Myasthenia+Gravis

=Myasthenia Gravis=

**Definition** Myasthenia Gravis is a chronic autoimmune neuromuscular disorder that affects muscle activity of the body causing weakness (1,2). As Myasthenia gravis is an autoimmune disorder, antibodies that are produced by the body block the muscles from receiving signals from nerve cells (1). The main characteristic of Myasthenia Gravis is muscle weakness that increases with activity but improves after rest. The muscles commonly affected include those that control eye and eyelid movement, facial expression, chewing, talking, swallowing, breathing, and neck and limb movement (2). Symptoms (1):
 * Impaired breathing
 * Impaired chewing or swallowing
 * Difficulty climbing stairs, lifting objects, or coming from sit to stand
 * Impaired talking
 * Drooping head or eyelids
 * Fatigue
 * Double vision
 * Facial muscle involvement (paralysis, weakness)
 * Hoarseness
 * Trouble maintaining steady gaze

=**Epidemiology**=

The prevalence of myasthenia gravis in the United States is estimated at 14 to 20 per 100,000 population, approximately 36,000 to 60,000 cases in the United States. However, myasthenia gravis is probably under diagnosed and the prevalence is probably higher. Previous studies showed that women are more often affected than men. The most common age at onset is the second and third decades in women and the seventh and eighth decades in men. As the population ages, the average age at onset has increased correspondingly, and now males are more often affected than females, and the onset of symptoms is usually after age 50.

=**Pathophysiology**=

Myasthenia Gravis is an autoimmune disorder characterized by antibody-mediated destruction of acetylcholine receptors in the neuromuscular junction. It remains unclear what specifically triggers the autoimmune response, but abnormal T-lymphocyte function is thought to be the mechanism. Approximately 75% of people with MG have some sort of thymic abnormality, such as thymoma (thymic tumor) or thymic hyperplasia.
 * About 10% of infants born to mothers with MG develop neonatal myasthenia gravis due to placental transfer of the acetylcholine receptor antibody. However, the symptoms usually spontaneously resolve within a few months after birth.
 * Lambert-Eaton myasthenic syndrome is a myasthenic syndrome that develops in association with neoplasms, specifically small cell carcinoma of the lung. Lambert- Eaton myasthenic syndrome is also thought to be an autoimmune process, but results in a decrease in release of acetylcholine instead of a destruction of receptors.

=**Diagnosis**=

How is MG diagnosed?

Weakness and fatigue are common in the general population, but the degree and pattern of these symptoms — particularly diplopia, ptosis and other signs of [|weakness in the eye muscles] — should alert a neurologist to the possibility of MG.

The neurologist is likely to ask many questions and to conduct a //physical exam// to determine the extent of weakness. To look for evidence of increased weakness following exertion, he or she might ask the patient to look up without blinking for one or two minutes, hold the arms out for as long as possible or climb up steps.

If the physical exam is consistent with MG, the neurologist usually orders a //blood test// designed to detect antibodies to the ACh receptor. (A blood test for MuSK antibodies also should be available soon.) A positive test result confirms a diagnosis of MG.

If the blood tests are negative, the next step is usually //electrodiagnostic testing,// in which electrodes are used to measure the electrical signals in muscle. Surface electrodes (similar to those used in electrocardiograms) deliver small shocks to a nerve in the arm, leg or face, while other surface electrodes record the responses in muscle. In MG, a muscle’s response to repeated nerve stimulation declines rapidly.

In addition to or in place of electrodiagnosis, the neurologist might try giving an intravenous injection of //edrophonium (Tensilon)//, a fast-acting cholinesterase inhibitor. A temporary increase in strength after this "Tensilon test" is consistent with either MG or CMS.

