Department of Neurology and Neurosurgery, Children's Clinical University Hospital, Riga, Latvia.
Department of Doctoral Studies, Riga Stradins University, Riga, Latvia.
Eur J Neurol. 2021 Mar;28(3):974-981. doi: 10.1111/ene.14689. Epub 2021 Jan 6.
Charcot-Marie-Tooth (CMT) disease is a chronic, slowly progressing disorder. The lack of specific disease progression biomarkers limits the execution of clinical trials. However, neurofilament light chain (NfL) has been suggested as a potential biomarker for peripheral nervous system disorders.
Ninety-six CMT disease patients and 60 healthy controls were enrolled in the study. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Blood plasma NfL concentrations were measured using the single-molecule array NfL assay.
The NfL concentration was significantly higher in the CMT disease patient group than in the controls (p < 0.001). Of the CMT disease patients, those with type CMTX1 had a higher NfL level than those in the two other analysed subgroups (CMT1A and other CMT disease types) (p = 0.0498). The NfL concentration had a significant but weak correlation with the CMTNSv2 (r = 0.25, p = 0.012). In one CMT disease patient with an extremely elevated NfL level, overlap with chronic inflammatory demyelinating polyneuropathy was suspected. Receiver operating characteristic analysis showed that an NfL concentration of 8.9 pg/ml could be used to discriminate CMT disease patients from controls, with an area under the curve of 0.881.
Our study confirmed that the plasma NfL concentration is significantly higher in CMT disease patients than in controls. Plasma NfL concentration was found to significantly, albeit weakly, reflect the clinical severity of CMT disease. In the future, NfL may be used, either individually or collaboratively, as a biomarker in the clinical context of suspected CMT disease; however, several issues need to be addressed first.
Charcot-Marie-Tooth（CMT）病是一种慢性、进行性疾病。缺乏特异性疾病进展生物标志物限制了临床试验的开展。然而，神经丝轻链（NfL）已被提议作为周围神经系统疾病的潜在生物标志物。
本研究纳入了 96 名 CMT 病患者和 60 名健康对照者。疾病严重程度评估包括使用 CMT 神经病评分 2 版（CMTNSv2）进行临床评估。使用单分子阵列 NfL 检测法测量血浆 NfL 浓度。
CMT 病患者组的 NfL 浓度明显高于对照组（p<0.001）。在 CMT 病患者中，CMTX1 型患者的 NfL 水平高于其他两种分析亚组（CMT1A 和其他 CMT 病类型）（p=0.0498）。NfL 浓度与 CMTNSv2 显著相关（r=0.25，p=0.012），但相关性较弱。在一名 NfL 水平极高的 CMT 病患者中，疑似重叠慢性炎症性脱髓鞘性多发性神经病。受试者工作特征分析显示，8.9pg/ml 的 NfL 浓度可用于区分 CMT 病患者和对照组，曲线下面积为 0.881。
本研究证实，CMT 病患者的血浆 NfL 浓度明显高于对照组。发现血浆 NfL 浓度与 CMT 病的临床严重程度显著相关，尽管相关性较弱。未来，NfL 可能会单独或联合用作疑似 CMT 病临床情况下的生物标志物；然而，首先需要解决几个问题。
