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

In 4 out of 11 cebus apella monkeys given haloperidol (0.05 - 1.0 mg/kg/d) orally for up to 35 months signs of tardive dyskinesia (TD) hav developed: 1) One monkey developed barely noticeable TD after 4 months, but showed marked and increasing symtpoms of both generalized choreic and buccolingual TD after 8 months. This animal died 3 months after discontinuation of haloperidol. At that time the signs of TD were still prominent. 2) In one monkey bucco-lingual TD appeared after 3 months and was still reversible on discontinuation of haloperidol at 5 months. After a further 12 months of haloperidol, the TD signs proved to be long lasting, possibly irreversible, in this animal. 3) A third monkey showed slight and transient signs of TD at 14 months, but following a further 20 months af haloperidol administration a choreiform syndrome became porminent after drug withdrawal. 4) After 34 months a similar syndrome of choreic movements has been noticed in another animal, increasing after withdrawal of haloperidol. The other 7 monkeys have received haloperidol for 3 - 15 months, without developing any signs of TD. Attacks of acute dystonia have been noticed in all animals, sometimes necessitating anticholinergic medication or decreases in the daily haloperidol dose.
 ...
PMID:Development of acute dystonia and tardive dyskinesia in cebus monkeys. 11 74

Continuous administration of haloperidol, sulpiride, or cis-flupenthixol, but not of domperidone or apomorphine, to Wistar rats for up to 3 weeks caused an increase in spontaneous purposeless chewing movements. Treatment with physostigmine and pilocarpine, but not neostigmine, for up to 3 weeks increased chewing, whilst scopolamine decreased chewing. Metergoline and cyproheptadine, but not quipazine, increased chewing after only 1 and 7 days but not thereafter. Chewing was not altered following treatment with compounds acting on GABA or noradrenaline systems or by a range of non-neuroleptic agents inducing dystonia in man. The enhancement of chewing induced by neuroleptic and cholinomimetic drugs was reduced by acute treatment with scopolamine, and reverted to control levels following drug withdrawal. Neuroleptic-induced purposeless chewing in Wistar rats appears to be primarily influenced by cerebral dopamine and acetylcholine function and may resemble acute dystonia, rather than tardive dyskinesia.
 ...
PMID:Pharmacological characterisation of spontaneous or drug-associated purposeless chewing movements in rats. 285 1

Forty-four adult patients with various forms of dystonia were treated with anticholinergics slowly increased to maximum tolerated doses. Thirty-seven per cent of the 35 idiopathic dystonia patients had a moderate to marked improvement with an average dosage of 21.5 mg of trihexyphenidyl. Younger patients with a shorter duration of dystonia and those who tolerated higher doses tended to benefit most. However there were exceptions to all of these factors. None of the nine patients with symptomatic dystonias improved more than mildly and most had no benefit despite the use of dosages similar to those resulting in improvement in idiopathic dystonia patients. Side effects were common. These often forced drug withdrawal at lower doses than those which might have resulted in improvement. These results suggest that high dose anticholinergics should be the first line of therapy for disabling dystonia.
 ...
PMID:High dose anticholinergic therapy in adult dystonia. 286 32

About 2.5% of patients treated with neuroleptic drugs develop acute dystonia within 48 h of commencing therapy. The symptoms remit on drug withdrawal or following anticholinergic therapy. Acute dystonia can also be reliably induced in many primate species by neuroleptic treatment with comparable time course, symptomatology and pharmacological characteristics to those observed in man. In general, New World monkeys appear more susceptible to acute dystonia than Old World primates. It is at present not clear whether all primates, including man, would exhibit dystonia if a sufficiently high dose of neuroleptic was administered. Alternatively, some unknown, possibly species-specific or even genetic, factors may determine an individual's susceptibility to develop dystonia. Use of a rodent model of dystonia might enable more detailed analysis of biochemical correlates of dystonic behaviour. Whilst rodents do not exhibit overt dystonic behaviour after neuroleptic treatment, they may develop oral dyskinesias which bear a close pharmacological similarity to dystonia in man and primates. However, it is not known whether chewing induced by neuroleptic drugs in rats resembles acute dystonia in primates or whether this is another movement disorder possibly unique to rodent species. The pathophysiology of acute dystonia remains unknown, but may involve striatal dopaminergic and cholinergic function. In view of the close similarity between dystonia in man and other primates, studies on the mechanisms whereby neuroleptic drugs cause acute dystonic reactions in monkeys may give some clues to the pathogenesis of spontaneous dystonia in man.
 ...
PMID:Acute dystonia induced by neuroleptic drugs. 287 78

Focal dystonia of the right hand and speech impairment as a result of a circumscribed left-sided anterior thalamic lesion is reported in a 9-year-old girl with borderline normal psychomotor development. Both focal dystonia and speech impairment improved during anticholinergic treatment and worsened after drug withdrawal.
 ...
PMID:Focal dystonia and speech impairment responding to anticholinergic therapy. 770 99

