Patterns of Brain Atrophy in Recently-Diagnosed Relapsing-Remitting Multiple Sclerosis

Rozanna Meijboom , Elizabeth N. York, Agniete Kampaite, Mathew A. Harris, Nicole White, Maria del C. Valdés Hernández , Michael J. Thrippleton, N. J. J. MacDougall, Peter Connick, David P. J. Hunt, Siddharthan Chandran, Adam D. Waldman ,on behalf of the FutureMS Consortium


Recurrent neuroinflammation in relapsing-remitting MS (RRMS) is thought to lead to neurodegeneration, resulting in progressive disability. Repeated magnetic resonance imaging (MRI) of the brain provides non-invasive measures of atrophy over time, a key marker of neurodegeneration. This study investigates regional neurodegeneration of the brain in recently-diagnosed RRMS using volumetry and voxel-based morphometry (VBM). RRMS patients (N = 354) underwent 3T structural MRI <6 months after diagnosis and 1-year follow-up, as part of the Scottish multicentre ‘FutureMS’ study.


Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease affecting two million people worldwide [1–3]. Disease progression and severity varies between individuals, and symptoms are diverse, including mobility and vision problems, pain, depression, fatigue and cognitive impairment [4]. Several MS subtypes have been identified, of which relapsing-remitting disease (RRMS) is the most common [5,6].

Materials and methods

Participants with a recent diagnosis of RRMS according to the 2017 McDonald criteria (< 6 months) [7], were recruited (2016–2019) across five neurology sites in Scotland: Aberdeen, Dundee, Edinburgh, Inverness and Glasgow, as part of the FutureMS study [40,41]. Participants were 18 years or older and had the capacity to provide informed consent. Exclusion criteria were participation in a clinical trial prior to baseline assessment,contraindications for MRI, and intake of DMTs prescribed prior to baseline assessment. The latter criteria was selected because DMT intake in the Scottish population is very low compared with other countries, creating a unique opportunity to develop natural history predictive tools. Study visits took place at baseline (wave 0 [w0])) and 1-year follow-up (w1) and participants underwent brain MRI and expanded-disability status scale (EDSS) assessment at both time points. Full details of the FutureMS study have been previously described in Kearns et al. 2021 [40].


Twelve clusters of various sizes (Table 4) showed a change in local concentration of GM over time. The largest clusters were centred within 1) the temporal lobe and subcortical areas, 2) cerebellum, 3) anterior cingulum and supplementary motor cortex. Additional smaller clusters were also observed in the temporal lobe and cerebellum. Furthermore, four smaller clusters were observed in the occipital lobe, as well as one cluster in the posterior frontal lobe and one in the parietal supramarginal and angular gyrus. See Fig 4 for VBM results. See Fig 5 for a visual comparison of volumetric (regional GM, cerebellar GM and subcortical areas) and VBM results.


Widespread NAWM and GM atrophy was observed using both approaches. With the volumetric approach, people with recently-diagnosed RRMS showed brain volume loss in the brainstem, all subcortical regions and the cerebellar GM but not NAWM, over one year. Furthermore, cerebral NAWM and GM volume loss over one year was also evident. Specifically, GM and NAWM volume decreased in nearly all temporal, parietal and occipital regions and in about half of frontal regions. Slightly more NAWM regions showed volume decrease in the temporal-parietal lobes and slightly more GM regions showed a volume decrease in the frontal lobe. Additionally, more left frontal GM and NAWM regions showed volume decrease than right frontal regions. 


