Multiple Sclerosis (MS) is the most common disabling neurological disease of young adults with symptom onset generally occurring between the ages of 20 to 40 years. In MS, the immune system cells that normally protect us from viruses, bacteria, and unhealthy cells mistakenly attack myelin in the central nervous system (brain, optic nerves, and spinal cord), a substance that makes up the protective sheath (called the myelin sheath) that coats nerve fibers (axons).

MS is a chronic disease that affects people differently. A small number of those with MS will have a mild course with little to no disability, whereas others will have a steadily worsening disease that leads to increased disability over time. Most people with MS, however, will have short periods of symptoms followed by long stretches of relative quiescence (inactivity or dormancy), with partial or full recovery. Women are affected more frequently with MS compared to men. The disease is rarely fatal and most people with MS have a normal life expectancy. New treatments can reduce long-term disability for many people with MS. Currently there are still no cures and no clear ways to prevent the disease from developing.

Myelin and the immune system

MS attacks axons in the central nervous system protected by myelin, which are commonly called white matter. MS also damages the nerve cell bodies, which are found in the brain’s gray matter, as well as the axons themselves in the brain, spinal cord, and optic nerves that transmit visual information from the eye to the brain. As the disease progresses, the outermost layer of the brain, called the cerebral cortex, shrinks (what is known as cortical atrophy).

The term multiple sclerosis refers to the distinctive areas of scar tissue (sclerosis—also called plaques or lesions) that result from the attack on myelin by the immune system. These plaques are visible using magnetic resonance imaging in the white and/or gray matter of people who have MS. Plaques can be as small as a pinhead or as large as a golf ball.

During an MS exacerbation, most of the myelin, and to a lesser extent the axons within the affected area, is damaged or destroyed by different types of immune cells (also known as inflammation). The symptoms of MS depend on the severity of the inflammatory reaction as well as the location and extent of the plaques, which primarily appear in the brain stem, cerebellum (involved with balance and coordination of movement, among other functions), spinal cord, optic nerves, and the white matter around the brain ventricles (fluid-filled spaces).

Multiple sclerosis is a condition characterized by areas of damage (lesions) on the brain and spinal cord. These lesions are associated with destruction of the covering that protects nerves and promotes the efficient transmission of nerve impulses (the myelin sheath) and damage to nerve cells. Multiple sclerosis is considered an autoimmune disorder; autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs, in this case tissues of the nervous system.

Multiple sclerosis usually begins in early adulthood, between ages 20 and 40. The symptoms vary widely, and affected individuals can experience one or more effects of nervous system damage. Multiple sclerosis often causes sensory disturbances in the limbs, including a prickling or tingling sensation (paresthesia), numbness, pain, and itching. Some people experience Lhermitte sign, which is an electrical shock-like sensation that runs down the back and into the limbs. This sensation usually occurs when the head is bent forward. Problems with muscle control are common in people with multiple sclerosis. Affected individuals may have tremors, muscle stiffness (spasticity), exaggerated reflexes (hyperreflexia), weakness or partial paralysis of the muscles of the limbs, difficulty walking, or poor bladder control. Multiple sclerosis is also associated with vision problems, such as blurred or double vision or partial or complete vision loss. Infections that cause fever can make the symptoms worse.

There are several forms of multiple sclerosis: relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive relapsing MS. The most common is the relapsing-remitting form, which affects approximately 80 percent of people with multiple sclerosis. Individuals with this form of the condition have periods during which they experience symptoms, called clinical attacks, followed by periods without any symptoms (remission). The triggers of clinical attacks and remissions are unknown. After about 10 years, relapsing-remitting MS usually develops into another form of the disorder called secondary progressive MS. In this form, there are no remissions, and symptoms of the condition continually worsen.

Primary progressive MS is the next most common form, affecting approximately 10 to 20 percent of people with multiple sclerosis. This form is characterized by constant symptoms that worsen over time, with no clinical attacks or remissions. Primary progressive MS typically begins later than the other forms, around age 40.

Progressive relapsing MS is a rare form of multiple sclerosis that initially appears like primary progressive MS, with constant symptoms. However, people with progressive relapsing MS also experience clinical attacks of more severe symptoms.

An estimated 1.1 to 2.5 million people worldwide have multiple sclerosis. Although the reason is unclear, this condition is more common in regions that are farther away from the equator. In Canada, parts of the northern United States, western and northern Europe, Russia, and southeastern Australia, the condition affects approximately 1 in 2,000 to 2,400 people. It is less common closer to the equator, such as in Asia, sub-Saharan Africa, and parts of South America, where about 1 in 20,000 people are affected. For unknown reasons, most forms of multiple sclerosis affect women twice as often as men; however, women and men are equally affected by primary progressive MS.

What is it?

Multiple sclerosis (MS) is a nervous system disease that affects the brain, optic nerve (which helps you see), and spinal cord. The immune system attacks myelin—the coating on nerve fibers—and makes it harder for those cells to send signals across the body. The exact cause of MS is unknown, but it’s linked to a number of infectious diseases like the Epstein-Barr virus, which can cause the disease commonly experienced by teenagers or young adults known as mononucleosis or mono. Environmental factors like low levels of vitamin D and genetic factors also play a role. People typically experience their first symptoms between ages 20 and 40.

Symptoms of an MS attack develop and peak within a few days, and then slowly resolve over the next several days or weeks. In the early stages of the disease, symptom attacks happen about once a year. As the disease progresses, symptoms can arrive more frequently, and resolve less completely. MS is different for everyone, and in its most severe forms it can impair walking or standing, and it can even lead to partial or complete inability to move.

Symptoms and diagnosis

Different people have different experiences with MS. Some cases can be less severe, and others can be disabling. Symptoms can include:

• Double vision
• Blurred vision or blindness in one eye
• Colors look different
• Muscle weakness
• Dizziness
• Difficulty with balance
• Numbness, prickling, or a “pins and needles” sensation
• Pain
• Tremors

Many people experience mental symptoms as well, such as:

• Difficulty speaking
• Impaired concentration, attention, and memory
• Depression

Because MS has so many different symptoms, it can be difficult to diagnose. People with MS might be diagnosed soon after developing symptoms, while others might spend years with confusing symptoms and multiple diagnoses. An MRI to look for scars in the brain and spine can help medical professionals make an accurate diagnosis.

