What organs are affected by myasthenia gravis?

Myasthenia Gravis

Myasthenia gravis is an autoimmune disease that affects the contact point between nerves and muscles. For some unknown reason, the body’s immune system, which normally helps fight infections, attacks the acetylcholine receptors found on muscles.

These receptors normally receive a chemical called acetylcholine, which is released by the nerves at the neuromuscular junction (the point of contact between nerve and muscle) and signals the muscles to contract. Once these receptors are damaged or processes involved with the receptors are altered, the muscles cannot respond to the nerve signals and the muscles become weak.

Myasthenia gravis is almost twice as common in women as in men. It is most commonly diagnosed in women under 40 and men over 50 but it can occur at any age. Children are very unlikely to suffer from this disease. People from all continents are equally susceptible.

A closely related disease called congenital myasthenic syndrome is genetically inherited. Myasthenia gravis itself probably has a genetic component, but the children of people with this condition are only slightly more likely than average to suffer from autoimmune disease.

Myasthenia gravis is a serious condition, but not usually life-threatening. Most people with myasthenia gravis have a life expectancy that is the same as for someone without it. People affected with myasthenia gravis have reduced physical activities, reduced quality of life, and spend more days being sick. In severe cases, the chest muscles can become so weak that patients have trouble breathing on their own and may require a ventilator for a few days to a few weeks.

Causes

The exact cause of myasthenia gravis is not known. One theory is that the condition may be triggered by a virus or other infection that has a similar structure to a part of the acetylcholine receptor (found in the neuromuscular junction and needed for normal function). The antibodies that the immune system produces to fight the virus then also mistakenly attack the receptors.

What we do know is that certain antibodies have been found in the blood of people with myasthenia gravis that are built to attack acetylcholine receptors.

Sometimes women with myasthenia gravis who give birth transmit these particular antibodies to their babies, causing muscle weakness in the infant. This is called neonatal myasthenia and occurs in about 12% of babies whose mother has myasthenia gravis. It is different from congenital myasthenia because the infant gets better in a few weeks as the antibody blood levels go down.

Some people with myasthenia gravis do not have antibodies to acetylcholine receptors. Many of these people, though, have antibodies to an enzyme involved in acetylcholine receptor function.

The other abnormality that often shows up in people with myasthenia gravis is an overactive, overlarge, or otherwise malfunctioning thymus. The thymus is a gland located where the neck joins the chest. It is important for the normal development of the immune system. Normally, the thymus is larger in childhood than in adulthood and becomes inactive around puberty. In people with myasthenia gravis, however, it often keeps going into adulthood.

Some people with myasthenia gravis turn out to have a thymoma (a tumour in the thymus). This is a type of cancer, but very few people die of thymomas (see «Treatment and Prevention»).

Along with infection, symptoms may be triggered by surgery or medications.

Symptoms and Complications

The most common symptoms of myasthenia gravis are double vision (diplopia), drooping eyelids (ptosis), and muscle weakness that usually gets worse after exercise or at the end of the day and improves with rest.

The muscles around the eyes are particularly likely to be affected by myasthenia gravis, and eye problems are the first sign of the disease in about 40% of cases. Eventually, 85% of people with myasthenia gravis will experience eye symptoms. About 15% of people experience symptoms only around the eyes and nowhere else – this is called ocular myasthenia gravis. Those who do get symptoms elsewhere will usually develop them within the first 3 years.

Other common symptoms of this disease include:

• blurred vision
• difficulty chewing or swallowing
• inability to stand up without using hands
• unstable or unusual gait
• weakness in the arms, legs, hands, and fingers
• weakness in the muscles of facial expression

Many people find that their symptoms rise and fall in intensity many times in the course of a single day. Often, they follow a similar pattern each day, with muscle fatigue at its worst in the evening.

People who find it temporarily impossible to eat may have to be admitted to hospital and be fed intravenously. Of more immediate danger is when the disease causes difficulty in breathing. This is called a myasthenic crisis, and it’s responsible for most of the small number of deaths due to myasthenia gravis. People with breathing problems must go to a hospital immediately.

Making the Diagnosis

Your doctor will ask you questions about your symptoms and perform a physical exam. To help diagnose myasthenia gravis, your doctor may order blood tests to detect antibodies that may be affecting the function of acetylcholine receptors.

Your doctor may use the ice pack test as part of the physical exam if your eyelids are noticeably drooping. An ice pack is placed on the closed lid for 2 minutes, and if the drooping improves after the test, you’re more likely be diagnosed with myasthenia gravis.

Another important diagnostic test is called electromyography (EMG) and single-fibre EMG. These tests are used to determine whether the nerve-to-muscle contact is working properly.

