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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.
Glossary
- EDSS=
- Expanded Disability Status Scale;
- FLAIR=
- fluid-attenuated inversion recovery;
- JE=
- Jacobian expansion value;
- MS=
- multiple sclerosis;
- MS-SMART=
- MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial;
- MSFC=
- Multiple Sclerosis Functional Composite;
- MTR=
- magnetization transfer ratio;
- NBV=
- normalized brain volume;
- NHPT=
- Nine-Hole Peg Test;
- PASAT=
- Paced Auditory Serial Addition Test;
- PBH=
- persistent black hole;
- PBVC=
- percent brain volume change;
- PPMS=
- primary progressive multiple sclerosis;
- pu=
- percent units;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SDMT=
- Symbol Digit Modalities Test;
- SEL=
- slowly expanding lesion;
- SPMS=
- secondary progressive multiple sclerosis;
- T25FW=
- Timed 25-Foot Walk
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
MS SMART Investigators are listed at links.lww.com/WNL/B868.
Editorial, page 699
Infographic: links.lww.com/WNL/B914
- Received March 7, 2021.
- Accepted in final form January 18, 2022.
- © 2022 American Academy of Neurology
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