Pogoda-Wesołowska Aleksandra, Stachura Ignacy, Sługocka Nina, Kania-Pudło Marta, Staszewski Jacek, Stępień Adam
Neurology Clinic, Military Institute of Medicine - National Research Institute, Warsaw, Poland.
Faculty of Physics, University of Warsaw, Warsaw, Poland.
Front Immunol. 2025 Aug 26;16:1640607. doi: 10.3389/fimmu.2025.1640607. eCollection 2025.
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-to-year 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.
脑萎缩可能是复发缓解型多发性硬化症（RRMS）病情进展的一个有前景的标志物，但在临床实践中仍未得到充分利用。本探索性研究评估了用扩展残疾状态量表（EDSS）衡量的残疾与独立于复发活动的疾病进展（PIRA）之间的相关性，以及接受克拉屈滨片（CLAD）或阿仑单抗（ALEM）治疗的RRMS患者的体积变化。
对RRMS患者的临床和磁共振成像（MRI）数据在四个时间点进行回顾性分析：治疗前以及随访三年期间每年一次。使用FreeSurfer进行体积测量。将年度体积和EDSS变化汇总在一起以评估短期关联，并进行患者层面的纵向分析。
纳入了33例接受CLAD治疗的患者和19例接受ALEM治疗的患者。分析逐年相关性时，发现EDSS与杏仁核体积变化之间存在显著正相关（p = 0.00009，η² = 0.15657）。苍白球也观察到这种情况（p = 0.02605，η² = 0.05384）。相反，在CLAD组中，丘脑体积变化与EDSS之间存在负相关（p = 0.04551，η² = 0.07203）。当比较三组（疾病进展组n = 10、病情稳定组n = 11、无变化组n = 74）患者每年的体积变化百分比与EDSS进展情况时，杏仁核（p = 0.00640；1.98%，-4%，-0.8%）、丘脑（p = 0.04390；-0.54%，2.98%，0.1%）和苍白球（p = 0.02904；1.98%，-6.96%，-0.23%）存在显著差异。最后，在10例EDSS进展的患者中，3例PIRA患者的杏仁核体积增加，而7例EDSS进展与复发活动相关的患者中未观察到这种情况（p = 0.0188；4.60%对0.004%）。
在RRMS患者三年的随访中，EDSS进展与杏仁核体积增加呈正相关，在较小程度上与苍白球体积增加相关，而残疾恶化与丘脑萎缩相关。值得注意的是，杏仁核增大仅见于PIRA患者，而非复发相关的病情恶化患者，这突出了其作为疾病进展体积生物标志物的潜力。然而，这是一项探索性的、产生假设的观察，需要进一步研究来验证这些发现并阐明潜在机制。
