Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania.
Department of Neurology, Clinical Rehabilitation Hospital, 700661 Iași, Romania.
Medicina (Kaunas). 2024 Aug 26;60(9):1401. doi: 10.3390/medicina60091401.
: Although available therapies have changed the natural evolution of multiple sclerosis (MS), in time some patients assume a progressive course and no longer respond to treatment. There is no definitive clinical or laboratory parameter to certify MS progression from relapsing remitting MS (RRMS) to secondary progressive MS (SPMS) in early phases of transition. Our study aims to evaluate the value of clinical parameters and serum neurofilament light chain levels (sNfLs) as early warning signs of conversion to SPMS. : The Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), 25-foot walk test (25FWT) and Symbol Digit Modalities Test (SDMT) were evaluated at 12 months apart in a cohort of 83 RRMS treated patients. sNfLs were evaluated at the second time point. sNfLs correlate with EDSS and SDMT, with EDSS change and disease duration. Clinical parameters correlate among themselves and perform well in supporting the diagnosis of SPMS in logistic regression and ROC curves analysis. Eighty percent of the RRMS patients in our study (of which 65% are treated with high-efficacy disease-modifying drugs) showed some type of progression independent of relapses (PIRA) after 12 months, with one in five patients experiencing isolated cognitive worsening and almost two-thirds some type of motor worsening. We found no differences in terms of progression between patients treated with platform drugs versus high-efficacy drugs. : An elevated level of progression independent of relapses (PIRA) was found in our cohort, with high-efficacy drugs providing no supplementary protection. As sNfL levels were correlated with the progression of EDSS (the main clinical progression marker), they may be considered potential prognostic markers, but further studies are necessary to precisely define their role in this direction. The lack of early sensitive markers for risk of progression may contribute to therapeutic delay and failure.
尽管现有的治疗方法已经改变了多发性硬化症（MS）的自然病程，但随着时间的推移，一些患者会出现进行性病程，且不再对治疗有反应。在疾病向继发性进展性 MS（SPMS）转变的早期阶段，没有明确的临床或实验室参数可以证实 MS 从缓解复发型 MS（RRMS）进展而来。我们的研究旨在评估临床参数和血清神经丝轻链水平（sNfL）作为向 SPMS 转化的早期预警指标的价值。
我们对 83 例接受治疗的 RRMS 患者进行了队列研究，在 12 个月的时间间隔内评估扩展残疾状况量表（EDSS）、九孔钉测试（9HPT）、25 英尺步行测试（25FWT）和符号数字模态测试（SDMT），并在第二次评估时检测 sNfL。sNfL 与 EDSS 和 SDMT 相关，与 EDSS 变化和疾病持续时间相关。临床参数之间相互关联，在逻辑回归和 ROC 曲线分析中对 SPMS 的诊断支持良好。我们的研究中有 80%的 RRMS 患者在 12 个月后出现了某种类型的与复发无关的进展（PIRA），其中 65%接受了高效疾病修饰药物治疗，五分之一的患者出现了孤立性认知恶化，近三分之二的患者出现了某种类型的运动恶化。我们没有发现平台药物与高效药物治疗患者之间的进展差异。
我们的队列中发现了与复发无关的进展水平升高（PIRA），高效药物并没有提供额外的保护。由于 sNfL 水平与 EDSS 的进展相关（主要的临床进展标志物），它们可能被认为是潜在的预后标志物，但需要进一步的研究来精确确定它们在这方面的作用。缺乏进展风险的早期敏感标志物可能导致治疗延迟和失败。
