@article{b39837bfd4b34963b1f6f7203f51d231,
title = "Ongoing microstructural changes in the cervical cord underpin disability progression in early primary progressive multiple sclerosis",
abstract = "Background: Pathology in the spinal cord of patients with primary progressive multiple sclerosis (PPMS) contributes to disability progression. We previously reported abnormal Q-space imaging (QSI)-derived indices in the spinal cord at baseline in patients with early PPMS, suggesting early neurodegeneration. Objective: The aim was to investigate whether changes in spinal cord QSI over 3 years in the same cohort are associated with disability progression and if baseline QSI metrics predict clinical outcome. Methods: Twenty-three PPMS patients and 23 healthy controls recruited at baseline were invited for follow-up cervical cord 3T magnetic resonance imaging (MRI) and clinical assessment after 1 year and 3 years. Cord cross-sectional area (CSA) and QSI measures were obtained, together with standard brain MRI measures. Mixed-effect models assessed MRI changes over time and their association with clinical changes. Linear regression identified baseline MRI indices associated with disability at 3 years. Results: Over time, patients deteriorated clinically and showed an increase in cord QSI indices of perpendicular diffusivity that was associated with disability worsening, independently of the decrease in CSA. Higher perpendicular diffusivity and lower CSA at baseline predicted worse disability at 3 years. Conclusion: Increasing spinal cord perpendicular diffusivity may indicate ongoing neurodegeneration, which underpins disability progression in PPMS, independently of the development of spinal cord atrophy.",
keywords = "Multiple sclerosis, diffusion, magnetic resonance imaging, progressive, spinal cord",
author = "Rosa Cortese and Carmen Tur and Ferran Prados and Torben Schneider and Baris Kanber and Marcello Moccia and Wheeler-Kingshott, {Claudia A. M. Gandini} and Thompson, {Alan J.} and Frederik Barkhof and Olga Ciccarelli",
note = "Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: R.C. and T.S. have no disclosures. C.T. has received a post-doctoral research ECTRIMS fellowship (2015). She has also received honoraria and support for travelling from Teva Pharmaceuticals Europe and Ismar Healthcare. F.P. is a non-clinical guarantor of brain fellow. He has also received honoraria from Bioclinica Inc. M.M. has received research grants from ECTRIMS-MAGNIMS, UK MS Society and Merck, and honoraria from Biogen, Merck, Roche and Sanofi-Genzyme. C.A.M.G.W.-K. receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020 and NIHR/MRC. A.J.T. has received honoraria and support for travel from Eisai and EXCEMED. He received support for travel from the International Progressive MS Alliance as chair of their Scientific Steering Committee, and from the National MS Society (USA) as a member of their Research Programs Advisory Committee. He receives an honorarium from SAGE Publishers as Editor-in-Chief of MSJ. Support from the NIHR UCLH Biomedical Research Centre is acknowledged. F.B. acts as a consultant to Biogen-Idec, Janssen Alzheimer Immunotherapy, Bayer-Schering, Merck-Serono, Roche, Novartis, Genzyme and Sanofi-aventis. He has received sponsorship from EU-H2020, NWO, SMSR, EU-FP7, TEVA, Novartis and Toshiba. He is on the editorial board of Radiology, Brain, Neuroradiology, MSJ and Neurology. O.C. is a National Institute for Health Research (NIHR) research professor; she has received grants from the UK MS Society, National MS Society, NIHR UCLH BRC, Progressive MS Alliance, Bioclinica, GE Neuro, the EU2020, Spinal Cord Research Foundation and Rosetrees Trust; has received personal fees from Novartis, Teva, Roche, Biogen and Merck; and receives an honorarium from the journal Neurology. Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This research study was funded by the UK MS Society (programme grant number 984) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Publisher Copyright: {\textcopyright} The Author(s), 2020. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jan,
doi = "https://doi.org/10.1177/1352458519900971",
language = "English",
volume = "27",
pages = "28--38",
journal = "MULTIPLE SCLEROSIS JOURNAL",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "1",
}