Predictive factors of the contracture test for diagnosing malignant hyperthermia in a Brazilian population sample: a retrospective observational study
Fatores preditivos no teste de contratura muscular para diagnóstico de hipertermia maligna em amostra brasileira: estudo observacional retrospectivo
Jean Marcel de Mello, Pamela Vieira Andrade, Joilson Moura Santos, Acary Souza Bulle Oliveira, Mariz Vainzof, José Luiz Gomes do Amaral, Helga Cristina Almeida da Silva
Abstract
Introduction
Malignant Hyperthermia (MH) is a pharmacogenetic, hereditary and autosomal dominant syndrome triggered by halogenates/succinylcholine. The In Vitro Contracture Test (IVCT) is the gold standard diagnostic test for MH, and it evaluates abnormal skeletal muscle reactions of susceptible individuals (earlier/greater contracture) when exposed to caffeine/halothane. MH susceptibility episodes and IVCT seem to be related to individual features.
Objective
To assess variables that correlate with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH.
Methods
We examined IVCTs of 80 patients investigated for MH between 2004‒2019. We recorded clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation, IVCT result) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering contracture of 0.2g, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation).
Results
Mean age of the sample was 35±13.3 years, and most of the subjects were female (n=43 or 54%) and MH susceptible (60%). Of the 20 subjects undergoing genetic investigation, 65% showed variants in RYR1/CACNA1S genes. We found no difference between the positive and negative IVCT groups regarding age, sex, number of probands, presence of muscle weakness or myopathy with muscle biopsy showing cores. Regression analysis revealed that the best predictors of positive IVCT were male sex (+12%), absence of muscle weakness (+20%), and personal MH background (+17%).
Conclusions
Positive IVCT results have been correlated to male probands, in accordance with early publications. Furthermore, normal muscle strength has been confirmed as a significant predictor of positive IVCT while investigating suspected MH cases.
Keywords
Resumo
Introdução: A hipertermia maligna (HM) é uma síndrome farmacogenética, hereditária e autossômica dominante, desencadeada por halogenados/succinilcolina. O teste de contratura in vitro (IVCT) é o teste diagnóstico padrão de HM, e avalia reações anormais do músculo esquelético de suscetíveis (contratura mais precoce/maior) quando exposto a cafeína/halotano. Suscetibilidade à crise de HM e o IVCT parecem associar-se a características individuais.
Objetivo: Avaliar variáveis que se associaram ao IVCT em pacientes brasileiros encaminhados por HM pessoal/familiar.
Métodos: Analisamos IVCTs de 80 pacientes investigados por HM entre 2004-2019. Coletamos dados clínicos (idade, sexo, presença de fraqueza muscular ou miopatia com cores, estudo genético, resultado do IVCT) e características do IVCT (contração máxima inicial e final, concentração de cafeína/halotano em que houve contratura de 0,2 g, contratura a 2 e 32 mM de cafeína e 2% de halotano e contração após estímulo a 100 Hz).
Resultados: A média de idade da amostra foi de 35+13,3 anos, com maioria feminina (43/54%) e suscetível à HM (60%). Variantes nos genes RYR1/CACNA1S foram identificadas em 65% dos 20 indivíduos testados. Não houve diferença entre grupos com IVCT positivo e negativo quanto à idade, sexo, número de probandos, presença de fraqueza muscular ou miopatia com cores. Os melhores preditores do IVCT positivo na regressão foram sexo masculino (+12%), ausência de fraqueza muscular (+20%) e HM pessoal (+17%).
Conclusões: Em concordância com estudos prévios, resultado positivo no IVCT se relacionou a probandos do sexo masculino. Adicionalmente, força muscular normal demonstrou ser preditor significativo no contexto da suspeita de HM.
Palavras-chave
References
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Submitted date:
09/21/2021
Accepted date:
06/03/2022
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