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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Multiple Sclerosis and Neuroimmunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1640607

Amygdala volume changes as a potential marker of multiple sclerosis progression: links to EDSS scores and PIRA

Provisionally accepted
  • 1Neurology Clinic, Military Institute of Medicine (Poland), Warsaw, Poland
  • 2Uniwersytet Warszawski Wydzial Fizyki, Warsaw, Poland
  • 3Faculty of Medicine, University of Warsaw, Warsaw, Poland
  • 4Department of Medical Radiology, Military Institute of Medicine (Poland), Warsaw, Poland

The final, formatted version of the article will be published soon.

Brain atrophy may be a promising marker of relapsing-remitting multiple sclerosis (RRMS) progression, yet it remains underutilized in clinical practice. This exploratory study evaluated correlations between disability-as measured by the Expanded Disability Status Scale (EDSS) and progression independent of relapse activity (PIRA)-and volumetric changes in RRMS patients treated with cladribine tablets (CLAD) or alemtuzumab (ALEM).Clinical and magnetic resonance imaging (MRI) data from patients with RRMS were retrospectively analyzed at four time points: pretreatment and annually over three years of follow-up. Volumetric measurements were obtained using FreeSurfer. Annual volumetric and EDSS changes were pooled together to assess short-term associations and patient-wise longitudinal analyses were performed.33 patients treated with CLAD and 19 patients treated with ALEM were included. Analyzing year-toyear correlations, a significant positive correlation was found between EDSS and amygdala volume changes (p = 0.00009, η²=0,15657). It was also observed for the pallidum (p=0,02605, η²=0,05384). On the contrary, a negative correlation between thalamic volume changes and EDSS in CLAD group was noted (p=0,04551, η²=0,07203).When comparing annual percentage volume changes across three groups-years with EDSS progression (n = 10), regression (n = 11), and no changes (n = 74)significant differences were reported in amygdala (p=0,00640; 1.98%, -4%, -0.8%), thalamus (p = 0,04390; -0.54%, 2.98%, 0.1%) and pallidum (p = 0,02904; 1.98%, -6.96%, -0.23%). Finally, among the 10 patients with EDSS progression, an increase in amygdala volume was observed in 3 patients with PIRA, whereas it was not seen in the 7 patients whose EDSS progression was associated with relapsing activity (p = 0.0188; 4.60% vs. 0.004%).Over three years of follow-up in RRMS patients, EDSS progression was positively associated with increases in amygdala-and, to a lesser extent, pallidum-volumes, while worsening disability correlated with thalamic atrophy. Notably, amygdala enlargement was exclusive to patients with PIRA versus relapse-associated worsening, highlighting its potential as a volumetric biomarker of disease progression. However it was exploratory, hypothesis-generating observation and further studies are warranted to validate these findings and elucidate the underlying mechanisms.

Keywords: Multiple Sclerosis, Disability progression, EDSS, PIRA, Atrophy, Amygdala

Received: 03 Jun 2025; Accepted: 01 Aug 2025.

Copyright: © 2025 Pogoda-Wesołowska, Stachura, Sługocka, Kania-Pudło, Staszewski and Stepien. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Aleksandra Pogoda-Wesołowska, Neurology Clinic, Military Institute of Medicine (Poland), Warsaw, Poland

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