Elsevier

Revue Neurologique

Volume 172, Issue 1, January 2016, Pages 3-13
Revue Neurologique

Neuroepidemiology
Epidemiology of multiple sclerosis

https://doi.org/10.1016/j.neurol.2015.10.006Get rights and content

Abstract

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).

Introduction

Multiple sclerosis (MS) is the most common demyelinating disease seen in high-income countries, and has a heterogeneous prevalence worldwide: it is highest in North America (140/100,000 population) and Europe (108/100,000), and lowest in East Asia (2.2/100,000 population) and sub-Saharan Africa (2.1/100,000). The global median prevalence of MS has increased from 30/100,000 in 2008 to 33/100,000 in 2013, according to a report by the MS International Federation. In Europe in particular, a North-South prevalence gradient has been described for distribution of the disease (higher in the North, lower in the South). France is located in the middle of Western Europe between zones of high MS prevalence (such as the Scandinavian countries and United Kingdom) and areas of low MS prevalence (Italy, Greece, Spain), and also appears to reflect the European epidemiology of the disease rather well. Given this situation, MS mortality, incidence and prevalence data and their evolution over time in France are important in that they provide a pertinent view of the epidemiology.

Analyzing such data is an essential first step towards taking into account the considerable knowledge and numerous hypotheses regarding the cause(s) of MS and, above all, the environmental risk factors. Also, extensive databases for large groups of MS patients provide accurate information on the natural history of MS as a two-stage disease (first the focal inflammatory process, and then the second, which is independent of focal inflammatory markers). All of these descriptive and analytical epidemiological data will lead to a better understanding of the risk factors for MS, and may even have implications for therapeutic strategies.

Section snippets

MS mortality

To our knowledge, around 40 epidemiological studies of mortality have been conducted in patients afflicted with MS. According to one published series [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], 70–88% of patients are still alive 25 years after clinical onset, and the median time from onset to death ranges from 24 years to > 45 years. These differences can be explained by differences in study periods, geographical areas and methodology (such as study population, duration,

Risk factors of MS

The cause of MS is multifactorial: both genetic and environmental risk factors contribute to disease risk. Several factors have been assessed and are reviewed below. However, the specific causes of MS are still largely unknown and, at present, there are no well-established factors to assist disease prevention [20], [21].

Prevalence and incidence

The distribution and frequency of MS are assessed by estimates of prevalence and incidence. ‘Prevalence’ refers to the proportion of a population that has the disease at or during a specified time, while ‘incidence’ refers to the proportion of new cases arising during a specific time period. Prevalence reflects the ‘stock’ of patients, while incidence reflects the dynamic dimension of the disease.

As mentioned above, assessment of the different incidences and prevalences across populations can

Gender ratio

Over the past 30 years, the MS gender ratio has changed due to an increase in the incidence of MS in women. Between 1960 and 2005, the gender ratio adjusted for the year of MS onset increased from 1.68 to 2.45 (P = 0.017), according to data from the Lyon MS database collected by the European Database for Multiple Sclerosis (EDMUS) system. This analysis was conducted in 4495 patients, including 3030 women (67.4%). However, the change in gender ratio over time was observed only for the relapsing

The natural history of MS in France

Only studies of large groups of MS patients using extensive databases can give accurate information on the natural history of MS. Specifically, the requirements for such studies include identifying a geographically defined population with MS at the early stages, achieving complete ascertainment and a complete follow-up for an appropriate period, and applying outcome measurements that detect all possible relevant outcomes. No large published cohorts have completely satisfied these requirements.

Lessons from the natural history of MS

Understanding the dissociation between early and late disability progression, and the role of relapses, is central to the debate on the putative mechanisms of disability progression in MS. Some studies [79], [81], [84] have suggested that age is a key factor (if not the only one) in the natural history of MS, leading to the concept of MS as a single-stage disorder with chronic age-related neurodegeneration following onset of the disease [85].

However, the Rennes cohort [86] suggests a two-stage

Conclusion

Given the mortality, prevalence, incidence, evolution of the gender ratio and geographical distribution of MS in France, this country can now be more precisely defined as a high-risk country for MS. Improved knowledge of the natural history of MS, with the dissociation between early and late disability progression and the impact of relapses on disability progression, has led to a better understanding of MS mechanisms and better guidance for therapeutic strategies.

As stated by Simpson et al. in

Disclosure of interest

The authors declare that they have no competing interest.

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