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Muscle Na⁺ channelopathies

MRI detects intracellular ²³Na accumulation during episodic weakness

From the Departments of Radiology (M.-A.W., M.E., H.-U.K.) and Medical Physics in Radiology (S.N.-V.), German Cancer Research Center, Heidelberg; and Department of Applied Physiology (K.J.-R., F.L.-H.), University of Ulm, Germany.

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 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.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the October 10 issue to find the title link for this article.

This article was previously published in electronic format as an Expedited E-Pub on August 23, 2006, at www.neurology.org.

Supported by the Medical School Research Council of the University of Heidelberg (196/2002), the German Research Foundation (DFG, JU470/1), and the European Community's Human Potential Program under contract HPRN-CT-2002-00331, EC coupling in striated muscle.

Disclosure: The authors report no conflicts of interest.

Received February 16, 2006. Accepted in final form June 1, 2006.

Address correspondence on in vitro data to Dr. Frank Lehmann-Horn, Department of Applied Physiology, Ulm University, Albert-Einstein-Allee 11, D-89069 Ulm, Germany; e-mail: frank.lehmann-horn{at}uni-ulm.de. Address correspondence on in vivo data to Dr. Marc-André Weber, Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; e-mail: m.a.weber{at}dkfz.de

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