Leray E, Moreau T, Fromont A, Edan G
Biostatistics and Epidemiology Department, EHESP, avenue du Professeur-Léon-Bernard, 35000 Rennes, France.
Neurology Department, EA 4184, University Hospital of Dijon, 14, rue Gaffarel, 21000 Dijon, France.
Rev Neurol (Paris). 2016 Jan;172(1):3-13. doi: 10.1016/j.neurol.2015.10.006. Epub 2015 Dec 21.
Multiple sclerosis (MS) is the most frequently seen demyelinating disease, with a prevalence that varies considerably, from high levels in North America and Europe (>100/100,000 inhabitants) to low rates in Eastern Asia and sub-Saharan Africa (2/100,000 population). Knowledge of the geographical distribution of the disease and its survival data, and a better understanding of the natural history of the disease, have improved our understanding of the respective roles of endogenous and exogenous causes of MS. Concerning mortality, in a large French cohort of 27,603 patients, there was no difference between MS patients and controls in the first 20 years of the disease, although life expectancy was reduced by 6-7 years in MS patients. In 2004, the prevalence of MS in France was 94.7/100,000 population, according to data from the French National Health Insurance Agency for Salaried Workers (Caisse nationale d'assurance maladie des travailleurs Salariés [CNAM-TS]), which insures 87% of the French population. This prevalence was higher in the North and East of France. In several countries, including France, the gender ratio for MS incidence (women/men) went from 2/1 to 3/1 from the 1950s to the 2000s, but only for the relapsing-remitting form. As for risk factors of MS, the most pertinent environmental factors are infection with Epstein-Barr virus (EBV), especially if it arises after childhood and is symptomatic. The role of smoking in MS risk has been confirmed, but is modest. In contrast, vaccines, stress, traumatic events and allergies have not been identified as risk factors, while the involvement of vitamin D has yet to be confirmed. From a genetic point of view, the association between HLA-DRB1*15:01 and a high risk of MS has been known for decades. More recently, immunogenetic markers have been identified (IL2RA, IL7RA) and, in particular thanks to studies of genome-wide associations, more than 100 genetic variants have been reported. Most of these are involved in the immune response and often associated with other autoimmune diseases. Studies of the natural history of MS suggest it is a two-phase disease: in the first phase, inflammation is focal with flares; and in the second phase, disability progresses independently of focal inflammation. This has clear implications for therapy. Age may also be a key factor in the phenotype of the disease. In conclusion, France is a high-risk country for MS, but it only slightly reduces life expectancy. MS is a multifactorial disease and the implications of immunogenetics are major. Preventative approaches might be derived from knowledge of the risk factors and natural history of the disease (smoking, vitamin D).
多发性硬化症（MS）是最常见的脱髓鞘疾病，其患病率差异很大，从北美和欧洲的高水平（>100/100,000居民）到东亚和撒哈拉以南非洲的低水平（2/100,000人口）。对该疾病地理分布及其生存数据的了解，以及对疾病自然史的更好理解，增进了我们对MS内源性和外源性病因各自作用的认识。关于死亡率，在法国一个由27,603名患者组成的大型队列中，疾病最初20年里MS患者与对照组之间没有差异，不过MS患者的预期寿命缩短了6 - 7年。根据法国国家工薪族健康保险局（Caisse nationale d'assurance maladie des travailleurs Salariés [CNAM-TS]）的数据，2004年法国MS的患病率为94.7/100,000人口，该机构为87%的法国人口提供保险。这种患病率在法国北部和东部较高。在包括法国在内的几个国家，MS发病率的性别比（女性/男性）从20世纪50年代到21世纪初从2/1升至3/1，但仅针对复发缓解型。至于MS的风险因素，最相关的环境因素是感染爱泼斯坦 - 巴尔病毒（EBV），尤其是在儿童期之后感染且出现症状的情况。吸烟在MS风险中的作用已得到证实，但作用较小。相比之下，疫苗、压力、创伤事件和过敏尚未被确定为风险因素，而维生素D的影响尚未得到证实。从遗传学角度来看，HLA-DRB1*15:01与MS高风险之间的关联已为人所知数十年。最近，免疫遗传标记已被确定（IL2RA、IL7RA），特别是由于全基因组关联研究，已报告了100多个基因变体。其中大多数参与免疫反应，且常常与其他自身免疫性疾病相关。MS自然史研究表明它是一种两阶段疾病：在第一阶段，炎症是局灶性的且有发作；在第二阶段，残疾进展与局灶性炎症无关。这对治疗有明确的启示。年龄也可能是该疾病表型的一个关键因素。总之，法国是MS的高风险国家，但它只是略微降低了预期寿命。MS是一种多因素疾病，免疫遗传学的影响很大。预防方法可能源自对疾病风险因素和自然史（吸烟、维生素D）的了解。
