Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perioral behaviors induced by neuroleptic drugs have been interpreted as an animal model of tardive dyskinesia. However, these behaviors have also been induced or enhanced by physostigmine, a cholinesterase inhibitor. The latter result is contradictory to the clinical effect of physostigmine in human tardive dyskinesia. In view of this contradiction and other considerations, perioral behaviors have also been interpreted as a model of acute dystonia. The present experiments replicated an earlier failure to observe spontaneous perioral behaviors after long-term neuroleptic treatment in rats as well as the paradoxical effect of physostigmine. The effect of physostigmine was also compared to phenylmethanesulfonyl fluoride and methanesulfonyl fluoride, irreversible CNS active cholinesterase inhibitors. There were significant differences between the effects of the various cholinesterase inhibitors and their interactions with perioral behaviors and neuroleptic treatment. It is concluded that the effects of cholinesterase inhibitors on perioral behaviors in rodents may not be accounted for entirely by cholinesterase inhibition. Further experiments using additional agonists and antagonists will be required to clarify the behavioral effects of these cholinesterase inhibitors.
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PMID:Perioral behaviors induced by cholinesterase inhibitors: a controversial animal model. 380 24

Anticholinergic therapy provides symptomatic relief in many patients with dystonia. The mechanism underlying this therapeutic action is poorly understood; however, one possibility is that the degradation of acetylcholine is perturbed in these conditions. To investigate this possibility, acetylcholinesterase activity was measured in erythrocyte membranes from healthy volunteers and patients with torsion dystonia. Enzyme activities in erythrocytes from 14 patients with adult-onset, childhood-onset idiopathic, and childhood-onset familial dystonias did not differ significantly from activities measured in erythrocyte membranes from 17 healthy volunteers. Moreover, when blood samples from several members of a family with dominant inheritance of dystonia were assayed simultaneously, similar enzyme activities were found in the affected and unaffected individuals. The data suggest that a generalized acetylcholinesterase deficiency is not involved in the pathogenesis of torsion dystonia.
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PMID:Acetylcholinesterase activity in patients with torsion dystonia. Measurement in erythrocyte membranes. 397 44

The mouse mutant Dystonia musculorum exhibits pathological changes in the magnocellular neurons of the red nucleus. The present study shows that allelic differences occur in the age of onset and severity of this pathology. The magnocellular neurons of the Jackson allele (dtJ) almost completely disappear prior to 4 weeks of age while some of these cells are retained in the adult of the Albany strain (dtAlb). However, acetylcholinesterase histochemistry suggests that the remaining rubral neurons in dtAlb are nonfunctional. This pathology may contribute to the severe locomotor disturbances seen in these animals.
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PMID:Effects of age and strain differences on the red nucleus of the mouse mutant Dystonia musculorum. 661 14

Six patients who developed extrapyramidal manifestations following poisoning with the organophosphorus (OP) insecticide fenthion are reported. The extrapyramidal features, in order of frequency, were dystonia, rest tremor, cog-wheel rigidity, and choreo-athetosis. The delay in onset of these signs, following poisoning, varied from 4 to 40 days, and they disappeared spontaneously in about 1 to 4 weeks in those who survived. The human extrapyramidal system is rich in cholinergic neurons and acetylcholinesterase (AChE). Inhibition of AChE by fenthion, which has ready access to central neurons on account of its lipid solubility, is postulated as the mechanism underlying the extrapyramidal manifestations.
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PMID:Extrapyramidal manifestations complicating organophosphorus insecticide poisoning. 757 21

The effects of botulinum toxin-A was compared on both extrafusal and intrafusal muscle fibers in the biceps femoris of Wistar rats. Four days after injection no action potentials were elicited with stimulation single-fiber electromyography on the injected side. Fourteen days after injection, jitter became measurable and these values were increased on the injected side. Extrafusal muscle fibers began to atrophy on the 4th day and this continued to the 14th day postinjection. Atrophy was also evident and progressive in intrafusal muscle fibers. Increased terminal innervation ratios, end-plate spread of cholinesterase, and increased density of very small myelinated fibers in large intramuscular nerves were observed 14 days postinjection. Both extrafusal and intrafusal fibers are cholinergically innervated, and both were progressively affected by botulinum toxin, perhaps varying in degree only. In addition to partial denervation, Botulinum toxin effects in dystonia may also be related to modified spindle afferent discharge.
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PMID:Extrafusal and intrafusal muscle effects in experimental botulinum toxin-A injection. 862 28

A 14-year-old female attempted suicide by ingesting the organophosphate methyl parathion. A severe acute poisoning developed with the characteristic symptomatology: muscarinic, nicotinic and neurologic, as well serum cholinesterase activity decreased 88%. An extrapyramidal syndrome appeared suddenly nine days after the onset with ocular and buccal crisis, neck and trunk dystonic movements, and hypertonia and tremors. The patient improved with the administration of i.v. diphenhydramine. Other causes of toxic extrapyramidalism and organophosphate intermediate syndrome were discarded. Although an absolute causal relationship of the transient extrapyramidal symptomatology to the organophosphate exposure cannot be clearly established in this case, we speculate a possible delayed inhibition of the dopaminergic receptors in the substantia nigra and the basal ganglia.
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PMID:[Acute methyl parathion poisoning with extrapyramidal manifestations not previously reported]. 1020 15

