Zhang Linjing, Ji Tuo, Wu Chujun, Zhang Shuo, Tang Lu, Zhang Nan, Liu Xiangyi, Fan Dongsheng
Department of Neurology, Peking University Third Hospital, Beijing, China.
Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China.
Front Neurol. 2022 Feb 23;13:833507. doi: 10.3389/fneur.2022.833507. eCollection 2022.
Objectives The aims of this study were to investigate whether serum neurofilament light chain (NfL) levels were correlated with the severity of the axonal degeneration of lower motor neurons (LMNs) in the early symptomatic phase of amyotrophic lateral sclerosis (ALS). Methods In this prospective study, the serum samples used for NfL measurement were obtained from 103 sporadic ALS outpatients within 2 years of disease duration. The severity of axonal degeneration was assessed by assessing the decrease in the compound muscle action potentials (CMAPs) within a 1-month interval from serum sampling. Results The NfL levels showed a significant positive correlation with the relative score as a proxy for the axonal damage of LMNs in patients with ALS (coefficient: 0.264, = 0.009). Furthermore, this correlation became stronger (coefficient: 0.582, = 0.037) when estimated only among patients with disease subtypes that involve only LMNs, that is, patients with flail arm or leg syndrome (FAS or FLS). The levels of NfL increased with the severity of axonal damage of LMNs (F = 6.694, = 0.0001). Conclusions Serum NfL levels mirrored the severity of the axonal degeneration of LMNs, particularly in patients with signs of predominant LMN involvement. These results may have a profound effect on the selection of patients and the monitoring of treatment efficacy in future disease-modifying clinical trials.
目的 本研究旨在调查在肌萎缩侧索硬化症（ALS）早期症状阶段，血清神经丝轻链（NfL）水平是否与下运动神经元（LMNs）轴突退变的严重程度相关。方法 在这项前瞻性研究中，用于测量NfL的血清样本取自103例疾病病程在2年以内的散发性ALS门诊患者。通过评估血清采样后1个月内复合肌肉动作电位（CMAPs）的下降情况来评估轴突退变的严重程度。结果 NfL水平与作为ALS患者LMNs轴突损伤替代指标的相对评分呈显著正相关（系数：0.264，P = 0.009）。此外，仅在仅累及LMNs的疾病亚型患者中进行评估时，即连枷臂或连枷腿综合征（FAS或FLS）患者中，这种相关性更强（系数：0.582，P = 0.037）。NfL水平随着LMNs轴突损伤严重程度的增加而升高（F = 6.694，P = 0.0001）。结论 血清NfL水平反映了LMNs轴突退变的严重程度，特别是在主要表现为LMNs受累迹象的患者中。这些结果可能对未来疾病修饰临床试验中的患者选择和治疗疗效监测产生深远影响。
