Antibodies

Your nerves communicate with your muscles by releasing chemicals (neurotransmitters) that fit precisely into receptor sites on the muscle cells at the nerve-muscular 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 may also block the function of a protein called a muscle-specific receptor tyrosine kinase (TIE-roh-seen KIE-nays). This protein is involved in forming the nerve-muscular junction. When antibodies block the function of this protein, it may lead to myasthenia gravis. Research continues to study how the antibodies inhibiting this protein are related to the development of myasthenia gravis.

Thymus gland

Researchers believe that the thymus gland, a part of your immune system situated in the upper chest beneath your breastbone, may trigger or maintain the production of the antibodies that block acetylcholine.

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

Other causes

Some people may have myasthenia gravis that isn't caused by antibodies blocking acetylcholine or the muscle-specific receptor tyrosine kinase. This type of myasthenia gravis is called antibody-negative myasthenia gravis. Antibodies against another protein, called lipoprotein-related protein 4, may play a part in the development of this condition.

Genetic factors also may be associated with myasthenia gravis.

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, called congenital myasthenic syndrome.

Factors that can worsen myasthenia gravis

• Fatigue
• Illness
• Stress
• Some medications — such as beta blockers, quinidine gluconate, quinidine sulfate, quinine (Qualaquin), phenytoin (Dilantin), certain anesthetics and some antibiotics

Overview

Myasthenia gravis is a condition that happens when communication between nerves and muscles breaks down. This causes muscles to feel weak and get tired quickly. This condition may affect any of the muscles you control, called voluntary muscles. Certain muscle groups are more commonly affected than others. These include muscles in the face, throat, arms and legs.

Your eyelids may droop, you may have double vision, trouble speaking or eating, or you may have trouble holding up your head because of weak neck muscles. Myasthenia gravis can happen at any age. But it's more common in people younger than 40 who were assigned female at birth and people older than 60 who were assigned male at birth.

There's no way to prevent or cure myasthenia gravis. But treatment can help manage symptoms.

Symptoms

Thymus gland

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

The thymus gland is large in babies and small in adults who don't have health conditions. In some adults with myasthenia gravis, the thymus gland is larger than usual. Some people with myasthenia gravis also have tumors of the thymus gland. These tumors are called thymomas. Thymomas are cancer, but they usually aren't malignant. This means the cancer typically does not spread throughout the body. These tumors may be removed with surgery.

Causes

Other causes

Children born to people with myasthenia gravis may rarely have the condition at birth. 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. Congenital myasthenic syndrome is often treated with medicine to manage symptoms.

Factors that can make myasthenia gravis worse include:

• Fatigue.
• Illness or infection.
• Surgery.
• Stress.
• Some medicines:
  • Beta blockers.
  • Quinidine gluconate, quinine sulfate (such as Qualaquin).
  • Phenytoin (such as Dilantin).
  • Some anesthetics and antibiotics.
• Pregnancy.
• Menstrual periods.

Risk factors

While the exact cause of myasthenia gravis is not fully understood, certain factors may increase the likelihood of having it.

• Genetics. A personal or family history of autoimmune conditions may put you at higher risk.
• Thymus gland issues. Having an enlarged thymus or a thymoma may play a role in myasthenia gravis.
• Age and sex assigned at birth. Myasthenia gravis is more common in people younger than 40 who were assigned female at birth, and in people older than 60 who were assigned male at birth.
• Lifestyle and health. Stress, infections and some medicines may trigger the condition in some people.

These factors increase the risk but do not mean you will get myasthenia gravis.

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 breathe on their own.

Thymus gland tumors

Some people with myasthenia gravis have tumors in their thymus glands. The thymus gland lies under the breastbone and is part of the immune system. Most of these tumors, called thymomas, are not malignant, meaning they likely will not spread and can be removed with surgery.

Other conditions

People with myasthenia gravis often have other autoimmune conditions, such as:

• Thyroid disease. The thyroid is a gland located in the neck that helps manage metabolism. Metabolism is how the body uses energy. If your thyroid is too active or not active enough, you may have a hard time managing body temperature and weight and you may have other symptoms.
• Rheumatoid arthritis. This condition causes inflammation and pain, typically in the bones of joints.
• Lupus. In this condition, the immune system attacks healthy tissues throughout the body. This can damage the skin, joints, kidneys, heart and brain. Symptoms range from mild, such as fatigue, joint pain and skin rashes, to severe, such as kidney inflammation or cardiovascular issues.

Diagnosis

Your healthcare professional talks to you about your symptoms, reviews your medical history and does a physical exam. Your health professional also does a neurological exam.

Neurological exam

During a neurological exam, your health professional may test:

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

There are several other tests your care team may use to diagnose myasthenia gravis.

