Multiple Sclerosis
Multiple sclerosis is a disorder in which patches of myelin and underlying nerve fibers in the eyes, brain, and spinal cord are damaged or destroyed.
The term "multiple sclerosis" refers to the many areas of scarring (sclerosis) that result from demyelination of nerves. In the United States, about 400,000 people, mostly young adults, have multiple sclerosis. Most commonly, it begins between the ages of 20 and 40. It is more common among women than among men. Most people with multiple sclerosis have periods of relatively good health (remissions) alternating with debilitating flare-ups (relapses). However, the disorder often worsens slowly over time.
Causes
The cause of multiple sclerosis is unknown, but a likely explanation is that a virus (possibly a herpesvirus or retrovirus) or some unknown antigen somehow triggers a reaction directed against the body's own tissues (autoimmune reaction (see Section 16, Chapter 186)), usually early in life. The autoimmune reaction results in inflammation, destruction of myelin, and damage to the myelin sheath and the underlying nerve fiber.
Heredity seems to have a role in multiple sclerosis. About 5% of people with the disorder have a brother or sister who is affected, and about 15% have a close relative who is affected. Also, multiple sclerosis is more likely to develop in people with certain genetic markers for proteins (human leukocyte antigens (see Section 16, Chapter 183)) that help the body to distinguish self from nonself.
Environment also has a role in multiple sclerosis. Where people spend the first 15 years of life affects their chance of developing multiple sclerosis. Multiple sclerosis 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 almost never occurs in people who grow up near the equator. The climate in which later years are spent does not change the chances of developing the disorder.
Symptoms
The 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. If nerve fibers that carry sensory information are demyelinated, abnormal sensations (sensory symptoms) result. If nerve fibers that carry signals to muscles are 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.
Multiple sclerosis may progress and regress unpredictably. However, there are several patterns of symptoms. In the relapsing-remitting pattern, flare-ups (relapses) alternate with remissions, in which symptoms are stable. Remissions may last months or years. Relapses can occur spontaneously or can be triggered by an infection such as influenza. High temperatures, such as very warm weather, a hot bath or shower, or a fever, can also trigger relapses or intensify symptoms. In the primary progressive pattern, the disease progresses gradually with no remissions, although there may be temporary plateaus during which the disease does not progress. The secondary progressive pattern begins with relapses alternating with remissions, followed by gradual progression of the disease. In the progressive relapsing pattern, the disease progresses gradually, but progression is interrupted by sudden relapses. This pattern is rare. About 20% of people with multiple sclerosis have one episode, after which the disease progresses little if at all. Very rarely, multiple sclerosis progresses quickly, resulting in severe disability or death soon after the symptoms develop.
Common early symptoms include tingling, numbness, pain, burning, and itching in the arms, legs, trunk, or face and loss of strength or dexterity in a leg or hand. A person may feel unusually tired. Mild psychologic or neurologic symptoms (such as mood swings, inappropriate giddiness, euphoria, depression, and apathy) may occur. Cognitive problems include memory disturbances, decreased judgment, and inattention. These vague symptoms of demyelination in the brain sometimes begin long before the disorder is diagnosed.
Some people develop only eye symptoms, such as partial blindness and pain in one eye, dim or blurred vision, or loss of central vision; peripheral vision is not affected. Such symptoms are due to inflammation of the optic nerve (optic neuritis). Eye movements may be uncoordinated, sometimes resulting in double vision (a condition called internuclear ophthalmoplegia).
When the back part of the spinal cord in the neck is affected, bending the neck forward causes 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's 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.
As the disorder progresses, movements may become shaky, irregular, and ineffective. Muscle weakness and spasticity may interfere with walking, sometimes eventually making it impossible. Multiple sclerosis can cause partial or complete paralysis. Speech may become slow, slurred, and hesitant. Late in the disorder, dementia and mania (excessive elation) may develop. The nerves that control urination or bowel movements can also be affected, leading to frequent and strong urges to urinate, retention of urine, constipation, and, occasionally, urinary and fecal incontinence.
If relapses become more frequent, people become increasingly disabled, sometimes permanently. Nonetheless, about 75% of people who have multiple sclerosis never need a wheelchair, and for about 40%, normal activities are not disrupted. Most people with multiple sclerosis have a normal life span.
