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Multiple Sclerosis (MS)

By

Michael C. Levin

, MD, College of Medicine, University of Saskatchewan

Reviewed/Revised May 2023
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In multiple sclerosis, patches of myelin (the substance that covers most nerve fibers) and underlying nerve fibers in the brain, optic nerves, and spinal cord are damaged or destroyed.

  • The cause is unknown but may involve an attack by the immune system against the body’s own tissues (autoimmune reaction).

  • In most people with multiple sclerosis, periods of relatively good health alternate with episodes of worsening symptoms, but over time, multiple sclerosis gradually worsens.

  • People may have vision problems and abnormal sensations, and movements may be weak and clumsy.

  • Usually, doctors diagnose multiple sclerosis based on symptoms and results of a physical examination and magnetic resonance imaging.

  • Treatment includes corticosteroids, medications that help keep the immune system from attacking the myelin sheath, and medications to relieve symptoms.

  • Life span is unaffected unless the disorder is very severe.

Multiple Sclerosis
VIDEO

The term “multiple sclerosis” refers to the many areas of scarring (sclerosis) that result from destruction of the tissues that wrap around nerves (myelin sheath) in the brain and spinal cord. This destruction is called demyelination Overview of Demyelinating Disorders Most nerve fibers inside and outside the brain are wrapped with many layers of tissue composed of a fat (lipoprotein) called myelin. These layers form the myelin sheath. Much like the insulation... read more . Sometimes the nerve fibers that send messages (axons) are also damaged. Over time, the brain may shrink in size because axons are destroyed.

World wide, about 2.8 million people have multiple sclerosis, and about 107,000 people are diagnosed with multiple sclerosis each year.

Most commonly, multiple sclerosis begins between the ages of 20 and 40, but it can begin anytime between ages 15 and 60 years. It is somewhat more common among women. Multiple sclerosis is uncommon among children.

Most people with multiple sclerosis have periods of relatively good health (remissions) alternating with periods of worsening symptoms (flare-ups or relapses). Relapses can be mild or debilitating. Recovery during remission is good but often incomplete. Thus, multiple sclerosis worsens slowly over time.

Causes of Multiple Sclerosis

The cause of multiple sclerosis is unknown, but a likely explanation is that people are exposed early in life to a virus (possibly a herpesvirus or retrovirus) or some unknown substance that somehow triggers the immune system to attack the body’s own tissues (autoimmune reaction Autoimmune Disorders An autoimmune disorder is a malfunction of the body's immune system that causes the body to attack its own tissues. What triggers an autoimmune disorder is not known. Symptoms vary depending... read more ). The autoimmune reaction results in inflammation, which damages the myelin sheath and the underlying nerve fiber.

Autoimmune Disorders
VIDEO

Genes seem to have a role in multiple sclerosis. For example, having a parent or sibling (brother or sister) with multiple sclerosis increases the risk of acquiring the disease several-fold. Also, multiple sclerosis is more likely to develop in people with certain genetic markers on the surface of their cells. Normally, these markers (called human leukocyte antigens Recognition ) help the body to distinguish self from nonself and thus know which substances to attack.

Environment also has a role in multiple sclerosis. Where people spend the first 15 years of life affects their chance of developing multiple sclerosis. It occurs as follows:

  • In about 1 of about 2,000 people who grow up in a temperate climate

  • In only 1 of about 10,000 people who grow up in a tropical climate

  • Much less commonly in people who grow up near the equator

These differences may be related to vitamin D levels. When the skin is exposed to sunlight, the body forms vitamin D. Thus, people who grow up in temperate climates may have a lower vitamin D level. People with a low level of vitamin D are more likely to develop multiple sclerosis. Also, in people who have the disorder and a low vitamin D level, symptoms appear to occur more frequently and are worse. But how vitamin D may protect against the disorder is unknown.

Where people live later in life—regardless of the climate—does not change their chances of developing multiple sclerosis.

Cigarette smoking also appears to increase the chances of developing multiple sclerosis. The reason is unknown.

Did You Know...

  • Spending the first 15 years of life in a temperate (rather than tropical) climate increases the risk of multiple sclerosis.

  • Three fourths of people with multiple sclerosis never need a wheelchair.

Symptoms of Multiple Sclerosis

Symptoms of multiple sclerosis vary greatly, from person to person and from time to time in one person, depending on which nerve fibers are demyelinated:

Nerve Cells and Fibers
VIDEO
  • If nerve fibers that carry sensory information become demyelinated, problems with sensations (sensory symptoms) result.

