Muscle Na+ channelopathies -: MRI detects intracellular 23Na accumulation during episodic weakness

Background: Muscle channelopathies such as paramyotonia, hyperkalemic periodic paralysis, and potassium-aggravated myotonia are caused by gain-of-function Na+ channel mutations. Methods: Implementation of a three-dimensional radial Na-23 magnetic resonance (MR) sequence with ultra-short echo times allowed the authors to quantify changes in the total muscular Na-23 signal intensity. By this technique and T2-weighted H-1 MRI, the authors studied whether the affected muscles take up Na+ and water during episodes of myotonic stiffness or of cold- or exercise-induced weakness. Results: A 22% increase in the Na-23 signal intensity and edema-like changes on T2-weighted H-1 MR images were associated with cold-induced weakness in all 10 paramyotonia patients; signal increase and weakness disappeared within 1 day. A 10% increase in Na-23, but no increase in the T2-weighted H-1 signal, occurred during cold- or exercise-induced weakness in seven hyperkalemic periodic paralysis patients, and no MR changes were observed in controls or exercise-induced stiffness in six potassium-aggravated myotonia patients. Measurements on native muscle fibers revealed provocation-induced, intracellular Na+ accumulation and membrane depolarization by -41 mV for paramyotonia, by -30 mV for hyperkalemic periodic paralysis, and by -20 mV for potassium-aggravated myotonia. The combined in vivo and in vitro approach showed a close correlation between the increase in Na-23 MR signal intensity and the membrane depolarization (r = 0.92). Conclusions: The increase in the total Na-23 signal intensity reflects intracellular changes, the cold-induced Na+ shifts are greatest and osmotically relevant in paramyotonia patients, and even osmotically irrelevant Na+ shifts can be detected by the implemented Na-23 MR technique.