Myasthenia gravis is a rare long-term condition that causes certain muscles to become weak.
It mainly affects muscles that are controlled voluntarily – often those controlling eye and eyelid movement, facial expression, chewing, swallowing and speaking.
Sometimes, the muscles that control breathing, neck and limb movements are also affected.
The muscle weakness associated with myasthenia gravis is usually worse during, or just after, physical activity and improves with rest. The symptoms are often described as being at their worst when a person is tired, for example, at the end of the day.
What causes myasthenia gravis?
Myasthenia gravis is an autoimmune condition that affects the nerves and muscles. Autoimmune conditions are caused by the body's immune system mistakenly attacking healthy tissue.
In myasthenia gravis, the immune system produces antibodies (proteins) that block or damage muscle receptor cells.
This prevents messages being passed from the nerve endings to the muscles, which results in the muscles not contracting (tightening) and becoming weak.
It's not fully understood why some people's immune systems produce specific antibodies that block the nerve's signal to the muscle.
Diagnosing myasthenia gravis
The process of diagnosing myasthenia gravis can take a long time because muscle weakness is a common symptom of many different conditions.
Your GP will look at your medical history and symptoms. They may suspect myasthenia gravis if your eye movements are impaired or if you have muscle weakness but you're still able to feel things. Around half of people with myasthenia gravis initially develop symptoms of double vision or eyelid droop, with more than 90% of people developing these symptoms at some point during the illness.
You may be referred to a neurologist (specialist in nervous system disorders), who will carry out some tests to help confirm the diagnosis.
Treating myasthenia gravis
Although there's no cure for myasthenia gravis, treatments are available to help control the symptoms and improve muscle weakness.
Medication can be used to improve communication between the nerves and muscles, and to increase muscle strength.
Immunosuppressants are a type of medication used to improve muscle strength by controlling the production of abnormal antibodies.
In some cases of myasthenia gravis, surgery may be recommended to remove the thymus gland (a thymectomy). The thymus gland is found underneath the breastbone and is part of the immune system. It's often abnormal in people with myasthenia gravis.
Some people may experience a temporary or permanent period of remission (where there are no longer symptoms) and treatment can be stopped.
Permanent remissions occur in about a third of all people who have a thymectomy. Removing a thymus gland tumour (thymoma) usually has little or no effect on the underlying myasthenia gravis.
Who is affected by myasthenia gravis?
Myasthenia gravis is a rare condition, affecting about 15 in every 100,000 people in the UK.
It can develop at any age, but most commonly affects women under 40 years of age and men over 60. Cases of myasthenia gravis are increasing, particularly in people over 50, but the reasons for this increase aren't fully understood.
Symptoms of myasthenia gravis
Muscle weakness is the main symptom of myasthenia gravis. The eye and facial muscles and those that control swallowing are commonly affected.
The symptoms of myasthenia gravis can come on suddenly, but it may take some time before the condition is correctly diagnosed.
Weakness of the eye muscles is often the first symptom to develop in around 50% of cases. However, slurred speech, swallowing problems or neck or limb weakness can occur first. The severity of muscle weakness varies from one person to another.
The muscle weakness of myasthenia gravis isn't usually painful in itself, but people with the condition often experience aching muscles, particularly during, or after, periods of physical activity.
Eyes, eyelids and face
In myasthenia gravis, one or both eyelids may droop (ptosis). There may also be blurred or double vision, often at the end of the day or when a person is tired. Around 90% of people with the condition have problems with their eye muscles at some point.
In some cases, the eye muscles remain the only muscles affected (ocular myasthenia). If this continues for a period of two years or more, it becomes increasingly unlikely for other symptoms of myasthenia gravis to develop.
Where the facial muscles are involved, a person's facial expression may be affected. For example, in some cases, a person may appear to have a "snarling" smile because of lower facial weakness.
Swallowing and breathing
If the muscles around the mouth or tongue become weak, this may lead to difficulty chewing and talking (dysarthria) and may cause husky or quiet speech or a nasal sounding voice.
