Myasthenia gravis

Myasthenia gravis (my-us-THEE-nee-uh GRAY-vis) is characterized by weakness and rapid fatigue of any of the muscles under your voluntary control. It's caused by a breakdown in the normal communication between nerves and muscles.

There's no cure for myasthenia gravis, but treatment can help relieve signs and symptoms, such as weakness of arm or leg muscles, double vision, drooping eyelids, and difficulties with speech, chewing, swallowing and breathing.

Though this disease can affect people of any age, it's more common in women younger than 40 and in men older than 60.

Symptoms

Muscle weakness caused by myasthenia gravis worsens as the affected muscle is used. Because symptoms usually improve with rest, muscle weakness can come and go. However, the symptoms tend to progress over time, usually reaching their worst within a few years after the onset of the disease.

Although myasthenia gravis can affect any of the muscles that you control voluntarily, certain muscle groups are more commonly affected than others.

Eye muscles

In more than half of people who develop myasthenia gravis, their first signs and symptoms involve eye problems, such as:

• Drooping of one or both eyelids (ptosis)
• Double vision (diplopia), which may be horizontal or vertical, and improves or resolves when one eye is closed

Face and throat muscles

In about 15% of people with myasthenia gravis, the first symptoms involve face and throat muscles, which can:

• Impair speaking. Your speech might sound soft or nasal, depending on which muscles have been affected.
• Cause difficulty swallowing. You might choke easily, making it difficult to eat, drink or take pills. In some cases, liquids you're trying to swallow come out your nose.
• Affect chewing. The muscles used for chewing might tire halfway through a meal, particularly if you've been eating something hard to chew, such as steak.
• Change facial expressions. For example, your smile might look like a snarl.

Neck and limb muscles

Myasthenia gravis can also cause weakness in your neck, arms and legs. Weakness in your legs can affect how you walk. Weak neck muscles make it hard to hold up your head.

When to see a doctor

Talk to your doctor if you have difficulty:

• Breathing
• Seeing
• Swallowing
• Chewing
• Walking
• Using your arms or hands
• Holding up your head

Causes

Antibodies

Your nerves communicate with your muscles by releasing chemicals (neurotransmitters) that fit precisely into receptor sites on the muscle cells at the nerve-muscle junction.

In myasthenia gravis, your immune system produces antibodies that block or destroy many of your muscles' receptor sites for a neurotransmitter called acetylcholine (as-uh-teel-KOH-leen). With fewer receptor sites available, your muscles receive fewer nerve signals, resulting in weakness.

Antibodies can also block the function of a protein called muscle-specific receptor tyrosine kinase (TIE-roh-seen KIE-nays), sometimes referred to as MuSK. This protein is involved in forming the nerve-muscle junction. Antibodies against this protein can lead to myasthenia gravis. Antibodies against another protein, called lipoprotein-related protein 4 (LRP4), can play a part in the development of this condition. Other antibodies have been reported in research studies and the number of antibodies involved will likely expand over time. Some people have myasthenia gravis that isn't caused by antibodies blocking acetylcholine, MuSK or LRP4. This type of myasthenia gravis is called seronegative myasthenia gravis or antibody-negative myasthenia gravis. In general, researchers assume that these types of myasthenia gravis still have an autoimmune basis but the antibodies involved are just not detectable yet.

Symptoms

Thymus gland

The thymus gland is a part of your immune system situated in the upper chest beneath your breastbone. Researchers believe that the thymus gland triggers or maintains the production of the antibodies that block acetylcholine.

Large in infancy, the thymus gland is small in healthy adults. In some adults with myasthenia gravis, however, the thymus gland is abnormally large. Some people with myasthenia gravis also have tumors of the thymus gland (thymomas). Usually, thymomas aren't cancerous (malignant), but they can become cancerous.

Causes

Other causes

Rarely, mothers with myasthenia gravis have children who are born with myasthenia gravis (neonatal myasthenia gravis). If treated promptly, children generally recover within two months after birth.

Some children are born with a rare, hereditary form of myasthenia gravis, called congenital myasthenic syndrome.

