Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, potentially debilitating disease that affects your central nervous system,
which is made up of your brain and spinal cord. Multiple sclerosis is widely believed to be an autoimmune
disease, a condition in which your immune system attacks components of your body as if they're foreign.

In multiple sclerosis, the body mistakenly directs antibodies and white blood cells against proteins in the myelin
sheath, a fatty substance that insulates nerve fibers in your brain and spinal cord. This results in inflammation
and injury to the sheath and ultimately to the nerves that it surrounds. The result may be multiple areas of
scarring (sclerosis). Eventually, this damage can slow or block the nerve signals that control muscle
coordination, strength, sensation and vision.

Multiple sclerosis affects an estimated 300,000 people in the United States and probably more than 1 million
people around the world — including twice as many women as men. Most people experience their first signs or
symptoms between ages 20 and 40.

Multiple sclerosis is unpredictable and varies in severity. In some people, multiple sclerosis is a mild illness, but
it can lead to permanent disability in others. Treatments can modify the course of the disease and relieve
symptoms.

Signs and symptoms

Signs and symptoms of multiple sclerosis vary widely, depending on the location of affected nerve fibers.
Multiple sclerosis symptoms may include:

• Numbness or weakness in one or more limbs, which typically occurs on one side of your body at a time
or the bottom half of your body
• Partial or complete loss of vision, usually in one eye at a time, often with pain during eye movement
• Double vision or blurring of vision
• Tingling or pain in parts of your body
• Electric-shock sensations that occur with certain head movements
• Tremor, lack of coordination or unsteady gait
• Fatigue
• Dizziness

In some cases, people with multiple sclerosis may also develop muscle stiffness or spasticity, slurred speech,
paralysis, or problems with bladder, bowel or sexual function. Mental changes, such as forgetfulness or
difficulties with concentration, also may occur.

Causes

Your central nervous system contains millions of nerve cells that send their electrical signals to and from your
brain along wire-like extensions of the cells called axons, or nerve fibers. Myelin is the fatty substance that
coats and protects these fibers, similar to the way insulation shields electrical wires.

In people with multiple sclerosis, the immune system mistakenly destroys the cells that produce the myelin
sheath. As a result, myelin becomes inflamed and swollen and detaches from the nerve fibers. The detached
myelin may eventually be destroyed. Firm or hardened (sclerosed) patches of scar tissue form over the fibers.
When nerve impulses reach a damaged area, some impulses are blocked or delayed from traveling to or from
your brain. Ultimately, this process leads to degeneration of the nerves themselves, which likely accounts for
the permanent disabilities that may develop in MS.

Doctors and researchers don't understand what causes this autoimmune reaction. Something seems to trigger
the condition in susceptible people.

Genetic factors may make certain people more susceptible to multiple sclerosis. But genetic susceptibility is
only part of the explanation. A number of researchers believe the disorder is related to a protein that mimics the
myelin protein, which may be introduced into the body by a virus. Other researchers believe that the immune
system overreacts toward myelin proteins in people with MS, which leads to an abnormal tendency to develop
autoimmune disease.

A period of disease activity (exacerbation) may be triggered by a viral infection, such as a cold or flu, or by
changes in the immune system during the first six months following a pregnancy.

Patterns of MS
Whatever the multiple sclerosis cause or trigger, the disease occurs in four main patterns:

• Relapsing remitting. This type of multiple sclerosis is characterized by clearly defined flare-ups,
followed by periods of remission. The flare-ups typically appear suddenly, last a few weeks or months,
and then gradually disappear. Most people with MS have this form at the time of diagnosis.
• Primary progressive. People with this less common form of multiple sclerosis experience a gradual
decline, without periods of remission. People with this form of MS are usually older than 40 when signs
or symptoms begin.
• Secondary progressive. More than half the people with relapsing remitting MS eventually enter a
stage of continuous deterioration referred to as secondary progressive MS. Sudden relapses may
occur, superimposed upon the continuous deterioration that characterizes this type of multiple sclerosis.
• Progressive relapsing. This is primary progressive MS with the addition of sudden episodes of new
symptoms or worsened existing ones. This form is relatively uncommon.

Treatment

If your attacks are mild or infrequent, your doctor may advise a wait-and-see approach, with counseling and
observation.

Medications for relapsing MS

If you have a relapsing form of the disease, your doctor may recommend treatment with disease-modifying
medications early in the course of disease. You can't take these medications if you're pregnant or may become
pregnant. These medications for multiple sclerosis treatment include:

• Beta interferons. Interferon beta-1b (Betaseron) and interferon beta-1a (Avonex, Rebif) are genetically
engineered copies of proteins that occur naturally in your body. They help fight viral infection and
regulate your immune system.

If you use Betaseron, you inject yourself under your skin (subcutaneously) every other day. If you use
Rebif, you inject yourself subcutaneously three times a week. You self-inject Avonex into your muscle
(intramuscularly) once a week. These medications reduce but don't eliminate flare-ups of multiple
sclerosis. It's uncertain which of their many actions lead to a reduction in disease activity and what their
 long-term benefits are. Beta interferons aren't used in combination with one another; only one of these
medications is used at a time.

The Food and Drug Administration (FDA) has approved beta interferons only for people with relapsing
forms of MS who can still walk. Beta interferons don't reverse damage and haven't been proved to
significantly alter long-term development of permanent disability. Some people develop antibodies to
beta interferons, which may make them less effective. Other people can't tolerate the side effects,
which may include symptoms similar to those of the flu (influenza).

