Cerebrospinal fluid biomarkers for predicting development of multiple sclerosis in acute optic neuritis: a population-based prospective cohort study
Cerebrospinal fluid biomarkers for predicting development of multiple sclerosis in acute optic neuritis: a population-based prospective cohort study
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DOI：
10.1186/s12974-019-1440-5
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发表时间：
2019-03-11
影响因子：
9.3
通讯作者：
Asgari, N.
中科院分区：
文献类型：
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作者：
Olesen, M. N.;Soelberg, K.;Asgari, N.
背景：多发性硬化症（MS）的长期预后取决于早期治疗。在早期炎症事件急性视神经炎（ON）患者中，我们研究了脑脊液（CSF）中可能预测ms诊断的标志物。方法招募了40例急性视神经炎患者，以人群为基础，中位随访29个月（范围19-41）。在治疗前14天（范围2-38天）内采集配对CSF和血清样本。前瞻性，16/40的患者被统一算法诊断为多发性硬化（MS-ON）， 24例患者在随访期间继续表现为孤立性多发性硬化（ION）。在急性ON发病时测量细胞因子和神经丝轻链（NF-L）水平，并与健康对照（HC）进行比较。对多重比较的显著性水平进行校正(q)。生物标志物的预测值由多变量预测模型确定。结果MS-ON患者的scsf TNF-、IL-10和CXCL13水平较ION患者升高（q分别为0.021、0.004和0.0006）。与ION相比，MS-ON患者脑脊液多细胞增多、IgG指数和寡克隆带（ocb）增加（q=0.0007、q=0.0058和q=0.0021）。MS-ON患者CSF中IL-10、TNF-a、IL-17A和CXCL13水平与白细胞计数相关（p < 0.05）
BackgroundLong-term outcome in multiple sclerosis (MS) depends on early treatment. In patients with acute optic neuritis (ON), an early inflammatory event, we investigated markers in cerebrospinal fluid (CSF), which may predict a diagnosis of MS.MethodsForty patients with acute ON were recruited in a prospective population-based cohort with median 29months (range 19-41) of follow-up. Paired CSF and serum samples were takenwithin 14days (range 2-38), prior to treatment. Prospectively, 16/40 patients were by a uniform algorithm diagnosed with MS (MS-ON) and 24 patients continued to manifest isolated ON (ION) during follow-up. Levels of cytokines and neurofilament light chain (NF-L) were measured at the onset of acute ON and compared to healthy controls (HC). Significance levels were corrected for multiple comparisons (q). The predictive value of biomarkers was determined with multivariable prediction models using nomograms.ResultsCSF TNF-, IL-10, and CXCL13 levels were increased in MS-ON compared to those in ION patients (q=0.021, 0.004, and 0.0006, respectively). MS-ON patients had increased CSF pleocytosis, IgG indices, and oligoclonal bands (OCBs) compared to ION (q=0.0007, q=0.0058, and q=0.0021, respectively). CSF levels of IL-10, TNF-a, IL-17A, and CXCL13 in MS-ON patients correlated with leukocyte counts (r>0.69 and p0.55, p