If a diagnosis of MG is confirmed, a CT scan, chest X-rays or magnetic resonance imaging (MRI) will be used to examine the thymus and look for evidence of thymoma. //This segment is taken directly from// [], //this website has a lot of good information on MG facts, who it affects, its pathophysiology, etc.//

=**Prognosis**=

There is no cure, but long-term remission is possible. With treatment, most individuals with myasthenia can significantly improve their muscle weakness and lead normal or nearly normal lives. Some cases of myasthenia gravis may go into remission and muscle weakness may disappear completely so that medications can be discontinued. People who have only eye symptoms (ocular myasthenia gravis), may develop generalized myasthenia over time. Stable, long-lasting complete remissions are the goal of thymectomy and may occur in about 50 percent of individuals who undergo this procedure. In a few cases, the severe weakness of myasthenia gravis may cause respiratory failure, which requires immediate emergency medical care. Pregnancy is possible for a woman with myasthenia gravis but should be closely supervised. The baby may be temporarily weak and require medications for a few weeks after birth but usually does not develop the disorder.

=**Myasthenia Gravis in Pediatrics**=

There are three types of MG in children, including the following:
 * Congenital MG - this is a very rare non-immune form of MG that is inherited as an autosomal recessive disease. This means that both males and females are equally affected and that two copies of the gene, one inherited from each parent, are necessary to have the condition. Symptoms of congenital MG usually begin in the baby's first year and are life-long.
 * Transient neonatal MG <span class="definition_seperator">- <span class="definition_text">between 10 and 15 percent of babies born to mothers with MG may have a temporary form of MG. This occurs when antibodies common in MG cross the placenta to the developing fetus. Neonatal MG usually lasts only a few weeks, and babies are not at greater risk for developing MG later in life.
 * <span class="definition_term">Juvenile MG <span class="definition_seperator">- <span class="definition_text">this auto-immune disorder develops typically in female adolescents - especially Caucasian females. It is a life-long condition that may go in and out of remission. About 10 percent of MG cases are juvenile-onset.

The following are the most common symptoms of myasthenia gravis. However, each child may experience symptoms differently. Symptoms may include:
 * Babies with neonatal MG may be weak, with a poor suck, and may have respiratory difficulty. A few babies may need the help of a mechanical breathing machine if their respiratory muscles are too weak to breathe on their own. Symptoms go away as the maternal antibodies disappear over time.
 * Congenital MG symptoms may begin in the first year, with generalized weakness in the arms and legs, and delays in motor skills such as crawling, sitting, and walking. Babies may have difficulty feeding and may have weak eyelids and poor head control.
 * Juvenile MG symptoms may begin gradually over weeks or months. The child may become excessively tired after very little activity, and begin to have problems chewing and swallowing. Drooping eyelids may be so severe that the child cannot see.

In pediatrics, it is important to know that the symptoms of myasthenia gravis may resemble other conditions. Always consult your child's physician for a diagnosis. []

**Treatment**There is no known cure for Myasthenia Gravis, but there are effective treatments to control the symptoms. Treatment options take into account the child’s age, health, medical history, severity of MG condition, child’s tolerance to medications and procedures, and the family’s preference. The primary goal of MG treatment is to prevent respiratory problems because the swallowing, breathing, and eye muscles are primarily affected by this condition. __Medications:__ -Anticholinesterase agents (Mestinon®)- acetylcholine remains at neuromuscular junction longer so more receptor sites can be activated, improve muscle contraction and muscle strength Side effects: GI upset, excessive salivation and tearing, frequent urination

-Corticosteroids (Prednisone)- suppress the abnormal immune system, limits the production of abnormal antibodies Side effects: bone thinning, weight gain, diabetes, increased body fat

-Immunosuppresant agents (Imuran®)- suppress the abnormal immune system Side effects: risk of infection, liver damage, infertility, increased risk of cancer

