Ocampo-Pineda Mario, Cagol Alessandro, Benkert Pascal, Barakovic Muhamed, Lu Po-Jui, Müller Jannis, Schaedelin Sabine Anna, Melie-Garcia Lester, Weigel Matthias, Sormani Maria Pia, Kappos Ludwig, Kuhle Jens, Granziera Cristina
Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Switzerland.
Multiple Sclerosis Centre, Department of Neurology, University Hospital Basel, Switzerland.
Neurol Neuroimmunol Neuroinflamm. 2025 May;12(3):e200388. doi: 10.1212/NXI.0000000000200388. Epub 2025 Apr 16.
Progression independent of relapse activity (PIRA) is associated with worse outcomes in people with multiple sclerosis (pwMS). Although previous research has linked PIRA to accelerated brain and spinal cord atrophy and compartmentalized chronic inflammation, the role of white matter (WM) tract degeneration remains unclear. This study aimed to explore the relationship between PIRA and the integrity of major WM tracts using diffusion tensor imaging (DTI).
A cohort of 258 pwMS was stratified based on the presence or absence of PIRA over a 4-year follow-up period. At the end of follow-up, DTI metrics were compared between groups using propensity score-weighted linear regression models to account for potential confounders.
PwMS with ≥1 PIRA event (n = 39) exhibited significant reductions in fractional anisotropy and increases in radial, axial, and mean diffusivity within the corpus callosum and motor tracts (false discovery rate-adjusted ≤ 0.04) compared with those without PIRA, indicating more pronounced WM damage.
Our findings highlight an association between PIRA and microstructural damage in key WM tracts. The observed DTI changes likely reflect processes such as Wallerian degeneration and contribute to the growing evidence linking PIRA to neurodegeneration.
在多发性硬化症患者（pwMS）中，与复发活动无关的病情进展（PIRA）与更差的预后相关。尽管先前的研究已将PIRA与脑和脊髓加速萎缩以及局灶性慢性炎症联系起来，但白质（WM）束变性的作用仍不清楚。本研究旨在使用扩散张量成像（DTI）探索PIRA与主要WM束完整性之间的关系。
在4年的随访期内，根据是否存在PIRA对258例pwMS队列进行分层。随访结束时，使用倾向评分加权线性回归模型比较两组之间的DTI指标，以解释潜在的混杂因素。
与无PIRA的患者相比，发生≥1次PIRA事件的pwMS患者（n = 39）在胼胝体和运动束内的各向异性分数显著降低，径向、轴向和平均扩散率增加（错误发现率校正≤0.04），表明WM损伤更明显。
我们的研究结果突出了PIRA与关键WM束微观结构损伤之间的关联。观察到的DTI变化可能反映了诸如沃勒变性等过程，并为将PIRA与神经退行性变联系起来的越来越多的证据做出了贡献。