If tongue or palate weakness develops, this can lead to swallowing difficulties (dysphagia) with coughing and choking symptoms. Sometimes, this leads to recurrent chest infections.
A small number of people with myasthenia gravis also have breathing difficulties, particularly when lying flat in bed or after exercise.
Moderate to severe swallowing or breathing problems may require urgent admission to hospital for medical care.
Limbs and movement
Myasthenia gravis can sometimes affect the muscles of the arms, legs and neck. This can cause mobility problems, such as a waddling gait, head drop and difficulty performing physical tasks such as lifting.
The specific muscles affected (promixal muscles) often leads to difficulty:
rising from sitting to standing
brushing teeth (particularly with the repetitive action involved)
Physical activity often leads to tiredness because the muscles are weak.
Causes of myasthenia gravis
Myasthenia gravis is caused by a problem with the transmission of nerve signals to the muscles.
It's an autoimmune condition, which means the body's immune system (specific antibodies) attacks its own tissues.
Nerve signals travel down the nerves and stimulate the nerve endings to release a chemical substance called acetylcholine.
When acetylcholine comes into contact with specific receptors on the muscle membrane, the receptors are activated and cause the muscles to contract (tighten).
However, in myasthenia gravis the immune system produces antibodies (proteins) that block or damage the muscle acetylcholine receptors, which prevents the muscles contracting.
The disruption between your nerves and muscles means your muscles become weak and easily tired.
The thymus gland
It's not fully understood why some people's immune systems produce antibodies that act against the muscle receptors.
However, it's thought the thymus gland, which is part of the immune system, may be linked to the production of the antibodies.
During infancy, the thymus gland is large and gradually increases in size before getting smaller during adulthood.
However, some adults with myasthenia gravis develop abnormal enlargement of the thymus gland. In around 10% of people, there's evidence of a thymus gland tumour (thymoma). This is more common in older people.
Diagnosing myasthenia gravis
Confirming a diagnosis of myasthenia gravis can take a long time because the condition is rare and muscle weakness can be a symptom of many conditions.
Your GP will look at your medical history and your symptoms. They may suspect myasthenia gravis if your eye movements are impaired or you have muscle weakness but are still able to feel things.
However, as these symptoms are common in a number of different conditions, you'll need to have some tests before a diagnosis of myasthenia gravis can be confirmed.
If your GP thinks you may have myasthenia gravis, they'll refer you to a neurologist (specialist in nervous system disorders), or sometimes an opthalmologist (eye specialist). Some tests can be carried out to confirm whether or not you have the condition.
A number of tests can be used to help diagnose myasthenia gravis.
A special type of blood test can be used to detect the antibodies (proteins) that block or damage the muscle receptors. Most people with myasthenia gravis have an abnormally high number of acetylcholine receptor antibodies.
The antibody blood tests are quite specific, which means they're almost never detected in patients who don't have myasthenia gravis.
However, in people whose symptoms are limited to the eyes, (ocular myasthenia), high levels of antibodies may only be detected in around half of cases.
A small amount people with myasthenia gravis may test negative for acetylcholine receptor antibodies but have anti-MuSK antibodies instead.
Nerve conduction tests
Electromyography is a procedure that can be used to identify communication problems between the nerves and muscles. It involves inserting a needle electrode through the skin into the muscle.
This produces an electrical recording of the muscle activity. If you have myasthenia gravis, your muscles won't respond well to nerve stimulation.
Repeated nerve stimulation can be used to test for muscle fatigue. In myasthenia gravis, the transmission of signals between the nerve and muscle declines during repeated stimulation.
Single-fibre EMG is the most sensitive electrical test for detecting disruption of the signal between the nerve ending and the muscle membrane (as in myasthenia gravis). It usually involves taking a recording from a very small needle in one of the muscles around the eye, forehead, or sometimes in the forearm.
An edrophonium test involves having an injection of a type of medication called edrophonium chloride. Edrophonium chloride prevents the substance acetylcholine from being broken down, which temporarily increases the amount of acetylcholine around the muscle.