Symptoms

Factors that can worsen myasthenia gravis

• Fatigue
• Illness or infection
• Surgery
• Stress
• Some medications — such as beta blockers, quinidine gluconate, quinidine sulfate, quinine (Qualaquin), phenytoin, certain anesthetics and some antibiotics
• Pregnancy
• Menstrual periods

Complications

Complications of myasthenia gravis are treatable, but some can be life-threatening.

Myasthenic crisis

Myasthenic crisis is a life-threatening condition that occurs when the muscles that control breathing become too weak to work. Emergency treatment and mechanical assistance with breathing are needed. Medications and blood-filtering therapies help people to again breathe on their own.

Thymus gland tumors

Some people with myasthenia gravis have a tumor in the thymus gland, a gland under the breastbone that is involved with the immune system. Most of these tumors, called thymomas, aren't cancerous (malignant).

Other disorders

People with myasthenia gravis are more likely to have the following conditions:

• Underactive or overactive thyroid. The thyroid gland, which is in the neck, secretes hormones that regulate your metabolism. If your thyroid is underactive, you might have difficulties dealing with cold, weight gain and other issues. An overactive thyroid can cause difficulties dealing with heat, weight loss and other issues.
• Autoimmune conditions. People with myasthenia gravis might be more likely to have autoimmune conditions, such as rheumatoid arthritis or lupus.

Diagnosis

Your doctor will review your symptoms and your medical history and conduct a physical examination. Your doctor might use several tests, including:

Neurological examination

Your doctor may check your neurological health by testing:

• Reflexes
• Muscle strength
• Muscle tone
• Senses of touch and sight
• Coordination
• Balance

Tests to help confirm a diagnosis of myasthenia gravis might include:

Ice pack test

If you have a droopy eyelid, your doctor might place a bag filled with ice on your eyelid. After two minutes, your doctor removes the bag and analyzes your droopy eyelid for signs of improvement.

Blood analysis

A blood test might reveal the presence of abnormal antibodies that disrupt the receptor sites where nerve impulses signal your muscles to move.

Repetitive nerve stimulation

In this nerve conduction study, doctors attach electrodes to your skin over the muscles to be tested. Doctors send small pulses of electricity through the electrodes to measure the nerve's ability to send a signal to your muscle.

To diagnose myasthenia gravis, doctors will test the nerve repeatedly to see if its ability to send signals worsens with fatigue.

Single-fiber electromyography (EMG)

This test measures the electrical activity traveling between your brain and your muscle. It involves inserting a fine wire electrode through your skin and into a muscle to test a single muscle fiber.

Imaging

Your doctor might order a CT scan or an MRI to check if there's a tumor or other abnormality in your thymus.

Pulmonary function tests

These tests evaluate whether your condition is affecting your breathing.

Treatment

Various treatments, alone or in combination, can relieve symptoms of myasthenia gravis. Your treatment will depend on your age, how severe your disease is and how fast it's progressing.

Medications

• Cholinesterase inhibitors. Medications such as pyridostigmine (Mestinon, Regonal) enhance communication between nerves and muscles. These medications aren't a cure, but they can improve muscle contraction and muscle strength in some people.

  Possible side effects include gastrointestinal upset, diarrhea, nausea, and excessive salivation and sweating.

• Corticosteroids. Corticosteroids such as prednisone (Rayos) inhibit the immune system, limiting antibody production. Prolonged use of corticosteroids, however, can lead to serious side effects, such as bone thinning, weight gain, diabetes and increased risk of some infections.

• Immunosuppressants. Your doctor might also prescribe other medications that alter your immune system, such as azathioprine (Azasan, Imuran), mycophenolate mofetil (Cellcept), cyclosporine (Sandimmune, Gengraf, others), methotrexate (Trexall) or tacrolimus (Astrograf XL, Prograf, others). These drugs, which can take months to work, might be used with corticosteroids.

  Side effects of immunosuppressants, such as increased risk of infection and liver or kidney damage, can be serious.

Intravenous therapy

The following therapies are usually used in the short term to treat a sudden worsening of symptoms or before surgery or other therapies.

