BMJ Neurology Open (Sep 2024)
Brain reserve and physical disability in secondary progressive multiple sclerosis
- ,
- Nevin John,
- Jeremy Chataway,
- Jacqueline Palace,
- Gavin Giovannoni,
- David Paling,
- Frederik Barkhof,
- Floriana De Angelis,
- Lorraine Smith,
- Thomas Williams,
- Martin Duddy,
- James Overell,
- Basil Sharrack,
- Sebastien Ourselin,
- Allan Walker,
- Siddharthan Chandran,
- Richard Nicholas,
- Shuna Colville,
- Peter Connick,
- Carolyn Young,
- Jeremy Hobart,
- Anisha Doshi,
- Sharmilee Gnanapavan,
- Helen Ford,
- Baljean Dhillon,
- Thanh Phan,
- Arman Eshaghi,
- Julia Aram,
- Nigel Stallard,
- James Cameron,
- Brendan McLean,
- Matthew Craner,
- Domenico Plantone,
- Jonathan Stutters,
- Ferran Prados Carrasco,
- Marie Braisher,
- Moira Ross,
- Gina Cranswick,
- Sue H Pavitt,
- Clive Hawkins,
- Roger Bastow,
- Daisy Mollison,
- Waqar Rashid,
- Joe Guadagno,
- Nikolaos Evangelou,
- Seema Kalra,
- Alberto Calvi,
- Yingtong Li,
- Tiggy Beyene,
- Vanessa Bassan,
- Alvin Zapata,
- Dawn Lyle,
- Heinke Arndt
Affiliations
- 1Department of Anesthesiology, Critical Care and Pain Management, Hospital for Special Surgery, New York, USA
- Nevin John
- Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK
- Jeremy Chataway
- Medical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK
- Jacqueline Palace
- Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK
- Gavin Giovannoni
- Blizard Institute, Queen Mary University of London, London, UK
- David Paling
- Department of Clinical Neurology, Royal Hallamshire Hospital, Sheffield, UK
- Frederik Barkhof
- NMR Research Unit, Department of Neuroinflammation & Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London Queen Square Institute of Neurology, London, UK
- Floriana De Angelis
- 1 Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, UCL, London, UK
- Lorraine Smith
- Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France
- Thomas Williams
- 1Royal National Hospital for Rheumatic Diseases, Rheumatology, Bath, United Kingdom
- Martin Duddy
- James Overell
- 2 University of Glasgow, Glasgow, UK
- Basil Sharrack
- Department of Neuroscience and Sheffield NIHR Translational Neuroscience Biomedical Research Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Sebastien Ourselin
- School of Biomedical Engineering and Imaging Sciences, King`s College London, London, UK
- Allan Walker
- 2 Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK
- Siddharthan Chandran
- Edinburgh Medical School & Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
- Richard Nicholas
- Imperial College, London, UK
- Shuna Colville
- 1 Centre of Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
- Peter Connick
- Anne Rowling Regenerative Neurology Clinic, The University of Edinburgh, Edinburgh, UK
- Carolyn Young
- The Walton Centre NHS Foundation Trust, Liverpool, UK
- Jeremy Hobart
- Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK
- Anisha Doshi
- 1UCL Institute of Neurology, Faculty of Brain Sciences, University College London
- Sharmilee Gnanapavan
- Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, London, UK
- Helen Ford
- consultant
- Baljean Dhillon
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
- Thanh Phan
- Medicine, Monash University, Clayton, Victoria, Australia
- Arman Eshaghi
- 1 Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Julia Aram
- senior house officer in general medicine
- Nigel Stallard
- professor
- James Cameron
- Murdoch Childrens Research Institute, Parkville, Victoria, Australia
- Brendan McLean
- 1 Royal Cornwall Hospital
- Matthew Craner
- Department of Neurology, John Radcliffe Hospital NHS Trust, Oxford, UK
- Domenico Plantone
- 2 Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK
- Jonathan Stutters
- 1 Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Ferran Prados Carrasco
- 2 Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK
- Marie Braisher
- 2 Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, UK
- Moira Ross
- 3 Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
- Gina Cranswick
- Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK
- Sue H Pavitt
- 6 Dental Translational and Clinical Research Unit (part of the NIHR Leeds CRF), University of Leeds, Leeds, UK
- Clive Hawkins
- 9 Keele Medical School and Institute for Science and Technology in Medicine, Keele University, Keele, UK
- Roger Bastow
- 11 MS Society Patient Representative, London, UK
- Daisy Mollison
- Waqar Rashid
- St George`s University Hospitals NHS Foundation Trust, London, UK
- Joe Guadagno
- Royal Victoria Infirmary, Newcastle Hospitals, Newcastle upon Tyne, UK
- Nikolaos Evangelou
- Seema Kalra
- University Hospital North Staffordshire
- Alberto Calvi
- 1 Department of Pathophysiology and Transplantation, Neurodegenerative Disease Unit, University of Milan, Centro Dino Ferrari, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Yingtong Li
- 1Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Tiggy Beyene
- Vanessa Bassan
- Alvin Zapata
- Dawn Lyle
- Heinke Arndt
- DOI
- https://doi.org/10.1136/bmjno-2024-000670
- Journal volume & issue
-
Vol. 6,
no. 2
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.
