G.P.2.01 Acute Quadriplegic Myopathy: Underlying mechanisms, improved diagnostic methods and specific intervention strategies

Exertional heat stroke (EHS) is usually triggered by strenuous exercise performed under hot and humid environmental conditions. It is associated with a classical symptomatology, i.e. increased body temperature and neurologic impairment that could lead to coma, with the addition of rhabdomyolysis-induced myoglobinuria and acute renal failure. Malignant hyperthermia (MH) is an autosomal condition triggered by exposition to halogenated volatile anaesthetics and usually associated to mutations of a calcium channel, the ryanodine receptor (RYR1).While the pathogenesis of EHS differs from a MH crisis, both conditions share some similarities in symptoms, such as the abnormal increase in core temperature. Furthermore, the connection between both syndromes has been substantiated by the presence of both positive IVCT and the presence of RYR1 mutations in patients with a history of exercise induced heat stroke or rhabdomyolysis. The purpose of the present study was to further characterize the genetic and phenotypic connection, if any, between MH and EHS. A large panel of military patients who had developed a clear and well documented EHS was investigated retrospectively. At least 6 months after the EHS episode, in vitro halothane/caffeine contracture tests (IVCT) were performed in order to define their MH status. In addition, 31P magnetic resonance spectroscopy data were recorded during a standardized rest-exercise-recovery protocol in order to assess muscle energetics. Mutations in the RYR1 gene were investigated from the entire cDNA obtained from muscle samples belonging to 20 patients with an MHS-IVCT status. The corresponding data will be presented and discussed.