Clinical neurophysiology of neuromuscular junction disease

The neuromuscular junction (NMJ) is a cholinergic synapse where quantal release of acetylcholine (ACh) from motor nerve terminals generates a local endplate potential (EPP) on the muscle fiber. EPPs that reach threshold depolarize the entire muscle fiber and initiate the process of excitation-contraction coupling. Deficits of neuromuscular transmission result in clinical weakness that is fatigable and may fluctuate. Repetitive nerve stimulation (RNS) testing can unmask the reduced safety factor common to all NMJ disorders via depletion of immediate ACh stores at the presynaptic motor nerve terminal with decremental responses to low-frequency RNS (LF-RNS). The facilitated responses characterizing presynaptic NMJ disorders can be revealed by brief exercise or high stimulation rates that augment presynaptic calcium levels. Activation with isometric exercise may increase the sensitivity of RNS testing. Attention to technical detail and reproducibility of findings are essential in generating valid results in RNS testing. Motor unit potential (MUP) instability or jiggle is the main finding seen in NMJ disorders on conventional needle EMG and reflects the moment-to-moment variability in the number and synchrony of muscle fiber action potentials (MFAPs) that compose a MUP. Single fiber EMG (SFEMG) is a highly selective technique that assesses jitter, the temporal variability in MFAPs generated in response to motor nerve action potentials.