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 steroids (also called glucocorticoids or corticosteroids), medications that help keep the immune system from attacking the myelin sheath in the optic nerve, brain, and spinal cord; care from experts in rehabilitation; and medications to relieve symptoms.
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) in the optic nerve, brain, and spinal cord. This destruction is called demyelination. Sometimes the nerve fibers that send messages (axons) are also damaged. Over time, the brain may shrink in size because axons are destroyed.
Worldwide, about 2.8 million people have multiple sclerosis. The prevalence of multiple sclerosis is higher among people living in temperate, compared to tropical, climates.
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, such as Epstein-Barr virus, or a retrovirus) or some unknown substance that somehow triggers the immune system to attack the body’s own tissues (autoimmune reaction). 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 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) 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 with decreased sun exposure 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.
Prior infection with Epstein-Barr virus (which causes mononucleosis) appears to increase the risk of developing multiple sclerosis.
Cigarette smoking also appears to increase the chances of developing multiple sclerosis. The reason is unknown.
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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:
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. Muscle weakness most often affects the lower limbs.
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.
Secondary progressive pattern: This pattern begins with relapses alternating with remissions (the relapsing-remission pattern), followed by gradual progression of the disease. If a relapse, new MRI lesion or rapid worsening occurs during this phase. This is known as active secondary progressive MS, and may alter which MS medication the doctor recommends.
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.
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 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. Most frequently, people lose the ability to see when looking straight ahead (central vision) while peripheral (side) vision is less affected. People with multiples sclerosis may also have the following vision problems:
Internuclear ophthalmoplegia: The nerve fibers that coordinate the eyes when they move horizontally (look from side to side) are damaged. One eye cannot turn inward, causing double vision when looking toward the side opposite the affected eye. The unaffected eye may move involuntarily, moving rapidly and repetitively in one direction, then slowly drifting back (a symptom called nystagmus).
Optic neuritis (inflammation of the optic nerve): Vision may be partially lost in one eye, and pain occurs when the eye is moved.
Walking and balance may be affected. Dizziness and vertigo are common, as is fatigue.
Excess heat—for example, warm weather, a hot bath or shower, or a fever—may temporarily make symptoms worse (known as Uhthoff's phenomenon).
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 (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.
Multiple sclerosis often affects the nerves that control urination or bowel movements. As a result, most people with multiple sclerosis have problems controlling their bladder, such as the following:
Frequent and strong urges to urinate
Involuntary passage of urine (urinary incontinence)
Difficulty starting to urinate
Inability to empty their bladder completely (urinary retention)
Retained urine can lead to bacterial growth, making urinary tract infections more likely to develop.
People may also be constipated or, occasionally, pass stool involuntarily (fecal incontinence).
Rarely, late in the disorder, dementia develops.
If relapses become more frequent, people become increasingly disabled.
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 | Partial or complete loss of vision 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 | |
Muscles and coordination | Weakness and clumsiness Difficulty walking or maintaining balance Uncoordinated movements Stiffness, unsteadiness, and unusual fatigue | |
Intestine and bladder | Problems controlling urination and bowel movements Constipation | |
Speech | Slow, slurred, and hesitant speech | |
Mood | Apathy Mood swings Inappropriate elation or giddiness (euphoria) Inability to control emotions (for example, crying or laughing without reason) | |
Mental function | Subtle or obvious mental impairment Memory loss Poor judgment Inattention | |
Other | ||
Diagnosis of Multiple Sclerosis
Medical history and physical examination
Magnetic resonance imaging
Sometimes additional tests
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. People should clearly describe all of the symptoms they have had to their doctor, particularly if the symptoms are not present when they visit their doctor.
When doctors suspect multiple sclerosis, they thoroughly evaluate the nervous system (neurologic examination) during a physical examination. They examine the back of the eye (retina) with 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 (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 if it is 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:
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. In people with multiple sclerosis, the brain’s response to stimuli may be slow because the demyelinated nerve fibers cannot conduct nerve signals normally. This test can also detect slight damage to the optic nerve that is not causing symptoms.
Spinal tap (lumbar puncture): A sample of cerebrospinal fluid is removed and analyzed. 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.
Other tests can help doctors distinguish multiple sclerosis from disorders that cause similar symptoms, such as advanced HIV infection, tropical spastic paraparesis, vasculitis, arthritis of the neck, Guillain-Barré syndrome, hereditary ataxias, lupus, Lyme disease, rupture of a spinal disc, syphilis, and a cyst in the spinal cord (syringomyelia). For example, blood tests may be done to rule out Lyme disease, syphilis, advanced HIV infection, tropical spastic paraparesis, and lupus, and imaging tests can help rule out arthritis of the neck, rupture of a spinal disk, and syringomyelia.
Blood tests to measure an antibody specific for neuromyelitis optica spectrum disorder may be done to differentiate that disorder from multiple sclerosis.
Treatment of Multiple Sclerosis
Steroids (sometimes called corticosteroids or glucocorticoids) to treat exacerbations and relapses
Disease-modifying medications to help keep the immune system from attacking myelin sheaths
Rehabilitative care and measures to control symptoms
No treatment for multiple sclerosis is uniformly effective.
Steroids
For an acute attack, steroids 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 or methylprednisolone may be taken by mouth, or methylprednisolone may be given intravenously. Although steroids may shorten relapses and temporarily slow the progression of multiple sclerosis, they do not stop its long-term progression.For an acute attack, steroids 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 or methylprednisolone may be taken by mouth, or methylprednisolone may be given intravenously. Although steroids may shorten relapses and temporarily slow the progression of multiple sclerosis, they do not stop its long-term progression.
Steroids 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. Steroids are started and stopped as needed.