A chest X-ray or CAT scan of the chest may be done to look for a thymoma. Breathing tests called pulmonary function tests may also be done.

Treatment and Prevention

Myasthenia gravis can be managed well with treatment. A treatment plan may involve one or more of the following:

Medications: Anticholinesterase-inhibiting medications like pyridostigmine and neostigmine control symptoms. Corticosteroids (e.g., prednisone) and immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus, mycophenolate mofetil, cyclophosphamide) can slow or stop the disease process. Although these medications don’t cure it, they are the mainstay of long-term management.

Plasmapheresis: Large amounts of blood are removed, then put in a centrifuge to separate the red and white cells from the serum, the liquid that contains the immune antibodies which are doing the damage. The red and white cells are then replaced, along with donated or synthetic serum.

Immunoglobulin: The fact that this treatment works suggests that a weakened immune system is part of the cause of myasthenia gravis. Immunoglobulin therapy involves injections of blood serum from a person without autoimmune disease. It lowers the numbers of tissue-attacking antibodies in the bloodstream of the person with myasthenia gravis.

Monoclonal Antibodies: Monoclonal antibodies are a treatment option for people who have a disease that has not responded to other therapies. The medication eculizumab is a manufactured antibody which helps suppress specific parts of the immune system.

Thymectomy: The thymus isn’t essential in adults and it can be surgically removed without negative effects. Symptoms will improve in about 70% of people who have a thymectomy, and some of these people may be cured. Many others can reduce the dose of their medication(s). In fact, the cure rate in myasthenia gravis patients with thymomas is about the same as in people with an apparently healthy thymus or a malfunctioning but non-cancerous thymus.

Some people diagnosed with myasthenia gravis are diagnosed with thymoma at the same time. Fortunately, thymomas are slow-growing tumours, and while they’re not actually benign (noncancerous), they have a low chance of spreading in any given year. Most thymomas are found while they’re still localized in the thymus, and removing that organ usually provides a complete and lasting cure for both the myasthenia and the cancer. In fact, myasthenia gravis is often a lifesaver, because it alerts doctors to a tumour while there’s still plenty of time to do something about it.

Nothing can prevent this disease, since we don’t know what causes it. However, serious complications can be prevented if people with myasthenia gravis go to the hospital if they ever have difficulty breathing. Up to 20% of people with this disease will face a myasthenic crisis at some point.

It is also recommended to get a seasonal influenza vaccination for all people receiving immunosuppressive therapy, and for those with neurologic conditions such as myasthenia gravis. Studies have shown that people who received the influenza vaccine had a lower incidence of symptom aggravation compared to those who had an influenza-like illness.

Myasthenia Gravis (MG)

People with myasthenia gravis (MG) have muscle weakness that worsens throughout the day. This autoimmune disease affects the neuromuscular system. Drooping eyelids are often the first sign. Eventually, you may find it difficult to control your neck and limbs. Medications and surgery can help relieve the symptoms of this lifelong illness.

Overview

What is myasthenia gravis?

Myasthenia gravis (MG) is an autoimmune disease, meaning the body’s immune system mistakenly attacks its own parts. MG affects the communication between nerves and muscles (the neuromuscular junction).

People with MG lose the ability to control muscles voluntarily. They experience muscle weakness and fatigue of various severity. They may not be able to move muscles in the eyes, face, neck and limbs. MG is a lifelong neuromuscular disease. There isn’t a cure, but treatments can help and some patients may achieve remission.

How common is myasthenia gravis?

MG affects about 20 out of every 100,000 people. Experts estimate that 36,000 to 60,000 Americans have this neuromuscular disease. The actual number of people affected may be higher, as some people with mild cases may not know they have the disease.

Who might get myasthenia gravis?

MG mostly affects women aged 20 to 40 and men aged 50 to 80. About one in 10 cases of MG occur in teenagers (juvenile MG). The illness can affect people of all ages but is rare in children.

These factors increase risk:

• History of other autoimmune diseases, such as rheumatoid arthritis and lupus.
• Infections.
• Medications for malaria, heart arrhythmias and cancer.
• Surgical procedures.
• Thyroid disease.

What are the types of myasthenia gravis?

Autoimmune MG is the most common form of this neuromuscular disease. Autoimmune MG may be:

• Ocular: The muscles that move the eyes and eyelids weaken. Your eyelids may droop, or you may not be able to keep your eyes open. Some people have double vision. Eye weakness is often the first sign of MG. Nearly half of people with ocular MG evolve into the generalized form within two years of the first symptom.
• Generalized: Muscle weakness affects the eye and other body parts such as the face, neck, arms, legs and throat. You may find it difficult to speak or swallow, lift your arms over your head, stand up from a seated position, walk long distances and climb stairs.