In people with myasthenia gravis, the increased amount of acetylcholine produces a sudden but temporary improvement in muscle power. However, this won't usually occur in people with other causes of muscle weakness.
There are significant side effects associated with the edrophonium test, such as heart rate and breathing problems, that may occur during the investigation. For this reason, the test is rarely performed.
This test should only be considered if myasthenia gravis is still suspected despite negative blood and electrical tests. If performed, the test should only be carried out by experienced neurology doctors in specialist centres with resuscitation equipment available.
Imaging tests, such as a CT scan or MRI scan, are sometimes used to detect an enlarged thymus gland or a tumour on the thymus gland.
Treating myasthenia gravis
Treatment for myasthenia gravis can significantly improve symptoms of muscle weakness and many people with the condition are able to lead a relatively normal life. However, severe or chronic symptoms frequently require long-term treatment.
If symptoms are mild, many people find that getting plenty of rest helps improve their symptoms without the need for additional treatment.
Medicines such as pyridostigmine, an acetylcholinesterase inhibitor, prevent the breakdown of acetylcholine, an important chemical that helps the muscles contract (tighten).
These medicines tend to work best in mild myasthenia gravis. They can improve muscle contractions and strength in affected muscles. They're often used if the initial symptoms aren't too severe but pyridostigmine isn't a suitable long-term treatment for most people.
However, they can cause side effects, such as stomach cramps, muscle twitching, diarrhoea and nausea. Other medications may be prescribed to counteract these side effects.
If initial treatment with pyridostigmine isn't effective, or only suitable for temporary use, then steroid tablets, such as prednisolone, are used at a low dose. The dose can be increased gradually over time and is usually kept at a high dose for several months until remission is achieved.
Immunosuppressant medication may be prescribed if remission isn't achieved or the high dose of prednisolone isn't suitable. This is usuallyazathioprine, mycophenolate or methotrexate. These are used to help achieve remission so the prednisolone dose can be reduced and eventually stopped.
Your blood will have to be regularly monitored when taking immunosuppressants, which may take at least a year to take full effect.
If long-term remission is achieved over time (usually years), it may be possible to stop all immunosuppressant medication.
In some cases of myasthenia gravis, surgery to remove the thymus gland (a thymectomy) may be recommended.
In some studies, thymectomy has been shown to improve the symptoms of people who don't have tumours (thymomas) on their thymus gland. The improvement often happens within the first few months, although continued benefit may be seen for up to two years after surgery. Nowadays, the thymus gland is usually removed using keyhole surgery.
The current recommendations for people under 45 years old, with general symptoms of myasthenia gravis, no thymomas and have had the illness for less than two years, thymectomy gives:
a 25% chance of remission
a 50% chance of improvement of symptoms, still requiring long-term immunosuppression
a 25% chance of no benefit
A thymectomy often has little effect on the symptoms of myasthenia gravis for people with thymomas. However, removal is often recommended to avoid complications caused by the tumour spreading in the chest.
Plasmapheresis and immunoglobulin therapy
Plasmapheresis or intravenous immunoglobulin therapy may be needed in very severe cases of myasthenia gravis, where a person's muscle weakness is causing life-threatening breathing or swallowing problems.
These treatments are given in hospital and involve:
plasmapheresis – your blood is circulated through a machine that removes the plasma containing some of the harmful antibodies
intravenous immunoglobulin therapy – injections of normal immunoglobulin, taken from healthy donated blood, that temporarily change the way your immune system operates
Both treatments can improve the symptoms of myasthenia gravis, but the benefits usually only last a few weeks. They aren't suitable as long-term treatments for myasthenia gravis, and are usually only used to treat people who are seriously ill.
Myasthenia Gravis Association
Myaware (the Myasthenia Gravis Association) is a UK registered charity that provides additional useful information about living with myasthenia gravis.
The charity also has a patient forum on its website, plus details of other support services that are available.