Kesenheimer Eva Maria, Wendebourg Maria Janina, Weidensteiner Claudia, Sander Laura, Weigel Matthias, Haas Tanja, Fischer Dirk, Neuwirth Christoph, Braun Nathalie, Weber Markus, Granziera Cristina, Sinnreich Michael, Bieri Oliver, Schlaeger Regina
Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland.
Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
J Neurol. 2025 Jan 7;272(1):102. doi: 10.1007/s00415-024-12740-3.
With the approval of disease-modifying treatments for 5q-spinal muscular atrophy (SMA), there is an increasing need for biomarkers for disease course and therapeutic response monitoring. Radially sampled Averaged Magnetization Inversion Recovery Acquisitions (rAMIRA) MR-imaging enables spinal cord (SC) gray matter (GM) delineation and quantification in vivo. This study aims to assess SC GM atrophy in patients with 5q-SMA and its associations with clinical disability.
Twenty-one patients with 5q-SMA and twenty-one age- and sex-matched healthy controls (HCs) prospectively underwent 3 T axial 2D-rAMIRA MR-imaging at the intervertebral disc levels C2/C3-C5/C6 and T (lumbar enlargement level). Associations between SC GM areas with muscle strength tested by dynamometry, Motor Function Measure (MFM), revised upper limb module (RULM), Revised Hammersmith Scale (RHS), and SMA-Functional Rating Scale (SMA-FRS) were assessed by Spearman Rank correlations and linear regression analysis.
Compared to HCs, patients had significantly reduced SC GM areas at levels C3/C4 (relative reduction (RR) = 13.6%, p < 0.0001); C4/C5 (RR = 16.7%, p < 0.0001), C5/C6 (RR = 17.1%, p < 0.0001), and T (RR = 17.4%, p < 0.0001). Significant correlations were found between cervical SC GM areas and muscle strength, RULM, MFM, RHS, and SMA-FRS. In linear regression analysis, GM area C3/C4 explained 33% of RHS variance.
SC GM atrophy is detectable in patients with 5q-SMA and is consistently associated with clinical measures of upper limb function, physiotherapeutic assessments, and SMA-FRS indicating the clinical relevance of the observed atrophy. Further longitudinal investigations are necessary next steps to evaluate this novel and easily applicable imaging marker as a potential disease course and therapeutic response marker.
随着5q型脊髓性肌萎缩症（SMA）疾病修饰治疗方法的获批，对用于疾病进程和治疗反应监测的生物标志物的需求日益增加。径向采样平均磁化反转恢复采集（rAMIRA）磁共振成像能够在体内描绘和量化脊髓（SC）灰质（GM）。本研究旨在评估5q-SMA患者的脊髓灰质萎缩情况及其与临床残疾的关联。
21例5q-SMA患者和21例年龄及性别匹配的健康对照者（HCs）前瞻性地接受了3T轴向二维rAMIRA磁共振成像检查，检查部位为C2/C3至C5/C6椎间盘水平以及T（腰膨大水平）。通过Spearman等级相关性分析和线性回归分析评估脊髓灰质区域与通过测力计测试的肌肉力量、运动功能测量（MFM）、修订上肢模块（RULM）、修订哈默史密斯量表（RHS）和SMA功能评定量表（SMA-FRS）之间的关联。
与健康对照者相比，患者在C3/C4水平（相对减少（RR）=13.6%，p<0.0001）、C4/C5水平（RR=16.7%，p<0.0001）、C5/C6水平（RR=17.1%，p<0.0001）和T水平（RR=17.4%，p<0.0001）的脊髓灰质区域明显减少。发现颈段脊髓灰质区域与肌肉力量、RULM、MFM、RHS和SMA-FRS之间存在显著相关性。在线性回归分析中，C3/C4灰质区域解释了RHS方差的33%。
5q-SMA患者可检测到脊髓灰质萎缩，且与上肢功能的临床测量、物理治疗评估以及SMA-FRS持续相关，这表明所观察到的萎缩具有临床相关性。下一步有必要进行进一步的纵向研究，以评估这种新型且易于应用的成像标志物作为潜在的疾病进程和治疗反应标志物。