 See the table Common Symptoms of Multiple Sclerosis.
Diagnosis
Because the 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 scattered parts of the body. Symptoms that fluctuate 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 (see Section 6, Chapter 77). The optic nerve may be inflamed or unusually pale, as detected by examination of the back of the eye (retina) with an ophthalmoscope (see Section 20, Chapter 225).
No single test is diagnostic, but laboratory tests can help doctors distinguish multiple sclerosis from other disorders that produce similar symptoms, such as AIDS, amyotrophic lateral sclerosis (Lou Gehrig's disease), arteritis, 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).
Doctors may perform a spinal tap (lumbar puncture (see Section 6, Chapter 77)) to obtain a sample of cerebrospinal fluid. The white blood cell count and protein content of the fluid may be higher than normal. The concentration of antibodies in the cerebrospinal fluid may be high, and a specific pattern of antibodies is detected in up to 90% of people with multiple sclerosis.
Magnetic resonance imaging (MRI) is the best imaging procedure for detecting multiple sclerosis and is used to confirm the diagnosis. It usually detects areas of demyelination in the brain and spinal cord. MRI with gadolinium, a paramagnetic contrast agent, helps distinguish areas of recent demyelination and active inflammation from areas of long-standing demyelination.
A procedure involving evoked responses (see Section 6, Chapter 77) may be performed. Sensory stimuli, such as flashing lights, are used to activate certain areas of the brain, and the brain's electrical responses are recorded. In people with multiple sclerosis, the brain's response to stimuli may be slow because signal conduction along demyelinated nerve fibers is impaired. This procedure can also detect slight damage to the optic nerve.
Treatment
No treatment for multiple sclerosis is uniformly effective. Corticosteroids, the main form of therapy, are given for short periods to relieve immediate symptoms. For example, prednisone may be taken by mouth, or methylprednisolone may be given intravenously. Corticosteroids seem to work by suppressing the immune system. Although corticosteroids may shorten the duration of relapses, they do not stop disability from progressing over the long term.
Corticosteroids given intravenously are recommended for people who have inflammation of the optic nerve but do not have other symptoms of multiple sclerosis. For these people, taking corticosteroids by mouth may increase the risk of developing other symptoms of multiple sclerosis.
Corticosteroids are rarely used for a long time, because they can cause many side effects, such as increased susceptibility to infection, diabetes, weight gain, fatigue, decreased bone density (osteoporosis), and ulcers. Corticosteroids are started and stopped as needed.
Interferon-beta injections reduce the frequency of relapses and may help prevent or delay later disability. Glatiramer acetate injections may have similar benefits for people with early mild multiple sclerosis. The chemotherapy drug mitoxantrone can reduce the frequency of relapses and slow the progression of the disease. It can be given for only up to 3 years because it can eventually lead to heart damage. These drugs work by interfering with the immune system's attack on myelin sheaths.
Other promising treatments include other types of interferons and gamma globulins, which help keep the body from attacking its own myelin. The benefits of plasmapheresis (a procedure in which blood is withdrawn, the abnormal antibodies are removed from it, and the blood is returned to the person (see Section 14, Chapter 171)) have not been established. However, some experts continue to recommend it for severe relapses not controlled by corticosteroids.
Other drugs can be used to treat specific symptoms. For example, baclofen, tizanidine, or the sedative diazepam can relieve muscle spasms. Oxybutynin, bethanechol, or tamsulosin can help control urinary incontinence. The anticonvulsant gabapentin may be used to relieve the pain due to abnormalities in the nervous system. The beta-blocker propranolol may reduce the severity of tremors. Amantadine, a drug sometimes used to treat influenza, may help relieve fatigue. Antidepressants such as sertraline or amitriptyline may be given to treat depression.
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, walking ability, and range of motion as well as reduce spasticity and weakness. Avoiding high temperatures--for example, by not taking hot baths or showers--can help prevent the aggravation of symptoms.
People with urine retention can learn to catheterize themselves to empty the bladder, and those with constipation can take stool softeners or laxatives regularly. People who become weak and unable to move easily may develop bedsores (pressure sores), so they and their caregivers must take extra care to prevent bedsores (see Section 18, Chapter 205).
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