TY - JOUR
T1 - Association of Slowly Expanding Lesions on MRI With Disability in People With Secondary Progressive Multiple Sclerosis
AU - Calvi, Alberto
AU - Carrasco, Ferran Prados
AU - Tur, Carmen
AU - Chard, Declan T.
AU - Stutters, Jonathan
AU - de Angelis, Floriana
AU - John, Nevin
AU - Williams, Thomas
AU - Doshi, Anisha
AU - Samson, Rebecca S.
AU - MacManus, David
AU - Gandini Wheeler-Kingshott, Claudia A.
AU - Ciccarelli, Olga
AU - Chataway, Jeremy
AU - Barkhof, Frederik
N1 - Funding Information: A. Calvi is supported by an ECTRIMS-MAGNIMS fellowship (2018), Guarantors of Brain “Entry” clinical fellowship (2019), and the UK MS Society PhD studentship (2020). F. Prados Carrasco received a Guarantors of Brain fellowship 2017–2020 and is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre initiative at University College London Hospitals (UCLH). C. Tur has received an ECTRIMS Postdoctoral Research Fellowship in 2015; and honoraria and support for traveling from Merck Serono, Sanofi, Roche, TEVA Pharmaceuticals, Novartis, Biogen, Bayer, and Ismar Healthcare. D. Chard is a consultant for Biogen and Hoffmann-La Roche and is supported by the NIHR Biomedical Research Centre initiative at UCLH, the International Progressive MS Alliance, and the UK MS Society. F. De Angelis, N. John, T. Williams, A. Doshi, J. Stutters, and D. MacManus declare no conflicts of interest with respect to this work. R.S. Samson receives research funding from the MS Society (77), CureDRPLA, and Ataxia UK. C. Gandini Wheeler-Kingshott receives research funding from the MS Society (77), Wings for Life (169111), Horizon2020 (CDS-QUAMRI, 634541), BRC (RC704/CAP/CGW), UCL Global Challenges Research Fund (GCRF), and MRC (MR/S026088/1); and is a shareholder in Queen Square Analytics Ltd. O. Ciccarelli received research funding from the NIHR Biomedical Research Centre initiative at UCLH, UK and National MS Societies, and Rosetrees trust; serves as consultant for Novartis, Roche, and Teva; and is an Associate Editor for Neurology®. J. Chataway has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and NIHR Biomedical Research Centre initiative at UCLH partnership and the Health Technology Assessment (HTA) Programme, the UK MS Society, the US National MS Society, and the Rosetrees Trust; has been a local principal investigator for a trial in MS funded by the Canadian MS society and a local principal investigator for commercial trials funded by Actelion, Biogen, Novartis, and Roche; has received an investigator grant from Novartis; and has taken part in advisory boards/consultancy for Azadyne, Biogen, Celgene, Janssen, MedDay, Merck, Novartis, and Roche. F. Barkhof is supported by the NIHR Biomedical Research Centre initiative at UCLH; serves on the editorial boards of Brain, European Radiology, Journal of Neurology, Neurosurgery & Psychiatry, Neurology, Multiple Sclerosis, and Neuroradiology; and serves as consultant for Bayer Schering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA Pharmaceuticals, Genzyme, Merck-Serono, Novartis, Roche, Synthon, Jansen Research, and Lundbeck. The MS-SMART trial, an investigator-led project sponsored by University College London, was funded by the Efficacy and Mechanism Evaluation program as project number 11/30/11. This independent research is awarded by and funded by the MRC, the UK MS Society, and the National MS Society and is managed by the NIHR on behalf of the MRC–National Institute for Health partnership. Additional support came from the University of Edinburgh; the NIHR UCLH Biomedical Research Center and University College London; and the NIHR Leeds Clinical Research Facility (Dental Translational and Clinical Research Unit). Riluzole was provided without charge by Sanofi-Genzyme, which was not involved in the trial design, running of the trial or analysis. Go to Neurology.org/N for full disclosures. Publisher Copyright: © American Academy of Neurology.
