Electromyography guides toward subgroups of mutations in muscle channelopathies

Abstract

Myotonic syndromes and periodic paralyses are rare disorders of skeletal muscle characterized mainly by muscle stiffness or episodic attacks of weakness. Familial forms are caused by mutations in genes coding for skeletal muscle voltage-gated ion channels. Exercise is known to trigger, aggravate, or relieve the symptoms. Therefore, exercise can be used as a functional test in electromyography to improve the diagnosis of these muscle disorders. Abnormal changes in the compound muscle action potential can be disclosed using different exercise tests. We report the outcome of an inclusive electromyographic survey of a large population of patients with identified ion channel gene defects. Standardized protocols comprising short and long exercise tests were applied on 41 unaffected control subjects and on 51 case patients with chloride, sodium, or calcium channel mutations known to cause myotonia or periodic paralysis. These tests disclosed significant changes of compound muscle action potential, which generally matched the clinical symptoms. Combining the responses to the different tests defined five electromyographic patterns (I-V) that correlated with subgroups of mutations and may be used in clinical practice as guides for molecular diagnosis. We hypothesize that mutations are segregated into the different electromyographic patterns according to the underlying pathophysiological mechanisms.

Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations

“…*McNemar xnot expressed in the muscle). A standardized protocol ensuring reproducible and painless electrophysiological testing of skeletal muscle excitability was used (28). Briefly, compound muscle action potentials were recorded from the right and left abductor digiti minimi muscles after supramaximal electrical stimulation of the ulnar nerves at the wrists.…”

Renal, Ocular, and Neuromuscular Involvements in Patients with CLDN19 Mutations

“…Abnormal CMAP amplitude is observed in approximately 70% to 80% of patients with periodic paralysis (19,20). The electrophysiological pattern observed in our patients (pattern V; CMAP declines after long exercise without preliminary increment) is more frequently associated with mutations in Ca 2ϩ or K ϩ channel CACNA1A, KCNJ2, and SCN4A genes (13,21,22). Whether isolated neuromuscular defects may be induced by some CLDN19 mutations thus accounting for channelopathies of unknown origin remains to be tested.…”

“…A needle electromyography showed neither nerve conduction defect nor myotonic or paramyotonic abnormalities. Muscle-channel dysfunction was thus explored by recording surface compound motor action potential (CMAP) changes after exercise tests (repeating short exercises at room temperature and, after cooling, an extended period of exercise, as described by Fournier et al [13]). CMAP amplitude correlates with the number of functional muscle fibers.…”

Management and Treatment of Andersen-Tawil Syndrome (ATS)

“…Such challenges should not be used for diagnostic purposes in ATS because of the risk of precipitating or worsening cardiac arrhythmias. Electrophysiologic studies are helpful in confirming the presence of skeletal muscle membrane inexcitability using the exercise nerve conduction study protocol first described by McManis et al 14 Fournier et al 15 have further refined this protocol to distinguish patients with known sodium, chloride, and calcium channel mutations according to their response to the short-exercise EMG response pattern. A positive long exercise nerve conduction study has been reported in ATS patients, 16 but no ATS patients have been studied with the more elaborate Fournier protocol to see if they have a unique pattern.…”