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Updated: Aug 11, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
The sequence of regional structural disconnectivity due to multiple sclerosis lesions
Ceren Tozlu1, Emily Olafson1, Keith Jamison1
1Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
Objective:
Prediction of disease progression is challenging in multiple sclerosis (MS) as the sequence of lesion development and retention of inflammation within a subset of chronic lesions is heterogeneous among patients. We investigated the sequence of lesion-related regional structural disconnectivity across the spectrum of disability and cognitive impairment in MS.
Methods:
In a full cohort of 482 patients, the Expanded Disability Status Scale was used to classify patients into (i) no or mild vs (ii) moderate or severe disability groups. In 363 out of 482 patients, Quantitative Susceptibility Mapping was used to identify paramagnetic rim lesions (PRL), which are maintained by a rim of iron-laden innate immune cells. In 171 out of 482 patients, Brief International Cognitive Assessment was used to identify subjects with cognitive impairment. Network Modification Tool was used to estimate the regional structural disconnectivity due to MS lesions. Discriminative event-based modeling was applied to investigate the sequence of regional structural disconnectivity due to all representative lesions across the spectrum of disability and cognitive impairment.
Results:
Structural disconnection in the ventral attention and subcortical networks was an early biomarker of moderate or severe disability. The earliest biomarkers of disability progression were structural disconnections due to PRL in the motor-related regions. Subcortical structural disconnection was an early biomarker of cognitive impairment.
Interpretation:
MS lesion-related structural disconnections in the subcortex is an early biomarker for both disability and cognitive impairment in MS. PRL-related structural disconnection in the motor cortex may identify the patients at risk for moderate or severe disability in MS.
Insights
Structural disconnectivity in multiple sclerosis (MS) predicts disability and cognitive decline. Early subcortical and motor cortex disconnections, particularly from paramagnetic rim lesions (PRLs), signal disease progression.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Multiple sclerosis (MS) disease progression is difficult to predict due to heterogeneous lesion development and inflammation.
- Understanding the sequence of structural disconnectivity related to MS lesions is crucial for predicting disability and cognitive impairment.
Approach:
- Investigated lesion-related structural disconnectivity in 482 MS patients across disability and cognitive impairment spectrums.
- Utilized Quantitative Susceptibility Mapping to identify paramagnetic rim lesions (PRLs) and the Network Modification Tool to assess regional structural disconnectivity.
- Applied discriminative event-based modeling to determine the sequence of structural disconnectivity associated with MS lesions.
Key Points:
- Structural disconnections in ventral attention and subcortical networks were early indicators of moderate to severe disability.
- Paramagnetic rim lesions (PRLs) in motor regions represented the earliest biomarkers for disability progression.
- Subcortical structural disconnection emerged as an early biomarker for cognitive impairment.
Conclusions:
- Subcortical MS lesion-related structural disconnections serve as early biomarkers for both disability and cognitive impairment.
- PRL-related structural disconnection in the motor cortex may identify MS patients at risk for significant disability.
