Myasthenia Gravis

Myasthenia gravis is a condition where muscles become easily tired and weak. It is due to a problem with how the nerves stimulate the muscles to contract. The muscles around the eyes are commonly affected first. This causes drooping of the eyelid and double vision. Treatment is usually effective.

Understanding muscle

There are three types of muscle:

• Skeletal muscles are attached to bones and move the arms, legs, face, eyes, etc. Each muscle is made up from many muscle fibres.
• Smooth muscle forms part of body organs that need to contract such as the bladder, uterus, gut, etc.
• Heart (cardiac) muscle is a special type of muscle that pumps blood.

Myasthenia gravis only affects skeletal muscle. Each skeletal muscle is supplied by a nerve which divides into smaller nerves that spread along the muscle fibres. There is a tiny gap between the ends of the nerves and the surface of the muscle fibres. This gap is called the neuromuscular junction (see diagram below).

The brain sends messages down the nerves to the muscles it wants to contract. The nerve endings release a chemical called a neurotransmitter into the neuromuscular junction. The neurotransmitter for skeletal muscle is called acetylcholine. This quickly attaches to receptors on the muscle fibres. This in turn triggers the muscle fibres to contract. There are many acetylcholine receptors on each muscle fibre.

What happens in myasthenia gravis and what causes it?

People with myasthenia gravis have a fault in the way nerve messages are passed from the nerves to the muscles. The muscles are not stimulated properly, and so do not contract well and become easily tired and weak.

The fault is is due to a problem with the immune system. Myasthenia gravis is an 'autoimmune disease'. The immune system normally makes antibodies (special proteins) to attack bacteria, viruses and other 'germs'. In people with autoimmune diseases, the immune system makes antibodies against part or parts of the body.

In most people with myasthenia gravis, antibodies are made against the acetylcholine receptors on muscle fibres (described above). An antibody can block or cause damage to a receptor. The acetylcholine cannot then attach to the receptor and so the stimulus for a muscle to contract is reduced.

The receptors are continually being replaced and repaired and there is ongoing competition for the receptors between the acetylcholine and the abnormal antibodies. How easily a muscle tires and its degree of weakness depends on how many of its receptors are damaged or blocked at any given time.

What causes the abnormal antibodies to be made?
The reason why the body's immune system starts to make abnormal antibodies against muscle receptors is not known. Some factor probably 'triggers' the immune system in people who are prone to this condition from their genetic makeup. (One known trigger is a medicine called penicillamine which is sometimes used to treat arthritis. However, in most cases of myasthenia gravis, the trigger is not known - it may be a virus or some other factor in the environment.)

Abnormal antibodies are made in various parts of the immune system which includes: the bone marrow; blood; lymph glands; thymus gland. However, the thymus gland is thought to be a main source of the abnormal antibodies (or where antibodies made in other parts of the immune system are 'programmed' to attack the muscle receptors). This explains why removing the thymus gland often cures or improves the condition (see below).

Who gets myasthenia gravis?

Myasthenia gravis can develop at any age. It occurs in all areas of the world. About 1 in 100,000 people in the UK develop myasthenia gravis each year. It is not strictly hereditary but genetic factors play a part. Therefore close relatives of an affected person have a slightly higher chance of developing myasthenia gravis than average.

Variants of myasthenia gravis

A different antibody
About 3 in 20 people with myasthenia gravis do not have the classical antibody against the acetylcholine receptor. It is thought that these people have a different antibody that attacks a different part of the muscle. However, the symptoms that result are the same.

Thymus abnormalities
The thymus gland is a small gland at the root of the neck just behind the upper sternum (breastbone). It is part of the immune system. The thymus is abnormal in many people with myasthenia gravis, particularly in those who develop myasthenia gravis before the age of 40. Cells in the abnormal thymus are thought play a major role in myasthenia gravis in about 6 in 10 people who develop myasthenia gravis before the age of 40. Their exact role is not clear but they may have something to do with 'programming' or making antibodies against acetylcholine receptors.

A small number of people with myasthenia gravis develop a tumour (growth) of the thymus gland called a thymoma. If it occurs it is usually benign (non-cancerous) but it is malignant (cancerous) in a small number of cases.

Congenital myasthenia
There are a variety of rare disorders caused by inherited abnormal muscle receptors and related structures. These are not dealt with further in this leaflet.

What are the symptoms of myasthenia gravis?

The typical main symptom is weakness of muscles that gets worse with activity and improves with rest. In effect, affected muscles tire or become fatigued very easily. Symptoms may come and go at first when using the muscles.

