Related Experiment Video
Updated: Dec 29, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Covarying patterns of white matter lesions and cortical atrophy predict progression in early MS
Muthuraman Muthuraman1, Vinzenz Fleischer1, Julia Kroth1
1From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
Objective:
We applied longitudinal 3T MRI and advanced computational models in 2 independent cohorts of patients with early MS to investigate how white matter (WM) lesion distribution and cortical atrophy topographically interrelate and affect functional disability.
Methods:
Clinical disability was measured using the Expanded Disability Status Scale Score at baseline and at 1-year follow-up in a cohort of 119 patients with early relapsing-remitting MS and in a replication cohort of 81 patients. Covarying patterns of cortical atrophy and baseline lesion distribution were extracted by parallel independent component analysis. Predictive power of covarying patterns for disability progression was tested by receiver operating characteristic analysis at the group level and support vector machine for individual patient outcome.
Results:
In the study cohort, we identified 3 distinct distribution types of WM lesions (cerebellar, bihemispheric, and left lateralized) that were associated with characteristic cortical atrophy distributions. The cerebellar and left-lateralized patterns were reproducibly detected in the second cohort. Each of the patterns predicted to different extents, short-term disability progression, whereas the cerebellar pattern was associated with the highest risk of clinical worsening, predicting individual disability progression with an accuracy of 88% (study cohort) and 89% (replication cohort), respectively.
Conclusion:
These findings highlight the role of distinct spatial distribution of cortical atrophy and WM lesions predicting disability. The cerebellar involvement is shown as a key determinant of rapid clinical deterioration.
Insights
Distinct white matter lesion and cortical atrophy patterns in early multiple sclerosis (MS) predict disability progression. Cerebellar involvement is a key factor for rapid clinical worsening in MS patients.
Area of Science:
- Neuroimaging
- Computational modeling
- Neurology
Background:
- Early multiple sclerosis (MS) involves white matter (WM) lesions and cortical atrophy.
- The topographical relationship between these pathologies and functional disability is not fully understood.
Purpose of the Study:
- To investigate the interrelation between WM lesion distribution and cortical atrophy in early MS.
- To determine how these patterns predict functional disability progression.
Main Methods:
- Longitudinal 3T MRI and computational models were used in two independent patient cohorts.
- Parallel independent component analysis identified covarying patterns of atrophy and lesions.
- Receiver operating characteristic analysis and support vector machines assessed predictive power for disability.
Main Results:
- Three distinct WM lesion distribution patterns (cerebellar, bihemispheric, left lateralized) were associated with specific cortical atrophy patterns.
- These patterns predicted short-term disability progression.
- The cerebellar pattern showed the highest risk, predicting individual disability progression with 88-89% accuracy.
Conclusions:
- Distinct spatial distributions of cortical atrophy and WM lesions are crucial predictors of disability in MS.
- Cerebellar involvement emerges as a significant determinant of rapid clinical deterioration in MS.
