A 66-year-old man comes to the office with diplopia that progressively worsens toward the end of the day. The patient has no shortness of breath, trouble swallowing, or generalized weakness. He is currently receiving low-dose pyridostigmine for treatment of his condition and claims good compliance without significant side effects. Physical examination reveals fatigable asymmetric ptosis and binocular horizontal diplopia. Infusion of edrophonium elicits a significant improvement in his symptoms. Which of the following is the best next step in management of this patient?

Question

A 66-year-old man comes to the office with diplopia that progressively worsens toward the end of the day.  The patient has no shortness of breath, trouble swallowing, or generalized weakness.  He is currently receiving low-dose pyridostigmine for treatment of his condition and claims good compliance without significant side effects.  Physical examination reveals fatigable asymmetric ptosis and binocular horizontal diplopia.  Infusion of edrophonium elicits a significant improvement in his symptoms.  Which of the following is the best next step in management of this patient?

Quizplus · Accepted Answer

Myasthenia gravis is an autoimmune disease caused by autoantibodies directed against nicotinic acetylcholine receptors on the postsynaptic membrane of the neuromuscular junction. Action potential propagation is impaired in these patients as antibody binding leads to receptor degradation and complement-mediated damage of the postsynaptic membrane. Patients typically present with fluctuating weakness that worsens over the course of the day and most often involves the extraocular (eg, ptosis, diplopia) and bulbar (eg, fatigable chewing, dysphagia) muscles. Acetylcholinesterase (AChE) is an enzyme that degrades acetylcholine in the synaptic cleft. Long-acting AChE inhibitors (eg, pyridostigmine) are used in the symptomatic treatment of myasthenia gravis as they increase acetylcholine concentration in the neuromuscular junction, prolonging its effect on the postsynaptic membrane. Exacerbations of myasthenia gravis in patients being treated with AChE inhibitors may occur for 2 reasons. First, if the patient is undertreated (receives suboptimal doses of medication), not enough acetylcholine is available in the neuromuscular junction (myasthenic crisis). Infusion of the short-acting AChE inhibitor edrophonium (Tensilon test) increases neuromuscular transmission and can provide temporary improvement in symptoms (Choice C). The pyridostigmine dose should be increased in the long-term management of these patients. The second (rare) cause of exacerbation is cholinergic crisis. In this condition, a patient receives inappropriately high doses of AChE inhibitor and has excessive acetylcholine in the synaptic cleft. This causes excessive stimulation of the skeletal muscles and results in muscle that is refractory to future impulses. Cholinergic crisis also presents with muscle weakness; however, because the neuromuscular junction becomes insensitive to acetylcholine, edrophonium infusion produces no improvement in symptoms. AChE inhibitors should be temporarily discontinued in patients with cholinergic crisis (Choice E). (Choice A) Atropine is a muscarinic acetylcholine receptor antagonist that may be used in organophosphate poisoning and as a mydriatic agent (dilates pupils). However, it does not affect nicotinic receptors and is not used to treat myasthenic crisis. (Choice B) Pralidoxime is also used in organophosphate poisoning. Pralidoxime reverses the effects of both muscarinic and nicotinic overstimulation by "regenerating" AChE in the neuromuscular junction. Educational objective: Exacerbation of myasthenia gravis in a patient treated with long-acting acetylcholinesterase inhibitors (eg, pyridostigmine) occurs due to myasthenic or cholinergic crisis. The edrophonium (Tensilon) test helps to differentiate these 2 conditions. Clinical improvement after edrophonium administration indicates that the patient is undertreated (myasthenic crisis). __________ References: Myasthenia gravis: a review. (http://www.ncbi.nlm.nih.gov/pubmed/23193443)

A 66-Year-Old Man Comes to the Office with Diplopia That