Treatment

There is currently no cure for MS. Treatment plans depend on the severity of the disease and can include:

• Steroids to improve symptoms of an attack
• FDA-approved drugs that reduce the number of relapses, change how the body responds to inflammation, and improve mobility
• Muscle relaxants and tranquilizers that reduce stiffness
• Drugs that decrease fatigue

Multiple sclerosis by the numbers

• 2.5 million—The number of people worldwide with MS
• 60 percent—The amount of people with MS who can walk without assistance
• 1878—The year MS was first recognized as a specific disease in the United States
• 300 percent—How much more likely it is for women to develop MS compared to men

Researchers are looking at several possible explanations for why the immune system attacks central nervous system myelin, including:

• Fighting an infectious agent (for example, a virus) that has components that mimic components of the brain (called molecular mimicry)
• Destroying brain cells because they are unhealthy
• Mistakenly identifying normal brain cells as foreign

There is also something known as the blood-brain barrier, which separates the brain and spinal cord from the immune system. If there is a break in this barrier, it exposes the brain to the immune system. When this happens, the immune system may misinterpret structures in the brain, such as myelin, as “foreign.”

Research shows that genetic vulnerabilities combined with environmental factors may cause MS.

Genetic susceptibility

MS itself is not inherited, but susceptibility to MS may be inherited. Studies show that some individuals with MS have one or more family member or relative who also have MS.

Current research suggests that dozens of genes and possibly hundreds of variations in the genetic code (called gene variants) combine to create vulnerability to MS. Some of these genes have been identified, and most are associated with functions of the immune system. Many of the known genes are similar to those that have been identified in people with other autoimmune diseases as type 1 diabetes, rheumatoid arthritis, or lupus.

Infectious factors and viruses

Several viruses have been found in people with MS, but the virus most consistently linked to the development of MS is the Epstein-Barr virus (EBV) which causes infectious mononucleosis.

Only about 5 percent of the population has notbeen infected by EBV. These individuals are at a lower risk for developing MS than those who have been infected. People who were infected with EBV in adolescence or adulthood and who therefore develop an exaggerated immune response to EBV are at a significantly higher risk for developing MS than those who were infected in early childhood. This suggests that it may be the type of immune response to EBV that may lead to MS, rather than EBV infection itself. However, there is still no proof that EBV causes MS and the mechanisms that underlie this process are poorly understood.

Environmental factors

Several studies indicate that people who spend more time in the sun and those with relatively higher levels of vitamin D are less likely to develop MS or have a less severe course of disease and fewer relapses. Bright sunlight helps human skin produce vitamin D. Researchers believe that vitamin D may help regulate the immune system in ways that reduce the risk of MS or autoimmunity in general. People from regions near the equator, where there is a great deal of bright sunlight, generally have a much lower risk of MS than people from temperate areas such as the United States and Canada.

Studies have found that people who smoke are more likely to develop MS and have a more aggressive disease course. Indeed, People who smoke tend to have more brain lesions and brain shrinkage than non-smokers. The reasons for this are currently unclear.

Normal Function

The CYP27B1 gene provides instructions for making an enzyme called 1-alpha-hydroxylase (1α-hydroxylase). This enzyme carries out the second of two reactions to convert vitamin D to its active form, 1,25-dihydroxyvitamin D3, also known as calcitriol. Vitamin D can be acquired from foods in the diet or can be made in the body with the help of sunlight exposure. When active, this vitamin is involved in maintaining the proper balance of several minerals in the body, including calcium and phosphate, which are essential for the normal formation of bones and teeth. One of vitamin D's major roles is to control the absorption of calcium and phosphate from the intestines into the bloodstream. Vitamin D is also involved in several processes unrelated to bone and tooth formation.

Health Conditions Related to Genetic Changes

Vitamin D-dependent rickets

At least 70 mutations in the CYP27B1 gene have been found to cause vitamin D-dependent rickets type 1A (VDDR1A), also known as vitamin D 1α-hydroxylase deficiency. This disorder of bone development is characterized by low levels of calcium (hypocalcemia) and phosphate (hypophosphatemia) in the blood, which lead to soft, weak bones that are prone to fracture. A common feature of this condition is abnormally curved (bowed) legs.

The CYP27B1 gene mutations that cause this condition reduce or eliminate the function of 1α-hydroxylase. As a result, vitamin D does not get converted to its active form and cannot control mineral absorption. The resulting reduction in calcium and phosphate absorption from the intestines into the blood means there is less of these minerals to be deposited in developing bones (bone mineralization), which leads to soft, weak bones and other features of VDDR1A. Hypocalcemia also causes muscle weakness and seizures in some affected individuals.

Autoimmune Addison disease

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Multiple sclerosis

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Other Names for This Gene

• 1alpha(OH)ase
• 25 hydroxyvitamin D3-1-alpha hydroxylase
• 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
• 25-OHD-1 alpha-hydroxylase
• CYP1alpha
• CYP27B
• cytochrome p450 27B1
• cytochrome P450 subfamily XXVIIB polypeptide 1
• cytochrome P450, family 27, subfamily B, polypeptide 1
• cytochrome P450C1 alpha
• cytochrome P450VD1-alpha
• P450c1
• VD3 1A hydroxylase

Genomic Location

Normal Function

The HLA-DRB1 gene provides instructions for making a protein that plays a critical role in the immune system. The HLA-DRB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.

The HLA complex is the human version of the major histocompatibility complex (MHC), a gene family that occurs in many species. The HLA-DRB1 gene belongs to a group of MHC genes called MHC class II. MHC class II genes provide instructions for making proteins that are present on the surface of certain immune system cells. These proteins attach to protein fragments (peptides) outside the cell. MHC class II proteins display these peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it triggers a response to attack the invading viruses or bacteria.

The protein produced from the HLA-DRB1 gene, called the beta chain, attaches (binds) to another protein called the alpha chain, which is produced from the HLA-DRA gene. Together, they form a functional protein complex called the HLA-DR antigen-binding heterodimer. This complex displays foreign peptides to the immune system to trigger the body's immune response.

Each MHC class II gene has many possible variations, allowing the immune system to react to a wide range of foreign invaders. Researchers have identified hundreds of different versions (alleles) of the HLA-DRB1 gene, each of which is given a particular number (such as HLA-DRB1*04:01).

Health Conditions Related to Genetic Changes

Alopecia areata

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Autoimmune Addison disease

Certain variations in the HLA-DRB1 gene have been linked to an increased risk of developing an autoimmune disorder called autoimmune Addison disease. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. In autoimmune Addison disease, the immune system attacks the adrenal glands, which are small hormone-producing glands located on top of each kidney. Loss of hormones produced by the adrenal glands leads to the features of the condition, which include extreme tiredness (fatigue), nausea, low blood pressure (hypotension), and abnormally dark areas of skin (hyperpigmentation), especially in regions that experience a lot of friction such as the armpits, elbows, and knuckles. A particular HLA-DRB1 gene variant called HLA-DRB1*04:04 is the most well-known risk factor for autoimmune Addison disease.

