Spinal cord lesions and brain grey matter atrophy independently predict clinical worsening in definite multiple sclerosis: A 5-year, multicentre study

Maria A. Rocca, Paola Valsasina, Alessandro Meani, Claudio Gobbi, Chiara Zecca, Frederik Barkhof, Menno M. Schoonheim, Eva M. Strijbis, Hugo Vrenken, Antonio Gallo, Alvino Bisecco, Olga Ciccarelli, Marios Yiannakas, Alex Rovira, Jaume Sastre-Garriga, Jacqueline Palace, Lucy Matthews, Achim Gass, Philipp Eisele, Carsten LukasBarbara Bellenberg, Monica Margoni, Paolo Preziosa, Massimo Filippi

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Objectives: To evaluate the combined contribution of brain and cervical cord damage in predicting 5-year clinical worsening in a multicentre cohort of definite multiple sclerosis (MS) patients. Methods: Baseline 3.0T brain and cervical cord T2-weighted and three-dimensional T1-weighted MRI was acquired in 367 patients with MS (326 relapse-onset and 41 progressive-onset) and 179 healthy controls. Expanded Disability Status Scale (EDSS) score was obtained at baseline and after a median follow-up of 5.1 years (IQR=4.8-5.2). At follow-up, patients were classified as clinically stable/worsened according to EDSS changes. Generalised linear mixed models identified predictors of clinical worsening, evolution to secondary progressive (SP) MS and reaching EDSS=3.0, 4.0 and 6.0 milestones at 5 years. Results: At follow-up, 120/367 (33%) patients with MS worsened clinically; 36/256 (14%) patients with relapsing-remitting evolved to SPMS. Baseline predictors of EDSS worsening were progressive-onset versus relapse-onset MS (standardised beta (β)=0.97), higher EDSS (β=0.41), higher cord lesion number (β=0.41), lower normalised cortical volume (β=-0.15) and lower cord area (β=-0.28) (C-index=0.81). Older age (β=0.86), higher EDSS (β=1.40) and cord lesion number (β=0.87) independently predicted SPMS conversion (C-index=0.91). Predictors of reaching EDSS=3.0 after 5 years were higher baseline EDSS (β=1.49), cord lesion number (β=1.02) and lower normalised cortical volume (β=-0.56) (C-index=0.88). Baseline age (β=0.30), higher EDSS (β=2.03), higher cord lesion number (β=0.66) and lower cord area (β=-0.41) predicted EDSS=4.0 (C-index=0.92). Finally, higher baseline EDSS (β=1.87) and cord lesion number (β=0.54) predicted EDSS=6.0 (C-index=0.91). Conclusions: Spinal cord damage and, to a lesser extent, cortical volume loss helped predicting worse 5-year clinical outcomes in MS.
Original languageEnglish
Article number329854
Pages (from-to)10-18
Number of pages9
JournalJournal of Neurology, Neurosurgery and Psychiatry
Issue number1
Early online date2022
Publication statusPublished - 28 Sept 2022


  • MRI

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