Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 31-year old male developed malignant hyperthermia (MH) during the initial minutes of Halothane induction. CPK rose to 6120 U/ml and decreased to normal levels as the patient became afebrile over a 10 day period of cooling measures and metabolic management. Muscle weakness, predominantly proximal and depressed deep tendon reflexes were found upon examination during convalescence. Muscle biopsy showed neurogenic changes characterized by fiber type grouping and targetoid fibers. CPK was elevated in one of the patient's children. This case supports the view of underlying hereditary neuromyopathy in MH.
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PMID:Neuromyopathy in malignant hyperthermia. 58 Feb 62

In order to investigate the relationship between neuromuscular disease and malignant hyperthermia (MH) susceptibility, the caffeine and halothane in vitro contracture test (European Malignant Hyperthermia Group Protocol) were performed in 60 patients who underwent muscle biopsy for investigation of a clinically suspected neuromuscular disorder. Two test results were classified as MH susceptible, 10 as MH equivocal and 48 MH negative. The large number of equivocal results is thought to indicate the lack of specificity of the individual components of this test in patients with clinical or histological evidence of neuromuscular disease. The increased in vitro sensitivity to the drugs tested may nevertheless provide some explanation for several in vivo "MH-like reactions" reported frequently in these patients. These reactions, however, are likely to be based on pathophysiological mechanisms different from those responsible for a true MH crisis.
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PMID:In vitro contracture tests in patients with various neuromuscular diseases. 173 72

Neuromuscular diseases raise a lot of anesthesia related problems. The first is the hitherto unknown disease discovered by an unexpected adverse reaction to anesthetics or/and muscle relaxants up to a life-threatening incident. A second problem is the probable, suspected or proven disposition to malignant hyperthermia in patients with other neuromuscular diseases. Furthermore, severe rhabdomyolysis can be induced in myopathic muscle by the application of succinylcholine alone or in combination with inhalational anesthetics resulting in hyperkalemia, myoglobinuria and CK-elevation, sometimes followed by cardiac arrest. Cardiomyopathy is a common feature in many neuromuscular diseases. All cardiodepressant agents must be avoided. Specific problems with muscle relaxants arise in myasthenia gravis and in the myotonias. In the later stages of severe neuromuscular diseases the main problem concerning anesthesia is respiratory failure. The individual risk of every patient has to be evaluated before anesthesia. Recommendations for the anesthetic management are given.
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PMID:Anesthesia in neuromuscular diseases. 219 54

Central core disease (CCD) is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown but the condition is probably more common than other congenital myopathies. CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness pronounced in the hip girdle; orthopaedic complications are common and malignant hyperthermia susceptibility (MHS) is a frequent complication. CCD and MHS are allelic conditions both due to (predominantly dominant) mutations in the skeletal muscle ryanodine receptor (RYR1) gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1). Altered excitability and/or changes in calcium homeostasis within muscle cells due to mutation-induced conformational changes of the RyR protein are considered the main pathogenetic mechanism(s). The diagnosis of CCD is based on the presence of suggestive clinical features and central cores on muscle biopsy; muscle MRI may show a characteristic pattern of selective muscle involvement and aid the diagnosis in cases with equivocal histopathological findings. Mutational analysis of the RYR1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to anticipate susceptibility to potentially life-threatening reactions to general anaesthesia. Further evaluation of the underlying molecular mechanisms may provide the basis for future rational pharmacological treatment. In the majority of patients, weakness is static or only slowly progressive, with a favourable long-term outcome.
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PMID:Central core disease. 1750 18

Multi-minicore Disease (MmD) is a recessively inherited neuromuscular disorder characterized by multiple cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown. Marked clinical variability corresponds to genetic heterogeneity: the most instantly recognizable classic phenotype characterized by spinal rigidity, early scoliosis and respiratory impairment is due to recessive mutations in the selenoprotein N (SEPN1) gene, whereas recessive mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been associated with a wider range of clinical features comprising external ophthalmoplegia, distal weakness and wasting or predominant hip girdle involvement resembling central core disease (CCD). In the latter forms, there may also be a histopathologic continuum with CCD due to dominant RYR1 mutations, reflecting the common genetic background. Pathogenetic mechanisms of RYR1-related MmD are currently not well understood, but likely to involve altered excitability and/or changes in calcium homeoestasis; calcium-binding motifs within the selenoprotein N protein also suggest a possible role in calcium handling. The diagnosis of MmD is based on the presence of suggestive clinical features and multiple cores on muscle biopsy; muscle MRI may aid genetic testing as patterns of selective muscle involvement are distinct depending on the genetic background. Mutational analysis of the RYR1 or the SEPN1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to address the risk of marked respiratory impairment in SEPN1-related MmD and the possibility of malignant hyperthermia susceptibility in RYR1-related forms. In the majority of patients, weakness is static or only slowly progressive, with the degree of respiratory impairment being the most important prognostic factor.
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PMID:Multi-minicore Disease. 1763 Oct 35

Central core myopathy is a rare, inherited neuromuscular disorder with a wide spectrum of phenotypic presentations. It is also considered an allelic disease of malignant hyperthermia. We report a case of central core myopathy in a Chinese adolescent boy presenting with atypical clinical features and a moderately elevated serum creatine kinase level. The diagnosis was made from the histopathological findings of central cores on muscle biopsy, and confirmed by the molecular genetic testing for the RYR1 gene mutation. This is the first case of central core myopathy confirmed by molecular study in our locality.
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PMID:RYR1-related central core myopathy in a Chinese adolescent boy. 2128 29

Children with neuromuscular diseases present a wide range of clinical manifestations and clinical implications for the anaesthesiologist. Neuromuscular diseases in children affect muscle strength by either directly weakening the muscle fibrils or indirectly by a degenerative nerve supply and weak neuromuscular junction. Of the more than 200 neuromuscular disorders known, the vast majority are genetic in origin. This review focuses on four of the more common neuromuscular disorders with emphasis on their pathophysiology and clinical implications for anaesthesiologists: malignant hyperthermia, the muscular dystrophies (Duchenne's, Becker's, and Emery-Dreifuss), mitochondrial disorders, and cerebral palsy.
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PMID:Perioperative management of the paediatric patient with coexisting neuromuscular disease. 2215 73