Multiple sclerosis

Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord (central nervous system).

In MS, the immune system attacks the protective sheath (myelin) that covers nerve fibers and causes communication problems between your brain and the rest of your body. Eventually, the disease can cause permanent damage or deterioration of the nerves.

Signs and symptoms of MS vary widely and depend on the amount of nerve damage and which nerves are affected. Some people with severe MS may lose the ability to walk independently or at all, while others may experience long periods of remission without any new symptoms.

There's no cure for multiple sclerosis. However, treatments can help speed recovery from attacks, modify the course of the disease and manage symptoms.

Symptoms

Multiple sclerosis signs and symptoms may differ greatly from person to person and over the course of the disease depending on the location of affected nerve fibers. Symptoms often affect movement, such as:

• Numbness or weakness in one or more limbs that typically occurs on one side of your body at a time, or your legs and trunk
• Electric-shock sensations that occur with certain neck movements, especially bending the neck forward (Lhermitte sign)
• Tremor, lack of coordination or unsteady gait

Vision problems are also common, including:

• Partial or complete loss of vision, usually in one eye at a time, often with pain during eye movement
• Prolonged double vision
• Blurry vision

Multiple sclerosis symptoms may also include:

• Slurred speech
• Fatigue
• Dizziness
• Tingling or pain in parts of your body
• Problems with sexual, bowel and bladder function

When to see a doctor

See a doctor if you experience any of the above symptoms for unknown reasons.

Disease course

Most people with MS have a relapsing-remitting disease course. They experience periods of new symptoms or relapses that develop over days or weeks and usually improve partially or completely. These relapses are followed by quiet periods of disease remission that can last months or even years.

Small increases in body temperature can temporarily worsen signs and symptoms of MS, but these aren't considered true disease relapses.

At least 50% of those with relapsing-remitting MS eventually develop a steady progression of symptoms, with or without periods of remission, within 10 to 20 years from disease onset. This is known as secondary-progressive MS.

The worsening of symptoms usually includes problems with mobility and gait. The rate of disease progression varies greatly among people with secondary-progressive MS.

Some people with MS experience a gradual onset and steady progression of signs and symptoms without any relapses, known as primary-progressive MS.

Causes

The cause of multiple sclerosis is unknown. It's considered an autoimmune disease in which the body's immune system attacks its own tissues. In the case of MS, this immune system malfunction destroys the fatty substance that coats and protects nerve fibers in the brain and spinal cord (myelin).

Myelin can be compared to the insulation coating on electrical wires. When the protective myelin is damaged and the nerve fiber is exposed, the messages that travel along that nerve fiber may be slowed or blocked.

It isn't clear why MS develops in some people and not others. A combination of genetics and environmental factors appears to be responsible.

Risk factors

These factors may increase your risk of developing multiple sclerosis:

• Age. MS can occur at any age, but onset usually occurs around 20 and 40 years of age. However, younger and older people can be affected.
• Sex. Women are more than two to three times as likely as men are to have relapsing-remitting MS.
• Family history. If one of your parents or siblings has had MS, you are at higher risk of developing the disease.
• Certain infections. A variety of viruses have been linked to MS, including Epstein-Barr, the virus that causes infectious mononucleosis.
• Race. White people, particularly those of Northern European descent, are at highest risk of developing MS. People of Asian, African or Native American descent have the lowest risk.
• Climate. MS is far more common in countries with temperate climates, including Canada, the northern United States, New Zealand, southeastern Australia and Europe.
• Vitamin D. Having low levels of vitamin D and low exposure to sunlight is associated with a greater risk of MS.
• Certain autoimmune diseases. You have a slightly higher risk of developing MS if you have other autoimmune disorders such as thyroid disease, pernicious anemia, psoriasis, type 1 diabetes or inflammatory bowel disease.
• Smoking. Smokers who experience an initial event of symptoms that may signal MS are more likely than nonsmokers to develop a second event that confirms relapsing-remitting MS.