How does myasthenia gravis affect pregnancy?

In rare instances, pregnancy brings on MG symptoms for the first time. If you already have MG, symptoms may worsen during the first trimester or immediately after childbirth. In some patients, MG symptoms improve during pregnancy.

Certain MG treatments are not safe during pregnancy or breastfeeding. Your healthcare provider can guide you through this time, ensuring a healthy pregnancy.

Is myasthenia gravis inherited?

In general, autoimmune MG isn’t inherited. It’s rare for more than one member of the same family to receive a diagnosis of autoimmune MG. The non-autoimmune form of MG (also called congenital myasthenic syndrome) can affect more than one member of the same family.

A pregnant woman cannot pass MG to her infant. However, about one in 10 babies born to women with MG develop a temporary condition called neonatal myasthenia. These infants may have weak cries or sucking reflexes at birth. These symptoms go away in a few weeks. This condition doesn’t increase a child’s risk of developing MG in the future.

Symptoms and Causes

What causes myasthenia gravis?

MG is an autoimmune disease. For unknown reasons, the body’s immune system attacks itself.

In someone with a healthy immune system, nerves and muscles communicate a bit like a tiny baseball game:

1. Nerves (the pitcher) send signals to muscles (the catcher) across a synapse (connection) called the neuromuscular junction. To communicate, nerves release a molecule called acetylcholine (the baseball).
2. Muscles have sites called acetylcholine receptors (the catcher’s glove). The acetylcholine binds to the receptors in the muscle tissue, like a ball landing in a glove.
3. When the acetylcholine binds to the receptor, it triggers the muscle fiber to contract.

In a healthy person, nerves signal muscles work effortlessly, like one ballplayer catching a ball and throwing it to a teammate.

But people with MG have antibodies that destroy the receptor sites, blocking nerve-muscle communication. The “catcher” can’t catch the ball, and communication becomes sluggish or doesn’t work at all.

What is the connection between thymus gland problems and MG?

Many people with MG have thymus gland conditions that may bring on MG. The thymus is a small organ in the upper chest that is part of the lymphatic system. It makes white blood cells that fight infections. Two-thirds of young people with MG have overactive thymic cells (thymic hyperplasia). About one in 10 people with MG have thymus gland tumors called thymomas, which may be benign (not cancer) or cancerous.

What are the symptoms of myasthenia gravis?

Initial symptoms of MG often come on suddenly. The neuromuscular disease causes your muscles to get weaker when you’re active. Muscle strength returns when you rest.

The intensity of muscle weakness often changes from day to day. Most people feel strongest at the start of the day and weakest at the end of the day.

Symptoms of MG include:

• Double vision.
• Drooping eyelids (ptosis).
• Difficulty speaking, chewing or swallowing.
• Difficulty moving their neck up or holding up their head.
• Limb weakness.
• Trouble walking.

In rare instances, MG affects muscles in your respiratory system. You may have shortness of breath or more serious breathing problems.

Diagnosis and Tests

How is myasthenia gravis diagnosed?

Your healthcare provider will perform a physical exam and assess your symptoms. You may undergo these tests:

• Ice pack test: If you have severely drooping eyelids, your provider may place ice packs on your eyes or have you rest with your eyes shut in a dark room for a few minutes. If the drooping improves after the ice application or rest, you may have MG.
• Antibody tests: About 85% of people with MG have unusually high levels of acetylcholine receptor antibodies in their blood. Approximately 6% patients have muscle-specific kinase (MuSK) antibodies. Antibodies may not be detected in less than 10% of MG patients.
• Imaging scans: An MRI or CT scan can check for thymus gland problems like tumors.
• Electromyogram (EMG): An EMG measures the electrical activity of muscles and nerves. This test detects communication problems between nerves and muscles.

Management and Treatment

What are the complications of myasthenia gravis?

Weakness and fatigue from MG can keep you from participating in activities you enjoy. This may lead to depression.

Up to one in five people with MG experience a myasthenic crisis or severe respiratory muscle weakness. They may need a respirator or other treatments to help them breathe. This is a life-threatening medical emergency. Weak muscles, infections, fevers and reactions to medications can cause a crisis.

How is myasthenia gravis treated?

Myasthenia gravis is a treatable disease and most patients will live a relatively normal life with treatment.

