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)

Experimental and clinical data clearly demonstrate that calcium antagonists (CA) may have an action on the central nervous system (CNS). The cerebrovascular action of CA justifies their use in cerebral ischaemia, vasospasm and hypoxia. Several clinical trials have demonstrated such beneficial effects. On the other hand a number of reports indicate that CA may have a direct neuronal effect, although most of such trials have not been verified or are mere case reports. In addition, the large number of conditions susceptible to being corrected by CA is impressive: epilepsy, pain, dystonia, dyskinesia, psychiatric conditions, etc. Other papers are disconcerting that report extrapyramidal disorders induced by flunarizine and cinnarizine in the elderly, whereas nicardipine does not produce such side effects and may even alleviate some parkinsonian symptoms. In various experimental models (e.g. stroke, oedema), pharmacological effects have been shown to vary from one compound to the other. Two main questions are yet to be answered: 1) has the direct neuronal effect of CA been clearly established? 2) are the multiple clinical effects on the CNS really linked to calcium antagonism?
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PMID:Clinical neuropharmacology of calcium antagonists. 269 95

Two siblings of juvenile parkinson's disease dystonic type (JPA Yokochi type 3) and hereditary progressive dystonia with marked diurnal fluctuation (Segawa, HPD) were reported. The family had consanguinity. The elder brother suffered from resting tremor of legs, left foot dystonia and left pes equinovarus at the age of 12 years and 5 months. At the age of 15, he developed tremor and rigidity of upper extremities. These symptoms did not show diurnal fluctuation and markedly responded to L-dopa treatment. He implicated wearing-off phenomenon at the age of 16, and on-off phenomenon and L-dopa-induced dyskinesia at the age of 18. He was diagnosed as JPA Yokochi type 3. The younger brother suffered from left pes equinovarus, right scoliosis and foot dystonia at the age of 8 years. These symptoms showed remarkable diurnal fluctuation, which ameliorated after sleep or rest and worsened afternoon. He noticed fine postural tremor of upper extremities at psychological tense state and right pes varus at the age of 16. He received L-dopa at the age of 17 and became to be remission. He was diagnosed as HPD. Since these two disorders related to basal ganglia show similar clinical symptoms mainly consisting of foot dystonia and similar clinicopharmacological response to L-dopa, it has been assumed that shared abnormalities in pathomechanism can exist between them. This study indicates that the same gene-regulated abnormality may participate in the development of these two disorders.
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PMID:[Two siblings of juvenile Parkinson's disease dystonic type (Yokochi type 3) and hereditary progressive dystonia with marked diurnal fluctuation (Segawa)]. 280 13

Movement abnormalities in neuroleptic-treated, psychiatric patients are classified as (a) initial syndromes, including dystonia, parkinsonism, and hyperkinetic abnormalities such as initial dyskinesia (ID) and akathisia, all of which are related to the neuroleptic dose and can be considered as overdose phenomena; (b) tardive syndromes, mainly the classic tardive dyskinesia (TD) syndrome, more seldom tardive akathisia and tardive dystonia, which may all develop or aggravate after withdrawal of neuroleptic treatment; and (c) age-related, spontaneous dyskinesia, akathisia, and dystonia, and schizophrenia-related, hyperkinetic, often stereotyped, movements and restlessness. ID and TD can occur simultaneously, and may depend, at least partially, on identical mechanisms. The pathophysiology of TD is still not clear, and the traditional dopamine (DA) hypersensitivity model seems inadequate. Animal experiments suggest that blockade of some DA receptors in the brain (e.g., in ventromedian striatum) may counteract hyperkinesia and produce parkinsonism, while a concomitant blockade of other similar receptors in other brain regions (e.g., in anterodorsal striatum) may aggravate movements. This offers an explanation for the concomitant occurrence of parkinsonism and hyperkinetic movement abnormalities (ID and akathisia) relatively early in a neuroleptic treatment, and may also contribute to the understanding of the pathophysiology of TD. It is concluded that pathophysiologically TD is a heterogeneous syndrome depending on a subtle balance between several neurotransmitters in the brain, including DA receptor blockade and hypersensitivity of DA and GABA receptors.
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PMID:Pathophysiological mechanisms underlying tardive dyskinesia. 286 Jun 66

Tardive dyskinesia seems to occur as a result of diminished cholinergic and enhanced dopaminergic activity in the striatum. Meclofenoxate has been shown to increase cerebral cholinergic activity. To ameliorate the tardive dyskinesia, meclofenoxate was given orally, 600-1200 mg/day, for 6-12 weeks. The effects of the drug were evaluated by scoring the degree of involuntary movement. Among 11 subjects with tardive dyskinesia or dystonia, 4 improved markedly, 1 moderately, 2 slightly, and there was no improvement in 4. One patient with subacute oral dyskinesia, induced by administration of neuroleptics for 1 month, improved markedly. The possibility that meclofenoxate may be effective in dealing with dyskinesias that are induced by neuroleptics warrants further attention.
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PMID:Meclofenoxate therapy in tardive dyskinesia: a preliminary report. 286 61

Selective D1 and D2 dopamine (DA) antagonists and agonists were given to 4 Cebus monkeys who had previously received haloperidol treatment for 4 years. SCH 23390 (a selective D1 antagonist) and raclopride (a selective D2 antagonist) induced identical syndromes consisting of dystonia and oral dyskinesia. Biperiden (an anticholinergic drug) and LY 171555 (a selective D2 agonist) completely antagonized the dystonia and dyskinesia induced by SCH 23390 as well as raclopride. The combined treatment with LY 171555 and SCH 23390 (but not LY 171555 and raclopride) caused pronounced sedation. LY 171555 induced repetitive movements of head, legs and trunk, but no oral dyskinesia. SKF 38393 (a partial D1 agonist) caused slight sedation, minimal oral dyskinesia and a significant reduction in D2 agonist-induced repetitive movements.
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PMID:Selective D1 and D2 receptor manipulation in Cebus monkeys: relevance for dystonia and dyskinesia in humans. 289 Nov 33

