Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Department of Chronic Disease, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
Neuropathol Appl Neurobiol. 2019 Apr;45(3):291-304. doi: 10.1111/nan.12511. Epub 2018 Jul 18.
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.
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.
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.
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.
肌萎缩侧索硬化症（ALS）是最常见的运动神经元退行性疾病，从症状出现到确诊的平均时间约为 1 年。在 ALS 中，血液神经丝轻链（NfL）水平升高，但尚不清楚是什么导致了这种升高，以及血清 NfL 的诊断性能在预测值和似然比方面如何。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 模拟患者，并研究血清 NfL 与运动神经元退行性变之间的关系。
血清 NfL 的诊断性能基于 149 例 ALS 患者、19 例 ALS 模拟患者和 82 例疾病对照患者的血清样本队列。将血清 NfL 水平与显示上运动神经元（UMN）和/或下运动神经元退行性变的区域（胸部、延髓、上肢和下肢）数量相关联。基于 Cox 回归分析，研究了血清 NfL 的预后性能。
建立了区分 ALS 患者和 ALS 模拟患者的相关预测值和似然比。血清 NfL 与 UMN 退行性变驱动的运动神经元退行性变相关，并且与 ALS 患者的生存独立相关。
综上所述，这些发现表明，ALS 中升高的血清 NfL 水平是由 UMN 退行性变驱动的，疾病进展速度与诊断时的生存独立相关。
