Rosa Cortese1, Carmen Tur1, Ferran Prados2, Torben Schneider3, Baris Kanber4, Marcello Moccia5, Claudia Am Gandini Wheeler-Kingshott6, Alan J Thompson1, Frederik Barkhof7, Olga Ciccarelli8. 1. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK. 2. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK/Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College of London, London, UK/Universitat Oberta de Catalunya, Barcelona, Spain. 3. Philips, Guilford, UK. 4. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK/Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College of London, London, UK/Biomedical Research Centre, University College London Hospitals (UCLH), National Institute for Health Research (NIHR), London, UK. 5. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK/MS Clinical Care and Research Centre, Department of Neuroscience, Federico II University, Naples, Italy. 6. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK/Brain MRI 3T Research Center, C. Mondino National Neurological Institute, Pavia, Italy/Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy. 7. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK/Department of Radiology and Nuclear Medicine, MS Centre Amsterdam, VU Medical Centre, Amsterdam, The Netherlands/Biomedical Research Centre, University College London Hospitals (UCLH), National Institute for Health Research (NIHR), London, UK. 8. Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK/Biomedical Research Centre, University College London Hospitals (UCLH), National Institute for Health Research (NIHR), London, UK.
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.
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.
Entities:
Keywords:
Multiple sclerosis; diffusion; magnetic resonance imaging; progressive; spinal cord
Authors: Cristina Granziera; Jens Wuerfel; Frederik Barkhof; Massimiliano Calabrese; Nicola De Stefano; Christian Enzinger; Nikos Evangelou; Massimo Filippi; Jeroen J G Geurts; Daniel S Reich; Maria A Rocca; Stefan Ropele; Àlex Rovira; Pascal Sati; Ahmed T Toosy; Hugo Vrenken; Claudia A M Gandini Wheeler-Kingshott; Ludwig Kappos Journal: Brain Date: 2021-06-22 Impact factor: 13.501
Authors: Francisco Carlos Pérez-Miralles; Daniel Prefasi; Antonio García-Merino; José Ramón Ara; Guillermo Izquierdo; Virginia Meca-Lallana; Francisco Gascón-Giménez; María Luisa Martínez-Ginés; Lluis Ramió-Torrentà; Lucienne Costa-Frossard; Óscar Fernández; Sara Moreno-García; Jorge Maurino; Joan Carreres-Polo; Bonaventura Casanova Journal: Brain Behav Date: 2021-01-23 Impact factor: 2.708
Authors: Alan J Thompson; William Carroll; Olga Ciccarelli; Giancarlo Comi; Anne Cross; Alexis Donnelly; Anthony Feinstein; Robert J Fox; Anne Helme; Reinhard Hohlfeld; Robert Hyde; Pamela Kanellis; Douglas Landsman; Catherine Lubetzki; Ruth Ann Marrie; Julia Morahan; Xavier Montalban; Bruno Musch; Sarah Rawlings; Marco Salvetti; Finn Sellebjerg; Caroline Sincock; Kathryn E Smith; Jon Strum; Paola Zaratin; Timothy Coetzee Journal: Mult Scler Date: 2021-12-01 Impact factor: 6.312