Monograph: Use of Therapeutic Plasma Exchange in Autoimmune Neuromuscular Disorders-Article

Article

Pdf Summary

This 2026 AANEM monograph by Jonathan M. Morena in Muscle & Nerve reviews the electrodiagnostic evaluation of neuromuscular junction (NMJ) disorders—myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and botulism—that impair synaptic transmission causing weakness. It emphasizes the importance of repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG) in diagnosis, differentiating presynaptic (LEMS, botulism) from postsynaptic (MG) defects.<br /><br />Normal NMJ transmission involves acetylcholine (ACh) release from presynaptic nerve terminals binding to nicotinic ACh receptors on the postsynaptic muscle endplate, generating an endplate potential (EPP) with a large “safety factor” ensuring reliable muscle fiber action potentials. In disease states, reduced safety factor due to fewer ACh quanta (presynaptic) or impaired receptor function (postsynaptic) causes transmission failure visible as decrement in compound muscle action potential (CMAP) amplitude during low-frequency RNS.<br /><br />RNS testing stimulates a motor nerve repetitively, recording CMAP amplitude changes; postsynaptic disorders show characteristic decremental responses at low frequency, partially reversible by brief exercise (postactivation exhaustion), whereas presynaptic disorders have low baseline CMAPs with marked postactivation facilitation. Proper technique—supra-maximal stimulation, muscle warming, and electrode stability—is critical to avoid artifacts.<br /><br />SFEMG, the most sensitive test, measures “jitter,” the temporal variability in neuromuscular transmission between muscle fibers innervated by the same motor neuron. Increased jitter and blocking indicate defective transmission. Fiber density differentiates primary NMJ disorders (normal density) from reinnervation states in neuropathies. SFEMG can be performed via single-fiber or concentric needle electrodes, with disposables now providing good accuracy.<br /><br />MG shows increased jitter and decrement, especially in weak muscles, with SFEMG exhibiting higher sensitivity than RNS or antibody testing, particularly in ocular MG. LEMS displays greater jitter increases correlated with severity and improves with treatment. Botulism shares incremental responses similar to LEMS but with distinctive persistence at high-frequency stimulation. Jitter abnormalities can also be seen in neuropathies, motor neuron disease, and mitochondrial myopathies like chronic progressive external ophthalmoplegia.<br /><br />The article concludes that careful electrodiagnostic testing, interpreted alongside clinical context, is essential for accurate NMJ disorder diagnosis, severity assessment, and management guidance. SFEMG also serves as a valuable biomarker for disease monitoring in MG.

Keywords

neuromuscular junction disorders

myasthenia gravis

Lambert-Eaton myasthenic syndrome

botulism

repetitive nerve stimulation

single-fiber electromyography

acetylcholine transmission

compound muscle action potential

jitter measurement

electrodiagnostic evaluation