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
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.
Weber
M-A
MA
Department of Radiology, German Cancer Research Center, Heidelberg, Germany.
Nielles-Vallespin
S
S
Essig
M
M
Jurkat-Rott
K
K
Kauczor
H-U
HU
Lehmann-Horn
F
F
D000328:Adult; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D018908:Muscle Weakness / Q000175:diagnosis / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000175:diagnosis* / Q000378:metabolism*; D020967:Myotonic Disorders / Q000175:diagnosis / Q000378:metabolism; D020513:Paralysis, Hyperkalemic Periodic / Q000175:diagnosis / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D012975:Sodium Isotopes / Q000493:pharmacokinetics*
D015222:Sodium Channels; D012975:Sodium Isotopes