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Brain Advance Access originally published online on August 18, 2006
Brain 2006 129(10):2628-2634; doi:10.1093/brain/awl222
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© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years

M. Rovaris1,2, E. Judica1,2, A. Gallo1, B. Benedetti1,2, M. P. Sormani1,3, D. Caputo5, A. Ghezzi6, E. Montanari7, A. Bertolotto8, G. Mancardi4, R. Bergamaschi9, V. Martinelli2, G. Comi2 and M. Filippi1,2

1 Neuroimaging Research Unit, Department of Neurology, San Raffaele Scientific Institute Milan, Italy 2 Department of Neurology, San Raffaele Scientific Institute Milan, Italy 3 Biostatistics Unit, Department of Health Sciences, University of Genoa Genoa, Italy 4 Department of Neurological Sciences, University of Genoa Genoa, Italy 5 Department of Neurology, Don Gnocchi Scientific Institute Milan, Italy 6 Multiple Sclerosis Center, Ospedale di Gallarate Gallarate, Italy 7 Multiple Sclerosis Center, Ospedale di Fidenza Fidenza, Italy 8 Department of Neurology, Ospedale di Orbassano Orbassano, Italy 9 Department of Neurological Sciences, Mondino Scientific Institute, University of Pavia Pavia, Italy

Correspondence to: Massimo Filippi, Neuroimaging Research Unit, Department of Neurology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy E-mail: filippi.massimo{at}hsr.it

Reliable prognostic markers of primary progressive (PP) multiple sclerosis evolution are still needed. Diffusion tensor (DT) MRI can quantify normal-appearing white matter (NAWM) and grey matter (GM) damage in multiple sclerosis patients. We investigated whether conventional and DT-MRI-derived measures can predict the long-term clinical evolution of PP multiple sclerosis. In 54 PP multiple sclerosis patients, conventional and DT-MRI scans of the brain and T1-weighted scans of the cervical cord were acquired at baseline and after a median follow-up of 15 months. Another clinical evaluation was performed, 56 months after baseline, in 52 patients. Measures of lesion load, brain and cord atrophy were obtained. Histograms of the mean diffusivity (MD) and fractional anisotropy (FA) values from the NAWM and GM were analysed. At follow-up, 35 patients (65%) experienced a confirmed disability progression. Baseline expanded disability status scale score and average GM MD were independent predictors of subsequent clinical deterioration in a multivariable model (Nagelkerke R2: 0.44; discriminating ability: 81%). A lower level of disability and a more severe GM damage identify PP multiple sclerosis patients with an increased risk of disease progression over the subsequent 5 years. These data may be relevant to select patients for future exploratory phase II trials.

Key Words: diffusion tensor MRI; disease evolution; grey matter; magnetic resonance imaging; primary progressive multiple sclerosis

Abbreviations: CSA, cross-sectional cord area; DT, diffusion tensor; EDSS, expanded disability status scale; FA, fractional anisotropy; FU1 and FU2, follow-up visit 1 and 2; GM, grey matter; MP-RAGE, magnetization prepared rapid acquisition gradient echo; MD, mean diffusivity; NAWM, normal-appearing white matter; PP, primary progressive

Received May 25, 2006. Revised July 17, 2006. Accepted July 25, 2006.


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