title: Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI.
abstract: The mechanisms underlying the progressive course of multiple sclerosis (MS) are not fully understood yet. Since diffusion tensor (DT) MRI can provide quantitative estimates of both MRI-visible and MRI-occult brain damage related to MS, the present study investigated the value of DT MRI-derived measures for the assessment of the short-term accumulation of white and gray matter (GM) pathology in patients with primary progressive (PP) and secondary progressive (SP) MS. Fifty-four patients with PPMS and 22 with SPMS were studied at baseline and after a mean follow-up of 15 months. Dual-echo, T1-weighted, and DT MRI scans of the brain were acquired on both occasions. Total lesion volumes (TLV) and percentage brain volume changes (PBVC) were computed. Mean diffusivity (MD) and fractional anisotropy (FA) maps of the normal-appearing white (NAWM) and gray matter (NAGM) were produced, and histogram analysis was performed. In both patient groups, a significant increase of average lesion MD (P = 0.01) and of average NAGM MD (P = 0.007) was found at follow-up. No significant differences between PPMS and SPMS patient groups were found for the on-study changes of any MRI-derived measure. No significant correlations were found between the percentage changes of DT MRI-derived measures and those of TLV and PBVC. No significant changes of DT MRI-derived measures were observed in age-matched healthy controls over the same study period. Over a 1-year period of follow-up, DT MRI can detect tissue changes beyond the resolution of conventional MRI in the NAGM of patients with progressive MS. The accumulation of DT MRI-detectable gray matter damage does not seem to merely depend upon the concomitant increase of T2-visible lesion load and the reduction of brain volume. These observations suggest that progressive NAGM damage might yet be an additional factor leading to the accumulation of disability in progressive MS.
authors.affiliation: Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
authors.forename: Antonio
authors.initials: A
authors.lastname: Gallo
authors.forename: Paola
authors.initials: P
authors.lastname: Valsasina
authors.forename: Beatrice
authors.initials: B
authors.lastname: Benedetti
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.forename: Angelo
authors.initials: A
authors.lastname: Ghezzi
authors.forename: Enrico
authors.initials: E
authors.lastname: Montanari
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mancardi
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology*; D016896:Treatment Outcome