__Plasmapheresis__: removing the abnormal antibodies from the plasma in the blood, initial improvement but it is short-lived because the abnormal antibodies continue to grow, used prior to surgery to boost immune system or during severe MG weakness __Thymectomy__: Sometimes the thymus is surgically removed (thymectomy). While the thymus gland’s role is not completely understood in relation to Myasthenia Gravis, its removal may decrease the patient’s symptoms. The thymus is responsible for production of T-cells. In 90 percent of people with Myasthenia Gravis there is an abnormality in the thymus gland- 70 percent have an enlarged thymus gland (hyperplasia) and 20 percent have a benign tumor (thymomas). In most cases, removal leads to a significant decrease of symptoms or many years symptom-free. Thymectomy has been shown to be safe for children with high rates of remission and improvement without adverse events (Essa et al., 2003). __Physical therapy__: maintain ROM and strength, prevent muscle atrophy, diaphragmatic breathing exercises, patient education on energy conservation & use of adaptive equipment to lessen load of body

=**Organizations with Information on Myasthenia Gravis and Support**=

The following link is a website to the Australian Myasthenia Gravis Association. It has a large amount of information about symptoms, causes, diagnosis and treatment of MG. [] Myasthenia Gravis Association – KC [] Myasthenia Gravis Foundation of America []

=**Websites**=

This is a website from Livestrong.com that discusses the importance of exercise for people with MG. []

Another link from the same source, but this page contains information of fatigue after exercise and the involvement of a physical therapist in creating an exercise program to conserve energy for those with MG. []

This link is entirely dedicated to physical therapy for MG from the Livestrong site: []

Elliiptical Machines being used as source of exercise for those with MG. Because feet stay put, people do not have to worry as much about tripping or falling while performing exercise. []

Researchers believe the thymus gland plays a role in the development of auto-immune disorder MG. Not common in children and usually inherited from mother at birth and typically goes away. However, it can develop into full-blown MG. []

=**Adaptive Equipment for Children**=

For this child, we thought the Amtryke will be an appropriate form of adaptive equipment. She is able to walk and transfer independently, however her balance and LE weakness make it difficult for her to play on a standard tricyle, which she enjoys doing. Amtryke offers many different types of adaptive tricycles and bicycles. They are made to offer more trunk and/or head support, pedals with straps, handles that are placed close to the body, or able to pedal to assist in propulsion. This is a video of a child with an Amtryke that we would recommend. media type="youtube" key="daVzkID0Wes" width="425" height="350"

