BACKGROUND: In a retrospective multicentre cohort study, we explored the association between brain atrophy and multiple sclerosis (MS) disability using different MRI scanners and protocols at multiple sites. METHODS: Relapse-onset MS patients were included if they had two clinical MRIs 12 months apart and ≥2 Expanded Disability Status Scale (EDSS) scores. Percentage brain volume change (PBVC), percentage grey matter change (PGMC), fluid-attenuated inversion recovery (FLAIR) lesion volume change, whole brain volume (BV), grey matter volume (GMV), FLAIR lesion volume and T1 hypointense lesion volume were assessed by icobrain. Disability was measured by EDSS scores and 6-month confirmed disability progression (CDP). RESULTS: Of the 260 relapse-onset MS patients included, 204 (78%) MRI pairs were performed in the same scanner and 56 (22%) pairs were from different scanners. 93% of patients were on treatment and mean PBVC was -0.26% (±0.52). During the median follow-up of 2.8 years from the second MRI, median EDSS change was 0.0 and 12% patients experienced 6-month CDP. Cross-sectional BV and GMV at the later MRI showed a trend for association with CDP (HR 0.99; 95% CI 0.98 to 1.00; p=0.06). Only BV at the later MRI was associated with EDSS score (β -0.03, SE 0.01, p<0.001) and the rate of EDSS change over time (β -0.001, SE 0.0003, p=0.02). There was no association between longitudinal PBVC or PGMC and CDP or EDSS (p>0.05). CONCLUSION: In this highly treated MS cohort with low disability accrual, only cross-sectional BV showed an association with future EDSS scores, while no MRI metric predicted 6-month CDP. These findings highlight the limitations of current clinical MRI measures in predicting disability worsening in real-world settings.

AI Supported Modelling in Clinical Sciences Vrije Universiteit Brussel Brussels Belgium

Brain and Mind Centre The University of Sydney Sydney New South Wales Australia

Centre for Brain and Mental Health The University of Newcastle Hunter Medical Research Institute New Lambton New South Wales Australia

Centro de Esclerosis Múltiple de Buenos Aires Buenos Aires Argentina

CORe Department of Medicine The University of Melbourne Melbourne Victoria Australia

Department of Health Sciences Biostatistics Unit University of Genoa Genoa Italy

Department of Medical Imaging Royal Melbourne Hospital Melbourne Victoria Australia

Department of Medicine Surgery and Neuroscience University of Siena Siena Italy

Department of Neurology and Center of Clinical Neuroscience Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Prague Czech Republic

Department of Neurology Ghent University Hospital Gent Belgium

Department of Neurology John Hunter Hospital New Lambton Heights New South Wales Australia

Department of Neurology Universite catholique de Louvain Louvain la Neuve Belgium

Department of Neuroscience School of Translational Medicine Monash University Melbourne Victoria Australia

Department of Radiology 1st Faculty of Medicine General University Hospital Prague Prague Czech Republic

Department of Radiology Box Hill Hospital Box Hill Victoria Australia

Department of Radiology University of Melbourne Melbourne Victoria Australia

National MS Center Melsbroek Melsbroek Belgium

Neuroimmunology Centre The Royal Melbourne Hospital Melbourne Victoria Australia

Neurology State University of New York at Buffalo Buffalo New York USA

Neuroscience University of Catania Department of Surgical and Medical Sciences and Advanced Technologies 'G F Ingrassia' Catania Italy

Research and Development Icometrix Leuven Belgium

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