Severity of Myasthenia Gravis Influences the Relationship between Train-of-four Ratio and Twitch Tension and Run-down of Rat Endplate Potentials

Abstract

Background Train-of-four ratio (TOFR) is often used to evaluate muscle relaxation caused by neuromuscular-blocking agents (NMBAs). However, it is unknown whether TOFR reliably correlates with the first twitch tension (T1) in patients with myasthenia gravis (MG). By using rat models of experimental autoimmune MG (EAMG), the authors verified the hypothesis that the severity of MG influences the relationship between TOFR and T1. Methods EAMG rats were divided into sham, moderate MG, and severe MG groups. Isometric twitch tension of the hemidiaphragm was elicited by phrenic nerve stimulation with and without use of the NMBA rocuronium to measure TOFR and T1, and run-down of endplate potentials was estimated in the three groups. Changes around the neuromuscular junction in EAMG rats were investigated by observation of electron micrographs. Results With similar attenuation of T1, TOFR was significantly (n = 6) different among the three groups in the presence of 50% inhibitory concentrations of rocuronium (IC50). Run-down in the sham group was significantly (n = 8) greater with exposure to IC50, whereas that in the severe MG group was statistically insignificant. Width of the primary synaptic cleft in the severe MG group was significantly (n = 80) greater than that in the other groups. Conclusions Severity of MG influences the relationship between TOFR and T1, together with changes in run-down of endplate potentials and those around the neuromuscular junction in rats. TOFR may, therefore, not be an accurate indicator of recovery from NMBAs in MG patients.

Successful Neuromuscular Blockade Reversal Using Sugammadex and Neostigmine Failed to Prevent Myasthenic Crisis After Emergency Surgery: A Case Report

“…It was found that while T1 of the TOF decreased to the same extent in severe and moderate groups, the TOF ratio in the severe group did not decrease to the same extent that the moderate group value did. The researchers concluded that the discrepancy in TOF ratio changes can cause an overestimation of recovery from NMB [ 15 ]. In our patient, despite unchanged TOF ratios, an obvious clinical improvement was noted following 4 mg of neostigmine and the second dose of sugammadex.…”

“…In both cases, rapid reversal was observed with adequate TOF restoration. Both patients were observed for a period of 30-40 minutes to ensure that no residual curarization was present before extubation was performed [ 15 ]. Literature supports the use of sugammadex in MG patients receiving non-depolarizing steroidal NMBAs for surgery to prevent postoperative MC.…”

Post-synaptic specialization of the neuromuscular junction: junctional folds formation, function, and disorders

“…In the early onset stage of this MG, autoimmune antibodies in situ masking the membrane receptors induced the AChRs internalization and depression at the crest [ 122 ]. In the moderate and severe group, followed by systematic destruction, the receptor-containing crests of the JFs were destructed, and the JFs were degenerated, which resulted in the post-synaptic membrane was simplification [ 123 ]. In LG2 agrin mutation-induced MG, biopsy results from the right deltoid muscle showed that the JFs were simplified, and the diameter of the primary and secondary synaptic clefts was increased [ 124 ].…”