Normally, the immune system responds only to proteins made by foreign invaders, not to the body's own proteins. In autoimmune Addison disease, however, an immune response is triggered by a normal adrenal gland protein; in about 85 percent of people with autoimmune Addison disease, the protein is 21-hydroxylase. 21-hydroxylase is found in the adrenal glands where it plays a key role in producing a variety of hormones that regulate many essential functions in the body. The prolonged immune attack triggered by 21-hydroxylase damages the adrenal glands (specifically the outer layers of the glands known, collectively, as the adrenal cortex), preventing hormone production. A shortage of adrenal hormones (adrenal insufficiency) disrupts several normal functions in the body, leading to the diverse features of autoimmune Addison disease. It is not clear how HLA-DRB1*04:04 and other HLA-DRB1 variations are involved in the inappropriate immune response that causes autoimmune Addison disease.

Crohn's disease

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Graves' disease

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Hashimoto's disease

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Idiopathic inflammatory myopathy

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Idiopathic pulmonary fibrosis

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Juvenile idiopathic arthritis

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Lyme disease

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Multiple sclerosis

Variations in the HLA-DRB1 gene have been associated with an increased risk of developing multiple sclerosis. This condition affects the brain and spinal cord (central nervous system), causing muscle weakness, poor coordination, numbness, and a variety of other health problems. One variant of this gene, called HLA-DRB1*15:01, is the most strongly linked genetic factor for the risk of multiple sclerosis.

Because the HLA-DRB1 gene is involved in the immune system, changes in it might be related to the autoimmune response and inflammation that damage nerves and the protective coating surrounding them (the myelin sheath), leading to the signs and symptoms of multiple sclerosis. However, it is unclear exactly what role HLA-DRB1 gene variants play in development of multiple sclerosis. A combination of genetic and environmental factors is likely involved in this condition.

Narcolepsy

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Psoriatic arthritis

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Rheumatoid arthritis

Several common variations of the HLA-DRB1 gene are associated with a person's risk of developing rheumatoid arthritis. This disease causes chronic abnormal inflammation that primarily affects the joints. HLA-DRB1 is one of several genes in the HLA complex that have been associated with rheumatoid arthritis; variations of this gene are the most significant known genetic risk factor for the disease.

The HLA-DRB1 gene variations associated with an increased risk of rheumatoid arthritis affect single protein building blocks (amino acids) in the beta chain. These changes occur near the antigen-recognizing binding groove, which is the part of the protein that attaches (binds) to viral or bacterial peptides. This binding triggers the immune response that attacks foreign invaders. Although the mechanism by which HLA-DRB1 gene variations increase the risk of rheumatoid arthritis is unclear, researchers suspect it is related to changes in peptide binding that stimulate an abnormal immune response. However, many other genetic and environmental factors also contribute to a person's overall risk of developing rheumatoid arthritis.

A few variations of the HLA-DRB1 gene appear to decrease the risk of developing rheumatoid arthritis. It is unclear why these particular changes may be protective.

Rosacea

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Type 1 diabetes

Combinations of variations in the HLA-DRB1 gene and other HLA genes affect the risk of type 1 diabetes. Type 1 diabetes is characterized by high levels of blood glucose, also called blood sugar, resulting from a shortage of the hormone insulin and is caused by autoimmune damage to insulin-producing cells in the pancreas.

Type 1 diabetes risk is most increased by two specific combinations of variations of the HLA-DRB1 gene and other HLA genes called HLA-DQA1 and HLA-DQB1. Combinations of HLA gene variants are called HLA haplotypes. One haplotype, written as DRB1*03:01-DQA1*05:01-DQB1*02, is called DR3. The other haplotype, written as DRB1*04:01/02/04/05/08-DQA1*03:01-DQB1*02, is called DR4. People at highest risk of developing type 1 diabetes have one copy of the DR3 haplotype and one copy of the DR4 haplotype in each cell. Other HLA haplotypes only mildly increase the risk of type 1 diabetes, while some haplotypes seem to protect against developing this condition. Variations in other genes and environmental factors are also thought to affect the risk of this complex disorder.

Autoimmune disorders

Normal variations of the HLA-DRB1 gene have been associated with many other autoimmune disorders, including pemphigus, sarcoidosis, and others listed on this page. Pemphigus is a condition that causes severe blistering of the skin and mucous membranes (such as the moist lining of the mouth). Sarcoidosis is a disorder in which inflammation occurs in many organs and tissues of the body.

It is unclear how different versions of the HLA-DRB1 gene influence the risk of developing autoimmune disorders. These disorders typically result from a combination of multiple environmental and genetic factors. Changes in other HLA and non-HLA genes, some of which remain unknown, also likely contribute to the risk of developing these complex conditions.

Other Names for This Gene

• 2B13_HUMAN
• 2B1F_HUMAN
• 2B1G_HUMAN
• DRB1
• DRw10
• DW2.2/DR2.2
• HLA class II histocompatibility antigen, DR-1 beta chain
• HLA-DR1B
• HLA-DRB
• human leucocyte antigen DRB1
• lymphocyte antigen DRB1
• major histocompatibility complex, class II, DR beta 1 precursor
• MHC class II antigen
• MHC class II HLA-DR beta 1 chain
• MHC class II HLA-DR-beta cell surface glycoprotein
• MHC class II HLA-DRw10-beta
• SS1

Genomic Location

Normal Function

The IL7R gene provides instructions for making a protein called interleukin 7 (IL-7) receptor alpha chain. This protein is one piece of both the IL-7 receptor and the thymic stromal lymphopoietin (TSLP) receptor. These receptors are embedded in the cell membrane of immune system cells. The IL-7 receptor is found in B cells and T cells as well as the early blood-forming cells that give rise to them. The TSLP receptor is found in several types of immune cells, including B cells, T cells, monocytes, and dendritic cells. These cells identify foreign substances and defend the body against infection and disease.

At the cell surface, the IL-7 receptor interacts with a protein called IL-7. IL-7 is a cytokine, which is a protein that regulates the activity of immune system cells. The receptor and cytokine fit together like a lock and its key, triggering a series of chemical signals inside the cell. In early blood-forming cells, signaling through the IL-7 receptor ensures the development of mature B cells and T cells. IL-7 receptor signaling also stimulates the later growth and division (proliferation) and survival of these cells.

Similarly, the TSLP receptor interacts with the cytokine TSLP. Attachment of TSLP to its receptor triggers a set of signals that support proliferation and maturation of a variety of immune system cells.

