Multiple Sclerosis

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). Myelin is a substance that makes up the protective sheath (myelin sheath) that coats nerve fibers (axons).

MS is a chronic disease that affects people differently. A small number of people 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. The disease is rarely fatal and most people with MS have a normal life expectancy.

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 in a process 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 (MRI). Plaques can be as small as a pinhead or as large as a golf ball.

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 cavaties).

Signs and symptoms of MS

The natural course of MS is different for each person, which makes it difficult to predict. The onset and duration of MS symptoms usually depend 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:

There are some rare and unusual variants of MS, such as:

Early MS symptoms often include:

MS may also cause later symptoms, such as:

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. Painful limb spasms and sharp pain shooting down the legs or around the abdomen can also be symptoms of MS.

Conditions associated with MS

Females are more frequently affected than males. Researchers are looking at several possible explanations for why the immune system attacks central nervous system myelin, including:

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 (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 five percent of the population has not been 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 U.S. 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.

Diagnosing MS

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 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:

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 disability progression 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 at early stages of the disease.

Injectable medications include:

Infusion treatments include:

Oral treatments include:

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, may also 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 (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 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 75 percent 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.

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. 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.

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 conducted by NINDS scientists or through NIH grants to universities and other sites across the U.S. 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:

Scientists sponsored by NIAID are testing an experimental stem cell treatment titled, autologous hematopoietic stem cell transplantation (AHSCT), against the best available biologic therapies for severe forms of relapsing MS.

Investigators in the clinical trial BEAT-MS (BEst Available Therapy versus autologous hematopoietic stem cell transplant for Multiple Sclerosis) are removing some 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 CNS.

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 MRIs 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. Investigators 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 among scientists working at NIH. Together, they have:

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. However, current 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:

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

All types of volunteers 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.

Information may be available from the following organizations and resources:

Accelerated Cure Project for Multiple SclerosisPhone: 781-487-0008

Autoimmune AssociationPhone: 586-776-3900

Multiple Sclerosis Association of America (MSAA)Phone: 856-488-4500 or 800-532-7667

Multiple Sclerosis Foundation (MS Focus)Phone: 954-776-6805 or 888 673-6287

Myelin Repair Foundation (MRF)Phone: 408-871-2410

National Ataxia Foundation (NAF)Phone: 763-553-0020

National Multiple Sclerosis SocietyPhone: 800-344-4867

National Organization for Rare Disorders (NORD)Phone: 203-744-0100

National Rehabilitation Information Center (NARIC)Phone: 301-459-5900 or 800-346-2742; 301-459-5984

Paralyzed Veterans of AmericaPhone: 202-872-1300 or 800-555-9140