Functional impairments, fatigue and quality of life in RYR1-related myopathies: A questionnaire study.

Mutations in RYR1 are a common genetic cause of non-dystrophic neuromuscular disorders. To obtain baseline data concerning the prevalence of fatigue, the psychological disease burden and quality of life associated with these common conditions, we performed a questionnaire study. Seventy-two patients were included in this study, 33 with a congenital myopathy and 39 with malignant hyperthermia or exertional rhabdomyolysis. Our results showed that patients with RYR1-related myopathies have more functional impairments and significant chronic fatigue compared to healthy controls, with almost half of patients being severely fatigued. Whilst fatigue, pain and associated physical and social difficulties were more pronounced in those with permanent phenotypes, individuals with intermittent phenotypes also scored higher in all relevant categories compared to healthy controls. These findings indicate that RYR1-related myopathies, despite being often considered relatively mild conditions, are nevertheless associated with severe fatigue and functional limitations, resulting in substantial loss of quality of life. Moreover, milder but in essence similar findings in patients with RYR1-related malignant hyperthermia and rhabdomyolysis suggest that those phenotypes are not truly episodic but in fact associated with a substantial permanent disease burden. These preliminary data should help to design more comprehensive quality of life studies to inform standards of care.

[In-vivo diagnosis of malignant hyperthermia susceptibility: a microdialysis study]. / In-vivo-Diagnostik einer malignen-Hyperthermie-Disposition: Eine Mikrodialysestudie.

BACKGROUND: In malignant hyperthermia (MH), volatile anesthetics induce hypermetabolism, lactic acidosis and rhabdomyolysis in predisposed patients. The authors hypothesized that intramuscular caffeine and halothane application would increase local lactate concentration in MH susceptible (MHS) individuals more than in non-susceptible (MHN) subjects without initiating the full MH syndrome. METHODS: In 14 MHS, 12 MHN and 7 control individuals, microdialysis probes were placed in the rectus femoris muscle and perfused with Ringer's solution at 1 microl/min. After equilibration, 250 microl caffeine (80 mM) was injected through the first microdialysis probe, halothane 10 vol% dissolved in soybean oil was perfused through a second microdialysis probe and a third probe was used for control measurements. Dialysate samples were analyzed for lactate spectrophotometrically. Systemic hemodynamic and metabolic parameters were measured. Data are presented as median and quartiles. RESULTS: Intramuscular caffeine and halothane significantly increased local peak concentrations of lactate in MHS probands [5.0 mM (3.4-8.1 mM) and 3.7 mM (2.6-5.0 mM), respectively] compared to MHN [1.6 mM (1.3-2.0 mM) and 1.9 mM (1.6-2.0 mM)] or control individuals [2.1 mM (1.9-2.3 mM) and 2.0 mM (1.6-2.1 mM)]. This was accompanied by a higher serum creatine kinase level in the MHS group. Hemodynamic and metabolic parameters were normal in the investigated groups. CONCLUSION: Intramuscular caffeine and halothane application induces a temporary and abnormal increase of local lactate in MHS individuals. No serious systemic side effects occurred. This study presents evidence that metabolic monitoring with local stimulation by caffeine and halothane may allow a minimally invasive diagnosis of MH susceptibility.

Malignant hyperthermia.

Malignant hyperthermia, also known as malignant hyperpyrexia, is a pharmacogenetic condition which can develop during general anaesthesia and can be fatal. The author suggests that more awareness of the condition is needed by ward-based nurses who are involved with patients undergoing surgery. The article describes the management of the condition, the nursing care and the screening available for susceptible patients.

[Living with the diagnosis of malignant hyperthermia].

This is the summary of a special lecture presented by a malignant hyperthermia (MH) patient at 24th Japanese Symposium of Malignant Hyperthermia in Yamagata City (August 25, 2001). Thirteen years ago, he developed acute crisis of MH on general anesthesia for tonsillectomy and was diagnosed as MH-susceptible (MHS) with muscle biopsy test. His personal troublesome experiences related to MHS, i.e. local anesthesia, sports under hot environment etc., have presented him with many difficulties and problems to be solved in actual life after discharge from hospital. He hoped in the lecture for advances in noninvasive diagnosis for MHS and safe anesthetic method for MHS-patients. Important missions of anesthesiologists include consultation of the medical problems of MHS patients and supporting their safety in daily life.

Behavioural and pituitary-adrenal characteristics of pigs differing by their susceptibility to the malignant hyperthermia syndrome induced by halothane anesthesia. 1. Behavioural measures.

Behavioural responses were compared in Pietrain pigs and in Large White pigs differing by their susceptibility to the malignant hyperthermia syndrome induced by halothane. Non reactive Pietran pigs (P--) displayed a higher level of locomotor activity in a new environment than either reactive Pietrain pigs (P+) or Large White pigs. Pietran pigs performed better in a latent learning proceudre (latency of approach or feeding response, after exploration of the new environment) and in a continuound P-- did not reach significance, but P+ pigs tended to be superior to P-- animals. The three groups did not differ on a measure of passive avoidance. These results suggest that Large White pigs are characterized by a lower ability to initiate active responding when confronted with aversive events. The same would be true when Pietrain positive pigs are compared with Pietrain negative pigs, although to a lesser extent.