system. lesions demyelination in ms: on klüver-barrera myelin staining, decoloration in the area of the lesion can be appreciated. the name multiple sclerosis refers to the scars (sclerae – better known as plaques or lesions) that form in the nervous system. these lesions most commonly affect the white matter in the optic nerve, brain stem, basal ganglia, and spinal cord, or white matter tracts close to the lateral ventricles. the function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of the body. the peripheral nervous system is rarely involved. to be specific, ms involves the loss of oligodendrocytes, the cells responsible for creating and maintaining a fatty layer—known as the myelin sheath—which helps the neurons carry electrical signals (action potentials). this results in a thinning or complete loss of myelin, and as the disease advances, the breakdown of the axons of neurons. when the myelin is lost, a neuron can no longer effectively conduct electrical signals. a repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell's myelin sheath. repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons. these scars are the origin of the symptoms and during an attack magnetic resonance imaging (mri) often shows more than 10 new plaques. this could indicate that some number of lesions exist, below which the brain is capable of repairing itself without producing noticeable consequences. another process involved in the creation of lesions is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons. a number of lesion patterns have been described. inflammation apart from demyelination, the other sign of the disease is inflammation. fitting with an immunological explanation, the inflammatory process is caused by t cells, a kind of lymphocytes that plays an important role in the body's defenses. t cells gain entry into the brain as a result of disruptions in the blood–brain barrier. the t cells recognize myelin as foreign and attack it, explaining why these cells are also called "autoreactive lymphocytes." the attack on myelin starts inflammatory processes, which trigger other immune cells and the release of soluble factors like cytokines and antibodies. a further breakdown of the blood-brain barrier, in turn, causes a number of other damaging effects, such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins. inflammation can potentially reduce transmission of information between neurons in at least three ways. the soluble factors released might stop neurotransmission by intact neurons. these factors could lead to or enhance the loss of myelin, or they may cause the axon to break down completely. blood–brain barrier the blood–brain barrier (bbb) is a part of the capillary system that prevents the entry of t cells into the central nervous system. it may become permeable to these types of cells secondary to an infection by a virus or bacteria. after it repairs itself, typically once the infection has cleared, t cells may remain trapped inside the brain. gadolinium cannot cross a normal bbb, so gadolinium-enhanced mri is used to show bbb breakdowns. diagnosis main article: multiple sclerosis diagnosis animation showing dissemination of brain lesions in time and space as demonstrated by monthly mri studies along a year multiple sclerosis as seen on mri multiple sclerosis is typically diagnosed based on the presenting signs and symptoms, in combination with supporting medical imaging and laboratory testing. it can be difficult to confirm, especially early on, since the signs and symptoms may be similar to those of other medical problems. the mcdonald criteria, which focus on clinical, laboratory, and radiologic evidence of lesions at different times and in different areas, is the most commonly used method of diagnosis with the schumacher and poser criteria being of mostly historical significance. as of 2017, no single test (including biopsy) can provide a definitive diagnosis. magnetic resonance imaging (mri) of the brain and spine may show areas of demyelination (lesions or plaques). gadolinium can be administered intravenously as a contrast agent to highlight active plaques, and by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation. central vein signs (cvss) have been proposed as a good indicator of ms in comparison with other conditions causing white lesions. one small study found fewer cvss in older and hypertensive people. further research on cvs as a biomarker for ms is ongoing. brain atrophy is seen as an indicator of ms. testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation in the central nervous system. the cerebrospinal fluid is tested for oligoclonal bands of igg on electrophoresis, which are inflammation markers found in 75–85% of people with ms. differential diagnosis several diseases present similarly to ms. medical professionals use a patient's specific presentation, history, and exam findings to make an individualized differential. red flags are findings that suggest an alternate diagnosis, although they do not rule out ms. red flags include a patient younger than 15 or older than 60, less than 24 hours of symptoms, involvement of multiple cranial nerves, involvement of organs outside of the nervous system, and atypical lab and exam findings. in an emergency setting, it is important to rule out a stroke or bleeding in the brain. intractable vomiting, severe optic neuritis, or bilateral optic neuritis raises suspicion for neuromyelitis optica spectrum disorder (nmosd). infectious diseases that may look similar to multiple sclerosis include hiv, lyme disease, and syphilis. autoimmune diseases include sarcoidosis, lupus, guillain-barré syndrome, acute disseminated encephalomyelitis, and behçet's disease. psychiatric conditions such as anxiety or conversion disorder may also present in a similar way. other rare diseases on the differential include cns lymphoma, congenital leukodystrophies, and anti-mog-associated myelitis. types and variants several phenotypes (commonly termed "types"), or patterns of progression, have been described. phenotypes use the past course of the disease in an attempt to predict the future course. they are important not only for prognosis, but also for treatment decisions. the international advisory committee on clinical trials of ms describes four types of ms (revised in 2013) in what is known as the lublin classification: clinically isolated syndrome (cis) relapsing-remitting ms (rrms) primary progressive ms (ppms) secondary progressive ms (spms) rrms is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. deficits that occur during attacks may either resolve or leave problems, the latter in about 40% of attacks and being more common the longer a person has had the disease. this describes the initial course of 80% of individuals with ms. the relapsing-remitting subtype usually begins with a clinically isolated syndrome (cis). in cis, a person has an attack suggestive of demyelination, but does not fulfill the criteria for multiple sclerosis. 