison of pre versus post contrast loads and of manual versus semi automated threshold techniques for lesion segmentation Multiple Sclerosis, October 1, 1998; 4(5): 408 - 412. [Abstract] [PDF]
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G Giovannoni, A J. Green, and E J Thompson Are there any body fluid markers of brain atrophy in multiple sclerosis? Multiple Sclerosis, June 1, 1998; 4(3): 138 - 142. [Abstract] [PDF]
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P. Stinissen, R. Medaer, and J. Raus Myelin reactive T cells in the autoimmune pathogenesis of multiple sclerosis Multiple Sclerosis, June 1, 1998; 4(3): 203 - 211. [Abstract] [PDF]
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