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SHARE: Myasthenia Gravis
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            What is myasthenia gravis?

Myasthenia gravis is a chronic neuromuscular disease that causes weakness in the voluntary muscles. Voluntary muscles include muscles that connect to a person’s bones, muscles in the face, throat, and diaphragm. They contract to move the arms and legs and are essential for breathing, swallowing and facial movements. Myasthenia gravis is an autoimmune disease, which means that the body’s defense system mistakenly attacks healthy cells or proteins needed for normal functioning.

The onset of the disorder may be sudden. Symptoms may not be immediately recognized as myasthenia gravis. The degree of muscle weakness involved varies greatly among individuals.

Symptoms of myasthenia gravis

Symptoms commonly associated with myasthenia gravis include:

Weakness of the eye muscles (ocular myasthenia)
	Drooping of one or both eyelids (ptosis)
	Blurred or double vision (diplopia)
	Changes in facial expressions

Difficulty swallowing
	Shortness of breath
	Impaired speech (dysarthria)
	Weakness in the arms, hands, fingers, legs, and neck

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. A myasthenic crisis may be triggered by infection, stress, surgery, or an adverse reaction to medication. Approximately 15-20% 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 myasthenic crisis.

Who is more likely to get myasthenia gravis?

Myasthenia gravis affects both men and women and occurs across all racial and ethnic groups. It most commonly impacts young adult women (under 40) and older men (over 60), but it can occur at any age, including childhood. Myasthenia gravis is not inherited or contagious. Occasionally, the disease may occur in more than one member of the same family.

Myasthenia in children and infants

Although myasthenia gravis is rarely seen in infants, in a condition called neonatal myasthenia the fetus may acquire antibodies from the mother. Neonatal myasthenia gravis is generally temporary, and the child's symptoms usually disappear within two to three months after birth.

Rarely, children of healthy parents may develop congenital myasthenia. This is not an autoimmune disorder but is caused by mutations in genes required for normal function of the neuromuscular junction (the place where nerve cells connect with the muscles they control) and can cause similar symptoms to myasthenia gravis.

Scientists supported by NINDS are studying congenital myasthenic syndromes to improve diagnosis, treatment, and prevention, including developing targeted gene therapy for treating the disorders.

Causes of myasthenia gravis

Myasthenia gravis is caused by an error in how nerve signals are sent to muscles, specifically when communication between the nerve and muscle is interrupted at the neuromuscular junction.

Neurotransmitters are chemicals that neurons, or brain cells, use to communicate. When electrical signals or impulses travel down a nerve responsible for triggering movement in the muscle, the nerve endings release a neurotransmitter called acetylcholine. Acetylcholine binds to receptors on the muscle and activate a process that causes the muscle to contract.

In myasthenia gravis, antibodies (immune proteins produced by the body's immune system) block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction, which prevents the muscle from contracting. This is most often caused by antibodies to the acetylcholine receptor itself, but antibodies to other proteins, such as MuSK (Muscle-Specific Kinase) protein, also can impair transmission at the neuromuscular junction.

The thymus gland controls immune function and may be associated with myasthenia gravis. The thymus gland grows gradually until a person reaches puberty and then gets smaller until it is replaced by fat. Throughout childhood, the thymus plays an important role in the development of the immune system because it is responsible for producing T-lymphocytes or T cells, a specific type of white blood cell that protects the body from viruses and infections.

In many adults with myasthenia gravis, the thymus gland remains large even after a person becomes an adult. People with the disease typically have clusters of immune cells in their thymus gland and may develop tumors in the thymus gland known as thymomas. Thymomas are most often harmless, but they can become cancerous. Scientists believe the thymus gland may give incorrect instructions to developing immune cells, ultimately causing the immune system to attack its own cells and tissues and produce acetylcholine receptor antibodies.

Several common medications, including statins, which are prescribed to help lower cholesterol, may rarely worsen myasthenia gravis. Individuals with myasthenia gravis should talk with their healthcare provider about how any medication might interact with the disorder.

How is myasthenia gravis diagnosed and treated?

Diagnosing myasthenia gravis

There are several tests that can confirm a diagnosis of myasthenia gravis:

**Physical and neurological examination**—A doctor will review your medical history and conduct a physical examination. In a neurological examination, the physician will check:

	Muscle strength and tone
		Coordination
		Sense of touch
		Eye movements
	**Electrodiagnostics**—Diagnostic tests include:
	*Repetitive nerve stimulation*repeatedly stimulates the nerves with small pulses of electricity and tests the electrical responses of the muscle receiving those stimuli.
		*Single fiber electromyography (EMG),*which is considered the most sensitive test for myasthenia gravis, detects impaired nerve-to-muscle transmission. EMG can be very helpful in diagnosing mild cases of myasthenia gravis when other tests fail to demonstrate abnormalities.
	**Blood test**—People living with myasthenia gravis may have abnormally elevated levels of acetylcholine receptor antibodies or anti-MuSK antibodies. A blood test also can detect these antibodies. In some individuals with myasthenia gravis, neither of these antibodies is present; this is called seronegative (negative antibody) myasthenia.Because weakness is a common symptom of many other disorders, it can be difficult to diagnose myasthenia gravis in people who have mild weakness or whose weakness is restricted to only a few muscles.

