multiple sclerosis multiple sclerosis multiple sclerosis (ms) is the most common 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 transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. specific symptoms can include double vision, visual loss, muscle weakness, and trouble with sensation or coordination. ms takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). in the relapsing forms of ms, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances. multiple sclerosisother namesmultiple cerebral sclerosis, multiple cerebro-spinal sclerosis, disseminated sclerosis, encephalomyelitis disseminatacd68-stained tissue shows several macrophages in the area of a demyelinated lesion caused by ms.specialtyneurologysymptomsvariable, including almost any neurological symptom or sign, with autonomic, visual, motor, and sensory problems being the most common.usual onsetage 20–50durationlong termcausesunknowndiagnostic methodbased on symptoms and medical teststreatmentdisease-modifying therapies physiotherapy occupational therapyfrequency0.032% (world) while the cause is unclear, 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 viral infections. ms is usually diagnosed based on the presenting signs and symptoms and the results of supporting medical tests. no cure for multiple sclerosis is known. treatments attempt to improve function after an attack and prevent new attacks. physical therapy and occupational therapy can help with people's ability to function. many people pursue alternative treatments, despite a lack of evidence of benefit. the long-term outcome is difficult to predict; better outcomes are 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. multiple sclerosis is the most common immune-mediated disorder affecting the central nervous system. nearly one million people have ms in the united states in 2022, and in 2020, about 2.8 million people were affected globally, with rates varying widely in different regions and among different populations. the disease usually begins between the ages of 20 and 50 and is twice as common in women as in men. ms was first described in 1868 by french neurologist jean-martin charcot. the name "multiple sclerosis" is short for multiple cerebro-spinal sclerosis, which refers to the numerous glial scars (or sclerae – essentially plaques or lesions) that develop on the white matter of the brain and spinal cord. signs and symptoms main article: multiple sclerosis signs and symptoms main symptoms of multiple sclerosis 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, blurred vision, pronounced reflexes, muscle spasms, 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 (such as neurogenic bladder), among others. when multiple sclerosis is more advanced, walking difficulties can occur and the risk of falling increases. difficulties thinking and emotional problems such as depression or unstable mood are also common. the primary deficit in cognitive function that people with ms experience is slowed information-processing speed, with memory also commonly affected, and executive function less commonly. intelligence, language, and semantic memory are usually preserved, and the level of cognitive impairment varies considerably between people with ms. 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. edss is also correlated with falls in people with ms. while it is a popular measure, edss has been criticized for some of its limitations, such as relying too much on walking. the condition begins in 85% of cases as a clinically isolated syndrome (cis) 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. 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 been found not to affect relapse rates including vaccination, breast feeding, physical trauma, and uhthoff's phenomenon. prodromal phase ms may have a prodromal phase in the years leading up to ms manifestation, characterized by psychiatric issues, cognitive impairment, and increased use of healthcare. causes the cause of ms is unknown, but it is believed to occur as a result of some combination of genetic and environmental factors, such as infectious agents. infectious agents many microbes have been proposed as triggers of ms. one hypothesis is that infection by a widespread microbe contributes to disease development, and the geographic distribution of this organism influences the epidemiology of ms. two opposing versions of this hypothesis include the hygiene hypothesis and the prevalence hypothesis, the former being more favored. the hygiene hypothesis proposes that exposure to certain infectious agents early in life is protective; the disease is a response to a late encounter with such agents. the prevalence hypothesis proposes that an early, persistent, and silent infection increases risk of disease, thus the disease is more common where the infectious agent is more common. only in a few cases and after many years does it cause demyelination. 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 demyelinating encephalomyelitis, and the occurrence of demyelination in animals caused by some viral infections. epstein-barr herpes virus (ebv) can cause infectious mononucleosis and infects about 95% of adults. in combination with other genetic and environmental factors, there is "compelling epidemiological and mechanistic evidence for a causal role of ebv in multiple sclerosis", though only a small proportion of those infected with ebv later develop ms. a study of individuals in the united states military between 1993 and 2013 (total population greater than 10 million) compared 801 people who developed ms on or after military service to 1,566 matched controls who did not develop ms during this observation period. the study found a 32-fold increased risk of developing ms after infection with ebv. it did not find an increased risk after infection with other viruses, including the similarly transmitted cytomegalovirus. the finding strongly suggests that ebv plays a role in the onset of ms, although ebv alone may be insufficient to cause it. genetics hla region of chromosome 6: changes in this area increase the probability of getting ms. ms is not considered a hereditary disease, but several genetic variations have been shown to increase the risk. some of these genes appear to have higher levels of expression in microglial cells than expected by chance. the probability of developing the disease is higher in relatives of an affected person, with a greater risk among those more closely related. an identical twin of an affected individual has a 30% chance of developing ms, 5% for a nonidentical twin, 2.5% for a sibling, and an even lower chance for a half sibling. 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 differences in the hla region are related to susceptibility has been known since the 1980s, and this same region has also 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. hla differences account for an estimated 20 to 60% of the genetic predisposition. modern genetic methods (genome-wide association studies) have revealed at least 200 variants outside the hla locus that modestly increase the probability of 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 and that live far from the equator such as the sami, amerindians, canadian hutterites, new zealand māori, and canada's inuit, as well as groups that have a relatively high risk and that live closer to the equator such as sardinians, inland sicilians, palestinians, and parsi. 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, so the geographic variation may simply reflect the global distribution of these high-risk populations. a relationship between season of birth and ms lends support to this idea, with fewer people born in the northern hemisphere in november 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 of ms. if migration takes place after age 15, the persons retain the risk of their home country. some evidence indicates that the effect of moving may still apply to people older than 15. other smoking may 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 organic solvents—has been evaluated, but no clear conclusions have been reached. vaccinations were studied as causal factors; most studies, though, show no association. several other possible risk factors, such as diet and hormone intake, have been evaluated, but 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. obesity during adolescence and young adulthood is a risk factor for ms. pathophysiology main article: pathophysiology of multiple sclerosis multiple sclerosis the three main characteristics of ms are the formation of lesions in the central nervous system (also called plaques), inflammation, and the destruction of myelin sheaths of neurons. these features interact in a complex and not yet fully understood manner to produce the breakdown of nerve tissue, and in turn, the signs and symptoms of the disease. cholesterol crystals are believed both to impair myelin repair and aggravate inflammation. ms is believed to be an immune-mediated disorder that develops from an interaction of the individual's genetics and as yet unidentified environmental causes. damage is believed to be caused, at least in part, by attack on the nervous system by a person's own immune