Doctors generally recommend beta interferons for people who have more than one attack of MS a year
and for those who don't recover well from flare-ups. The treatment may also be used for people who
have a significant buildup of new lesions as seen on an MRI scan, even when there may not be major
new symptoms of disease activity.

The FDA has approved the use of several beta interferons for people who've experienced a single
attack that suggests multiple sclerosis, and who may be at risk of future attacks and developing definite
MS. Risk of MS may also be suggested when an MRI scan of the brain shows lesions that predict a
high risk of conversion to definite MS. Controversy exists as to whether these people should take these
expensive and often inconvenient drugs for indefinite periods, especially because some people do well
both in the short term and long term without therapy. Some doctors prefer to observe people at high risk
with follow-up examinations and MRI scans to document any ongoing inflammatory disease activity
before recommending long-term therapies such as beta interferon.

• Glatiramer (Copaxone). This medication is an alternative to beta interferons if you have relapsing
remitting MS. Doctors believe that glatiramer works by blocking your immune system's attack on
myelin. You must inject glatiramer subcutaneously once daily. Side effects may include flushing and
shortness of breath after injection.
• Natalizumab (Tysabri). This drug is administered intravenously once a month. It works by blocking the
attachment of immune cells to brain blood vessels — a necessary step for immune cells to cross into
the brain — thus reducing the immune cells' inflammatory action on brain nerve cells.

During clinical trials, this drug was shown to significantly reduce the frequency of attacks in people with
relapsing MS. After receiving FDA approval, however, the drug was withdrawn from the market because
of reports from three people who developed a rare, often fatal, brain disorder called progressive
multifocal leukoencephalopathy.

In 2006, after reconsideration of the drug's benefits for people with multiple sclerosis, the FDA agreed
to allow the drug to be marketed again under specific conditions. Chief among these conditions is the
requirement that doctors, pharmacists and patients be involved in a special distribution program known
as TOUCH in order to prescribe, dispense or receive the drug. Because of the drug's risks, it's generally
recommended only for people whose condition hasn't responded to other forms of MS therapy.
Furthermore, there has been no study direct comparing natalizumab to existing treatments to prove
whether it's superior to existing treatments.

• Other medications. Mitoxantrone (Novantrone) is a chemotherapy drug used for many cancers. This
drug is also FDA-approved for treatment of aggressive forms of relapsing remitting MS, as well as
certain forms of progressive MS. It's given intravenously, typically every three months.

Mitoxantrone may cause serious side effects, such as heart damage, after long-term use, so it's
typically not used for longer than two to three years. And it's typically reserved for people with severe
 attacks or rapidly advancing disease who don't respond to other treatments. Close monitoring is critical
for anyone on this medication.

Some doctors are also prescribing other chemotherapy drugs, such as cyclophosphamide (Cytoxan),
for people with severe, rapidly progressing MS. However, these medications aren't FDA-approved for
treatment of MS.

Medications for progressive MS

Some medications may relieve symptoms of progressive MS. They include:

• Corticosteroids. Doctors most often prescribe short courses of oral or intravenous corticosteroids to
reduce inflammation in nerve tissue and to shorten the duration of flare-ups. Prolonged use of these
medications, however, may cause side effects, such as osteoporosis and high blood pressure
(hypertension), and the benefit of long-term therapy in multiple sclerosis isn't established.
• Muscle relaxants. Baclofen (Lioresal) and tizanidine (Zanaflex) are oral treatments for muscle
spasticity. If you have multiple sclerosis, you may experience muscle stiffening or spasms, particularly
in your legs, which can be painful and uncontrollable. This typically occurs in people with persisting or
progressive weakness of their legs. Baclofen may temporarily increase weakness in your legs.
Tizanidine controls muscle spasms without causing your legs to feel weak, but can be associated with
drowsiness or a dry mouth.
• Medications to reduce fatigue. To help combat fatigue, your doctor may prescribe an antidepressant
medication, the antiviral drug amantadine (Symmetrel) or a medication for narcolepsy called modafinil
(Provigil). All drugs prescribed for this purpose appear to work because of their stimulant properties.
One study has showed that aspirin treatment may be effective in controlling MS-related fatigue; further
research is planned to address the benefits of aspirin on fatigue.
• Other medications. Many medications are used for the muscle stiffness, depression, pain and bladder
control problems associated with multiple sclerosis. Drugs for arthritis and medications that suppress
the immune system may slow MS in some cases.

MS treatments other than medications

In addition to medications, these treatments also may be helpful:

• Physical and occupational therapy. A physical or occupational therapist can teach you strengthening
exercises and show you how to use devices that can ease the performance of daily tasks. Therapists
are usually supervised by doctors (physiatrists) who advise and coordinate the therapy that you might
receive. Therapists can assist you in finding optimal mobility assistance devices such as canes,
wheelchairs and motorized scooters. These devices and exercises can help preserve your
independence.
• Counseling. Individual or group therapy may help you cope with multiple sclerosis and relieve
emotional stress. Your family members or caregivers also may benefit from seeing a counselor.
• Plasma exchange (plasmapheresis). Plasma exchange may help restore neurological function in
people with sudden severe attacks of MS-related disability who don't respond to high doses of steroid
treatment. This procedure involves removing some of your blood and mechanically separating the
blood cells from the fluid (plasma). Your blood cells then are mixed with a replacement solution,
typically albumin, or a synthetic fluid with properties like plasma. The solution with your blood is then
returned to your body.

Replacing your plasma may dilute the activity of the destructive factors in your immune system,
including antibodies that attack myelin, and help you to recover. Plasma exchange has no proven
benefit beyond three months from the onset of the neurological symptoms.