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Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression

BACKGROUND AND OBJECTIVES: Chronic active lesions contribute to multiple sclerosis (MS) severity, but their association with long-term disease progression has not been evaluated yet. White matter (WM) lesions showing linear expansion over time on serial T(1)- and T(2)-weighted scans (i.e., slowly ex...

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Autores principales: Preziosa, Paolo, Pagani, Elisabetta, Meani, Alessandro, Moiola, Lucia, Rodegher, Mariaemma, Filippi, Massimo, Rocca, Maria A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808355/
https://www.ncbi.nlm.nih.gov/pubmed/35105685
http://dx.doi.org/10.1212/NXI.0000000000001139
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author Preziosa, Paolo
Pagani, Elisabetta
Meani, Alessandro
Moiola, Lucia
Rodegher, Mariaemma
Filippi, Massimo
Rocca, Maria A.
author_facet Preziosa, Paolo
Pagani, Elisabetta
Meani, Alessandro
Moiola, Lucia
Rodegher, Mariaemma
Filippi, Massimo
Rocca, Maria A.
author_sort Preziosa, Paolo
collection PubMed
description BACKGROUND AND OBJECTIVES: Chronic active lesions contribute to multiple sclerosis (MS) severity, but their association with long-term disease progression has not been evaluated yet. White matter (WM) lesions showing linear expansion over time on serial T(1)- and T(2)-weighted scans (i.e., slowly expanding lesions [SELs]) have been proposed as a marker of chronic inflammation. In this study, we assessed whether SEL burden and microstructural abnormalities were associated with Expanded Disability Status Scale (EDSS) score worsening and secondary progressive (SP) conversion at 9.1-year follow-up in patients with relapsing-remitting (RR) MS. METHODS: In 52 patients with RRMS, SELs were identified among WM lesions by linearly fitting the Jacobian of the nonlinear deformation field between time points obtained combining 3T brain T(1)- and T(2)-weighted scans acquired at baseline and months 6, 12, and 24. Logistic regression analysis was applied to investigate the associations of SEL number, volume, magnetization transfer ratio (MTR), and T(1)-weighted signal intensity with disability worsening (i.e., EDSS score increase) and SP conversion after a median follow-up of 9.1 years. RESULTS: At follow-up, 20/52 (38%) patients with MS showed EDSS score worsening; 13/52 (25%) showed SP conversion. A higher baseline EDSS score (for each point higher: OR = 3.15 [95% CI = 1.61; 8.38], p = 0.003), a higher proportion of SELs among baseline lesions (for each % increase: OR = 1.22 [1.04; 1.58], p = 0.04), and lower baseline MTR values of SELs (for each % higher: OR = 0.66 [0.41; 0.92], p = 0.033) were significant independent predictors of EDSS score worsening at follow-up (C-index = 0.892). A higher baseline EDSS score (for each point higher: OR = 6.37 [1.98; 20.53], p = 0.002) and lower baseline MTR values of SELs (for each % higher: OR = 0.48 [0.25; 0.89], p = 0.02) independently predicted SPMS conversion (C-index = 0.947). DISCUSSION: The proportion of SELs is associated with MS progression after 9 years. More severe SEL microstructural abnormalities independently predict EDSS score worsening and SPMS conversion. The quantification of SEL burden and damage using T(1)-, T(2)-weighted, and MTR sequences may identify patients with RRMS at a higher risk of long-term disability progression and SPMS conversion. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with RRMS starting treatment with natalizumab or fingolimod, the proportion of SELs on brain MRI was associated with EDSS score worsening and SPMS conversion at 9-year follow-up.
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spelling pubmed-88083552022-02-02 Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression Preziosa, Paolo Pagani, Elisabetta Meani, Alessandro Moiola, Lucia Rodegher, Mariaemma Filippi, Massimo Rocca, Maria A. Neurol Neuroimmunol Neuroinflamm Article BACKGROUND AND OBJECTIVES: Chronic active lesions contribute to multiple sclerosis (MS) severity, but their association with long-term disease progression has not been evaluated yet. White matter (WM) lesions showing linear expansion over time on serial T(1)- and T(2)-weighted scans (i.e., slowly expanding lesions [SELs]) have been proposed as a marker of chronic inflammation. In this study, we assessed whether SEL burden and microstructural abnormalities were associated with Expanded Disability Status Scale (EDSS) score worsening and secondary progressive (SP) conversion at 9.1-year follow-up in patients with relapsing-remitting (RR) MS. METHODS: In 52 patients with RRMS, SELs were identified among WM lesions by linearly fitting the Jacobian of the nonlinear deformation field between time points obtained combining 3T brain T(1)- and T(2)-weighted scans acquired at baseline and months 6, 12, and 24. Logistic regression analysis was applied to investigate the associations of SEL number, volume, magnetization transfer ratio (MTR), and T(1)-weighted signal intensity with disability worsening (i.e., EDSS score increase) and SP conversion after a median follow-up of 9.1 years. RESULTS: At follow-up, 20/52 (38%) patients with MS showed EDSS score worsening; 13/52 (25%) showed SP conversion. A higher baseline EDSS score (for each point higher: OR = 3.15 [95% CI = 1.61; 8.38], p = 0.003), a higher proportion of SELs among baseline lesions (for each % increase: OR = 1.22 [1.04; 1.58], p = 0.04), and lower baseline MTR values of SELs (for each % higher: OR = 0.66 [0.41; 0.92], p = 0.033) were significant independent predictors of EDSS score worsening at follow-up (C-index = 0.892). A higher baseline EDSS score (for each point higher: OR = 6.37 [1.98; 20.53], p = 0.002) and lower baseline MTR values of SELs (for each % higher: OR = 0.48 [0.25; 0.89], p = 0.02) independently predicted SPMS conversion (C-index = 0.947). DISCUSSION: The proportion of SELs is associated with MS progression after 9 years. More severe SEL microstructural abnormalities independently predict EDSS score worsening and SPMS conversion. The quantification of SEL burden and damage using T(1)-, T(2)-weighted, and MTR sequences may identify patients with RRMS at a higher risk of long-term disability progression and SPMS conversion. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with RRMS starting treatment with natalizumab or fingolimod, the proportion of SELs on brain MRI was associated with EDSS score worsening and SPMS conversion at 9-year follow-up. Lippincott Williams & Wilkins 2022-02-01 /pmc/articles/PMC8808355/ /pubmed/35105685 http://dx.doi.org/10.1212/NXI.0000000000001139 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Preziosa, Paolo
Pagani, Elisabetta
Meani, Alessandro
Moiola, Lucia
Rodegher, Mariaemma
Filippi, Massimo
Rocca, Maria A.
Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression
title Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression
title_full Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression
title_fullStr Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression
title_full_unstemmed Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression
title_short Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression
title_sort slowly expanding lesions predict 9-year multiple sclerosis disease progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808355/
https://www.ncbi.nlm.nih.gov/pubmed/35105685
http://dx.doi.org/10.1212/NXI.0000000000001139
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