Myasthenia gravis

Myasthenia gravis (MG) is a neuromuscular disorder characterized by weakness and fatigability of skeletal muscles.
The underlying defect is a decrease in the number of available acetylcholine receptors (AChRs) at neuromuscular junctions due to an antibody-mediated autoimmune attack

1. MYASTHENIA GRAVIS Presented by: VIVEK DEV

2. BACKGROUND OF THE DISEASE Myasthenia gravis (MG) is a neuromuscular disorder characterized by weakness and fatigability of skeletal muscles. The underlying defect is a decrease in the number of available acetylcholine receptors ( AChRs ) at neuromuscular junctions due to an antibody-mediated autoimmune attack .

3. The hallmark of myasthenia gravis is muscle weakness that worsen after period of activity and improves after period of rest. As a clinical entity, myasthenia gravis was not recognized until Samuel Wilks in 1877 described bulbar and peripheral muscular weakness. In the Lancet of June 2, 1934, the remarkable discovery of physostigmine treatment by Dr. Mary Walker was published, which was to become the mainstay of symptomatic treatment.

4. Certain muscles such as those that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are often (but not always) involved in the disorder. The muscle that control breathing and neck and limb movements may also be affected. There is no known cure but available treatments can control the symptoms and often allow people to have a relatively high quality of life.

5. CAUSES In MG, the receptors at the muscle surface are destroyed or deformed by antibodies that prevent a normal muscular reaction from occurring. The causative factor is unknown, but the disorder may have a genetic link. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, drooping eyelids, trouble talking, and trouble walking. Those affected often have a large thymus gland or develop a thymoma .

6. Factors that can worsen myasthenia gravis Fatigue Illness Stress Extreme heat Some medications — such as beta blockers, calcium channel blockers, quinine and some antibiotics

7. INCIDENCE MG is rare, having a prevalence of 2–7 in 10,000. Myasthenia Gravis is most common in the people at the age of 40 and above. This mainly affects the older people and the middle aged people. There are more women than men and the age of the participants ranged from 40to 82. The prevalence of this disease is found to be more in China (64,942) followed by India (53,253) and is found to be least in Bhutan (109).

8. The following table attempts to extrapolate the prevalence rate for Myasthenia Gravis to the populations of various countries and regions in Asia:

9. PATHOPHYSIOLOGY In MG, antibodies are directed toward the acetylcholine receptor at the neuromuscular junction of the skeletal muscle Resulting in: Decreased number of acetylcholine receptors at the post synaptic muscle membrane postsynaptic folds are simplified or flattened Decreased neuromuscular transmission Weakness of muscle contraction Therefore, although Ach is released normally, it produces small end-plate potentials that may fail to trigger muscle action potentials.

10. Failure of transmission at many neuromuscular junctions results in weakness of muscle contraction. The amount of Ach released per impulse normally declines on repeated activity (termed presynaptic rundown).

11. An immune response to muscle-specific kinase (musk), a protein involved in achR clustering at neuromuscular junctions, can also result in myasthenia gravis, with reduction of achRs demonstrated experimentally. The pathogenic antibodies are igG , and are t cell dependent. Immunotherapeutic strategies directed against either the antibody-producing b cells or helper t cells are effective in this antibody-mediated disease.

12. The autoimmune response is initiated and maintained in mg is not completely understood, but the thymus appears to play a role in this process. The thymus is abnormal in ∼75% of patients with MG; in ∼65% the thymus is “hyperplastic,” with the presence of active germinal centers detected histologically, though the hyperplastic thymus is not necessarily enlarged. An additional 10% of patients have thymic tumors ( thymomas ). Muscle-like cells within the thymus ( myoid cells), *Bear AChRs on their surface * May serve as a source of autoantigen and trigger the autoimmune reaction within the thymus gland.

13. Thymus gland, a part of your immune system located in the upper chest beneath the breastbone, may trigger or maintain the production of antibodies that result in the muscle weakness common in MG.

14. PREDISPOSING FACTOR Myasthenia gravis may be inherited as a rare, genetic disease , acquired by babies born to mothers with MG Nerves communicate with the muscles by releasing chemicals, called neurotransmitters. Immune system produces antibodies that block or destroy many of the muscles' receptor sites for a neurotransmitter called acetylcholine . With fewer receptor sites available, muscles receive fewer nerve signals, resulting in weakness.

