Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark.
Department of Neurology, University Hospital, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Brain. 2020 Sep 1;143(9):2637-2652. doi: 10.1093/brain/awaa145.
In the past decade, changes have occurred in the spectrum of multiple sclerosis courses. The natural history of multiple sclerosis appears milder from the first sign of demyelinating disease to the progressive course, probably as a result of an interplay between several factors including changes in the diagnostic criteria, changes in the epidemiology of multiple sclerosis, impact of early and appropriate disease-modifying treatment and improvement of the general state of health in the population. It has been suggested to regard incidental findings of demyelinating lesions in MRI in individuals without any history of clinical symptoms consistent with neurological dysfunction, so-called radiological isolated syndrome, as the initial course of multiple sclerosis. New diagnostic criteria have enabled the multiple sclerosis diagnosis in many patients at the first clinical demyelinating event, clinically isolated syndrome. The remaining patients with clinically isolated syndrome have a more benign prognosis, and for relapsing-remitting multiple sclerosis, the prognosis has become more favourable. Reduced disease activity in patients with relapsing-remitting multiple sclerosis can partly be ascribed to more efficacious new disease-modifying therapies but decrease in disease activity has also be seen in placebo-treated patients in clinical trials. This may be explained by several factors: change in the diagnostic criteria, more explicit inclusion criteria, exclusion of high-risk patients e.g. patients with co-morbidities, and more rigorous definitions of relapses and disease worsening. However, these factors also make the disease course in patients treated with disease-modifying therapies seem more favourable. In addition, change in the therapeutic target to stable disease (no evidence of disease activity = no relapses, no disease worsening and no MRI activity) could by itself change the course in relapsing-remitting multiple sclerosis. The effectiveness of disease-modifying drugs has reduced the transition from relapsing-remitting to secondary progressive multiple sclerosis. The concept of progressive multiple sclerosis has also evolved from two very distinct categories (primary progressive and secondary progressive multiple sclerosis) to a unified category of progressive multiple sclerosis, which can then be split into the categories of active or inactive. Also, an increasing tendency to treat progressive multiple sclerosis with disease-modifying therapies may have contributed to change the course in progressive multiple sclerosis. In conclusion, during the past decade the entire course of multiple sclerosis from the first sign of a demyelinating disorder through the progressive course appears to be milder due to a complex interplay of several factors.
在过去的十年中，多发性硬化症的病程发生了变化。从脱髓鞘疾病的最初迹象到进展性病程，多发性硬化症的自然病史似乎变得更为轻微，这可能是由于多种因素相互作用的结果，包括诊断标准的变化、多发性硬化症流行病学的变化、早期和适当的疾病修饰治疗的影响以及人群健康状况的改善。有人建议将无任何与神经功能障碍一致的临床症状的病史的个体的 MRI 中脱髓鞘病变的偶然发现视为多发性硬化症的初始病程，即所谓的孤立性放射性综合征。新的诊断标准使得许多患者在首次临床脱髓鞘事件即孤立性临床综合征时就能够得到多发性硬化症的诊断。对于孤立性临床综合征患者，其预后更为良性，而对于复发缓解型多发性硬化症，其预后则变得更为有利。复发缓解型多发性硬化症患者的疾病活动度降低，这在一定程度上归因于更有效的新型疾病修饰疗法，但临床试验中接受安慰剂治疗的患者也观察到疾病活动度降低。这可能是由以下几个因素造成的：诊断标准的改变、更为明确的纳入标准、排除高风险患者（例如合并症患者）以及对复发和疾病恶化的更为严格的定义。然而，这些因素也使得接受疾病修饰疗法治疗的患者的疾病病程看起来更为有利。此外，治疗目标改变为稳定疾病（无疾病活动证据=无复发、无疾病恶化和无 MRI 活动）本身也可能改变复发缓解型多发性硬化症的病程。疾病修饰药物的有效性降低了从复发缓解型到继发进展型多发性硬化症的转变。进展型多发性硬化症的概念也从两个非常不同的类别（原发性进展型和继发性进展型多发性硬化症）演变为一个统一的进展型多发性硬化症类别，然后可以分为活动期或非活动期。此外，用疾病修饰疗法治疗进展型多发性硬化症的趋势不断增加，这可能也促成了进展型多发性硬化症病程的改变。总之，在过去的十年中，由于多种因素的复杂相互作用，从脱髓鞘疾病的最初迹象到进展性病程的整个多发性硬化症病程似乎都变得更为轻微。
