title: Gray matter damage predicts the accumulation of disability 13 years later in MS.
abstract: OBJECTIVE
  To assess the value of conventional and magnetization transfer (MT) MRI measures of white matter (WM) and gray matter (GM) damage, and their 12-month change, in predicting long-term disability and cognitive impairment in multiple sclerosis (MS).
  
  
  METHODS
  Conventional and MT MRI brain scans were obtained at baseline and at 12 months in 73 patients, who were followed prospectively with clinical visits and rating of the Expanded Disability Status Scale score and the MS severity score (MSSS) for a median period of 13.3 years. At 13-year follow-up, a neuropsychological assessment was also performed when possible. T2-hyperintense and T1-hypointense lesion volumes, GM fraction (GMF), WM fraction, thalamic fraction, average lesion MT ratio (MTR), average GM MTR, average normal-appearing WM MTR, and thalamic MTR were measured. Random forest and multivariable analyses were performed to identify the predictors of neurologic deterioration and cognitive impairment at 13 years.
  
  
  RESULTS
  At 13-year follow-up, 66% of patients showed significant worsening of disability and 37% had worsened cognitively. The multivariable model, in which Expanded Disability Status Scale deterioration at final follow-up was the dependent variable, identified baseline GMF (odds ratio [OR] = 0.79, p = 0.01) as the only predictor of worsening of disability (C-index = 0.69). Baseline disease duration (OR = 1.50, p = 0.08) and average GM MTR (OR = 0.87, p = 0.03) were independent variables associated with cognitive deterioration (C-index = 0.97). Baseline MSSS (β = 0.50, p < 0.0001) and baseline GMF (β = -0.32, p = 0.0005) predicted MSSS at follow-up (r(2) = 0.45).
  
  
  CONCLUSIONS
  GM damage is one of the key factors associated with long-term accumulation of disability and cognitive impairment in MS.
authors.affiliation: From the Neuroimaging Research Unit (M.F., P.P., G.R., M.A.R.), Institute of Experimental Neurology, and Department of Neurology (M.F., P.P., V.M., G.C., M.A.R.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Biostatistics Unit (M.C.), IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy; and Medical Physics Group (M.A.H.), Department of Cardiovascular Sciences, University of Leicester, Leicester Royal Infirmary, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.forename: Paolo
authors.initials: P
authors.lastname: Preziosa
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Gianna
authors.initials: G
authors.lastname: Riccitelli
authors.forename: Mark A
authors.initials: MA
authors.lastname: Horsfield
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D004185:Disability Evaluation; D006233:Persons with Disabilities; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000150:complications*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011237:Predictive Value of Tests; D012720:Severity of Illness Index