Subcortical Gray Matter Atrophy in Multiple Sclerosis: A Comparison Between RRMS and PMS Subtypes
Berat Goksu Celenk1, Fuad Allahverdi1, Onur Koc1, Baran Serdar Sunal2, Aysun Unal1
1Neurology, 2Radiology, Namik Kemal University, Tekirdag, Turkey
Objective:
This study aimed to compare deep gray matter (GM) atrophy patterns and their functional correlates between relapsing–remitting MS (RRMS) and progressive MS (PMS) patients.
Background:
MS is characterized by relapsing and progressive disease courses, with progressive forms showing greater neurodegenerative changes. Subcortical GM atrophy, particularly in the thalamus, hippocampus, and basal ganglia, has been associated with disability and cognitive decline.
Design/Methods:
We retrospectively analyzed 123 MS patients (82 RRMS, 41 PMS) followed between January 2021 and July 2025. All underwent 1.5T MRI; subcortical structures (thalamus, hippocampus, amygdala, globus pallidus, caudate, putamen, nucleus accumbens) were segmented with FSL-FIRST. Disability was measured with Expanded Disability Status Scale (EDSS), cognition with Symbol Digit Modalities Test (SDMT), and overall function with Multiple Sclerosis Functional Composite (MSFC).
Results:
PMS patients showed greater disease burden and atrophy than RRMS, with higher EDSS and lower SDMT/MSFC (all p<0.05). MRI volumetry demonstrated widespread subcortical GM loss in PMS -smaller bilateral thalamus, hippocampus, amygdala, globus pallidus, caudate, putamen, and nucleus accumbens- except right putamen . Sex-stratified analyses found larger absolute volumes in males overall; the PMS–RRMS volume gap was pronounced among females, whereas in males only the left thalamus was smaller in PMS. Across the cohort, longer disease duration correlated with smaller deep GM volumes (p<0.01). Higher SDMT correlated with larger thalamic, putaminal, and caudate volumes (ρ≈0.20–0.30), with associations more widespread in PMS. MSFC correlated positively with thalamic and putaminal volumes at the cohort level, but not within subgroups; amygdala and nucleus accumbens showed no MSFC relationships.
Conclusions:
PMS shows more extensive bilateral subcortical GM atrophy and greater cognitive/functional impairment than RRMS. Thalamic, hippocampal, and basal ganglia volumes correlate strongly with cognition (especially processing speed) supporting their use as imaging biomarkers of progression. Findings highlight neurodegeneration’s central role and suggest deep GM atrophy, particularly thalamic/basal ganglia loss, can inform prognosis and guide cognition-preserving therapies.
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