EPIDEMIOLOGY of MS

 

This map demonstrates unequal distribution of multiple sclerosis around the world.

Two main measures are used in epidemiological studies: incidence and prevalence. 

Incidence is the number of new cases per unit of person–time at risk (usually number of new cases per thousand person–years); while prevalence is the total number of cases of the disease in the population at a given time. 

Prevalence is known to depend not only on incidence, but also on survival rate and migrations of affected people. MS has a prevalence that ranges between 2 and 150 per 100,000 depending on the country or specific population. Studies on populational and geographical patterns of epidemiological measures have been very common in MS, and have led to the proposal of different etiological (causal) theories.

MS usually appears in adults in their thirties, but it can also appear in children, and the primary progressive subtype is more common in people in their fifties. As with many autoimmune disorders, the disease is more common in women, and the trend may be increasing. In children, the sex ratio may reach three females for each male. In people over fifty, MS affects males and females almost equally.

Ethnic groups such as the Samis have a reduced risk of MS, probably due to genetic factors.

There is a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere, with MS being much less common in people living near the equator.   Climate, sunlight and intake of vitamin D have been investigated as possible causes of the disease that could explain this latitude gradient. However, there are important exceptions to the north-south pattern such as incidence and prevalence in the Canary Islands and changes in prevalence rates over time; in general, this trend might be disappearing. This indicates that other factors such as environment or genetics have to be taken into account to explain the origin of MS.

Environmental factors during childhood may play an important role in the development of MS later in life. Several studies of migrants show that if migration occurs before the age of fifteen, the migrant acquires the new region's susceptibility to MS. If migration takes place after age fifteen, the migrant retains the susceptibility of his home country. However, the age–geographical risk for developing multiple sclerosis may span a larger timescale.

Even in regions where MS is common, some ethnic groups are at low risk of developing the disease, including the Samis, Turkmen, Amerindians, Canadian Hutterites, Africans, and New Zealand Maoris. Scotland appears to have one of the highest rates of MS in the world.

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).