Cross-sectional brain volumetric measures and disability outcomes in relapsing–remitting multiple sclerosis
BACKGROUND: Automated cross-sectional magnetic resonance imaging (MRI) measures of brain volume are becoming available in clinical practice; however, their prognostic utility in multiple sclerosis remains unclear. OBJECTIVES: We investigated associations between cross-sectional brain and brain lesion volume measures and subsequent disability outcomes in relapsing-remitting multiple sclerosis (RRMS). METHODS: We conducted a multicentre international cohort study using data collected prospectively in the MSBase Registry. MRI analysis was performed using icobrain ms. Associations between MRI volumetric measurements and confirmed disability worsening (CDW), progression independent of relapse activity (PIRA), secondary progressive multiple sclerosis (SPMS) and confirmed disability improvement (CDI) were examined using multivariable Cox proportional hazards models. RESULTS: A total of 1598 patients were included and 68.6% received high-efficacy disease-modifying therapy during follow-up. Normalised lateral ventricular volume (mL) was significantly associated with all disability outcomes, including PIRA (hazard ratio 1.007; 95% confidence interval 1.002 - 1.012; p = 0.009). Higher normalised whole brain, grey matter and white matter volumes were all significantly associated with a lower hazard of CDW and higher hazard of achieving CDI. Higher normalised white matter volume was also significantly associated with a lower hazard of PIRA. Higher T1-weighted black hole lesion volume was significantly associated with an increased hazard of conversion to SPMS; lesion volume measures were otherwise not significantly associated with disability outcomes. CONCLUSIONS: Automated MRI measures of brain volume from a single time point demonstrated prognostic utility in a highly treated cohort of people with RRMS. The results suggest that normalised lateral ventricular volume is a particularly informative prognostic marker across multiple disability outcomes.
Authors
- Ai‐Lan Nguyen (ORCID: https://orcid.org/0000-0003-0378-6005)
- M Hayes (ORCID: https://orcid.org/0000-0003-0614-1800)
- Daniel Merlo (ORCID: https://orcid.org/0000-0001-8766-3453)
- Mastura Monif (ORCID: https://orcid.org/0000-0001-6404-9768)
- Heidi N. Beadnall (ORCID: https://orcid.org/0000-0003-3734-4133)
- Diana M. Sima (ORCID: https://orcid.org/0000-0002-0118-2905)
- Dirk Smeets (ORCID: https://orcid.org/0000-0003-1153-094X)
- Helmut Butzkueven
- Francesco Patti
- Elaine Lui
- Katherine Buzzard
- Manuela Vaneckova
- Dana Horakova
- Chao Zhu
- Jeannette Lechner-Scott
- Wim Van Hecke
- Tomas Kalincik
- Michael Barnett
- Anneke van der Walt
- Guy Laureys
- Vincent Van Pesch
Institutions
- The University of Sydney (AU)
- Cliniques Universitaires Saint-Luc (BE)
- The Royal Melbourne Hospital (AU)
- Box Hill Hospital (AU)
- The University of Melbourne (AU)
- Charles University (CZ)
- Royal Prince Alfred Hospital (AU)
- John Hunter Hospital (AU)
- Ghent University Hospital (BE)
- University of Catania (IT)
- Eastern Health (AU)
- Monash Health (AU)
- Policlinico Universitario di Catania (IT)
- Melbourne Clinic (AU)
- Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco" (IT)
- General University Hospital in Prague (CZ)
- Icometrix (Belgium) (BE)
- Alfred Health (AU)
- Monash University (AU)
- University of Newcastle Australia (AU)
- UCLouvain (BE)
Publication Details
- Journal
- Journal of Neurology
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1007/s00415-026-13788-z
- Primary Topic
- Multiple Sclerosis Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Biogen
- Multiple Sclerosis Australia
- Monash University
- Medical Research Council
- National Health and Medical Research Council
- UCB Pharma