A 56-year-old man comes to the office due to muscle weakness. The patient once cycled 10-15 miles daily, but for the past several months, he could cycle only a few miles before his legs felt weak. He has also noticed occasional weakness of his arms and neck muscles and has had brief episodes of double vision in which his eyes could not properly focus. He was diagnosed with hypertension and hyperlipidemia 2 years ago and takes lisinopril and atorvastatin. The patient smoked a pack of cigarettes daily for 30 years before quitting 2 years ago. Vital signs are within normal limits. Physical examination shows normal pupils and ocular movements. Strength and deep tendon reflexes of the bilateral upper and lower extremities are normal. Which of the following would be most helpful for improving this patient's current symptoms?
Myasthenia gravis | |
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AChE = acetylcholinesterase; AChR-Ab = acetylcholine receptor antibodies; BBs = beta blockers; MgSO4 = magnesium sulfate. | |
This patient with episodic diplopia and proximal muscle weakness likely has myasthenia gravis (MG). MG is characterized by autoantibodies directed at the postsynaptic neuromuscular junction, resulting in fluctuating, fatigable weakness most prominent in the ocular (eg, ptosis, diplopia), bulbar (eg, dysphagia, dysarthria), facial (eg, myasthenic sneer), and proximal (eg, difficulty holding up the head or lifting the arms) muscles. Weakness typically worsens with activity (eg, cycling) and improves with rest; therefore, examination may be normal if repetitive movements are not performed.
Pyridostigmine, a long-acting oral acetylcholinesterase inhibitor, is usually the initial treatment of choice. It provides rapid symptomatic relief by inhibiting acetylcholine degradation and increasing acetylcholine availability at the neuromuscular junction. Patients who remain symptomatic despite pyridostigmine therapy generally require chronic immunosuppressive therapy (eg, corticosteroids, azathioprine), which may induce remission but generally takes weeks to reach clinical efficacy.
Thymectomy is also associated with long-term clinical improvement but may cause transient worsening of symptoms (eg, myasthenic crisis with respiratory failure), so patients should continue to receive pyridostigmine and immunosuppressants perioperatively.
(Choice A) Graded exercise programs are useful for deconditioning; supervised exercise programs are helpful for claudication. These conditions could affect this patient's ability to exercise but would not explain his diplopia or intermittent arm and neck weakness.
(Choice B) Hydroxychloroquine is used for systemic lupus erythematosus, which typically presents with rash, oral ulcers, renal failure, and/or joint pain; fluctuating muscle weakness is atypical. In patients with MG, hydroxychloroquine is one of the medications associated with worsening weakness and should be avoided.
(Choice C) Interferon beta-1a is used for multiple sclerosis, which causes neurologic symptoms (eg, weakness, incontinence) in discrete, noncontiguous domains. The symptoms typically occur over days to weeks and would not be expected to fluctuate through the day with activity (eg, examination with continued weakness and neurologic deficits).
(Choice E) Riluzole is indicated for amyotrophic lateral sclerosis, which causes chronic, progressive weakness with upper (eg, hyperreflexia, spasticity) and lower (eg, atrophy, fasciculations) motor neuron signs.
(Choice F) Statin myopathy can cause mild weakness; however, the weakness would not fluctuate, and diplopia would be unusual. Muscle pain and tenderness on examination are more typical.
Educational objective:
Myasthenia gravis is characterized by fluctuating, fatigable weakness that is most prominent in the ocular (eg, ptosis, diplopia), bulbar (eg, dysphagia, dysarthria), facial (eg, myasthenic sneer), and proximal (eg, difficulty holding up the head or lifting the arms) muscles. Pyridostigmine, a long-acting oral acetylcholinesterase inhibitor, is the initial drug of choice.