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Updated: Jul 10, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Regional patterns of grey matter volume decline in relapsing-remitting multiple sclerosis relative to healthy ageing
Max Korbmacher1, Ingrid Anne Lie2, Kristin Wesnes3
1Haukeland University Hospital, Neurology, Jonas Lies vei 71, Bergen, 5021, Norway; Western Norway University of Applied Sciences, Radiography, Inndalsveien 28, Bergen, 5020, Norway; Haraldsplass Diaconal Hospital, Mohn Medical Imaging and Visualisation centre, Ulriksdal 8, Bergen, 5009, Norway.
Background:
Grey matter volume loss (GM-VL) is an accurate marker of multiple sclerosis (MS)-related progression. However, long-term comparisons of GM-VL between MS and healthy controls (HC) are rare, and the brain regions with most significant GM-VL and their clinical importance still need robust and longitudinal validation.
Methods:
This multi-cohort longitudinal observational study used two relapsing remitting MS (RRMS) cohorts (N = 386, T1w-scans=940) sampled for up-to-12 years to localise grey matter volume loss (GM-VL) and disease progression (Expanded Disability Status Scale (EDSS), Paced Auditory Serial Addition Test (PASAT), Fatigue Severity Scale (FSS)). The identified region-specific significant GM-VL was compared with 2163 HCs (T1w-scans=4326).
Results:
The strongest, replicable, significant patterns of brain GM-VL in RRMS were found in the frontal lobes, specifically, in the superior frontal cortex (SFC, βage≤-0.27), pars orbitalis (βage≤-0.25), and thalami (βage≤-0.20). Compared with healthy controls (HCs) >20 years older, MS showed greater GM-VL in the right SFC, caudal-middle frontal cortex, caudate, and left frontal pole (all Z > 2.08, p < 0.019). The overlap of associations between volumetric and clinical outcome changes was limited to EDSS, which was significantly related to left hippocampal volumes βEDSS≤-0.19 in both cohorts.
Conclusions:
Our findings indicate GM-VL in people with RRMS comparable to 20-year older HC, and stronger in the SFC and thalamus, and cohort-specific relationships with disability-progression.
Insights
Grey matter volume loss in multiple sclerosis (MS) is comparable to 20-year older healthy controls, particularly in the frontal lobes and thalamus. This study highlights key brain regions affected by MS progression.
Area of Science:
- Neuroscience
- Radiology
- Clinical Neurology
Background:
- Grey matter volume loss (GM-VL) is a key marker for multiple sclerosis (MS) progression.
- Longitudinal data comparing GM-VL between MS patients and healthy controls (HC) is limited.
- Understanding specific brain regions affected by GM-VL and their clinical relevance requires further validation.
Purpose of the Study:
- To longitudinally investigate grey matter volume loss (GM-VL) in relapsing-remitting multiple sclerosis (RRMS).
- To compare GM-VL patterns in RRMS patients with a large cohort of healthy controls (HC).
- To explore the relationship between region-specific GM-VL and clinical measures of disease progression.
Main Methods:
- A multi-cohort longitudinal observational study involving 386 RRMS patients and 2,163 HC.
- Analysis of T1-weighted MRI scans collected over up to 12 years.
- Assessment of disease progression using Expanded Disability Status Scale (EDSS), Paced Auditory Serial Addition Test (PASAT), and Fatigue Severity Scale (FSS).
Main Results:
- Significant GM-VL in RRMS was most pronounced in the frontal lobes (superior frontal cortex, pars orbitalis) and thalami.
- RRMS patients exhibited greater GM-VL in specific frontal regions and the caudate compared to HC over 20 years older.
- A significant association between GM-VL and disability (EDSS) was observed in the left hippocampus.
Conclusions:
- GM-VL in RRMS patients can be equivalent to that of HC individuals 20 years their senior.
- The superior frontal cortex and thalamus show pronounced GM-VL in RRMS.
- Relationships between volumetric changes and disability progression are cohort-specific.
