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重复神经丝轻链测量未能捕捉到利鲁唑在肌萎缩侧索硬化症患者中的治疗效果。

Repeated neurofilament light chain measurements did not capture Riluzole therapeutic effect in amyotrophic lateral sclerosis patients.

机构信息

Explorations neurologiques et centre SLA, Univ Montpellier, CHU Gui de Chauliac, INM, INSERM, Montpellier, France.

LBPC-PPC, Univ Montpellier, CHU Montpellier, INSERM, INM Montpellier, Montpellier, France.

出版信息

CNS Neurosci Ther. 2022 Oct;28(10):1532-1538. doi: 10.1111/cns.13894. Epub 2022 Jun 25.

Abstract

BACKGROUND

Little is known about the influence of Riluzole on serum neurofilament light chain (sNfL) levels, a biomarker of prognosis in amyotrophic lateral sclerosis (ALS), and variations with time of sNfL concentrations are controversial.

METHODS

Sera from ALS patients (n = 141) and controls (n = 33) were collected at inclusion (sNfL1) and second visit (sNfL2, mean delay 10.4 ± 8.7 months). sNfL levels, determined by single-molecule array, were compared between ALS and controls at both time points. sNfL concentration changes were compared between patients with Riluzole (w/Ril) at inclusion in the study and those who were treated by Riluzole following inclusion (w/o Ril). The factors influencing sNfL concentrations and changes were studied using linear regression and multivariate analysis.

RESULTS

sNfL levels were higher in ALS patients than in controls at the two time points (p < 0.00001). In ALS patients, sNfL concentrations were higher in females for both sNfL1 (p = 0.014) and sNfL2 (p < 0.001). In the whole ALS group, sNfL levels were higher at sNfL2 than at sNfL1 (p < 0.001). sNfL1 and sNfL2 concentrations were similar between the two ALS subgroups (w/ and w/o Ril). ALS functional rating scale-revised rate of decline and gender were the two main factors significantly influencing both sNfL1 and sNfL2 levels (p < 0.01). However, only gender was shown to significantly influence sNfL changes with time (p = 0.003).

CONCLUSIONS

In this study, sNfL levels increased with time in ALS patients and there was no difference between subjects already treated by Riluzole and those treated after sNfL1. Further studies with larger population samples and different sampling intervals are warranted to better determine the real potential of sNfL measurement as a tool to monitor treatment response in ALS.

摘要

背景

利鲁唑对肌萎缩侧索硬化症(ALS)预后生物标志物血清神经丝轻链(sNfL)水平的影响知之甚少,sNfL 浓度随时间的变化存在争议。

方法

纳入时(sNfL1)和第二次就诊时(sNfL2,平均延迟 10.4±8.7 个月)收集了 141 例 ALS 患者和 33 名对照者的血清。通过单分子阵列法比较了两个时间点 ALS 患者和对照组之间 sNfL 水平的差异。比较了研究纳入时接受利鲁唑治疗(w/Ril)和纳入后接受利鲁唑治疗(w/o Ril)的患者 sNfL 浓度的变化。使用线性回归和多变量分析研究影响 sNfL 浓度和变化的因素。

结果

sNfL1 和 sNfL2 两个时间点,ALS 患者的 sNfL 水平均高于对照组(p<0.00001)。在 ALS 患者中,sNfL1 和 sNfL2 浓度女性均高于男性(p=0.014 和 p<0.001)。在整个 ALS 组中,sNfL2 时的 sNfL 水平高于 sNfL1(p<0.001)。两个 ALS 亚组(w/和 w/o Ril)的 sNfL1 和 sNfL2 浓度相似。ALS 功能评定量表修订后下降率和性别是显著影响 sNfL1 和 sNfL2 水平的两个主要因素(p<0.01)。然而,只有性别显著影响 sNfL 随时间的变化(p=0.003)。

结论

本研究中,ALS 患者的 sNfL 水平随时间增加,而已经接受利鲁唑治疗的患者和 sNfL1 后接受治疗的患者之间的 sNfL 水平没有差异。需要更大的人群样本和不同的采样间隔进一步研究,以更好地确定 sNfL 测量作为监测 ALS 治疗反应的工具的实际潜力。

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