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Relationship between brain atrophy and disability in a multi-site multiple sclerosis registry

Ai-Lan Nguyen, Dana Horakova, Eva H Havrdova, Michael Barnett, Maria Pia Sormani, Nicola De Stefano, Marco Battaglini, Manuela Vaneckova, Elaine Lui, Frank Gaillard, et al.
(2025) BMJ NEUROLOGY OPEN. 7(2).
Author
Organization
Abstract
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 (beta -0.03, SE 0.01, p<0.001) and the rate of EDSS change over time (beta -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.
Keywords
MULTIPLE SCLEROSIS, MRI, LONG-TERM DISABILITY, GRAY-MATTER ATROPHY, VOLUME, PROGRESSION, OUTCOMES, PREDICT

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MLA
Nguyen, Ai-Lan, et al. “Relationship between Brain Atrophy and Disability in a Multi-Site Multiple Sclerosis Registry.” BMJ NEUROLOGY OPEN, vol. 7, no. 2, 2025, doi:10.1136/bmjno-2025-001126.
APA
Nguyen, A.-L., Horakova, D., Havrdova, E. H., Barnett, M., Sormani, M. P., De Stefano, N., … Butzkueven, H. (2025). Relationship between brain atrophy and disability in a multi-site multiple sclerosis registry. BMJ NEUROLOGY OPEN, 7(2). https://doi.org/10.1136/bmjno-2025-001126
Chicago author-date
Nguyen, Ai-Lan, Dana Horakova, Eva H Havrdova, Michael Barnett, Maria Pia Sormani, Nicola De Stefano, Marco Battaglini, et al. 2025. “Relationship between Brain Atrophy and Disability in a Multi-Site Multiple Sclerosis Registry.” BMJ NEUROLOGY OPEN 7 (2). https://doi.org/10.1136/bmjno-2025-001126.
Chicago author-date (all authors)
Nguyen, Ai-Lan, Dana Horakova, Eva H Havrdova, Michael Barnett, Maria Pia Sormani, Nicola De Stefano, Marco Battaglini, Manuela Vaneckova, Elaine Lui, Frank Gaillard, Patricia M Desmond, Hayden Prime, Mineesh Datta, Anneke van der Walt, Vilija G Jokubaitis, Femke Podevyn, Robert Zivadinov, Bianca Weinstock-Guttman, Marie B D’hooghe, Guy Nagels, Vincent Van Pesch, Guy Laureys, Liesbeth Van Hijfte, Jeannette Lechner-Scott, Francesco Patti, Edgardo Cristiano, Juan I Rojas, Diana M Sima, Wim Van Hecke, Tomas Kalincik, and Helmut Butzkueven. 2025. “Relationship between Brain Atrophy and Disability in a Multi-Site Multiple Sclerosis Registry.” BMJ NEUROLOGY OPEN 7 (2). doi:10.1136/bmjno-2025-001126.
Vancouver
1.
Nguyen A-L, Horakova D, Havrdova EH, Barnett M, Sormani MP, De Stefano N, et al. Relationship between brain atrophy and disability in a multi-site multiple sclerosis registry. BMJ NEUROLOGY OPEN. 2025;7(2).
IEEE
[1]
A.-L. Nguyen et al., “Relationship between brain atrophy and disability in a multi-site multiple sclerosis registry,” BMJ NEUROLOGY OPEN, vol. 7, no. 2, 2025.
@article{01KEEP16MDDY02Z6YSKM48XTHQ,
  abstract     = {{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 (beta -0.03, SE 0.01, p<0.001) and the rate of EDSS change over time (beta -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.}},
  articleno    = {{e001126}},
  author       = {{Nguyen, Ai-Lan and Horakova, Dana and Havrdova, Eva H and Barnett, Michael and Sormani, Maria Pia and De Stefano, Nicola and Battaglini, Marco and Vaneckova, Manuela and Lui, Elaine and Gaillard, Frank and Desmond, Patricia M and Prime, Hayden and Datta, Mineesh and van der Walt, Anneke and Jokubaitis, Vilija G and Podevyn, Femke and Zivadinov, Robert and Weinstock-Guttman, Bianca and D’hooghe, Marie B and Nagels, Guy and Pesch, Vincent Van and Laureys, Guy and Van Hijfte, Liesbeth and Lechner-Scott, Jeannette and Patti, Francesco and Cristiano, Edgardo and Rojas, Juan I and Sima, Diana M and Van Hecke, Wim and Kalincik, Tomas and Butzkueven, Helmut}},
  issn         = {{2632-6140}},
  journal      = {{BMJ NEUROLOGY OPEN}},
  keywords     = {{MULTIPLE SCLEROSIS,MRI,LONG-TERM DISABILITY,GRAY-MATTER ATROPHY,VOLUME,PROGRESSION,OUTCOMES,PREDICT}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{9}},
  title        = {{Relationship between brain atrophy and disability in a multi-site multiple sclerosis registry}},
  url          = {{http://doi.org/10.1136/bmjno-2025-001126}},
  volume       = {{7}},
  year         = {{2025}},
}
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