It's Myasthenia Gravis Awareness Month

In recognition of June being National Myasthenia Gravis Awareness Month, Quest News Online is examining the disease from several perspectives. This article offers an overview of signs, symptoms, diagnosis and treatments for myasthenia gravis (MG), as well as some drugs for people with MG to avoid.

As one of the 43 diseases in MDA's program, MG is also the focus of more than a dozen current MDA-funded research projects. These projects, described below, range from identification of genetic causes and molecular underpinnings to development of potential new treatments.

About MG

MG is part of a large class of diseases known as "autoimmune," or "self-immune," disorders, in which the body's immune system deploys antibodies (proteins that identify and attack bacteria and other foreign substances) to attack its own tissues.

In MG, the attack occurs at the neuromuscular junction (NMJ) — the connection between muscle and nerve. 

In most cases of MG, the immune system targets the acetylcholine receptor, the part of a muscle cell that receives signals from a nerve cell. The receptors are destroyed faster than the body can replace them. Another form of the disease is characterized by an attack on muscle-specific kinase, a protein that helps organize acetylcholine receptors on the muscle cell. 

It remains unclear what triggers the disease, but the list of possibilities includes autoimmune responses to viruses or bacteria, and tumors or hyperactivity in the thymus gland, located in the upper chest. 

Signs and symptoms

Some 10 to 15 out of every 100,000 Americans have MG, which most commonly affects women between the ages of 30 and 40, and men in their 50s or 60s. In some cases, it affects children. Symptoms vary in type and severity, but generally involve weakness and fatigue of the body's voluntary muscles. 

Early symptoms often include weakness in the muscles that control movement of the eyes and eyelids, sometimes leading to partial paralysis of eye movements, double vision and droopy eyelids. 

Weakness in the neck and jaw, called "bulbar" weakness, also can occur early in MG. Such weakness can make it difficult to talk, chew, swallow and hold up the head. It also may affect speech, cause choking, and make eating unpleasant or difficult. 

Typically, as the disease progresses, weakness spreads from the face and neck to the upper limbs, the hands and then the lower limbs. People with MG may find it difficult to raise their arms over their head or stand up from a sitting position. They may lose the ability to walk long distances and climb stairs, and weakness in the arms and hands often leads to an inability to grip or hold on to heavy objects. 

In severe cases, weakness may spread to the muscles in the chest that control breathing. This can lead to respiratory distress or failure ("myasthenic crisis"), and the need for assisted ventilation. 

Diagnosis

Diagnosis of the disease is made via review of the individual's medical history, and physical and neurological examinations. Confirmatory tests may include: 

  • a blood test that detects the presence of immune system molecules or antibodies that target the acetylcholine receptors;
  • the edrophonium test, in which the individual is administered a drug that blocks the breakdown of acetylcholine, temporarily increasing the levels of the protein at the NMJ. In people with MG involving the eye muscles, the drug will temporarily relieve weakness;
  • nerve conduction studies, which evaluate muscle fatigue in response to repeated nerve stimulation;
  • single fiber electromyography (EMG), in which single muscle fibers are stimulated by electrical impulses to detect impaired nerve-to-muscle transmission;
  • computed tomography (CT), which can identify abnormalities in the thymus gland; and
  • pulmonary function testing, which measures breathing strength; this exam may help predict respiratory failure that could lead to myasthenic crisis.  

Treatments

There are a number of medications designed to help control MG, and with treatment many experience significant improvement of their muscle weakness. In some cases, MG may go into temporary remission and muscle weakness may disappear, allowing for the discontinuation of medication. 

