Joilson M Santos1, Pamela V Andrade1, Leonardo Galleni2, Mariz Vainzof2, Claudia F R Sobreira3, Beny Schmidt4, Acary S B Oliveira4, José L G Amaral1, Helga C A Silva5. 1. Center of Study, Diagnosis, and Investigation of Malignant Hyperthermia, Department of Surgery, Discipline of Anesthesiology, Pain and Intensive Care, São Paulo Medical School, Federal University of São Paulo, Rua Pedro de Toledo, 781 - 11°/ala direita, São Paulo, SP, CEP 04039-032, Brazil. 2. Human Genome and Stem Cells Research Center, Bioscience Institute, University of São Paulo, São Paulo, SP, Brazil. 3. Department of Neurosciences, Division of Neurology, Ribeirao Preto Medical School, University of Sao Paulo, São Paulo, SP, Brazil. 4. Neuromuscular Diseases Sector, Department of Neurology, São Paulo Medical School, Federal University of São Paulo, São Paulo, SP, Brazil. 5. Center of Study, Diagnosis, and Investigation of Malignant Hyperthermia, Department of Surgery, Discipline of Anesthesiology, Pain and Intensive Care, São Paulo Medical School, Federal University of São Paulo, Rua Pedro de Toledo, 781 - 11°/ala direita, São Paulo, SP, CEP 04039-032, Brazil. halsilva@uol.com.br.
Abstract
PURPOSE: HyperCKemia is a persistent rise in serum creatine kinase (CK) levels of at least 1.5 times the normal value, as evidenced by a minimum of two measurements at 30-day intervals. One of the neuromuscular diseases associated with hyperCKemia is malignant hyperthermia (MH). This study investigated the susceptibility to MH in patients with hyperCKemia via in vitro contracture testing (IVCT) and a search of mutations in the RYR1 gene. METHODS: Patients in an MH centre were followed from 1997-2012, and their epidemiologic, clinical, and laboratory data were analyzed, including IVCT, muscle histochemical analysis, and next-generation sequencing molecular analysis. RESULTS: There were nine patients (eight male) in our study with a mean (SD) age of 33 (12) yr. Four patients were Caucasian and five were African Brazilian. Most complained about myalgia or cramps, but all had a normal neurological examination. They persistently presented with hyperCKemia from three months to ten years, with a mean (SD) CK value of 788 (507) IU·L-1 ranging from 210-1,667 IU·L-1. These values corresponded to a 1.5- to nine-fold increase in the normal value (mean increase, 3.7-fold). Six patients were MH susceptible (MHS) after a positive IVCT. Histopathological muscular analysis disclosed unspecified changes in four of the MHS patients. Mitochondrial proliferation was observed in the other two MHS patients and in three MH negative patients. No pathogenic mutations were identified in the RYR1 gene in the five patients evaluated. CONCLUSION: When investigating patients with idiopathic hyperCKemia, susceptibility to MH should be taken into account, and guidance should be offered to prevent anesthetic complications in the family.
PURPOSE:HyperCKemia is a persistent rise in serum creatine kinase (CK) levels of at least 1.5 times the normal value, as evidenced by a minimum of two measurements at 30-day intervals. One of the neuromuscular diseases associated with hyperCKemia is malignant hyperthermia (MH). This study investigated the susceptibility to MH in patients with hyperCKemia via in vitro contracture testing (IVCT) and a search of mutations in the RYR1 gene. METHODS:Patients in an MH centre were followed from 1997-2012, and their epidemiologic, clinical, and laboratory data were analyzed, including IVCT, muscle histochemical analysis, and next-generation sequencing molecular analysis. RESULTS: There were nine patients (eight male) in our study with a mean (SD) age of 33 (12) yr. Four patients were Caucasian and five were African Brazilian. Most complained about myalgia or cramps, but all had a normal neurological examination. They persistently presented with hyperCKemia from three months to ten years, with a mean (SD) CK value of 788 (507) IU·L-1 ranging from 210-1,667 IU·L-1. These values corresponded to a 1.5- to nine-fold increase in the normal value (mean increase, 3.7-fold). Six patients were MH susceptible (MHS) after a positive IVCT. Histopathological muscular analysis disclosed unspecified changes in four of the MHSpatients. Mitochondrial proliferation was observed in the other two MHSpatients and in three MH negative patients. No pathogenic mutations were identified in the RYR1 gene in the five patients evaluated. CONCLUSION: When investigating patients with idiopathic hyperCKemia, susceptibility to MH should be taken into account, and guidance should be offered to prevent anesthetic complications in the family.
Authors: Philip M Jones; Britney N Allen; Richard A Cherry; Luc Dubois; Kelly N Vogt; Salimah Z Shariff; Krista M Bray Jenkyn; Sheila Riazi; Duminda N Wijeysundera Journal: Can J Anaesth Date: 2018-11-12 Impact factor: 5.063
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Authors: Joshua J Todd; Muslima S Razaqyar; Jessica W Witherspoon; Tokunbor A Lawal; Ami Mankodi; Irene C Chrismer; Carolyn Allen; Mary D Meyer; Anna Kuo; Monique S Shelton; Kim Amburgey; Dmitriy Niyazov; Pierre Fequiere; Carsten G Bönnemann; James J Dowling; Katherine G Meilleur Journal: Front Neurol Date: 2018-03-05 Impact factor: 4.003