A Brief Synopsis of Myasthenia Gravis

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Myasthenia gravis is a disease where the immune systems attacks and destroys acetylcholine receptors at the neuromuscular junction, resulting in muscular weakness.

Etiology & Incidence

Myasthenia gravis is an autoimmune disease where acetylcholine receptors at the neuromuscular junction are destroyed. The cause is unknown. Although the disease onset is most often between the ages of 20 and 40 years, it can occur at any age. Women appear to have the disorder more often than men. About 12% of the infants born to women with myasthenia gravis have a syndrome called neonatal myasthenia caused by antibodies passively crossing the placenta; this condition usually resolves itself in several days to weeks as the antibody levels decline.

Symptoms

Ptosis, diplopia and muscle fatigue after exercise are the three most common symptoms. Patients with advanced myasthenia gravis can display pronounced muscular weakness and difficulty sustaining movement. The disease can exist as a generalized disease or can be restricted to just the extraocular muscles as ocular myasthenia gravis. Note that the generalized form usually affects the ocular muscles as well, thus producing diplopia as one of the common symptoms of the disease.

Diagnosis

The ability of a short-acting (< 5 minutes) cholinesterase inhibitor (edrophonium) to reverse the presenting symptoms confirms the diagnosis of myasthenia gravis -- patients should show an immediate, short-lived improvement. Other tests reveal acetylcholine-receptor antibodies in 90% of the patients with the generalized form of the disease and in 50% of the patients with the ocular form, despite the fact that the antibody levels do not correlate with the severity of the disease..

**Diagnostic Procedure**
Recall that over stimulation of the neuromuscular junction (e.g., nerve gases such as sarin, organophosphate insecticides) can produce the same symptoms, so it's critically important to exercise care in performing the diagnostic procedure using the administration of a cholinesterase inhibitor -- the addition of the cholinesterase inhibitor would exacerbate the condition of a nerve gas victim. The procedure described below is from the Merck Manual online edition. A syringe is loaded with 10 mg; 2 mg is given IV, and if no reaction occurs within 30 sec, the rest is injected. If the patient has myasthenia gravis, muscle function improves suddenly and briefly. The test can also differentiate between myasthenic and cholinergic crisis: Patients with myasthenic crisis improve, but those with cholinergic crisis worsen. Because dangerous cardiorespiratory depression can occur, facilities to maintain respiration and atropine (as an antidote) must be available during the test.

Prognosis

Left untreated, the disorder may be stable or progressive. With appropriate treatment, myasthenia gravis can usually be effectively managed with little impact on life expectancy. However, about 10% of the patients have life-threatening respiratory muscle involvement.

Treatment

Cholinesterase inhibitors are used to manage the symptoms of the disease. Corticosteroids and immunosuppressive drugs may be useful to disrupt the autoimmune response. Thymectomy is helpful in patients with the generalized form of the disease, with 80% going into remission or using lower cholinesterase-inhibitor doses.

**Treatment Complication**
Selecting the correct dosage of cholinesterase inhibitor can be difficult, requiring the expertise of a physician experienced at treating this disorder. Excessive dosage of neostigmine or pyridostigmine causes weakness that cannot be differentiated clinically from myasthenia. The disease may become refractory to the drug. Thus, if a patient who has been doing well deteriorates, the cause must be determined with the IV edrophonium test. If the patient improves, the maintenance dosage is inadequate. If the patient worsens, dosage is excessive or the disease is refractory. (From the Merck Manual online edition)

Notable Cases

Aristotle Onassis

Online Resources

THE MERCK MANUAL, Sec. 14, Ch. 183, Disorders Of The Peripheral Nervous System

Revised 09 November 2001 21:27 EST

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