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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant hyperthermia (MH) is a rare clinical syndrome characterized by hypermetabolism and triggered by specific anesthetic agents. The mechanism of this abnormal reaction is due to uncontrolled calcium flux in the skeletal muscles resulting in a variable clinical syndrome of muscle rigidity, respiratory and metabolic acidosis, and elevation of temperature. The specific genetic defect underlying this condition has not been identified in humans, though in susceptible swine a mutation of the gene for the ryanodine receptor, a large protein which comprises the calcium channel in the sarcoplasmic reticulum, has been identified recently. Inheritance in humans appears to be autosomal dominant with variable penetrance. Patients with MH rarely have physical or laboratory signs of muscle disease. However, scattered case reports and investigations of individuals with known myopathies and other muscle related problems, such as acute rhabdomyolysis or idiopathic persistently elevated creatine kinase, suggest a possible association of MH with a variety of neuromuscular diseases and stress syndromes. This association is very strong in the case of central core disease (CCD) where it is supported by clinical and laboratory evidence, including the proximity of the CCD gene to the ryanodine receptor gene on chromosome 19. A variety of other diseases have been implicated and can be classified as possibly associated (King-Denborough syndrome, Duchenne muscular dystrophy) or unlikely to be associated (myotonia congenita, sudden infant death syndrome, limb girdle dystrophy, neuroleptic malignant syndrome, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant hyperthermia and neuromuscular disease. 148 40

Myotonia is defined as a persistent contraction of skeletal muscles after their stimulation. This contracture is not prevented or relieved by regional anaesthesia or muscle relaxants. The sensitivity to non-depolarizing muscle relaxants is usually normal. Suxamethonium, neostigmine, hypothermia, a rise in kalaemia should be avoided. There have been case reports of malignant hyperthermia in patients with myotonia congenita. Dystrophia myotonica is the second most frequent of the inherited muscle diseases, after Duchenne's dystrophy. The severity of the disease is due more to the muscular atrophy and the multiple organ involvement than to the abnormal contraction. Atrioventricular heart block and dysrhythmias are more common than heart failure. Prolonged apnoea and pneumonia are the main risks of anaesthesia. In severe cases, exists a restrictive respiratory insufficiency which is preceded by a fall in the maximum expiratory pressure. Dysphagias and inefficient coughing may occur early. An increased susceptibility to hypnotic drugs and opiates is a common feature. Spontaneous sleep apnoeas should be sought before anaesthesia, especially by using pulse oximetry. The anaesthetic implications are reemphasized.
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PMID:[Anesthesia in myotonia]. 253 24

We report a family in which two sisters with myotonia congenita (MyC) were referred for malignant hyperthermia (MH) evaluation after each developed muscle rigidity with anesthesia. Halothane contracture testing of skeletal muscle in both was consistent with MH susceptibility. A third sister without clinical evidence of MyC was negative on contracture testing. These results suggest an association between MyC and MH susceptibility.
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PMID:Malignant hyperthermia in myotonia congenita. 336 83

The association of malignant hyperthermia (MH) with neuromuscular disorders has been recognized since 1970. These disorders include central core disease, Duchenne muscular dystrophy, myotonia congenita, myotonic dystrophy, nonspecific myopathies, and King-Denborough syndrome. In order to assess the anesthetic risk of MH in the neuromuscular population, we performed halothane and caffeine contracture testing for MH susceptibility on biopsied muscle removed from 25 consecutive neuromuscular patients during diagnostic evaluation. Positive contracture tests were found in 7 of 18 patients with myopathic disorders and 3 of 7 patients with neurogenic disorders. Two of our patients had anesthetic events suggesting MH. These findings suggest that myopathic and neuropathic disorders share pathogenic mechanisms with MH, resulting in positive contracture tests and possibly leading to clinical events during anesthesia. Although there is controversy regarding the interpretation of a positive contracture test, contracture testing remains the most widely accepted test for MH susceptibility. Thus, a variety of neuromuscular disorders may be associated with MH susceptibility, and caution should be exercised during anesthesia in this group of patients.
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PMID:Halothane-caffeine contracture testing in neuromuscular diseases. 337 16

Six goats with myotonia congenita were exposed for 1 h to 1% halothane and a single injection of suxamethonium i.v. in an attempt to induce malignant hyperthermia. No evidence of malignant hyperthermia occurred. Suxamethonium did produce a myotonic response in each goat, lasting 10-20s, which was accompanied by a transient increase in aerobic metabolism as indicated by a decrease in PvO2 from 6.6 to 5.7 kPa, an increase in PaCO2 from 5.1 to 6.1 kPa and an increase in PVCO2 from 5.5 to 6.3 kPa. There was no evidence of any metabolic acidosis since the transient changes in pH and buffer base were consistent with the increase in carbon dioxide tension. It is concluded that in goats myotonia congenita does not predispose to susceptibility to malignant hyperthermia.
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PMID:Failure to induce malignant hyperthermia in myotonic goats. 682 23

Many physiological processes depend upon the proper functioning of plasma membrane ion channels. This is most apparent in absorptive and secretory epithelia, and in electrically excitable tissues such as nerve and muscle. Disturbances in the operation of ion channels in these settings can alter normal physiology and cause disease. This review illustrates the use of molecular genetics in identifying hereditary diseases caused by mutations in genes which encode various skeletal muscle ion channels. Recent advances in the discovery of genetic mutations in the skeletal muscle voltage-gated sodium channel in certain forms of periodic paralysis, mutations in the skeletal muscle chloride channel gene in myotonia congenita, and defects in two distinct calcium channels that underlie disorders of excitation-contraction coupling (murine muscular dysgenesis, malignant hyperthermia susceptibility) will be presented. In each case, prior knowledge of abnormal ion channel function prompted the search for mutations in candidate genes. This work is beginning to shed new light on the relationship between ion channel structure and function by studies of naturally occurring channel mutations.
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PMID:Molecular genetics of ion channel diseases. 856 79

