Dong Siqi, Liu Xiaoni, Zhou Yanni, Li Jiatong, Qi Zihan, Wang Zihan, Yang Wenbo, Chen Xiangjun
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
National Center for Neurological Disorders, Shanghai, People's Republic of China.
Brain Behav. 2025 Jan;15(1):e70256. doi: 10.1002/brb3.70256.
The diagnostic and prognostic values of serum neurofilament light chain (sNfL), in comparison to cerebrospinal fluid (CSF) neurofilament light chain (cNfL), and other clinical parameters in amyotrophic lateral sclerosis (ALS) at the time of diagnosis remain elusive.
We examine paired serum and CSF samples from 80 ALS patients and 21 control subjects, all obtained at the time of diagnosis. Additional serum samples were collected from 51 other ALS patients. NfL concentrations were quantified using the single molecule array (Simoa) technique.
Our findings demonstrate a robust correlation between NfL levels in matched CSF and serum samples. Notably, both sNfL (p < 0.0001) and cNfL (p < 0.0001) exhibited significantly elevated levels in ALS patients compared to controls. Furthermore, baseline sNfL concentrations, as well as cNfL levels, emerged as predictive indicators of subsequent disease progression rate (sNfL: p < 0.0001, cNfL: p = 0.0005) and overall survival (sNfL: p = 0.0073, cNfL: p = 0.0044). Employing a Cox regression model, we identified baseline sNfL level (HR = 1.01, p = 0.013), and diagnostic delay (HR = 0.94, p = 0.003) as independent prognostic factors for mortality. Furthermore, we constructed a nomogram model that incorporates both sNfL and pertinent clinical variables, which substantially enhances the accuracy of predicting disease outcomes (Concordance Index, 0.808).
Our study underscores the robust correlation between sNfL and cNfL in ALS patients and establishes baseline sNfL as a potent and independent prognostic marker for mortality.
与脑脊液（CSF）神经丝轻链（cNfL）相比，血清神经丝轻链（sNfL）在肌萎缩侧索硬化症（ALS）诊断时的诊断和预后价值，以及与其他临床参数的关系仍不明确。
我们检测了80例ALS患者和21例对照受试者在诊断时采集的配对血清和脑脊液样本。另外还从51例其他ALS患者中采集了血清样本。使用单分子阵列（Simoa）技术对NfL浓度进行定量。
我们的研究结果表明，匹配的脑脊液和血清样本中的NfL水平之间存在密切相关性。值得注意的是，与对照组相比，ALS患者的sNfL（p < 0.0001）和cNfL（p < 0.0001）水平均显著升高。此外，基线sNfL浓度以及cNfL水平是后续疾病进展率（sNfL：p < 0.0001，cNfL：p = 0.0005）和总生存期（sNfL：p = 0.0073，cNfL：p = 0.0044）的预测指标。采用Cox回归模型，我们确定基线sNfL水平（HR = 1.01，p = 0.013）和诊断延迟（HR = 0.94，p = 0.003）是死亡率的独立预后因素。此外，我们构建了一个包含sNfL和相关临床变量的列线图模型，该模型显著提高了预测疾病结局的准确性（一致性指数，0.808）。
我们的研究强调了ALS患者中sNfL和cNfL之间的密切相关性，并将基线sNfL确立为死亡率的有力且独立的预后标志物。
