与皮质损伤相关的 CSF 特征可预测多发性硬化症的活动。

The CSF Profile Linked to Cortical Damage Predicts Multiple Sclerosis Activity.

机构信息

Regional Multiple Sclerosis Center, Neurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.

出版信息

Ann Neurol. 2020 Sep;88(3):562-573. doi: 10.1002/ana.25786. Epub 2020 Jul 9.

DOI:10.1002/ana.25786

PMID:32418239

Abstract

OBJECTIVE

Intrathecal inflammation correlates with the grey matter damage since the early stages of multiple sclerosis (MS), but whether the cerebrospinal fluid (CSF) profile can help to identify patients at risk of disease activity is still unclear.

METHODS

We evaluated the association between CSF levels of 18 cytokines, previously found to be associated to grey matter damage, and the disease activity, among 99 patients with relapsing-remitting MS, who underwent blinded clinical and 3 T magnetic resonance imaging (MRI) evaluations for 4 years. Groups with evidence of disease activity (EDA) or no evidence of disease activity (NEDA; occurrence of relapses, new white matter lesions, and Expanded Disability Status Scale [EDSS] change) were identified. Cortical lesions and the annualized cortical thinning were also evaluated.

RESULTS

Forty-one patients experienced EDA and, compared to the NEDA group, had at diagnosis higher CSF levels of CXCL13, CXCL12, IFNγ, TNF, sCD163, LIGHT, and APRIL (p < 0.001). In the multivariate analysis, CXCL13 (hazard ratio [HR] = 1.35; p = 0.0002), LIGHT (HR = 1.22; p = 0.005) and APRIL (HR = 1.78; p = 0.0001) were the CSF molecules more strongly associated with the risk of EDA. The model, including CSF variables, predicted more accurately the occurrence of disease activity than the model with only clinical/MRI parameters (C-index at 4 years = 71% vs 44%). Finally, higher CSF levels of CXCL13 (β = 4.710 ; p < 0.001), TNF (β = 3.110 ; p = 0.004), LIGHT (β = 2.610 ; p = 0.003), sCD163 (β = 4.310 ; p = 0.009), and TWEAK (β = 3.4*10 ; p = 0.024) were associated with more severe cortical thinning.

INTERPRETATION

A specific CSF profile, mainly characterized by elevated levels of B-cell related cytokines, distinguishes patients at high risk of disease activity and severe cortical damage. The CSF analysis may allow stratifications of patients at diagnosis for optimizing therapeutic approaches. ANN NEUROL 2020;88:562-573.

摘要

目的

鞘内炎症与多发性硬化症（MS）早期的灰质损伤相关，但脑脊液（CSF）特征是否有助于识别疾病活动风险患者尚不清楚。

方法

我们评估了 99 例复发缓解型 MS 患者 CSF 中 18 种细胞因子的水平与疾病活动之间的关联，这些患者在 4 年内接受了盲法临床和 3T 磁共振成像（MRI）评估。根据有无疾病活动证据（EDA）或无疾病活动证据（NEDA；复发、新的白质病变和扩展残疾状况量表[EDSS]变化）将患者分组。还评估了皮质病变和皮质年度变薄。

结果

41 例患者出现 EDA，与 NEDA 组相比，诊断时 CSF 中 CXCL13、CXCL12、IFNγ、TNF、sCD163、LIGHT 和 APRIL 水平更高（p<0.001）。在多变量分析中，CXCL13（危险比[HR]=1.35；p=0.0002）、LIGHT（HR=1.22；p=0.005）和 APRIL（HR=1.78；p=0.0001）是与 EDA 风险相关性最强的 CSF 分子。包括 CSF 变量在内的模型比仅基于临床/MRI 参数的模型（4 年时 C 指数=71%比 44%）更能准确预测疾病活动的发生。最后，CXCL13（β=4.710；p<0.001）、TNF（β=3.110；p=0.004）、LIGHT（β=2.610；p=0.003）、sCD163（β=4.310；p=0.009）和 TWEAK（β=3.4*10；p=0.024）的 CSF 水平升高与更严重的皮质变薄相关。