• Plasmapheresis (plaz-muh-fuh-REE-sis). This procedure uses a filtering process similar to dialysis. Your blood is routed through a machine that removes the antibodies that block transmission of signals from your nerve endings to your muscles' receptor sites. However, the good effects usually last only a few weeks, and repeated procedures can lead to difficulty accessing veins for the treatment.

  Risks associated with plasmapheresis include a drop in blood pressure, bleeding, heart rhythm problems or muscle cramps. Some people develop an allergic reaction to the solutions used to replace the plasma.

• Intravenous immunoglobulin (IVIg). This therapy provides your body with normal antibodies, which alters your immune system response. Benefits are usually seen in less than a week and can last 3 to 6 weeks.

  Side effects, which usually are mild, can include chills, dizziness, headaches and fluid retention.

• Monoclonal antibody. Rituximab (Rituxan) and the more recently approved eculizumab (Soliris) are intravenous medications for myasthenia gravis. These drugs are usually used for people who don't respond to other treatments. They can have serious side effects.

Surgery

Some people with myasthenia gravis have a tumor in the thymus gland. If you have a tumor, called a thymoma, doctors will surgically remove your thymus gland (thymectomy).

Even if you don't have a tumor in the thymus gland, removing the gland might improve your myasthenia gravis symptoms. However, the benefits of thymectomy can take years to develop.

A thymectomy can be performed as an open surgery or as a minimally invasive surgery. In open surgery, your surgeon splits the central breastbone (sternum) to open your chest and remove your thymus gland.

Minimally invasive surgery to remove the thymus gland uses smaller incisions. It might also involve:

• Video-assisted thymectomy. In one form of this surgery, surgeons make a small incision in your neck or a few small incisions in the side of your chest. They then use a long, thin camera (video endoscope) and small instruments to see and remove the thymus gland.
• Robot-assisted thymectomy. In this form of thymectomy, surgeons make several small incisions in the side of your chest and remove the thymus gland using a robotic system, which includes a camera arm and mechanical arms.

These procedures might cause less blood loss, less pain, lower mortality rates and shorter hospital stays compared with open surgery.

Lifestyle and home remedies

To help you make the most of your energy and cope with the symptoms of myasthenia gravis:

• Adjust your eating routine. Try to eat when you have good muscle strength. Take your time chewing your food, and take a break between bites of food. You might find it easier to eat small meals several times a day. Also, try eating mainly soft foods and avoid foods that require more chewing, such as raw fruits or vegetables.
• Use safety precautions at home. Install grab bars or railings in places where you need support, such as next to the bathtub or next to steps. Keep your floors clean, and move area rugs. Outside your home, keep paths, sidewalks and driveways cleared of leaves, snow and other debris that could cause you to stumble.
• Use electric appliances and power tools. To help you maintain your energy, try using an electric toothbrush, electric can openers and other electrical tools to perform tasks.
• Wear an eye patch. If you have double vision, an eye patch can help relieve the problem. Try wearing one to write, read or watch television. Periodically switch the eye patch to the other eye to help reduce eyestrain.
• Plan. If you have chores, shopping or errands to do, plan the activity for when you have the most energy.

Coping and support

Coping with myasthenia gravis can be difficult for you and your loved ones. Stress can worsen your condition, so find ways to relax. Ask for help when you need it.

Learn all you can about your condition, and have your loved ones learn about it as well. You all might benefit from a support group, where you can meet people who understand what you and your family members are going through.

Preparing for an appointment

You're likely to first see your family doctor, who will then refer you to a doctor trained in nervous system conditions (neurologist) for further evaluation.

Here's information to help you get ready for your appointment.

What you can do

Take a friend or family member along to help you absorb the information you're given. Make a list of:

• Your symptoms and when they began
• All medications, vitamins or supplements you take, including doses
• Questions to ask your doctor

For myasthenia gravis, questions to ask your doctor include:

• What is likely causing my symptoms?
• What tests do I need?
• What course of action do you recommend?
• What are the alternatives to the approach you're suggesting?
• I have other health conditions. How can I best manage them together?
• Are there restrictions I need to follow?
• Are there brochures or other printed materials I can have? What websites do you recommend?

Don't hesitate to ask other questions.

What to expect from your doctor

Be prepared to answer questions your doctor is likely to ask, such as:

• 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?

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