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British Journal of Anaesthesia Aug 2022
Topics: Calcium Channels, L-Type; Czech Republic; Humans; Malignant Hyperthermia; Mutation; Ryanodine Receptor Calcium Release Channel; Slovakia
PubMed: 35718563
DOI: 10.1016/j.bja.2022.04.029 -
Anesthesiology Jan 2018
Review
Topics: Anesthesia; Disease Susceptibility; Humans; Malignant Hyperthermia
PubMed: 28902673
DOI: 10.1097/ALN.0000000000001877 -
Journal of Biochemistry Jul 2023Biochemical reactions in cells serve as the endogenous source of heat, maintaining a constant body temperature. This process requires proper control; otherwise, serious... (Review)
Review
Biochemical reactions in cells serve as the endogenous source of heat, maintaining a constant body temperature. This process requires proper control; otherwise, serious consequences can arise due to the unwanted but unavoidable responses of biological systems to heat. This review aims to present a range of responses to heat in biological systems across various spatial scales. We begin by examining the impaired thermogenesis of malignant hyperthermia in model mice and skeletal muscle cells, demonstrating that the progression of this disease is caused by a positive feedback loop between thermally driven Ca2+ signaling and thermogenesis at the subcellular scale. After we explore thermally driven force generation in both muscle and non-muscle cells, we illustrate how in vitro assays using purified proteins can reveal the heat-responsive properties of proteins and protein assemblies. Building on these experimental findings, we propose the concept of 'trans-scale thermal signaling'.
Topics: Animals; Mice; Ryanodine Receptor Calcium Release Channel; Malignant Hyperthermia; Calcium; Muscle, Skeletal
PubMed: 37461189
DOI: 10.1093/jb/mvad053 -
Anesthesia and Analgesia Dec 2019
Topics: Ambulatory Surgical Procedures; Anesthesia; Anesthesiologists; Anesthesiology; Humans; Malignant Hyperthermia; United States
PubMed: 31743208
DOI: 10.1213/ANE.0000000000004449 -
Brain Communications 2022Malignant hyperthermia and exertional rhabdomyolysis have conventionally been considered episodic phenotypes that occur in otherwise healthy individuals in response to...
Malignant hyperthermia and exertional rhabdomyolysis have conventionally been considered episodic phenotypes that occur in otherwise healthy individuals in response to an external trigger. However, recent studies have demonstrated a clinical and histopathological continuum between patients with a history of malignant hyperthermia susceptibility and/or exertional rhabdomyolysis and -related congenital myopathies. We hypothesize that patients with a history of -related exertional rhabdomyolysis or malignant hyperthermia susceptibility do have permanent neuromuscular symptoms between malignant hyperthermia or exertional rhabdomyolysis episodes. We performed a prospective cross-sectional observational clinical study of neuromuscular features in patients with a history of -related exertional rhabdomyolysis and/or malignant hyperthermia susceptibility ( = 40) compared with healthy controls ( = 80). Patients with an -related congenital myopathy, manifesting as muscle weakness preceding other symptoms as well as other (neuromuscular) diseases resulting in muscle weakness were excluded. Study procedures included a standardized history of neuromuscular symptoms, a review of all relevant ancillary diagnostic tests performed up to the point of inclusion and a comprehensive, standardized neuromuscular assessment. Results of the standardized neuromuscular history were compared with healthy controls. Results of the neuromuscular assessment were compared with validated reference values. The proportion of patients suffering from cramps ( < 0.001), myalgia ( < 0.001) and exertional myalgia ( < 0.001) was higher compared with healthy controls. Healthcare professionals were consulted because of apparent neuromuscular symptoms by 17/40 (42.5%) patients and 7/80 (8.8%) healthy controls ( < 0.001). Apart from elevated creatine kinase levels in 19/40 (47.5%) patients and mild abnormalities on muscle biopsies identified in 13/16 (81.3%), ancillary investigations were normal in most patients. The Medical Research Council sum score, spirometry and results of functional measurements were also mostly normal. Three of 40 patients (7.5%) suffered from late-onset muscle weakness, most prominent in the proximal lower extremity muscles. Patients with variants resulting in malignant hyperthermia susceptibility and/or exertional rhabdomyolysis frequently report additional neuromuscular symptoms such as myalgia and muscle cramps compared with healthy controls. These symptoms result in frequent consultation of healthcare professionals and sometimes in unnecessary invasive diagnostic procedures. Most patients do have normal strength at a younger age but may develop muscle weakness later in life.
