Myasthenia Gravis

What Causes Myasthenia Gravis?

MG is caused by interference in the transmission of nerve impulses between nerve cells and muscles. Under normal circumstances, these impulses are transmitted when a chemical called acetylcholine is released by nerve cells and binds to receptors in muscle cells. In MG patients, the body’s immune system blocks acetylcholine’s reception by the muscles, resulting in weakness and fatigue.

In some less common cases, MG symptoms are not caused by an immune reaction to acetylcholine but because of the presence of antibodies to other compounds that are crucial for muscle activity.

Scientists are not sure what causes the immune system to produce antibodies that attack acetylcholine receptors. Many MG patients have an abnormally large thymus gland, an organ that plays a role in developing the immune system. The thymus usually is its largest in children, and it shrinks considerably after puberty. In many adults with MG, the thymus does not shrink and remains unusually active in producing immune cells. The exact nature of the connection between thymus activity and MG is still unclear, however.

Is Myasthenia Gravis Hereditary?

MG is not inherited, and scientists have not discovered any genetic factors that appear to be associated with the disorder. In a small number of cases, however, more than one person in a family is affected by the disease. This suggests that there may be some rare, slight genetic predisposition to develop MG or other autoimmune disorders.

In about 12% of cases, a mother with MG passes the disease-causing antibodies to her child at birth. In these cases, the infant may develop symptoms of the disorder, but the condition usually resolves with treatment within a few months.

A rare form of the disorder called congenital myasthenia can affect children from birth. It is a distinct disorder from MG caused by a genetic abnormality, not the immune system. The symptoms of congenital myasthenia are similar to those of MG.

How Is Myasthenia Gravis Detected?

MG’s symptoms usually respond well to treatment, so early detection of the disorder can help sufferers have an improved quality of life as soon as possible.

The majority of MG patients experience symptoms first in the muscles that control their eyes. Only the eyes are affected in 10-40% of patients. Eye-related symptoms include drooping eyelids, double vision, or blurred vision.

In about 15% of patients, the first symptoms of MG occur in the muscles of the face and throat. These early symptoms can include difficulty swallowing or chewing, difficulty speaking, or difficulty maintaining normal facial expressions.

How Is Myasthenia Gravis Diagnosed?

The process for diagnosing MG begins with a physical exam and medical history. If those steps do not reveal another cause for the symptoms, the doctor will move on to other diagnostic steps, which may include:

• Neurological exam. This exam will look at neurological functions such as muscle strength and tone, reflexes, balance, coordination, and sensory perception.
• Edrophonium test. This test involves the injection of an enzyme that blocks the breakdown of acetylcholine. An injection of edrophonium usually temporarily relieves MG symptoms, so improvement after the injection may indicate the disorder’s presence.
• Blood tests. These tests can detect elevated levels of acetylcholine receptor antibodies or anti-MuSK antibodies, both potential MG indicators. However, high levels of these antibodies are not present in some MG cases, so blood tests do not always detect the disorder.
• Repetitive nerve stimulation and single-fiber electromyography (EMG). These tests measure the electrical activity between the patient’s brain, nerves, and muscles.
• Imaging tests. Computerized tomography (CT) or magnetic resonance imaging (MRI) may be used to examine the thymus. Many MG patients have tumors (often benign) in the gland.
• Pulmonary function tests. These tests measure the strength and function of the muscles associated with breathing. The test can help determine if the patient is at risk of a myasthenic crisis.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Myasthenia Gravis Treated?

The symptoms of MG may be treated with a variety of medications and therapies. In some cases, thymus-removal surgery may be recommended.

Medications

• Anticholinesterase medications. These medications help slow the breakdown of acetylcholine and can improve muscle function and strength. Anticholinesterase drugs include pyridostigmine and neostigmine.
• Immunosuppressive drugs. These drugs help reduce symptoms by limiting the production of the disease-causing antibodies. Immunosuppressive drugs include prednisone, azathioprine, mycophenolate mofetil, tacrolimus, and rituximab. These medications can make the patient susceptible to infections and can have other serious side effects.

Intravenous Therapies

• Plasmapheresis. This treatment is similar to dialysis. The patient’s blood is passed through a filter that removes abnormal antibodies. The effects of plasmapheresis last a few weeks, and the procedure must be repeated for lasting relief from symptoms.
• Intravenous immunoglobulin. This procedure involves the intravenous introduction of normal antibodies to the patient’s bloodstream. As with plasmapheresis, the effects of the process are temporary.

