Myasthenia gravis

Understanding muscle

Each muscle is supplied by a nerve which splits into smaller nerves as they spread along the muscle fibres. There is a tiny gap between the ends of the nerves and the surface of the muscle. This gap is called the neuromuscular junction (see diagram below).

Myasthenia gravis

The brain sends messages down the nerves to the muscles it wants to tighten (contract). The nerve endings release a chemical called a neurotransmitter into the neuromuscular junction. This neurotransmitter is called acetylcholine. The acetylcholine moves across the neuromuscular junction and quickly attaches to receptors on the muscles. This triggers the muscle to tighten (contract). There are lots of acetylcholine receptors on each muscle fibre.

People with myasthenia gravis have a fault in the way nerve messages are passed from the nerves to the muscles at the neuromuscular junction. The muscles become easily tired and weak.

Myasthenia gravis is an autoimmune disease. This means that Immunsystems (which normally protects the body from infections) mistakenly attacks itself. (Other autoimmune diseases include Typ-1-Diabetes and thyroid disorders.) In most people with myasthenia gravis, antibodies are made which block, alter or destroy the acetylcholine receptors on muscles. The acetylcholine cannot then attach to the receptor on the muscle fibre at the neuromuscular junction and so the muscle is less able to tighten (contract).

What causes the abnormal antibodies to be made?

Myasthenia gravis usually occurs in people whose bodies have particular DNA which makes them more likely to have myasthenia gravis.

The reason why the body's immune system starts to make abnormal antibodies against muscle receptors is not known. Abnormal antibodies are made in various parts of the immune system, including:

• The bone marrow.

• Blood.

• Lymph glands.

• The thymus gland.

Myasthenia gravis is a rare condition. It can occur at any age but most commonly affects women aged between 30 and 40 and men aged 50-70 years. Women are slightly more likely than men to have myasthenia gravis, particularly in certain ethnic backgrounds. It can occur in more than one member of the same family.

The thymus gland is a small gland in the upper chest just behind the breastbone (sternum). It is part of the immune system. The thymus is abnormal in many people with myasthenia gravis. The exact role of the cells in the thymus is not clear. However, the cells may have something to do with programming or making antibodies against acetylcholine receptors. For some people, surgical removal of the thymus gland by an operation can improve their symptoms or allow them to take less medication to manage their symptoms.

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

The typical main symptom is weakness of muscles that becomes worse with activity and improves with rest. Affected muscles tire or become fatigued very easily. This means that symptoms are usually worse at the end of the day and after exercising. Fatigue is also a very common symptom.

The symptoms vary enormously between people with myasthenia gravis:

• The muscles around the eyes are commonly affected first. This causes drooping of the eyelid (ptosis), and double vision (diplopia). In some people, the muscles around the eyes are the only ones affected. This is known as ocular myasthenia and affects 1 in 7 people with myasthenia gravis. Some people with ocular myasthenia (they only have eye symptoms) develop generalised myasthenia (affecting other parts of their body) within the first few years of their symptoms starting.

• Muscles around the face and throat are often affected. Difficulty swallowing, slurred speech, voice changes or repeatedly coughing or choking when eating may be the first signs of myasthenia gravis.

• Weakness in the arms, legs and neck may develop.

• Weakness in the chest muscles sometimes occurs. If this is severe, a myasthenic crisis may result (see below).

The severity of symptoms (how easily the muscles tire) can vary from mild to severe. Most people notice their symptoms are at their most troublesome in the first couple of years. Infection, stress and certain medications can make symptoms worse.

It is not uncommon for the diagnosis of myasthenia gravis to take some time. This is because it is a rare condition and the symptoms often start gradually. If a doctor thinks you may have myasthenia gravis they will examine you to check for muscle weakness, and to see if your muscles tire quickly.

Tests that may then be done include the following:

• A blood test to detect the abnormal antibodies and confirm the diagnosis in most cases.

• Blood tests may be done to look for other autoimmune conditions.

• Muscle and nerve tests may be needed in some cases where the diagnosis is not clear. These usually happen in hospital settings.

• If you are diagnosed with myasthenia gravis, further tests will include:

  • More blood tests to look for other autoimmune disease which may exist alongside.

  • A CT scan of the chest to assess the thymus gland.

• Breathing tests are performed in those people who have weakness of the chest muscles.

• People who have double vision (diplopia) will have a scan of their brain. This is to check that there are no masses inside the brain which could be causing the double vision. If this scan is normal, the medical team can be more confident the double vision is caused by myasthenia gravis.

In most cases, myasthenia gravis can be effectively treated. Often, combinations of these treatments are needed to best control symptoms.

Anticholinesterase medicines

These medicines slow the breakdown of the neurotransmitter acetylcholine when it is released from the nerve endings. More acetylcholine is then available to compete against the abnormal antibodies for the muscle receptors, which then improves the strength of the muscles. These medicines work best when the disease is mild and the level of antibody is low. The most commonly prescribed anticholinesterase medicine is called pyridostigmine. Diarrhoea is a common side-effect of this but it usually resolves without treatment.

Removal of the thymus (thymectomy)

This is an option in some cases and can improve symptoms for some people with myasthenia gravis.

Immunosuppressant medication

Steroid medication

Steroid medication such as Prednisolon tablets is often used in the treatment of myasthenia gravis. Steroids suppress the immune system and prevent the abnormal antibodies from being made.

It may take several months for the steroids to have their maximum benefit on your symptoms. Once improved, the dose is usually reduced gradually to find the lowest dose needed to prevent symptoms. This is to try and avoid the long term side-effects of this medicine. In some people, the dose of steroid needed to control the disease may be quite high and lead to side-effects. See the separate leaflet called Oral steroids for more details.

Other immunosuppressant medicines

An immunosuppressant medicine such as Azathioprin may be advised in addition to steroid medication. These medicines work by suppressing the immune system. If these medicines are not effective or you are unable to take them, there are alternatives. These alternatives also work to dampen how well your immune system works.

A steroid plus another immunosuppressant tends to be prescribed. This can work better than either alone and allow a lower dose of steroid to be needed, reducing the risk of steroid side-effects.

A myasthenic crisis occurs when the muscles that control breathing weaken to the point that breathing becomes very difficult. This can happen quickly and may be triggered by an infection, stress or particular medications which can lead to a worsening of symptoms. Admission to hospital for a week or more is usually needed and you are likely to need a ventilator to help you breathe.

Steroids and rapid acting treatments such as plasma exchange (PLEX) or intravenous immunoglobulins (IVIG) may be given to help your body during a myasthenic crisis. The aim of these treatments is to quickly reduce the abnormal antibodies in your body so you can recover.

The current available treatment options usually mean that people with myasthenia gravis have a near-normal life expectancy. Treatment usually works well but many people continue to have some symptoms. Myasthenia gravis is a very variable condition and can cause long-term difficulties with daily activities.

Myasthenia crisis is a life-threatening event. When people are diagnosed with myasthenia gravis, they will be given advice about how to reduce the risk of triggering a myasthenia crisis. This involves advice about how to avoid infections, the importance of taking medications as they are prescribed, stopping smoking and the importance of having immunisations to protect against infection.