Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS
Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS
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DOI：
10.1212/nxi.0000000000000555
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发表时间：
2019-05-01
影响因子：
8.8
通讯作者：
Ziemssen, Tjalf
中科院分区：
文献类型：
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作者：
Akguen, Katja;Kretschmann, Nicole;Ziemssen, Tjalf
目的评估个体神经丝轻链（NfL）随病程时间的变化以及 NfL 测量预测 MS 患者治疗反应的潜力。方法我们调查了 15 名接受阿仑单抗（ATZ）免疫重建治疗后的 MS 患者。在长达 102 个月的观察期内，每月血清 NfL (sNFL) 测量值与扩展残疾状态量表 (EDSS)、MRI 和复发活动相关。结果在 ATZ 之前，sNfL 显着增加，与之前的复发/MRI 活动相关。 ATZ 后，sNfL 在前 6 个月内迅速下降。在分类为 NEDA-3 的患者中，sNfL 下降并持续在个体低稳态水平，可检测到增加 20 倍，这与临床或 MRI 疾病活动相关。即使患者报告的复发可疑症状（由于复发伴随着 sNfL，尚未得到证实）也会增加，建议将 sNfL 评估作为复发活动的标志。 sNfL最早在5个月前开始增加，在临床发病时达到峰值，并在4-5个月内恢复。与有反应的患者相比，需要 ATZ 重新治疗的活跃患者的 sNfL 水平较高。在 2 次有记录的妊娠期间，sNfL 处于较低水平，而产后短暂的 sNfL 增加却没有任何活动迹象。结论本研究在接受 ATZ 治疗的队列中应用了长期高频 sNfL 评估，允许在个体层面进行整体分析，并强调 sNfL 可以在临床实践中很好地补充个体临床和 MRI 监测。
ObjectiveTo evaluate individual neurofilament light chain (NfL) variation over the time of disease course and the potential of NfL measurement to predict treatment response in patients with MS.MethodsWe investigated 15 patients with MS after immune reconstitution treatment with alemtuzumab (ATZ). Monthly serum NfL (sNFL) measurements were correlated with Expanded Disability Status Scale (EDSS), MRI, and relapse activity over an observational period of up to 102 months.ResultsBefore ATZ, sNfL was significantly increased in correlation with previous relapse/MRI activity. After ATZ, sNfL decreased quickly within the first 6 months. In patients classified as NEDA-3, sNfL declined and persisted at an individual low steady-state level of 20 fold increase could be detected, which were associated with clinical or MRI disease activity. Even patient-reported relapse-suspicious symptoms, which have not been confirmed because relapses were accompanied by sNfL, increase, proposing sNfL assessment as a marker for relapse activity. sNfL started to increase earliest 5 months before, peaked at clinical onset, and recovered within 4-5 months. sNfL presented at higher levels in active patients requiring ATZ retreatment compared with responder patients. During 2 documented pregnancies, sNfL was at a low level, whereas a postpartum transient sNfL increase was seen without any signs of activity.ConclusionsThis study applied a long-term high-frequency sNfL assessment in an ATZ-treated cohort, allowing a holistic profiling on the individual level and highlighted that sNfL can eminently complement the individual clinical and MRI monitoring in clinical practice.