Health Conditions Related to Genetic Changes

Multiple sclerosis

A common variation of the IL-7R gene increases the risk of developing multiple sclerosis. This condition affects the brain and spinal cord (central nervous system), causing muscle weakness, poor coordination, numbness, and a variety of other health problems. The genetic variation involved in multiple sclerosis affects a single protein building block (amino acid) in the IL-7 receptor alpha chain, specifying the amino acid isoleucine at position 244 instead of the amino acid threonine (written as Thr244Ile). The IL-7 receptor that contains this version of the alpha chain is not embedded in the cell surface but is instead found inside the cell. It is not clear if this alpha chain variant affects the TSLP receptor.

Because the IL7R gene is involved in regulation of the immune system, changes in it might be involved in the autoimmune response and inflammation that damage nerves and the protective coating surrounding them (the myelin sheath), leading to the signs and symptoms of multiple sclerosis. (Autoimmunity occurs when the immune system malfunctions and attacks the body's own tissues and organs, in this case tissues of the nervous system.) However, it is unclear exactly what role the IL-7R gene variant plays in development of multiple sclerosis. It is likely that a combination of genetic and environmental factors is involved.

Omenn syndrome

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Other disorders

Mutations in the IL7R gene can cause a form of severe combined immunodeficiency (SCID), in which affected individuals have decreased immune function and are prone to recurrent and persistent infections. Affected individuals with IL7R gene mutations have few or no T cells but normal numbers of B cells and another type of immune cell called NK cells. This form of the condition is called T-B+NK+ SCID. Many IL7R gene mutations that cause SCID prevent the production of the IL-7 receptor alpha chain, which impairs IL-7 receptor and TSLP receptor signaling. Without this signaling, development of T cells is disrupted. A lack of T cells reduces the immune system's ability to fight infections, leading to recurrent infections in people with T-B+NK+ SCID.

Mutations in the IL7R gene can also cause cancers of blood-forming cells, specifically B-cell acute lymphoblastic leukemia (ALL), which is characterized by elevated numbers of B cells in the blood, and T-cell ALL, characterized by elevated numbers of T cells. The mutations associated with these cancers lead to an altered IL-7 receptor alpha chain. With this alteration, signaling pathways like those triggered by the IL-7 receptor or the TSLP receptor are constantly turned on (constitutively active) even without cytokine interaction. Constant signaling increases proliferation and survival of B cells or T cells, leading to ALL.

Other Names for This Gene

• CD127
• CD127 antigen
• CDW127
• IL-7 receptor subunit alpha
• IL-7R subunit alpha
• IL-7R-alpha
• IL-7RA
• IL7RA
• IL7RA_HUMAN
• ILRA
• interleukin 7 receptor alpha chain
• interleukin 7 receptor isoform H5-6
• interleukin-7 receptor subunit alpha
• interleukin-7 receptor subunit alpha precursor

Genomic Location

Normal Function

The TNFRSF1A gene provides instructions for making a protein called tumor necrosis factor receptor 1 (TNFR1). This protein is found spanning the membrane of cells, with part of the TNFR1 protein outside the cell and part of the protein inside the cell. Outside the cell, the TNFR1 protein attaches (binds) to another protein called tumor necrosis factor (TNF). The interaction of the TNF protein with the TNFR1 protein causes the TNFR1 protein to bind to two other TNFR1 proteins, forming a three-protein complex called a trimer. This trimer formation is necessary for the TNFR1 protein to be functional.

The binding of the TNF and TNFR1 proteins causes the TNFR1 protein to send signals inside the cell. Signaling from the TNFR1 protein can trigger either inflammation or self-destruction of the cell (apoptosis). Signaling within the cell initiates a pathway that turns on a protein called nuclear factor kappa B, which triggers inflammation and leads to the production of immune system proteins called cytokines. Apoptosis is initiated when the TNFR1 protein, bound to the TNF protein, is brought into the cell and starts a process known as the caspase cascade.

Health Conditions Related to Genetic Changes

Tumor necrosis factor receptor-associated periodic syndrome

More than 60 mutations in the TNFRSF1A gene have been found to cause tumor necrosis factor receptor-associated periodic syndrome (commonly known as TRAPS). Most of these mutations lead to changes in single protein building blocks (amino acids), typically involving the amino acid cysteine. Cysteines contain sulfur atoms that form connections, called disulfide bonds, with other cysteines. Disulfide bonds help a protein fold by connecting cysteines in different regions of the protein. These bonds stabilize the protein and give it the appropriate shape to carry out its particular function.

When cysteines within the TNFR1 protein are replaced with other amino acids, the disulfide bonds are not formed, and the protein is misfolded. These misfolded proteins are trapped within the cell, unable to get to the cell surface to interact with TNF. Inside the cell, these proteins clump together and are thought to trigger alternative pathways that initiate inflammation. The clumps of protein constantly activate these alternative inflammation pathways, leading to excess inflammation in people with TRAPS. Additionally, because only one copy of the TNFRSF1A gene has a mutation, some normal TNFR1 proteins are produced and can bind to the TNF protein, leading to additional inflammation. It is unclear if disruption of the apoptosis pathway plays a role in the signs and symptoms of TRAPS.

Some people with mutations in the TNFRSF1A gene do not develop TRAPS, or they develop very mild features of the disorder. The reason for this variability is unclear, but researchers believe that other factors, such as additional genetic changes or environmental factors, may play a role in causing TRAPS.

Multiple sclerosis

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Other Names for This Gene

• p55
• p55-R
• TNF-R
• TNF-R1
• TNF-R55
• TNFR-I
• TNFR1
• TNFR55
• TNR1A_HUMAN
• tumor necrosis factor binding protein 1
• tumor necrosis factor receptor superfamily member 1A
• tumor necrosis factor receptor superfamily, member 1A
• tumor necrosis factor receptor type 1
• tumor necrosis factor-alpha receptor

Genomic Location

The inheritance pattern of multiple sclerosis is unknown, although the condition does appear to be passed down through generations in families. The risk of developing multiple sclerosis is higher for siblings or children of a person with the condition than for the general population.

The natural course of MS is different for each person, which makes it difficult to predict. The onset and duration of MS symptoms usually depends on the specific type but may begin over a few days and go away quickly or develop more slowly and gradually over many years.
There are four main types of MS, named according to the progression of symptoms over time:

• Relapsing-remitting MS. Symptoms in this type come in attacks and, in-between attacks, people recover or return to their usual level of disability. The occurrence of symptoms in this form of MS is called an attack, or in medical terms, a relapse or exacerbation. The periods of disease inactivity or quiescence between MS attacks is referred to as remission. Weeks, months, or even years may pass before another attack occurs, followed again by a period of inactivity. Most people with MS (approximately 80%) are initially diagnosed with this form of the disease.
• Secondary-progressive MS. People with this form of MS usually have had a previous history of MS attacks, but then start to develop gradual and steady symptoms and deterioration in their function over time. Most individuals with severe relapsing-remitting MS may go on to develop secondary progressive MS if they are untreated.
• Primary-progressive MS. This type of MS is less common and is characterized by progressively worsening symptoms from the beginning with no noticeable relapses or exacerbations of the disease, although there may be temporary or minor relief from symptoms.
• Progressive-relapsing MS. This rarest form of MS is characterized by a steady worsening of symptoms from the beginning, with acute relapses that can occur over time during the disease course.

