Massimo Filippi1, Paolo Preziosa, Massimiliano Copetti, Gianna Riccitelli, Mark A Horsfield, Vittorio Martinelli, Giancarlo Comi, Maria A Rocca. 1. 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.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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: Mike P Wattjes; Àlex Rovira; David Miller; Tarek A Yousry; Maria P Sormani; Maria P de Stefano; Mar Tintoré; Cristina Auger; Carmen Tur; Massimo Filippi; Maria A Rocca; Franz Fazekas; Ludwig Kappos; Chris Polman Journal: Nat Rev Neurol Date: 2015-09-15 Impact factor: 42.937
Authors: Christian Enzinger; Frederik Barkhof; Olga Ciccarelli; Massimo Filippi; Ludwig Kappos; Maria A Rocca; Stefan Ropele; Àlex Rovira; Torben Schneider; Nicola de Stefano; Hugo Vrenken; Claudia Wheeler-Kingshott; Jens Wuerfel; Franz Fazekas Journal: Nat Rev Neurol Date: 2015-11-03 Impact factor: 42.937
Authors: Nicola De Stefano; Laura Airas; Nikolaos Grigoriadis; Heinrich P Mattle; Jonathan O'Riordan; Celia Oreja-Guevara; Finn Sellebjerg; Bruno Stankoff; Agata Walczak; Heinz Wiendl; Bernd C Kieseier Journal: CNS Drugs Date: 2014-02 Impact factor: 5.749
Authors: Maria A Rocca; Marco Battaglini; Ralph H B Benedict; Nicola De Stefano; Jeroen J G Geurts; Roland G Henry; Mark A Horsfield; Mark Jenkinson; Elisabetta Pagani; Massimo Filippi Journal: Neurology Date: 2016-12-16 Impact factor: 9.910
Authors: Daniel L Schwartz; Ian Tagge; Katherine Powers; Sinyeob Ahn; Rohit Bakshi; Peter A Calabresi; R Todd Constable; John Grinstead; Roland G Henry; Govind Nair; Nico Papinutto; Daniel Pelletier; Russell Shinohara; Jiwon Oh; Daniel S Reich; Nancy L Sicotte; William D Rooney Journal: J Magn Reson Imaging Date: 2019-01-16 Impact factor: 4.813