PubMed: 36751502
DOI: 10.1093/braincomms/fcac292 -
Anesthesiology Dec 2020It is timely to consider the utility and practicability of screening for malignant hyperthermia susceptibility using genomic testing. Here the authors pose a simple, but... (Review)
Review
It is timely to consider the utility and practicability of screening for malignant hyperthermia susceptibility using genomic testing. Here the authors pose a simple, but bold question: what would it take to end deaths from malignant hyperthermia? The authors review recent advances and propose a scientific and clinical pathway toward this audacious goal to provoke discussion in the field.
Topics: Genetic Predisposition to Disease; Genetic Testing; Genomics; Humans; Malignant Hyperthermia
PubMed: 32898259
DOI: 10.1097/ALN.0000000000003547 -
Der Anaesthesist Dec 2014Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy. Trigger substances, such as volatile anesthetic agents and the depolarizing muscle... (Review)
Review
Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy. Trigger substances, such as volatile anesthetic agents and the depolarizing muscle relaxant succinylcholine can induce a potentially fatal metabolic increase in predisposed patients caused by a dysregulation of the myoplasmic calcium (Ca) concentration. Mutations in the dihydropyridine ryanodine receptor complex in combination with the trigger substances are responsible for an uncontrolled release of Ca from the sarcoplasmic reticulum. This leads to activation of the contractile apparatus and a massive increase in cellular energy production. Exhaustion of the cellular energy reserves ultimately results in local muscle cell destruction and subsequent cardiovascular failure. The clinical picture of MH episodes is very variable. Early symptoms are hypoxia, hypercapnia and cardiac arrhythmia whereas the body temperature rise, after which MH is named, often occurs later. Decisive for the course of MH episodes is a timely targeted therapy. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced to well under 10 %. An MH predisposition can be detected using the invasive in vitro contracture test (IVCT) or mutation analysis. Few elaborate diagnostic procedures are in the developmental stage.
Topics: Anesthesia; Calcium; Dantrolene; Humans; Malignant Hyperthermia; Muscle Relaxants, Central; Mutation; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum
PubMed: 25384957
DOI: 10.1007/s00101-014-2392-x -
Korean Journal of Anesthesiology Feb 2019
Topics: Dantrolene; Humans; Malignant Hyperthermia
PubMed: 29921086
DOI: 10.4097/kja.d.18.00139 -
Anesthesiology Clinics Jun 2017A significant number of commonly administered medications in anesthesia show wide clinical interpatient variability. Some of these include neuromuscular blockers,... (Review)
Review
A significant number of commonly administered medications in anesthesia show wide clinical interpatient variability. Some of these include neuromuscular blockers, opioids, local anesthetics, and inhalation anesthetics. Individual genetic makeup may account for and predict cardiovascular outcomes after cardiac surgery. These interactions can manifest at any point in the perioperative period and may also only affect a specific system. A better understanding of pharmacogenomics will allow for more individually tailored anesthetics and may ultimately lead to better outcomes, decreased hospital stays, and improved patient satisfaction.
Topics: Analgesics, Opioid; Anesthesia; Anesthetics, Inhalation; Genomics; Humans; Malignant Hyperthermia; Neuromuscular Blocking Agents; Perioperative Period; Postoperative Nausea and Vomiting
PubMed: 28526149
DOI: 10.1016/j.anclin.2017.01.014 -
Clinical Genetics Mar 2024Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early... (Review)
Review
Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.
Topics: Humans; Malignant Hyperthermia; Ryanodine Receptor Calcium Release Channel; Risk Factors; Risk Assessment
PubMed: 38148504
DOI: 10.1111/cge.14475