Multiple Sclerosis

Condition

Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminata, is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a wide range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may disappear completely; however, permanent neurological problems often occur, especially as the disease advances.

While the cause is not clear, the underlying mechanism is thought to be either destruction by the immune system or failure of the myelin-producing cells. Proposed causes for this include genetics and environmental factors such as infections. MS is usually diagnosed based on the presenting signs and symptoms and the results of supporting medical tests.

There is no known cure for multiple sclerosis. Treatments attempt to improve function after an attack and prevent new attacks. Medications used to treat MS, while modestly effective, can have adverse effects and be poorly tolerated. Many people pursue alternative treatments, despite a lack of evidence. The long-term outcome is difficult to predict, with good outcomes more often seen in women, those who develop the disease early in life, those with a relapsing course, and those who initially experienced few attacks. Life expectancy is on average 5 to 10 years lower than that of an unaffected population.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. As of 2008, between 2 and 2.5 million people are affected globally with rates varying widely in different regions of the world and among different populations. In 2013, 20,000 people died worldwide from MS, up from 12,000 in 1990. The disease usually begins between the ages of 20 and 50 and is twice as common in women as in men. The name multiple sclerosis refers to scars (sclerae—better known as plaques or lesions) in particular in the white matter of the brain and spinal cord. MS was first described in 1868 by Jean-Martin Charcot. A number of new treatments and diagnostic methods are under development.
Definitions

Signs

A person with MS can have almost any neurological symptom or sign, with autonomic, visual, motor, and sensory problems being the most common. The specific symptoms are determined by the locations of the lesions within the nervous system, and may include loss of sensitivity or changes in sensation such as tingling, pins and needles or numbness, muscle weakness, very pronounced reflexes, muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems with speech or swallowing, visual problems (nystagmus, optic neuritis or double vision), feeling tired, acute or chronic pain, and bladder and bowel difficulties, among others. Difficulties thinking and emotional problems such as depression or unstable mood are also common. Uhthoff’s phenomenon, a worsening of symptoms due to exposure to higher than usual temperatures, and Lhermitte’s sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS. The main measure of disability and severity is the expanded disability status scale (EDSS), with other measures such as the multiple sclerosis functional composite being increasingly used in research.

The condition begins in 85% of cases as a clinically isolated syndrome over a number of days with 45% having motor or sensory problems, 20% having optic neuritis, and 10% having symptoms related to brainstem dysfunction, while the remaining 25% have more than one of the previous difficulties.[16] The course of symptoms occurs in two main patterns initially: either as episodes of sudden worsening that last a few days to months (called relapses, exacerbations, bouts, attacks, or flare-ups) followed by improvement (85% of cases) or as a gradual worsening over time without periods of recovery (10-15% of cases). A combination of these two patterns may also occur or people may start in a relapsing and remitting course that then becomes progressive later on. Relapses are usually not predictable, occurring without warning. Exacerbations rarely occur more frequently than twice per year. Some relapses, however, are preceded by common triggers and they occur more frequently during spring and summer. Similarly, viral infections such as the common cold, influenza, or gastroenteritis increase their risk. Stress may also trigger an attack. Women with MS who become pregnant experience fewer relapses; however, during the first months after delivery the risk increases. Overall, pregnancy does not seem to influence long-term disability. Many events have not been found to affect relapse rates including vaccination, breast feeding, physical trauma, and Uhthoff’s phenomenon.

Causes

The cause of MS is unknown; however, it is believed to occur as a result of some combination of genetic and environmental factors such as infectious agents. Theories try to combine the data into likely explanations, but none has proved definitive. While there are a number of environmental risk factors and although some are partly modifiable, further research is needed to determine whether their elimination can prevent MS.

Geography
MS is more common in people who live farther from the equator, although exceptions exist. These exceptions include ethnic groups that are at low risk far from the equator such as the Samis, Amerindians, Canadian Hutterites, New Zealand Māori, and Canada’s Inuit, as well as groups that have a relatively high risk close to the equator such as Sardinians, inland Sicilians, Palestinians and Parsis. The cause of this geographical pattern is not clear. While the north-south gradient of incidence is decreasing, as of 2010 it is still present.

