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)

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.
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PMID:Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. 352 59

Two patients with mitochondrial myopathy (Kearns-Sayre syndrome) received general anaesthesia. In the first case propofol-alfentanil anaesthesia was carried out; the second patient received propofol-fentanyl anaesthesia. Muscle relaxation was provided with vecuronium. In both cases we observed a short episode of bradycardia (heart rate < 50.min-1), which was successfully treated with atropine. After the propofol infusion had been stopped, both patients rapidly gained consciousness and were extubated after prompt spontaneous ventilation had returned. Reversal of neuromuscular blockade in the second patient was achieved within 5 min by neostigmine. Special anaesthetic problems in patients with mitochondrial myopathies such as myocardial conduction disturbances, postoperative muscle hypotonia, and possible increased susceptibility to malignant hyperthermia can be overcome by the described anaesthetic management.
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PMID:[General anesthesia in two patients with mitochondrial myopathy]. 847 Jul 83

Children frequently undergo muscle biopsy for the workup of hypotonia under general anaesthesia which poses unique risks in patients with undiagnosed muscle disease. Mitochondrial myopathies are a relatively newly recognized cause of myopathy and multisystem disease in both adults and children. The diagnosis is complex. In addition to causing myopathy, there are metabolic derangements present in some cases that may be life-threatening. We present three cases of children with hypotonia where the diagnosis was suspected in two patients, and confirmed in the third. The question of whether patients with mitochondrial myopathies are at increased risk for developing malignant hyperthermia is discussed.
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PMID:Mitochondrial myopathies: an unusual cause of hypotonia in infants and children. 882 50

Gamstorp's disease or hyperkaliemic periodic paralysis is a rare pathology leading to spells of generalized hypotonia due to hyperkaliema. It is hard to say how far pregnancy affects the course of the disease and what is the impact of the disease on pregnancy. We report a case of Gamstorp's disease during pregnancy and we insist on the fact that because it can be crippling during its acute phases, close surveillance is needed during pregnancy. Screening for malignant hyperthermia should be carried out. During labour, kaliemia level should be monitored repeatedly and the expulsion phase kept as short as possible if necessary by forceps delivery.
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PMID:[Gamstorp's disease and pregnancy. A case report]. 902 13

We report on two boys aged 2 and 6 years-old respectively with dysmorphic face, ptosis, down-slanting palpebral fissures, hypertelorism, epicanthic folds, low-set ears, malar hypoplasia, micrognathia, high-arched palate, clinodactyly, palmar simian line, pectus excavatum, winging of the scapulae, lumbar lordosis and mild thoracic scoliosis who present congenital hypotonia, slightly delayed motor development, diffuse joint hyperextensibility and mild proximal weakness. The muscle biopsy revealed minimal but identifiable changes represented by size fiber variability, type I fiber predominance and atrophy, perimysial fibrous infiltration and some disarray of the intermyofibrillary network. These cases correspond to the first Brazilian reports of the King-Denborough syndrome and our objective is increasing the awareness of this disorder as these patients are predisposed to developing malignant hyperthermia.
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PMID:King-Denborough Syndrome: report of two Brazilian cases. 1236 41

Central core disease (CCD) is a dominantly inherited congenital myopathy allelic to malignant hyperthermia (MH) caused by mutations in the RYR1 gene on chromosome 19q13.1. Eleven individuals with RYR1 mutations are described. Four index cases showed features consistent with a congenital myopathy (hypotonia, delayed motor milestones, and skeletal abnormalities including congenital hip dislocation and scoliosis). All four cases and subsequently seven other family members were found to possess novel mutations in the RYR1 gene. The degree of disability varied from one clinically normal individual, to another who had never achieved independent ambulation (the only patient with a de novo mutation). Four cases showed a mild reduction in vital capacity, repeated nocturnal polysomnography showed hypoxaemia in one case. A variety of muscle biopsy features were found; central cores were absent in the youngest case, and the biopsy specimens from two others were more suggestive of mini-core myopathy. In all cases missense mutations in exons 101, 102, and 103 of the RYR1 gene on were found. Future laboratory diagnosis of suspected cases and family members will be less invasive and more accurate with DNA analysis. Clinicians, especially paediatricians and orthopaedic surgeons, should be aware of this disorder because of the potential risk of MH.
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PMID:Central core disease: clinical, pathological, and genetic features. 1467 Jul 67

