Myasthenia gravis (MG)

Myasthenia gravis (MG) is a chronic autoimmune condition that causes fatigable muscle weakness. This means it is a long-term condition where the immune system attacks the body. It causes muscles to become weak when they are used repeatedly. The muscles around the eyes are usually affected first.

Myasthenia gravis is more common in women than men. Symptoms usually start in women under 40 and men over 60, but the condition can affect people of all ages.

Myasthenia gravis can vary in severity and areas of weakness. It is usually manageable with medication and supportive therapies.

Myasthenia gravis causes weakness that gets worse with repeated muscle use and improves with rest. This is called fatigable muscle weakness. Symptoms fluctuate and are typically worse towards the end of the day.

Myasthenia gravis can be classified as either ocular myasthenia or generalised myasthenia gravis:

• Ocular myasthenia only affects the eye muscles.
• Generalised myasthenia gravis begins in the eyes and spreads to other muscle groups in the body. This type is more common.

Eye and vision symptoms

In most cases, myasthenia gravis affects the muscles controlling eyelid and eye movements first. This can cause droopy eyelids (ptosis), where one or both eyelids weaken and may cover the eyes and affect vision.

It can also lead to blurred or double vision (diplopia). The severity can change day to day and is often worse at the end of the day.

Face, mouth and throat symptoms

Facial muscle weakness in generalised myasthenia gravis can make it difficult to make typical facial expressions, such as smiling or frowning. It can also affect speech.

Weakness in the mouth and throat muscles can cause difficulty chewing and swallowing (dysphagia). This may result in coughing and choking during meals, feeling like food is stuck in the throat or chest, or the inhalation of food or drink into the lungs (aspiration). Inhalation can lead to chest infections (aspiration pneumonia).

Those affected may have slurred speech and a quiet or nasal-sounding voice. Their breathing muscles may be mildly affected and cause shortness of breath when lying down or after exercise.

Weakness in the rest of the body

Weakness can affect other parts of the body such as the neck, arms, and legs in generalised myasthenia gravis. The severity is different for everyone and fluctuates.

• Neck weakness can make it difficult to hold the head up.
• Arm weakness can make it difficult to raise the arms above the shoulders. This can make everyday tasks, such as reaching for objects or getting dressed, harder.
• Leg weakness can make it difficult to walk longer distances and climb stairs. As a result, there may be an increase in the risk of falls.

Fatigue 

People with myasthenia gravis often experience fatigue. This feels like exhaustion and affects energy levels and the ability to perform daily activities. Fatigue can still be experienced even if the condition is well managed. Read about fatigue and managing fatigue.

Myasthenia gravis is an autoimmune condition. This means the body’s immune system mistakenly attacks its own healthy tissues or proteins. It makes antibodies that disrupt communication between nerves and muscles, leading to muscle weakness.

It’s not clear why this happens. In some cases, the thymus gland in the chest might trigger the abnormal immune response, especially in younger people.

Some people are more likely to develop autoimmune conditions because of their genetic makeup. They may have inherited small changes in their genes.

There are different types of myasthenia gravis categorised by the antibodies produced:

• AChR – in most cases, people with myasthenia gravis produce antibodies against a protein called the acetylcholine receptor (AChR). The acetylocholine receptor is found at the point where the nerves and muscles meet (the neuromuscular junction). It helps muscles move by receiving signals from nerves. The antibodies people with myasthenia gravis produce block these receptors and make it harder for muscles to get the signal. This causes muscle weakness, which worsens with repeated muscle use.
• MuSK – some people with myasthenia gravis produce antibodies against the protein muscle-specific kinase (MuSK). This also disrupts communication between nerves and muscles, leading to similar muscle weakness.
• LRP4 – Other rare antibodies, such as LRP4, have been found in some people with myasthenia gravis.
• There are some people without known antibodies. This is called seronegative myasthenia gravis.

A GP can make a referral to a neurologist for testing.

A neurologist specialises in conditions affecting the muscles and nervous system.

• They will carry out a physical examination and discuss medical history.
• This includes a blood test which can look for a high level of specific antibodies associated with myasthenia gravis.
• Some people with myasthenia gravis, especially ocular myasthenia, may not have high levels of antibodies. In these cases, the blood test may be repeated if symptoms continue or worsen.
• Additional tests, such as electrical testing, and a chest scan (CT or MRI) may also be used.
• The chest scan will check the thymus gland for abnormalities.

Treatment options will be discussed once someone is diagnosed.

For more information, see our diagnosis page.

A multi-disciplinary approach is important in the treatment of myasthenia gravis. This means different healthcare professionals work together to manage the condition and symptoms and improve wellbeing.

Myasthenia gravis is managed through medical treatment and by avoiding triggers.

Specialist care and follow up

People with myasthenia gravis should have access to a multi-disciplinary healthcare team to assess their condition and discuss treatment. Usually, the lead professional will be a neurologist in a specialist neuromuscular clinic. If you do not have contact with a neurologist or specialist doctor, speak to your GP about getting access.

Managing triggers

Symptoms of myasthenia gravis sometimes have a trigger. Common triggers include:

• Stress
• Tiredness and atigue
• Infections – people should receive a pneumococcal vaccine and annual flu jab (advice is needed before having a “live” vaccine)
• Certain medications and anaesthetics
• Hot weather
• Menstrual periods

Noticing and avoiding triggers, where possible, may help reduce symptoms.

Pyridostigmine 

The first treatment for myasthenia gravis is pyridostigmine. It helps electrical signals travel between the nerves and muscles. It reduces muscle weakness, but the effect only lasts about four hours, so it needs to be taken regularly.

