Myasthenia gravis

Overview

Myasthenia gravis (my-us-THEE-nee-uh GRAY-vis) causes muscles under your voluntary control to feel weak and get tired quickly. This happens when the communication between nerves and muscles breaks down.

There's no cure for myasthenia gravis. Treatment can help with symptoms. These symptoms can include weakness of arm or leg muscles, double vision, drooping eyelids, and problems with speaking, chewing, swallowing and breathing.

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

Symptoms

Muscle weakness caused by myasthenia gravis gets worse when the affected muscle is used. Because symptoms usually get better with rest, muscle weakness can come and go. However, the symptoms tend to progress over time. They usually reach their worst within a few years after the disease begins.

Myasthenia gravis may affect any of the muscles that you can control. Certain muscle groups are more commonly affected than others.

Eye muscles

In more than half the people who develop myasthenia gravis, their first symptoms affect the eyes. Symptoms include:

• Drooping of one or both eyelids, called ptosis.
• Double vision, called 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. These symptoms can:

• Make speaking difficult. Your speech might sound soft or nasal, depending on which muscles are affected.
• Cause problems with swallowing. You might choke easily, making it difficult to eat, drink or take pills. Sometimes, liquids you're trying to swallow come out your nose.
• Affect chewing. The muscles used for chewing might tire halfway through a meal. This is especially true 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 also can cause weakness in the neck, arms and legs. Weakness in the legs can affect how you walk. Weak neck muscles make it hard to hold up the head.

When to see a doctor

Talk to your health care provider if you have problems:

• 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, called neurotransmitters, that fit into places on the muscle cells, called receptor sites, at the nerve-muscle junction.

In myasthenia gravis, the immune system makes 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. This causes weakness.

Antibodies also can block a protein called muscle-specific receptor tyrosine kinase (TIE-roh-seen KIE-nays), sometimes referred to as MuSK. This protein helps form 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 this condition. Research studies have found other antibodies and the number of antibodies involved will likely grow 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, also known as antibody-negative myasthenia gravis. In general, researchers believe that this type of myasthenia gravis still comes from a problem with autoimmunity, but the antibodies involved just can't be found yet.

Symptoms

Thymus gland

The thymus gland is a part of your immune system. This gland is located in the upper chest beneath the breastbone. Researchers believe that the thymus gland makes or helps produce the antibodies that block acetylcholine.

The thymus gland is large in babies and small in healthy adults. In some adults with myasthenia gravis, however, the thymus gland is larger than usual. Some people with myasthenia gravis also have tumors of the thymus gland, called thymomas. Usually, thymomas aren't cancerous, also known as malignant. But thymomas can become cancerous.

Causes

Other causes

Rarely, mothers with myasthenia gravis have children who are born with myasthenia gravis. This is called neonatal myasthenia gravis. If treated immediately, children usually recover within two months after birth.

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

Factors that can make myasthenia gravis worse include:

• Fatigue.
• Illness or infection.
• Surgery.
• Stress.
• Some medicines — such as beta blockers, quinidine gluconate, quinidine sulfate, quinine (Qualaquin), phenytoin (Dilantin), 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. It happens when the muscles that control breathing become too weak to work. Emergency treatment and mechanical assistance with breathing are needed. Medicines and therapies that filter the blood help people to breathe on their own.

Thymus gland tumors

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

Other disorders

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

• Underactive or overactive thyroid. The thyroid gland in the neck secretes hormones that regulate the metabolism. If the thyroid is underactive, you might have problems dealing with cold, weight gain and other issues. An overactive thyroid can cause problems 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 health care provider will look at your symptoms and medical history and conduct a physical examination. Your provider might use several tests, including:

Neurological examination

Your provider 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 provider might put a bag filled with ice on your eyelid. After two minutes, your provider removes the bag and analyzes your droopy eyelid for improvement.

Blood analysis

A blood test might show nontypical antibodies that interrupt the receptor sites where nerves signal your muscles to move.

Repetitive nerve stimulation

In this nerve conduction study, providers attach electrodes to your skin over the muscles to be tested. Small pulses of electricity run through the electrodes. These pulses measure whether the nerve can send a signal to the muscle.

During this test, the nerve is tested several times to see if its ability to send signals gets worse with fatigue. Results from this test help inform a diagnosis of myasthenia gravis.

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 provider might order a CT scan or an MRI to check if there's a tumor or other problem with your thymus.

Pulmonary function tests

These tests measure whether your condition is affecting your breathing.

Treatment

Various treatments, alone or together, can help with 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. Medicines such as pyridostigmine (Mestinon, Regonal) improve communication between nerves and muscles. These medicines 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 too much salivation and sweating.

• Corticosteroids. Corticosteroids such as prednisone (Rayos) block the immune system, making it less able to produce antibodies. Use of corticosteroids over a long period of time, however, can lead to serious side effects. These include bone thinning, weight gain, diabetes and higher risk of some infections.

• Immunosuppressants. Your provider also might prescribe other medicines that change your immune system. These medicines could include azathioprine (Azasan, Imuran), mycophenolate mofetil (Cellcept), cyclosporine (Sandimmune, Gengraf, others), methotrexate (Trexall) or tacrolimus (Astagraf XL, Prograf, others). These medicines, which can take months to work, might be used with corticosteroids.

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

Intravenous therapy

The following therapies are usually used for a short time to treat symptoms that suddenly get worse or before surgery or other therapies.

• Plasmapheresis (plaz-muh-fuh-REE-sis). This procedure uses a filtering process that's like dialysis. Your blood is put through a machine that removes the antibodies that block transmission of signals from your nerve endings to your muscles. However, the good effects from this procedure usually last only a few weeks. Having several procedures can lead to problems finding veins for the treatment.

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

• Intravenous immunoglobulin (IVIg). This therapy provides your body with typical 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 eculizumab (Soliris) are medicines given by vein for myasthenia gravis. These medicines are usually used when other treatments don't work. 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, you'll need surgery to remove the thymus gland, called thymectomy.

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

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

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

• Video-assisted thymectomy. In one form of this surgery, surgeons make a small opening in the neck or a few small openings in the side of the chest. They then use a long, thin camera, called a video endoscope, and small instruments to see and remove the thymus gland.
• Robot-assisted thymectomy. In this form of thymectomy, surgeons make several small openings in the side of the chest. They use a robotic system to remove the thymus gland. This system 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 trip.
• Use electric appliances and power tools. To save 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. Try wearing one to write, read or watch television. Switch the eye patch to the other eye regularly 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 make your condition worse, 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 primary care provider, who will then refer you to a doctor trained in nervous system conditions, called a 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 understand the information you're given. Make a list of:

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

For myasthenia gravis, questions to ask your provider 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 provider 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?