Brain reserve and physical disability in secondary progressive multiple sclerosis

BackgroundThe 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...

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Published in:BMJ neurology open Vol. 6; no. 2; p. e000670
Main Authors: John, Nevin, 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, Jeremy, Ourselin, Sebastien, Braisher, Marie, Beyene, Tiggy, Bassan, Vanessa, Zapata, Alvin, Chandran, Siddharthan, Connick, Peter, Lyle, Dawn, Cameron, James, Mollison, Daisy, Colville, Shuna, Dhillon, Baljean, Ross, Moira, Cranswick, Gina, Walker, Allan, Smith, Lorraine, Giovannoni, Gavin, Gnanapavan, Sharmilee, Nicholas, Richard, Rashid, Waqar, Aram, Julia, Ford, Helen, Pavitt, Sue H, Overell, James, Young, Carolyn, Arndt, Heinke, Duddy, Martin, Guadagno, Joe, Evangelou, Nikolaos, Craner, Matthew, Palace, Jacqueline, Hobart, Jeremy, Sharrack, Basil, Paling, David, Hawkins, Clive, Kalra, Seema, McLean, Brendan, Stallard, Nigel, Bastow, Roger
Format: Journal Article
Language:English
Published: England BMJ Publishing Group Ltd 07.09.2024
BMJ Publishing Group LTD
BMJ Publishing Group
Subjects:
Age
Brain research
Cross-sectional studies
Dementia
Hypotheses
MULTIPLE SCLEROSIS
NEUROIMMUNOLOGY
Original Research
Pathology
United Kingdom > UK
MULTIPLE SCLEROSIS
NEUROIMMUNOLOGY
ISSN:2632-6140, 2632-6140
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Summary:BackgroundThe 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.MethodsWe 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.Results383 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.ConclusionLarger 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 numberNCT01910259.
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NJ and YL are joint first authors.
Additional supplemental material is published online only. To view, please visit the journal online (https://doi.org/10.1136/bmjno-2024-000670).
NJ is a local principal investigator on commercial MS studies funded by Novartis, Roche and Sanofi. He has received speakers honoraria from Merck and congress sponsorship covering registration and travel from Novartis. FB serves on the editorial boards of Brain, European Radiology, Journal of Neurology, Neurosurgery & Psychiatry, Neurology, Multiple Sclerosis and Neuroradiology, and serves as consultant for Bayer Schering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA Pharmaceuticals, Genzyme, Merck-Serono, Novartis, Roche, Synthon, Jansen Research and Lundbeck. CAGW-K has received research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon 2020, NIHR/MRC, MRC and is a shareholder of Queen Square Analytics. In the last 3 years, JC has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by the Canadian MS Society. A local principal investigator for commercial trials funded by: Actelion, Biogen, Novartis and Roche; has received an investigator grant from Novartis; and has taken part in advisory boards/consultancy for Azadyne, Biogen, Celgene, Janssen, MedDay, Merck, NervGen, Novartis and Roche.
NJ and YL contributed equally.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
ISSN:2632-6140
2632-6140
DOI:10.1136/bmjno-2024-000670