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Brain Advance Access published online on August 18, 2006
Brain, 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
Received May 25, 2006
Revised July 17, 2006
Accepted July 25, 2006

Article

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

M. Rovaris 1, E. Judica 1, A. Gallo 2, B. Benedetti 1, M. P. Sormani 3, D. Caputo 4, A. Ghezzi 5, E. Montanari 6, A. Bertolotto 7, G. Mancardi 8, R. Bergamaschi 9, V. Martinelli 10, G. Comi 10, and M. Filippi 1 *

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

* To whom correspondence should be addressed.
M. Filippi, E-mail: filippi.massimo{at}hsr.it


  Abstract

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.

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