Tardive dyskinesia (TD) is a syndrome of involuntary movements that develops in predisposed individuals during neuroleptic drug treatment, with an average prevalence of 15%. Neuroleptic (antidopaminergic) drugs are the predominant etiological factor. Although no simple correlation can be established, both dosage and treatment duration seem to be of importance for the development of dyskinesia. It is still uncertain whether some neuroleptics carry a higher risk than others, but it appears that the atypical neuroleptic clozapine, which causes no or minimal dystonia, parkinsonism, or akathisia, also carries no or minimal risk of TD. The pathophysiological mechanisms underlying TD are unclear. The traditional dopamine hypersensitivity theory is no longer viable, whereby new hypotheses have been advanced: TD can be due to the blockade of a subset of striatal dopamine receptors, while parkinsonism is due to the blockade of another such subset, and/or can be due to a reduced GABA turnover in a subgroup of neurons connecting striatum with globus pallidus and substantia nigra. TD is best prevented by a course of neuroleptic medication involving as little antidopamine effect as possible, including minimal doses and shortest possible length of treatment. The main TD treatment principle consists of a gradual dose reduction, possibly over years. It should be added, however, that more recent investigations indicate that traditional antidopaminergic treatment in moderate doses may be safely continued over a long period without an increased risk of TD progression.
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PMID:Tardive dyskinesia. 289 70

Follow-up data from the first 100 patients with early dyskinesia are presented. After an average of 40.9 months, the cohort showed statistically significant decreases in tardive dyskinesia (TD) ratings. After TD onset, ratings decreased for 4 years, then plateaued and rose during the 7th year. Age was not a negative prognostic factor in this cohort. Improvement in TD correlated significantly with fewer neuroleptic-free periods before and more neuroleptic-free periods after TD onset. Neuroleptic dosage correlated negatively with improvement in trunk and dystonia ratings. Improvement in TD is the usual finding in longitudinal studies of TD cohorts. Follow-up studies of neuroleptic-treated groups with varying proportions of patients showing TD, by contrast, tend to show increased TD because new TD cases more than offset improvement. A naturalistic study with pharmacotherapy tailored to the underlying psychiatric disorder and conducted long-term from TD onset is the ideal design for investigating the natural history of TD.
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PMID:The natural history of tardive dyskinesia. 290 68

The prevalences and inter-relationships of five types of movement disorders were evaluated in a large, developmentally disabled (DD) population (n = 1227); prevalence was evaluated with regard to severity, age, gender and antipsychotic-drug (APD) exposure. Dyskinesia was found in 48% of the sample, dystonia in 29%, akathisia in 13%, Parkinsonism in 3% and paroxysms in 4%. Many persons had more than one symptom so that 72% had one or more of the five target symptoms. Although the five movement-disorder categories were not mutually exclusive, analysis supported the individuality of the categories as defined in this study. The prevalences of dyskinesia and Parkinsonism were considerably greater than those in the general population. On the other hand, the prevalence of dyskinesia was similar to that reported for psychiatric and institutionalized geriatric populations. Parkinsonism increased with age and male gender, while dyskinesia increased with age and female gender. APD-exposure was significantly correlated only with akathisia.
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PMID:Prevalence of dyskinesia and related movement disorders in a developmentally disabled population. 292 98

Glutaric acidemia, which is due to inherited deficiency of glutaryl-CoA dehydrogenase, is characterized clinically by progressive dystonia and dyskinesia in childhood, and pathologically by degeneration of the caudate and putamen. Results using newer imaging techniques (computer tomography and magnetic resonance image scanning) suggest that neurological involvement in this condition begins before birth, and that gliosis of the basal ganglia is a relatively late event. Glutaric acidemia type II is usually due to inherited deficiency of electron transfer flavoprotein (ETF) or ETF:ubiquinone oxidoreductase, but some patients with typical disease may have another, to date undefined, abnormality. There may also be a clinical phenotype of glutaric acidemia type II which, like glutaryl-CoA dehydrogenase deficiency, is characterized by a movement disorder and by degeneration of the basal ganglia.
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PMID:Recent progress in understanding glutaric acidemias. 312 45

The experience that the supplementation of depleted dopamine in the nigro-striatal system of parkinsonian patients with L-dopa improves the clinical triad, akinesia, rigidity and tremor, mainly applies to long-term treatment in the early phase of Parkinson's disease. Complications in motor performance, like on-off response, wearing-off phenomena, peak-dose dyskinesia, biphasic dyskinesia, off-period dystonia and others, after more than 3 to 5 years following the onset of treatment indicate fluctuations in the dopaminergic feedback control system. It is suggested that these complications are due to progressive presynaptic degeneration and late changes in postsynaptic receptor amplification. However, as fluctuations are not imperative in all patients, an important additional aspect seems to be the topography of denervation, which involves different portions of the striatum to varying degrees. Location and extent of denervation are criteria which appear to have predictive value for the malignancy of the disease, the therapeutic response of drugs and complications in long-term treatment.
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PMID:Factors contributing to fluctuations of the dopaminergic nigro-striatal feedback system in Parkinson's disease. 316 34


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