Autosomal dominant disorder due to mutation in alpha subunit of the muscle sodium channel on 17q23.1. Allelic to HyperKPP and myotonia fluctuans.
SCN4A
Myotonia that worsens on exercise, especially demonstrable in the eyelids.
A clinical test is to have the patient forcibly close his or her eyes in a repetitive manner. After each repetition, the difficulty with relaxation may be accentuated until eventually the patient cannot open the eyes at all.
Exposure to cold not only worsens the myotonia but may provoke muscle weakness.
Patients may notice weakness when swallowing ice cream or going out into winter weather to shovel snow.
Eyelid myotonia is demonstrable by having the patient sustain an upward gaze for a few seconds and then look down. The eyelids remain up, baring the sclera above the iris. A useful test for paramyotonia is to soak a small towel in ice water and lay it over the patient’s eyes for 2 minutes. When muscle is sufficiently chilled, the paramyotonia disappears, and the muscle is flaccid and paralyzed.
The weakness may far outlast the exposure to cold, and it is common for the muscle not to regain its full use for hours after returning to room temperature.
The diagnosis of potassium-sensitive conditions relies on demonstration of the genetic defects. However, the diagnosis should be suspected when high serum potassium levels coincide with bouts of weakness.
Neurophysiology: Routine sensory and motor NCS are normal. EMG: myotonic discharges on percussion or movement of the muscles. CMAP amplitude show decremental response on repeated short exercise test, which is worse when performed with the extremity cooled. PEMPs are seen following SET in patients with PMC after a single supramaximal stimulus.
SET shows Fournier type 1 pattern: Little or no decrement in CMAP amplitude or area immediately following exercise. With the subsequent 6 stimuli the amplitude declines providing a curve with a negative slope. The magnitude of this response becomes more dramatic in the 2nd or 3rd trials. There is most dramatic response with cooling, however. SET with limb cooling, or rewarming following cooling demonstrates a CMAP amplitude or area decrement of >20% in response to cooling with or without rewarming is thought to be pathognomonic of PMC. PEMPs seen in response to single or repetitive stimuli following brief exercise – found in all PMC patients. PEMPs dissipate within an individual trials and between subsequent SETs.
LET in PMC: Significant and persistent CMAP amplitude and area decrement occurs averaging a 66% reduction in comparison to baseline.
Myotonic discharges in EMG.
PMC phenotype (Q270 K) SET has a unique signature. SET test without cooling demonstrates type 2 pattern identical to MC (ie) an initial CMAP amplitude and/or area decrement immediately post-exercise that improves within the 1st trial and then between subsequent trials. SET with cooling reverts to type I pattern typically seen in PMC, that is CMAP amplitude/area decrements with a downward slope within the 1st trial and declines further with each subsequent two trials.
ECG may show the changes of hyperkalemia, and the serum CK concentration may be elevated during or after an attack.
Treatment. Mexiletine 200 mg PO tid. Check QTc first before starting medication.