title: Determinants of disability in multiple sclerosis: an immunological and MRI study.
abstract: Multiple sclerosis (MS) is characterized by a wide interpatient clinical variability and available biomarkers of disease severity still have suboptimal reliability. We aimed to assess immunological and MRI-derived measures of brain tissue damage in patients with different motor impairment degrees, for in vivo investigating the pathogenesis of MS-related disability. Twenty-two benign (B), 26 secondary progressive (SP), and 11 early, nondisabled relapsing-remitting (RR) MS patients and 37 healthy controls (HC) underwent conventional and diffusion tensor brain MRI and, as regards MS patients, immunophenotypic and functional analysis of stimulated peripheral blood mononuclear cells (PBMC). Corticospinal tract (CST) fractional anisotropy and grey matter volume were lower and CST diffusivity was higher in SPMS compared to RRMS and BMS patients. CD14+IL6+ and CD4+IL25+ cell percentages were higher in BMS than in SPMS patients. A multivariable model having EDSS as the dependent variable retained the following independent predictors: grey matter volume, CD14+IL6+ and CD4+IL25+ cell percentages. In patients without motor impairment after long-lasting MS, the grey matter and CST damage degree seem to remain as low as in the earlier disease stages and an immunological pattern suggestive of balanced pro- and anti-inflammatory activity is observed. MRI-derived and immunological measures might be used as complementary biomarkers of MS severity.
authors.affiliation: Unit of Motor Neurorehabilitation, Multiple Sclerosis Center, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tortorella
authors.affiliation: MR Research Laboratory, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Maria Marcella
authors.initials: MM
authors.lastname: Laganà
authors.affiliation: Immunology Research Laboratory, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Saresella
authors.affiliation: Unit of Motor Neurorehabilitation, Multiple Sclerosis Center, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Tavazzi
authors.affiliation: MR Research Laboratory, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy ; Bioengineering Department, Politecnico di Milano, Piazza Leonardo da Vinci, 20133 Milan, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Preti
authors.affiliation: Epidemiology and Statistics Unit, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy ; Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Cristian
authors.identifier: 0000-0003-4113-8682
authors.initials: C
authors.lastname: Ricci
authors.affiliation: MR Research Laboratory, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baglio
authors.affiliation: Immunology Research Laboratory, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Marventano
authors.affiliation: Immunology Research Laboratory, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Piancone
authors.affiliation: Bioengineering Department, Politecnico di Milano, Piazza Leonardo da Vinci, 20133 Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Baselli
authors.affiliation: MR Research Laboratory, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cecconi
authors.affiliation: Unit of Motor Neurorehabilitation, Multiple Sclerosis Center, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.affiliation: Immunology Research Laboratory, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Mario
authors.identifier: 0000-0002-2382-3638
authors.initials: M
authors.lastname: Clerici
authors.affiliation: Unit of Motor Neurorehabilitation, Multiple Sclerosis Center, Fondazione Don Gnocchi, IRCCS Santa Maria Nascente, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis; D003710:Demography; D038524:Diffusion Magnetic Resonance Imaging; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000276:immunology*; D010641:Phenotype
chemical_list: D016207:Cytokines