Article Text

Download PDFPDF
Original research
Linear brain atrophy measures in multiple sclerosis and clinically isolated syndromes: a 30-year follow-up
  1. Lukas Haider1,2,
  2. Karen Chung3,
  3. Giselle Birch3,
  4. Arman Eshaghi3,4,
  5. Stephanie Mangesius5,6,
  6. Ferran Prados7,8,
  7. Carmen Tur3,
  8. Olga Ciccarelli3,9,
  9. Frederik Barkhof3,10,
  10. Declan Chard3,9
  1. 1UCL Queen Square Institute of Neurology, UCL, London, UK
  2. 2Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Wien, Wien, Austria
  3. 3NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London, London, London, UK
  4. 4Department of Medical Physics and Biomedical Engineering, University College London, London, London, UK
  5. 5Department of Neuroradiology, Medizinische Universitat Innsbruck, Innsbruck, Austria
  6. 6Neuroimaging Core Facility, Medizinische Universitat Innsbruck, Innsbruck, Tirol, Austria
  7. 7Centre for Medical Image Computing (CMIC), Department of Medical Physics and Bioengineering, University College London, London, London, UK
  8. 8Universitat Oberta de Catalunya, Barcelona, Catalunya, Spain
  9. 9University College London Hospitals (UCLH) Biomedical Research Centre, National Institute for Health Research, London, London, UK
  10. 10Department of Radiology and Nuclear Medicine, VU University Medical Centre Amsterdam, Amsterdam, Noord-Holland, Netherlands
  1. Correspondence to Dr Karen Chung, NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London, London WC1B 5EH, UK; k.chung{at}ucl.ac.uk

Abstract

Objective To determine 30-year brain atrophy rates following clinically isolated syndromes and the relationship of atrophy in the first 5 years and clinical outcomes 25 years later.

Methods A cohort of 132 people who presented with a clinically isolated syndrome suggestive of multiple sclerosis (MS) were recruited between 1984–1987. Clinical and MRI data were collected prospectively over 30 years. Widths of the third ventricle and the medulla oblongata were used as linear atrophy measures.

Results At 30 years, 27 participants remained classified as having had a clinically isolated syndrome, 34 converted to relapsing remitting MS, 26 to secondary progressive MS and 16 had died due to MS. The mean age at baseline was 31.7 years (SD 7.5) and the mean disease duration was 30.8 years (SD 0.9). Change in medullary and third ventricular width within the first 5 years, allowing for white matter lesion accrual and Expanded Disability Status Scale increases over the same period, predicted clinical outcome measures at 30 years. 1 mm of medullary atrophy within the first 5 years increased the risk for secondary progressive MS or MS related death by 30 years by 583% (OR 5.83, 95% CI 1.74 to 19.61, p<0.005), using logistic regression.

Conclusions Our findings show that brain regional atrophy within 5 years of a clinically isolated syndrome predicts progressive MS or a related death, and disability 25 years later.

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. N/A.

Statistics from Altmetric.com

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. N/A.

View Full Text

Footnotes

  • Twitter @es_arman

  • Contributors LH had full access to all the data and was responsible for data and statistical analysis, interpretation of the results, prepared the first draft of the manuscript (together with KC and DC), and edited subsequent versions. KC was responsible for clinical and MRI data collection at 30 years, and collecting and archiving clinical and MRI data from previous time points. She contributed to image analyses, prepared the first draft of the manuscript (together with LH and DC), and edited subsequent versions. GB contributed to image analysis. AE participated and supervised in statistical analysis and interpretation. SM contributed to image analysis. FP participated and supervised in image preparation, analysis and interpretation. CT participated and supervised in statistical analysis and interpretation. OC reviewed the manuscript and contributed to results interpretation. FB contributed to study supervision, supervised in image analysis, reviewed the manuscript and contributed to results interpretation. DC contributed to the study design, securing funding and study supervision. He had full access to the data and was responsible for data and statistical analysis, interpretation of the results, prepared the first draft of the manuscript (together with KC and LH), and edited subsequent versions. All coauthors have reviewed and approved the submission of this manuscript.

  • Funding This study was funded by the MS Society of Great Britain and Northern Ireland (20; 984). LH was supported by the European Society of Neuroradiology (2018) and an ECTRIMS/MAGNIMS research fellowship (2019). SM gratefully acknowledges research funding from ÖAW (Österreichische Akademie der Wis-senschaften; GDNG_2018-041_MedCorpInn) and the Jubliäumsfonds der Universität Innsbruck und der Medizinischen Universität Innsbruck (2019) outside of the submitted work. FP has received a non-clinical Guarantors of Brain fellowship. OC has received research funding from: UK and National MS Societies, and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). FB is supported by the NIHR UCL BRC. DC has received research funding from the International Progressive MS Alliance, the MS Society, and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre.

  • Competing interests LH has nothing to declare. KC has received honoraria for speaking at meetings, advisory work or support to attend meetings from Biogen, Sanofi-Genzyme and Roche. GB, AE, SM, FP and CT have nothing to declare. OC serves as a consultant for Novartis, Roche, Teva and Merck, and receives personal fees from Neurology and Multiple Sclerosis Journal. Outside the submitted work, she has received research grants from Spinal Cord Research Foundation, Rosetrees trust, Progressive MS Alliance, Bioclinica & GE Neuro, and EU-H2020. FB serves as a consultant for Bayer Schering Pharma, Sanofi-Genzyme, Biogen Idec, Teva, Merck Serono, Novartis, Roche, IXICO, GeNeuro, Apitope and Jansen Research. DC is a consultant for Biogen and Roche.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • 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.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.