Surgery

A procedure to remove the thymus, called a thymectomy, may be recommended when a thymus tumor (thymoma) is present. Recent research has shown that a thymectomy may also help patients even if there is no thymoma. As many as 50% of MG patients may experience complete remission of symptoms after a thymectomy. However, the remission may take years to completely develop.

The thymus is located in the chest, and its removal may require a significant surgical procedure. Newer techniques sometimes allow surgeons to remove the gland using a minimally invasive procedure that reduces the risk of infection and other complications.

How Does Myasthenia Gravis Progress?

In some MG patients, symptoms are confined to the eyes and do not progress to other parts of the body. In most cases, however, symptoms worsen over time and often extend to the muscles of the face, throat, neck, and/or limbs.

With treatment, MG symptoms are usually manageable and not life-threatening. A myasthenic crisis, however, requires immediate emergency care.

Some circumstances that may trigger a worsening of symptoms include:

• Stress
• Illness or infection
• Thyroid problems (hyperthyroidism or hypothyroidism)
• Pregnancy
• Menstrual cycles
• High body temperature
• Reactions to drugs that affect the immune system

How Is Myasthenia Gravis Prevented?

There is no known way to prevent MG from developing. Some circumstances might make your symptoms worse, however. You can reduce your risk of flare-ups if you take some precautionary steps, including:

• Get plenty of rest, especially after periods of increased activity
• Eat a healthy diet
• Avoid potential exposure to infections, especially respiratory infections such as colds or flu
• Practice stress-management techniques
• Avoid environments with extreme temperatures
• Be on the lookout for drug reactions, and tell your doctor if any medications seem to make your symptoms worse

Myasthenia Gravis Caregiver Tips

If you’re caring for a loved one affected by myasthenia gravis, there are some things you can do to make symptom flare-ups less likely:

• Help your loved one to manage stress, to a point. Be alert to the daily causes of stress, and do what you can to reduce them. But don’t go too far and make your loved one feel overwhelmed by your involvement. Communicate so you know when you can help and when the best course of action is to step aside.
• Watch out for environmental triggers. MG flare-ups can be caused by situations that catch you by surprise. Don’t let your loved one inadvertently get into an environment–such as being outside on a warm day without access to shade–that could make symptoms worse. Always be alert to the potential dangers, and always have a recovery plan.
• Support a healthy lifestyle. Ensure your loved one eats well, takes all their medication as directed, and gets plenty of rest.

Many people with MG also suffer from other brain-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with MG:

• Nearly half of people with MG suffer from depression.
• About a third of people with MG also have an anxiety disorder such as generalized anxiety disorder, social anxiety disorder, panic disorder, or agoraphobia.
• Obsessive-compulsive disorder (OCD) risk is higher in people with MG.

Myasthenia Gravis Brain Science

MG interferes with the brain’s ability to communicate effectively with muscles, but the interference happens at the junction between nerve endings and muscle cells, not in the brain itself. MG patients do often suffer from brain-related problems such as depression and sleep disorders. Given that acetylcholine is also present in the brain, there has been some speculation that MG (or the drugs used to treat it) might impair brain function in some way that produces these co-existing disorders.

Most scientists agree that such a direct effect is unlikely. The form of acetylcholine in the brain differs from that at the nerve-muscle junction, and the brain form of the chemical is unlikely to be affected by the antibodies that cause MG or the drugs used to treat MG’s symptoms.

The more likely connection between MG and other brain disorders lies with the secondary effects of MG. For example, sleep disorders may result from poor night-time breathing patterns caused by weak muscles. Depression and other similar psychiatric disorders are often seen in patients suffering from chronic, physically debilitating illnesses. The stress of living with MG is the more likely cause of co-existent depression rather than a direct biochemical result of the disease itself.

Myasthenia Gravis Research

Title: A Pilot Study to Explore the Role of Gut Flora in Myasthenia Gravis

Stage: Recruiting

Principal investigator:  Sabine Hazan, MD

ProgenaBiome

Ventura, CA

This study seeks to correlate microbiome sequencing data with information provided by patients and their medical records. This Research Study aims to better understand how the genetic information in the subject’s microbiome correlates to Myasthenia Gravis.

Title: The EXPLORE MG Registry for Myasthenia Gravis

Stage: Recruiting

Principal investigator:  Richard Nowak, MD, MS

Yale-New Haven Hospital

New Haven, CT

This registry will allow for the research of several mechanisms of Myasthenia Gravis (MG) by studying peripheral blood, stool, disease status and course, and treatment of subjects with MG. The EXPLORE-MG Registry focuses on varied aspects of MG such as disease management, health care utilization, health costs, disease characteristics, and diagnostic tools. As such, it will aid in a broader understanding of MG, while providing a registry from which questions about the disease may be better answered.