Although the diagnosis of autoimmune myasthenia gravis usually can be made from the history, signs, and symptoms, its differentiation from certain neurasthenic, infectious, endocrine, congenital, neoplastic, and degenerative neuromuscular diseases can be challenging. Myasthenia gravis is the only condition in which the muscular weakness can be improved dramatically by anti-ChE medication. The edrophonium test for evaluation of possible myasthenia gravis is performed by rapid intravenous injection of 2 mg of edrophonium chloride, followed 45 seconds later by an additional 8 mg if the first dose is without effect; a positive response consists of brief improvement in strength, unaccompanied by lingual fasciculation (which generally occurs in nonmyasthenic patients). An excessive dose of an anti-ChE drug results in a cholinergic crisis, characterized by skeletal muscle weakness (due to depolarization blockade of nicotinic receptors at the neuromuscular junction) and other features (see above) from excess ACh at muscarinic receptors. The distinction between the weakness of cholinergic crisis/anti-AChE overdose and myasthenic weakness is of practical importance: the former is treated by withholding, and the latter by administering, the anti-ChE agent. When the edrophonium test is performed cautiously (limiting the dose to 2 mg and with facilities for respiratory resuscitation available) a further decrease in strength indicates cholinergic crisis, while improvement signifies myasthenic weakness. Atropine sulfate, 0.4-0.6 mg or more intravenously, should be given immediately if a severe muscarinic reaction ensues. Detection of antireceptor antibodies in muscle biopsies or plasma is now widely employed to establish the diagnosis.

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