Schneider Christian, Wassermann Meike K, Grether Nicolai B, Fink Gereon R, Wunderlich Gilbert, Lehmann Helmar C
Department of Neurology, University of Cologne, Cologne, Germany.
Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany.
Eur J Neurol. 2021 Sep;28(9):3022-3029. doi: 10.1111/ene.15005. Epub 2021 Jul 20.
The aim was to assess the organization and short-term changes of motor units in adult patients with spinal muscular atrophy (SMA) treated with nusinersen.
In this single-centre cross-sectional and longitudinal study 15 adult patients with SMA type 3 were assessed and compared to 15 age-matched healthy controls and nine patients with amyotrophic lateral sclerosis. Moreover, 10 patients with SMA were followed up after 4-8 months. All patients were investigated clinically and by the motor unit number estimation method MScanFit of the abductor pollicis brevis muscle.
The number of motor units (p < 0.001) was significantly lower in patients with SMA compared to healthy controls at study entry. Mean unit amplitude, median amplitude and largest unit (p < 0.001) were significantly increased in patients with SMA. Patients with amyotrophic lateral sclerosis showed a significant reduction of compound muscle action potential (p = 0.005) and number of motor units (p = 0.03) compared to patients with SMA, accompanied by a larger median amplitude (p = 0.03). A prospective analysis identified patients with the ability to walk to improve the number of motor units (p = 0.046) accompanied by a decreased median amplitude (p = 0.03). Electrophysiological measures showed a moderate to strong correlation with clinical scores.
Patients with SMA show loss of motor units in distal muscles. MScanFit variables indicate that compound muscle action potential amplitudes are maintained by collateral sprouting. Prospective analyses suggest that milder affected adult patients with SMA preferentially benefit from nusinersen treatment through recovery of smaller motor units. Correlations with clinical scores underline the potential of MScanFit as a surrogate marker.
本研究旨在评估接受诺西那生治疗的成年脊髓性肌萎缩症（SMA）患者运动单位的组织情况及短期变化。
在这项单中心横断面及纵向研究中，对15例3型成年SMA患者进行评估，并与15例年龄匹配的健康对照者以及9例肌萎缩侧索硬化症患者进行比较。此外，对10例SMA患者进行了4 - 8个月的随访。所有患者均接受临床检查，并采用拇短展肌运动单位数量估计方法MScanFit进行检测。
在研究开始时，SMA患者的运动单位数量（p < 0.001）显著低于健康对照者。SMA患者的平均运动单位波幅、中位波幅及最大运动单位波幅（p < 0.001）均显著增加。与SMA患者相比，肌萎缩侧索硬化症患者的复合肌肉动作电位显著降低（p = 0.005），运动单位数量显著减少（p = 0.03），同时中位波幅更大（p = 0.03）。一项前瞻性分析发现，能够行走的患者运动单位数量增加（p = 0.046），同时中位波幅降低（p = 0.03）。电生理测量结果与临床评分显示出中度至强相关性。
SMA患者的远端肌肉存在运动单位丢失。MScanFit变量表明，复合肌肉动作电位波幅通过侧支发芽得以维持。前瞻性分析表明，病情较轻的成年SMA患者通过较小运动单位的恢复，优先从诺西那生治疗中获益。与临床评分的相关性突显了MScanFit作为替代标志物的潜力。
