Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
APST Research GmbH, Berlin, Germany.
Eur J Neurol. 2023 Jun;30(6):1600-1610. doi: 10.1111/ene.15773. Epub 2023 Mar 26.
The objective was to assess the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of progression, duration and tracheostomy invasive ventilation (TIV).
A prospective cross-sectional study at 12 ALS centers in Germany was performed. sNfL concentrations were age adjusted using sNfL Z scores expressing the number of standard deviations from the mean of a control reference database and correlated to ALS duration and ALS progression rate (ALS-PR), defined by the decline of the ALS Functional Rating Scale.
In the total ALS cohort (n = 1378) the sNfL Z score was elevated (3.04; 2.46-3.43; 99.88th percentile). There was a strong correlation of sNfL Z score with ALS-PR (p < 0.001). In patients with long (5-10 years, n = 167) or very long ALS duration (>10 years, n = 94) the sNfL Z score was significantly lower compared to the typical ALS duration of <5 years (n = 1059) (p < 0.001). Furthermore, in patients with TIV, decreasing sNfL Z scores were found in correlation with TIV duration and ALS-PR (p = 0.002; p < 0.001).
The finding of moderate sNfL elevation in patients with long ALS duration underlined the favorable prognosis of low sNfL. The strong correlation of sNfL Z score with ALS-PR strengthened its value as progression marker in clinical management and research. The lowering of sNfL in correlation with long TIV duration could reflect a reduction either in disease activity or in the neuroaxonal substrate of biomarker formation during the protracted course of ALS.
本研究旨在评估血清神经丝轻链（sNfL）在广泛疾病病程中的表现，包括进展、持续时间和气管切开有创通气（TIV）。
在德国的 12 个 ALS 中心进行了一项前瞻性横断面研究。使用 sNfL Z 分数来调整 sNfL 浓度，该分数表示与对照参考数据库平均值的标准差数量，并将其与 ALS 持续时间和 ALS 进展率（ALS-PR）相关联，定义为 ALS 功能评定量表的下降。
在总 ALS 队列（n=1378）中，sNfL Z 评分升高（3.04；2.46-3.43；99.88 百分位）。sNfL Z 评分与 ALS-PR 有很强的相关性（p<0.001）。在 ALS 持续时间较长（5-10 年，n=167）或非常长（>10 年，n=94）的患者中，sNfL Z 评分明显低于持续时间<5 年的典型 ALS 患者（n=1059）（p<0.001）。此外，在接受 TIV 的患者中，sNfL Z 评分与 TIV 持续时间和 ALS-PR 呈负相关（p=0.002；p<0.001）。
在 ALS 持续时间较长的患者中发现中度 sNfL 升高，这强调了低 sNfL 的良好预后。sNfL Z 评分与 ALS-PR 的强相关性增强了其作为临床管理和研究中进展标志物的价值。sNfL 随着 TIV 持续时间的延长而降低，可能反映了在 ALS 迁延过程中，疾病活动度降低或生物标志物形成的神经轴突基质减少。
