Multiple Sclerosis

What is multiple sclerosis?

Multiple sclerosis (MS) is a chronic neurological disorder. It is an autoimmune disorder, meaning that in MS the immune system—which normally protects us from viruses, bacteria, and other threats—mistakenly attacks healthy cells. MS symptoms usually begin in young adults, between the ages of 20 and 40.  

MS affects people differently. A small number of people with MS will have mild symptoms with little disability, whereas others will experience worsening symptoms that will lead to increased disability over time. Most people with MS have short periods of symptoms that resolve fully or partially after they appear. These periods are followed by long stretches without noticeable symptoms. Most people with MS have a normal life expectancy. 

Myelin and the immune system

In MS, the immune system attacks myelin in the central nervous system. Myelin is a mixture of protein and fatty acids that makes up the protective cover (known as the myelin sheath) that coats nerve fibers (axons). Myelin is what gives the brain’s white matter its whitish appearance and helps with communication between neurons. The central nervous system is made up of the brain, the spinal cord, and the optic nerves, which connect the eyes to the brain 

In addition to causing damage to the myelin sheath, MS also damages the nerve cell bodies, which are found in the brain's gray matter, as well as the axons themselves. As the disease progresses, the outermost layer of the brain, called the cerebral cortex, shrinks. This process is known as cortical atrophy. The way that cortical atrophy happens in MS may connect it with some neurodegenerative disorders.  

Sclerosis is a medical term for the distinctive areas of scar-like tissue (also called plaques or lesions) that result from the attack on myelin by the immune system. These areas are visible on an MRI (magnetic resonance imaging). The patches of scar-like tissue can be as small as the head of a pin or as large as a golf ball.

The symptoms of MS depend on the severity of the attacks as well as the location and size of the plaques.

Types of multiple sclerosis

The course of MS is different for each person, which makes it difficult to predict how an individual will do with the disease. While many different courses or progressions of MS have been used over the years, these are changing as the scientific and medical community better understands different ways the disease can progress. 

Currently, the five courses used to describe MS are:

1. Clinically isolated syndrome—Symptoms come from a single attack (also called "exacerbation" or "relapse") followed by complete or near-complete recovery. MRI and other tests, such as a spinal tap or electrical vision tests, may show “silent” damage in other places in the central nervous system. If this damage is identified, it could allow a full diagnosis of MS even after a single attack.
2. Relapsing-remitting MS—Symptoms come in the form of recurrent attacks with total or partial recovery. The periods of disease inactivity between MS attacks are referred to as remission. Weeks, months, or even years may pass before another attack occurs, followed again by a period of inactivity. Treatment with disease-modifying therapies can reduce the frequency of attacks or eliminate them entirely. Most people with MS are initially diagnosed with this form.
3. Secondary-progressive MS—Relapsing-remitting MS can gradually evolve into secondary-progressive MS. Attacks become less and less common but may still occur, and people gradually develop steady symptoms with deterioration in their functioning over time. Secondary-progressive MS with attacks is called “active,” whereas secondary-progressive MS without attacks is called “non-relapsing.” Disease-modifying therapy for relapsing-remitting MS can delay and sometimes prevent secondary progressive MS, but the transition can occur even with treatment.
4. Primary-progressive MS—This course of MS is less common and is characterized by progressively worsening symptoms from the beginning, with no noticeable acute attacks, although there may be temporary or minor worsening of, or relief from, symptoms.
5. Radiologically isolated syndrome—This is the rarest course of MS in which a person has abnormal MRI results that look like MS, but doesn’t have MS symptoms. However, symptoms (attacks or progression) may occur in the future.

Symptoms of MS

Early MS symptoms often include:

• Vision problems, such double vision or optic neuritis (inflammation of the optic nerve), which causes pain with eye movement and vision loss
• Muscle weakness, often in the arms and legs, and muscle stiffness with painful muscle spasms
• Tingling, numbness, or pain in the arms, legs, trunk, or face
• Clumsiness, especially difficulty staying balanced when walking
• Bladder control problems
• Intermittent or constant dizziness

MS may also cause other symptoms, such as:

• Mental or physical fatigue
• Mood changes such as depression or difficulty with emotional expression or control
• Cognitive changes, including problems concentrating, multitasking, thinking, or 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. The use of a wheelchair is not uncommon, particularly in individuals who are untreated or have advanced disease. Many people with MS find that their symptoms are worse when they have a fever or are exposed to heat or following common infections.

Pain is rarely the first sign of MS, but pain often occurs with optic neuritis and trigeminal neuralgia. Painful limb spasms and sharp pain shooting down the legs or around the abdomen can also be symptoms of MS.

Who is more likely to get multiple sclerosis?

Women are more likely to get MS than men. People of all races and ethnicities can get MS, but it is most common in White people.  