There are some rare and unusual variants of MS. One of these is Marburg variant MS (also called malignant MS), which causes swift and relentless symptoms and decline in function, which can result in significant disability or even death shortly after disease onset. Balo’s concentric sclerosis, which causes concentric rings of myelin destruction that can be seen on an MRI, is another variant type of MS that can progress rapidly.

Early MS symptoms often include:

• Vision problems such as blurred or double vision, or optic neuritis, which causes pain with eye movement and a rapid loss of vision
• Muscle weakness, often in the hands and legs, and muscle stiffness accompanied by painful muscle spasms
• Tingling, numbness, or pain in the arms, legs, trunk, or face
• Clumsiness, particularly difficulty staying balanced when walking
• Bladder control problems
• Intermittent or more constant dizziness

MS may also cause later symptoms such as:

• Mental or physical fatigue which accompanies the early symptoms during an attack
• Mood changes such as depression or difficulty with emotional expression or control
• Cognitive dysfunction—problems concentrating, multitasking, thinking, learning, or difficulties with memory or judgment

Muscle weakness, stiffness, and spasms may be severe enough to affect walking or standing. In some cases, MS leads to partial or complete paralysis and the use of a wheelchair is not uncommon, particularly in individuals who are untreated or have advanced disease. Many people with MS find that weakness and fatigue are worse when they have a fever or when they are exposed to heat. MS exacerbations may occur following common infections.

Pain is rarely the first sign of MS, but pain often occurs with optic neuritis and trigeminal neuralgia, a disorder that affects one of the nerves that provides sensation to different parts of the face (see Conditions associated with MS section below). Painful limb spasms and sharp pain shooting down the legs or around the abdomen can also be symptoms of MS.
Many individuals with MS may experience difficulties with coordination and balance. Some may have a continuous trembling of the head, limbs, and body, especially during movement.

MS exacerbation

An exacerbation—which is also called a relapse, flare-up, or attack—is a sudden worsening of MS symptoms, or the appearance of new symptoms that lasts for at least 24 hours. MS relapses are thought to be associated with the development of new areas of damage in the brain. Exacerbations are characteristic of relapsing-remitting MS.
An exacerbation may be mild, or severe enough to significantly interfere with life's daily activities. Most exacerbations last from several days to several weeks, although some have lasted for as long as a few months. When the symptoms of the attack subside, an individual with MS is said to be in remission, characterized by disease quiescence.

Conditions associated with MS

Transverse myelitis (an inflammation of the spinal cord)may develop in those with MS. Transverse myelitis can affect spinal cord function over several hours to several weeks before partial or complete recovery. It usually begins as a sudden onset of lower back pain, muscle weakness, abnormal sensations in the toes and feet, or difficulties with bladder control or bowel movements. This can rapidly progress to more severe symptoms, including arm and/or leg paralysis. In most cases, people recover at least some function within the first 12 weeks after an attack begins.

Neuromyelitis optica is a disorder associated with transverse myelitis as well as optic nerve inflammation (also known as optic neuritis). People with this disorder usually have abnormal antibodies (proteins that normally target viruses and bacteria) against a specific channel in optic nerves, the brain stem or spinal cord, called the aquaporin-4 channel. These individuals respond to certain treatments, which are different than those commonly used to treat MS.

Trigeminal neuralgia is a chronic pain condition that causes sporadic, sudden burning or shock-like facial pain. The condition is more common in young adults with MS and is caused by lesions in the brain stem, the part of the brain that controls facial sensation.

There is no single test used to diagnose MS. The disease is confirmed when symptoms and signs develop and are related to different parts of the nervous system at more than one interval in time and after other alternative diagnoses have been excluded.

Doctors use different tests to rule out or confirm the diagnosis. In addition to a complete medical history, physical examination, and a detailed neurological examination, a doctor may recommend:

• MRI scans of the brain and spinal cord to look for the characteristic lesions of MS. A special dye or contrast agent may be injected into a vein to enhance brain images of the active MS lesions.
• Lumbar puncture (sometimes called a spinal tap) to obtain a sample of cerebrospinal fluid and examine it for proteins and inflammatory cells associated with the disease. Spinal tap analysis also can rule out diseases that may look like MS.

Evoked potential tests, which use electrodes placed on the skin and painless electric signals to measure how quickly and accurately the nervous system responds to stimulation.

There is no cure for MS, but there are treatments that can reduce the number and severity of relapses and delay the long-term disability progression of the disease.

Treatments for attacks

• Corticosteroids, such as intravenous (infused into a vein) methylprednisolone, are prescribed over the course of 3 to 5 days. Intravenous steroids quickly and potently suppress the immune system and reduce inflammation. They may be followed by a tapered dose of oral corticosteroids. Clinical trials have shown that these drugs hasten recovery from MS attacks, but do not alter the long-term outcome of the disease.
• Plasma exchange (plasmapheresis) can treat severe flare-ups in people with relapsing forms of MS who do not have a good response to methylprednisolone. Plasma exchange involves taking blood out of the body and removing components in the blood’s plasma that are thought to be harmful. The rest of the blood, plus replacement plasma, is then transfused back into the body. This treatment has not been shown to be effective for secondary progressive or chronic progressive MS.

Disease-modifying treatments

Current therapies approved by the U.S. Food and Drug Administration (FDA) for MS are designed to modulate or suppress the inflammatory reactions of the disease. They are most effective for relapsing-remitting MS at early stages of the disease.

Injectable medications include:

• Beta interferon drugs are among the most common medications to treat MS. Interferons are signaling molecules that regulate immune cells. Potential side effects of these drugs include flu-like symptoms (which usually fade with continued therapy), depression, or elevation of liver enzymes. Some individuals will notice a decrease in the effectiveness of the drugs after 18 to 24 months of treatment. If flare-ups occur or symptoms worsen, doctors may switch treatment to alternative drugs.
• Glatiramer acetate changes the balance of immune cells in the body, but how it works is not entirely clear. Side effects are usually mild and consist of local injection site reactions or swelling.