PY - 2022/4/26
Y1 - 2022/4/26
N2 - Background and ObjectiveTo explore the relationship between slowly expanding lesions (SELs) on MRI and disability in secondary progressive multiple sclerosis (SPMS).MethodsWe retrospectively studied 345 patients with SPMS enrolled in the MS-SMART trial. They underwent brain MRI at baseline and at 24 and 96 weeks. Definite SELs were defined as concentrically expanding T2 lesions, as assessed by nonlinear deformation of volumetric T1-weighted images. Associations of SEL volumes with other MRI metrics and disability were assessed through Pearson correlations and regression analyses.ResultsAveraged across patients, 29% of T2 lesions were classified as being definite SELs. A greater volume of definite SELs correlated with a higher total baseline T2 lesion volume (r = 0.55, p < 0.001) and percentage brain volume reduction (r = -0.26, p < 0.001), a higher number of new persisting T1 black holes (r = 0.19, p < 0.001), and, in a subset of 106 patients, with a greater reduction in magnetization transfer ratio (adjusted difference 0.52, p < 0.001). In regression analyses, a higher definite SEL volume was associated with increasing disability, as assessed by the Expanded Disability Status Scale (β = 0.23, p = 0.020), z scores of the Multiple Sclerosis Functional Composite (β = -0.47, p = 0.048), Timed 25-Foot Walk Test (β = -2.10, p = 0.001), and Paced Auditory Serial Addition Task (β = -0.27, p = 0.006), and increased risk of disability progression (odds ratio 1.92, p = 0.025).DiscussionDefinite SELs represent almost one-third of T2 lesions in SPMS. They are associated with neurodegenerative MRI markers and related to clinical worsening, suggesting that they may contribute to disease progression and be a new target for therapeutic interventions.
AB - Background and ObjectiveTo explore the relationship between slowly expanding lesions (SELs) on MRI and disability in secondary progressive multiple sclerosis (SPMS).MethodsWe retrospectively studied 345 patients with SPMS enrolled in the MS-SMART trial. They underwent brain MRI at baseline and at 24 and 96 weeks. Definite SELs were defined as concentrically expanding T2 lesions, as assessed by nonlinear deformation of volumetric T1-weighted images. Associations of SEL volumes with other MRI metrics and disability were assessed through Pearson correlations and regression analyses.ResultsAveraged across patients, 29% of T2 lesions were classified as being definite SELs. A greater volume of definite SELs correlated with a higher total baseline T2 lesion volume (r = 0.55, p < 0.001) and percentage brain volume reduction (r = -0.26, p < 0.001), a higher number of new persisting T1 black holes (r = 0.19, p < 0.001), and, in a subset of 106 patients, with a greater reduction in magnetization transfer ratio (adjusted difference 0.52, p < 0.001). In regression analyses, a higher definite SEL volume was associated with increasing disability, as assessed by the Expanded Disability Status Scale (β = 0.23, p = 0.020), z scores of the Multiple Sclerosis Functional Composite (β = -0.47, p = 0.048), Timed 25-Foot Walk Test (β = -2.10, p = 0.001), and Paced Auditory Serial Addition Task (β = -0.27, p = 0.006), and increased risk of disability progression (odds ratio 1.92, p = 0.025).DiscussionDefinite SELs represent almost one-third of T2 lesions in SPMS. They are associated with neurodegenerative MRI markers and related to clinical worsening, suggesting that they may contribute to disease progression and be a new target for therapeutic interventions.
UR - http://www.scopus.com/inward/record.url?scp=85127427924&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000200144
DO - https://doi.org/10.1212/WNL.0000000000200144
M3 - Article
C2 - 35277438
SN - 0028-3878
VL - 98
SP - E1783-E1793
JO - Neurology
JF - Neurology
IS - 17
ER -