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=**Summary of Evidence: Is Exercise Beneficial for Patients with Myasthenia Gravis?**=
 * **AUTHOR** || **SOURCE** || **DATE** || **TITLE** || **SAMPLE** || **METHODOLOGY/ MAIN IDEA** || **RESULTS** ||
 * Davidson et al. || NZ Journal of Physiotherapy || 2005 || Exercise prescription in the physiotherapeutic management of Myasthenia Gravis: a case report || 78 year old male diagnosed with MG presenting with symptoms of double vision, ptosis and balance difficulties || Case report examining effects of a 6 week exercise program consisting of LE strengthening and walking on muscle strength, endurance and fatigue. || The exercise program showed moderate gains in strength and endurance, decrease in fatigue, and improved quality of life as stated by patient. ||
 * Lohi et al. || Arch Phys Med Rehabil || 1993 || Physical Training Effects in Myasthenia Gravis || 11 subjects 25 to 50 years of age (10 women, 1 man) with mild or moderate MG without other severe or disabling disease || Study examined effects of a dynamic strength training program (27 to 30 sessions over 10 weeks) on elbow extension, elbow flexion, and knee extension maximal muscle force and fatigue of MG subjects. Subjects completed standardized maximal muscle force and endurance measurements before and after their training period. The 10 week training session was completed with loose weights. Subjects completed 2-3 sets of 10 repetitions during each session using a preset weight based on their maximal muscle force found prior to training. || Some patients were not able to follow the specified training protocol. However, all patients reported improved strength and resistance to fatigue while training. Maximal muscle force of knee extension increased 22.9% on the trained side versus 4.3% on the untrained side. Only small changes were seen in elbow flexion and extension maximal muscle force and with resistance to fatigue. ||
 * Stout et al. || Medicine & Science in Sports & Exercise || 2000 || Effects of resistance exercise and creatine supplementation on myasthenia gravis: a case study || 26 year old male diagnosed with MG at 21 yo, unilateral ptosis progressing to bilateral ptosis, diplopia, muscle atrophy || Case study of effects of resistance training (3-4 sets per major muscle group, 3 times a week) and 5g of Creatine per day for 15 weeks || Results indicated an increase in body weight, fat-free mass, isokinetic peak strength leg flexion (12.4%) and leg extension (37%), upper body volume load and lower body volume load. ||
 * Lucia et al. || Muscle & Nerve || 2007 || Double Trouble (McArdle's Disease and Myasthenia Gravis) How can Exercise Help? || Case Report: 29 year old female diagnosed with McArdle's Disease at age 22 and at age 24 diagnosed with Myasthenia Gravis. Subject complained of muscle weakness, easy fatigability and exercise intolerance. || Subject performed 5 weekly sessions of low to moderate intensity exercise progressing from 10 to 60 minutes of aerobic exercise. Intensity of exercise was at 60% of max HR. Walking was the chosen mode of exercise by the subject. Before each session, subject would ingest ~100g of complex carbs and ~330ml of commercialized sports drink. || Subject had 44% increase in exercise time and 50% increase in VO2max. Subject reported improved feeling of well being and ability to perform increased ADL's. ||
 * Fregonezi et al. || Chest || 2005 || Effects of 8-week, interval-based inspiratory muscle training and breathing retraining in patients with generalized myasthenia gravis || 27 patients with stable generalized MG (16 women, 11 men; age range: 33-75 years) || Prospective randomized trial; Control group received conventional medical treatment, treatment group received conventional medical treatment & underwent 8-week interval based inspiratory muscle training (IMT) (3x/week: 10 minutes of the following: diaphragmatic breathing, interval IMT, and pursed lip breathing). Subjects performed training 1x/week at hospital under supervision and 2x/week at home. || The training group demonstrated improvements in respiratory muscle strength, chest wall mobility, respiratory pattern, and respiratory endurance compared to the control group. ||

== Example Letter of Medical Necessity:

= = =**References**= 1. PubMed Health. (2011). Myasthenia Gravis. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001731/ 2. National Institute of Neurological Disorders and Stroke. (2011). Myasthenia Gravis Fact Sheet. [|http://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.htm#180023153] 3. Stout, Jeffrey R., Joan M. Eckerson, Eric May, Cynthia Coulter, and Greg E. Bradley-Popovich. "Effect of resistance exercise and creatine supplementation on myasthenia gravis: a case study." //Medicine & Science in Sports & Exercise// Sept. (2000): 869-72. Web. 16 Nov. 2011. 4. Lucia et al. 2007. "Double trouble (McArdles Disease and Myasthenia Gravis): How can exercise help?". //Muscle & Nerve//. 35: 125-128. 5. Myasthenia Gravis Foundation of America, Inc. [] 6. Mayo Foundation for Medical Education and Research. Myasthenia Gravis: treatment. [] 7. Children's Hospital Boston, Myasthenia gravis. [] 8. Lucile Packard Children's Hospital at Stanford. Myasthenia Gravis. [] 9. Fregonezi et al. (2005). "Effects of 8-week, interval-based inspiratory muscle training and breathing retraining in patients with generalized myasthenia gravis." //CHEST//, 128, 1524-1530. 10. Lohi, E-L., Lindberg, C., & Andersen, O. (1993). Physical training effects in myasthenia gravis. //Arch Phys Med Rehabil//, 74, 1178-1180. 11. Porth, C. (2007). //Essentials of Pathophysiology, 2nd Edition.// Philadelphia, PA: Lippincott Williams & Wilkins. 12. Essa M. et al. (2003). Maximal thymectomy in children with myasthenia gravis. //European Journal of Cardio-Thoracic Surgery//, 24(2), 187-191.