Infusion treatments include:

• Natalizumab is administered intravenously once a month. It works by preventing cells of the immune system from entering the brain and spinal cord. It is very effective but is associated with an increased risk of a serious and potentially fatal viral infection of the brain called progressive multifocal leukoencephalopathy (PML). Natalizumab is generally recommended only for individuals who have not responded well to or who are unable to tolerate other first-line therapies.
• Ocrelizumab is administered intravenously every six months and treats adults with relapsing or primary progressive forms of MS. It is the only FDA-approved disease-modifying therapy for primary-progressive MS. The drug targets the circulating immune cells that produce antibodies, which also play a role in the formation of MS lesions. Side effects include infusion-related reactions and increased risk of infections. Ocrelizumab may increase the risk of cancer as well.
• Alemtuzumab is administered for 5 consecutive days followed by 3 days of infusions one year later. It targets proteins on the surface of immune cells. Because this drug increases the risk of autoimmune disorders it is recommended for those who have had inadequate responses to two or more MS therapies.
• Mitoxantrone, which is administered intravenously four times a year, has been approved for especially severe forms of relapsing-remitting and secondary progressive MS. Side effects include the development of certain types of blood cancers in up to one percent of those with MS, as well as with heart damage. This drug should be considered as a last resort to treat people with a form of MS that leads to rapid loss of function and for whom other treatments did not work.

Oral treatments include:

• Fingolimod is a once-daily medication that reduces the MS relapse rate in adults and children. It is the first FDA-approved drug to treat MS in adolescents and children ages 10 years and older. The drug prevents white blood cells called lymphocytes from leaving the lymph nodes and entering the blood, brain, and spinal cord. Fingolimod may result in a slow heart rate and eye problems when first taken. Fingolimod can also increase the risk of infections, such as herpes virus infections, or in rare cases be associated with PML.
• Dimethyl fumarate is a twice-daily medication used to treat relapsing forms of MS. Its exact mechanism of action is not currently known. Side effects of dimethyl fumarate are flushing, diarrhea, nausea, and lowered white blood cell count.
• Teriflunomide is a once-daily medication that reduces the rate of proliferation of activated immune cells. Teriflunomide side effects can include nausea, diarrhea, liver damage, and hair loss.
• Cladribine is administered as two courses of tablets about one year apart. Cladribine targets certain types of white blood cells that drive immune attacks in MS. The drug may increase the risk of developing cancer and should be considered for individuals who have not responded well to other MS treatments.
• Diroximel fumarate is a twice-daily drug similar to dimethyl fumarate (brand name Tecfidera) but with fewer gastrointestinal side effects. Scientists suspect these drugs, which have been approved to treat secondary progressive MS, reduce damage to the brain and spinal cord by making the immune response less inflammatory, although their exact mechanism of action is poorly understood.
• Siponimod tablets (Mayzent) is taken orally and has a similar mechanism of action to fingolimod. Siponimod has been approved by the FDA to treat secondary-progressive MS.

Clinical trials have shown that cladribine, diroximel fumarate, and dimethyl fumarate decrease the number of relapses, delay the progress of physical disability, and slow the development of brain lesions.

Managing MS symptoms

MS causes a variety of symptoms that can interfere with daily activities but can usually be treated or managed. Many of these issues are best treated by neurologists who have advanced training in the treatment of MS and who can prescribe specific medications to treat these problems.

Eye and vision problems are common in people with MS but rarely result in permanent blindness. Inflammation of the optic nerve (optic neuritis) or damage to the myelin that covers the nerve fibers in the visual system can cause blurred or grayed vision, temporary blindness in one eye, loss of normal color vision, depth perception, or loss of vision in parts of the visual field. Uncontrolled horizontal or vertical eye movements (nystagmus), “jumping vision" (opsoclonus), and double vision (diplopia) are common in people with MS. Intravenous steroid medications, special eyeglasses, and periodically resting the eyes may be helpful.

Muscle weakness and spasticity is common in MS. Mild spasticity can be managed by stretching and exercising muscles using water therapy, yoga, or physical therapy. Medications such as gabapentin or baclofen can reduce spasticity. It is very important that people with MS stay physically active because physical inactivity can contribute to worsening stiffness, weakness, pain, fatigue, and other symptoms.

Tremor, or uncontrollable shaking, develops in some people with MS. Assistive devices and weights attached to utensils or even limbs are sometimes helpful for people with tremor. Deep brain stimulation and drugs, such as clonazepam, also may be useful.

Problems with walking and balance occur in many people with MS. The most common walking problem is ataxia—unsteady, uncoordinated movements—due to damage to the areas of the brain that coordinate muscle balance. People with severe ataxia generally benefit from the use of a cane, walker, or other assistive device. Physical therapy also can reduce walking problems. The FDA has approved the drug dalfampridine to improve walking speed in people with MS.

Fatigue is a common symptom of MS and may be both physical (for example, tiredness in the arms or legs) and cognitive (slowed processing speed or mental exhaustion). Daily physical activity programs of mild to moderate intensity can significantly reduce fatigue, although people should avoid excessive physical activity and minimize exposure to hot weather conditions or ambient temperature. Other drugs that may reduce fatigue include amantadine, methylphenidate, and modafinil. Occupational therapy can help people learn how to walk using an assistive device or in a way that saves physical energy. Stress management programs, relaxation training, membership in an MS support group, or individual psychotherapy may help some people.

Pain from MS can be felt in different parts of the body. Trigeminal neuralgia (facial pain) is treated with anticonvulsant or antispasmodic drugs, or less commonly painkillers. Central pain, a syndrome caused by damage to the brain and/or spinal cord, can be treated with gabapentin and nortriptyline. Treatments for chronic back or other musculoskeletal pain may include heat, massage, ultrasound, and physical therapy.

Problems with bladder control and constipation may include urinary frequency, urgency, or the loss of bladder control. A small number of individuals retain large amounts of urine. Medical treatments are available for bladder-related problems. Constipation is also common and can be treated with a high-fiber diet, laxatives, and stool softeners.

Sexual dysfunction can result from damage to nerves running through the spinal cord. Sexual problems may also stem from MS symptoms such as fatigue, cramped or spastic muscles, and psychological factors. Some of these problems can be corrected with medications. Psychological counseling also may be helpful.

Clinical depression is frequent among people with MS. MS may cause depression as part of the disease process and chemical imbalance in the brain. Depression can intensify symptoms of fatigue, pain, and sexual dysfunction. It is most often treated with cognitive behavioral therapy, and selective serotonin reuptake inhibitor (SSRI) antidepressant medications, which are less likely than other antidepressant medications to cause fatigue.

Inappropriate and involuntary expressions of laughter, crying, or anger—symptoms of a condition called pseudobulbar affect—sometimes are associated with MS. These expressions are often incongruent with mood; for example, people with MS may cry when they are actually happy or laugh when they are not especially happy. The combination treatment of the drugs dextromethorphan and quinidine can treat pseudobulbar affect, as can other drugs such as amitriptyline or citalopram.

