Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis
Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis
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DOI：
10.1111/nan.12511
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发表时间：
2019-04-01
影响因子：
5
通讯作者：
Poesen, K.
中科院分区：
文献类型：
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作者：
Gille, B.;De Schaepdryver, M.;Poesen, K.
肌萎缩侧索硬化症（Amyotrophiclateralsclerosis，ALS）是最常见的运动神经元变性疾病，发病后诊断延迟约1年。在ALS中，血液神经丝轻链（NfL）水平升高，但尚不完全清楚是什么驱动了这种增加，以及血清NfL在预测值和似然比方面的诊断性能。本研究的目的是进一步探讨血清NfL的预后和诊断性能，以区分ALS患者和ALS模拟，并探讨血清NfL与运动神经元变性之间的关系。方法对149例ALS患者血清、19例类似ALS患者血清和82例疾病对照患者血清进行NfL检测。血清NfL水平与显示上和/或下运动神经元变性的区域（胸部、延髓、上肢和下肢）的数量相关。基于考克斯回归分析研究血清NfL的预后性能。结果建立了区分ALS患者和ALS拟态患者的相关预测值和似然比。血清NfL与由上运动神经元（UMN）变性驱动的运动神经元变性相关，并与ALS患者的生存率独立相关。总之，这些研究结果表明，ALS患者血清NfL水平升高是由UMN变性和疾病进展率驱动的，并且与诊断时的生存率独立相关。
Aims Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about 1 year after symptoms onset. In ALS, blood neurofilament light chain (NfL) levels are elevated, but it is not entirely clear what drives this increase and what the diagnostic performance of serum NfL is in terms of predictive values and likelihood ratios. The aims of this study were to further explore the prognostic and diagnostic performances of serum NfL to discriminate between patients with ALS and ALS mimics, and to investigate the relationship between serum NfL with motor neuron degeneration. Methods The diagnostic performances of serum NfL were based on a cohort of 149 serum samples of patients with ALS, 19 serum samples of patients with a disease mimicking ALS and 82 serum samples of disease control patients. The serum NfL levels were correlated with the number of regions (thoracic, bulbar, upper limb and lower limb) displaying upper and/or lower motor neuron degeneration. The prognostic performances of serum NfL were investigated based on a Cox regression analysis. Results The associated predictive values and likelihood ratio to discriminate patients with ALS and ALS mimics were established. Serum NfL was associated with motor neuron degeneration driven by upper motor neuron (UMN) degeneration and was independently associated with survival in patients with ALS. Conclusions Altogether, these findings suggest that elevated serum NfL levels in ALS are driven by UMN degeneration and the disease progression rate and are independently associated with survival at time of diagnosis.