Clinical Pearls & Morning Reports
Ptosis, double vision, and axial and proximal limb weakness strongly suggest a neuromuscular junction disorder such as myasthenia gravis or the Lambert–Eaton myasthenic syndrome. Read the latest Clinical Problem-Solving article here.
Q: Acetylcholine receptor antibodies are found in what percentage of patients with myasthenia gravis?
A: Acetylcholine receptor antibodies are found in 80% of patients with myasthenia gravis; muscle-specific tyrosine kinase antibodies are found in only 1 to 10%.
Q: What is the function of muscle-specific tyrosine kinase?
A: Muscle-specific tyrosine kinase is a receptor tyrosine kinase at the postsynaptic membrane that plays an important role in the formation and maintenance of the neuromuscular junction by inducing acetylcholine receptor clustering and differentiation of nerve terminals. Disruption of this pathway by autoantibodies binding to muscle-specific tyrosine kinase leads to a neuromuscular transmission defect.
A: Both myasthenia gravis associated with acetylcholine receptor antibodies and myasthenia gravis associated with muscle-specific tyrosine kinase antibodies are characterized by fatigable weakness, but they have several distinguishing features. Large case series indicate that patients with muscle-specific tyrosine kinase antibodies are more often female and have earlier disease onset (in the third or fourth decade of life) than patients with acetylcholine receptor antibodies. Ptosis and double vision are the most common manifestations with acetylcholine receptor antibodies, but are less common — and typically milder — with muscle-specific tyrosine kinase antibodies. Muscle-specific tyrosine kinase antibodies are more commonly associated with bulbar dysfunction (in 67% of patients), axial weakness (in 92%), facial weakness (in 96%), and respiratory distress (in 60%), conditions that often lead to crisis and hospitalization.
A: Pyridostigmine, an acetylcholine esterase inhibitor, may improve strength but should be used with caution during a myasthenic crisis, because its cholinergic effects cause increased salivation, which poses a risk of aspiration. Pyridostigmine is reportedly less effective in patients with muscle-specific tyrosine kinase antibodies than in patients with acetylcholine receptor antibodies. Prednisone is a first-line immunosuppressive treatment for myasthenia gravis, with efficacy supported by large case series and small controlled trials, but it has short-term and long-term adverse effects. A recent multicenter, blinded, prospective review showed higher remission rates, better functional outcomes, and lower use of glucocorticoids and glucocorticoid-sparing agents in patients with muscle-specific tyrosine kinase antibodies who were treated with rituximab than in patients not treated with rituximab.