31Phosphorus magnetic resonance spectroscopy characterization of muscular metabolic anomalies in patients with malignant hyperthermia -: Application to diagnosis

Background: Metabolic anomalies are known in skeletal muscles of patients with malignant hyperthermia (MH). Methods: The authors used 31-phosphorus (P-31) magnetic resonance spectroscopy (MRS) to compare metabolic changes of the finger flexor muscles recorded throughout two rest-exercise-recovery protocols (each including aerobic or ischemic exercise) in 26 healthy persons and in 13 MH-susceptible (MHS) persons who were unequivocally diagnosed by in vitro halothane-caffeine contracture tests on muscle biopsies. Results: No abnormality was observed at rest and during recovery periods. A larger phosphocreatine decrease associated with an early drop of pH was noted during the first minute of both exercise periods for the MHS patients compared with controls. The early pH decrease indicated a disorder affecting glycolytic activation, probably reflecting defects of Ca2+ cycling, and provided a sensitivity of 77% for MHS diagnosis. A diagnostic strategy based on the retrospective analysis of 19 selected MR parameters was developed. An MRS score, corresponding to the number of abnormal values among the 19 parameters, was calculated and provided sensitivity and specificity rates of 100%; that is, no false-positive or false-negative results were found. A prospective analysis of 10 new participants further confirmed these findings. Conclusions: These results (1) further confirm that MH is associated with the preexistence of latent muscular disorders; (2) enhance the potential diagnostic capacity of MRS, although it should be tested prospectively on a larger group of participants; and (3) allows the characterization of several abnormal metabolic profiles, in persons with MHS, reflecting the recently described polymorphism of MH.