15. SYMPTOMATOLOGY The main symptom of myasthenia gravis is weakness in the voluntary skeletal muscles, which are muscles under our control. The failure of muscles to contract normally occurs because they can’t respond to nerve impulses. Without proper transmission of the impulse, a blocked communication occurs between nerve and muscle and weakness results. Weakness associated with myasthenia gravis typically gets worse with more activity and improves with rest. Some of the main symptoms to be noticed are:

16. EYE MUSCLES In more than half the people who develop MG, their first signs and symptoms involve eye problems: Drooping of one or both eyelids (ptosis) Double vision (diplopia ) Blurred vision, which may come and go

17. FACE AND THROAT MUSCLE In about 15 percent of people with myasthenia gravis, the first symptoms involve face and throat muscles , which can cause difficulties with: Speaking . The speech may be very soft or sound nasal, depending upon which muscles have been affected. Swallowing . May choke very easily, which makes it difficult to eat, drink or take pills. In some cases .

18. FACE AND THROAT MUSCLE Chewing . The muscles used for chewing may wear out halfway through a meal, particularly if eating. Facial expressions . Family members may note "lost smile" if the muscles that control facial expressions are affected

19. ARM AND LEG MUSCLES Myasthenia gravis can cause weakness in arms and legs, but this usually happens in conjunction with muscle weakness in other parts of the body – such as eyes, face or throat. The disorder usually affects arms more often than legs. If it affects legs, may waddle when walking. Normal dumbbell Weakness dumbbell

20. WHEN TO SEE A DOCTOR If having trouble with: Breathing Seeing Swallowing Chewing Walking

21. DIAGONOSIS OF MYSTHENIA GRAVIS History Diplopia, ptosis, Weakness in characteristic distribution, Fluctuation and fatigue: worse with repeated activity, improved by rest Effects of previous treatments . Physical examination Ptosis, diplopia Motor power survey : quantitative testing of muscle strength ,Forward arm abduction time (5 min ), Vital capacity, Absence of other neurologic signs.

22. LABORATORY TESTING Edrophonium test : Injection of the chemical edrophonium ( Tensilon ) may result in a sudden, although temporary, improvement in muscle strength — an indication that may have myasthenia gravis. Edrophonium - acts to block an enzyme that breaks down acetylcholine, the chemical that transmits signals from nerve endings to muscle receptor sites. Blood analysis : A blood test may reveal the presence of abnormal antibodies that disrupt the receptor sites where nerve impulses signal muscles to move .

23. Single-fiber electromyography (EMG): EMG measures the electrical activity traveling between brain and muscle . It involves inserting a very fine wire electrode through skin and into a muscle. In single-fiber EMGs, a single muscle fiber is tested. Imaging scans : CT scan or an MRI to confirm a tumor or other abnormality in thymus. SINGLE FIBER-EMG CT CHEST

24. PRINCIPLES OF MANAGEMENT A . THERAPEUTIC MANAGEMENT : Cholinesterase inhibitors . Drugs like pyridostigmine ( Mestinon ) enhance communication between nerves and muscles. These drugs don't cure, but improves muscle contraction and strength. Corticosteroids. These types of drugs inhibit the immune system, limiting antibody production. Prolonged use of corticosteroids, can lead to serious side effects, like bone thinning, weight gain, diabetes, increased risk of some infections, and increase and redistribution of body fat. Immunosuppressants . Doctor may also prescribe other medications that alter immune system, like azathioprine (Imuran), cyclosporine ( Sandimmune )

25. THERAPY Plasmapheresis . This procedure uses a filtering process similar to dialysis. Blood is routed through a machine that removes the antibodies that are blocking transmission of signals from nerve endings to muscles' receptor sites. However, the beneficial effects usually last only a few weeks. Intravenous immune globulin . This therapy provides body with normal antibodies , which alters immune system response. It has a lower risk of side effects than do plasmapheresis and immune-suppressing , but it can take a week or two to start working and the benefits usually last less than a month or two.

26. B. NON-THERAPEUTIC MANAGEMENT Thymectomy - surgical removal of the thymus gland. The role of the thymus gland in MG is not fully understood, and the thymectomy may or may not improve a child's symptoms.

27. C. PREVENTION Because the cause of myasthenia gravis is unknown, there is no way to prevent it. However, once the disease has developed, there may be ways to prevent episodes of worsening symptoms or flare-ups: Give yourself plenty of rest. Avoid strenuous, exhausting activities. Avoid excessive heat and cold. Avoid emotional stress.

28. Whenever possible, avoid exposure to any kind of infection, including colds and influenza (flu). You should be vaccinated against common infections, such as influenza. Work with your doctor to monitor your reactions to prescription medications. Some drugs commonly prescribed for other problems, such as infections, heart disease or hypertension, may make myasthenia gravis worse. You may need to choose alternative therapies or avoid some medications entirely.

29. REFERENCES Harrisons Neurology in clinical medicine http ://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.htm ( for fact sheet & possible questions asked by patient’s family ) http:// www.drugs.com/health-guide/myasthenia-gravis.html https :// en.wikipedia.org/wiki/Myasthenia_gravis Myasthenia Gravis A Manual for the Health Care Provider , Jemes F. Haward , M. D

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