We would like to thank non-author contributors of the FutureMS consortium as follows: Amit Akula, Sergio Baranzini, Fiona Barret, Mark Bastin, Chris Batchelor, Emily Beswick, Fraser Brown, Tracy Brunton, Javier Carod Artal, Jessie Chang, Yingdi Chen, Shuna Colville, Annette Cooper, Denise Cranley, Rachel Dakin, Baljean Dhillon, Elizabeth Elliott, James Finlayson, Peter Foley, Stella Glasmacher, Angus Grossart, Haane Haagenrud, Katarzyna Hafezi, Emily Harrison, Adil Harroud, Sara Hathorn, Tracey Hopkins, Aidan Hutchison, Charlotte Jardine, Kiran Jayprakash, Matt Justin, Patrick Kearns, Gwen Kennedy, Lucy Kessler, Michaela Kleynhans, Juan Larraz, Katherine Love, Dawn Lyle, James MacDonald, Jen MacFarlane, Lesley Macfarlane, Alan Maclean, Bev MacLennan, Margaret-Ann MacLeod, Nicola Macleod, Don Mahad, Sarah-Jane Martin, Conni McCarthy, Ian Megson, Daisy Mollison, Mary Monaghan, Lee Murphy, Katy Murray, Judith Newton, Julian Ng Kee Kwong, Jonathan O’Riordan, David Perry, Suzanne Quigley, Adam Scotson, Scott Semple, Amy Stenson, Christine Weaver, Stuart Webb, Belinda Weller, Anna Williams, Stewart Wiseman, Charis Wong, Michael Wong and Rosie Woodward. With special thanks to all FutureMS participants who have made this study possible. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.

Citation: Meijboom R, York EN, Kampaite A, Harris MA, White N, Valdés Hernández MdC, et al. (2023) Patterns of brain atrophy in recently-diagnosed relapsing-remitting multiple sclerosis. PLoS ONE 18(7): e0288967.

Editor: Niels Bergsland, University at Buffalo, UNITED STATES

Received: November 7, 2022; Accepted: July 7, 2023; Published: July 28, 2023

Copyright: © 2023 Meijboom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The FutureMS project agreement, under reference LG/CPH/UOF001.2011, between The University Courts of the University of Glasgow, Edinburgh and Aberdeen, as well as the Grampian, Tayside, Lothian and Greater Glasgow Health boards, states that personal data cannot be released or made available to any third party unless the FutureMS steering committee have expressly permitted the data sharing, or personal data has been anonymized sufficiently. The magnetic resonance imaging data used in the current paper are not defaced and hence not sufficiently anonymized for open data sharing. Unrestricted access to these images in current form would present a confidentiality/privacy risk for participants. Additionally, the informed consent, approved by the South East Scotland Research Ethics Committee 02 under reference 15/SS/0233, states that by consenting to the FutureMS study, participants agree to sharing their data with the wider study team. The authors have not obtained explicit consent for deidentified data sharing beyond the wider study team. As such, they cannot make deidentified data openly available. The authors do, however, highly encourage collaboration with other research teams, and any researchers may request access to anonymized patient data from FutureMS-1 by contacting [email protected]. Proposals will be reviewed by the FutureMS steering committee and if approved, a signed data sharing agreement will be issued.

Funding: With thanks to FutureMS, hosted by Precision Medicine Scotland Innovation Centre (PMS-IC) and funded by a grant from the Chief Scientist Office, Scotland, to PMS-IC and Biogen Idec Ltd Insurance (combined funding under reference Exemplar SMS_IC010). Additional funding for authors came from the MS Society Edinburgh Centre for MS Research (grant reference 133; RM, AK), Chief Scientist Office – SPRINT MND/MS program (grant reference MMPP/01; ENY), Anne Rowling Regenerative Neurology Clinic (ENY), NHS Lothian Research and Development Office (MJT), the Row Fogo Charitable Trust (grant reference BROD.FID3668413; MVH), Wellcome Trust Senior Research Fellowship (grant reference 215621/Z/19/Z; DPJH), Medical Research Foundation (DPJH), and the UK Dementia Research Institute (SC), which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. Additional funding for the Edinburgh university 3T MRI Research scanner in RIE is funded by the Wellcome Trust (104916/Z/14/Z), Dunhill Trust (R380R/1114), Edinburgh and Lothians Health Foundation (2012/17), Muir Maxwell Research Fund, Edinburgh Imaging, and University of Edinburgh. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

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