Having a parent or sibling with MS increases the likelihood of a person getting MS, although MS itself is not an inherited disorder. Research suggests that hundreds of genes and 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. Some of the known genes are similar to those that have been identified in people with other autoimmune diseases, such as inflammatory bowel disease, celiac disease, type 1 diabetes, rheumatoid arthritis, or lupus.

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. Almost everyone has been infected by EBV at some point in their lives. Only about 5% of the population has not been infected, and these individuals are at a lower risk for developing MS than those who have been infected. People who got EBV during childhood are at a lower risk of getting MS than people who infected with EBV in adolescence or adulthood. However, the vast majority of people who get infected with EBV are not going to develop MS.

Research indicates that people who spend more time in the sun, and those with relatively higher levels of vitamin D, are less likely to develop MS than those who do not. Additionally, people with MS who spend significant time in the sun and/or have higher vitamin D levels 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 and autoimmune disorders 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 U.S. and Canada, where sunshine is highly variable throughout the year.

Studies have found that people who smoke are more likely to develop MS and have a more aggressive disease course. They also tend to have more brain lesions and brain shrinkage than non-smokers. 

How is multiple sclerosis diagnosed and treated?

Diagnosing MS

There is no single test used to diagnose MS. 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 the brain images.

In addition, a doctor may recommend:

• 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. This can also test for 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
• MRI of the optic nerves, optic coherence tomography (OCT), or visual evoked potentials to detect optic nerve lesions

In most cases, doctors can diagnose MS by assessing symptoms and identifying characteristic MS signs on an MRI. 

Treating MS

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

Corticosteroids, such as methylprednisolone, are prescribed over for three to five days and are usually injected into a vein. Corticosteroids 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.

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 or secondary-progressive MS with residual attacks. They are also effective in some cases of radiologically isolated syndrome to prevent development of clinical MS. Radiologically isolated syndrome is a condition in which a person has abnormal MRI results that look like MS, but doesn’t have MS symptoms.

Infusion treatments include:

• Natalizumab (brand name: Tysabri®) works by preventing cells of the immune system from entering the central nervous system. 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). Regular blood tests for antibodies to the virus that causes PML can help address this risk. 
• Ocrelizumab (brand name: Ocrevus®) treats adults with relapsing-remitting, active secondary-progressive, or primary-progressive MS. It is currently the only FDA-approved disease-modifying therapy for primary-progressive MS. The drug targets circulating immune cells (“B cells”) that have many functions, including giving rise to the cells that produce antibodies. Side effects include infusion-related reactions and increased risk of infections. Ocrelizumab may slightly increase the risk of cancer and reduce the effectiveness of some vaccines.
• Alemtuzumab targets proteins on the surface of immune cells. Because this drug increases the risk of autoimmune disorders, it is usually used in those who have not responded sufficiently to two or more MS therapies.

Oral treatments include:

• Fingolimod (brand name: Gilenya®) reduces the MS relapse rate in adults and children. It is the first FDA-approved drug to treat MS in adolescents and children age 10 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. Siponimod has a similar mechanism of action to fingolimod. Siponimod has been approved by the FDA to treat secondary-progressive MS.
• Dimethyl fumarate (brand name: Tecfidera®) is used to treat relapsing forms of MS. Its exact mechanism of action is not currently known. Side effects of dimethyl fumarate are flushing (temporary reddening of the skin), diarrhea, nausea, and lowered white blood cell count. Diroximel fumarate (brand name: Vumerity®) is a drug similar to dimethyl fumarate, but with fewer gastrointestinal side effects. 
• Teriflunomide (brand name: Aubagio®) reduces the rate of growth in the number of activated immune cells. Teriflunomide side effects can include nausea, diarrhea, liver damage, and hair loss.
• Cladribine (brand names: Mavenclad® and Leustatin® DSC) targets certain types of white blood cells that drive immune attacks in MS. The drug may increase the person’s risk of developing cancer.

Injectable medications include:

• Beta interferon drugs, which were once the most commonly used treatments for MS but are rarely used now. Potential side effects of these drugs include flu-like symptoms (which usually fade with continued therapy), depression, or elevation of liver enzymes. 
• Glatiramer acetate, which can reduce the frequency of attacks in relapsing-remitting MS.  

Clinical trials have shown that cladribine, diroximel fumarate, and dimethyl fumarate decrease the number of relapses, delay the progression 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. Fortunately, many of the symptoms of MS can usually be treated or managed. Neurologists with advanced training in the treatment of MS can prescribe specific medications to treat these problems.

Eye and vision problems

Eye and vision problems are common in people with MS but rarely result in permanent blindness. Symptoms may include blurred or grayed vision, temporary blindness in one eye, loss of normal color vision, issues with 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. Vision therapy exercises, special eyeglasses, and resting the eyes may be helpful.