In 1954, when he was five years old, a patient suffered from encephalitis with a prolonged lethargic state. Following this episode, he presented a severe parkinsonian syndrome which was associated, after a few years, with an axial dystonia and stereotyped involuntary movements of the upper limbs. These abnormal movements were particular by their coordinated appearance, their rhythmicity and their relative slowness. Treatment with L-dopa suppressed all akinetic, dystonic and dyskinetic symptoms. At age of 40 years, all the akinetic, dystonic and dyskinetic symptoms reappeared after drug withdrawal. Cerebral computed tomography, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography were normal. Fluorodopa positron emission tomography revealed a significant bilateral reduction of tracer accumulation in the posterior part of both putamen, similar to that observed in patients with idiopathic Parkinson's disease. In this patient, pharmacological tests revealed that effectiveness of L-dopa was abolished by administration of a D2 antagonist, and was fully reproduced by a D2 agonist. Clinical signs, pharmacological data and past-medical history strongly suggested a limited lesion of the zona compacta of substantia nigra induced by viral agression. This complex and progressive extrapyramidal syndrome had strong similarities with the lethargic encephalitis of Von Economo and its late symptoms. Other diseases associating akinesia and dyskinesia or dystonic phenomena, like dopa-sensitive dystonia and juvenile Parkinson's disease, are very unlikely. Thus, the persistance of sporadic forms of Von Economo's encephalitis could be discussed.
 ...
PMID:[Parkinsonian syndrome and post-encephalitic stereotyped involuntary movements responsive to L-dopa]. 876 55

Parkinsonism, tremor, chorea-ballismus, dystonia, tardive dyskinesia, myoclonus, tics and akathisia can be induced by many drugs. The drugs that are most frequently implicated in movement disorders are antipsychotics, calcium antagonists, orthopramides and substituted benzamides (e.g. metoclopramide, sulpiride, clebopride, domperidone), CNS stimulants, antidepressants, anticonvulsants, antiparkinsonian drugs and lithium. It is possible for a single drug to induce 2 or more types of movement disorders in the same patient. Movement disorders are not always reversible after drug withdrawal.
 ...
PMID:Drug-induced movement disorders. 909 56

The objective of this paper was to evaluate the efficacy of diphenhydramine hydrochloride (DPH) in dystonic patients. In 1995, Truong et al reported encouraging results in five patients with idiopathic torsion dystonia (ITD) treated with DPH, an H1 antagonist with sedative and anticholinergic properties. Five patients with generalized ITD, one with secondary generalized dystonia and one with idiopathic segmental dystonia were included in the prospective study. Initially the response to intravenous administration of DPH versus placebo in two sessions a week apart was evaluated. Two weeks later all patients started oral DPH in increasing doses (range 100-300 mg, mean 164 mg). The degree of dystonia was determined by a modified University of Columbia Scale evaluating the baseline score, after placebo and DPH I.V. administration then at one and six months after starting oral treatment. The results were analyzed by Friedman's test for repeated measurements. On comparing scores for baseline severity, I.V. placebo and I.V. DPH presented a highly significant correlation (12.09; p = 0.00) as well as comparing baseline score with oral DPH at one and 6 months, treatment (12.78; p = 0.00). Functional score results were 9.5 p = 0.01 and 8.4 p = 0.02 at one and 6 months respectively. The most common side effects were somnolence and dizziness. It can be concluded that DPH proved effective in our patients with mild to moderate adverse effects not requiring drug withdrawal in any case. However, I.V. challenge was unable to predict the long-term response to oral medication perhaps due to the limited number of cases.
 ...
PMID:Beneficial effects of diphenhydramine in dystonia. 1034 17

To investigate the safety (e.g., weight gain, liver function, extrapyramidal side effects, and seizures) and efficacy of the long-term use of risperidone in children and adolescents and to ascertain the effects of drug withdrawal in a semi-naturalistic prospective, subjects with autism or pervasive developmental disorders not otherwise specified (PDDNOS) were treated with risperidone for 6 months after which parents were given the option of continuing for a further 6 months (final assessment at 12 months). Behavioral rating included Childhood Autism Rating Scale (CARS), Child Psychiatric Rating Scale (CPRS), Clinical Global Impression (CGI), and Child-Global Assessment Scale (C-GAS). Risperidone significantly ameliorated behavioral symptoms of PDD in 10 out of 11 subjects, with the effects on core symptoms being of smaller amplitude and of slower onset. No loss of effectiveness was observed in patients who continued risperidone for 12 months, while a relapse of associated behavioral symptoms occurred in the others. Weight gain was common, although the rate of increase lessened over a period of time; after drug withdrawal, considerable weight loss was observed in the patient who had previously shown the most significant increase. After 6 months of therapy, two patients developed facial dystonia: this disappeared after reducing dosage in one case, after drug discontinuation in the other. Amenorrhea was also observed, but no changes in liver function, blood tests or EEG were reported. The data indicate that risperidone is an effective and relatively safe drug for long term treatment of behavioral disruption in autistic children and adolescents.
 ...
PMID:Long-term risperidone for pervasive developmental disorder: efficacy, tolerability, and discontinuation. 1093 18

Intrathecal baclofen infusion is an accepted treatment for spasticity. Evidence also exists for the treatment of secondary generalized dystonia with intrathecal baclofen infusion. Benefits include decreased tone, improved positioning, and decreased decubitus ulcers. Despite these benefits, there are significant complications that can occur with this therapy, including drug withdrawal, catheter infection, drug overdose, failure, and pump failure. In some cases, practitioners encourage a trial dose of intrathecal baclofen by injection or catheter infusion before pump implantation. To improve patient selection and outcomes many centers offering intrathecal baclofen therapy use a multidisciplinary team composed of physicians, surgeons, and physical therapists.
 ...
PMID:Intrathecal Baclofen Infusion for the Treatment of Movement Disorders. 3089 71


1