Which of the following is correct regarding the diagnosis of autoimmune myasthenia gravis?
ExplanationB. Edrophonium is an intravenous acetylcholinesterase inhibitor that increases the presence of acetylcholine at the neuromuscular junction (NMJ). In patients with myasthenia, administration of edrophonium leads to transient improvement of weakness within minutes of administration; the edrophonium (Tensilon) test has therefore been used in the diagnosis of myasthenia gravis. Laboratory testing for serum autoantibodies also aids in the diagnosis; positive tests confirm the diagnosis of autoimmune myasthenia gravis in the appropriate clinical setting, but their absence does not exclude it. Acetylcholine receptor binding antibodies can be detected by measuring binding to purified acetylcholine receptors radiolabeled with α-bungarotoxin. The sensitivity of this test is highest for generalized myasthenia, detecting antibodies in 70% to 95% of patients and lower for patients with ocular myasthenia. Patients who are initially seronegative for binding, blocking, or modulating antibodies may seroconvert later in the course of their disease. In a minority of patients with autoimmune myasthenia in whom the binding antibody is not detectable, modulating or blocking antibodies may be present. False-positive testing for these antibodies is rare, but can occur in patients with other autoimmune disorders. Anti striational muscle antibodies can be positive in myasthenia patients with thymoma, but they are much less sensitive and specific than acetylcholine receptor antibodies for the diagnosis of myasthenia gravis. The patient’s clinical picture, rather than antibody levels, is used to monitor response to therapy. In approximately half of all patients who are seronegative for antibodies against the acetylcholine receptor, anti–muscle-specific tyrosine kinase antibodies are present (discussed in question 27). EMG findings in myasthenia gravis include electrodecremental response and jitter. The presence of a 10% or greater decrement in amplitude of a CMAP between the first and fourth to fifth stimuli with repetitive nerve stimulation suggests an NMJ disorder (see Chapter 9). If there is not an abnormality present on repetitive nerve stimulation but there is a high clinical suspicion for myasthenia gravis and it cannot be confirmed with serologic testing, a single-fiber EMG can be performed. Single-fiber EMG is the most sensitive test of NMJ transmission. Jitter is the variability in the measure of interpotential difference between two muscle fiber action potentials during consecutive discharges of the same motor unit. Increased jitter (or increased interpotential time) is present in patients with NMJ abnormalities, but is not specific for myasthenia gravis. Blocking on single-fiber EMG is failure of a single muscle fiber action potential to appear during the motor unit discharge, and occurs when there is significantly increased jitter.
