title: Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years.
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.
authors.affiliation: Neuroimaging Research Unit, Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rovaris
authors.forename: E
authors.initials: E
authors.lastname: Judica
authors.forename: A
authors.initials: A
authors.lastname: Gallo
authors.forename: B
authors.initials: B
authors.lastname: Benedetti
authors.forename: M P
authors.initials: MP
authors.lastname: Sormani
authors.forename: D
authors.initials: D
authors.lastname: Caputo
authors.forename: A
authors.initials: A
authors.lastname: Ghezzi
authors.forename: E
authors.initials: E
authors.lastname: Montanari
authors.forename: A
authors.initials: A
authors.lastname: Bertolotto
authors.forename: G
authors.initials: G
authors.lastname: Mancardi
authors.forename: R
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: V
authors.initials: V
authors.lastname: Martinelli
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: M
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D002574:Cervical Vertebrae; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology*; D015999:Multivariate Analysis; D011379:Prognosis; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013116:Spinal Cord / Q000473:pathology