Complications

People with multiple sclerosis may also develop:

• Muscle stiffness or spasms
• Paralysis, typically in the legs
• Problems with bladder, bowel or sexual function
• Mental changes, such as forgetfulness or mood swings
• Depression
• Epilepsy

Diagnosis

There are no specific tests for MS. Instead, a diagnosis of multiple sclerosis often relies on ruling out other conditions that might produce similar signs and symptoms, known as a differential diagnosis.

Your doctor is likely to start with a thorough medical history and examination.

Your doctor may then recommend:

• Blood tests, to help rule out other diseases with symptoms similar to MS. Tests to check for specific biomarkers associated with MS are currently under development and may also aid in diagnosing the disease.
• Spinal tap (lumbar puncture), in which a small sample of cerebrospinal fluid is removed from your spinal canal for laboratory analysis. This sample can show abnormalities in antibodies that are associated with MS. A spinal tap can also help rule out infections and other conditions with symptoms similar to MS.
• MRI, which can reveal areas of MS (lesions) on your brain and spinal cord. You may receive an intravenous injection of a contrast material to highlight lesions that indicate your disease is in an active phase.
• Evoked potential tests, which record the electrical signals produced by your nervous system in response to stimuli. An evoked potential test may use visual stimuli or electrical stimuli. In these tests, you watch a moving visual pattern, or short electrical impulses are applied to nerves in your legs or arms. Electrodes measure how quickly the information travels down your nerve pathways.

In most people with relapsing-remitting MS, the diagnosis is fairly straightforward and based on a pattern of symptoms consistent with the disease and confirmed by brain imaging scans, such as MRI.

Diagnosing MS can be more difficult in people with unusual symptoms or progressive disease. In these cases, further testing with spinal fluid analysis, evoked potentials and additional imaging may be needed.

Treatment

There is no cure for multiple sclerosis. Treatment typically focuses on speeding recovery from attacks, slowing the progression of the disease and managing MS symptoms. Some people have such mild symptoms that no treatment is necessary.

Treatments for MS attacks

• Corticosteroids, such as oral prednisone and intravenous methylprednisolone, are prescribed to reduce nerve inflammation. Side effects may include insomnia, increased blood pressure, increased blood glucose levels, mood swings and fluid retention.
• Plasma exchange (plasmapheresis). The liquid portion of part of your blood (plasma) is removed and separated from your blood cells. The blood cells are then mixed with a protein solution (albumin) and put back into your body. Plasma exchange may be used if your symptoms are new, severe and haven't responded to steroids.

Treatments to modify progression

For primary-progressive MS, ocrelizumab (Ocrevus) is the only FDA-approved disease-modifying therapy (DMT). Those who receive this treatment are slightly less likely to progress than those who are untreated.

For relapsing-remitting MS, several disease-modifying therapies are available.

Much of the immune response associated with MS occurs in the early stages of the disease. Aggressive treatment with these medications as early as possible can lower the relapse rate, slow the formation of new lesions, and potentially reduce risk of brain atrophy and disability accumulation.

Many of the disease-modifying therapies used to treat MS carry significant health risks. Selecting the right therapy for you will depend on careful consideration of many factors, including duration and severity of disease, effectiveness of previous MS treatments, other health issues, cost, and child-bearing status.

Treatment options for relapsing-remitting MS include injectable and oral medications.

Injectable treatments include:

• Interferon beta medications.These drugs are among the most commonly prescribed medications to treat MS. They are injected under the skin or into muscle and can reduce the frequency and severity of relapses.

  Side effects of interferons may include flu-like symptoms and injection-site reactions.

  You'll need blood tests to monitor your liver enzymes because liver damage is a possible side effect of interferon use. People taking interferons may develop neutralizing antibodies that can reduce drug effectiveness.

• Glatiramer acetate (Copaxone, Glatopa). This medication may help block your immune system's attack on myelin and must be injected beneath the skin. Side effects may include skin irritation at the injection site.

Oral treatments include:

• Fingolimod (Gilenya). This once-daily oral medication reduces relapse rate.

  You'll need to have your heart rate and blood pressure monitored for six hours after the first dose because your heartbeat may be slowed. Other side effects include rare serious infections, headaches, high blood pressure and blurred vision.

