Myasthenia Gravis

Myasthenia gravis is a chronic condition where communication between nerves and muscles breaks down, causing muscles to feel weak and tire quickly. While there’s no cure, effective treatments can help most people manage symptoms and live full, active lives.

Table of contents

• What is Myasthenia Gravis?
• Symptoms
• Who Gets Myasthenia Gravis?
• Types of Myasthenia Gravis
• Causes
• Diagnosis
• Treatment Options
• Living with Myasthenia Gravis
• Outlook and Prognosis

What is Myasthenia Gravis?

Myasthenia gravis is a rare, chronic condition that affects how nerves and muscles communicate with each other^[1]. It is an autoimmune disease, which means the body’s defense system mistakenly attacks healthy parts of itself^[2]. In myasthenia gravis, the immune system damages the communication system between nerves and muscles at a place called the neuromuscular junction, making muscles weak and easily tired^[3].

The condition can affect any muscles you control voluntarily, but certain muscle groups are more commonly affected than others^[1]. These include muscles in the face, throat, eyes, arms, and legs. The muscle weakness typically gets worse when you use the affected muscles and improves after you rest^[2].

Myasthenia gravis affects about 20 out of every 100,000 people around the world^[3]. In the United States, there are approximately 60,000 to 100,000 people living with the condition at any given time^[3][13]. The actual number may be higher, as some people with mild cases may not know they have the condition^[3].

Symptoms

Symptoms of myasthenia gravis may come and go. They usually get better when the weak muscle is rested but get worse again when the muscle is used^[1]. Symptoms often progress and may be at their worst one or two years after the disease begins^[1]. The intensity of muscle weakness often changes from day to day, with most people feeling strongest at the start of the day and weakest at the end of the day^[3].

In more than half of people with myasthenia gravis, the first symptoms involve eye muscles^[1]. Common eye-related symptoms include:

• Drooping of one or both eyelids, called ptosis^[1]
• Double vision, called diplopia, which may affect horizontal or vertical vision and may improve when one eye is closed^[1]
• Blurred vision^[2]

In about 15% of people with myasthenia gravis, the first symptoms involve face and throat muscles^[1]. These symptoms can include:

• Difficulty speaking, with speech that might sound soft or nasal^[1]
• Difficulty swallowing^[2]
• Trouble chewing^[3]
• Changes in facial expressions or limited facial expressions^[2]

Other common symptoms include:

• Weakness in the arms, hands, fingers, legs, and neck^[2]
• Fatigue^[3]
• Shortness of breath^[2]
• Trouble walking or getting up from a seated position^[3]

Sometimes the muscles that control breathing weaken to the point where a person needs a ventilator to breathe. This is called a myasthenic crisis and requires immediate emergency medical care^[2]. Approximately 15 to 20% of people with myasthenia gravis experience at least one myasthenic crisis, and up to 50% of those may not be able to identify a trigger for their crisis^[2]. A myasthenic crisis may be triggered by infection, stress, surgery, or an adverse reaction to medication^[2].

Who Gets Myasthenia Gravis?

Myasthenia gravis affects both men and women and occurs across all racial and ethnic groups^[2]. It can happen at any age, but it’s more common in certain groups. The condition most commonly affects young adult women under 40 and older men over 60^[1][2].

Myasthenia gravis is not inherited or contagious^[2]. Occasionally, the disease may occur in more than one member of the same family, but this is rare^[2].

Myasthenia in Children and Infants

Although myasthenia gravis is rarely seen in infants, a condition called neonatal myasthenia can occur when the fetus acquires antibodies from a mother who has myasthenia gravis^[2][3]. An infant may have a weak cry or sucking reflex at birth. Neonatal myasthenia gravis is generally temporary, and the child’s symptoms usually disappear within two to three months after birth^[2][3].

