Effort-induced hyperthermia, also called exertional heat stroke (EHS) is due to an imbalance between internal heat production and heat loss, generally exacerbated by several factors such as inadequate fluid, caloric, and/or electrolyte intake, and is associated with a classical symptomatology, i.e. increased body temperature (higher than 40°C), neurological impairment that could lead to coma with the addition of rhabdomyolysis-induced myoglobinuria and acute renal failure. EHS generally occurs during strenuous activity under hot and humid environmental conditions. Subjects are often healthy young adults with no apparent clinical or biological deficits. The pathogenesis of a EHS episode differs from a malignant hyperthermia (MH) crisis. However, both conditions share some similarities in symptoms, such as the abnormal increase in core temperature. The triggering agent is different. MH is a disorder of skeletal muscle in which volatile anaesthetics and depolarizing muscle relaxants trigger a sustained increase in myoplasmic calcium concentration, thereby producing hyper-metabolic and contractile activities. MH crisis occurs in predisposed subjects and leads to a dramatic increase in core temperature. In addition, neurological signs are rarely recorded during a MH crisis, and dantrolene is used to prevent a fatal issue, whereas cooling is largely used as therapy during EHS. DNA mutations involved in the susceptibility to MH have been reported for only 50% of subjects susceptible to MH and for the remaining 50% this information is still not available. With respect to EHS subjects, no information regarding MH mutations has been reported so far.

Due to some similarities between MH and EHS, it could be hypothesised that EHS, in the same way as MH, is associated with the existence of an infraclinical myopathy. In this respect, electromyographic, histological and metabolic studies have provided conflicting and scanty results. In the present study, we analysed the physiological (using in vitro contracture tests) and metabolic (using 31-phosphorus magnetic resonance spectroscopy, 31P MRS) bases of EHS. We addressed the issue of possible etiological similarity between the group of EHS subjects and MH susceptible (MHS) subjects for whom a noninvasive diagnostic strategy has been recently reported.

Using 31P magnetic resonance spectroscopy, we have analysed the muscle energetics of 26 EHS subjects for whom in vitro halothane-caffeine contracture tests were abnormal and investigated possible similarities with subjects susceptible to malignant hyperthermia. An early decrease of pH was noted during the first minute of exercise in EHS subjects as compared to controls. EHS subjects were divided into two subgroups according to the diagnostic score previously developed for MHS subjects. The 19 subjects (73%) with a score higher than 2 displayed a significantly larger caffeine-induced and earlier ryanodine-induced contractures on muscle biopsies as compared to the rest of the group (7 subjects). The results demonstrate that muscle energetics is abnormal in subjects who have suffered from EHS and suggest a possible link between MH and EH, although all EHS patients cannot be considered as MHS. Metabolic abnormalities in EHS subjects detected by 31P MRS may indicate a defect affecting the calcium release channel of the sarcoplasmic reticulum which translates as a very abnormal ryanodine contracture test by IVCT. We conclude that, similarly to MH crisis, EHS is related to a failure of muscle energetics that may be associated with a latent myopathy which is readily identified by non invasive 31P MR spectroscopy.