Ice pack test

If you have a droopy eyelid, your health professional might put a bag filled with ice on your eyelid. After two minutes, your health professional removes the bag and checks whether the eyelid is less droopy.

Blood test

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

Repetitive nerve stimulation

In this nerve conduction study, a healthcare professional attaches electrodes to the skin over the muscles to be tested. Small pulses of electricity are sent to the nerve going to that muscle. These pulses measure whether the nerve can send a signal to the muscle.

The nerve is tested several times to see if its ability to send signals gets worse with fatigue. If your nerve tires, this may be a sign of myasthenia gravis.

Single-fiber electromyography, also called EMG

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

Imaging

Your health professional might order a CT scan or an MRI to check for a tumor or other concerns 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 depends on your age, how severe your disease is and how fast it's progressing.

Medicines

• Cholinesterase inhibitors. Medicines such as pyridostigmine (Mestinon, Regonol) improve communication between nerves and muscles. These medicines aren't a cure but may improve muscle contraction and strength in some people.

  Possible side effects include gastrointestinal upset, diarrhea, nausea, and too much saliva and sweat.

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

• Immunosuppressants. Your health professional 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 a 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. They also may be used before other therapies or surgery.

• Plasmapheresis. This procedure uses a blood-filtering machine similar to that used for dialysis. The machine removes antibodies from the blood that block the transmission of signals from nerve endings to your muscles. However, the benefits from this procedure usually last only a few weeks. Having this done several times can make it hard to find veins for further treatments.

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

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

Side effects are usually mild. They may include chills, dizziness, headaches and fluid retention.

• Rituximab (Rituxan). This is a medicine injected into a vein to treat myasthenia gravis. It works by targeting proteins on B-cells. Other medicines that are similar B-cell-depleting monoclonal antibodies may increase over time. These medicines are usually used when other treatments don't work. They can have serious side effects.

Neonatal Fc receptor blockers

Neonatal Fc receptor blockers stick to and block a protein called the neonatal Fc receptor. This lowers the amount of certain antibodies in the body, including the ones that cause symptoms of myasthenia gravis. Examples include:

• Efgartigimod (Vyvgart). This medicine is given through an IV or an injection every week for 4 weeks. This is usually done several times.
• Rozanolixizumab (Rystiggo). This medicine is given through an IV every week for 6 weeks. This is usually done several times.

Other therapies

Molecular therapies target specific molecules in a cell. They work on a part of the immune system called the complement system. Therapies may include:

• Eculizumab (Soliris) and ravulizumab (Ultomiris). These medicines are given through an IV every 2 to 6 weeks. You must have a meningococcus vaccination or be on antibiotics to prevent meningococcus infection.
• Zilucoplan (Zilbrysq). This therapy is a daily injection that can be done at home. It blocks a harmful protein and helps stop muscle damage. Newer therapies also target a protein in the cells that breaks down the harmful antibodies more quickly. These newer therapies are called FcRN receptor blockers.
• Chimeric antigen receptor (CAR) T-cell therapy. This therapy is being studied to treat people with myasthenia gravis who do not respond to standard therapies.

These therapies also may be combined with traditional treatments and other therapies. For some, these may be promising alternatives, but research is ongoing.

Surgery

Some people with myasthenia gravis have tumors in their thymus glands. A thymus gland tumor is called a thymoma. If you have a thymoma, you'll likely need surgery to remove the thymus gland. The surgery is called thymectomy.

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

The thymectomy can be done as an open surgery or as a minimally invasive surgery.

During open surgery to remove the thymus, a surgeon splits the breastbone, called the sternum, to open the chest and remove the thymus gland.

During minimally invasive surgery, the surgeon uses video cameras or robot-assisted tools to help guide the surgery. This allows the surgeon to use smaller incisions to remove the thymus.

• Video-assisted thymectomy. Typically, 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. Surgeons make several small openings in the side of the chest. They use a robotic system that includes a camera and mechanical arms with attached surgical instruments to remove the thymus gland.

Minimally invasive surgeries may cause less blood loss and less pain than open surgery does. They also may increase survival rates and shorten hospital stays.

Your surgeon decides the type of surgery that is best for you. This may depend on your thymus gland, tumor and overall health.

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. 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 where you need support, such as next to bathtubs or stairs. Keep your floors clean and move area rugs to prevent tripping. 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 you have to do, plan the activity for times during the day when you typically have the most energy.

Coping and support

Coping with myasthenia gravis can be hard 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. Families may benefit from a support group to meet people who understand the challenges of managing myasthenia gravis.

Preparing for an appointment

You'll likely see your primary healthcare professional first. Your health professional may 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 and supplements you take, including doses.
• Questions to ask your healthcare professional.

For myasthenia gravis, questions to ask your healthcare professional 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 healthcare professional 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?