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Research paper
Cortical grey matter sodium accumulation is associated with disability and secondary progressive disease course in relapse-onset multiple sclerosis
  1. Wallace J Brownlee1,
  2. Bhavana Solanky1,
  3. Ferran Prados1,2,
  4. Marios Yiannakas1,
  5. Patricia Da Mota1,
  6. Frank Riemer3,
  7. Manuel Jorge Cardoso2,
  8. Sebastian Ourselin2,
  9. Xavier Golay4,
  10. Claudia Gandini Wheeler-Kingshott1,5,6,
  11. Olga Ciccarelli1,7
  1. 1 Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London, United Kingdom
  2. 2 Translational Imaging Group, Centre for Medical Image Computing (CMIC), Department of Medical Physics and Bioengineering, University College London, London, United Kingdom
  3. 3 Department of Radiology, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
  4. 4 Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom
  5. 5 BrainMRI 3T Research Centre, IRCCS Mondino Foundation, Pavia, Italy
  6. 6 Departmentof Brain and Behavioural Sciences, University of Pavia, Pavia, Italy
  7. 7 National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, London, United Kingdom
  1. Correspondence to Dr Wallace J Brownlee, Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, London WC1N 3BG, UK; w.brownlee{at}ucl.ac.uk

Abstract

Objective Sodium (23Na)-MRI is an emerging imaging technique to investigate in vivo changes in tissue viability, reflecting neuroaxonal integrity and metabolism. Using an optimised 23Na-MRI protocol with smaller voxel sizes and improved tissue contrast, we wanted to investigate whether brain total sodium concentration (TSC) is a biomarker for long-term disease outcomes in a cohort of patients with relapse-onset multiple sclerosis (MS), followed from disease onset.

Methods We performed a cross-sectional study in 96 patients followed up ~ 15 years after a clinically isolated syndrome (CIS) and 34 healthy controls. Disease course was classified as CIS, relapsing-remitting MS or secondary progressive MS (SPMS). We acquired 1H-MRI and 23Na-MRI and calculated the TSC in cortical grey matter (CGM), deep grey matter, normal-appearing white matter (WM) and WM lesions. Multivariable linear regression was used to identify independent associations of tissue-specific TSC with physical disability and cognition, with adjustment for tissue volumes.

Results TSC in all tissues was higher in patients with MS compared with healthy controls and patients who remained CIS, with differences driven by patients with SPMS. Higher CGM TSC was independently associated with Expanded Disability Status Scale (R2=0.26), timed 25-foot walk test (R2=0.23), 9-hole peg test (R2=0.23), Paced Auditory Serial Addition Test (R2=0.29), Symbol Digit Modalities Test (R2=0.31) and executive function (R2=0.36) test scores, independent of grey matter atrophy.

Conclusions Sodium accumulation in CGM reflects underlying neuroaxonal metabolic abnormalities relevant to disease course heterogeneity and disability in relapse-onset MS. TSC and should be considered as an outcome measure in future neuroprotection trials.

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Footnotes

  • Contributors WJB contributed to study concept/design, analysis and interpretation of data, statistical analysis and drafting manuscript. BS contributed to study concept/design, analysis and interpretation of data and manuscript revision. FP contributed to study concept/design, analysis and interpretation of data and manuscript revision. MY contributed to data acquisition, analysis and interpretation and manuscript revision. PDM contributed to analysis and interpretation of data and manuscript revision. FR contributed to study concept/design, analysis and interpretation of data and manuscript revision. MJC contributed to data analysis and manuscript revision. SO contributed to data analysis and manuscript revision XG contributed to study concept/design and manuscript revision. CW-K contributed to study concept/design, interpretation of data and manuscript revision. OC obtained funding and contributed to study concept/design, manuscript revision and provided study supervision.

  • Funding This study was funded by the United Kingdom MS Society and the Neurological Foundation of New Zealand and supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre.

  • Disclaimer WJB has received speaker fees from Merck Serono, Sanofi Genzyme and Roche. BS, FP, MY, PDM, FR, MJC, SO and XG report no financial disclosures relevant to this manuscript. OC serves as a consultant for Novartis, Teva, Roche, Genzyme and Biogen Idec.

  • Competing interests WJB has received speaker fees from Merck Serono, Sanofi Genzyme and Roche. BS, FP, MY, PDM, FR, MJC, SO and XG report no financial disclosures relevant to this manuscript. OC serves as a consultant for Novartis, Teva, Roche, Genzyme and Biogen Idec.

  • Patient consent for publication Not required.

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

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