Electromyography guides toward subgroups of mutations in muscle channelopathies

TLDR

Myotonic syndromes and periodic paralyses are rare skeletal muscle disorders marked by stiffness or episodic weakness, caused by mutations in voltage‑gated ion channel genes, and their symptoms can be triggered, worsened, or relieved by exercise. The study aims to use exercise‑based electromyography to improve diagnosis of these channelopathies, surveying many patients with known ion‑channel mutations and hypothesizing that mutation subgroups correspond to distinct electromyographic patterns. The authors applied standardized short and long exercise protocols to record compound muscle action potentials in 41 controls and 51 patients with chloride, sodium, or calcium channel mutations. The tests revealed significant compound muscle action potential changes that matched clinical symptoms and identified five patterns that correlate with mutation subgroups, offering diagnostic guidance. Ann Neurol 2004.

Abstract

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. Ann Neurol 2004