Cognitive impairment—a decline in the ability to think quickly and clearly and to remember easily—affects up to three-quarters of people with MS. These cognitive changes may appear at the same time as the physical symptoms or they may develop gradually over time. Drugs such as donepezil may be helpful in some cases.

Complementary and alternative therapies

Many people with MS benefit from complementary or alternative approaches such as acupuncture, aromatherapy, ayurvedic medicine, touch and energy therapies, physical movement disciplines such as yoga and tai chi, herbal supplements, and biofeedback.

Because of the risk of interactions between alternative and conventional therapies, people with MS should discuss all the therapies they are using with their doctor, especially herbal supplements. Herbal supplements have biologically active ingredients that could have harmful effects on their own or interact harmfully with other medications.

Multiple sclerosis (MS) is a disease of the central nervous system. In MS, the body’s immune system attacks myelin, which coats nerve cells. Symptoms of MS include muscle weakness (often in the hands and legs), tingling and burning sensations, numbness, chronic pain, coordination and balance problems, fatigue, vision problems, and difficulty with bladder control.

Although MS has no cure, some conventional treatments can improve symptoms, reduce the number and severity of relapses, and delay the disease’s progression. Many people with MS try some form of complementary health approach, often special diets and dietary supplements. Here are 7 things to know about complementary health approaches for MS.

1. Practicing yoga may help with fatigue and mood, but there’s no evidence that yoga can help with mobility or thinking ability.

2. Reflexology (applying pressure to the soles of the feet) may reduce a burning or prickling sensation sometimes associated with MS, but larger studies are needed to provide a reliable conclusion.

3. Studies of magnetic therapy, which involves devices that use an electrical current to generate a magnetic field, have shown mixed results for MS-related fatigue.

4. Chemicals in marijuana known as THC/cannabinoids may relieve spasticity and/or pain in people with MS. While no marijuana-derived medications are approved by the U.S. Food and Drug Administration to treat MS in the United States, Canada and some European countries have approved Sativex®, a mouth spray with THC/cannabinoids for muscle control related to MS.

5. Dietary supplements such as fish oil and ginkgo biloba have not been shown to be helpful for MS.

6. One large, 5-year study suggests that low blood levels of vitamin D may be a risk factor for long-term disease activity and progression. However, more studies need to be done to determine if vitamin D supplementation is beneficial.

7. Take charge of your health—talk with your health care providers about any complementary health approaches you use. Together, you can make shared, well-informed decisions.

The National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH), is the leading federal funder of research on the brain and nervous system, including research on MS.

In addition to NINDS, other NIH Institutes—including the National Institute of Allergy and Infectious Diseases (NIAID)—fund research on multiple sclerosis. More information on NIH efforts on multiple sclerosis research and on other disorders can be found using NIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and patents citing support from these projects.

Although researchers have not been able to identify the cause of MS with any certainty, there has been excellent progress in other areas of MS research—especially in the development of new treatments to prevent exacerbations of the disease. New discoveries are constantly changing MS treatment options and helping to reduce MS-related disability.

Research projects being conducted by NINDS scientists or through NIH grants to universities and other sites throughout the United States cover a wide range of topics such as comorbidities, mechanisms of cognitive impairment, blood-brain barrier breakdown in MS, the role of sleep and circadian rhythms, rehabilitation strategies, and telehealth. Other topics include:

• Biomarkers to accurately diagnose MS and monitor disease progression, including blood and imaging tests (such as MRI)
• Genetic and environmental risk factors for MS such as low Vitamin D or the Epstein-Barr virus
• The role of the gut microbiome and diet in MS
• Mechanisms that underlie gender differences in the incidence and presentation of MS
• MS risk factors and disease course in African American and Hispanic populations and disparities in care
• The role of the immune system in MS, including its function in the central nervous system (CNS)
• The role and crosstalk of various cell types in the CNS with relation to MS
• Basic functions of myelination, demyelilnation, and axonal degeneration, and strategies to overcome axonal and myelin loss

Scientists sponsored by NIH’s NIAID are testing an experimental stem cell treatment (called autologous hematopoietic stem cell transplantation, or AHSCT) against the best available biologic therapies for severe forms of relapsing MS. Investigators in the BEAT-MS (BEst Available Therapy versus autologous hematopoietic stem cell transplant for Multiple Sclerosis) trial are removing some of the person’s immune cells and then infusing some of the person’s own blood-forming stem cells to reset the immune system so it no longer attacks the central nervous system. For more information about BEAT-MS and how to apply to participate in this study or other clinical studies, visit www.clinicaltrials.gov.

Genetic research funded by NINDS is exploring the roles of "susceptibility genes"—genes that are associated with an increased risk for MS. Several candidate genes have been identified and researchers are studying their function in the nervous system to discover how they may lead to the development of MS.

Other studies aim to develop better neuroimaging tools, such as more powerful MRI methods, to diagnose MS, track disease progression, and assess treatments. NINDS scientists are collecting magnetic resonance imaging of the brain and spinal cord and scans of the retina, along with other clinical and biological data, from more than 100 individuals with MS and 50 individuals without the disease over a period of years to observe changes in the course of MS over time. Investigators also are using MRI to study the natural history of MS and to help define the mechanism of action and cause of side effects of disease modifying therapies.

Intramural research programs on MS

NINDS and other NIH Institutes have a very active MS intramural research program (scientists working at NIH). NINDS Intramural scientists have:

• Established and continue to develop magnetic resonance imaging as a critical tool for examining the natural course of the disease in humans, monitoring disease progression, assessing effects of treatments in clinical trials, and understanding MS biology
• Played an important role in understanding why some patients develop a rare and potentially fatal brain infection (progressive multifocal leukoencephalopathy) when taking potent MS drugs, and they are developing new treatments for this infection.
• Unraveled mechanisms by which viruses, especially the Epstein-Barr virus, contribute to the development of MS
• Conducted next-generation treatment trials targeting specific mechanisms of disease progression, using advanced MRI and fluid biomarkers as outcome measures
• Developed the first MRI method to visualize the lymph vessels surrounding the brain, which play a critical role in neuro-immune communication

Translational research

NIH supports translational studies to develop therapies that will stop or reverse the course of the disease, focusing on pathways that modify immune system function, repair damaged myelin, or protect neurons from damage. Researchers are also developing animal models of MS to more accurately predict drug response in human disease. Currently available animal models share some of the disease mechanisms and symptoms of MS but do not fully mimic the disease, especially in its clinically progressive phase.

Focus on progressive MS therapies

Scientists continue to study the biology and mechanisms of relapsing-remitting MS while increasing efforts to stop or prevent the steady decline in function that occurs in progressive MS. In the MS-SPRINT trial, the NINDS NeuroNEXT clinical trials network tested the drug ibudilast as a potential neuroprotective drug for progressive MS and showed that the drug slowed the rate of brain shrinkage as compared to a placebo. NINDS Intramural scientists are conducting proof-of-concept clinical trials to address a key driver of clinical progression called the “slowly expanding lesion.”