Rarely, children of healthy parents may develop congenital myasthenic syndrome. This is not an autoimmune disorder but is caused by mutations in genes required for normal function of the neuromuscular junction and can cause similar symptoms to myasthenia gravis^[2][3].

Types of Myasthenia Gravis

Myasthenia gravis can be classified into several types based on the muscles affected and the type of antibodies involved^[5]. Each type responds differently to treatment^[5].

The main types include:

• Autoimmune myasthenia: This is the most common type, where the likely cause is the production of certain types of antibodies^[3]
• Neonatal myasthenia: A temporary condition where a fetus gets certain antibodies from their birth mother who has myasthenia gravis^[3]
• Congenital myasthenia: This is not an autoimmune condition; a genetic change causes this type^[3]

There are two main subtypes of autoimmune myasthenia:

Ocular myasthenia gravis: The muscles that move the eyes and eyelids weaken. Eyelids may droop, or a person may not be able to keep their eyes open. Some people have double vision. Eye weakness is often the first sign of myasthenia. Ocular myasthenia gravis may evolve into the generalized form for nearly half of all people diagnosed with this type^[3].

Generalized myasthenia gravis: Muscle weakness affects eye muscles and others in the face, neck, arms, legs, and throat. People may find it difficult to speak or swallow, lift their arms over their head, stand up from a seated position, walk long distances, and climb stairs^[3].

Myasthenia gravis can also be classified based on age of onset and associated features:

• Early-onset MG: Age at onset less than 50 years with thymic hyperplasia^[5]
• Late-onset MG: Age at onset greater than 50 years with thymic atrophy^[5]
• Thymoma-associated MG: Associated with a tumor of the thymus gland^[5]

Causes

Myasthenia gravis is caused by a problem with the signals sent between the nerves and muscles^[4]. As an autoimmune condition, it results from the immune system mistakenly attacking a healthy part of the body^[4].

In myasthenia gravis, the immune system damages the communication system between nerves and muscles, making the muscles weak and easily tired^[4]. It’s not clear why this happens, but the condition occurs in genetically susceptible individuals^[5]. Precipitating factors can include conditions like infections, immunization, surgeries, and certain drugs^[5].

The commonly implicated proteins in the neuromuscular junction against which autoantibodies are produced include the nicotinic acetylcholine receptors, muscle-specific kinase, and lipoprotein-related protein 4^[5]. The reduction in the number of acetylcholine receptors results in a characteristic pattern of progressively reduced muscle strength with repeated use and recovery of muscle strength after a period of rest^[7].

The condition has been linked to issues with the thymus gland, a gland in the chest that’s part of the immune system^[4]. Many people with myasthenia gravis have a thymus gland that’s larger than normal. Around 1 in 10 people have an abnormal growth of the thymus called a thymoma^[4]. Approximately 10% of patients with myasthenia gravis have a thymoma, and it is implicated in the production of autoantibodies^[5].

Diagnosis

Your healthcare professional talks to you about your symptoms, reviews your medical history, and does a physical exam^[8]. They also perform a neurological exam to test reflexes, muscle strength, muscle tone, senses of touch and sight, coordination, and balance^[8].

Several tests may be used to diagnose myasthenia gravis:

Ice Pack Test

If you have a droopy eyelid, your health professional might put a bag filled with ice on your eyelid. After two minutes, they remove the bag and check whether the eyelid is less droopy^[8].

Blood Test

A blood test might show antibodies that interrupt the receptor sites where nerves signal your muscles to move^[8]. This test can be used to check for antibodies against acetylcholine receptors or other related proteins.

Repetitive Nerve Stimulation

In this nerve conduction study, a healthcare professional attaches electrodes to the skin over the muscles to be tested. Small pulses of electricity are sent to the nerve going to that muscle. These pulses measure whether the nerve can send a signal to the muscle. The nerve is tested several times to see if its ability to send signals gets worse with fatigue^[8].

