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

Abstract

BACKGROUND:

Muscle channelopathies such as paramyotonia, hyperkalemic periodic paralysis, and potassium-aggravated myotonia are caused by gain-of-function Na+ channel mutations.

METHODS:

Methods: Implementation of a three-dimensional radial 23Na magnetic resonance (MR) sequence with ultra-short echo times allowed the authors to quantify changes in the total muscular 23Na signal intensity. By this technique and T2-weighted 1H 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 23Na signal intensity and edema-like changes on T2-weighted 1H 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 23Na, but no increase in the T2-weighted 1H 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 23Na MR signal intensity and the membrane depolarization (r = 0.92).

CONCLUSIONS:

The increase in the total 23Na 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 23Na MR technique.

• Authors: M-A Weber, S Nielles-Vallespin, M Essig, K Jurkat-Rott, H-U Kauczor, F Lehmann-Horn
• Journal: Neurology (Neurology) Vol. 67 Issue 7 Pg. 1151-8 (Oct 10 2006) ISSN: 1526-632X [Electronic] United States
• PMID: 16931510 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sodium Channels
• Sodium Isotopes

Topics

• Adult
• Female
• Humans
• Magnetic Resonance Imaging (methods)
• Male
• Metabolic Clearance Rate
• Middle Aged
• Muscle Weakness (diagnosis, metabolism)
• Muscle, Skeletal (metabolism, pathology)
• Muscular Diseases (diagnosis, metabolism)
• Myotonic Disorders (diagnosis, metabolism)
• Paralysis, Hyperkalemic Periodic (diagnosis, metabolism)
• Sodium Channels (genetics, metabolism)
• Sodium Isotopes (pharmacokinetics)