• Dimethyl fumarate (Tecfidera). This twice-daily oral medication can reduce relapses. Side effects may include flushing, diarrhea, nausea and lowered white blood cell count. This drug requires blood test monitoring on a regular basis.
• Diroximel fumarate (Vumerity). This twice-daily capsule is similar to dimethyl fumarate but typically causes fewer side effects. It's approved for the treatment of relapsing forms of MS.
• Teriflunomide (Aubagio). This once-daily oral medication can reduce relapse rate. Teriflunomide can cause liver damage, hair loss and other side effects. This drug is associated with birth defects when taken by both men and women. Therefore, use contraception when taking this medication and for up to two years afterward. Couples who wish to become pregnant should talk to their doctor about ways to speed elimination of the drug from the body. This drug requires blood test monitoring in a regular basis.
• Siponimod (Mayzent). Research shows that this once-daily oral medication can reduce relapse rate and help slow progression of MS. It's also approved for secondary-progressive MS. Possible side effects include viral infections, liver problems and low white blood cell count. Other possible side effects include changes in heart rate, headaches and vision problems. Siponimod is harmful to a developing fetus, so women who may become pregnant should use contraception when taking this medication and for 10 days after stopping the medication. Some might need to have the heart rate and blood pressure monitored for six hours after the first dose. This drug requires blood test monitoring on a regular basis
• Cladribine (Mavenclad). This medication is generally prescribed as second line treatment for those with relapsing-remitting MS. It was also approved for secondary-progressive MS. It is given in two treatment courses, spread over a two-week period, over the course of two years. Side effects include upper respiratory infections, headaches, tumors, serious infections and reduced levels of white blood cells. People who have active chronic infections or cancer should not take this drug, nor should women who are pregnant or breast-feeding. Men and women should use contraception when taking this medication and for the following six months. You may need monitoring with blood tests while taking cladribine.

Infusion treatments include:

• Ocrelizumab (Ocrevus). This humanized monoclonal antibody medication is the only DMT approved by the FDA to treat both the relapse-remitting and primary-progressive forms of MS. Clinical trials showed that it reduced relapse rate in relapsing disease and slowed worsening of disability in both forms of the disease.

  Ocrelizumab is given via an intravenous infusion by a medical professional. Infusion-related side effects may include irritation at the injection site, low blood pressure, a fever and nausea, among others. Some people may not be able to take ocrelizumab, including those with a hepatitis B infection. Ocrelizumab may also increase the risk of infections and some types of cancer, particularly breast cancer.

• Natalizumab (Tysabri). This medication is designed to block the movement of potentially damaging immune cells from your bloodstream to your brain and spinal cord. It may be considered a first line treatment for some people with severe MS or as a second line treatment in others.

  This medication increases the risk of a potentially serious viral infection of the brain called progressive multifocal leukoencephalopathy (PML) in people who are positive for antibodies to the causative agent of PML JC virus. People who don't have the antibodies have extremely low risk of PML.

• Alemtuzumab (Campath, Lemtrada). This drug helps reduce relapses of MS by targeting a protein on the surface of immune cells and depleting white blood cells. This effect can limit potential nerve damage caused by the white blood cells. But it also increases the risk of infections and autoimmune disorders, including a high risk of thyroid autoimmune diseases and rare immune mediated kidney disease.

  Treatment with alemtuzumab involves five consecutive days of drug infusions followed by another three days of infusions a year later. Infusion reactions are common with alemtuzumab.

  The drug is only available from registered providers, and people treated with the drug must be registered in a special drug safety monitoring program. Alemtuzumab is usually recommended for those with aggressive MS or as second line treatment for patients who failed another MS medication.

Treatments for MS signs and symptoms

• Physical therapy. A physical or occupational therapist can teach you stretching and strengthening exercises and show you how to use devices to make it easier to perform daily tasks.

  Physical therapy along with the use of a mobility aid when necessary can also help manage leg weakness and other gait problems often associated with MS.

