Association of slowly expanding lesions on MRI with disability in people with secondary progressive multiple sclerosis

Calvi, A; Carrasco, F.P; Tur, C; Chard, D.T; Stutters, J; De Angelis, F; John , N; Williams, T; Doshi, A; Samson, R.S; MacManus, D; Gandini Wheeler-Kingshott, C.A; Ciccarelli, O; Chataway, J; Barkhof, F

Association of slowly expanding lesions on MRI with disability in people with secondary progressive multiple sclerosis

Authors

Calvi, A

Carrasco, F.P

Tur, C

Chard, D.T

Stutters, J

De Angelis, F

John , N

Williams, T

Doshi, A

Samson, R.S

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Issue Date

2022

Type

Scientific Paper

Keywords

Research Subject Categories::MEDICINE::Dermatology and venerology,clinical genetics, internal medicine::Internal medicine::Neurology

Abstract

Background and objective: To explore the relationship between slowly expanding lesions (SELs) on MRI and disability in secondary progressive multiple sclerosis (SPMS). Methods: We 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. Results: Averaged 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). Discussion: Definite 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. © 2022 American Academy of Neurology. PubMed Disclaimer Comment in Slowly Expanding Lesions: A New Target for Progressive Multiple Sclerosis Trials? Simmons SB, Ontaneda D. Neurology. 2022 Apr 26;98(17):699-700. doi: 10.1212/WNL.0000000000200230. Epub 2022 Mar 11. PMID: 35277445 No abstract available. Slowly expanding lesions are linked to multiple sclerosis progression. Wood H. Nat Rev Neurol. 2022 May;18(5):252. doi: 10.1038/s41582-022-00654-5. PMID: 35361966 No abstract available. Similar articles Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis. Calvi A, Mendelsohn Z, Hamed W, Chard D, Tur C, Stutters J, MacManus D, Kanber B, Wheeler-Kingshott CAMG, Barkhof F, Prados F. Eur J Neurol. 2024 Jan;31(1):e16092. doi: 10.1111/ene.16092. Epub 2023 Oct 12. PMID: 37823722 Slowly expanding lesions relate to persisting black-holes and clinical outcomes in relapse-onset multiple sclerosis. Calvi A, Tur C, Chard D, Stutters J, Ciccarelli O, Cortese R, Battaglini M, Pietroboni A, De Riz M, Galimberti D, Scarpini E, De Stefano N, Prados F, Barkhof F. Neuroimage Clin. 2022;35:103048. doi: 10.1016/j.nicl.2022.103048. Epub 2022 May 16. PMID: 35598462 Free PMC article. Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis. Elliott C, Belachew S, Wolinsky JS, Hauser SL, Kappos L, Barkhof F, Bernasconi C, Fecker J, Model F, Wei W, Arnold DL. Brain. 2019 Sep 1;142(9):2787-2799. doi: 10.1093/brain/awz212. PMID: 31497864 Free PMC article. Clinical Trial. Mitoxantrone: a review of its use in multiple sclerosis. Scott LJ, Figgitt DP. CNS Drugs. 2004;18(6):379-96. doi: 10.2165/00023210-200418060-00010. PMID: 15089110 Review. The role of magnetic resonance techniques in understanding and managing multiple sclerosis. Miller DH, Grossman RI, Reingold SC, McFarland HF. Brain. 1998 Jan;121 ( Pt 1):3-24. doi: 10.1093/brain/121.1.3. PMID: 9549485 Review. See all similar articles Cited by Systemic inflammation associates with and precedes cord atrophy in progressive multiple sclerosis. Stuart CM, Varatharaj A, Zou Y, Darekar A, Domjan J, Gandini Wheeler-Kingshott CAM, Perry VH, Galea I. Brain Commun. 2024 Apr 20;6(3):fcae143. doi: 10.1093/braincomms/fcae143. eCollection 2024. PMID: 38712323 Free PMC article. Effect of siponimod on lymphocyte subsets in active secondary progressive multiple sclerosis and clinical implications. Spiezia AL, Scalia G, Petracca M, Caliendo D, Moccia M, Fiore A, Cerbone V, Lanzillo R, Brescia Morra V, Carotenuto A. J Neurol. 2024 Apr 17. doi: 10.1007/s00415-024-12362-9. Online ahead of print. PMID: 38632126 Basic Science of Neuroinflammation and Involvement of the Inflammatory Response in Disorders of the Nervous System. Parsi S, Zhu C, Motlagh NJ, Kim D, Küllenberg EG, Kim HH, Gillani RL, Chen JW. Magn Reson Imaging Clin N Am. 2024 May;32(2):375-384. doi: 10.1016/j.mric.2024.01.003. Epub 2024 Feb 6. PMID: 38555147 Review. Understanding multiple sclerosis as a disease spectrum: above and below the clinical threshold. Krieger S, Cook K, Hersh CM. Curr Opin Neurol. 2024 Jun 1;37(3):189-201. doi: 10.1097/WCO.0000000000001262. Epub 2024 Apr 9. PMID: 38535979 Free PMC article. Review. Transcript Profiles of Microglia/Macrophage Cells at the Borders of Chronic Active and Subpial Gray Matter Lesions in Multiple Sclerosis. Chomyk A, Kucinski R, Kim J, Christie E, Cyncynatus K, Gossman Z, Chen Z, Richardson B, Cameron M, Turner T, Dutta R, Trapp B. Ann Neurol. 2024 May;95(5):907-916. doi: 10.1002/ana.26877. Epub 2024 Feb 12. PMID: 38345145 See all "Cited by" articles MeSH terms Brain / pathology Humans Magnetic Resonance Imaging / methods Multiple Sclerosis* Multiple Sclerosis, Chronic Progressive* / complications Multiple Sclerosis, Chronic Progressive* / diagnostic imaging Multiple Sclerosis, Chronic Progressive* / drug therapy Retrospective Studies Related information MedGen Grants and funding MC_PC_13089/MRC_/Medical Research Council/United Kingdom LinkOut - more resources Full Text Sources Atypon Ingenta plc Ovid Technologies, Inc. Medical Genetic Alliance MedlinePlus Health Information

Citation

Calvi A, Carrasco FP, Tur C, Chard DT, Stutters J, De Angelis F, John N, Williams T, Doshi A, Samson RS, MacManus D, Gandini Wheeler-Kingshott CA, Ciccarelli O, Chataway J, Barkhof F; MS SMART Investigators. Association of Slowly Expanding Lesions on MRI With Disability in People With Secondary Progressive Multiple Sclerosis. Neurology. 2022 Apr 26;98(17):e1783-e1793. doi: 10.1212/WNL.0000000000200144. Epub 2022 Mar 11. PMID: 35277438.

ISSN

https://www.neurology.org/doi/10.1212/WNL.0000000000200144

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Clinical Service Line 05 - Respiratory, Cardiology, Stroke, Neurology, Medical wards, Cardiac Centre

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