当前位置: X-MOL 学术Brain › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Neurofilament light levels predict clinical progression and death in multiple system atrophy
Brain ( IF 10.6 ) Pub Date : 2022-07-29 , DOI: 10.1093/brain/awac253
Viorica Chelban 1, 2 , Elham Nikram 3 , Alexandra Perez-Soriano 4, 5, 6 , Carlo Wilke 7, 8 , Alexandra Foubert-Samier 9, 10, 11, 12 , Nirosen Vijiaratnam 13 , Tong Guo 13 , Edwin Jabbari 13 , Simisola Olufodun 1 , Mariel Gonzalez 1 , Konstantin Senkevich 14, 15, 16, 17 , Brice Laurens 9, 10 , Patrice Péran 18 , Olivier Rascol 19, 20, 21 , Anne Pavy Le Traon 19, 22 , Emily G Todd 23 , Alyssa A Costantini 13 , Sondos Alikhwan 1 , Ambreen Tariq 1 , Bai Lin Ng 24 , Esteban Muñoz 4, 5, 6 , Celia Painous 4, 5, 6 , Yaroslau Compta 4, 5, 6 , Carme Junque 5, 6, 25 , Barbara Segura 5, 6, 25 , Kristina Zhelcheska 1 , Henny Wellington 26 , Ludger Schöls 7, 8 , Zane Jaunmuktane 27 , Christopher Kobylecki 28, 29 , Alistair Church 30 , Michele T M Hu 31 , James B Rowe 32, 33, 34 , P Nigel Leigh 35 , Luke Massey 36 , David J Burn 37 , Nicola Pavese 38 , Tom Foltynie 13 , Sofya Pchelina 16, 17 , Nicholas Wood 13 , Amanda J Heslegrave 26 , Henrik Zetterberg 26, 38, 39, 40, 41 , Martina Bocchetta 23 , Jonathan D Rohrer 23 , Maria J Marti 4, 5, 6 , Matthis Synofzik 7, 8 , Huw R Morris 13 , Wassilios G Meissner 9, 10, 42, 43 , Henry Houlden 1
Affiliation  

Disease-modifying treatments are currently being trialed in multiple system atrophy (MSA). Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data in multiple system atrophy have been limited. Therefore, neurofilament light chain is not yet routinely used as an outcome measure in MSA. We aimed to comprehensively investigate the role and dynamics of neurofilament light chain in multiple system atrophy combined with cross-sectional and longitudinal clinical and imaging scales and for subject trial selection. In this cohort study we recruited cross-sectional and longitudinal cases in multicentre European set-up. Plasma and cerebrospinal fluid neurofilament light chain concentrations were measured at baseline from 212 multiple system atrophy cases, annually for a mean period of 2 years in 44 multiple system atrophy patients in conjunction with clinical, neuropsychological and MRI brain assessments. Baseline neurofilament light chain characteristics were compared between groups. Cox regression was used to assess survival; ROC analysis to assess the ability of neurofilament light chain to distinguish between multiple system atrophy patients and healthy controls. Multivariate linear mixed effects models were used to analyse longitudinal neurofilament light chain changes and correlated with clinical and imaging parameters. Polynomial models were used to determine the differential trajectories of neurofilament light chain in multiple system atrophy. We estimated sample sizes for trials aiming to decrease NfL levels. We show that in multiple system atrophy, baseline plasma neurofilament light chain levels were better predictors of clinical progression, survival, and degree of brain atrophy than the NfL rate of change. Comparative analysis of multiple system atrophy progression over the course of disease, using plasma neurofilament light chain and clinical rating scales, indicated that neurofilament light chain levels rise as the motor symptoms progress, followed by deceleration in advanced stages. Sample size prediction suggested that significantly lower trial participant numbers would be needed to demonstrate treatment effects when incorporating plasma neurofilament light chain values into multiple system atrophy clinical trials in comparison to clinical measures alone. In conclusion, neurofilament light chain correlates with clinical disease severity, progression, and prognosis in multiple system atrophy. Combined with clinical and imaging analysis, neurofilament light chain can inform patient stratification and serve as a reliable biomarker of treatment response in future multiple system atrophy trials of putative disease-modifying agents.

中文翻译:

神经丝光水平预测多系统萎缩的临床进展和死亡

目前正在多系统萎缩症 (MSA) 中试用疾病改善疗法。仅基于临床措施的方法受到表型异质性和致病复杂性的挑战。神经丝轻链蛋白已被探索为多种神经退行性疾病的可靠生物标志物,但多系统萎缩的数据有限。因此,神经丝轻链尚未常规用作 MSA 的结果测量。我们的目的是综合研究神经丝轻链在多系统萎缩中的作用和动力学,结合横断面和纵向临床和影像学量表,并用于受试者试验选择。在这项队列研究中,我们在多中心欧洲机构中招募了横断面和纵向病例。结合临床、神经心理学和 MRI 大脑评估,对 212 名多系统萎缩患者的血浆和脑脊液神经丝轻链浓度进行了基线测量,平均每年对 44 名多系统萎缩患者进行为期 2 年的测量。比较各组的基线神经丝轻链特征。Cox回归用于评估生存;ROC 分析评估神经丝轻链区分多系统萎缩患者和健康对照的能力。多元线性混合效应模型用于分析纵向神经丝轻链变化并与临床和成像参数相关联。多项式模型用于确定多系统萎缩中神经丝轻链的差异轨迹。我们估计了旨在降低 NfL 水平的试验的样本量。我们表明,在多系统萎缩中,基线血浆神经丝轻链水平比 NfL 变化率更能预测临床进展、生存和脑萎缩程度。使用血浆神经丝轻链和临床评定量表对病程中多系统萎缩进展的比较分析表明,神经丝轻链水平随着运动症状的进展而升高,随后在晚期阶段减速。样本量预测表明,与单独的临床措施相比,将血浆神经丝轻链值纳入多系统萎缩临床试验时,需要显着减少试验参与者数量来证明治疗效果。综上所述,神经丝轻链与多系统萎缩的临床疾病严重程度、进展和预后相关。结合临床和影像学分析,神经丝轻链可以为患者分层提供信息,并在未来推定的疾病改善剂的多系统萎缩试验中作为治疗反应的可靠生物标志物。
更新日期:2022-07-29
down
wechat
bug