As pointed out earlier, a reduction in ionizable calcium and magnesium is associated with involuntary cramp-like spasms; in their mildest form they appear as distal carpopedal spasms, but they may involve any of the muscles except the extraocular ones. Under these circumstances, stimulation of a muscle through its nerve at high frequencies (15 to 20 times per second) reproduces spasms, and hyperventilation and ischemia increase the tendency. Indeed, the Trousseau sign—carpal spasms with occlusion of the blood supply to the arm—takes advantage of the latter phenomenon. Hypocalcemic tetany is attributable to an unstable depolarization of the axonal membrane of the nerve fiber. This mechanism is affirmed by (1) the sensitivity of nerve to percussion (e.g., tapping over the facial nerve near its foramen of exit induces a facial twitch, or Chvostek sign), (2) fast-frequency doublets and triplets of motor unit potentials in the EMG indicating excessive neural excitability, (3) evocation of spasm by application of a tourniquet to proximal parts of a limb (causing ischemia of segments of nerve beneath the tourniquet), and (4) the associated tingling, prickling paresthesias from excitation of sensory nerve fibers. Hypocalcemia also causes a lesser change in the muscle fibers themselves; hence nerve block does not completely eradicate tetany. We comment here that the Chvostek sign is found in some normal individuals, without obvious explanation.
The previously described idiopathic benign cramps resemble tetany but without measurable hypocalcemia (pseudotetany). Just as in tetany, in about half of cases of benign cramp, stimulation of nerve at 15 or more times per second produces repetitive discharges. Biopsies have disclosed no abnormalities of the muscle fibers except for a few ringbinden (circumferential bands of myofibrils encircling a normal core of longitudinally oriented myofibrils). Calcium and diazepam are of no therapeutic value, but some patients respond to phenytoin, quinine (no longer widely used because of the risk of arrhythmia), procainamide, or chlorpromazine.
A familial (autosomal dominant) form of the benign cramp syndrome has been reported; the cramps affected the distal limb muscles, began in childhood and adolescence, and persisted throughout life. Another such family with cramps beginning somewhat later in life and affecting the anterior neck, arm, and abdominal muscles as well as those of the thigh and calf has been described. Also, a familial myalgic-cramp syndrome alluded to early in this chapter has been associated with deletion of part of the dystrophin gene (but with little or no dystrophic weakness). A tendency to cramp and pain has also been noted in a number of the congenital myopathies and in some families with Duchenne and Becker dystrophies.
Satoyoshi described a group of patients who, in addition to widespread and severe cramping of muscle, developed universal alopecia, amenorrhea, intestinal malabsorption with frequent diarrhea, and some developed epiphyseal destruction and retarded growth. Most Japanese patients he described were younger than 20 years, but the 2 cases we have observed in whites were middle-aged. The serum calcium in these patients is normal, and the EMG shows only high-frequency discharges that are characteristic of cramps. A patient of ours with this condition had decades of chronic diarrhea, alopecia, and continuous, extremely painful calf cramps that had the gross appearance of fasciculations. This triad virtually identifies the disease. The cause of the disorder is obscure but is tentatively presumed to be autoimmune. Glucocorticoids, particularly in high doses over short periods, have been tried with some success; dantrolene has also been used and we had the impression that plasma exchange may have been helpful in one case.
Continuous Muscle Fiber Activity Due to Disorders of Nerve and Distal Axons (See Chap. 46)