目的:临床孤立综合征(CIS)是多发性硬化症(MS)的临床前阶段。CIS到临床明确MS(CDMS)的进展速度在不同人群中差异显著,确定疾病进展的预测因子对早期诊断和治疗至关重要.我们的目的是调查中国队列中CIS进展到CDMS的预测因素。
方法:对2018年至2021年中国新诊断的CIS患者进行单中心队列研究。所有患者均接受了全面的临床评估,包括神经检查,磁共振成像,和实验室测试。定期进行随访评估以监测疾病进展。CDMS的进展是根据2017年麦当劳标准定义的。年龄,性别,扩展残疾状况量表(EDSS)评分,磁共振成像钆增强(Gd+)病变的患者数量,T2病变和Gd+病变计数,CSF细胞计数,CSF总蛋白,CSF和血清神经丝轻链(NfL),测量了颗粒蛋白前体(PGRN)和Th17相关细胞因子(IL-6,IL-17,IL-21,IL-22,IL-23和TGF-β)与CDMS进展风险的相关性。
结果:本研究共招募了96CIS患者。在至少24个月的随访期间,57例(59.38%)CIS患者进展为CDMS,而39例(40.62%)无进展的患者在S.多因素分析显示发病年龄较小(OR=43.43,95%CI=1.76-1071.68,p<0.021),脑脊液蛋白升高(OR=58.64,95%CI=2.72-1264.51,p=0.009),较高的CSFNfL水平(OR=97.00,95%CI=4.68-2012.99,p=0.003)和较高的CSFIL-23水平(OR=412.02,95%CI=6.56-25869.60,p=0.004)与进展为CDMS的高风险相关.
结论:发病年龄较小,CSFNfL升高,IL-23和蛋白质水平可能是中国人群CIS向CDMS进展的预测因子。
OBJECTIVE: Clinically isolated syndrome (CIS) is a preclinical phase of multiple sclerosis (MS). The progression rate of CIS to clinical definite MS (CDMS) varies significantly across different populations, and identifying predictors of progression is crucial for early diagnosis and treatment. We aimed to investigate predictors of progression from CIS to CDMS in a Chinese cohort.
METHODS: A single-center cohort study was conducted with newly diagnosed patients with CIS in
China between 2018 and 2021. All patients underwent a comprehensive clinical evaluation, including neurological examination, magnetic resonance imaging, and laboratory tests. Follow-up assessments were conducted at regular intervals to monitor disease progression. Progression to CDMS was defined according to the 2017 McDonald criteria. Age, sex, Expanded Disability Status Scale (EDSS) score, number of patients with magnetic resonance imaging gadolinium-enhancing (Gd+) lesions, T2 lesions and Gd+ lesions count, CSF cell count, CSF total protein, CSF and serum neurofilament light chain (NfL), progranulin (PGRN) and Th17-related cytokines (IL-6, IL-17, IL-21, IL-22, IL-23 and TGF-β) were measured for association with risk of progression to CDMS.
RESULTS: A total of 96 CIS patients were recruited in the study. During the at least 24 months follow-up period, 57 (59.38 %) CIS patients progressed to CDMS, while 39 (40.62 %) patients without progression remained stable as CIS. Multivariate analysis revealed that younger age at onset (OR= 43.43, 95 % CI= 1.76-1071.68, p<0.021), higher CSF elevated protein (OR=58.64, 95 % CI=2.72-1264.51, p=0.009), higher CSF NfL levels (OR= 97.00, 95 % CI= 4.68-2012.99, p=0.003) and higher CSF IL-23 levels (OR= 412.02, 95 % CI=6.56-25869.60, p=0.004) were associated with high risk of progression to CDMS.
CONCLUSIONS: Younger age at onset, elevated CSF NfL, IL-23 and protein levels might be progression predictors of CIS to CDMS in Chinese population.