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Myasthenia Gravis: Getting the Message Across
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patients with MG. Others may complain of difficulty when chewing tough or fibrous foods, swallowing, and speaking. The degree of muscle weakness varies among patients. It is generally less severe in the morning and worsens as the day progresses, particularly after using the muscles for prolonged periods. In some patients, MG may affect only muscles of the eye, while others experience multi-system involvement. Rarely, patients may develop respiratory failure leading to myasthenic crisis.
• Body composition analysis
yasthenia gravis (MG) is a term derived from Latin and Greek origins and means “grave muscle weakness.” The classic sign of MG is muscle weakness that worsens during activity and improves after rest. People of any age, gender, or ethnicity can be affected by MG; however, it is more common in women under 40 and men over 60 years of age. There are currently about 36,000 to 60,000 cases of MG in the United States. This disorder is not contagious nor is it directly passed genetically from parents to child. The reason why some people develop MG is unknown.
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Causes of Muscle Weakness in MG
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Nerves release chemicals known as neurotransmitters that interact with various cells of the body to produce specific responses. Acetylcholine (ACh) is an important neurotransmitter that exerts many functions, one of which is muscle contraction. Myasthenia gravis is an autoimmune disease, that is, the patient’s immune system produces antibodies that alter, block, or destroy ACh receptors on muscle cells. Fewer messages reach the muscles, thus disrupting normal contraction and resulting in muscle weakness.
In mild cases, the signs and symptoms of MG may appear similar to other medical conditions, thus delaying its diagnosis. It is essential that the physician completes a thorough medical history and performs a comprehensive physical and neuromuscular examination. If MG is suspected, tests may be ordered to confirm the diagnosis.
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The thymus gland is part of the immune system and located in the upper chest underneath the breastbone. In adults with MG, the thymus gland is larger than normal and, in some patients, its removal can result in symptom improvement. Research continues on the role of the thymus gland in MG. Drugs have been reported to produce/ worsen symptoms in patients with MG. Penicillamine, interferon, botulinum toxin and a host of other compounds should be avoided in patients with this disease. An extensive list of drugs that may affect patients with MG is available from the Myasthenia Gravis Foundation of America (link to this URL http://www.myasthenia. org/docs/MGFA_MedicationsandMG.pdf ).
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Symptoms Muscle weakness in the eye and blurred or double vision are the initial signs in most
Diagnosis and Testing
• Edrophonium chloride (Tensilon®) test The drug edrophonium blocks the normal destruction of (ACh) and raises the levels of this neurotransmitter. This results in temporary improvement in muscle strength. Neostigmine (Prostigmin) may be used in infants and children as it has a longer duration of action and provides additional time to observe muscle function. A trial of daily pyridostigmine (Mestinon) may be used if edrophonium and neostigmine do not yield satisfactory results. These tests are useful in patients who present with double vision or eye muscle weakness. • Blood analysis This may reveal the presence of antibodies to ACh receptors. Most patients have an increased level of antibodies, but this may not be the case in those whose symptoms are limited to the eyes. • Electromyography repetitive nerve stimulation (RNS) Electrodes are attached to the muscles being tested and small pulses of electricity are delivered to detect any reduction in response resulting from muscle fatigue.
Myasthenia Gravis: Getting the Message Across • Single-fiber electromyography (EMG) A very fine wire electrode is inserted through the skin and into a single muscle and measures nerve-to-muscle electrical activity. The EMG is considered the most sensitive clinical test of neuromuscular transmission. • Imaging scans Computed tomography (CT) scan or magnetic resonance imaging (MRI) is used to identify the presence of a tumor or other changes in the thymus gland. • Lung function examination These tests are used to measure respiratory function and can be helpful in evaluating the patient’s capacity for air exchange. A significant decrease in pulmonary function may precede what is referred to as myasthenic crisis.
Treatment A number of nonpharmacologic and pharmacologic options are available for managing MG. With the variety of treatment alternatives and frequently unpredictable responses, therapy must be individualized. It is critical that the patient be treated by a physician (usually a neurologist) familiar with this disease. • Lifestyle changes may be beneficial in managing the complications of MG. Patients can use appliances such as an electric toothbrush to conserve muscle energy. Eye patches may be helpful in those with double vision. Installation of sidebars and railings may prevent falls during periods of weakness.
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A publication of: Mylan School of Pharmacy Center for Pharmacy Care Pharmaceutical Information Center (PIC) Additional information on newsletter topics: Pharmaceutical Information Center 412-396-4600 pic@duq.edu Questions about screenings or programs: Christine O’Neil, Pharm.D, B.C.P.S. 412-396-6417
Newsletter Contributors John G. Lech, Pharm.D. Van M. Mai, Pharm.D. Kelly A. Olearchick, Pharm.D. Candidate Melanie K. Kidder, Pharm.D. Candidate
the antibodies responsible for the signs and symptoms associated with the disease. Corticosteroids, most commonly prednisone, are often used for managing acute symptoms; however, they may also be used for more extended periods. Cyclosporine, azathioprine, and mycophenolate mofetil (CellCept) may be used on a chronic basis for treating patients with more severe forms of MG. Symptoms are decreased or reversed in most patients using these agents, but adverse effects can be severe.
• Surgery to remove the thymus (thymectomy) may be considered in some circumstances. Response is unpredictable, but usually most effective in young patients with early disease. • Plasmapheresis is a procedure whereby antibodies responsible for MG are removed from the bloodstream. Almost all patients receive some benefit from this procedure. • Acetylcholinesterase inhibitors (AChEIs) such as pyridostigmine and neostigmine are considered first-line therapy in MG. These drugs interfere with the enzyme (acetylcholinesterase) that normally destroys ACh, thus increasing its concentration at the muscle site. These compounds do not directly affect the underlying cause of MG, but do improve muscle function and strength. Again, response is variable and a given patient may even note improvement in one muscle group and not another. Interestingly, factors such as weather, stress, and infection may also influence patient response to these drugs. • Immunosuppressive drugs are useful in MG because they decrease production of
• The intravenous injection of immune globulin (IVIG; gamma globulin) blocks the effects of the antibodies causing MG. Response may be rapid, but the duration is highly variable. It produces fewer adverse effects than immunosuppressive drugs. The accompanying table includes the approximate time to improvement, duration of response, and adverse effects associated with these treatments. Today, the outlook for the majority of patients with MG is optimistic. Most can lead a normal life if they receive appropriate medical supervision and treatment.
Treatment Options in Myasthenia Gravis time to improvement AChEIs
Duration of effect
Common adverse events
~1 hour
3-4 hours
~2 weeks
Highest improvement occurs in first 6-8 weeks; best for new onset symptoms
↑risk of infection osteoporosis ↑weight ↑ blood sugar
Azathioprine
4-8 months
Maintained for extent of therapy
↑risk of infection liver toxicity
Cyclosporine
1-2 months with maximum improvement in 6 months
Maintained for extent of therapy
↑risk of infection kidney toxicity
Exact onset not determined, but considered faster than azathioprine
Not determined
↑risk of infection
1 week
1-2 months
infusion reactions
As early as the first exchange
Several weeks to months
↑risk of infection blood clots
2-5 years
Not determined
Corticosteroids
Mycophenolate mofetil
IVIG Plasmapheresis Thymectomy
digestive complaints ↑secretions ↑urination
surgical complications
For more information, please visit the following Web sites: • www.mayoclinic.com/health/myasthenia-gravis/DS00375/METHOD=print • www.ninds.nih.gov/disorders/myasthenia_gravis/myasthenia_gravis.htm • www.myasthenia.org/hp_clinicaloverview.cfm
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