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Updated: Sep 27, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Time course of lesion-induced atrophy in multiple sclerosis
Keith Carolus1, Tom A Fuchs1,2, Niels Bergsland1,3
1Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Background And Purpose:
White matter (WM) tract disruption impacts volume loss in connected deep gray matter (DGM) over 5 years in people with multiple sclerosis (PwMS). However, the timeline of this phenomenon remains poorly characterized.
Materials And Methods:
Annual serial MRI for 181 PwMS was retrospectively analyzed from a 10-year clinical trial database. Annualized thalamic atrophy, DGM atrophy, and disruption of connected WM tracts were measured. For time series analysis, ~700 epochs were collated using a sliding 5-year window, and regression models predicting 1-year atrophy were applied to characterize the influence of new tract disruption from preceding years, while controlling for whole brain atrophy and other relevant factors.
Results:
Disruptions of WM tracts connected to the thalamus were significantly associated with thalamic atrophy 1 year later (β: 0.048-0.103). This effect was not observed for thalamic tract disruption concurrent with the time of atrophy nor for thalamic tract disruption preceding the atrophy by 2-4 years. Similarly, disruptions of white matter tracts connected to the DGM were significantly associated with DGM atrophy 1 year later (β: 0.078-0.111), but not for tract disruption concurrent with, nor preceding the atrophy by 2-4 years.
Conclusion:
Increased rates of thalamic and DGM atrophy were restricted to 1 year following newly developed disruption in connected WM tracts. In research and clinical settings, additional gray matter atrophy may be expected 1 year following new lesion growth in connected white matter.
Insights
White matter (WM) tract disruption causes deep gray matter (DGM) atrophy in people with multiple sclerosis (PwMS). Atrophy occurs one year after new WM tract damage, not concurrently or years later.
Area of Science:
- Neuroimaging
- Neurology
- Multiple Sclerosis Research
Background:
- White matter (WM) tract disruption is linked to deep gray matter (DGM) volume loss in people with multiple sclerosis (PwMS).
- The precise timing of this relationship is not well understood.
Purpose of the Study:
- To investigate the temporal relationship between white matter (WM) tract disruption and deep gray matter (DGM) atrophy in people with multiple sclerosis (PwMS).
- To determine the time lag between new WM lesions and subsequent DGM volume loss.
Main Methods:
- Retrospective analysis of annual serial MRI scans from 181 PwMS over 10 years.
- Measurement of annualized thalamic and DGM atrophy and connected WM tract disruption.
- Time series analysis using sliding windows and regression models to assess the predictive influence of WM disruption on DGM atrophy.
Main Results:
- WM tract disruptions connected to the thalamus were significantly associated with thalamic atrophy one year later.
- WM tract disruptions connected to the DGM were significantly associated with DGM atrophy one year later.
- No significant association was found for concurrent WM disruption or disruption preceding atrophy by 2-4 years.
Conclusions:
- Thalamic and DGM atrophy rates in PwMS are elevated specifically within one year following new WM tract disruption.
- Clinicians and researchers should anticipate gray matter atrophy approximately one year after new lesion development in connected white matter.
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