Blizard Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, UK/ Departments of Neurology and Biomedicine, University Hospital Basel, University of Basel, Switzerland.
Blizard Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, UK.
Mult Scler. 2015 Jul;21(8):1013-24. doi: 10.1177/1352458514568827. Epub 2015 Feb 13.
We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort.
Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS.
At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres.
We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
我们在一个大型国际队列中探讨了哪些临床和生化变量可预测临床孤立综合征（CIS）向临床确诊多发性硬化（CDMS）的转化。
33 个中心提供了 1047 例 CIS 患者的血清样本，这些患者的随访时间至少为 2 年。对年龄、性别、临床表现、T2 高信号病变、脑脊液（CSF）寡克隆带（OCB）、CSF IgG 指数、CSF 细胞计数、血清 25-羟维生素 D3（25-OH-D）、可替宁和针对 EBNA-1 和巨细胞病毒的 IgG 效价与 CDMS 风险的相关性进行了检测。
在中位随访时间 4.31 年时，623 例 CIS 患者转化为 CDMS。多变量分析中的转化预测因素为 OCB（HR=2.18，95%CI=1.71-2.77，p<0.001）、T2 病变数量（2-9 个病变与 0/1 个病变：HR=1.97，95%CI=1.52-2.55，p<0.001；>9 个病变与 0/1 个病变：HR=2.74，95%CI=2.04-3.68，p<0.001）和 CIS 时的年龄（每增加 1 岁 HR 呈反比增加=0.98，95%CI=0.98-0.99，p<0.001）。单变量分析中，较低的 25-OH-D 水平与 CDMS 相关，但在多变量模型中这种相关性减弱。OCB 阳性与较高的 EBNA-1 IgG 效价相关。
我们在多中心环境中验证了 MRI 病变负荷、OCB 和 CIS 时的年龄是转化为 CDMS 的最强独立预测因素。维生素 D 的作用虽然得到提示，但需要进一步研究。
