Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The triad of rigidity, fever, and elevation of serum creatine phosphokinase (CPK) levels, labeled 'neuroleptic malignant syndrome' (NMS), is a dangerous complication of neuroleptic drug treatment. Amantadine was introduced for the pharmacological management of NMS because of its beneficial effects in Parkinson's disease which were attributed to direct or indirect dopaminomimetic properties of amantadine. While the dopaminomimetic effects of amantadine are weak under experimental conditions, recent studies have confirmed that amantadine is an antagonist at the N-methyl-D-aspartate (NMDA) type of glutamate receptor. Two lines of evidence suggest that amantadine or other NMDA receptor antagonists could be effective drugs for the reversal of NMS symptoms. First, glutamate antagonists restore the balance between glutamatergic and dopaminergic systems when dopaminergic transmission has been antagonized by neuroleptic drugs. Second, by virtue of their effects against rigor and spasticity, NMDA antagonists may reduce increased muscle tone and prevent rhabdomyolysis. In conclusion, NMS may be considered an iatrogenic excitatory aminoacid syndrome which is amenable to NMDA receptor antagonist therapy.
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PMID:A rationale for NMDA receptor antagonist therapy of the neuroleptic malignant syndrome. 133 36

Neuroleptic malignant syndrome is characterized by altered consciousness, fever, extrapyramidal signs, autonomic instability, elevated creatine kinase level, and leukocytosis. Although originally described in patients receiving neuroleptic drugs, this syndrome may also occur in patients with Parkinson's disease during withdrawal or reduction of levodopa therapy or other dopaminergic drug therapy. We have encountered three cases of neuroleptic malignant syndrome related to withdrawal of levodopa therapy. These cases illustrate the variety of circumstances in which alteration of therapy with dopaminergic drugs can cause this syndrome and the relative unfamiliarity of the neuroleptic malignant syndrome-levodopa relationship among physicians who do not treat large numbers of patients with Parkinson's disease. An understanding of the role of brain dopamine in the pathogenesis of neuroleptic malignant syndrome and an appreciation of the great variety of drugs whose manipulation can result in this potentially fatal syndrome will aid its proper and timely recognition, especially when the offending pharmacologic manipulation does not involve neuroleptic drugs.
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PMID:Neuroleptic malignant syndrome in Parkinson's disease after withdrawal or alteration of dopaminergic therapy. 149 12

The neuroleptic malignant syndrome (NMS) is a dangerous, often fatal, idiosyncratic disorder presumably of the basal ganglia and hypothalamus. It is usually associated with neuroleptic medications, and it is believed to be related to blockage of dopamine receptors in the brain. The NMS has also been reported in patients with Parkinson's disease after withdrawal of antiparkinsonian agents during "drug holidays." Cardinal features include fever, muscular rigidity, an elevated serum level of creatine phosphokinase, changes in mental status, and autonomic dysfunction. Although treatment has been largely supportive, dopamine agonists, such as bromocriptine, and a direct-acting muscle relaxant, dantrolene, have been used with good clinical outcome. Guidelines for reinstitution of neuroleptics are suggested.
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PMID:Neuroleptic malignant syndrome: guidelines for treatment and reinstitution of neuroleptics. 289 58

A 63-year-old woman with diagnosis of Parkinson's disease developed an unusual symptom complex which consisted of extrapyramidal symptoms, disturbances of consciousness, diaphoresis, fever, and increased serum creatine phosphokinase following the discontinuation of large doses of combined antiparkinsonian drugs. After the patient's condition did not improve with the first 14 days of treatment consisting of intravenous fluids and antibiotics, a trial administration of L-dopa and carbidopa brought about definite clinical improvement. The symptoms strongly resembled neuroleptic malignant syndrome which is often a serious complication of antipsychotic drugs. The symptoms and the treatment of the present case suggest that dopaminergic hypoactivity in the brain may be an important factor in antiparkinsonian drug withdrawal syndrome and that similar neurochemical mechanisms may exist in neuroleptic malignant syndrome.
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PMID:Neuroleptic malignant syndrome-like state following a withdrawal of antiparkinsonian drugs. 611 84

Interpretation of biochemical measurements in the human brain after death is complicated by a variety of premortem, perimortem, and postmortem factors. The activity of glutamic acid decarboxylase (GAD) in particular has been found to vary considerably among human brains. In contrast to neurotransmitter-associated enzymes, metabolic enzymes are present in all brain cells and should not be specifically lost by patterned neuronal cell loss such as that which occurs in Parkinson disease. We compared the activity of GAD to that of the metabolic enzymes creatine kinase (CK), adenylate kinase, hexokinase, beta-glucuronidase, and malate, lactate, glucose-6-phosphate, and isocitrate dehydrogenases in 24 regions of six human brains. Of the metabolic enzymes, only CK showed a 5-fold variation approaching that of GAD. Like GAD, CK activity was stable postmortem, but its activity was apparently inversely related to the severity and duration of the preterminal illness. CK may be a useful marker of agonal deterioration.
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PMID:Regional activities of metabolic enzymes and glutamate decarboxylase in human brain. 731 90