Single-Fiber Electromyography (EMG)

This test measures the electrical activity traveling between your brain and your muscles. It involves inserting a fine wire electrode through your skin and into a muscle to test a single muscle fiber^[8].

Imaging

Your health professional might order a CT scan or an MRI to check for a tumor or other concerns with your thymus^[8].

Pulmonary Function Tests

These tests measure whether your condition is affecting your breathing^[8].

Treatment Options

While there is no cure for myasthenia gravis, there are several treatments that can help improve symptoms^[11]. Treatment can help keep the symptoms under control so that you’re able to live a largely normal life^[9]. The outlook for most people with myasthenia gravis is positive, as current treatment options are often effective^[6].

Avoiding Triggers

The symptoms of myasthenia gravis can sometimes have a specific trigger. Doing what you can to avoid triggers may help^[9]. Common triggers include:

• Tiredness and exhaustion—getting plenty of rest and not overexerting yourself may help^[9]
• Stress—managing stress levels is important^[9]
• Infections—you may be advised to have annual flu jabs and the pneumococcal vaccine^[9]
• Certain medicines—make sure your doctor is aware of your condition before taking any new medication^[9]
• Surgery—make sure your surgeon is aware of your condition before having any operations^[9]

Medicine

Pyridostigmine: The first medicine used for myasthenia gravis is usually a tablet called pyridostigmine, which helps electrical signals travel between the nerves and muscles^[9][11]. It can reduce muscle weakness, but the effect only lasts a few hours, so you’ll need to take it several times a day. For some people, this is the only medicine they need to control their symptoms^[9].

Steroids: If pyridostigmine does not help or only provides short-term relief, your doctor may suggest taking steroid tablets such as prednisone^[9][11]. These work by reducing the activity of your immune system to stop it attacking the communication system between the nerves and muscles^[9]. Prednisone is usually started in hospital if you have problems with swallowing or breathing, or if your symptoms keep getting worse^[9].

Immunosuppressants: If steroids are not controlling your symptoms, or you need to take a high dose of steroids, or steroids cause significant side effects, your doctor may suggest taking a different medicine that reduces the activity of your immune system^[9]. These include azathioprine, mycophenolate mofetil, cyclosporine, and others^[11].

Targeted treatments: Several newer medications have been approved for myasthenia gravis, including complement inhibitors and neonatal Fc receptor blockers^[11]. These provide more treatment options for patients who don’t respond well to traditional therapies^[13].

Intravenous immunoglobulin (IVIg): This treatment is commonly prescribed to treat myasthenic crisis and in some cases of refractory myasthenia gravis^[11][12].

Plasmapheresis: This is a procedure that filters antibodies from the blood. It is commonly prescribed to treat myasthenic crisis and in some cases of refractory myasthenia gravis^[11][12].

Surgery

Surgery to remove the thymus gland, known as a thymectomy, may sometimes be recommended^[9][11]. Data shows clear evidence that thymectomy is beneficial in patients with acetylcholine receptor antibody-positive generalized myasthenia gravis, up to the age of 65 years^[12].

This has been shown to improve myasthenia symptoms in some people with an unusually large thymus, although not in people with a thymoma^[9]. Symptoms will usually improve in the first few months after surgery but may keep getting better for one to two years, and in some cases, for a few more years after that^[9].

Surgery can reduce the dose of steroids you need to take, reduce the chances of needing to take other immunosuppressants, and reduce the chances of needing to go into hospital because of worsening symptoms^[9]. If you have a thymoma, a thymectomy will often be recommended because the tumor can cause problems if it’s left to keep getting bigger^[9].

Living with Myasthenia Gravis

Living with myasthenia gravis presents unique challenges, but with the right strategies and support, most patients can lead fulfilling lives^[19]. The first step to managing your condition is to accept that you have it^[16].

