Neuromuscular junction: Repetitive nerve stimulation in myasthenia gravis

Repetitive nerve stimulation (RNS) electromyography is a test commonly used to diagnose myasthenia gravis (MG), a disease caused by autoantibodies that target and competitively inhibit the acetylcholine receptor (AChR) on the motor end plate of the neuromuscular junction. The test measures the amplitude of action potentials while a muscle is repetitively stimulated at a frequency of 2 to 5 Hz. A reproducible decrease in the amplitude of the signal by ≥ 10% by the fourth or fifth stimuli is considered diagnostic for MG. RNS results for normal and MG individuals are shown in Figure 1.

Figure 1 RNS tracings from a normal subject (A), an individual with MG (B and C), the individual with MG immediately following 30 seconds of exercise (D), and the individual with MG 4 minutes after 30 seconds of exercise (E)

Single-fiber electromyography (SFEMG) is a more sensitive diagnostic test for MG. SFEMG is performed with a specialized needle electrode that allows simultaneous recording of the action potentials of two muscle fibers innervated by the same motor axon. The variability in the interpotential interval (IPI) – the time between the action potentials of the two muscle fibers – is called "jitter". Increased jitter occurs when neuromuscular transmission is impaired because the physiological excess in the amount of neurotransmitter required to produce an action potential is increased, leading to variable timing of nerve impulse transmission between the first and second muscle. SFEMG results for an MG patient are shown in Figure 2.

Figure 2 Single-fiber electromyography (SFEMG) set-up that is monitoring the action potentials of the muscle fibers innervated by the same motor neuron (Figure 2A); SFEMG results show the end-plate potential (EPP2) of the second muscle fiber (Figure 2B, left pane) and the corresponding interpotential interval (IPI) between the first and second muscle fiber (Figure 2B, right pane)