Treatments include: 

  • immune system suppression with drugs such as corticosteroids (prednisone and prednisolone); azathioprine (Imuran); mycophenylate mofetil (CellCept); cyclosporine (Neoral, Sandimmune); and cyclophosphamide (Cytoxan, Neosar);
  • medications designed to block the activity of the protein that normally breaks down acetylcholine (an enzyme called acetylcholinesterase) such as pyridostigmine (Mestinon);
  • removal of harmful antibodies through plasma exchange, in which an intravenous line removes the antibodies from the blood;
  • intravenous immnoglobulin (IVIg) therapy, which involves the injection of nonspecific antibodies as a means to decrease the immune system's own antibody production; and
  • removal of the thymus gland ("thymectomy"), which has been shown to produce complete remission in some people with the disease. 

People with MG also should be aware that many prescription drugs can worsen their disease. Those with MG should avoid: 

  • muscle relaxants used during surgery
  • aminoglycoside and quinolone antibiotics
  • cardiac anti-arrhythmics
  • local anesthetics
  • magnesium salts (including milk of magnesia) 

Current MDA-funded research

MDA currently funds 13 worldwide research projects focused on MG, totaling $3,365,757 through 2012. These projects, listed below, are helping to reveal numerous facets of the disease, from the identification of genetic causes and molecular underpinnings to a number of specific treatment strategies. 

  • At the Hellenic Pasteur Institute in Athens, Greece, Socrates Tzartos is working on development of an MG-specific therapeutic approach that involves removing harmful antibodies from the blood.
  • At the Open University of Israel in Raanana, Miriam Souroujon is working on a method to suppress MG by increasing numbers of immune system helper cells known as regulatory T cells. Souroujon's team plans to treat rats and mice with these cells to see if it ameliorates the disease. Favorable results could lead to human clinical trials.
  • In Phoenix, at St. Joseph's Hospital & Medical Center, Fu-Dong Shi is studying a newly discovered subtype of cells, called Th17 cells, that may be involved in causing MG. Shi's team is examining the role the cells play in a mouse model of human MG.
  • Michael Ferns of the University of California at Davis is probing the molecular mechanism behind normal and antibody-influenced acetylcholine receptor levels in the NMJ. Also at UC Davis, David Richman is studying whether an attack of antibodies on muscle-specific kinase protein is responsible for a form of MG that involves severe muscle atrophy.
  • Lin Mei at the Medical College of Georgia Research Institute in Augusta, Ga., is delving into the role of a protein called LRP4 in signaling, formation and function of the NMJ.
  • Matthew Meriggioli at the University of Illinois at Chicago, is using a growth factor called GM-CSF to mobilize immune regulatory cells and suppress MG in mice. At that same institution, JianRong Sheng is looking at ways to generate specific immune cells called "regulatory B cells" using GM-CSF, and evaluating those cells' therapeutic potential.
  • At the Jackson Laboratory in Bar Harbor, Maine, Laurent Bogdanik is working to characterize a new research mouse model for MG so it can be used to more effectively study human myasthenia mechanisms and treatments.
  • At the University of Michigan at Ann Arbor, Daniel Goldman is studying the potential for a type of drug called a histone deacetylase inhibitor that may be able to stop disruption of NMJ signaling.
  • Samia Ragheb at Wayne State University in Detroit is looking at the role of a newly discovered molecule called Baff that appears to help some immune system cells survive and multiply.
  • At St. Louis University in Missouri, Jindrich Soltys is examining the role of a membrane-attack complex called "the complement system" at the NMJ that ultimately causes the cell to swell and burst. Results may reveal the therapeutic potential for complement inhibition.
  • At the University of Texas Medical Branch at Galveston, Premkumar Christadoss is studying the possibility that proteins produced as the result of infection may trigger autoimmune response and MG.   

MG clinical trials and advocacy

For information about MG-related clinical trials, visit ClinicalTrials.gov, click on "Search for Clinical Trials," and enter "myasthenia gravis" in the search box. You always should discuss any interest in participation in a clinical trial with your MDA physician. 

To find out how you can help raise awareness for MG, learn about key legislative issues that may affect you or family members with MG, or get involved in the search for a cure, visit MDA's advocacy home page or contact your local health care service coordinator by using MDA's office locator or by calling (800) 572-1717.

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