It is difficult to definitely predict the occurrence of malignant hyperthermia (MH) and to identify patients at risk before anesthesia. Preoperative increase of serum creatine kinase activity (CK) at rest is considered one of the risk factors for MH susceptibility.  However, the use of CK determination as a screening test for malignant hyperthermia susceptibility (MHS) has failed in some patients. [2,3] We present a case of a patients with MHS with normal resting CK level who showed asymptomatic delayed recovery of exercise-induced CK elevation.
A 28-yr-old, 79-kg muscular man, who was scheduled for excision of herniated lumbar disc during general anesthesia, demonstrated increased serum CK level of 3,794 U/l (normal, 45–195 U/l) with an MM type of 99% on the day of admission. The CK had been 185 U/l before an uneventful appendectomy with spinal analgesia 9 months earlier. The present surgery was postponed, and serial serum CK values decreased daily, but it took 17 days to return to the normal range. During that period, examinations by the neurologists failed to reveal myositis or apparent neuromuscular diseases. There was neither remarkable medical history nor family history of MH or any muscular disease. However, the patient was sometimes aware of muscle cramps and dark-colored urine after exercise. He ran a 20-km race 23 days before admission to the hospital and had not been exercising since the race because low back pain had developed. This was later diagnosed as one of the symptoms of herniated disc. That race was presumed to be the cause of his high CK values his, delayed recovery of CK, and the episodes of rhabdomyolysis suggested underlying muscular disease. Diagnostic muscle biopsy from the quadriceps femoris muscle was obtained for caffeine-halothane contracture test (CHCT), calcium-induced calcium release (CICR) test, and histopathologie examination.
Histopathologic study showed no specific changes such as central core disease or other neuromuscular diseases, but a mild myopathy was recognized. The patient was diagnosed as having MHS based on CHCT according to the protocol of the European Malignant Hyperthermia Group (the threshold concentrations of caffeine and halothane for 0.2-g increase of tension were 2 mM and 1%, respectively) and that of the North American Malignant Hyperthermia Group (0.4-g and 1.2-g contracture on exposure to 2 mM caffeine and 3% halothane, respectively). CICR rate was not accelerated.  Phosphorus-31 nuclear magnetic resonance (sup 31 P NMR) spectroscopy  demonstrated a greater decrease and slower recovery in forearm muscle pH after exercise and an early depletion of phosphocreatine during the exercise compared with a control subject confirmed as MH negative by CHCT (Figure 1).
Surgery was uneventfully performed during spinal analgesia 3 months later. The CK levels peaked at 391 U/l on the following day and normalized in 3 days.
Even in a healthy person, gross increases in serum CK level after high-intensity or prolonged weight-bearing exercises, such as a marathon, have been reported.  However, considering that CK levels generally normalize in 3–7 days, it would be assumed that if serum CK activity exceeds 10,000 U/l after the exercise or 5,000 U/l more than 24 h after the event, subclinical myopathy predisposing the person to the risk of rhabdomyolysis was likely to be present. [8,9] Our patient showed a serum CK level of more than 3,000 U/l 23 days after a 20-km run, suggesting the presence of subclinical myopathy.
Subclinical myopathy is often related to MH. Although the primary defect in MH patients lies in the sarcoplasmic reticulum of skeletal muscle cells, histologic examination cannot detect any specific findings of MH with a few exceptions, such as patients with central core disease or King-Denborough syndrome.  Pathophysiologically, MH may be regarded as a subclinical primary myopathy with secondary systemic changes.  Epidemiologic studies show that many MHS patients have episodes of muscular cramps, pain, and pyrexia after exercise,  which suggests that these patients are associated with an underlying myopathy. Sporadically reported MHS subjects linked with exercise-induced myolysis [13,14] support this idea. Allsop et al. also showed that MHS subjects showed decreased power output and suggested the presence of an underlying myopathy manifested by high-intensity exercise in MHS patients. 
This patient was diagnosed as MHS by CHCT. However, a functioning abnormality in the ryanodine receptor of the sarcoplasmic reticulum could not be identified as the cause of MHS because CICR was not accelerated. The mechanism of persistent increased CK values after the semi-marathon suggests increased leakage of CK through the muscle cell membrane caused by the loss of membrane integrity maintained by high energy compounds such as phosphocreatine and ATP, which might be the explanation for the patient's episodic rhabdomyolysis. Early depletion and slow recovery of such high energy compounds during and after muscle-loading exercise, which occurs when the production of ATP via metabolic pathway is deteriorated or when the breakdown of ATP is accelerated, might play a role in disturbing the function of the muscle cell membrane.
We conclude that delayed recovery of CK level increase after prolonged weight-bearing exercise in this patient represents an underlying myopathy that might be associated with MHS. We should not overlook the possibility of MHS in an otherwise healthy person showing an abnormal CK increase after exercise.