• The muscles around the eyes are commonly affected first as these are constantly used and can quickly tire. This causes drooping of the eyelid (ptosis) and double vision. These are the first symptoms to occur in about 2 in 3 cases. In some people the muscles around the eyes are the only ones affected (when the level of abnormal antibody is low). If symptoms only affect the muscles around the eyes for longer than two years then the condition is unlikely to progress to other muscles. However, it commonly progresses to affect other muscles.
• Muscles around the neck, face and throat are commonly affected. This can cause difficulty in swallowing, speaking and chewing. You may have difficulty in holding your head up.
• Weakness in the arms, legs and other skeletal muscles may develop.
• Weakness in the chest muscles sometimes occurs. If this is severe a 'myasthenic crisis' may result. This is when breathing is affected due to severe weakness of the muscles used to breathe. A myasthenic crisis is unusual, but can be life-threatening.

The severity of symptoms (how easily the muscles tire) can vary from mild to severe. Infection or stress can make symptoms worse.

Are tests needed?

• A blood test can detect the abnormal antibody and confirm the diagnosis in most cases.
• Muscle and nerve tests may be needed in some cases where the diagnosis is not clear.
• A scan of the upper chest may be advised to look for a thymoma (described above) which occurs in a small number of cases.
• Tests to detect other autoimmune disorders may be done. For example, thyroid hormone tests. (People with myasthenia gravis have a higher than average chance of developing other autoimmune disorders such as thyroid disorders.)

What is the treatment for myasthenia gravis?

Anticholinesterase medicines
These medicines delay the breakdown of acetylcholine when it is released from the nerve endings (see diagram above). More acetylcholine is then available to compete against the abnormal antibodies for the muscle receptors. These medicines work best when the disease is mild and the level of antibody is low. For example, in people who just have the eye muscle symptoms. The most commonly prescribed anticholinesterase medicine is called pyridostigmine.

Thymectomy (removal of the thymus)
This is an option in some cases. The thymus gland lies just behind the sternum (breast-bone). It is most commonly removed in people below the age of 40 where the thymus gland is often a major factor in the making of the abnormal antibodies. Marked improvement is expected in about half of cases, and a 'cure' in about 3 in 10 people with myasthenia gravis who:

• are under 40.
• have the classic antibody causing myasthenia gravis.
• have widespread symptoms - not just confined to around the eyes.

Steroid medication
Steroid medication such as prednisolone tablets is commonly used if the above measures do not control symptoms. Steroids suppress the immune system and prevent the abnormal antibodies from being made. Treatment with steroids usually work well. A low dose, often on alternate days, is usually enough for people where symptoms only affect muscles around the eye. Higher doses may be needed to prevent symptoms if muscles other than around the eyes are affected.

It may take several months to bring symptoms under control with steroids. But once improved, the dose is commonly reduced gradually to find the lowest dose needed to prevent symptoms. In some people the dose of steroid needed to control the disease may be quite high and lead to side-effects. (A separate leaflet discusses steroid tablets and their side-effects in more detail.)

Immunosuppressant medicines
An immunosuppressant medicine such as azothiaprine may be advised in some cases in addition to steroid medication. These medicines work by suppressing the immune system. A steroid plus an immunosuppressant tends to work better than either alone. Also, the dose of steroid needed may be less if an immunosuppressant is added. This means that any side-effects from steroids are likely to be less serious.

Intensive care
Admission to hospital may be needed in a few cases if a 'myasthenia crisis' develops (see above). This may involve intensive care and assisted breathing by a ventilator machine for a while. Plasma exchange may be given. This is where your plasma is exchanged for blood donor's plasma which is free of abnormal antibody. This quickly gets rid of the abnormal antibody for a short while. This then gives time for other treatments described above to be started or modified.

What is the course of the disease and prognosis (outlook)?

Without treatment
Untreated, the disease is typically 'active' for 5-7 years and symptoms may progressively get worse over this time. Symptoms can vary in severity from person to person and from time to time in the same person. After this time the symptoms may reduce or even go away completely (a spontaneous remission). Up to 1 in 5 people with myasthenia gravis can expect a spontaneous remission where the disease 'goes away'. However, recurrences may occur sometime in the future even if symptoms do clear. Also, without treatment, up to 3 in 10 people would die within 10 years of developing myasthenia gravis.

With treatment
Treatment usually works well. With treatment, most people with myasthenia gravis can expect improvement and many will become free of symptoms. So, although myasthenia gravis literally means 'grave muscle weakness', the outlook is not as 'grave' as it once was. Life expectancy is now normal in most cases. In the cases where the disease 'goes away' after a few years, then treatment such as steroids or immunosuppressive medicines can be stopped.

Further help and information

Myasthenia Gravis Association
Keynes House, Chester Park, Alfreton Road, Derby, DE21 4AS
Tel (helpline): 0800 919 922  Web: www.mgauk.org

© EMIS and PIP 2005   Updated: September 2005