背景:神经丝蛋白在肌萎缩侧索硬化症(ALS)中被改变。这项研究的目的是评估ALS中神经丝的诊断和预后效用。
方法:在电子数据库中进行了研究(PubMed/MEDLINE,Embase,WebofScience,和CochraneCENTRAL)从开始到2023年8月17日,并研究了ALS中的神经丝光(NfL)或磷酸化神经丝重链(pNfH)。研究设计,入学标准,神经丝浓度,测试精度,脑脊液(CSF)中的神经丝与血液之间的关系,并记录临床结果。协议在PROSPERO注册,CRD42022376939。
结果:纳入了60项研究,8801名参与者。在CSF中测量的NfL和pNfH在区分ALS与疾病模拟物方面均显示出高灵敏度和特异性。在CSF中测量的NfL和pNfH与它们在血液(血浆或血清)中的相应水平相关;然而,CSFNfL与血液NfL之间有更强的相关性。在血液中测量的NfL在区分ALS与对照方面表现出高灵敏度和特异性。血液或CSF中测得的更高水平的NfL和pNfH与ALS功能评定量表修订评分评估的更严重的症状相关,并且疾病进展速度更快;然而,只有血液NfL水平与较短的生存期相关。
结论:在CSF或血液中测量的NfL和pNfH均显示出较高的诊断效用,并与ALS功能评分和疾病进展相关,虽然CSFNfL与血液(血浆或血清)密切相关,也与生存有关,支持其在临床诊断和预后中的使用。未来的工作必须以标准化的生物样本收集方法和分析平台的前瞻性方式进行,进一步改进用于定量血液中pNfH的免疫测定,以及ALS光谱和对照的截止值的识别。
Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.
Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.
Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.
Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.