Prognostic value of serum neurofilaments in patients with clinically isolated syndromes

Objectives: To assess the prognostic role of serum neurofilament light chains (Nfls) for Clinically Defined Multiple Sclerosis (CDMS) and McDonald 2017 MS in patients with Clinically Isolated Syndromes (CIS).

Methods: we retrospectively analyzed data of patients admitted at our neurological department between 2000 to 2015 for a first demyelinating event. We evaluated baseline serum Nfls in addition to CSF, MRI, and clinical data.

Results: Amongst 222 patients who were enrolled (mean follow-up 100.6 months), 45 patients (20%) developed CDMS and 141 patients (63.5%) developed 2017 MS at two years. Serum Nfls (median 22.0, IQR 11.6-40.4 pg/ml) were noticeably increased in patients who have suffered a recent relapse, with a high number of T2 and Gd enhancing lesions at baseline MRI. Serum Nfls were prognostic for both CDMS and McDonald 2017 MS, with a three-fold and a two-fold respective reduction in CDMS and 2017 MS risk in those patients with low and extremely low levels of Nfl. The results remained unchanged subsequent to adjustment for such established MS prognostic factors as oligoclonal bands’ presence, Gd-enhancing lesion, and a high T2 lesion load at baseline MRI. Nfls were associated with baseline disability but not at follow-up.

Conclusions: Serum Nfls have a prognostic value for CIS patient conversion to MS. Nfls might play a twin role as biomarkers in MS as peak level measurements can act as a quantitative marker of serious inflammatory activity, while steady-state levels can be a reflection of neurodegenerative and chronic inflammatory processes.

研究目的：旨在评估血清神经丝轻链（serum neurofilament light chains, Nfls）对临床孤立综合征（Clinically Isolated Syndromes, CIS）患者进展为临床确诊多发性硬化（Clinically Defined Multiple Sclerosis, CDMS）及麦克唐纳2017版多发性硬化的预后价值。

研究方法：我们回顾性分析了2000年至2015年间因首次脱髓鞘事件入住我院神经内科的患者数据。除脑脊液（cerebrospinal fluid, CSF）、磁共振成像（Magnetic Resonance Imaging, MRI）及临床资料外，还检测了受试者的基线血清Nfls水平。

研究结果：本研究共纳入222例患者，平均随访时长为100.6个月。其中45例（20%）患者进展为CDMS，141例（63.5%）患者在随访2年时符合麦克唐纳2017版多发性硬化诊断标准。基线血清Nfls中位数为22.0 pg/ml，四分位间距为11.6~40.4 pg/ml；在近期复发、基线MRI显示大量T2加权病变及钆增强病变的患者中，血清Nfls水平显著升高。血清Nfls水平对CDMS及麦克唐纳2017版多发性硬化均具有预后预测价值：血清Nfls水平较低的患者进展为CDMS的风险降低3倍，水平极低的患者进展为麦克唐纳2017版多发性硬化的风险降低2倍。在校正了寡克隆带阳性、钆增强病变及基线MRI高T2病变负荷等已确立的多发性硬化预后因素后，上述结果仍保持稳定。血清Nfls水平与患者基线残疾程度相关，但与随访期末的残疾程度无显著关联。

研究结论：血清Nfls对CIS患者向多发性硬化的转化具有预后评估价值。Nfls在多发性硬化中可发挥双重生物标志物作用：峰值水平可作为严重炎症活动的定量检测指标，而稳态水平则可反映神经退行性变与慢性炎症过程。