As in hyperkalemic paralysis, the muscular weakness in this disease is associated with a decrease in the amplitude, and eventual loss, of muscle action potentials and there is failure of excitation by supramaximal stimulation of peripheral nerve or by strong voluntary effort. A decline in strength precedes the loss of motor unit potentials and the failure of propagation of action potentials over the surface of the fiber. The polarization potentials of muscle fibers measured by intracellular recordings are initially normal despite the failure of impulse propagation by the sarcolemma. One would expect the muscle fiber to be hyperpolarized as K moves into it, but it actually becomes depolarized. Rüdel and associates attribute the latter change to an increased Na conductance. The ECG changes also begin at levels of K that are slightly below normal (about 3 mEq/L); they consist of prolonged PR, QRS, and QT intervals and flattening of T waves.
Diagnosis at a time when the patient is normal may be facilitated by provocative tests. With the patient carefully monitored, including the use of ECG, the oral administration of 50 to 100 g of glucose or loading with 2 g of NaCl every hour for 7 doses, followed by vigorous exercise, brings on an attack, which then can be terminated by 2 to 4 g of oral KCl (the opposite of what pertains in hyperkalemic periodic paralysis).
Pathologic changes The muscle fibers are uniformly somewhat large but the most striking change, particularly in the late degenerative phases of the disease, is vacuolization of the sarcoplasm. The myofibrils are separated by round or oval vacuoles containing clear fluid, presumably water, and a few periodic acid-Schiff (PAS)-positive granules. There are pathologic changes in myofibrils and mitochondria as well, and focal increases in muscle glycogen. Isolated muscle fibers may undergo segmental degeneration. Electron microscopic studies have shown that the vacuoles arise as a result of proliferation and degeneration of membranous organelles within the sarcoplasmic reticulum and transverse tubules (A.G. Engel).
Treatment A low-sodium diet (less than 160 mEq/d), avoidance of large meals and of exposure to cold, and acetazolamide 250 mg tid may be helpful in preventing attacks. That acetazolamide reduces attacks is somewhat surprising as it is kaluretic, but it may work through the production of acidosis; a few patients have worsened with the drug. Patients who are unresponsive to acetazolamide may be treated with the more potent carbonic anhydrase inhibitor, dichlorphenamide, 50 to 150 mg/d, or with the potassium-sparing diuretics spironolactone or triamterene (both in doses of 25 to 100 mg/d), but caution must then be exercised with the simultaneous administration of oral potassium supplements. The daily administration of 5 to 10 g of KCl orally in an unsweetened aqueous solution prevents attacks in many patients and apparently, this program can be maintained indefinitely. If this approach fails, a low-carbohydrate, low-salt, high-K diet combined with a slow-release K preparation may be effective.