The contracted muscles, unlike muscles in other involuntary spasms, no longer use energy and they are more or less electrically silent (i.e., no electrical activity is recorded from maximally contracted muscle during the cramps). Moreover, the muscle does not produce lactic acid. The shortened state is spoken of as physiologic contracture as discussed in the introductory sections of this chapter. Ischemia contributes to this condition by denying glucose to the muscle, which then cannot function adequately on fatty acids and nonglucose substrates. These features are the basis of the forearm ischemic exercise test, which, although controversial in its use and sensitivity, may be helpful if performed carefully. An indwelling catheter is placed in the antecubital vein and a basal blood sample is obtained. Above the elbow, a sphygmomanometer cuff is inflated to exceed arterial pressure. After 1 min of vigorous hand exercise (30 hand closures against an ergometer), blood samples are obtained at 1 and 3 min. Normal individuals show a 3to 5-fold increase in blood lactate. In patients with either McArdle or Tarui disease, the lactate fails to rise. This procedure has reportedly caused a localized rhabdomyolysis (Meinck et al), for which reason Griggs and associates recommend that the test be carried out without a blood pressure cuff. Problems with consistency in conducting the test and in processing blood samples for lactate limit its validity unless it is performed by experienced individuals and laboratories. Definitive diagnosis depends more on the histochemical stains of biopsied muscle, which reveal an absence of phosphorylase activity (in McArdle disease) or of phosphofructokinase activity (in Tarui disease). Genetic analysis, can be used to corroborate the diagnosis, but it is unnecessary if the histochemical tests are definitive.
Treatment The main treatment is a planned reduction and intermittency in physical activity. Sucrose, taken as 75 g in a beverage, has been shown by Vissing and Haller to cause a short-lived improvement in exercise tolerance, and they propose that exercise-induced rhabdomyolysis can be avoided by a well-timed drink. Fructose and creatine taken orally are also said to be helpful in some cases, but the reported results are not as impressive as they are for sucrose. Improvement has also been described after the administration of glucagon (Kono et al) and with a high-protein diet (Slonim and Goans), but these effects are not consistent.
Other Forms of Glycogenosis (See Table 45-5)
Of the remaining glycogen storage diseases, type III (debranching enzyme deficiency; Cori-Forbes disease, AGL Mutation) affects muscle but only inconsistently. The childhood form is characterized mainly by a benign hepatopathy, sometimes accompanied by diminished muscle strength and tone. An adult form beginning in the third and fourth decades presents with proximal and distal myopathy. The course is slowly progressive and may be associated with wasting of the leg and hand muscles. Several patients have developed weakness during adult life complained of rapid fatigue and aching of muscles, occurring with exertion and first noticed at an early age. Serum CK values were elevated and the EMG showed a myopathic picture as well as increased insertional activity, pseudomyotonic discharges, and fibrillation potentials. Rarely in the adult form, glycogen also accumulates in the peripheral nerves, giving rise to mild symptoms of polyneuropathy. The enzymatic defect is one of amylo-1,6-glucosidase deficiency.