Muscle and mobility problems

Muscle weakness and spasticity are common in MS. 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. Stretching and exercising muscles through water therapy, yoga, or physical therapy (PT) can help manage mild spasticity. Medications can also help reduce spasticity. 

Tremor, or uncontrollable shaking, develops in some people with MS. Assistive devices are sometimes helpful for people with tremor. Deep brain stimulation and medications may also help.

Many people with MS have difficulty with balance and walking. 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 can also reduce walking problems. Occupational therapy (OT) can help people learn how to walk using an assistive device or in a way that saves physical energy. The FDA has approved the drug dalfampridine to improve walking speed in people with MS. 

Fatigue 

Fatigue is a common symptom of MS and may be both physical (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 high temperatures. PT and OT can sometimes help manage fatigue. PT provides personalized treatments, while OT teaches ways to use energy wisely. They also help find the right changes in the person’s environment. Stress management programs or relaxation training may help some people.

Bladder control and constipation issues

Problems with bladder control and constipation may include problems with frequency of urination, 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

Sexual dysfunction can result from damage to nerves running through the spinal cord. Sexual problems may also stem from MS symptoms, including fatigue, muscle symptoms, and psychological factors. Some of these problems can be corrected with medications. Counseling (therapy) may be helpful.

Mental and emotional problems

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—called pseudobulbar symptoms—are sometimes associated with MS, although this is not as common as in some other neurological disorders. 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 problems

Cognitive impairment—a decline in the ability to think, learn, and remember—affects up to 75% of people with MS. These cognitive changes may appear at the same time as the physical symptoms, or they may develop gradually over time. Sometimes, cognitive impairment in people with MS is caused by depression. It is important to rule out depression, first. If cognitive impairment is caused by depression, it can be treated. Drugs such as donepezil may be helpful in some cases.

Complementary approaches

Some people with MS report improvement in their symptoms from complementary or alternative approaches. These include acupuncture, aromatherapy, ayurvedic medicine, touch and energy therapies, physical movement disciplines such as yoga and tai chi, herbal supplements, and biofeedback. Learn more about research on complementary health approaches for MS. 

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.

What are the latest updates on multiple sclerosis?

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. Other components of NIH are funding research on topics relevant to MS, including cognitive impairment, rehabilitation strategies, and telehealth. 

Although researchers have not been able to identify the exact cause(s) of MS, 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 improving and expanding MS treatment options and helping to reduce MS-related disability.

NINDS-supported research projects cover a wide range of topics. These include co-occurring conditions, 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 and treatment response, including blood and imaging tests 
• Genetic and environmental risk factors for MS
• The role of the gut microbiome and diet in MS
• Mechanisms that underlie sex differences in the incidence and presentation of MS
• MS risk factors and disease course in African American and Hispanic populations
• Social determinants of health that influence disease outcome and disparities in care
• The role of the immune system in MS, including its function in the central nervous system
• The role and crosstalk of various cell types in the central nervous system with relation to MS
• Basic functions of myelination, demyelination, and axonal degeneration, and strategies to overcome axonal and myelin loss

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. Investigators are also 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 among scientists working at NIH (known as “intramural” research). Together, they have:

• Established and continue to develop MRI as a critical tool for examining the natural course of MS in humans, monitoring disease progression, assessing effects of treatments in clinical trials, and understanding MS biology.
• Played an important role in understanding why some people develop a rare and potentially fatal brain infection (called progressive multifocal leukoencephalopathy) when taking potent MS drugs. Research teams are now developing new treatments for this infection.
• Unraveled mechanisms by which viruses 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 in the peripheral and central nervous system, repair damaged myelin, or protect neurons from damage. Researchers are also developing improved disease models of MS in animals to more accurately predict drug response in human disease. 

Progressive MS therapies

While scientists continue to study relapsing-remitting MS, research is also investigating treatments that slow or prevent the steady decline in function 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 on a key driver of clinical progression called the “chronic active lesion.”

Biomarkers for MS

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:

1. The Central Vein Sign in MS (CAVS-MS) study, which is testing whether a rapid MRI approach designed by NINDS 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 rapid yet accurate diagnosis and reduce misdiagnosis, which may affect up to 20% of people currently diagnosed with MS.
2. A study to test whether a simple new blood test that measures small amounts of neuron-derived proteins (neurofilaments) can be used to predict the severity of disease and help determine whether MS drugs are working to protect brain tissues.

In addition to NINDS, other NIH Institutes fund research on multiple sclerosis. Find more information on NIH research efforts through 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.

How can I or my loved one help improve care for people with multiple sclerosis?

Consider participating in a clinical trial so clinicians and scientists can learn more about MS and related disorders. Clinical research with human participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with MS at Clinicaltrials.gov.