MS is more common in regions with northern European populations and the geographic variation may simply reflect the global distribution of these high-risk populations. Decreased sunlight exposure resulting in decreased vitamin D production has also been put forward as an explanation. A relationship between season of birth and MS lends support to this idea, with fewer people born in the northern hemisphere in November as compared to May being affected later in life. Environmental factors may play a role during childhood, with several studies finding that people who move to a different region of the world before the age of 15 acquire the new region’s risk to MS. If migration takes place after age 15, however, the person retains the risk of his home country. There is some evidence that the effect of moving may still apply to people older than 15.

Genetics

HLA region of Chromosome 6. Changes in this area increase the probability of getting MS.
MS is not considered a hereditary disease; however, a number of genetic variations have been shown to increase the risk. The probability is higher in relatives of an affected person, with a greater risk among those more closely related. In identical twins both are affected about 30% of the time, while around 5% for non-identical twins and 2.5% of siblings are affected with a lower percentage of half-siblings. If both parents are affected the risk in their children is 10 times that of the general population. MS is also more common in some ethnic groups than others.

Specific genes that have been linked with MS include differences in the human leukocyte antigen (HLA) system—a group of genes on chromosome 6 that serves as the major histocompatibility complex (MHC). That changes in the HLA region are related to susceptibility has been known since the 1980s, and additionally this same region has been implicated in the development of other autoimmune diseases such as diabetes type I and systemic lupus erythematosus. 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 and HLA-DRB1*11. Overall, it has been estimated that HLA changes account for between 20 and 60% of the genetic predisposition. Modern genetic methods (genome-wide association studies) have discovered at least twelve other genes outside the HLA locus that modestly increase the probability of MS.

Infectious agents
Many microbes have been proposed as triggers of MS, but none have been confirmed. Moving at an early age from one location in the world to another alters a person’s subsequent risk of MS.An explanation for this could be that some kind of infection, produced by a widespread microbe rather than a rare one, is related to the disease. Proposed mechanisms include the hygiene hypothesis and the prevalence hypothesis. The hygiene hypothesis proposes that exposure to certain infectious agents early in life is protective, the disease being a response to a late encounter with such agents. The prevalence hypothesis proposes that the disease is due to an infectious agent more common in regions where MS is common and where in most individuals it causes an ongoing infection without symptoms. Only in a few cases and after many years does it cause demyelination. The hygiene hypothesis has received more support than the prevalence hypothesis.

Evidence for a virus as a cause include: the presence of oligoclonal bands in the brain and cerebrospinal fluid of most people with MS, the association of several viruses with human demyelination encephalomyelitis, and the occurrence of demyelination in animals caused by some viral infection. Human herpes viruses are a candidate group of viruses. Individuals having never been infected by the Epstein–Barr virus are at a reduced risk of getting MS, whereas those infected as young adults are at a greater risk than those having 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 with the causative virus relatively late in life that is the trigger for the disease. Other diseases that may be related include measles, mumps and rubella.

Other
Smoking has been shown to be an independent risk factor for MS. Stress may be a risk factor although the evidence to support this is weak. Association with occupational exposures and toxins—mainly solvents—has been evaluated, but no clear conclusions have been reached. Vaccinations were studied as causal factors; however, most studies show no association. Several other possible risk factors, such as diet and hormone intake, have been looked at; however, evidence on their relation with the disease is “sparse and unpersuasive”. Gout occurs less than would be expected and lower levels of uric acid have been found in people with MS. This has led to the theory that uric acid is protective, although its exact importance remains unknown.

Management

Although there is no known cure for multiple sclerosis, several therapies have proven helpful. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of MS have several adverse effects. Alternative treatments are pursued by some people, despite the shortage of supporting evidence.

Acute attacks
During symptomatic attacks, administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the usual therapy, with oral corticosteroids seeming to have a similar efficacy and safety profile Although, in general, effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery.[54] The consequences of severe attacks that do not respond to corticosteroids might be treatable by plasmapheresis.

Alternative treatments
Over 50% of people with MS may use complementary and alternative medicine, although percentages vary depending on how alternative medicine is defined.[84] The evidence for the effectiveness for such treatments in most cases is weak or absent. Treatments of unproven benefit used by people with MS include dietary supplementation and regimens, vitamin D, relaxation techniques such as yoga,[84] herbal medicine (including medical cannabis), hyperbaric oxygen therapy,[90] self-infection with hookworms, reflexology, and acupuncture. Regarding the characteristics of users, they are more frequently women, have had MS for a longer time, tend to be more disabled and have lower levels of satisfaction with conventional healthcare.

Source: Wikipedia

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Risa Ravitz, MD
Neurology / Pain Medicine

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