Lu Ching-Hua, Macdonald-Wallis Corrie, Gray Elizabeth, Pearce Neil, Petzold Axel, Norgren Niklas, Giovannoni Gavin, Fratta Pietro, Sidle Katie, Fish Mark, Orrell Richard, Howard Robin, Talbot Kevin, Greensmith Linda, Kuhle Jens, Turner Martin R, Malaspina Andrea
From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC Integrative Epidemiology Unit (C.M.-W.), University of Bristol; Nuffield Department of Clinical Neurosciences (E.G., K.T., M.R.T.), University of Oxford; Department of Medical Statistics (N.P.), London School of Hygiene and Tropical Medicine, London, UK; UmanDiagnostics (N.N.), Umeå, Sweden; Medicine Clinical Trial Unit (M.F.), Musgrove Park Hospital, Taunton, UK; National Hospital for Neurology and Neurosurgery (R.O., R.H., A.M.), London, UK; Neurology (J.K.), University Hospital Basel, Switzerland; North-East London and Essex MND Care and Research Centre (A.M.), London; and Basildon and Thurrock University Hospitals NHS Foundation Trust (A.M.), Basildon, UK.
Neurology. 2015 Jun 2;84(22):2247-57. doi: 10.1212/WNL.0000000000001642. Epub 2015 May 1.
To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS).
Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale-Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan-Meier analysis.
CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels (r = 0.78, p < 0.0001). Blood NfL levels were approximately 4 times as high in patients with ALS compared with controls in both cohorts, and maintained a relatively constant expression during follow-up. Blood NfL levels at recruitment were strong, independent predictors of survival. The highest tertile of blood NfL at baseline had a mortality hazard ratio of 3.91 (95% confidence interval 1.98-7.94, p < 0.001).
Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials.
This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls.
检测血和脑脊液神经丝轻链（NfL）水平与肌萎缩侧索硬化症（ALS）疾病进展及生存情况的关系。
采用电化学发光免疫分析法，对来自伦敦（ALS/对照组，血浆：n = 103/42）和牛津（ALS/对照组，血清：n = 64/36；配对脑脊液：n = 38/20）的2组散发性ALS患者和健康对照的样本进行NfL水平检测。对患者的NfL水平进行长达3年的定期检测。使用修订的ALS功能评定量表评分变化来评估疾病进展。采用Cox回归和Kaplan-Meier分析评估生存情况。
脑脊液、血清和血浆NfL能以高灵敏度（分别为97%、89%、90%）和特异性（分别为95%、75%、71%）区分ALS患者与健康对照。脑脊液NfL与血清水平高度相关（r = 0.78，p < 0.0001）。在两个队列中，ALS患者的血NfL水平约为对照组的4倍，且在随访期间保持相对稳定的表达。入组时的血NfL水平是生存的强有力独立预测指标。基线时血NfL最高三分位数的死亡风险比为3.91（95%置信区间1.98 - 7.94，p < 0.001）。
血源性NfL水平是一种易于获取的生物标志物，对ALS具有预后价值。其个体纵向相对稳定的水平为NfL在未来治疗试验中作为药效学生物标志物提供了潜力。
本报告提供III类证据，表明NfL电化学发光免疫分析法能准确区分散发性ALS患者与健康对照。