• Muscle relaxants. You may experience painful or uncontrollable muscle stiffness or spasms, particularly in your legs. Muscle relaxants such as baclofen (Lioresal, Gablofen), tizanidine (Zanaflex) and cyclobenzaprine may help. Onabotulinumtoxin A treatment is another option in those with spasticity.
• Medications to reduce fatigue. Amantadine (Gocovri, Osmolex), modafinil (Provigil) and methylphenidate (Ritalin) may be helpful in reducing MS-related fatigue. Some drugs used to treat depression, including selective serotonin reuptake inhibitors, may be recommended.
• Medication to increase walking speed. Dalfampridine (Ampyra) may help to slightly increase walking speed in some people. People with a history of seizures or kidney dysfunction should not take this medication.
• Other medications. Medications also may be prescribed for depression, pain, sexual dysfunction, insomnia, and bladder or bowel control problems that are associated with MS.

Lifestyle and home remedies

To help relieve the signs and symptoms of MS, try to:

• Get plenty of rest. Look at your sleep habits to make sure you're getting the best possible sleep. To make sure you're getting enough sleep, you may need to be evaluated — and possibly treated — for sleep disorders such as obstructive sleep apnea.
• Exercise. If you have mild to moderate MS, regular exercise can help improve your strength, muscle tone, balance and coordination. Swimming or other water exercises are good options if you're bothered by heat. Other types of mild to moderate exercise recommended for people with MS include walking, stretching, low-impact aerobics, stationary bicycling, yoga and tai chi.
• Cool down. MS symptoms often worsen when the body temperature rises in some people with MS. Avoiding exposure to heat and using devices such as cooling scarves or vests can be helpful.
• Eat a balanced diet. Since there's little evidence to support a particular diet, experts recommend a generally healthy diet. Some research suggests that vitamin D may have potential benefit for people with MS.
• Relieve stress. Stress may trigger or worsen your signs and symptoms. Yoga, tai chi, massage, meditation or deep breathing may help.

Alternative medicine

Many people with MS use a variety of alternative or complementary treatments or both to help manage their symptoms, such as fatigue and muscle pain.

Activities such as exercise, meditation, yoga, massage, eating a healthier diet, acupuncture and relaxation techniques may help boost overall mental and physical well-being, but there are few studies to back up their use in managing symptoms of MS.

According to guidelines from the American Academy of Neurology, research strongly indicates that oral cannabis extract (OCE) may improve symptoms of muscle spasticity and pain. There is a lack of evidence that cannabis in any other form is effective in managing other MS symptoms.

Daily intake of vitamin D3 of 2,000-5,000 international units daily is recommended in those with MS. The connection between vitamin D and MS is supported by the association with exposure to sunlight and the risk of MS.

Coping and support

Living with any chronic illness can be difficult. To manage the stress of living with MS, consider these suggestions:

• Maintain normal daily activities as best you can.
• Stay connected to friends and family.
• Continue to pursue hobbies that you enjoy and are able to do.
• Contact a support group, for yourself or for family members.
• Discuss your feelings and concerns about living with MS with your doctor or a counselor.

Preparing for an appointment

You may be referred to a doctor who specializes in disorders of the brain and nervous system (neurologist).

What you can do

• Write down your symptoms, including any that may seem unrelated to the reason why you scheduled the appointment.
• Make a list of all your medications, vitamins and supplements.
• Bring any clinical notes, scans, laboratory test results or other information from your primary care provider to your neurologist.
• Write down your key medical information, including other conditions.
• Write down key personal information, including any recent changes or stressors in your life.
• Write down questions to ask your doctor.
• Ask a relative or friend to accompany you, to help you remember what the doctor says.

What to expect from your doctor

Your doctor is likely to ask you a number of questions. Being ready to answer them may reserve time to go over points you want to spend more time on. You may be asked:

• When did you begin experiencing symptoms?
• Have your symptoms been continuous or occasional?
• How severe are your symptoms?
• What, if anything, seems to improve your symptoms?
• What, if anything, appears to worsen your symptoms?
• Does anyone in your family have multiple sclerosis?

Questions to ask your doctor

• What's the most likely cause of my symptoms?
• What kinds of tests do I need? Do they require any special preparation?
• Is my condition likely temporary or chronic?
• Will my condition progress?
• What treatments are available?
• I have these other health conditions. How can I best manage them together?

In addition to the questions that you've prepared to ask your doctor, don't hesitate to ask other questions during your appointment.

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