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Multiple Sclerosis (MS)

by Brian R. Apatoff, MD, PhD

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).

  • Usually, periods of relatively good health alternate with episodes of worsening symptoms.

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

  • Usually, doctors base the diagnosis on symptoms and results of a physical examination and magnetic resonance imaging.

  • Treatment includes corticosteroids, drugs that help keep the immune system from attacking the body, and drugs to relieve symptoms.

  • Often, the disorder slowly worsens, disabling some people, but life span is unaffected unless the disorder is very severe.

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). This destruction is called demyelination (see Overview of Demyelinating Disorders). Sometimes the nerve fibers that send messages (axons) are also damaged. Over time, the brain may shrink in size because axons are destroyed.

In the United States, more than 400,000 people, mostly young adults, have multiple sclerosis. Most commonly, it begins between the ages of 20 and 40. It is somewhat more common among women. Most people 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 incomplete. Thus, the disorder worsens slowly over time.

Causes

The cause 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—see Autoimmune Disorders). The autoimmune reaction results in inflammation, which damages the myelin sheath and the underlying nerve fiber.

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 severalfold. Also, multiple sclerosis is more likely to develop in people with certain genetic markers on the surface of their cells called human leukocyte antigens (see Biology of the Immune System:Recognition). These markers 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 in 1 of 2,000 people who grow up in a temperate climate but in only 1 of 10,000 people who grow up in a tropical climate. Multiple sclerosis occurs 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 be worse. But how vitamin D may protect against the disorder is unknown. The climate in which later years are spent does not change the chances of developing the disorder.

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

Symptoms

Symptoms vary greatly, from person to person and from time to time in one person, depending on which nerve fibers are demyelinated. 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. Symptoms often come and go, affecting one or several parts of the body. The fluctuating symptoms result from damage to myelin sheaths, followed by repair, followed by more damage. Symptoms may become more severe when people are exposed to high temperatures, such as in very warm weather, in a hot bath or shower, or during a fever.

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 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, 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.

Vague symptoms of demyelination in the brain sometimes begin long before the disorder is diagnosed. For example, tingling, numbness, pain, burning, and itching may occur in the arms, legs, trunk, or face. The sense of touch may be reduced. People may lose strength or dexterity in a leg or hand, which may become stiff.

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. In some people, one eye becomes weaker than the other, causing double vision when looking from one side to the other. This disorder is called internuclear ophthalmoplegia (see Internuclear Ophthalmoplegia). The stronger eye may move involuntarily, moving rapidly and repetitively in one direction, then slowly drifting back (a symptom called nystagmus). Partial blindness may develop in one eye, and pain occurs when the eye is moved. These symptoms result from inflammation of the optic nerve (optic neuritis).

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.

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. People who cannot walk may develop osteoporosis (decreased bone density—see Osteoporosis).

Speech may become slow, slurred, and hesitant.

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

The nerves that control urination or bowel movements can be affected, leading to frequent and strong urges to urinate, retention of urine, constipation, and, occasionally, urinary and fecal incontinence. Rarely, late in the disorder, dementia develops.

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

Common Symptoms of Multiple Sclerosis

Part of the Body

Examples

  • Nerves (affecting sensation)

  • Numbness

  • Tingling

  • A reduced sense of touch

  • Pain or burning

  • Itching

  • Eyes

  • Double vision

  • Partial blindness and pain in one eye

  • Dim or blurred vision

  • Inability to see when looking straight ahead

  • Uncoordinated eye movements

  • Genital organs

  • Difficulty reaching orgasm

  • Lack of sensation in the genital area

  • In men, erectile dysfunction (impotence)

  • Muscles and coordination

  • Weakness and clumsiness

  • Difficulty walking or maintaining balance

  • Tremor

  • Uncoordinated movements

  • Stiffness, unsteadiness, and unusual fatigue

  • Intestine and bladder

  • Problems controlling urination and bowel movements

  • Constipation

Speech

Slow, slurred, and hesitant speech

  • Mood

  • Mood swings

  • Inappropriate elation or giddiness

  • Depression

  • Inability to control emotions (for example, crying or laughing without reason)

  • Brain

  • Subtle or obvious mental impairment

  • Memory loss

  • Poor judgment

  • Inattention

  • Other

  • Dizziness or vertigo

Diagnosis

Because symptoms vary widely, doctors may not recognize the disorder in its early stages. Doctors suspect multiple sclerosis in younger people who suddenly develop blurred vision, double vision, or movement problems and abnormal sensations in various unrelated parts of the body. Fluctuating symptoms and a pattern of relapses and remissions support the diagnosis.