Disease-modifying therapies
Disease-modifying therapies (sometimes called DMTs) are medications that help keep the immune system from attacking myelin sheaths. They are most often used to help reduce future relapses, new MRI lesions, and disability. They include moderately effective medications (interferon-beta, glatiramer acetate, and a variety of other classes of medication), and highly effective medications, which include monoclonal antibodies and immunosuppressive therapies.Disease-modifying therapies (sometimes called DMTs) are medications that help keep the immune system from attacking myelin sheaths. They are most often used to help reduce future relapses, new MRI lesions, and disability. They include moderately effective medications (interferon-beta, glatiramer acetate, and a variety of other classes of medication), and highly effective medications, which include monoclonal antibodies and immunosuppressive therapies.
Moderately effective medications:
Interferon-beta injections reduce the frequency of relapses and may help delay disability. They can cause a flu-like syndrome with muscles aches, a low white blood cell count and abnormal liver tests.
Glatiramer acetate injectionsGlatiramer acetate injections may have similar benefits for people with early mild multiple sclerosis. It can cause injection site reactions and flushing.
Teriflunomide, dimethyl fumarate, monomethyl fumarate, diroximel fumarate, fingolimod, siponimod, ozanimod,Teriflunomide, dimethyl fumarate, monomethyl fumarate, diroximel fumarate, fingolimod, siponimod, ozanimod, and ponesimodponesimod 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. Progressive multifocal leukoencephalopathy (PML) is a rare fatal viral infection of the brain and spinal cord causing speech, vision, balance and mental clarity problems.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. Progressive multifocal leukoencephalopathy (PML) is a rare fatal viral infection of the brain and spinal cord causing speech, vision, balance and mental clarity problems.
Highly effective medications:
Natalizumab, rituximab, ocrelizumab, ofatumumab, ublituximab, and alemtuzumabNatalizumab, rituximab, ocrelizumab, ofatumumab, ublituximab, and alemtuzumab are all monoclonal antibodies, medications that block parts of the immune response. They tend be more effective than interferon-beta and glatiramer acetate. They are given by vein and can cause infusion reactions, which may include rash, itching, difficulty breathing, swelling of the throat, dizziness, low blood pressure and fast heart rate. Cladribine, a chemotherapeutic medication, is also classified as highly effective medication and is given orally for relapsing MS.are all monoclonal antibodies, medications that block parts of the immune response. They tend be more effective than interferon-beta and glatiramer acetate. They are given by vein and can cause infusion reactions, which may include rash, itching, difficulty breathing, swelling of the throat, dizziness, low blood pressure and fast heart rate. Cladribine, a chemotherapeutic medication, is also classified as highly effective medication and is given orally for relapsing MS.
Other medications:
Mitoxantrone,Mitoxantrone, a chemotherapy medication that is also highly effective, 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.
Medications that increase the risk of progressive multifocal leukoencephalopathy 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 Jakob Creutzfeldt (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.Medications that increase the risk of progressive multifocal leukoencephalopathy 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 Jakob Creutzfeldt (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 is recommended by some experts for severe relapses not controlled by steroids. 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.
Stem cell transplantation, done at centers that specialize in stem cell transplantation, may be useful for severe, difficult-to-treat disease.
Rehabilitative care and symptom control
Rehabilitation specialists such as physical, occupational, and speech therapists may be contacted to address specific disabilities. Other medications can be used to relieve or control specific symptoms of multiple sclerosis:
Muscle spasms: Muscle relaxants (baclofen or tizanidine) or botulinum toxin injections into affected musclesMuscle relaxants (baclofen or tizanidine) or botulinum toxin injections into affected muscles
Problems with walking: Dalfampridine, taken by mouth, to improve walkingDalfampridine, taken by mouth, to improve walking
Pain due to abnormalities in nerves: Antiseizure medications (such as gabapentin, pregabalin, or carbamazepine) or sometimes tricyclic antidepressants (such as amitriptyline or desipramine)Antiseizure medications (such as gabapentin, pregabalin, or carbamazepine) or sometimes tricyclic antidepressants (such as amitriptyline or desipramine)
Tremors: Clonazepam or gabapentin or in severe cases, referral to a specialist who is experienced in injecting botulinum toxin (a bacterial toxin used to paralyze muscles or to treat wrinkles)Clonazepam or gabapentin or in severe cases, referral to a specialist who is experienced in injecting botulinum toxin (a bacterial toxin used to paralyze muscles or to treat wrinkles)
Fatigue: Amantadine (used to treat Parkinson disease) or, less often, medications used to treat excessive sleepiness (such as modafinil, armodafinil, or amphetamine)Amantadine (used to treat Parkinson disease) or, less often, medications used to treat excessive sleepiness (such as modafinil, armodafinil, or amphetamine)
Depression: Antidepressants such as sertraline or amitriptyline, counseling, or bothAntidepressants such as sertraline or amitriptyline, counseling, or both
Urinary incontinence: Oxybutynin, tamsulosin, mirabegron, Oxybutynin, tamsulosin, mirabegron,other incontinence medications, or botulinum toxin injections, depending on the type of incontinence
Constipation: Stool softeners or laxatives taken regularly
People with urine retention can be taught 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 psychological 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 tend to have more severe multiple sclerosis and because taking vitamin D may reduce the risk of developingosteoporosis, doctors usually recommend that people take vitamin D supplements. Whether vitamin D supplements can help slow the progression of multiple sclerosis is being studied., doctors usually recommend that people take vitamin D supplements. Whether vitamin D supplements can help slow the progression of multiple sclerosis is being studied.
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, 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
The effects of multiple sclerosis 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. Some patients with primary progressive MS may worsen more rapidly. 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.
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