30 to 70% of persons who experience cis, later develop ms. ppms occurs in roughly 10–20% of individuals with the disease, with no remission after the initial symptoms. it is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements. the usual age of onset for the primary progressive subtype is later than of the relapsing-remitting subtype. it is similar to the age that secondary progressive usually begins in rrms, around 40 years of age. spms occurs in around 65% of those with initial rrms, who eventually have progressive neurologic decline between acute attacks without any definite periods of remission. occasional relapses and minor remissions may appear. the most common length of time between disease onset and conversion from rrms to spms is 19 years. special courses independently of the types published by the ms associations, regulatory agencies such as the fda often consider special courses, trying to reflect some clinical trials results on their approval documents. some examples could be "highly active ms" (hams), "active secondary ms" (similar to the old progressive-relapsing) and "rapidly progressing ppms". also, deficits always resolving between attacks is sometimes referred to as "benign" ms, although people still build up some degree of disability in the long term. on the other hand, the term malignant multiple sclerosis is used to describe people with ms having reached significant level of disability in a short period. an international panel has published a standardized definition for the course hams. variants atypical variants of ms have been described; these include tumefactive multiple sclerosis, balo concentric sclerosis, schilder's diffuse sclerosis, and marburg multiple sclerosis. debate remains on whether they are ms variants or different diseases. some diseases previously considered ms variants, such as devic's disease, are now considered outside the ms spectrum. management main article: management of multiple sclerosis although no cure for multiple sclerosis has been found, several therapies have proven helpful. several effective treatments can decrease the number of attacks and the rate of progression. the primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. starting medications is generally recommended in people after the first attack when more than two lesions are seen on mri. the first approved medications used to treat ms were modestly effective, though were poorly tolerated and had many adverse effects. several treatment options with better safety and tolerability profiles have been introduced, improving the prognosis of ms. 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 of efficacy. initial management of acute flare 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 effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery. the long-term benefit is unclear in optic neuritis as of 2020. the consequences of severe attacks that do not respond to corticosteroids might be treatable by plasmapheresis. relapsing remitting multiple sclerosis multiple disease-modifying medications were approved by regulatory agencies for rrms; they are modestly effective at decreasing the number of attacks. interferons and glatiramer acetate are first-line treatments and are roughly equivalent, reducing relapses by approximately 30%. early-initiated long-term therapy is safe and improves outcomes. treatment of cis with interferons decreases the chance of progressing to clinical ms. efficacy of interferons and glatiramer acetate in children has been estimated to be roughly equivalent to that of adults. the role of some newer agents such as fingolimod, teriflunomide, and dimethyl fumarate, is not yet entirely clear. making firm conclusions about the best treatment is difficult, especially regarding the long‐term benefit and safety of early treatment, given the lack of studies directly comparing disease-modifying therapies or long-term monitoring of patient outcomes. the relative effectiveness of different treatments is unclear, as most have only been compared to placebo or a small number of other therapies. direct comparisons of interferons and glatiramer acetate indicate similar effects or only small differences in effects on relapse rate, disease progression, and mri measures. alemtuzumab, natalizumab, and fingolimod may be more effective than other drugs in reducing relapses over the short term in people with rrms. natalizumab and interferon beta-1a (rebif) may reduce relapses compared to both placebo and interferon beta-1a (avonex) while interferon beta-1b (betaseron), glatiramer acetate, and mitoxantrone may also prevent relapses. evidence on relative effectiveness in reducing disability progression is unclear. all medications are associated with adverse effects that may influence their risk to benefit profiles. ublituximab was approved for medical use in the united states in december 2022. progressive multiple sclerosis in 2011, mitoxantrone was the first medication approved for secondary progressive ms. in this population, tentative evidence supports mitoxantrone moderately slowing the progression of the disease and decreasing rates of relapses over two years. new approved medications continue to emerge in modern medicine. in march 2017, the fda approved ocrelizumab as a treatment for primary progressive ms in adults, the first drug to gain that approval, with requirements for several phase iv clinical trials. it is also used for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. according to