Oset Magdalena, Domowicz Małgorzata, Wildner Paula, Siger Małgorzata, Karlińska Iwona, Stasiołek Mariusz, Świderek-Matysiak Mariola
Department of Neurology, Medical University of Lodz, Lodz, Poland.
Front Neurol. 2023 Jul 25;14:1223220. doi: 10.3389/fneur.2023.1223220. eCollection 2023.
Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS). A clinical presentation of the disease is highly differentiated even from the earliest stages of the disease. The application of stratifying tests in clinical practice would allow for improving clinical decision-making including a proper assessment of treatment benefit/risk balance.
This prospective study included patients with MS diagnosed up to 1 year before recruitment. We analyzed serum biomarkers such as CXCL13, CHI3L1, OPN, IL-6, and GFAP and neurofilament light chains (NfLs); brain MRI parameters of linear atrophy such as bicaudate ratio (BCR), third ventricle width (TVW); and information processing speed were measured using the Symbol Digit Modalities Test (SDMT) during the 2 years follow-up.
The study included a total of 50 patients recruited shortly after the diagnosis of MS diagnosis (median 0 months; range 0-11 months), and the mean time of observation was 28 months (SD = 4.75). We observed a statistically significant increase in the EDSS score (Wilcoxon test: = 3.06, = 0.002), BCR (Wilcoxon test: = 4.66, < 0.001), and TVW (Wilcoxon test: = 2.84, = 0.005) after 2 years of disease. Patients who had a significantly higher baseline level of NfL suffered from a more severe disease course as per the EDSS score (Mann-Whitney U-test: = 107, = -2,74, = 0.006) and presence of relapse (Mann-Whitney U-test: = 188, = -2.01, = 0.044). In the logistic regression model, none of the parameters was a significant predictor for the achieving of no evidence of disease activity status (NEDA). In the model considering all assessed parameters, only the level of NfL had a significant impact on disease progression, measured as the increase in EDSS (logistic regression: β = 0.002, = 0.017).
We confirmed that NfL levels in serum are associated with more active disease. Moreover, we found that TVW at the time of diagnosis was associated with an impairment in cognitive function measured by information processing speed at the end of the 2-year observation. The inclusion of serum NfL and TVW assessment early in the disease may be a good predictor of disease progression independent of NEDA.
多发性硬化症（MS）是一种慢性自身免疫介导的中枢神经系统（CNS）脱髓鞘疾病。该疾病的临床表现即使在疾病的最早阶段也具有高度差异性。在临床实践中应用分层测试将有助于改善临床决策，包括对治疗益处/风险平衡的恰当评估。
这项前瞻性研究纳入了在招募前1年内被诊断为MS的患者。我们分析了血清生物标志物，如CXCL13、CHI3L1、骨桥蛋白（OPN）、白细胞介素-6（IL-6）和胶质纤维酸性蛋白（GFAP）以及神经丝轻链（NfLs）；测量了线性萎缩的脑MRI参数，如双侧尾状核比率（BCR）、第三脑室宽度（TVW）；并在2年随访期间使用符号数字模态测试（SDMT）测量了信息处理速度。
该研究共纳入了50例在MS诊断后不久招募的患者（中位数为0个月；范围为0 - 11个月），平均观察时间为28个月（标准差 = 4.75）。我们观察到疾病2年后扩展残疾状态量表（EDSS）评分（Wilcoxon检验：z = 3.06，p = 0.002）、BCR（Wilcoxon检验：z = 4.66，p < 0.001）和TVW（Wilcoxon检验：z = 2.84，p = 0.005）有统计学显著增加。根据EDSS评分（Mann-Whitney U检验：z = 107，r = -2.74，p = 0.006）和复发情况（Mann-Whitney U检验：z = 188，r = -2.01，p = 0.044），基线NfL水平显著更高的患者疾病进程更严重。在逻辑回归模型中，没有一个参数是实现无疾病活动状态（NEDA）的显著预测因子。在考虑所有评估参数的模型中，只有NfL水平对以EDSS增加衡量的疾病进展有显著影响（逻辑回归：β = 0.002，p = 0.017）。
我们证实血清NfL水平与更活跃的疾病相关。此外，我们发现诊断时的TVW与2年观察期末通过信息处理速度测量的认知功能损害相关。在疾病早期纳入血清NfL和TVW评估可能是独立于NEDA的疾病进展的良好预测指标。
