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Updated: Dec 25, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Conversion of diffusely abnormal white matter to focal lesions is linked to progression in secondary progressive
Mahsa Dadar1, Sridar Narayanan2, Douglas L Arnold2
1McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada/Department of Biomedical Engineering, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Background:
Diffusely abnormal white matter (DAWM) regions are observed in magnetic resonance images of secondary progressive multiple sclerosis (SPMS) patients. However, their role in clinical progression is still not established.
Objectives:
To characterize the longitudinal volumetric and intensity evolution of DAWM and focal white matter lesions (FWML) and assess their associations with clinical outcomes and progression in SPMS.
Methods:
Data include 589 SPMS participants followed up for 3 years (3951 time points). FWML and DAWM were automatically segmented. Screening DAWM volumes that transformed into FWML at the last visit (DAWM-to-FWML) and normalized T1-weighted intensities (indicating severity of damage) in those voxels were calculated.
Results:
FWML volume increased and DAWM volume decreased with an increase in disease duration (p < 0.001). The Expanded Disability Status Scale (EDSS) was positively associated with FWML volumes (p = 0.002), but not with DAWM. DAWM-to-FWML volume was higher in patients who progressed (2.75 cm3 vs. 1.70 cm3; p < 0.0001). Normalized T1-weighted intensity of DAWM-to-FWML was negatively associated with progression (p < 0.00001).
Conclusion:
DAWM transformed into FWML over time, and this transformation was associated with clinical progression. DAWM-to-FWML voxels had greater normalized T1-weighted intensity decrease over time, in keeping with relatively greater tissue damage. Evaluation of DAWM in progressive multiple sclerosis provides a useful measure for therapies aiming to protect this at-risk tissue with the potential to slow progression.
Insights
Diffusely abnormal white matter (DAWM) transforms into focal white matter lesions (FWML) in secondary progressive multiple sclerosis (SPMS), indicating disease progression. Monitoring DAWM may help develop therapies to slow SPMS advancement.
Area of Science:
- Neuroimaging
- Neurology
- Radiology
Background:
- Diffusely abnormal white matter (DAWM) is visible in MRI scans of secondary progressive multiple sclerosis (SPMS) patients.
- The clinical significance of DAWM in SPMS progression remains unclear.
Purpose of the Study:
- To analyze the longitudinal changes in volume and intensity of DAWM and focal white matter lesions (FWML) in SPMS.
- To determine the association between these white matter changes and clinical outcomes in SPMS.
Main Methods:
- Utilized MRI data from 589 SPMS participants over 3 years (3951 time points).
- Employed automated segmentation for FWML and DAWM.
- Calculated DAWM volumes that converted to FWML (DAWM-to-FWML) and their normalized T1-weighted intensities.
Main Results:
- FWML volume increased, while DAWM volume decreased with disease duration (p < 0.001).
- DAWM-to-FWML volume was significantly higher in progressing patients (2.75 cm³ vs. 1.70 cm³; p < 0.0001).
- DAWM-to-FWML showed a negative association with progression (p < 0.00001), indicating greater tissue damage.
Conclusions:
- DAWM evolves into FWML over time, correlating with clinical progression in SPMS.
- DAWM-to-FWML voxels exhibit increased tissue damage.
- Assessing DAWM offers a potential biomarker for therapies targeting progression in SPMS.