Treating myasthenia gravis

Currently, there is no known cure for myasthenia gravis. Most people with myasthenia gravis live to an average life expectancy. There are treatments available to help reduce and improve muscle weakness, including:

**Anticholinesterase medications**—Medications to treat myasthenia gravis include mestinon or pyridostigmine, which slow the breakdown of acetylcholine at the neuromuscular junction and improve neuromuscular transmission and increase muscle strength.
	**Thymectomy**—A thymectomy is an operation to remove the thymus gland. It can reduce a person’s symptoms, possibly by rebalancing the immune system. A NINDS-funded study of 126 people with myasthenia gravis with thymoma and those with no visible thymoma found the surgery reduced muscle weakness and the need for immunosuppressive drugs. Stable, long-lasting complete remissions are the goal of thymectomy and may occur in about 50 percent of individuals who undergo this procedure.
	**Complement inhibition**— Complement is a collection of naturally produced proteins that function as part of the immune response.  Complement activation contributes to the process by which acetylcholine antibodies injure the neuromuscular junction. The U.S. Food and Drug Administration (FDA) has approved the use of the medication eculizumab for the treatment of generalized myasthenia gravis in adults who test positive for the antiacetylcholine receptor (AchR) antibody. Eculizumab is an effective inhibitor of a key complement protein known to contribute to neuromuscular junction damage in myasthenia gravis.
	**Immunosuppressive drugs**—Immunosuppressive drugs can improve muscle strength by suppressing the production of abnormal antibodies, These medications include prednisone, azathioprine, mycophenolate mofetil, and tacrolimus. They can cause significant side effects and must be carefully monitored by a physician.
	**Plasmapheresis and intravenous immunoglobulin**—These therapies are used in severe cases of myasthenia gravis to remove destructive antibodies that attack the neuromuscular junction. They are usually only effective for a few weeks or months.
	 
	*Plasmapheresis*uses a machine to remove harmful antibodies in plasma.
		*Intravenous immunoglobulin*, a highly concentrated injection of antibodies collected from many healthy donors, temporarily changes the way the immune system works. It promotes the reduction of autoantibodies that interfere with the nerve-to-muscle communication.
	**Lifestyle changes**—Regular gentle exercise may be helpful for some people with myasthenia gravis.Some cases of myasthenia gravis may go into remission, either temporarily or permanently and muscle weakness may disappear completely. When that happens, the person can usually stop taking medications prescribed for the condition after talking with their doctor.

Assistive devices may also help people with myasthenia gravis with mobility.

What are the latest updates on myasthenia gravis?

NINDS is a component of the National Institutes of Health (NIH), a leading supporter of biomedical research in the world. Researchers continue to gain a better understanding about myasthenia gravis, its causes, and the structure and function of the neuromuscular junction. Technological advances have led to more timely and accurate diagnosis of myasthenia gravis and new and enhanced therapies have improved treatment options. Researchers are working to develop better medications, identify new ways to diagnose and treat individuals, and improve treatment options.

The NIH-funded MG Rare Disease Clinical Research Network (MGNet) seeks to gain a better understanding myasthenia graivs and to develop improved approaches for diagnosis and treatment. EXPLORE-MG2 (Exploring Outcomes and Characteristics of Myasthenia Gravis 2), a natural history study developed by MGNet, is collecting clinical data and biospecimens from people with myasthenia gravis to create a registry with the goals of enhancing clinical trials, improving care of people with the disorder, and ultimately finding a cure.

Medication

Investigators are testing new medications, either alone or in combination with existing drug therapies, to see if they are more effective in targeting the causes of the disease. NINDS-supported investigators are studying a therapy to target specific cells that play a critical role in the production of autoantibodies. Autoantibodies are antibodies or proteins produced by the immune system that target an individual's own proteins. This therapy may help with symptoms of myasthenia gravis for people who do not respond well to current treatment options.

Diagnostics and biomarkers

NINDS-funded researchers are exploring how the connections between nerves and muscle fibers form and function to understand the fundamental processes in neuromuscular development. The hope is that this research will help reveal new therapies for neuromuscular diseases like myasthenia gravis.

Researchers are also exploring better ways to treat myasthenia gravis by developing new tools to diagnose people with undetectable antibodies and identify potential biomarkers (biological signs of disease) to predict an individual's response to medications that suppress the immune system’s function.

More information about research on myasthenia gravis can be found usingNIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and resources from these projects.

For research articles and summaries on myasthenia gravis, searchPubMed, which contains citations from medical journals and other sites.

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Learn About Clinical Trials

Clinical trials are studies that allow us to learn more about disorders and improve care. They can help connect patients with new and upcoming treatment options.

How can I or my loved one help improve care for people with myasthenia gravis?

Consider participating in a clinical trial so clinicians and scientists can learn more about myasthenia gravis. Clinical research uses study participants to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visitNIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with myasthenia gravis atClinicaltrials.gov, a searchable database of current and past federal and private clinical studies.

Where can I find more information about myasthenia gravis?

Information may be available from the following organizations and resources:

Autoimmune Association
Phone: 586-776-3900 or 888-852-3456

MedlinePlus

MGNet

Muscular Dystrophy Association
Phone: 800-572-1717

Myasthenia Gravis Foundation of America
Phone: 800-541-5454​​​
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