Multiple sclerosis (MS) is a progressive, debilitating, immune-mediated, and eventually fatal neurodegenerative disorder where the myelin sheath – the insulating cover of all neurons — in the central nervous system (CNS) become damaged due to inflammation. The body’s immune system attacks the myelin (the fatty substance that surrounds and insulates the nerve fibers) when the T-cells cross the blood-brain barrier to attack the epitopes presented by the myelin sheath cells. As a result, many experts believe MS should more appropriately be termed an immune-mediated disease rather than an autoimmune disease, as the exact target of these T-cells and the cause of their behavior remains unknown.
This attack disturbs and progressively destroys the conduction of nerve impulses, leading to scarring and permanent damage to the myelin sheath and the nerve fibers, and resulting in severe neurodegenerative complications, such as impaired vision, loss of senses, loss of balance, loss of control over voluntary muscles, and all other bodily functions connected to the CNS. A classic hallmark of MS is the exacerbation or flare-ups of symptoms which occur repeatedly over months or years in the relapsing-remitting form of the disease.
Researchers are constantly seeking a cure for MS. Current medications treat symptoms and flare-ups, but do not guarantee long-term effects.
Proper diagnosis and a thorough check-up can help a physician zero in on the possibility of an MS diagnosis, along with with MRI and CSF testing to show typical scars or plaque in the brain considered to be the most definitive way to confirm multiple sclerosis. MS has the potential of causing severe damage in its initial phases of attacks, and the earlier the treatment starts, the more effective it is for the patient.
Since the condition is serious and progressive, there is an issue of emotional stress, as well. Clinicians have noted that it is very important that friends and family of MS patients provide as much support as possible. It is vital that MS patients maintain a healthy lifestyle to prevent additional flare-ups.
Epidemiology of Multiple Sclerosis
MS affects around 2 to 2.5 million people around the world; women are affected two or three times as often as men. It generally affects people between the ages 20 and 50. The average age of diagnosis of MS is 29 for women and 31 for men. According to data provided by the National Multiple Sclerosis Society, an estimated 400,000 people in the U.S. are affected by MS. But this is just an estimate, as the CDC does not require physicians in the U.S. to report new cases of MS, and the symptoms are also not pronounced during the initial stages. The prevalence estimate varies between 58 to 95 per 100,000 population.
It has been observed in epidemiologic studies that prevalence estimates of people with MS increase with latitude, implying that people living farthest from the equator (eg: Northern Europe) are more prone to MS than people living near the equator. However, there have been theories that defy this law of density gradient in estimating the prevalence. Proof in favor of this come from the fact that Parsis, Sardinians, and Palestinians are more susceptible to multiple sclerosis than in comparison to Chinese, Japanese, and African people. Migration also plays a key role in determining susceptibility. Immigrants moving to high-risk areas are more prone to being affected with MS. Apart from being most common in Caucasians, Latin Americans are also shown to have high chances of acquiring MS, according to independent studies.
There are a number of hypotheses for what contributes to development of MS, but the exact cause of the disease has not been deciphered by researchers yet. Etiological factors constitute a complex web of gender, ethnicity and heredity, with infectious diseases and environmental factors also playing roles as well.
It is observed in the U.S. population that people generally have a .1% chance of developing MS. Now, for a person with MS, his or her family members and all first degree familial connections are at an increased risk of developing MS. Siblings, children, and non-identical twins of this person are at 2-5% risk of developing MS, whereas identical twins (with the same set of genes as the patient) has a 25% chance of developing MS. This implies that the remaining 75% probability are an impact of geography, ethnicity and other environmental factors. In other words, it can be said that people with a genetic predisposition react to specific environmental factors which trigger the immune response against the CNS.
Another theory refers to polymorphisms and their effects in generation of immune response. Polymorphism refers to different forms of the same genes. They lead to encoding of different amounts of similar proteins and products. A single nucleotide polymorphism (SNP) might exist in a gene responsible for immune response (supposed to be the predisposing gene for MS) which leads to an alteration of the amount of product formed which might be so severe that it triggers an exaggerated immune response towards an antigen, leading to massive secretion of pro-inflammatory cytokines. This might lead to an automatic immune response towards the CNS. Research has been going on for some time to find a genetic connection in favour of MS. So far, the HLA-DRB1 gene of the Human Leukocyte Antigen (HLA) located on the human chromosome 6, has been linked to increased susceptibility to MS. Complementing it, studies have also hinted the role of the gene HLA-C*05 also located on the same chromosome, in conferring protection against MS.
Exposure to various viruses occurs in childhood. One such virus, the Epstein-Barr Virus (EBV) has been shown to cause demyelination and inflammation of nerve fibres. It is possible that the virus adopts molecular mimicry, and cross-reactivate the T-cells targeted against their viral epitope with those on the myelin sheath. This is why there is a huge influx of T-cells across the blood brain barrier. Again, these are all mere assumptions, as a number of other infectious agents have been assumed to have an impact on the development of MS and EBV is just one of them. It can also be said that the immunocompromised host affected by these viral infections is more susceptible to an immune mediated condition like MS.
Another observation from studies involving MS susceptibility suggests that immigrants, if moved to an area of higher incidence from a low risk area, later in life, then the chances of him or her developing MS remains low. It is only during early childhood, up to the age of 15 years (approximately) does the susceptibility to MS directly rely upon the risk associated with the area where he or she lives.
Vitamin D deficiencies have also been linked to the increased susceptibility to MS. Vitamin D is responsible for maintaining a balance between pro- and anti-inflammatory cytokines, with the down regulation of the former and the up regulation of the latter. Also, sunlight is an essential provider of vitamin D. This might explain why people living in higher latitudes with low incidence of sunlight, are more prone to developing MS than those living at lower latitudes (nearer to the equator) who have their vitamin D levels in check.
Smoking has also been attributed to increased susceptibility to MS. Smokers are at an increased risk of developing MS whereas if a person quits smoking even after the first incidence of symptomatic attacks, his chances of progressive MS are lowered.
Hence, it is seen that the factors believed to be responsible for development of MS are all interrelated, and interdependent, which paves way for an ambiguity in determining the independent roles of each etiologic agent.
Read more about multiple sclerosis symptoms.
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