  • If nerve fibers that carry signals to muscles become demyelinated, problems with movement (motor symptoms) result.

Patterns of multiple sclerosis

Multiple sclerosis may progress and regress unpredictably. However, there are several typical patterns of symptoms:

  • Relapsing-remitting pattern: Relapses (when symptoms worsen) alternate with remissions (when symptoms lessen or do not worsen). Remissions may last months or years. Relapses can occur spontaneously or can be triggered by an infection such as influenza.

  • Primary progressive pattern: The disease progresses gradually with no remissions or obvious relapses, although there may be temporary plateaus during which the disease does not progress.

  • Secondary progressive pattern: This pattern begins with relapses alternating with remissions (the relapsing-remission pattern), followed by gradual progression of the disease.

  • Progressive relapsing pattern: The disease progresses gradually, but progression is interrupted by sudden relapses. This pattern is rare.

On average, without treatment, people have about one relapse every 2 years, but frequency varies greatly.

Early symptoms of multiple sclerosis

Vague symptoms of demyelination in the brain sometimes begin long before the disorder is diagnosed. The most common early symptoms are the following:

  • Tingling, numbness, pain, burning, and itching in the arms, legs, trunk, or face and sometimes a reduced sense of touch

  • Loss of strength or dexterity in a leg or hand, which may become stiff

  • Problems with vision

Vision may become dim or blurred. Mainly, people lose the ability to see when looking straight ahead (central vision). Peripheral (side) vision is less affected. People with multiples sclerosis may also have the following vision problems:

Excess heat—for example, warm weather, a hot bath or shower, or a fever—may temporarily make symptoms worse.

When the back part of the spinal cord in the neck is affected, bending the neck forward may cause an electrical shock or a tingling sensation that shoots down the back, down both legs, down one arm, or down one side of the body (a response called Lhermitte sign). Usually, the sensation lasts only a moment and disappears when the neck is straightened. Often, it is felt as long as the neck remains bent forward.

Later symptoms of multiple sclerosis

As multiple sclerosis progresses, movements may become shaky, irregular, and ineffective. People may become partially or completely paralyzed. Weak muscles may contract involuntarily (called spasticity), sometimes causing painful cramps. Muscle weakness and spasticity may interfere with walking, eventually making it impossible, even with a walker or another assistive device. Some people are confined to a wheelchair. People who cannot walk may develop osteoporosis Osteoporosis (decreased bone density).

Speech may become slow, slurred, and hesitant.

People with multiple sclerosis may become unable to control emotional responses and may laugh or cry inappropriately. Depression is common, and thinking may be mildly impaired.

Retained urine can be a breeding ground for bacteria, making urinary tract infections more likely to develop.

If relapses become more frequent, people become increasingly disabled, sometimes permanently.

Table

Diagnosis of Multiple Sclerosis

  • A doctor's evaluation

  • Magnetic resonance imaging

  • Sometimes additional tests

When doctors suspect multiple sclerosis, they thoroughly evaluate the nervous system (neurologic examination Neurologic Examination When a neurologic disorder is suspected, doctors usually evaluate all of the body systems during the physical examination, but they focus on the different parts of the nervous system. Examination... read more ) during a physical examination. They examine the back of the eye (retina) with an ophthalmoscope What Is an Ophthalmoscope? What Is an Ophthalmoscope? . The optic disk (the spot where the optic nerve joins the retina) may be unusually pale, indicating damage to the optic nerve.

Magnetic resonance imaging Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (MRI) is a type of medical imaging that uses a strong magnetic field and very high frequency radio waves to produce highly detailed images. During an MRI, a computer... read more Magnetic Resonance Imaging (MRI) (MRI) is the best imaging test for detecting multiple sclerosis. It usually detects areas of demyelination in the brain and spinal cord. However, MRI cannot determine whether the demyelination has been there for a long time and is stable or it is very recent and still progressing. Nor can MRI determine whether immediate treatment is required. So doctors may inject gadolinium (a paramagnetic contrast agent) into the bloodstream and do MRI again. Gadolinium helps distinguish areas of recent demyelination from areas of long-standing demyelination. This information helps doctors plan treatment.

Sometimes demyelination is detected when MRI is done for another reason, before multiple sclerosis causes any symptoms.