People with mild symptoms may only need pyridostigmine to manage their condition, but most will need more treatments.

• Possible side effects include stomach cramps, diarrhoea, and feeling sick. A lower dose or other medication can be prescribed to help with side effects.

Steroids 

If pyridostigmine is not enough to control symptoms, steroid tablets can be prescribed. These reduce immune system activity.

The steroid prednisolone is started at a low dose and is gradually increased over a few weeks. Once symptoms improve and are stable, the dose is slowly reduced to the lowest effective amount. Some people can stop taking steroids if they go into remission (become symptom free).

Steroids can have side effects, such as:

• Increased risk of infections
• High blood pressure
• Weakening of the bones (osteoporosis)
• Increased blood sugar levels. This can lead to diabetes in people who are already at risk, even if they didn’t previously show symptoms.
• Weight gain. Maintaining a healthy diet is important to help manage the risk of weight gain.

Regular monitoring and additional medications can help manage these risks.

• Don’t stop taking steroids suddenly, as this is dangerous and has serious health risks. It’s important to carry a Steroid Emergency Card, because it provides important information for healthcare professionals in an emergency. You can get a card from a GP, community pharmacy, or specialist hospital team.

Other immunosuppressants 

If steroids are not controlling symptoms, or a very high dose is being used, doctors may prescribe immunosuppressants. These include:

• Azathioprine
• Methotrexate
• Mycophenolate
• Rituximab

These medications can help lower or even remove the need for steroids by reducing immune system activity, though they take a few months to work.

• Immunosuppressants have side effects, so regular blood tests are necessary.

New treatments 

Recent clinical trials have shown new treatments are effective for myasthenia gravis, including:

• Efgartigimod
• Rozanolixizumab
• Zilucoplan
• These treatments are currently being evaluated for use in the UK by the National Institute for Health and Care Excellence (NICE). We, at Muscular Dystrophy UK, play a key role in these appraisals, often acting as a formal Patient Expert. For more information, see our access to treatments page.

Surgery

The thymus gland, located in the upper chest behind the breastbone, can be enlarged in people with myasthenia gravis. Surgery to remove the thymus gland, called a thymectomy, is usually recommended for:

• Those with a thymoma.
• Some patients with AChR antibodies without thymoma.
• Younger patients (under 60 approximately) with more recent condition onset.

This surgery can help improve symptoms, depending on the specific antibody affected. Symptoms usually improve in the first few months after surgery but could continue to improve for years. Surgery may reduce the amount of medication needed and reduce the chance of worsening symptoms that require treatment in hospital.

Surgery should be discussed with a specialist. In many cases, this surgery can be done via keyhole surgery, which is less invasive and enables a quicker post-surgical recovery.

People who should not have a thymectomy include those with:

• MuSK antibodies.
• No detectable antibodies.

Thymomas and myasthenia gravis

A thymoma is a rare tumour of the thymus gland. It is usually a benign (non-cancerous) tumour. At least 1 in 10 people with myasthenia gravis have a thymoma, although estimates in some populations are much higher. Not all people with thymomas have symptoms of myasthenia gravis.

When thymomas are associated with myasthenia gravis, it’s recommended they are surgically removed. In some cases, additional treatment in the form of radiotherapy or chemotherapy may be necessary.

Emergency treatment/myasthenic crisis

A myasthenic crisis is a severe worsening of myasthenia gravis symptoms, leading to extreme weakness and severe breathing or swallowing problems. These symptoms are potentially life-threatening and require emergency hospital treatment.

Treatment can include:

• Plasma exchange (plasmapheresis), which removes harmful antibodies
• Intravenous immunoglobulin therapy (IVIg), which provides healthy antibodies
• Steroids

In severe cases, people may be admitted to the intensive care unit (ICU) to use a ventilator machine to assist breathing.

If treatment doesn’t work

Refractory myasthenia gravis is where treatments fail to control symptoms enough. It affects about 1 in 5 people. People with refractory myasthenia gravis will experience persistent or worsening symptoms despite medication. Treatment options are limited.

New treatments are being developed for myasthenia gravis. Information can be found on the access to treatments page.

It’s important for anyone with myasthenia gravis planning to have a baby to discuss this with their neuromuscular team. Ideally, pregnancy should be planned around treatment and any medications that could be unsafe for the baby are stopped.

Pregnancy and delivery can sometimes worsen symptoms of myasthenia gravis. There should be close working between neuromuscular and obstetric teams to ensure a safe pregnancy.

Transient neonatal myasthenia gravis

It’s also important to be aware that the baby could be affected by a condition known as transient neonatal myasthenia gravis. This occurs when antibodies pass across the placenta, temporarily affecting the baby at birth. Symptoms in the baby include a weak cry, feeding difficulties, and breathing problems. Treatment for the baby is like that of their parent and includes pyridostigmine. During pregnancy, additional scans and appointments are needed to check for signs of this.

Some medications can interfere with nerve to muscle transmission and worsen myasthenia gravis. These include some antibiotics, beta-blockers, and psychiatric drugs. A doctor must be made aware of a myasthenia gravis diagnosis before they prescribe new medication. A full list of medications to avoid can be found on Myaware.

If having surgery or a procedure that requires anaesthesia, the anaesthetist and surgical team must be aware of a myasthenia gravis diagnosis and any treatment. They should carry out a pre-operative assessment, extended post-operative monitoring and work with the treating myasthenia gravis neurologist.