From the Department of Neurology, MS Centre ErasMS (Y.Y.M.W., A.L.B., D.v.P., R.Q.H.), Department of Immunology (M.-J.M., A.F.W., R.Q.H.), and Department of Pediatric Neurology (R.F.N.), Erasmus MC, Rotterdam, the Netherlands; and Neurologic Clinic and Policlinic (C.B., Z.M., J.K.), University Hospital Basel, Switzerland.
Neurology. 2019 Sep 3;93(10):e968-e974. doi: 10.1212/WNL.0000000000008057. Epub 2019 Aug 5.
To explore the correlation between serum and CSF neurofilament light chain (NfL) and the association of NfL levels and future disease activity in pediatric patients with a first attack of acquired demyelinating syndromes (ADS).
In total, 102 children <18 years with a first attack of CNS demyelination and 23 age-matched controls were included. Clinically definite multiple sclerosis (CDMS) was set as an endpoint for analysis. CSF NfL was tested by the commercially available ELISA (UmanDiagnostics); serum NfL (sNfL) was tested with a Simoa assay. Hazard ratios (HR) were calculated with Cox regression analysis.
Of the 102 patients, 47 (46%) were tested for CSF NfL. CSF and serum NfL correlated significantly in the total group (ρ 0.532, < 0.001) and even more significantly in the subgroup of patients with future CDMS diagnosis (ρ 0.773, < 0.001). sNfL was higher in patients than in controls (geometric mean 6.1 pg/mL, < 0.001), and was highest in ADS presenting with encephalopathy (acute disseminated encephalomyelitis, n = 28, 100.4 pg/mL), followed by patients without encephalopathy (ADS-) with future CDMS diagnosis (n = 40, 32.5 pg/mL), and ADS- who remained monophasic (n = 34, 17.6 pg/mL). sNfL levels higher than a median of 26.7 pg/mL at baseline are associated with a shorter time to CDMS diagnosis in ADS- ( = 0.045). HR for CDMS diagnosis was 1.09 for each 10 pg/mL increase of sNfL, after correction for age, oligoclonal bands, and MRI measures ( = 0.012).
The significant correlation between CSF and serum NfL strengthens its reliability as a peripheral marker of neuroaxonal damage. Higher sNfL levels at baseline were associated with higher probability of future CDMS diagnosis in ADS-.
探讨血清和脑脊液神经丝轻链(NfL)之间的相关性,以及 NfL 水平与首次发生获得性脱髓鞘综合征(ADS)的儿科患者未来疾病活动的关联。
共纳入 102 例<18 岁的首次发生中枢神经系统脱髓鞘的儿童患者和 23 名年龄匹配的对照者。将临床确诊的多发性硬化症(CDMS)作为分析终点。通过商业上可用的 ELISA(UmanDiagnostics)检测 CSF NfL;使用 Simoa 测定法检测血清 NfL(sNfL)。使用 Cox 回归分析计算危险比(HR)。
在 102 例患者中,47 例(46%)进行了 CSF NfL 检测。在总人群中,CSF 和血清 NfL 显著相关(ρ 0.532,<0.001),在未来 CDMS 诊断的亚组中相关性更显著(ρ 0.773,<0.001)。与对照组相比,患者的 sNfL 更高(几何均数 6.1 pg/mL,<0.001),在表现为脑病的 ADS 患者中最高(急性播散性脑脊髓炎,n=28,100.4 pg/mL),其次是未来 CDMS 诊断无脑病的 ADS-患者(n=40,32.5 pg/mL),以及保持单相的 ADS-患者(n=34,17.6 pg/mL)。基线时 sNfL 水平高于中位数 26.7 pg/mL 与 ADS-患者的 CDMS 诊断时间更短相关(=0.045)。在校正年龄、寡克隆带和 MRI 测量值后,sNfL 每增加 10 pg/mL,CDMS 诊断的 HR 为 1.09(=0.012)。
CSF 和血清 NfL 之间的显著相关性增强了其作为神经轴突损伤的外周标志物的可靠性。ADS-患者基线时较高的 sNfL 水平与未来 CDMS 诊断的可能性更高相关。