Additional testing

A diagnosis of multiple sclerosis may be clear based on current symptoms, a history of relapses and remissions, the physical examination, and MRI. If not, other tests are done to obtain additional information:

Other tests can help doctors distinguish multiple sclerosis from disorders that cause similar symptoms, such as AIDS Acquired immunodeficiency syndrome (AIDS) Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and is treated with antiretroviral medications. If untreated, it can cause... read more Acquired immunodeficiency syndrome (AIDS) , tropical spastic paraparesis HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) HTLV-1–associated myelopathy/tropical spastic paraparesis is a slowly progressive disorder of the spinal cord caused by the human T-lymphotropic virus 1 (HTLV-1). The virus is spread through... read more , vasculitis Overview of Vasculitis Vasculitic disorders are caused by inflammation of the blood vessels (vasculitis). Vasculitis can be triggered by certain infections or drugs or can occur for unknown reasons. People may have... read more Overview of Vasculitis , arthritis of the neck, Guillain-Barré syndrome Guillain-Barré Syndrome (GBS) Guillain-Barré syndrome is a form of polyneuropathy causing muscle weakness, which usually worsens over a few days to weeks, then slowly improves or returns to normal on its own. With treatment... read more , hereditary ataxias Friedreich ataxia Coordination disorders often result from malfunction of the cerebellum, the part of the brain that coordinates voluntary movements and controls balance. The cerebellum malfunctions, causing... read more , lupus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic autoimmune inflammatory connective tissue disorder that can involve joints, kidneys, skin, mucous membranes, and blood vessel walls. Problems in the... read more Systemic Lupus Erythematosus (SLE) , Lyme disease Lyme Disease Lyme disease is a tick-transmitted infection caused by Borrelia species, primarily by Borrelia burgdorferi and sometimes by Borrelia mayonii in the United States. These... read more Lyme Disease , rupture of a spinal disk Herniated Disk A herniated disk occurs when the tough covering of a disk in the spine tears or ruptures. The soft, jelly-like interior of the disk may then bulge out (herniate) through the covering. Aging... read more Herniated Disk , syphilis Syphilis Syphilis is a sexually transmitted infection caused by the bacteria Treponema pallidum. It can occur in three stages of symptoms, separated by periods of apparent good health. Syphilis... read more Syphilis , and a cyst in the spinal cord (syringomyelia Syrinx of the Spinal Cord or Brain Stem A syrinx is a fluid-filled cavity that develops in the spinal cord (called syringomyelia), in the brain stem (called syringobulbia), or in both. Syrinxes may be present at birth or develop later... read more ). For example, blood tests may be done to rule out Lyme disease, syphilis, AIDS, tropical spastic paraparesis, and lupus, and imaging tests can help rule out arthritis of the neck, rupture of a spinal disk, and syringomyelia.

Treatment of Multiple Sclerosis

  • Corticosteroids

  • Medications that help keep the immune system from attacking myelin sheaths

  • Measures to control symptoms

No treatment for multiple sclerosis is uniformly effective.

Corticosteroids

For an acute attack, corticosteroids are most commonly used. They probably work by suppressing the immune system. They are given for short periods to relieve immediate symptoms (such as loss of vision, strength, or coordination) if the symptoms interfere with functioning. For example, prednisone may be taken by mouth, or methylprednisolone may be given intravenously. Although corticosteroids may shorten relapses and slow the progression of multiple sclerosis, they do not stop its progression.

Corticosteroids are rarely used for a long time because they can have many side effects, such as increased susceptibility to infection, diabetes, weight gain, fatigue, osteoporosis, and ulcers. Corticosteroids are started and stopped as needed.

Medications to help control the immune system

Medications that help keep the immune system from attacking myelin sheaths are usually also used. These medications help reduce the number of future relapses. They include the following:

  • Interferon-beta injections reduce the frequency of relapses and may help delay disability.

  • Glatiramer acetate injections may have similar benefits for people with early mild multiple sclerosis.

  • Fingolimod, ozanimod, ponesimod, siponimod, teriflunomide, cladribine, dimethyl fumarate, monomethyl fumarate, and diroximel fumarate may be used to treat multiple sclerosis that occurs in relapsing patterns. These medications can be taken by mouth. Fingolimod, dimethyl fumarate, monomethyl fumarate, and diroximel fumarate also increase the risk of progressive multifocal leukoencephalopathy, although the risk is much less than with natalizumab.

  • Ocrelizumab is a monoclonal antibody used to treat multiple sclerosis that occurs in relapsing or primary progressive patterns. It is given as an infusion into a vein every 6 months. It can cause infusion reactions, which may include a rash, itching, difficulty breathing, swelling of the throat, dizziness, low blood pressure, and a fast heart rate.

