THE DIAGNOSIS OF MALIGNANT HYPERTHERMIA S USCEPTIBILITY .1. SIGNIFICANCE OF THE IN-VITRO CONTRACTURE TEST

Molecular genetic findings indicate genetic heterogeneity in susceptib ility to malignant hyperthermia (MH). At present the in vitro contract ure test (IVCT) is still the most reliable diagnostic procedure for MH susceptibility. It must be performed in a standardized fashion. Metho ds. We investigated 350 patients (233 children and 117 adults) using t he protocol of the European MH Group for the IVCT. The test results we re classified as susceptible to MH (MHS), non-susceptible to MH (MHN) and equivocal (MHE), with an abnormal caffeine result designated MHEc and an abnormal halothane result designated MHEh. Reasons for the IVCT were a positive family history for MH susceptibility (n = 94), a MH r eaction (n = 157), creatine kinase elevation unknown aetiology (n = 53 ) and different neuromuscular diseases (NMD, n = 46). Physical, neurol ogical and laboratory work-up included serum enzymes, nerve conduction studies, electromyography and muscle biopsy evaluated by different te chniques. Thirty-one children and 11 adults were MHS, while 152 childr en and 80 adults were MHN. MHE findings were obtained in 50 children a nd 26 adults. While the MHS and MHN groups are diagnostically safe, th e equivocal group is not, with possible false-negative or false-positi ve interpretation. The high number of MHE findings most probably is ex plained by the high proportion of patients with NMD (53% of the childr en, 69% of the adults). Results. In a group of 18 boys with Duchenne o r Becker muscular dystrophy, ranging in age from 1.5 to 24 years, the IVCT results were twice MHS, once MHE, and MHN in the remaining 15 cas es. In seven other boys with Duchenne or Becker muscular dystrophy, pr oven by molecular techniques, there were anaesthetic complications wit h MH-like symptoms. After administration of trigger substances, five o ut of the seven suffered a cardiac arrest, two of whom died. In the su rviving five boys the IVCT results were three times MHN, once MHE and once MHS. Most probably these boys suffered from effects of succinylch oline, possibly potentiated by other trigger substances. The adverse c ardiac reactions are attributed to triggered rhabdomyolysis with assoc iated hyperkalemia but not a primary hereditary disposition to MH. Con clusion. In patients with NMD, MHS and MHE test results do not indicat e a hereditary, heterogeneous disposition to MH; the majority will be caused by a secondary induced disturbance of calcium homoeostasis in t he diseased muscle cells. These results do, however, indicate the foll owing: (1) Patients with NMD exposed to trigger substances are at high er risk than the general population for MH-like episodes, including su dden death. (2) NMD therefore should be diagnosed as early as possible and patients should not be exposed to trigger substances when alterna tives are at hand. (3) Diagnostic procedures in patients having suffer ed an MH-like episode should include IVCT and special investigations t o exclude or substantiate other NMD. The work-up may be changed if a f amily member is properly classified as MH susceptible. (4) In patients with known NMD there is no indication for performing IVCT, since the results may even be misleading.