Recent advances in the field of molecular myology have provided significant insight into the pathological mechanisms underlying a variety of neuromuscular disorders. Genetic abnormalities can now be linked to primary and secondary pathophysiological changes in muscle fibres which compromise structural, metabolic, regulatory or contractile mechanisms. Ion channel myopathies such as paramyotonia congenita, hyper- and hypokalaemic periodic paralysis, myotonia congenita, episodic ataxia and malignant hyperthermia were established as linked to mutations in genes encoding the sodium channel, dihydropyridine receptor, chloride channel, potassium channel and the ryanodine receptor calcium release channel, respectively. Metabolic disorders affecting skeletal muscle were found to be due to deficiencies in a variety of enzymes. Identification of defects in components belonging to the gigantic dystrophin-glycoprotein complex led to the discovery of the molecular pathogenesis of Duchenne muscular dystrophy and related disorders. Based on these molecular findings, it is now feasible to design and evaluate new techniques such as gene and myoblast transfer therapy in order to replace defective components in diseased muscle fibres.
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PMID:[Molecular pathogenesis of muscular diseases]. 903 37

By the introduction of technological advancement in methods of structural analysis, electronics, and recombinant DNA techniques, research in physiology has become molecular. Additionally, focus of interest has been moving away from classical physiology to become increasingly centered on mechanisms of disease. A wonderful example for this development, as evident by this review, is the field of ion channel research which would not be nearly as advanced had it not been for human diseases to clarify. It is for this reason that structure-function relationships and ion channel electrophysiology cannot be separated from the genetic and clinical description of ion channelopathies. Unique among reviews of this topic is that all known human hereditary diseases of voltage-gated ion channels are described covering various fields of medicine such as neurology (nocturnal frontal lobe epilepsy, benign neonatal convulsions, episodic ataxia, hemiplegic migraine, deafness, stationary night blindness), nephrology (X-linked recessive nephrolithiasis, Bartter), myology (hypokalemic and hyperkalemic periodic paralysis, myotonia congenita, paramyotonia, malignant hyperthermia), cardiology (LQT syndrome), and interesting parallels in mechanisms of disease emphasized. Likewise, all types of voltage-gated ion channels for cations (sodium, calcium, and potassium channels) and anions (chloride channels) are described together with all knowledge about pharmacology, structure, expression, isoforms, and encoding genes.
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PMID:Voltage-gated ion channels and hereditary disease. 1050 36

Rapid progress in the complementary fields of molecular genetics and cellular electrophysiology has led to a better understanding of many disorders which are caused by ion channel dysfunction. These channelopathies may manifest in a multitude of ways depending on the tissue specificity of the channel that is affected. Several important general medical conditions are now known to be channelopathies but the neurological members of this family are amongst the best characterized. Over recent years, ion channel dysfunction in skeletal muscle in particular has emerged as a paradigm for understanding neurological ion channel disorders. This review concentrates mainly on the diseases caused by dysfunction of the voltage-gated ion channels. We initially focus on the skeletal muscle channelopathies (the periodic paralyses, malignant hyperthermia, paramyotonia congenita and myotonia congenita). The central nervous system channelopathies are then explored, with particular reference to the advances which have implications for understanding the mechanisms of common neurological disorders such as epilepsy and migraine. Looking towards the new millennium, DNA-based diagnosis will become a realistic proposition for most neurological channelopathies. Furthermore, it seems likely that new therapies will be designed based on genotype and mode of ion channel dysfunction.
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PMID:Neurological channelopathies: diagnosis and therapy in the new millennium. 1068 Aug 55

Hereditary muscle channelopathies are caused by dominant mutations in the genes encoding for subunits of muscle voltage-gated ion channels. Point mutations on the human skeletal muscle Na+ channel (Nav1.4) give rise to hyperkalemic periodic paralysis, potassium aggravated myotonia, paramyotonia congenita and hypokalemic periodic paralysis type 2. Point mutations on the human skeletal muscle Ca2+ channel give rise to hypokalemic periodic paralysis and malignant hyperthermia. Point mutations in the human skeletal chloride channel CIC-1 give rise to myotonia congenita. Point mutations in the inwardly rectifying K+ channel Kir2.1 give rise to a syndrome characterized by periodic paralysis, severe cardiac arrhythmias and skeletal alterations (Andersen's syndrome). Involvement of the same ion channel can thus give rise to different phenotypes. In addition, the same mutation can lead to different phenotypes or similar phenotypes can be caused by different mutations on the same or on different channel subtypes. Bearing in mind, the complexity of this field, the growing number of potential channelopathies (such as the myotonic dystrophies), and the time and cost of the genetic procedures, before a biomolecular approach is addressed, it is mandatory to apply strict diagnostic protocols to screen the patients. In this study we propose a protocol to be applied in the diagnosis of the hereditary muscle channelopathies and we demonstrate that muscle biopsy studies and muscle cell cultures may significantly contribute towards the correct diagnosis of the channel involved. DNA-based diagnosis is now a reality for many of the channelopathies. This has obvious genetic counselling, prognostic and therapeutic implications.
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PMID:Muscle biopsy and cell cultures: potential diagnostic tools in hereditary skeletal muscle channelopathies. 1268 54


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