When doctors suspect multiple sclerosis, they thoroughly evaluate the nervous system during a physical examination. They examine the back of the eye (retina) with an ophthalmoscope (see Figure: What Is an Ophthalmoscope?). The optic disk (the spot where the optic nerve joins the retina) may be inflamed or unusually pale, indicating inflammation of the optic nerve.

Magnetic resonance imaging (MRI) is the best imaging test for detecting multiple sclerosis. It usually detects areas of demyelination in the brain and spinal cord. Before MRI, doctors may inject gadolinium, a paramagnetic contrast agent, into the bloodstream. Gadolinium helps distinguish areas of recent demyelination and active inflammation from areas of long-standing demyelination.

The diagnosis 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:

  • Spinal tap (lumbar puncture): A sample of cerebrospinal fluid is removed and analyzed (see Tests for Brain, Spinal Cord, and Nerve Disorders : Spinal Tap). The protein content of the fluid may be higher than normal. The concentration of antibodies may be high, and a specific pattern of antibodies (called oligoclonal banding) is detected in most people with multiple sclerosis.

  • Evoked responses: For this test, sensory stimuli, such as flashing lights, are used to activate certain areas of the brain, and the brain’s electrical responses are recorded (see Tests for Brain, Spinal Cord, and Nerve Disorders : Evoked Responses). In people with multiple sclerosis, the brain’s response to stimuli may be slow because signal conduction along demyelinated nerve fibers is impaired. This test can also detect slight damage to the optic nerve.

Other tests can help doctors distinguish multiple sclerosis from disorders that cause similar symptoms, such as AIDS, vasculitis, arthritis of the neck, Guillain-Barré syndrome, hereditary ataxias, lupus, Lyme disease, rupture of a spinal disk, syphilis, and a cyst in the spinal cord (syringomyelia). For example, blood tests may be done to rule out Lyme disease, syphilis, and lupus, and imaging tests can help rule out arthritis of the neck, rupture of a spinal disk, and syringomyelia.

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.

Prognosis

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.

Unless the disorder is very severe, life span is usually unaffected.

Treatment

No treatment for multiple sclerosis is uniformly effective. 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.

Drugs that help keep the immune system from attacking myelin sheaths are usually also used. These drugs 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.

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

  • Natalizumab is an antibody given intravenously as an infusion once a month. It is more effective than other drugs in reducing the number of relapses and preventing further damage in the brain. However, natalizumab may increase the risk of a rare, fatal infection of the brain and spinal cord (progressive multifocal leukoencephalopathy). Natalizumab is used only by specially trained doctors, and people who take it must be checked periodically for signs of progressive multifocal leukoencephalopathy.

  • Immune globulin, given intravenously once a month, occasionally helps when other drugs have been ineffective.

  • Fingolimod, teriflunomide, and dimethyl fumarate, which are relatively new drugs, may be used to treat multiple sclerosis that occurs in relapsing patterns (relapsing-remitting pattern and progressive relapsing pattern). These drugs can be taken by mouth.

Plasma exchange 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 (see Controlling Diseases by Purifying the Blood).

Other drugs can be used to relieve or control specific symptoms:

  • Muscle spasms: The muscle relaxants baclofen or tizanidine

  • Urinary incontinence: Oxybutynin or tamsulosin

  • Pain due to abnormalities in nerves: Anticonvulsants (such as gabapentin, pregabalin, or carbamazepine), sometimes tricyclic antidepressants (such as amitriptyline), or opioids

  • Tremors: The beta-blocker propranolol

  • Fatigue: Amantadine (used to treat Parkinson disease) or, less often, drugs used to treat excessive sleepiness (such as modafinil, armodafinil, or amphetamine)

  • Depression: Antidepressants such as sertraline or amitriptyline, counseling, or both

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. 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, doctors usually recommend that people take vitamin D supplements.

People with urine retention can learn to catheterize themselves and thus empty their bladder, and those with constipation can take stool softeners or laxatives regularly. People who become weak and unable to move easily may develop pressure sores, so they and their caregivers must take extra care to prevent the sores.

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

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Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • PROVIGIL
  • LIORESAL
  • NEURONTIN
  • INDERAL
  • NUVIGIL
  • No US brand name
  • LYRICA
  • DITROPAN XL
  • ZOLOFT
  • FLOMAX
  • MEDROL
  • TYSABRI
  • TEGRETOL
  • RAYOS
  • ZANAFLEX