title: Analysis of histomorphology in malignant hyperthermia-susceptible patients.
abstract: BACKGROUND
  Malignant hyperthermia (MH) is a potentially lethal disorder of skeletal muscle triggered by anesthetic agents. A histomorphological examination of diseased muscle may provide insight into MH pathophysiology, but it is not a routine part of standard-of-care practice for the identification of MH-susceptibility. In this study, we investigated muscle histomorphology in a large cohort of MH-susceptible (MHS) patients and examined its relationship to genotype and phenotype.
  
  
  METHODS
  All consenting patients who were identified as MHS based on a caffeine-halothane contracture test (CHCT) performed during 1992-2011 were retrospectively identified and recruited for this study. Results of the histomorphological examination, which is a routine part of our centre-specific practice, were reviewed. Patient demographics, MH proband status, histological features, CHCTs, and genetic results for MH-causative mutations were summarized.
  
  
  RESULTS
  Seven of the 399 patients classified as MHS had histological characteristics consistent with central core disease, and one patient was a carrier of Duchenne's muscular dystrophy. Eighty-six (22%) patients had histological abnormalities, and five (6%) of these had evidence of "frank" myopathy. No histologic abnormalities were consistent among the MHS patients; however, a higher proportion of MH probands had abnormal histomorphology compared with the general MHS population, and patients with evidence of "frank" myopathy showed similarities in clinical history, biochemistry, CHCT, and genetic testing.
  
  
  CONCLUSIONS
  Despite the inability of the histomorphological examination to identify consistent features in MHS patients, histology may serve as a potential adjunct to CHCT and aid in the identification of other myopathies. Nevertheless, the specifics of its utility ought to be assessed in other studies and by way of formal cost-effectiveness analysis.
authors.affiliation: Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, ON, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Orlov
authors.forename: Julia
authors.initials: J
authors.lastname: Keith
authors.forename: Derek
authors.initials: D
authors.lastname: Rosen
authors.forename: Sidney
authors.initials: S
authors.lastname: Croul
authors.forename: Natalia
authors.initials: N
authors.lastname: Kraeva
authors.forename: Sheila
authors.initials: S
authors.lastname: Riazi
mesh_terms: D000328:Adult; D002110:Caffeine; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006221:Halothane; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: D002110:Caffeine; D006221:Halothane