  • Alemtuzumab (used to treat leukemia), also a monoclonal antibody, is effective in treating multiple sclerosis that occurs in relapsing patterns (relapsing-remitting pattern and progressive relapsing pattern). It is given intravenously. However, it increases the risk of serious autoimmune disorders and certain cancers. Consequently, alemtuzumab is usually used only when treatment with two or more other medications has been ineffective.

  • Ofatumumab is used to treat relapsing forms of multiple sclerosis and multiple sclerosis that is actively progressing. It is injected under the skin (subcutaneously). People with multiple sclerosis can be taught to administer it themselves.

  • Ublituximab is also used to treat relapsing forms of multiple sclerosis and multiple sclerosis that is actively progressing. It is given intravenously. Ublituximab increases a person's susceptibility to infections (such as urinary tract infections, upper respiratory infections, and herpesvirus infections) Herpesvirus Infections because it suppresses the immune system.

  • Mitoxantrone, a chemotherapy medication, can reduce the frequency of relapses and slow the progression of the disorder. It is used only when other medications do not work and is typically given for only up to 2 years because it can eventually lead to heart damage.

  • Immune globulin, given intravenously once a month, occasionally helps when other medications have been ineffective. Immune globulin consists of antibodies obtained from the blood of people with a normal immune system.

Medications that increase the risk of progressive multifocal leukoencephalopathy (natalizumab, fingolimod, and dimethyl fumarate) are used only by specially trained doctors. Also, people who take them must be checked periodically for signs of progressive multifocal leukoencephalopathy. Blood tests for the JC virus, which causes progressive multifocal leukoencephalopathy, are done periodically. If a person taking natalizumab develops progressive multifocal leukoencephalopathy, plasma exchange can be done to remove the medication quickly.

Other treatments

Plasma exchange Plateletpheresis (platelet donation) In addition to normal blood donation and transfusion, special procedures are sometimes used. In plateletpheresis, a donor gives only platelets rather than whole blood. Whole blood is drawn from... read more is recommended by some experts for severe relapses not controlled by corticosteroids. However, the benefits of plasma exchange have not been established. For this treatment, blood is withdrawn, abnormal antibodies are removed from it, and the blood is returned to the person.

Symptom control

Other medications can be used to relieve or control specific symptoms of multiple sclerosis:

People with urine retention can learn to catheterize themselves and thus empty their bladder.

General measures

People with multiple sclerosis can often maintain an active lifestyle, although they may tire easily and may not be able to keep up with a demanding schedule. Encouragement and reassurance help.

Regular exercise such as riding a stationary bicycle, walking, swimming, or stretching reduces spasticity and helps maintain cardiovascular, muscular, and psychologic health.

Physical therapy can help with maintaining balance, the ability to walk, and range of motion and can help reduce spasticity and weakness. People should walk on their own for as long as possible. Doing so improves their quality of life and helps prevent depression.

Avoiding high temperatures—for example, by not taking hot baths or showers—can help because heat can worsen symptoms. People who smoke should stop.

Because people who have low levels of vitamin D tend to have more severe multiple sclerosis and because taking vitamin D may reduce the risk of developing osteoporosis Osteoporosis Osteoporosis is a condition in which a decrease in the density of bones weakens the bones, making breaks (fractures) likely. Aging, estrogen deficiency, low vitamin D or calcium intake, and... read more Osteoporosis , doctors usually recommend that people take vitamin D supplements. Whether vitamin D supplements can help slow the progression of multiple sclerosis is being studied.

If people are disabled, occupational, physical, and speech therapists can help with rehabilitation. They can help people learn to function despite disabilities caused by multiple sclerosis. Social workers can recommend and help arrange for needed services and equipment.

Prognosis for Multiple Sclerosis

What effects multiple sclerosis has and how quickly it progresses vary greatly and unpredictably. Remissions can last months up to 10 years or more. However, some people, such as men who develop the disorder during middle age and who have frequent attacks, may become rapidly incapacitated. Nonetheless, about 75% of people who have multiple sclerosis never need a wheelchair, and for about 40%, normal activities are not disrupted.

Smoking cigarettes may make the disease progress faster.

Unless multiple sclerosis is very severe, life span is usually unaffected.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

  • Multiple Sclerosis Association of America (MSAA): This web site provides general information about multiple sclerosis (including symptoms, diagnosis, and treatment), about prescription management, and about living with the disorder (including links to other people who have it, blogs, and an app that helps with managing multiple sclerosis).

  • National Multiple Sclerosis Society: This web site provides general information about multiple sclerosis (including symptoms, diagnosis, and treatment), tips (for diet, exercise, and mental health), and resources and support links.

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