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

Stuve Wiedemann syndrome (SWS) is an autosomal recessively inherited syndrome which is characterized by bowing of the long bones, camptodactyly, facial dysmorphism, hypotonia, feeding and swallowing difficulties, and respiratory distress. In most cases episodes of unexplained hyperthermia are present. Patients with SWS can develop hyperthermia in conjunction with anesthesia and surgery, and a relationship has been suggested between the syndrome and malignant hyperthermia. We describe a 3-year-old child diagnosed with SWS to whom we administered general anesthesia during the removal of a corneal ulcer and dilatation of the lacrimal duct. Our patient had received, uncomplicated, inhalational anesthesia five times previously for different operations. There were no anesthesia-related complications in the present or previous perioperative periods. On one occasion the patient developed mild postoperative hyperthermia. We believe that this hyperthermia is different from the specific disorder of malignant hyperthermia and that sevoflurane can be safely used in patients with SWS. We also describe symptomatically related syndromes and their theoretical risks for anesthesia.
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PMID:Stuve Wiedemann syndrome and related syndromes: case report and possible anesthetic complications. 1920 41

Hereditary sensory and autonomic neuropathy type IV (HSAN IV) is a very rare autosomal recessive disorder characterized by recurrent episodes of unexplained fever, extensive anhidrosis, total insensitivity to pain, hypotonia, and mental retardation. The absence of urticarial reaction to intradermal injection of histamine is a sign of great diagnostic value, but this is common to all types of HSAN. The most frequent complications of this disease are corneal scarring, multiple fractures, joint deformities, osteomyelitis, and disabling self-mutilations. Malignant hyperthermia and sepsis are major causes of mortality. We relate the first observations of two Tunisian children with genetically confirmed HSAN IV. Our goal is to review the clinical aspects of this mysterious neuropathy and to emphasize the peculiarities of its management. These two patients are brothers from 1st-degree consanguineous parents (cousins) with no particular medical history. The 1st patient, the family's 1st child, presented in the 1st h of life with hypotonia and persistent fever, which was refractory to antipyretics. At the age of 8 months, the patient presented recurrent febrile seizures and developed significant self-mutilations of the fingers and tongue. He died 3 months later in a context of multivisceral failure from sepsis and malignant hyperthermia. The 2nd patient, currently aged 4 years, was born after a normal sister. He consulted in the neonatal period for a high fever. The diagnosis of HSAN IV was rapidly suspected and genetically confirmed. In fact, this patient is homozygous for the NTRK1 gene, whereas his sister and both parents are heterozygous. Special predispositions have been taken to improve the course of the disease such as air conditioning to control hyperthermia, a dental tray to reduce the injuries resulting from self-mutilation, regular moistening of the eyes to avoid corneal drying, and chlorpromazine to control hyperactivity and reduce injuries. The good progression with all these predispositions and others underlines the importance of appropriate multidisciplinary management and close monitoring of patients suffering from HSAN IV, especially during the first 3 years of life. Indeed, mortality, behavioral disorders, and mental retardation significantly decrease after this age. New curative treatments are expected in the next decade.
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PMID:[Hereditary sensory and autonomic neuropathy type IV: a report on two cases]. 2139 70

We gave general anesthesia to a patient with scoliosis combined with central core disease (CCD). CCD is a slowly progressive autosomal dominant congenital myopathy. CCD is presented typically in infancy with hypotonia and delay of motor development, characterized by predominantly proximal weakness pronounced in the hip girdle. Orthopedic complications are common with congenital dislocation of the hips, scoliosis and foot deformity. CCD is due to mutations in the skeletal muscle ryanodine receptor (RYR1) gene at chromosome 19q13.1, which is also implicated in the malignant hyperthermia (MH). A patient with CCD is at risk of MH, with an abnormal response to suxamethonium and volatile anesthetics. The anesthetist ought to be aware of the diagnosis of CCD and to plan anesthetic management accordingly, avoiding potentially MH-triggering agents. We used total intravenous anesthesia (TIVA) in this case, and he showed no MH symptoms perioperatively. This report demonstrates that anesthesia in a patient with CCD could be successfully maintained with TIVA.
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PMID:[Anesthetic management for a patient with scoliosis combined with central core disease]. 2152 May 99


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