title: Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability.
abstract: Disability in primary progressive multiple sclerosis (PPMS) has been correlated with damage to the normal appearing brain tissues. Magnetization transfer ratio (MTR) and volume changes indicate that much of this damage occurs in the normal appearing grey matter, but the clinical significance of this remains uncertain. We aimed to localize these changes to distinct grey matter regions, and investigate the clinical impact of the MTR changes. 46 patients with early PPMS and 23 controls underwent MT and high-resolution T1-weighted imaging. Patients were scored on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite and subtests (Nine-Hole Peg Test, Timed Walk Test, Paced Auditory Serial Addition Test [PASAT]). Grey matter volume and MTR were compared between patients and controls, adjusting for age. Mean MTR for significant regions within the motor network and in areas relevant to PASAT performance were correlated with appropriate clinical scores, adjusting for grey matter volume. Patients showed reduced MTR and atrophy in the right pre- and left post-central gyri, right middle frontal gyrus, left insula, and thalamus bilaterally. Reduced MTR without significant atrophy occurred in the left pre-central gyrus, left superior frontal gyri, bilateral superior temporal gyri, right insula and visual cortex. Higher EDSS correlated with lower MTR in the right primary motor cortex (BA 4). In conclusion, localized grey matter damage occurs in early PPMS, and MTR change is more widespread than atrophy. Damage demonstrated by reduced MTR is clinically eloquent.
authors.affiliation: Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Khaleeli
authors.forename: M
authors.initials: M
authors.lastname: Cercignani
authors.forename: B
authors.initials: B
authors.lastname: Audoin
authors.forename: O
authors.initials: O
authors.lastname: Ciccarelli
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D001925:Brain Damage, Chronic / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D004185:Disability Evaluation; D004292:Dominance, Cerebral / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000473:pathology*; D009483:Neuropsychological Tests; D011340:Problem Solving / Q000502:physiology; D013223:Statistics as Topic; D013788:Thalamus / Q000473:pathology; D016138:Walking / Q000502:physiology