Gaiani Alessandra, Martinelli Ilaria, Bello Luca, Querin Giorgia, Puthenparampil Marco, Ruggero Susanna, Toffanin Elisabetta, Cagnin Annachiara, Briani Chiara, Pegoraro Elena, Sorarù Gianni
Department of Neurosciences, University of Padua, Padova, Italy.
Department of Neurosciences, General Hospital of Padua, Padova, Italy.
JAMA Neurol. 2017 May 1;74(5):525-532. doi: 10.1001/jamaneurol.2016.5398.
A clearer definition of the role of neurofilament light chain (NFL) as a biomarker in amyotrophic lateral sclerosis (ALS) is needed.
To assess the ability of NFL to serve as a diagnostic biomarker in ALS and the prognostic value of cerebrospinal fluid NFL in patients with ALS.
DESIGN, SETTING, AND PARTICIPANTS: In this single-center, retrospective, longitudinal study, disease progression was assessed by the ALS Functional Rating Score-Revised and the ALS Milano-Torino Staging system at baseline and 6, 12, 24, and 36 months. Cerebrospinal fluid samples were obtained from 176 patients admitted to the Department of Neurosciences of the University of Padua, Padova, Italy, from January 1, 2010, through February 29, 2016. Patients with ALS underwent ambulatory follow-up at the same department.
Levels of NFL.
The study included 94 patients with ALS (64 men [36.4%] and 30 women [17.0%]; median age, 62.5 years), 20 patients with frontotemporal dementia (FTD) (8 men [4.5%] and 12 women [6.8%]; median age, 65 years), 18 patients with motor neuropathies (14 men [8.0%] and 4 women [2.3%]; median age, 63 years), and 44 controls (24 men [13.6%] and 20 women [11.4%]; median age, 54 years). Log-transformed NFL (log[NFL]) concentrations were higher in the ALS and FTD groups compared with the motor neuropathies and control groups (hazard ratio [HR], 2.45; 95% CI, 1.66-3.61; P < .001). Patients with typical ALS (HR, 1.0 [reference]), progressive bulbar palsy (HR, 1.48; 95% CI, 0.58-3.75; P = .41), and upper motor neuron dominant ALS (HR, 0.12; 95% CI, 0.02-0.61; P = .01) had higher levels of NFL than did those with flail arm or leg syndrome (HR, 0.28; 95% CI, 0.08-0.10; P = .049) and progressive muscular atrophy (HR, 0.17; 95% CI, 0.22-1.36; P = .10). There was an inverse correlation between log[NFL] concentration and overall survival (HR, 2.45; 95% CI, 1.66-3.61; P < .001). There was no evidence of different log[NFL] concentrations and survival in genetic ALS.
This study confirms the role of NFL as a biomarker in ALS. Elevation in NFL levels in patients with upper motor neuron involvement and FTD might reflect the corticospinal tract degeneration. Low NFL levels in patients with lower motor neuron signs might be a prognostic indicator of milder phenotypes of disease.
需要更明确地界定神经丝轻链（NFL）作为肌萎缩侧索硬化症（ALS）生物标志物的作用。
评估NFL作为ALS诊断生物标志物的能力以及脑脊液NFL对ALS患者的预后价值。
设计、背景和参与者：在这项单中心、回顾性、纵向研究中，通过ALS功能评定量表修订版和ALS米兰-都灵分期系统在基线以及6、12、24和36个月时评估疾病进展。脑脊液样本取自2010年1月1日至2016年2月29日期间入住意大利帕多瓦大学神经科学系的176例患者。ALS患者在同一科室接受门诊随访。
NFL水平。
该研究纳入了94例ALS患者（64例男性[36.4%]和30例女性[17.0%]；中位年龄62.5岁）、20例额颞叶痴呆（FTD）患者（8例男性[4.5%]和12例女性[6.8%]；中位年龄65岁）、18例运动神经病患者（14例男性[8.0%]和4例女性[2.3%]；中位年龄63岁）以及44例对照者（24例男性[13.6%]和20例女性[11.4%]；中位年龄54岁）。与运动神经病组和对照组相比，ALS组和FTD组的对数转换NFL（log[NFL]）浓度更高（风险比[HR]，2.45；95%置信区间[CI]，1.66 - 3.61；P < .001）。典型ALS患者（HR，1.0[参照值]）、进行性延髓麻痹患者（HR，1.48；95%CI，0.58 - 3.75；P = .41）以及上运动神经元为主型ALS患者（HR，0.12；95%CI，0.02 - 0.61；P = .01）的NFL水平高于连枷臂或连枷腿综合征患者（HR，0.28；95%CI，0.08 - 0.10；P = .049）和进行性肌肉萎缩患者（HR，0.17；95%CI，0.22 - 1.36；P = .10）。log[NFL]浓度与总生存期呈负相关（HR，2.45；95%CI，1.66 - 3.61；P < .001）。在遗传性ALS中，未发现log[NFL]浓度与生存期存在差异的证据。
本研究证实了NFL作为ALS生物标志物的作用。上运动神经元受累和FTD患者中NFL水平升高可能反映皮质脊髓束变性。下运动神经元体征患者中NFL水平较低可能是疾病较轻表型的预后指标。
