Brain reserve and physical disability in secondary progressive multiple sclerosis

Abstract Background The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in pati...

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Autores: John, Nevin Alex, Li, Yingtong, De Angelis, Floriana, Stutters, Jonathan, Prados Carrasco, Ferran, Eshaghi, Arman, Doshi, Anisha, Calvi, Alberto, Williams, Thomas, Plantone, Domenico, Phan, Thanh, Barkhof, Frederik, Chataway, Simon Jeremy
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universitat Oberta de Catalunya (UOC)
Repositorio:O2, repositorio institucional de la UOC
OAI Identifier:oai:openaccess.uoc.edu:10609/153592
Acceso en línea:https://hdl.handle.net/10609/153592
http://doi.org/10.1136/bmjno-2024-000670
Access Level:acceso abierto
Palabra clave:multiple sclerosis
neuroimmunology
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spelling Brain reserve and physical disability in secondary progressive multiple sclerosisJohn, Nevin AlexLi, YingtongDe Angelis, FlorianaStutters, JonathanPrados Carrasco, FerranEshaghi, ArmanDoshi, AnishaCalvi, AlbertoWilliams, ThomasPlantone, DomenicoPhan, ThanhBarkhof, FrederikChataway, Simon Jeremymultiple sclerosisneuroimmunologyAbstract Background The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS. Methods We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial (NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression. Results 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0–6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW. Conclusion Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS. Trail registration number NCT01910259.BMJ Publishing Group Ltd202520252024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/10609/153592http://doi.org/10.1136/bmjno-2024-000670reponame:O2, repositorio institucional de la UOCinstname:Universitat Oberta de Catalunya (UOC)InglésBMJ Neurology Open, 2024, 6(2)Attribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:openaccess.uoc.edu:10609/1535922026-05-28T12:42:01Z
dc.title.none.fl_str_mv Brain reserve and physical disability in secondary progressive multiple sclerosis
title Brain reserve and physical disability in secondary progressive multiple sclerosis
spellingShingle Brain reserve and physical disability in secondary progressive multiple sclerosis
John, Nevin Alex
multiple sclerosis
neuroimmunology
title_short Brain reserve and physical disability in secondary progressive multiple sclerosis
title_full Brain reserve and physical disability in secondary progressive multiple sclerosis
title_fullStr Brain reserve and physical disability in secondary progressive multiple sclerosis
title_full_unstemmed Brain reserve and physical disability in secondary progressive multiple sclerosis
title_sort Brain reserve and physical disability in secondary progressive multiple sclerosis
dc.creator.none.fl_str_mv John, Nevin Alex
Li, Yingtong
De Angelis, Floriana
Stutters, Jonathan
Prados Carrasco, Ferran
Eshaghi, Arman
Doshi, Anisha
Calvi, Alberto
Williams, Thomas
Plantone, Domenico
Phan, Thanh
Barkhof, Frederik
Chataway, Simon Jeremy
author John, Nevin Alex
author_facet John, Nevin Alex
Li, Yingtong
De Angelis, Floriana
Stutters, Jonathan
Prados Carrasco, Ferran
Eshaghi, Arman
Doshi, Anisha
Calvi, Alberto
Williams, Thomas
Plantone, Domenico
Phan, Thanh
Barkhof, Frederik
Chataway, Simon Jeremy
author_role author
author2 Li, Yingtong
De Angelis, Floriana
Stutters, Jonathan
Prados Carrasco, Ferran
Eshaghi, Arman
Doshi, Anisha
Calvi, Alberto
Williams, Thomas
Plantone, Domenico
Phan, Thanh
Barkhof, Frederik
Chataway, Simon Jeremy
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv multiple sclerosis
neuroimmunology
topic multiple sclerosis
neuroimmunology
description Abstract Background The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS. Methods We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial (NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression. Results 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0–6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW. Conclusion Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS. Trail registration number NCT01910259.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/10609/153592
http://doi.org/10.1136/bmjno-2024-000670
url https://hdl.handle.net/10609/153592
http://doi.org/10.1136/bmjno-2024-000670
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BMJ Neurology Open, 2024, 6(2)
dc.rights.none.fl_str_mv Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BMJ Publishing Group Ltd
publisher.none.fl_str_mv BMJ Publishing Group Ltd
dc.source.none.fl_str_mv reponame:O2, repositorio institucional de la UOC
instname:Universitat Oberta de Catalunya (UOC)
instname_str Universitat Oberta de Catalunya (UOC)
reponame_str O2, repositorio institucional de la UOC
collection O2, repositorio institucional de la UOC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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