Myasthenia gravis: pathogenesis, symptoms and initial treatment
THE CONTEXT
Myasthenia gravis is an autoimmune disorder affecting muscle-endplate nicotinic receptors. Anticholinesterases improve muscle strength without correcting the underlying disorder.
Pathogenesis and clinical pattern
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Antibodies target nicotinic receptors at the muscle endplate, reducing available receptors and causing structural damage to the neuromuscular junction.
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Weakness and easy fatigability develop with repeated activity and recover after rest.
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Eyelid, external ocular, facial and pharyngeal muscles are generally involved first; limb and respiratory muscles become affected later.
Anticholinesterase treatment
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Neostigmine and its congeners are described as first-line drugs for restoring muscle strength.
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They allow acetylcholine released from prejunctional endings to accumulate and act over a larger receptor area, and they also directly depolarize the endplate.
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By inhibiting acetylcholinesterase, they allow the same acetylcholine molecules to interact repeatedly with available nicotinic receptors.
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Treatment is usually started with oral neostigmine 15 mg every 6 hours, with dose and frequency adjusted for optimal relief of weakness.
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Requirements fluctuate, with unpredictable remissions and exacerbations. Pyridostigmine is an alternative requiring less frequent dosing.
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Atropine can be added for intolerable muscarinic adverse effects.
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Anticholinesterases do not affect the basic disorder, which may progress until these drugs alone cannot restore adequate strength.
Thymectomy
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Thymectomy is generally advised for patients with generalised weakness, particularly younger patients and those with a thymoma.
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It is effective in the majority of cases and produces gradual improvement; complete remission has also been obtained.