Neuroleptic malignant syndrome (NMS) was first recognized as a life-threatening complication of dopamine receptor antagonists characterized by extrapyramidal disturbances, hyperthermia, and elevated serum creatine kinase levels. Concepts of NMS have changed because medications other than classic neuroleptic drugs have been implicated as triggering agents and because syndromes identical to NMS have been observed in patients with Parkinson's disease withdrawn from their medication or suffering akinetic hyperthermic parkinsonian crisis. The neurochemical key features in all these conditions are probably functional dopamine deficiency and ensuing hyperactivity of excitatory amino acid neurotransmission in the basal ganglia and hypothalamus. Recognition of NMS is the most important step in its management; the outcome is good if causative drugs are discontinued or if parkinsonian therapy is readjusted. Supportive care includes management of hyperthermia and fluid replacement. Controversial therapeutic measures include the application of dopamine receptor agonists, excitatory amino acid antagonists, or dantrolene. Psychiatric patients with a history of NMS and psychotic relapse necessitating neuroleptic drugs do not commonly redevelop NMS when reexposed to dopamine receptor antagonists but may be treated most safely with atypical neuroleptic drugs such as clozapine.
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PMID:Neuroleptic malignant syndrome. 795 45

In the long course of Parkinson disease, we encounter the elevation of serum creatine kinase (CK) occasionally. Such elevation was not necessarily accompanied by severe symptoms as malignant syndrome. To delineate the basis of its situation, we selected the patients showing CK-elevation from 697 cases of Parkinson disease who had entered our hospital and their serum CK level had been measured. The cases with common cause of CK-elevation like trauma or myocardial infarction were excluded in advance. Those patients with CK-elevation were investigated with reference to age, gender, severity, duration of illness, dementia, and psychiatric symptoms retrospectively. High CK level was observed in 95 cases who were composed predominantly of advanced male patients. No obvious anticipatory cause of CK-elevation like a modification of anti-parkinson drug was recognized in 65 cases. On the other hand, CK-elevation caused by the modification of anti-parkinson drug was recognized in 10 cases. CK-elevation was observed in patients with dementia, delirium, and hallucination at higher rate. Most of these patients with CK-elevation did not show high fever and did not necessarily meet the criteria of malignant syndrome. However, 9 cases who showed marked increase of CK level over 10 times of upper limit of normal value contained some cases who had features of malignant syndrome. In Parkinson disease, especially in advanced cases dopamine may be unstable controlled in a few locations of their brain. Some situation of the disease may elicit imbalance of dopamine in patients' brain and induce CK elevation as in the similar condition in which neuroleptics are administrated.
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PMID:[The elevation of serum creatine kinase in the course of Parkinson disease.--in relation to malignant syndrome]. 895 44

Systemic administration of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) produces parkinsonism in experimental animals by a mechanism involving impaired energy production. MPTP is converted by monoamine oxidase B to 1-methyl-4-phenylpyridinium (MPP+), which blocks complex I of the electron transport chain. Oral supplementation with creatine or cyclocreatine, which are substrates for creatine kinase, may increase phosphocreatine (PCr) or cyclophosphocreatine (PCCr) and buffer against ATP depletion and thereby exert neuroprotective effects. In the present study we found that oral supplementation with either creatine or cyclocreatine produced significant protection against MPTP-induced dopamine depletions in mice. Creatine protected against MPTP-induced loss of Nissl and tyrosine hydroxylase immunostained neurons in the substantia nigra. Creatine and cyclocreatine had no effects on the conversion of MPTP to MPP+ in vivo. These results further implicate metabolic dysfunction in MPTP neurotoxicity and suggest a novel therapeutic approach, which may have applicability for Parkinson's disease.
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PMID:Creatine and cyclocreatine attenuate MPTP neurotoxicity. 1022 17

We report a 60-year-old woman with juvenile Parkinson disease (PD) with vocal cord abductor paralysis (VCAP). She had suffered from juvenile PD for 30 years. She was admitted in February 1998 to our clinical unit, because of malignant syndrome induced by dehydration. Neurological examination revealed disturbance of consciousness, hand tremor, dyskinesia of the trunk and all extremities, and rigidity. Laboratory examinations disclosed leukocytosis, renal dysfunction, hypermyoglobinemia, and elevation of the serum creatine kinase. Six days after admission, dyspnea and inspiratory stridor were noted, and the respiratory distress worsened. Endoscopy of the upper airways revealed that the vocal cord was in the midline or paramedian position. There are some cases of PD with VCAP, but such a case is very rare in Japan. We discussed the pathogenic mechanisms of these conditions, and speculated that VCAP was associated with malignant syndrome in our case.
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PMID:[A case of juvenile Parkinson disease with vocal cord abductor paralysis in the course of malignant syndrome]. 1039 Oct 85

Neuroleptic malignant syndrome is a clinical syndrome characterized by fever, muscle rigidity, and mutism. Some patients with neuroleptic syndrome may have elevated creatine phosphokinase values and abnormal liver aminotransferase values. Precipitating factors are important clues for prompt diagnosis. Typical precipitating factors include antipsychotic agents and major tranquilizers. In Parkinson disease, drug withdrawal, menstruation, and hyponatremia are precipitating factors. We report a case of neuroleptic malignant syndrome in a patient with Parkinson disease and hypernatremia. In addition, we hypothesized that sudden change of sodium concentrations in the central nervous system could trigger neuroleptic malignant syndrome in patients with Parkinson disease. According to our experience, neuroleptic malignant syndrome is a clinical diagnosis and prompt diagnosis avoids unnecessary, expensive work-ups.
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PMID:Acute hypernatremia and neuroleptic malignant syndrome in Parkinson disease. 1040 64


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