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Supplemental material, MSJ837707_supplementary_appendix for Reduced dynamics of functional connectivity and cognitive impairment in multiple sclerosis by Alessandro d’Ambrosio, Paola Valsasina, Antonio Gallo, Nicola De Stefano, Deborah Pareto, Frederik Barkhof, Olga Ciccarelli, Christian Enzinger, Gioacchino Tedeschi, M Laura Stromillo, Maria J Arévalo, Hanneke E Hulst, Nils Muhlert, Marisa Koini, Massimo Filippi and Maria A Rocca in Multiple Sclerosis Journal

Supplemental material, MSJ-18-0794.R1_Supplementary_material for Reduced dynamics of functional connectivity and cognitive impairment in multiple sclerosis by Alessandro d’Ambrosio, Paola Valsasina, Antonio Gallo, Nicola De Stefano, Deborah Pareto, Frederik Barkhof, Olga Ciccarelli, Christian Enzinger, Gioacchino Tedeschi, M Laura Stromillo, Maria J Arévalo, Hanneke E Hulst, Nils Muhlert, Marisa Koini, Massimo Filippi and Maria A Rocca in Multiple Sclerosis Journal

ObjectiveGrey matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS.MethodsWe analysed 3,604 brain high-resolution T1-weighted MRI scans from 1,417 participants: 1,214 MS patients (253 clinically-isolated syndrome[CIS], 708 relapsingremitting[RRMS], 128 secondary-progressive[SPMS], 125 primary-progressive[PPMS]), over an average follow-up of 2.41 years (standard deviation[SD]=1.97), and 203 healthy controls (HCs) [average follow-up=1.83 year, SD=1.77], attending 7 European centres. Disability was assessed with the Expanded-Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem and cerebral white matter. Hierarchical mixed-models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression.ResultsSPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio=0.73, 95% CIs 0.65, 0.82; pppInterpretationThis large multi-centre and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions.