What is Myasthenia Gravis?
Myasthenia gravis (Myasthenia Gravis) is a neuromuscular disease that causes muscle weakness and unusual muscle fatigue. It can affect muscles anywhere in the body, but it most often affects muscles that control eye movements and other muscles of the face.
The symptoms of Myasthenia Gravis typically get worse the more the affected muscles are used, but weakness and fatigue usually improve if the muscles are allowed to rest. The severity of symptoms tends to get progressively worse after initial onset, but symptoms usually stabilize after a period of a few years.
Myasthenia Gravis can develop at any stage of life, but it is most common in women younger than 40 and men older than 60.
Symptoms of Myasthenia Gravis
Myasthenia Gravis symptoms can affect any voluntary muscle group, but the muscles of the face are most commonly affected. Symptoms get worse as the muscles are used and improve after a period of rest. This cycle causes symptoms to often be experienced intermittently.
Common symptoms include:
- Drooping eyelids in one or both eyes
- Double vision
- Speech impairment
- Difficulty chewing
- Difficulty swallowing
- Impaired facial expressions
Less common symptoms can include:
- Weakness in neck muscles
- Weakness in arms or legs
- Shortness of breath
About 15-20% of Myasthenia Gravis patients experience an episode of severe symptoms at least once in their lifetimes. These episodes, called myasthenic crises, can cause profound weakness in affected muscles. When a myasthenic crisis affects the muscles that control breathing, the episode can cause life-threatening complications. Myasthenic crises may be triggered by an illness, stress, or reaction to medications.
What Causes Myasthenia Gravis?
Myasthenia Gravis 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 Myasthenia Gravis patients, the body’s own immune system blocks the reception of acetylcholine by the muscles, resulting in weakness and fatigue.
In some less common cases, Myasthenia Gravis 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 Myasthenia Gravis patients have an abnormally large thymus gland, an organ that plays a role in the development of the immune system. The thymus usually is largest in children, and it shrinks considerably after puberty. In many adults with Myasthenia Gravis, the thymus does not shrink and remains unusually active in producing immune cells. The exact nature of the connection between thymus activity and Myasthenia Gravis is still unclear, however.
Is Myasthenia Gravis Hereditary?
Myasthenia Gravis 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, small genetic predisposition to develop Myasthenia Gravis or other autoimmune disorders.
In about 12% of cases, a mother with Myasthenia Gravis 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 Myasthenia Gravis caused by a genetic abnormality, not the immune system. The symptoms of congenital myasthenia are similar to those of Myasthenia Gravis.
How Is Myasthenia Gravis Detected?
Symptoms of Myasthenia Gravis usually respond well to treatment, so early detection of the disorder can help sufferers to have an improved quality of life as soon as possible.
The majority of Myasthenia Gravis 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 Myasthenia Gravis 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 Myasthenia Gravis 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 symptoms of Myasthenia Gravis, so improvement after the injection may be an indication of the presence of the disorder.
- Blood tests. These tests can detect elevated levels of acetylcholine receptor antibodies or anti-MuSK antibodies, both potential indicators of Myasthenia Gravis. Elevated levels of these antibodies are not present in some Myasthenia Gravis cases, however, so blood tests do not always detect the disorder.
- Repetitive nerve stimulation and single-fiber electromyography (EMyasthenia Gravis). 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 Myasthenia Gravis 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 Myasthenia Gravis may be treated with a variety of medications and therapies. In some cases, thymus-removal surgery may be recommended.
- 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 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.
- 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 procedure are temporary.
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 Myasthenia Gravis 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 major 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 Myasthenia Gravis patients, symptoms are confined to the eyes and do not progress to other parts of the body. In most cases, however, symptoms get worse over time and often extend to the muscles of the face, throat, neck, and/or limbs.
With treatment, Myasthenia Gravis 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:
- Illness or infection
- Thyroid problems (hyperthyroidism or hypothyroidism)
- 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 Myasthenia Gravis 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. Myasthenia Gravis 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 an escape plan.
- Support a healthy lifestyle. Make sure your loved one eats well, takes all their medication as directed, and gets plenty of rest.
Myasthenia Gravis Brain Science
Myasthenia Gravis 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. Myasthenia Gravis 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 Myasthenia Gravis (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 Myasthenia Gravis or the drugs used to treat Myasthenia Gravis’s symptoms.
The more likely connection between Myasthenia Gravis and other brain disorders lies with the secondary effects of Myasthenia Gravis. Sleep disorders, for example, may be a result of 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 Myasthenia Gravis is the more likely cause of co-existent depression, rather than a direct biochemical result of the disease itself.
Myasthenia Gravis Research
Title: A Phase II Study of Pyridostigmine With Ondansetron in Subjects With Anti-AchR Positive Myasthenia Gravis
Stage: Not Yet Recruiting
Contact: Henry Kaminiski, MD
George Washington University
Methodology: This is a phase II, a single-center, randomized, double-blind, placebo-controlled, study in patients with a diagnosis of anti-AchR antibody positive myasthenia gravis.
Study Design: The clinical trial will be conducted over a 6-week treatment period.
Group A: Patients currently taking pyridostigmine and experiencing pyridostigmine-related gastrointestinal (GI) adverse events (AEs) within the past 7 days
Group B: Patients not currently taking pyridostigmine due to GI AEs or that had their dose reduced due to pyridostigmine related GI AEs Group A will be enrolled in the study and randomized to either the control (pyridostigmine+ placebo) or the test group (pyridostigmine + ondansetron) and treated for 6 weeks. Following enrolment, patients may (if needed) titrate up their pyridostigmine dose at the investigator’s discretion each week to the highest dose deemed appropriate, tolerable and safe by the Investigator.
Group B patients not currently taking pyridostigmine due to GI AEs will initiate pyridostigmine at a dose determined by the investigator based on the patient’s history and may titrate as deemed tolerable and safe by Investigator during screening; patients on a reduced dose due to pyridostigmine related GI AEs may titrate pyridostigmine as deemed tolerable and safe by the investigator during screening. If patients in Group B experience GI AEs that fulfill enrollment criteria, along with all other inclusion/exclusion criteria, they will be enrolled into the study at that dose and randomized to either the control (pyridostigmine+ placebo) or the test group (pyridostigmine + ondansetron) and treated for 6 weeks. Following enrolment, patients may (if needed) titrate up their pyridostigmine dose at the investigator’s discretion each week to the highest dose deemed appropriate, tolerable and safe by the Investigator.
Title: Innovative Measures of Speech and Swallowing Dysfunction in Neurological Disorders (QUESST)
Principal investigator: Seward B Rutkove, MD
Beth Israel Deaconess Medical Center
Speech and swallowing abnormalities are important symptoms associated with disorders of the central nervous system, motor neuron disease (such as amyotrophic lateral sclerosis), myasthenia gravis, and primary muscle conditions. In addition to characterizing the evolution in muscle architecture that could underlie associated orofacial weakness, identifying new ways to measure these abnormalities is critical to the development and testing of novel treatment approaches. As painless, non-invasive, portable technologies, quantitative ultrasonography (QUS) and electrical impedance myography (EIM) could meet the need for objective measures of speech and swallowing dysfunction.
In QUS, acoustic energy is applied to a muscle of interest; the resultant pictorial data are translated into a single value that reflects the health of the imaged muscle. Similarly, in EIM, a high-frequency, low-intensity alternating electrical current is applied to individual muscles, and the resulting voltages measured. Impedance values reflect changes in muscle architecture, including fiber atrophy, inflammation, and the replacement of muscle with fat or connective tissue. Both of these user-friendly methods can provide sensitive indicators of neuromuscular disease status when applied to the limbs. Although they have also been used to evaluate orofacial muscles in healthy volunteers and patients with primary muscle disorders, they have not yet been systematically studied in patients with a range of neurological conditions.
When applied to muscles of the face and tongue, such tools could 1. Improve accuracy of early diagnosis; 2. Allow monitoring of speech and swallowing dysfunction over time; 3. Help individualize care; and 4. Serve as biomarkers in clinical trials. We propose that QUS and EIM will provide convenient, reliable, clinically meaningful surrogate markers of orofacial dysfunction in a variety of neurologic conditions.
Title: The EXPLORE Myasthenia Gravis Registry for Myasthenia Gravis
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 (Myasthenia Gravis) by studying peripheral blood, stool, disease status and course, and treatment of subjects with Myasthenia Gravis. The EXPLORE-Myasthenia Gravis Registry focuses on varied aspects of Myasthenia Gravis such as disease management, health care utilization, health costs, disease characteristics, and diagnostic tools. As such, it will aid in a broader understanding of Myasthenia Gravis, while providing a registry from which questions about the disease may be better answered.