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Multiple sclerosis – definition, epidemiology, history, causes

Multiple Sclerosis (MS) is a chronic, frequently progressive neurologic disease of the CNS of unknown etiology and uncertain trajectory. MS is characterized by the occurrence of small patches of demyelination of the white matter of the optic nerve, brain, and spinal cord. MS is characterized by exacerbations and remissions of symptoms over the course of the illness.


Multiple sclerosis (also known as disseminated sclerosis or encephalomyelitis disseminata) is an inflammatory  disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms.

MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other effectively. Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are contained within an insulating substance called myelin. In MS, the body’s own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals. The name multiple sclerosis refers to scars (scleroses—better known as plaques or lesions) particularly in the white matter of the brain and spinal cord, which is mainly composed of myelin.

MS was first described in 1868 by Jean Martin Charcot. MS is the most common CNS disease among young adults and the third leading cause of disability in the United States.


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 theories.

  • MS usually appears in adults in their thirties but it can also appear in children.
  • The primary progressive subtype is more common in people in their fifties.
  • The disorder is most commonly diagnosed between ages 20 and 40, but can be seen at any age.
  • As with many autoimmune disorders, the disease is more common in women, and the trend may be increasing.
  • In children, the sex ratio difference is higher; while in people over fifty, MS affects males and females almost equally.
  • 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 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. MS is also more common in regions with northern Europe populations.
  • 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 15, the migrant acquires the new region’s susceptibility to MS. If migration takes place after age 15, the migrant retains the susceptibility of his home country. However, the age–geographical risk for developing multiple sclerosis may span a larger timescale.
  • A relationship between season of birth and MS has also been found which lends support to an association with sunlight and vitamin D. For example fewer people with MS are born in November as compared to May.


  • The French neurologist Jean Martin Charcot (1825- 1893) was the first person to recognize multiple sclerosis as a distinct disease in 1868. Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of MS now known as Charcot’s triad 1 are nystagmus, intention tremor and telegraphic speech, though these are not unique to MS. Charcot also observed cognition changes, describing his patients as having a “marked enfeeblement of the memory” and “conceptions that formed slowly”.
  • Prior to Charcot, Robert Carswell (1793–1857), a British professor of pathology, and Jean Cruveilhier  (1791–1873), a French professor of pathologic anatomy, had described and illustrated many of the disease’s clinical details, but did not identify it as a separate disease. Specifically, Carswell described the injuries he found as “a remarkable lesion of the spinal cord accompanied with atrophy”.
  • Under the microscope, Swiss pathologist Georg Eduard Rindfleisch (1836–1908) noted in 1863 that the inflammation-associated lesions were distributed around blood vessels.
  • After Charcot’s description, Eugene Devic (1858–1930), Jozef Balo (1895–1979), Paul Ferdinand Schilder (1886–1940), and Otto Marburg (1874–1948) described special cases of the disease. During all the 20th century there was an important development on the theories about the cause and pathogenesis of MS while efficacious treatments began to appear in 1990.

Causes, incidence, and risk factors

It is unknown what exactly causes this to happen. The most common thought is that a virus or gene defect, or both, is to blame. Environmental factors may play a role.

You are slightly more likely to get this condition if you have a family history of MS or live in a part of the world where MS is more common.

Most likely MS occurs as a result of some combination of genetic, environmental and infectious factors, and possibly other factors like vascular problems. Theories try to combine the known data into plausible explanations, but none has proved definitive.


HLA region of Chromosome 6. Changes in this area increase the probability of suffering MS.

MS is not considered a hereditary disease. However, a number of genetic variations have been shown to increase the risk of developing the disease. The risk of acquiring MS is higher in relatives of a person with the disease than in the general population, especially in the case of siblings, parents, and children.

  • The disease has an overall familial recurrence rate of 20%.
  • In the case of monozygotic twins, concordance occurs only in about 35% of cases.
  • 5% in the case of siblings.
  • Even lower in half-siblings.

This indicates susceptibility is partly polygenically driven.

It seems to be more common in some ethnic groups than others. Apart from familial studies, specific genes have been linked with MS. Differences in the human leukocyte antigen (HLA) system—a group of genes in chromosome 6 that serves as the major histocompatibility complex (MHC) in humans—increase the probability of suffering MS. The most consistent finding is the association between multiple sclerosis and alleles of the MHC defined as DR15 and DQ6. Other loci have shown a protective effect, such as HLA-C554.

Environmental factors

Different environmental factors, both of infectious and non infectious origin have been proposed as risk factors for MS. Although some are partly modifiable, only further research—especially clinical trials—will reveal whether their elimination can help prevent MS.

  • MS is more common in people who live farther from the equator, although many exceptions exist. Decreased sunlight exposure has been linked with a higher risk of MS.
  • Decreased vitamin D production and intake has been the main biological mechanism used to explain the higher risk among those less exposed to sun.
  • Severe stress may also be a risk factor although evidence is weak.
  • Smoking has also been shown to be an independent risk factor for developing MS.
  • Association with occupational exposures and toxins has been evaluated, but no clear conclusions have been reached.
  • Vaccinations were also considered as causal factors for the disease; however, most studies show no association between MS and vaccines.
  • Several other possible risk factors, such as diet and hormone intake, have been investigated; however, evidence on their relation with the disease is “sparse and unpersuasive”.
  • Gout occurs less than would statistically be expected in people with MS, and low levels of uric acid have been found in MS patients as compared to normal individuals. This led to the theory that uric acid protects against MS, although its exact importance remains unknown.


Many microbes have been proposed as potential infectious triggers of MS, but none have been substantiated. Genetic susceptibility can explain some of the geographic and epidemiological variations in MS incidence, but does not account for other phenomena, such as the changes in risk that occur with migration at an early age. An explanation for this epidemiological finding could be that some kind of infection, produced by a widespread microbe rather than a rare pathogen, is the origin of the disease. Different hypotheses have elaborated on the mechanism by which this may occur.

  • The hygiene hypothesis proposes that exposure to several infectious agents early in life is protective against MS, the disease being a response to a later encounter with such agents.
  • The prevalence hypothesis proposes that the disease is due to a pathogen more common in regions of high MS prevalence. This pathogen is very common, causing in most individuals an asymptomatic persistent infection. Only in a few cases, and after many years since the original infection, does it cause demyelination.
  • The hygiene hypothesis has received more support than the prevalence hypothesis.

Evidence for viruses as a cause includes the presence of oligoclonal bands in the brain and cerebrospinal fluid of most patients, the association of several viruses with human demyelination encephalomyelitis, and induction of demyelination in animals through viral infection. Herpes Viruses are a candidate group of viruses linked to MS. Individuals who have never been infected by the Epstein Barr virus have a reduced risk of having the disease, and those infected as young adults have a greater risk than those who had it at a younger age. Although some consider that this goes against the hygiene hypothesis, since the non-infected have probably experienced a more hygienic upbringing, others believe that there is no contradiction since it is a first encounter at a later moment with the causative virus that is the trigger for the disease. Other diseases that have also been related with MS are measles, mumps and rubella.