Myasthenia gravis: immunotherapy, crisis and anticholinesterase overdose
THE CONTEXT
This passage covers treatment of advanced myasthenia gravis and contrasts respiratory crisis with weakness caused by excessive anticholinesterase treatment.
Corticosteroids
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Corticosteroids improve myasthenia gravis through immunosuppression. They inhibit production of antibodies against nicotinic receptors and may increase synthesis of new receptors.
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They are generally reserved for inadequate response to anticholinesterases when thymectomy has failed or is unsuitable.
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The passage describes prednisolone 30–60 mg/day as inducing remission in about 80% of advanced cases. After tapering, 10 mg daily or on alternate days can be used for maintenance.
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Long-term corticosteroid treatment has its own problems, which are not detailed in this passage.
Other immunosuppressants and plasma exchange
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Azathioprine and cyclosporine benefit advanced cases by affecting T cells and inhibiting receptor-antibody synthesis.
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Azathioprine is generally used first. Its onset is slow and remission may take months, but it is useful for maintaining remission.
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Plasmapheresis, or plasma exchange, removes antibodies and may produce dramatic but often short-lived improvement in myasthenic crisis.
Myasthenic crisis
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Myasthenic crisis is characterized by acute respiratory muscle weakness and is managed with tracheal intubation and mechanical ventilation.
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Intravenous methylprednisolone pulse therapy is generally given while anticholinesterases are withheld for 2–3 days and then gradually reintroduced.
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Most patients can be weaned from ventilation within 1–3 weeks; plasmapheresis hastens recovery.
Cholinergic weakness from overtreatment
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Failure to adjust anticholinesterase doses to fluctuating requirements may result in relative overdose.
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Overdose causes persistent muscle-endplate depolarization and cholinergic weakness.
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Late cases requiring high doses may alternate between myasthenic and cholinergic weakness, either of which may reach crisis proportions.
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The two forms require opposite treatments. The passage identifies the edrophonium test as a means of differentiation and associates improvement with myasthenic crisis.