Organophosphate poisonings are not uncommon, and are the leading cause of death in suicide patients in Taiwan. Acute cholinergic crisis caused by the inhibition of synaptic acetylcholinesterase is the major manifestation of organophosphate poisoning and may cause death within minutes. Delayed neurotoxicities include intermediate syndrome and delayed polyneuropathy have also been described. However, these symptoms may not characterize the complete picture of organophosphate poisoning. Among the 633 patients ever admitted to our hospital with organophosphate poisoning, three patients were found exhibiting impermanent neuromuscular dysfunction, including blepharoclonus, oculogyric crisis, intermittent dystonia, rigidity, and tremor, with two of them developing mask face, dyskinesia and akathisia later, following acute cholinergic crisis. The symptoms appeared within 4 days with the duration ranging from 25 days to 2 months. Other causes of the extrapyramidal syndrome noted on these patients have been excluded, and we consider the extrapyramidal syndrome a possible neurotoxic manifestation of organophosphate poisoning, which is transient, needs no treatment, and may be missed because of the critical condition, in a minority of patients. The mechanism remains to be identified, but may be related to the impediment of the function of acetylcholinesterase to modify nigrostriatal dopaminergic system, which is independent of hydrolyzing acetylcholine. More detailed observation for organophosphate poisoned patients and more studies for the biological functions of acetylcholinesterase including the influence on the nigrostriatal dopaminergic system are needed.
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PMID:Acetylcholinesterase inhibition and the extrapyramidal syndrome: a review of the neurotoxicity of organophosphate. 1157

Long-term administration of antipsychotics occasionally produces persistent dystonia of the trunk, a disorder known as Pisa syndrome (or pleurothotonus). The development of Pisa syndrome is most commonly associated with prolonged treatment with antipsychotics; however, it has also been reported, although less frequently, in patients who are receiving other medications (such as cholinesterase inhibitors and antiemetics), in those not receiving medication (idiopathic Pisa syndrome) and in those with neurodegenerative disorders. Drug-induced Pisa syndrome predominantly develops in females and in older patients with organic brain changes. It sometimes occurs after the addition of another antipsychotic to an established regimen of antipsychotics or insidiously arises in antipsychotic-treated patients for no apparent reason. The condition generally disappears after antipsychotic drugs are discontinued. Although a pharmacological therapy for drug-induced Pisa syndrome has not been established, we have reported that anticholinergic drugs are effective in about 40% of patients who have episodes of Pisa syndrome with the remaining patients responding to the withdrawal or reduction of daily doses of antipsychotic drugs. The characteristics of its development and prognosis indicate that drug-induced Pisa syndrome consists of two types of dystonia. Some patients develop clinical features of acute dystonia, whereas others develop symptoms similar to tardive dystonia. Like that of tardive dystonia, Pisa syndrome responds better than tardive dyskinesia to a relatively high daily dose of an anticholinergic. However, the significant improvement caused by the withdrawal of antipsychotic drugs in Pisa syndrome differentiates it from tardive dystonia. Thus, Pisa syndrome including these features is considered to be an atypical type of tardive dystonia. These clinical characteristics suggest that the underlying pathophysiology of drug-induced Pisa syndrome is complex. A dopaminergic-cholinergic imbalance, or serotonergic or noradrenergic dysfunction, may be implicated. Asymmetric brain functions or neural transmission may also be considered as underlying mechanisms of the development of Pisa syndrome that is resistant to anticholinergic drugs. Idiopathic Pisa syndrome is characterised by an adult-onset, segmental truncal dystonia in patients with no previous exposure to antipsychotics. It occurs rarely but shows a complete resolution with high doses of anticholinergic drugs.
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PMID:Drug-induced Pisa syndrome (pleurothotonus): epidemiology and management. 1188 37

Pisa syndrome is a rare type of truncal dystonia. Its development is associated commonly with neuroleptic treatment, but there are rare idiopathic cases or those related to neurodegenerative disorders. Recently, an association between cholinesterase inhibitors and Pisa syndrome has been described. The authors report two patients, one with Alzheimer's disease treated with risperidone and another with Parkinson's disease who presented this kind of dystonia after donepezil initiation. In the first patient the condition resolved after discontinuation of risperidone, and in the second one the condition resolved when donepezil was withdrawn. In patients with pharmacologic or degenerative dopaminergic neurotransmission disorders, cholinergic excess may induce this peculiar type of dystonia.
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PMID:Cholinergic-dopaminergic imbalance in Pisa syndrome. 1278 13

Dystonia musculorum (dt) mice suffer from a severe sensory neuropathy caused by mutations in the gene encoding the cytoskeletal cross-linker protein dystonin/bullous pemphigoid antigen 1 (Bpag1). Loss of function of dystonin/Bpag1 within neurons leads to a loss in the maintenance of cytoskeletal organization and to the development of focal axonal swellings prior to death of the neuron. In the present study, we demonstrate that neurons within the sciatic nerves of dt27J mice undergo axonal degeneration as has been previously reported for the dorsal roots. Furthermore, ultrastructural studies reveal a perturbed organization of the neurofilament and microtubule networks within the axons of sciatic nerves in dt27J mice. The disrupted cytoskeletal organization suggested that axonal transport is affected in dt mice. To address this, we assessed fast axonal transport by measuring the rate of accumulation of acetylcholinesterase (AChE) proximal and distal to a surgically introduced ligature on the sciatic nerves of normal and dt27J mice. Our findings demonstrate that axonal transport of AChE in both orthograde and retrograde directions is markedly affected, and allow us to conclude that axonal transport defects do exist in the sciatic nerves of dt27J mice.
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PMID:Impaired fast axonal transport in neurons of the sciatic nerves from dystonia musculorum mice. 1285 70


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