Focus on biomarkers

As part of a larger effort to develop and validate effective biomarkers (signs that may indicate risk of a disease or be used to monitor its progression) for neurological disease, NINDS is supporting two definitive multicenter MS studies:

• The Central Vein Sign in MS (CAVS-MS) study, which is testing whether a rapid MRI approach designed by NINDS Intramural scientists, can use the detection of a central vein passing through brain plaques to differentiate MS from other common neurological disorders that can mimic MS. The goal is to develop a reliable imaging test for MS in order to achieve a rapid but accurate diagnosis and reduce misdiagnosis, which may affect up to 20 percent of people currently diagnosed with MS.
• A study to test whether a simple new blood test, which measures small amounts of neuron-derived proteins (called neurofilaments), can be used to predict the severity of disease and help determine whether MS drugs are working to protect the brain tissues.

Most of the time, multiple sclerosis, or MS, starts mildly, with unpredictable symptoms that can seem baffling. Without treatment, the disease can worsen to the point that you can’t write, speak, or walk.

MS starts when the body’s immune system slowly attacks the fatty coating around nerves. Without an intact coating, communication between nerves and the brain becomes impaired. However, it may be years before the first symptoms appear.

The symptoms depend on which parts of the brain and spinal cord are affected. A typical symptom is blurry vision in one eye. It may develop over a day or two. It may be painful to move the eye. Or, you may have double vision. Another typical symptom is not being able to move or feel a leg.

These symptoms, also known as MS attacks, may last for days or weeks. Most people will have one attack that resolves over time. Later, they might have other attacks.

MS is usually diagnosed when people are young adults. But it can be diagnosed at any age. No one knows exactly how many people have MS. In the United States, at least 400,000 people do.

MS can be detected with an MRI scan of the brain and spinal cord. Areas where the immune system has attacked the coating around nerves will show up on an MRI scan.

MS is a complex disease. Nobody knows why it starts. If you have a family history, your chance of developing MS may be greater.

“We know that genes play a major role,” says Dr. Daniel S. Reich, an MS expert at NIH. Research shows that hundreds of genes are involved. Most of these genes are related to the immune system and the inflammation that it drives.

Researchers have noticed that your chance of developing MS may be lower if you don’t smoke and you maintain a healthy weight. They’ve also found that people who have not been infected with a common virus known as Epstein-Barr virus seem to be at lower risk of developing MS. But researchers don’t know why.

People who live near the equator seem at lower risk too. Researchers believe that it may be because there is more consistent sunlight there, which helps the body make vitamin D. Vitamin D may help the immune system work better and protect against MS.

“There is some kind of complex series of risk factors and triggers that may need to occur in a certain order,” Reich says. “But it’s very hard to figure out.”

MS can affect different people in very different ways. It can range from very mild to severe. Being diagnosed and treated early on can help prevent the disease from becoming more disabling.

“We now have more than a dozen effective medications that greatly reduce the number of new attacks,” Reich says. Imaging tests show that these treatments reduce the level of brain inflammation in people with MS.

Doctors hope that these treatments, and others under development, will help delay or even prevent MS from getting worse.

Early Symptoms of MS

Talk with your doctor if you have any of the following symptoms:

• Blurry or double vision
• Painful eye
• Leg and arm muscles that feel weak and stiff
• Painful muscle spasms
• Feeling numb or tingly in the legs or elsewhere
• Having trouble keeping your balance when walking
• Having problems with bladder control
• Feeling dizzy all the time

antibodies—proteins made by the immune system that bind to structures (antigens) they recognize as foreign to the body.

ataxia— a condition in which the muscles fail to function in a coordinated manner.

autoimmune disease—a disease in which the body's defense system malfunctions and attacks a part of the body itself rather than foreign matter.

blood-brain barrier—a network of blood vessels with closely spaced cells that controls the passage of substances from the blood into the central nervous system.

cerebrospinal fluid—the colorless liquid that circulates around and through the cavities of the brain and spinal cord. Physicians use a variety of to study cerebrospinal fluid for abnormalities often associated with MS.

deep brain stimulation—therapy that uses a surgically implanted, battery-operated medical device called a neurostimulator to deliver electrical stimulation to targeted areas in the brain that control movement, blocking the abnormal nerve signals that cause tremor and other movement symptoms.

demyelination—damage caused to myelin by recurrent attacks of inflammation. Demyelination ultimately results in nervous system scars, called plaques, which interrupt communications between the nerves and the rest of the body.

dysesthesias—abnormal sensations such as numbness, prickling, or "pins and needles."

exacerbation—a sudden worsening of symptoms or the appearance of new symptoms that lasts for at least 24 hours.

fatigue—tiredness that may accompany activity or may persist even without exertion.

gray matter—part of the brain that contains nerve cells and has a gray color.

immunosuppression— suppression of immune system functions. Many medications under investigation for the treatment of MS are immunosuppressants.

interferons—signaling molecules that regulate immune cells.

lesion—an abnormal change in the structure of an organ due to disease or injury. magnetic resonance imaging (MRI)—a non-invasive scanning technique that enables investigators to see and track MS lesions as they evolve.

myelin—a fatty covering insulating nerve cell fibers in the brain and spinal cord, myelin facilitates the smooth, high-speed transmission of electrochemical messages between these components of the central nervous system and the rest of the body. In MS, myelin is damaged through a process known as demyelination, which results in distorted or blocked signals.

oligodendrocytes—cells that make and maintain myelin.

optic neuritis—an inflammatory disorder of the optic nerve that usually occurs in only one eye and causes visual loss and sometimes blindness. It is generally temporary.

plasma—the liquid portion of the blood that is involved in controlling infection.

plasmapheresis—the process of taking blood out of the body and removing components in the blood’s plasma that are thought to be harmful before transfusing the blood back into the body (also called plasma exchange).

plaques—patchy areas of inflammation and demyelination typical of MS, plaques disrupt or block nerve signals that would normally pass through the regions affected by the plaques.

relapsing-remitting MS—a form of MS in which an episode of symptoms occurs and is followed by a recovery period before another attack occurs.

spasticity—involuntary muscle contractions leading to spasms and stiffness or rigidity. In MS, this condition primarily affects the lower limbs.

transverse myelitis—an acute spinal cord disorder causing sudden low back pain and muscle weakness and abnormal sensory sensations in the lower extremities. Transverse myelitis often remits spontaneously; however, severe or long-lasting cases may lead to permanent disability.

white matter—nerve fibers that are the site of many MS lesions and that connect areas of gray matter in the brain and spinal cord.