MALIGNANT HYPERTHERMIA AND NEUROMUSCULAR DISEASE

Malignant hyperthermia (MH) is a rare clinical syndrome characterized by hypermetabolism and triggered by specific anesthetic agents. The mechanism of this abnormal reaction is due to uncontrolled calcium flux in the skeletal muscles resulting in a variable clinical syndrome of muscle rigidity, respiratory and metabolic acidosis, and elevation of temperature. The specific genetic defect underlying this condition has not been identified in humans, though in susceptible swine a mutation of the gene for the ryanodine receptor, a large protein which comprises the calcium channel in the sarcoplasmic reticulum, has been identified recently. Inheritance in humans appears to be autosomal dominant with variable penetrance. Patients with MH rarely have physical or laboratory signs of muscle disease. However, scattered case reports and investigations of individuals with known myopathies and other muscle related problems, such as acute rhabdomyolysis or idiopathic persistently elevated creatine kinase, suggest a possible association of MH with a variety of neuromuscular diseases and stress syndromes. This association is very strong in the case of central core disease (CCD) where it is supported by clinical and laboratory evidence, including the proximity of the CCD gene to the ryanodine receptor gene on chromosome 19. A variety of other diseases have been implicated and can be classified as possibly associated (King-Denborough syndrome, Duchenne muscular dystrophy) or unlikely to be associated (myotonia congenita, sudden infant death syndrome, limb girdle dystrophy, neuroleptic malignant syndrome, etc.). Evidence for an association with MH in the latter group is based on sporadic clinical reports and muscle contracture test results, and may be explained by the coexistence of the MH gene with the reported disease, oversensitivity of the contracture testing or the location of the MH gene in close proximity to the genes for these diseases resulting in linkage. Until a more sensitive and specific screening test is available for MH, those patients with neuromuscular diseases which have been reported to be associated with MH should be carefully monitored for signs of clinical MH when undergoing anesthesia. While nontriggering anesthetics are not contraindicated for these patients or their families, succinylcholine should probably be avoided in any patient with significant neuromuscular disease.