Treatments for MG focus on improving symptoms. Treatments include:

• Medications: Cholinesterase inhibitors (anticholinesterase) boost signals between nerves and muscles to improve muscle strength. Immunosuppressants, including corticosteroids, decrease inflammation and reduce your body’s production of abnormal antibodies.
• Monoclonal antibodies: You receive intravenous (IV) infusions of biologically engineered proteins. These proteins suppress an overactive immune system.
• IV immunoglobulin (IVIG): You receive IV infusions of donor antibodies over a period of two to five days. IVIG can treat myasthenia crisis as well as generalized MG.
• Plasma exchange (plasmapheresis): An IV line removes abnormal antibodies from your blood.
• Surgery: A thymectomy is surgery to remove the thymus gland. Even if tests don’t show a problem with your thymus gland, surgical removal sometimes improves symptoms.

Myasthenia gravis

Myasthenia gravis is a neuromuscular disorder. Neuromuscular disorders involve the muscles and the nerves that control them.

Causes

Myasthenia gravis is a type of autoimmune disorder. An autoimmune disorder occurs when the immune system mistakenly attacks healthy tissue. Antibodies are proteins made by the body’s immune system when it detects harmful substances. Antibodies may be produced when the immune system mistakenly considers healthy tissue to be a harmful substance, such as in the case of myasthenia gravis. In people with myasthenia gravis, the body produces antibodies that block the muscle cells from receiving messages (neurotransmitters) from the nerve cells.

In some cases, myasthenia gravis is linked to tumors of the thymus (an organ of the immune system).

Myasthenia gravis can affect people at any age. It is most common in young women and older men.

Symptoms

Myasthenia gravis causes weakness of the voluntary muscles. These are muscles that you can control. Autonomic muscles of the heart and digestive tract are usually not affected. The muscle weakness of myasthenia gravis worsens with activity and improves with rest.

This muscle weakness can lead to a variety of symptoms, including:

• Breathing difficulty because of weakness of the chest wall muscles
• Chewing or swallowing difficulty, causing frequent gagging, choking, or drooling
• Difficulty climbing stairs, lifting objects, or rising from a seated position
• Difficulty talking
• Drooping head and eyelids
• Facial paralysis or weakness of the facial muscles
• Fatigue
• Hoarseness or changing voice
• Double vision
• Difficulty maintaining steady gaze

Exams and Tests

The health care provider will perform a physical exam. This includes a detailed nervous system (neurological) examination. This may show:

• Muscle weakness, with eye muscles usually affected first
• Weakness usually fluctuates and gets worse with exercise
• Normal reflexes and feeling (sensation)

Tests that may be done include:

• Blood test to check for acetylcholine receptor antibodies associated with this disease
• CT or MRI scan of the chest to look for a tumor
• Nerve conduction studies to test how fast electrical signals move through a nerve
• Electromyography (EMG) to test the health of the muscles and the nerves that control the muscles
• Pulmonary function tests to measure breathing and how well the lungs are functioning
• Edrophonium test to see if this medicine reverses the symptoms for a short time

Treatment

There is no known cure for myasthenia gravis. Treatment may allow you to have periods without any symptoms (remission).

Lifestyle changes can often help you continue your daily activities. The following may be recommended:

• Resting throughout the day
• Using an eye patch if double vision is bothersome
• Avoiding stress and heat exposure, which can make symptoms worse

Medicines that may be prescribed include:

• Neostigmine or pyridostigmine to improve communication between the nerves and muscles
• Prednisone and other drugs (such as azathioprine, cyclosporine, or mycophenolate mofetil) to suppress the immune system response if you have severe symptoms and other medicines have not worked well
• Other immunological therapies target specific immune cells or inflammatory response

Crisis situations are attacks of weakness of the breathing muscles. These attacks can occur without warning when either too much or too little medicine is taken. These attacks usually last no longer than a few weeks. You may need to be admitted to the hospital, where you may need breathing assistance with a ventilator.

A procedure called plasmapheresis may also be used to help end the crisis. This procedure involves removing the clear part of the blood (plasma), which contains the antibodies. This is replaced with donated plasma that is free of antibodies, or with other fluids. Plasmapheresis may also help reduce symptoms for 4 to 6 weeks and is often used before surgery.

A medicine called intravenous immunoglobulin (IVIg) may also be used

Surgery to remove the thymus (thymectomy) may result in permanent remission or less need for medicines, especially when there is a tumor present.

If you have eye problems, your doctor may suggest lens prisms to improve vision. Surgery may also be recommended to treat your eye muscles.

Physical therapy can help maintain your muscle strength. This is especially important for the muscles that support breathing.

Some medicines can worsen symptoms and should be avoided. Before taking any medicine, ask your doctor whether it is OK for you to take it.