From the Department of Clinical Neuroscience (A.M., P.S., M.K., F.P., T.O., I.K.), The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Karolinska Institutet; Centre for Molecular Medicine (A.M., P.S., M.K., F.P., T.O., I.K.), Karolinska University Hospital, Stockholm, Sweden; Departments of Medicine, Biomedicine, and Clinical Research (D.L., C.B., Z.M., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Switzerland; Institution of Neuroscience and Physiology (J.L.), Sahlgrenska Academy, University of Gothenburg, Gothenburg; Institute of Environmental Medicine (L.A.), Karolinska Institutet, Stockholm; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden.
Neurology. 2020 Jun 9;94(23):e2457-e2467. doi: 10.1212/WNL.0000000000009571. Epub 2020 May 20.
To investigate the association between plasma neurofilament light chain (pNfL) levels and the risk of developing sustained disability worsening.
Concentrations of pNfL were determined in 4,385 persons with multiple sclerosis (MS) and 1,026 randomly selected population-based sex- and age-matched controls using the highly sensitive Single Molecule Array (SimoaTM) NF-Light Advantage Kit. We assessed the impact of age-stratified pNfL levels above the 80th, 95th, and 99th percentiles among controls on the risk of Expanded Disability Status Scale (EDSS) worsening within the following year and reaching sustained EDSS scores of 3.0, 4.0, and 6.0 and conversion to secondary progressive multiple sclerosis (SPMS).
The median (interquartile range [IQR]) pNfL was 7.5 (4.1) pg/mL in controls and 11.4 (9.6) pg/mL in MS ( < 0.001). The median (IQR) duration of follow-up was 5 (5.1) years. High pNfL was associated with increased adjusted rates of EDSS worsening ranging between 1.4 (95% confidence intervals [CIs]: 1.1-1.8) and 1.7 (95% CI: 1.4-2.3). High pNfL was also associated with the risk of reaching a sustained EDSS score of 3.0, with adjusted rates ranging between 1.5 (95% CI: 1.2-1.8) and 1.55 (95% CI: 1.3-1.8) over all percentile cutoffs (all < 0.001). Similar increases were observed for the risk of sustained EDSS score 4.0. In contrast, the risk of reaching sustained EDSS score 6.0 and conversion to SPMS was not consistently significant.
Elevated pNfL levels at early stages of MS are associated with an increased risk of reaching sustained disability worsening. Hence, pNfL may serve as a prognostic tool to assess the risk of developing permanent disability in MS.
研究血浆神经丝轻链（pNfL）水平与持续性残疾恶化风险之间的关联。
使用高度敏感的单分子阵列（SimoaTM）NF-Light Advantage 试剂盒，在 4385 名多发性硬化症（MS）患者和 1026 名随机选择的基于人群的性别和年龄匹配对照者中测定 pNfL 的浓度。我们评估了在对照组中，按年龄分层的 pNfL 水平超过第 80、95 和 99 百分位数时，对次年扩展残疾状况量表（EDSS）恶化风险的影响，以及达到持续 EDSS 评分 3.0、4.0 和 6.0 以及向继发性进行性多发性硬化（SPMS）转化的风险。
对照组 pNfL 的中位数（四分位距[IQR]）为 7.5（4.1）pg/mL，MS 患者为 11.4（9.6）pg/mL（<0.001）。中位（IQR）随访时间为 5（5.1）年。高 pNfL 与 EDSS 恶化的调整后发生率增加相关，范围在 1.4（95%置信区间[CI]：1.1-1.8）至 1.7（95%CI：1.4-2.3）之间。高 pNfL 还与达到持续 EDSS 评分 3.0 的风险相关，所有百分位截断值的调整后发生率在 1.5（95%CI：1.2-1.8）至 1.55（95%CI：1.3-1.8）之间（均<0.001）。对于持续 EDSS 评分 4.0 的风险观察到类似的增加。相比之下，达到持续 EDSS 评分 6.0 和向 SPMS 转化的风险并不始终显著。
MS 早期升高的 pNfL 水平与持续性残疾恶化风险增加相关。因此，pNfL 可能作为评估 MS 患者发生永久性残疾风险的预后工具。