Energy Conservation and Pacing

Fatigue and muscle weakness can interfere with everyday activities, so energy conservation becomes essential^[19]. Many people learn to pace themselves and make choices about which are the important things for them to do^[20]. Plan for regular rest and spread activities throughout the day. It’s better to take small steps to manage symptoms and improve your quality of life^[20].

Focus activities at your strongest time of the day^[20]. Most people feel strongest at the start of the day and weakest at the end of the day^[3]. Instead of trying to push through, allow time for rest. This might mean building rest times into your workday or pausing in the middle of climbing stairs^[17].

Nutrition and Diet

A well-balanced diet and plenty of rest can really help^[20]. Nutritious foods rich in lean protein, calcium, and vitamins help maintain bone and muscle health^[19]. Soft foods and smaller meals may be easier to swallow, especially if you experience mouth or throat muscle fatigue^[19]. Avoid foods that are hard to chew, dry foods, or hot liquids that may trigger difficulty swallowing^[19].

Exercise and Physical Activity

When your myasthenia is not well controlled, exertion weakens muscles. Therefore, people should exercise within limits that don’t exceed their present capability^[20]. As your myasthenia becomes more controlled, you are encouraged to exercise as much as anyone else^[20]. Exercise has a strong benefit for myasthenia gravis. Consider taking pyridostigmine right before exercise and splitting exercise into shorter segments that engage different muscles^[15].

Managing Stress

Stress can be a major trigger for myasthenia gravis flare-ups^[17][20]. Practice mindfulness or deep breathing exercises to help relax. Limit overstimulation and multitasking, which can lead to mental fatigue. Build in downtime for activities that restore your energy^[19].

Practical Home Adaptations

Consider adapting your home to make life easier. This might include installing grab bars in the shower, using a chair in the shower, replacing old-fashioned tap spindles with tap mixers, and using assistive devices such as canes or walkers^[16][19].

Finding Support

Connecting with others who have myasthenia gravis can be life-changing. Patient support groups provide advice on managing fatigue, questions to ask doctors, and reassurance that you’re not alone^[23]. Having supportive, understanding, and patient people in your life can really help^[20].

Working with Your Healthcare Team

Regular follow-up and communication with your doctor is one of the best ways to find the right treatment regimen for you^[15]. Keep a diary to write down any questions or new symptoms that come up between appointments. A daily record of the effects of myasthenia is useful when applying for benefits or talking to an employer^[20]. Track your symptoms to help see patterns in your fatigue and identify triggers^[23].

Carry a patient passport or emergency medical card. This helps explain your condition to medical professionals who may not be experts in myasthenia^[20].

Outlook and Prognosis

Myasthenia gravis is a long-term condition that typically has phases when it improves and phases when it gets worse^[4]. It usually affects most of the body, spreading from the eyes and face to other areas over weeks, months, or years. But for some people with myasthenia gravis, only the eyes are affected^[4].

It is common for people to have flare-ups, where symptoms are very troublesome, followed by periods of remission, where symptoms improve^[4]. While remission can sometimes be permanent, this is rare in cases of myasthenia gravis^[4].

The first years after diagnosis are the most critical. This is when symptoms are most prevalent and the disease can progress^[22]. Most patients have a stable course of disease after the first few years and may even go into remission for long periods of time^[22].

Myasthenia gravis is no longer considered a fatal disease. Most people with myasthenia, with the help of either drugs and/or surgery, lead near-normal lives^[14]. If severe, myasthenia gravis can be life-threatening, but it does not have a significant impact on life expectancy for most people^[4].

Treatment does not always produce a complete remission. How often treatment is needed depends upon the severity and type of myasthenia gravis^[22]. People with myasthenia gravis who are on treatment have reduced symptoms and may feel little impact of the condition on their lifestyle^[22].

The outlook for most people with myasthenia gravis is positive. While existing treatments do not cure myasthenia gravis, most patients have improved muscle strength, and some even experience remission^[6]. New advances in research and clinical trials are helping us understand more about myasthenia gravis every day^[6].

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