학술논문
Remyelination varies between and within lesions in multiple sclerosis following bexarotene.
Document Type
Academic Journal
Author
Brown JWL; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.; NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Queen Square Institute of Neurology, London, UK.; Clinical Outcomes Research Unit (CORe), University of Melbourne, Melbourne, Australia.; Prados F; NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Queen Square Institute of Neurology, London, UK.; e-Health Center, Universitat Oberta de Catalunya, Barcelona, Spain.; Department of Medical Physics and Biomedical Engineering, Centre for Medical Image Computing, University College London, London, UK.; Altmann DR; Medical Statistics Department, London School of Hygiene & Tropical Medicine, London, UK.; Kanber B; NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Queen Square Institute of Neurology, London, UK.; Department of Medical Physics and Biomedical Engineering, Centre for Medical Image Computing, University College London, London, UK.; National Institute for Health Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust and University College London, London, UK.; Stutters J; NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Queen Square Institute of Neurology, London, UK.; Cunniffe NG; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.; Jones JL; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.; Georgieva ZG; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.; Needham EJ; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.; Daruwalla C; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.; Wheeler-Kingshott CG; NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Queen Square Institute of Neurology, London, UK.; Brain Connectivity Centre, IRCCS Mondino Foundation, Pavia, Italy.; Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.; Connick P; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.; Chandran S; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.; UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.; Franklin R; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; MacManus D; NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Queen Square Institute of Neurology, London, UK.; Samson R; NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Queen Square Institute of Neurology, London, UK.; Coles A; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.; Chard D; NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Queen Square Institute of Neurology, London, UK.; National Institute for Health Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust and University College London, London, UK.
Source
Publisher: Wiley Periodicals, Inc on behalf of American Neurological Association Country of Publication: United States NLM ID: 101623278 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2328-9503 (Electronic) Linking ISSN: 23289503 NLM ISO Abbreviation: Ann Clin Transl Neurol Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis. While the primary MRI outcome was negative, there was converging neurophysiological and MRI evidence of efficacy. Multiple factors influence lesion remyelination. In this study we undertook a systematic exploratory analysis to determine whether treatment response - measured by change in magnetisation transfer ratio - is influenced by location (tissue type and proximity to CSF) or the degree of abnormality (using baseline magnetisation transfer ratio and T1 values).
Methods: We examined treatment effects at the whole lesion level, the lesion component level (core, rim and perilesional tissues) and at the individual lesion voxel level.
Results: At the whole lesion level, significant treatment effects were seen in GM but not WM lesions. Voxel-level analyses detected significant treatment effects in WM lesion voxels with the lowest baseline MTR, and uncovered gradients of treatment effect in both WM and CGM lesional voxels, suggesting that treatment effects were lower near CSF spaces. Finally, larger treatment effects were seen in the outer and surrounding components of GM lesions compared to inner cores.
Interpretation: Remyelination varies markedly within and between lesions. The greater remyelinating effect in GM lesions is congruent with neuropathological observations. For future remyelination trials, whole GM lesion measures require less complex post-processing compared to WM lesions (which require voxel level analyses) and markedly reduce sample sizes.
(© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Methods: We examined treatment effects at the whole lesion level, the lesion component level (core, rim and perilesional tissues) and at the individual lesion voxel level.
Results: At the whole lesion level, significant treatment effects were seen in GM but not WM lesions. Voxel-level analyses detected significant treatment effects in WM lesion voxels with the lowest baseline MTR, and uncovered gradients of treatment effect in both WM and CGM lesional voxels, suggesting that treatment effects were lower near CSF spaces. Finally, larger treatment effects were seen in the outer and surrounding components of GM lesions compared to inner cores.
Interpretation: Remyelination varies markedly within and between lesions. The greater remyelinating effect in GM lesions is congruent with neuropathological observations. For future remyelination trials, whole GM lesion measures require less complex post-processing compared to WM lesions (which require voxel level analyses) and markedly reduce sample sizes.
(© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)